Progress in Neurobiology 122 (2014) 1–23

Brain alterations in paedophilia: A critical review

Sebastian Mohnke a,*, Sabine Muller a, Till Amelung b,Tillmann H.C. Kruger c, Jorge Ponseti d, Boris Schiffer e,Martin Walter f, Klaus M. Beier b, Henrik Walter a,**a Charite – Universitatsmedizin Berlin, Department of Psychiatry and Psychotherapy, Chariteplatz 1, 10117 Berlin, Germanyb Charite – Universitatsmedizin Berlin, Institute of Sexology and Sexual Medicine, Luisenstr. 57, 10117 Berlin, Germanyc Hannover Medical School, Department of Clinical Psychiatry, Social Psychiatry, and Psychotherapy, Carl-Neuberg-Str. 1, 30625 Hannover, Germanyd University Medical Center Schleswig-Holstein, Section for Sexual Medicine, Arnold-Heller-Str. 3, 24105 Kiel, Germanye Division of Forensic Psychiatry, Department of Psychiatry, Psychotherapy and Preventive Medicine, LWL-University Hospital, Bochum, Germanyf Otto-von-Guericke-University Magdeburg, Department of Psychiatry, Leipziger Str. 44, 39120 Magdeburg, Germany

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

1.1. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

1.2. Prevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

1.3. Paedophilia vs. sexual offending against children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

1.4. Aetiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

1.5. The neurophenomenological model of sexual arousal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

1.6. Literature search . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

A R T I C L E I N F O

Article history:

Received 5 December 2013

Received in revised form 25 July 2014

Accepted 31 July 2014

Available online 10 August 2014

Keywords:

Child sexual abuse

Sexual arousal

Sexual offending

Brain pathology

Magnetic resonance imaging

A B S T R A C T

Psychosocial and biological factors have been implicated in paedophilia, such as alterations in brain

structure and function. The purpose of this paper is to review the expanding body of literature on this

topic including brain abnormality case reports, as well as structural and functional neuroimaging

studies. Case studies of men who have committed sexual offences against children implicate frontal

and temporal abnormalities that may be associated with impaired impulse inhibition. Structural

neuroimaging investigations show volume reductions in paedophilic men. Although the findings have

been heterogeneous, smaller amygdala volume has been replicated repeatedly. Functional neuroimaging

investigations demonstrate an overlap between paedophiles and teleiophiles during sexual arousal

processing. While it is controversial among studies regarding group differences, reliable discrimination

between paedophilic and teleiophilic men may be achieved using functional activation patterns.

Nevertheless, the heterogeneous findings published so far suggest further research is necessary to

disentangle the neurobiological mechanisms of paedophilic preference. A number of methodological

confounds have been identified, which may account for the inconsistent results that could prove to be

beneficial for future investigations.

� 2014 Elsevier Ltd. All rights reserved.

Abbreviations: ICD-10, International Classification of Diseases and Related Health Problems, 10th Revision, World Health Organization; DSM-5, Diagnostic and Statistical

Manual of Mental Disorders, 5th Edition, American Psychiatric Association; CSA, child sexual abuse; CSO, child sexual offender; NSO, non-sexual offender; MRI, magnetic

resonance imaging; fMRI, functional magnetic resonance imaging; PET, positron emission tomography; CT, computed tomography; VBM, voxel-based morphometry; ROI,

region of interest; FWE, familywise error; FDR, false discovery rate.

* Corresponding author at: Charite – Universitatsmedizin Berlin, Campus Mitte, Department of Psychiatry and Psychotherapy, Division of Mind and Brain Research,

Chariteplatz 1, 10117 Berlin, Germany. Tel.: +49 30 450 517 223; fax: +49 30 450 517 906.** Corresponding author at: Charite – Universitatsmedizin Berlin, Campus Mitte, Department of Psychiatry and Psychotherapy, Division of Mind and Brain Research,

Contents lists available at ScienceDirect

Progress in Neurobiology

jo u rn al ho m epag e: ww w.els evier . c om / lo cat e/pn eu ro b io

Chariteplatz 1, 10117 Berlin, Germany. Tel.: +49 30 450 517 141; fax: +49 30 450 517 906.

E-mail addresses: sebastian.mohnke@charite.de (S. Mohnke), mueller.sabine@charite.de (S. Muller), till.amelung@charite.de (T. Amelung),

krueger.tillmann@mh-hannover.de (Tillmann H.C. Kruger), ponseti@sexmed.uni-kiel.de (J. Ponseti), boris.schiffer@uni-due.de (B. Schiffer), martin.walter@med.ovgu.de

(M. Walter), klaus.beier@charite.de (K.M. Beier), henrik.walter@charite.de (H. Walter).

http://dx.doi.org/10.1016/j.pneurobio.2014.07.005

0301-0082/� 2014 Elsevier Ltd. All rights reserved.

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–232

2. Neurological case reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

2.1. Brain tumours . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

2.2. Different forms of dementias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

2.3. Parkinson’s disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

2.4. Further neurological disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

3. Neuroimaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

3.1. Structural neuroimaging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

3.1.1. CT studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

3.1.2. MRI studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

3.2. Functional neuroimaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

3.2.1. PET studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

3.2.2. fMRI studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

3.3. Correlational analyses in neuroimaging studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

1. Introduction

1.1. Diagnosis

Paedophilia is commonly viewed as an adult sexual responsive-ness towards immature (prepubescent) subjects. Research distin-guishes it from teleiophilia as the sexual responsiveness to mature(postpubertal) subjects and hebephilia, the sexual responsivenessto pubertal children (Beier et al., 2013; Blanchard et al., 2000).Paedophilia appears in both psychiatric diagnostic systems, theICD-10 and the DSM-5, under disorders of sexual preference(paraphilia). Since the DSM-5, paedophilia is explicitly distin-guished from paedophilic disorder, defined via recurrent, intensesexually arousing fantasies, and sexual urges towards prepubes-cent children. The latter additionally requires either that thesesexual urges lead to marked distress, interpersonal difficulty, orthat the individual has acted out on these sexual urges. Therefore,by the redefinition of the term paedophilia (i.e., sexual focus onchildren without distress, interpersonal difficulty, and sexual actsinvolving children), the mere sexual preference for children hasbeen depathologized. This makes sense from both a clinical and aforensic perspective, since paedophilia which causes neithersuffering nor child harm requires no therapy or prosecution(although preventive measures could be indicated, because thepreference may still constitute a risk factor for later offending; seeSection 1.3).

Both ICD-10 and DSM-5 require that the affected person’ssexual urges/fantasies have been acted upon or cause markeddistress or interpersonal difficulty. Furthermore, both systemsspecify that the affected person must be 16 years and at least fiveyears older than the sexually desired children. In contrast to theICD-10, the DSM-5 further specifies that individuals in lateadolescence who are in ongoing sexual relationships with 12–13-year-olds do not fit the criteria for paedophilia. Furtherdisagreement between the diagnostic systems exists with regardto the (body) age of the desired children: ICD-10 definespaedophilia (F65.4) as a sexual preference for children who areeither prepubescent or in an early state of puberty, but might alsobe younger; in contrast, the DSM-5 defines paedophilia orpaedophilic disorder (302.2) by recurrent, intense sexuallyarousing fantasies, sexual urges, or behaviours involving sexualactivity with prepubescent children (generally age 13 years oryounger), which have to persist over a period of at least six months.Note that the sexual preference for pubertal children has beentermed hebephilia and was repeatedly described as a distinguish-able phenomenon (Beier et al., 2013; Blanchard, 2010). Further-more, a recent study using multiple taxometric analyses supportsthe view of paedophilia as a separate diagnostic entity (Schmidt

et al., 2013), implying that the sexual interest in prepubertalchildren would be distinguishable from the sexual interest inpubertal children. Contrary to early propositions, and after anextensive debate, the diagnosis of hebephilia was not included inthe DSM-5 (for a summary of this discussion see Blanchard, 2013).In addition, the ICD-10 requires the presence of recurrent sexualfantasies or urges towards children, and these elements are notnecessary according to the DSM-5. Following DSM-criteria sexualbehaviour with prepubescent children that persists more than sixmonths would be sufficient for the diagnosis of paedophilicdisorder, even in the absence of arousing fantasies or urges.

The DSM-5 distinguishes between an exclusive and a non-exclusive type of paedophilia (whether the person can be sexuallyaroused only by children or also by elder persons), a genderpreference, and a limitation to incest. Also, the criteria within eachdiagnostic system have been changed significantly during itsdevelopment (for DSM criteria, see Blanchard, 2010). Therefore,the different definitions of paedophilia comprise different popula-tions that have a common intersecting-set but are not identical(see Fig. 1).

The stability of paedophilia is also controversial. In general,paedophilia has been seen as a lifelong individual trait (e.g., Seto,2008, 2012). Cases in which paedophilic behaviours occurred afterbrain lesions have thus been discussed as behavioural manifesta-tions of pre-existent latent paedophilic urges due to generalimpulse disinhibition. In contrast, there are some reports claimingsuccessful therapeutic alteration of sexual preference and reducedreoffending in paedophilic child sexual offenders (CSO; Marshallet al., 2005; Marshall, 2008). Additionally, a change in psycho-physiological reaction to child sexual stimuli has been recentlydemonstrated in some men (Muller et al., 2014). Whether thechanges reported represent an ‘‘elimination’’ of paedophilia orrather a control of symptoms remains unclear. While the findingsremain anecdotal, they might still challenge the state of the artview of paedophilia as a stable and unchangeable condition.Neurobiological correlates may be particularly useful to disentan-gle whether paedophilia is mutable by: first, elucidating theaetiology of human sexual preference (see Section 1.4); andsecond, uncovering the link between preference and behaviourleading to the risk of potentially endangering others as suggestedby the hypothesis that paraphilic interest can become behaviou-rally manifest following brain damage (see also Section 1.3).

1.2. Prevalence

Due to the lack of epidemiological studies, the exact prevalenceof paedophilia is unknown. However, in the Berlin Male Study,conducted on a population-based sample of men between 40 and

Fig. 1. The diagnosis of paedophilia/paedophilic disorder according to the ICD-10 and the DSM-5.

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–23 3

79 years, 367 participants volunteered to anonymously fill outquestionnaires on paraphilic arousal patterns. Of these men 9.5%reported sexual fantasies involving children, 6% masturbated tothese fantasies, and 3.8% admitted sexual contact with childrenbelow 13 years of age (Ahlers et al., 2009). Of note, only twoparticipants (0.5%) reported to be distressed by their excitability bychildren. A population-based Finnish study on 3967 male twinsbetween the ages of 21 and 43 years found a 12-month-prevalenceof 0.3% (95% confidence interval: [0.08–0.61%]) for sexual interestin children (judging from respective sexual fantasies or actions;Mokros et al., 2012; Alanko et al., 2013). Furthermore, 2.7% of theparticipants reported masturbation phantasies involving childrenbelow the age of 16, and 0.3% had sexual contact with children ofthat age group during the past 12 months. Taking together, thepoint prevalence for paedophilia could be estimated to be around0.3–3.8% (Ahlers et al., 2009; Alanko et al., 2013). There are isolatedreports of paedophilia in women (Chow and Choy, 2002), althoughit seems to be substantially more frequent in men (Denov, 2003).

1.3. Paedophilia vs. sexual offending against children

The term paedophilia is often used interchangeably with sexualoffending against children, although research clearly shows that

they cannot be used synonymously. Not all CSOs havepaedophilia, just as not all paedophilic men necessarily commitchild sexual abuse (CSA). Therefore, CSOs can be grouped inthose: (1) without a sexual preference for children that havesexually abused children (e.g., sexually inexperienced adoles-cents seeking a surrogate; persons with antisocial personalitydisorders or perpetrators within general traumatizing familyconstellations; Seto, 2008), and, (2) with a sexual preference forchildren (e.g., paedophilia and/or hebephilia). The proportion ofpaedophiles in CSOs is about 40–50% (Maletzky and Steinhauser,2002; Seto and Lalumiere, 2001; Seto, 2008). Conversely, theproportion of paedophiles who sexually approach childrenseems to be similarly high with about 43% (Seto et al., 2006).In that respect, it has to be kept in mind that a paedophilicinclination in an individual does not mean that the inclinedperson will necessarily act on his fantasies. On the other hand,paedophilia is a major risk factor for committing sexual offencesagainst children, particularly for sexual recidivism (Hanson andMorton-Bourgon, 2005). The distinction between paedophiliaand CSA is important to consider, since most research has beenconducted on CSOs that have not always been reliablydiagnosed. Results from studies on these populations may beadditionally confounded by antisocial traits of the subjects and

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–234

the forensic settings. Very little is known about undiagnosedpaedophiles who have not sexually abused a child.

1.4. Aetiology

The aetiology of paedophilia is uncertain, but seems to bemultifactorial, comprising psychosocial and biological factors.

The conditioning hypothesis points to the relevance of first sexualcontact with same-aged peers during childhood (Marshall andEccles, 1993). During these experiences, an association betweenformerly neutral stimuli like a prepubescent body schema andunconditioned stimuli such as sexual gratification would belearned and result in the persistent sexual preference forrespective sexual partners. This theory is contrary to the fact thatmost people have their first sexual experiences during earlypuberty, but only a small percentage develops paedophilicallymotivated interest. Furthermore, some paedophilic men reportthat they were aware of their sexual interest in children beforetheir first sexual contacts (Dandescu and Wolfe, 2003).

Experience of having been sexually abused: Several reports showconcordantly that sexual offenders against children who have beenabused in childhood themselves, are more likely to developpaedophilic interest (e.g., Nunes et al., 2013). However, theevidence for this relationship in non-offender groups is substan-tially weaker (Fromuth et al., 1991) and, only a small proportion ofsexually abused children develop paedophilia. There is evidencethat this association might be moderated by further environmentalfactors (for instance, experiences of neglect in childhood, lack ofparental supervision, intrafamilial violence, poor parent-childattachment; Marshall and Marshall, 2000; Salter et al., 2003), andcertain characteristics of the experienced abuse (duration, timing,use of violence, penetration, relationship to the perpetrator, havingperpetrators of both sexes; Burton et al., 2002). The exactmechanism by which history of being sexually abused increasesthe likelihood of developing paedophilia is unknown. Theoretical-ly, learning mechanisms (e.g., imitation) as well as the facilitationof attitudes and beliefs supporting adult-child-sex are assumed(Seto, 2008). An alternative explanation for the facts that not allsexually abused children and not all children who had sexualcontact with other children develop paedophilia is an interactionwith biological factors, such as genetic predisposition.

Genetics: First clues regarding potential genetic influences onpaedophilia came from a study by Gaffney et al. (1984).Retrospectively reviewing medical records they found thatpaedophilia was significantly more prevalent in first-degreerelatives of patients fulfilling DSM-III criteria for paedophilia thanin families of patients with non-paedophilic paraphilias ordepression. While this investigation was limited by its smallsample size (n = 33 paedophilic patients, n = 21 non-paedophilicparaphilic patients, n = 33 depressed patients) and did not rule outalternative explanations for the familial accumulation, a largerrecent study by Alanko et al. (2013) gives further support for theassumption of genetic underpinnings. In the population-basedFinnish sample, the amount of non-additive genetic variance thatcould be accounted for sexual interest in children and youth belowthe age of 16 was 14.6%. However, this percentage also emphasizesthe importance of environmental factors.

Neurodevelopmental perturbations: Further research on thebiological aetiology of paedophilia mostly builds on the assump-tion, which is based on a multitude of indirect evidence, thatpaedophilia could result from neurodevelopmental abnormalities.There are reports of neuropsychological deficits including lowerintelligence, impaired response inhibition, dampened attention,reduced verbal and visuospatial learning abilities, slower proces-sing speed, diminished task switching, and cognitive reasoningabilities as well as an increased rate of left-handedness

(Cantor et al., 2004; Joyal et al., 2014; Kruger and Schiffer,2011; Schiffer and Vonlaufen, 2011). Additionally, Blanchard et al.(2002, 2003) detected an increased rate of head injuries withtemporary unconsciousness in paedophilic sex offenders. Impor-tantly, only the incidence of head injuries before the age of 13 waselevated in paedophiles, which points to possibly damaging effectson neuronal development.

Recent research began to shed light on the manifestations of thepresumed neurodevelopmental disruptions by exploring abnor-malities in brain function and structure. The aim of this paper is toreview the neuroimaging literature on paedophilic men to providean overview of published findings concerning abnormalities inbrain anatomy and functional processing during visual sexualstimulation. Historically, the first clues on brain structuresimplicated in paedophilic sexual arousal stem from severalneurological case reports describing paraphilia-like behaviourthat occurred with brain pathology. Therefore, we will start bysummarizing the findings from these case studies.

1.5. The neurophenomenological model of sexual arousal

A framework helpful to interpret the reviewed findings is theneurophenomenological model of sexual arousal (Fig. 2; Redouteet al., 2000; Stoleru et al., 1999). This model attempts to explain thespecific roles of different brain regions typically activated inhealthy men during stimulation with sexually arousing stimuli(Kuhn and Gallinat, 2011; Poeppl et al., 2014; Stoleru et al., 2012).It assigns sexual stimulation to intertwined psychological sub-processes: a cognitive component comprises the evaluation ofstimuli as sexually incentive (mediated by activity of the rightlateral orbitofrontal cortex and inferior temporal gyrus), the focusof attention on these stimuli (superior and inferior parietal lobule),and the motor imagery of potential sexual behaviour (ventralpremotor area, supplementary motor area, inferior parietal lobule,and cerebellum). The experience of the hedonic quality of sexualarousal is provided by an emotional component (somatosensorycortex, amygdala, and posterior insula), while a motivationalcomponent would orientate behaviour towards the desired goaland enable the perception of sexual desire (anterior cingulatecortex, claustrum, posterior parietal cortex, hypothalamus, sub-stantia nigra, and ventral striatum). A physiological componentwould control various somatic responses in order to prepare theorganism for sexual behaviour (anterior cingulate cortex, anteriorinsula, putamen, and hypothalamus). Last, the model proposesdifferent inhibitory processes, which include the prevention ofemergence of sexual arousal in unsuitable situations and cognitiveappraisal to reduce the incentiveness of stimuli (medial and leftlateral orbitofrontal cortex, and lateral temporal cortex) as well asthe control of executed sexual behaviour (caudate and caudalanterior cingulate cortex). When discussing the neural correlatesof paedophilia we will refer to this model, which might give furtherinsights into the meaning of the observed abnormalities.

1.6. Literature search

An extensive literature search was conducted using theelectronic databases PubMed, ISI Web of Science, and PsycInfoin order to identify all relevant articles published until April 2014.We used the following search terms in the title, abstract orkeywords: (‘‘pedophil*’’ or ‘‘child molest*’’ or ‘‘sexual abuse’’ or‘‘sexual offend*’’) and (‘‘imaging’’ or ‘‘magnetic resonance imaging’’or ‘‘computed tomography’’ or ‘‘positron emission tomography’’ or‘‘brain’’). Additional papers were searched by checking theliterature cited in the articles identified by the electronic databasesearch. Studies were included if they provided original data on (a)brain damage associated with paedophilia or sexual offending

Fig. 2. The neurophenomenological model of sexual arousal.

Adapted from Stoleru et al. (2012).

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–23 5

against prepubescent children, (b) structural neuroimaging insubjects diagnosed with paedophilia or who sexually offendedagainst prepubescent children or (c) functional neuroimagingstudies on sexual arousal processing in paedophiles or CSOs. Bothcase reports and studies comparing samples of paedophilicsubjects or CSOs against controls were included.

2. Neurological case reports

Before controlled imaging studies were available, the firstevidence implicating brain structures in paraphilia-like behaviourswas provided by neurological case reports. These reports show thatpaedophilic behaviour can be provoked by a variety of diseasessuch as brain tumours, different forms of dementias, Parkinson’sdisease, Huntington’s disease, hippocampal sclerosis as well asencephalitis, and may also result from surgical treatment, e.g.,temporal lobotomy or pallidotomy (see Table 1). In the followingsection we will review the literature pertaining to these casesseparately for the different diagnoses. We only consider reportsabout sexual behaviour or interest in prepubescent children. Thereare some papers in which sexual interest in pubertal children wastermed paedophile, which will not be discussed here.

2.1. Brain tumours

There are reports of CSA emergent from brain neoplasms in fourmarried men (Table 1). In three cases these were located in theright frontal lobe: medial paracentral (Lesniak et al., 1972), medialorbitofrontal (Burns and Swerdlow, 2003), and not further

specified in one case (Regestein and Reich, 1978). Another patientsuffered from a brainstem glioma additionally affecting the pons,ventral midbrain, thalamus, and hypothalamus, which affectedboth hemispheres, but was more pronounced in the lefthemisphere (Miller et al., 1986). In addition to the abuse ormolestation of children, an increase of general sexual interest, thepreoccupation with sex or a disinhibition of sexual behaviour wascommon to all cases. Therefore, none of the abnormalities werelimited to CSA, but instead suggested general hypersexuality.Furthermore, the abnormalities were not isolated to symptoms onthe sexual level; patients exhibited personality changes andimpulsivity (Burns and Swerdlow, 2003; Lesniak et al., 1972;Regestein and Reich, 1978) or diminished financial judgement(Miller et al., 1986). Three of these patients were testedneuropsychologically (the one not tested was described to havenormal intelligence; Miller et al., 1986) and demonstrated deficitsincluding reduced intelligence (Lesniak et al., 1972), reducedcognitive flexibility and attention (Regestein and Reich, 1978), anddisturbed memory recall, apraxia and agraphia (Burns andSwerdlow, 2003). In light of this additional symptomatology itappears unlikely that the tumours caused a specific change insexual preference. The variety of symptoms reported rather speakin favour of the assumption that the neoplasms led to unspecificdisinhibition, which also affected sexual experience and behaviour,thereby increasing the risk for sexual abusive behaviour. It isconceivable that such a disinhibition could result in acting outpremorbid paedophile interest (Burns and Swerdlow, 2003;Mendez and Shapira, 2011). An elevated sexual drive alone couldpotentially lead to behaviours involving minors of age even in the

Table 1Summary of case reports of paedophilic behaviour occurring with neurological disorders.

Refs. Age Diagnosis/Localization Paedophilic symptoms Further symptoms Neuropsychological

findings

Brain tumours

Lesniak et al. (1972) 56 Right-sided medial-

paracentral glioma or

meningioma

Sexual intercourse with

minor daughter, bathing

nude with children of both

sexes, exposition of penis

in front of children and

encouragement to touch

it, urination into the face

of minor boy

Sodomy, masochism, sadism,

repeated sex proposals to

different woman, impulse

control problems, personality

changes

Reduced intelligence

Regestein and Reich (1978) 56 Right-sided frontal

meningioma

Multiple molestation of

pre- and pubertal children

of both sexes

Increased sexual desire, more

frequent sexual intercourse

with wife, personality

changes, inability to sustain

erection, inability to learn

new music

Reduced attention and

cognitive flexibility

Miller et al. (1986) 34 Brainstem glioma involving

the thalamus, hypothalamus,

ventral midbrain and pons

(more pronounced in left

hemisphere) Idiopathic

hydrocephalus, Weber‘s

syndrome, Benedikt‘s

syndrome, hypothyroidism

Multiple sexual advances

towards young children,

including prepubertal

daughter

Collection of pornography,

difficulties with erection and

ejaculation, conversation

filled with sexual innuendo,

showing pornographic

pictures to visitors at home,

personality changes, poor

financial judgement

Normal intelligence

Burns and Swerdlow (2003) 40 Right-sided orbitofrontal

hemangiopericytoma

Interest in child

pornography, advances

towards prepubertal

stepdaughter, denied

previous attraction to

children

Increased sexual desire

(pornography, incl. child

pornography), sexual

advances towards female

medical staff and other

patients, suicidal ideation,

balance problems, urinated

on himself being

unconcerned of it; severe

headaches

Delayed recall, agraphia,

apraxia

Dementias

Mendez et al. (2000) 60 Frontotemporal dementia

(hypometabolism in right

inferior temporal region,

more subtle left)

Molestation of

prepubertal children,

exhibitionism

Sexualized behaviour,

disinhibited and aggressive

behaviour, compulsive

behaviour, decline in social

and personal awareness,

decreased judgement

Verbal stereotypies, mild

echolalia, diminished

memory and executive

functions

Mendez and Shapira (2011) 67 Frontotemporal dementia

(frontal atrophy and

hypoperfusion, more

pronounced in right

hemisphere)

Sexual advances towards

daughters

Preoccupation with sexuality,

multiple daily sexual

advances towards wife,

fondling of wife in public,

touching of women’s breasts

in magazines, decline in work

performance, disinhibited

behaviour, compulsive

behaviour

Reduced verbal fluency,

diminished memory and

executive functions

Mendez and Shapira (2011) 82 Vascular dementia following

stroke (subcortical lacunes in

left caudate head and right

globus pallidus,

hypometabolism in right

posterior cingulate cortex)

Molestation of

stepdaughter

Frequent masturbation,

talking about sex, sexualized

language, inappropriate

touching of others,

disinhibited behaviour

Deficits in attention,

verbal fluency, working

memory, executive

functions and visuospatial

construction

Rainero et al. (2011) 49 Frontotemporal dementia

(bilateral frontal atrophy and

hypoperfusion)

Sexual arousal and urges

towards 9-year-old-

daughter

Mutation in PGRN verbal and

physical hetero-directed

aggressive behaviour, no

further disinhibition

Mild episodic memory

impairment

Parkinson’s disease

Berger et al. (2003) 57 Unknown Repeated sexual

molestation of 10-year-

old boy and 6-year-old girl

Increased sexual urges,

problems with erections and

orgasms

Below average

intelligence

Mendez and Shapira (2011) 59 No known abnormalities Interest in child

pornography

Increased sexual urges, use of

pornography (incl. child

pornography)

No abnormalities

Mendez and Shapira (2011) 59 Pallidotomy, no further

abnormalities

Molestation of 5-year-old

granddaughter,

masturbation while

viewing photo of

granddaughter

Increased sexual urges

(hiring strippers and

prostitutes, use of

pornography, intrusive

sexual thoughts, forced wife

to have sex with him several

times a day, propositions to

wife’s female friends)

No abnormalities

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–236

Table 1 (Continued )

Refs. Age Diagnosis/Localization Paedophilic symptoms Further symptoms Neuropsychological

findings

Further neurological disorders

Fairweather (1947) 24 (of 154) patients with

postencephalitic

parkinsonism

Sexual molestation of

‘‘little girls’’

Unknown Unknown

Mendez et al. (2000) 67 Hippocampal sclerosis

(volume loss in mesial

temporal lobes and

hypometabolism in right

temporal lobe)

Molestation of 5-year-old

boy; son of patient

reported to have been

molested by him in

childhood

Sexual preoccupation, past

drug abuse, advances

towards female physician

Deficits in working

memory

Devinsky et al. (2010) 39 Epilepsy (symptoms started

after resecting posterior

temporal parts)

Use of child pornography Hypersexuality, coprophilia,

more frequent masturbations

and sexual intercourse with

wife, increased use of

pornography (incl. child

pornography)

Unknown

Mendez and Shapira (2011) 32 Huntington’s disease

(bilateral atrophy of caudate

and putamen nuclei;

hypometabolism of striatum)

Inappropriate touching of

6-year-old girl

Verbally and physically

aggressive, constricted affect,

moodiness, depression,

irritability, disorganization

Deficits in verbal fluency

and executive functions

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–23 7

absence of paedophilic preference. It might foster an unselectivesearch for sexual partners. The neurophenomenological modelsupports this interpretation since behavioural control functionsare ascribed to the implicated medial frontal areas (Redoute et al.,2000; Stoleru et al., 1999).

2.2. Different forms of dementias

There are three reports of frontotemporal dementia (Mendezand Shapira, 2011; Mendez et al., 2000; Rainero et al., 2011) andone of vascular dementia following stroke (Mendez and Shapira,2011) leading to sexual child molestation. Two men withfrontotemporal dementia exhibited frontal hypoperfusion andatrophies, while one had no structural abnormalities on themagnetic resonance imaging (MRI) scan; however, positronemission tomography (PET) revealed right anterior temporalhypoperfusion that may have been extended into the orbitofrontalcortex. Computed tomography (CT) of the patient with vasculardementia showed subcortical lacunes in the left caudate head andthe right globus pallidus while PET additionally revealed ahypometabolism in the right posterior cingulate. Three of thesefour men showed hypersexual behaviour not limited to children.This provides further evidence that brain pathology led todisinhibition rather than to a specific change in sexual agepreference. Additionally, in all cases personality changes, as well asobsessive-compulsive, impulsive or hetero-directed aggressivebehaviour were described. Furthermore, all patients also sufferedfrom neuropsychological deficits in executive functions, memory,attention, verbal fluency, visuospatial abilities or demonstratedverbal stereotypies, and echolalia. These reports suggested that thetemporal cortex, the basal ganglia, and the frontal regions, areinvolved in CSA via disinhibited sexual behaviour. A disinhibitedsexual drive following lesions of the temporal lobes and theamygdala is a well-known symptom of the Kluver–Bucy syndrome.Kluver and Bucy (1939) concluded that the temporal cortex exertsan inhibiting function on sexual behaviour. This is in line with theneurophenomenological model (Redoute et al., 2000; Stoleru et al.,1999), which ascribes inhibiting and action control functions to theimplicated structures.

2.3. Parkinson’s disease

CSA was also reported to occur in male patients suffering fromParkinson’s disease (Berger et al., 2003; Mendez and Shapira,

2011). As in most cases described above, CSA did not arise in anisolated manner, but in the context of marked hypersexuality. Inone patient the symptomatology appeared after a right pallidoto-my, which he underwent after suffering from Parkinson’s diseasefor 16 years (Mendez and Shapira, 2011). As for the other twoexamined patients, neuroimaging did not reveal any structuralalterations (Mendez and Shapira, 2011). All of these cases weremedicated with dopamine agonists, and no further psychiatric orneuropsychological abnormalities were reported. Despite asexually satisfying relationship with his wife, the patient describedby Berger et al. (2003) seems to have been aware of a pre-existingpaedophilic disposition. However, he never acted on it until hiswife refused sexual contact, which was mainly due to the patient’serectile and orgasmic dysfunctions. These symptoms developed atthe same time as an increased libido. Both followed dopaminergicmedication and were even more pronounced after the patientincreased medication on his own authority. This supports the ideathat brain pathology can lead to paraphilia-like behaviour withoutchanging an actual existing sexual preference. Instead, neuralalterations might have dampened inhibiting mechanisms, whichallowed for the manifestation of aberrant sexual behaviour,especially in the absence of other possibilities to act on stronglyincreased sexual urges. While again underlining a possible role ofthe pallidum, this also implies that anatomical abnormalities mustnot be a necessary prerequisite for the exertion of CSA, pointing tothe importance of changes on the functional level. This is furthersupported by the fact that all patients received dopaminergicmedication, which implies a potential role of this transmittersystem in evoking hypersexuality. A recent cross-sectional studyon 3090 patients with Parkinson’s disease confirmed effects ofdopaminergic drugs on impulse control disorders, includingcompulsive sexual behaviour (Weintraub et al., 2010). A possibleexplanation is that some substances non-selectively bind todopamine D1 and D2 receptors mainly located in the dorsalstriatum, and probably mediating motor effects, but also to D3

receptors abundant in the ventral striatum. The ventral striatum(which includes the pallidum) is well-known to be associated withbehavioural addiction and substance dependence (Potenza, 2013;Schacht et al., 2013). Dopaminergic medication has repeatedlybeen shown to alter activity of brain areas involved in reward andmotivation (Kassubek et al., 2011). A functional magneticresonance imaging (fMRI) investigation suggests that suchdopamine-mediated effects might already occur in very earlystages of sexual arousal processing. Oei et al. (2012) presented

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–238

healthy males with sexual photographs, which were shown so fast,that they could not be processed consciously. During thissubconscious processing, dopamine administration led to in-creased brain activation in brain regions associated with themotivational component of sexual arousal (Redoute et al., 2000;Stoleru et al., 1999), namely the nucleus accumbens and dorsalanterior cingulate. Since these regions are thought to regulatebehavioural drive towards a desired target (‘‘wanting’’; Berridgeand Robinson, 1998), dopaminergic medication could contribute tocompulsive behaviour as a result of stimulating a ‘‘running start’’ ofthis circuit.

2.4. Further neurological disorders

There are isolated accounts of CSA in other disorders. Mendezand Shapira (2011) described a patient suffering from Huntington’sdisease, who had bilateral atrophy of the caudate and putamennuclei as well as striatal hypometabolism. In one instance this maninappropriately touched a 6-year-old-girl. Amongst other symp-toms, he had impulse control problems, heightened irritability andaggression, and executive deficits. Another patient suffering fromhippocampal sclerosis had bilateral mesial temporal volumereductions and right temporal hypometabolism (Mendez et al.,2000). While also showing increased sexual interest and preoccu-pation, this man was reported to have molested prepubescent andpubescent boys. Clues for a possible premorbid paedophilicinterest existed, particularly the patient’s son claimed to havebeen molested by him as a child. Devinsky et al. (2010) reported apatient suffering from epilepsy, who began collecting childpornography following a second temporal lobotomy. Interestingly,this activity as well as hypersexuality did not evolve until hissecond temporal lobotomy during which more posterior temporalareas were resected. The first surgical intervention, in which moreanterior temporal regions and the amygdala were removed, did notentail the symptomatology. Finally, Fairweather (1947) noted thatin his sample of 154 postencephalitic male patients, 24 hadcommitted sexual offences against ‘‘little girls’’.

In none of the above cited cases, brain pathology specificallyled to paedophilia. Rather, in the majority of cases CSA occurredin the context of hypersexuality, broader changes in personality,impulse control problems and/or neuropsychological deficits.Thus, a change in sexual age preference caused by the involvedpathological processes may not be a sufficient explanation for thefull spectrum of symptoms observed. It is more likely that theabnormalities resulted in reduced behavioural control leading topaedophilia-like behaviour on the background of a premorbidsexual interest in children or a lack of more preferred sexualpartners. Brain damages described were located mainly frontal,temporal or within the basal ganglia. According to theneurophenomenological model (Redoute et al., 2000; Stoleruet al., 1999) these structures are implicated in inhibition andappraisal processes, which fits well with the interpretation madeabove.

Case reports naturally suffer from the shortcoming that they arebased on observations of single patients. In these studiespaedophilic preferences often have not been diagnosed thorough-ly. These studies were the first to uncover brain regions, whichcould provide evidence for why some patients act out abnormalsexual interests. It should be stressed that patients who acted ontheir urges were investigated, which could be the reason for thedetection of areas primarily implicated in control processes. Inorder to identify brain regions involved in the sexual preference forchildren, diagnosed paedophile patients would have to be directlycompared to non-paedophile control subjects. This has beenaccomplished in several neuroimaging studies conducted withinthe last years, which we will discuss in the following sections.

3. Neuroimaging

In this section we will review structural (Section 3.1) andfunctional neuroimaging studies (Section 3.2) on paedophilia. Inaddition to identifying brain areas associated with sexual arousalprocessing in paedophilia and analysing differences in brainstructure and function compared to a control group, numerousstudies also reported correlations between brain volume oractivity and parameters for paedophilic interest, offence char-acteristics or psychopathology. These results are discussed inSection 3.3.

3.1. Structural neuroimaging

3.1.1. CT studies

The first studies on structural brain abnormalities in paedo-philes employed CT. Graber et al. (1982) observed reduced braindensity in three men who had molested children (judging from thecase reports at least two of these did not show exclusivepaedophilic interest). This was also found by Hendricks et al.(1988) who collected data from 12 men incarcerated because ofmolestation of children or adolescents (no diagnosed paedophiles),10 patients from radiology without cerebral abnormalities, and 16healthy controls. The control group was inadequate since itincluded women (three in the radiology patient group and two inthe healthy control group), whereas all CSOs were male. Huckeret al. (1986) found enlargement of the left temporal and anteriorhorns to be more common in paedophilic sex offenders (n = 41)than in a non-sex offender control group (n = 14). Yet, these resultswere not replicated in subsequent CT studies (Langevin et al., 1989,1988; Wright et al., 1990). However, Wright et al. (1990) notedgreater brain asymmetry in paedophiles, mostly with smaller left-hemispheric widths, which was mainly attributable to thetemporal lobe. While the results from these studies are hardlycomparable, two of them implicate some temporal abnormalities.These abnormalities seem to be unspecific, since they were notonly present in paedophilic sex offenders (all CT studies werecarried out with forensic samples), but also in other sexuallyaggressive men (e.g., non-paedophilic incest offenders; Langevinet al., 1988). This further supports the notion that temporalabnormalities might play a role in disinhibited behaviour. Besidesthe low spatial resolution, CT studies are limited to the analyses offrequencies of rater-classified structural pathology, therebypossibly missing more subtle abnormalities. In addition, conclu-sions about paedophilia from these reports are impossible becausethe necessary distinction between paedophilic men and CSOs ismissing.

3.1.2. MRI studies

The first study using MRI to study structural brain abnormali-ties in a sample including paedophilic men was conducted inAustria. Eher et al. (2000) investigated a sample of 38 imprisonedsexual offenders of which 15 had offended against minors andeight met diagnostic criteria for paedophilia. Similar to previous CTstudies, and unlike subsequent MRI studies (which used morequantitative methods, see below), a qualitative analysis approachwas chosen investigating narrative reports of neuroradiologists.These were coded for the presence of brain abnormalities andsubsequently, respective frequencies were compared betweengroups. In a total of 38 sexual offenders, 17 were found to havestructural abnormalities: four cortical atrophy, one periventricularlesions, six deep white matter lesions, one ventricular enlarge-ments, and five multiple lesions. Additionally, in offenders withoutanatomical abnormalities self-perceived aggressiveness was cor-related with self-reported interpersonal problems, and socialanxiety. This association with aggressiveness was not found in the

Table 2Summary of structural MRI studies.

Refs. Sample Sexual orientation Medication Method Main findings Significance

Schiltz et al. (2007) 15 CSO, inpatient

15 community

controls

Exclusive-type

paedophilia in at

least 13 CSOs

Gender orientation

unknown

None in at

least 13 CSOs

VBM/MM GM reductions in

paedophiles:

Amygdala R,

Hypothalamus L/R,

Innominate substance L/R,

Bed nucleus striae

terminalis L/R, Septal

region R

Enlargement of the

temporal horn R in

paedophiles

p < .05 corrected

for multiple

comparisons

within ROIs

Schiffer et al. (2007) 18 CSO, inpatient

24 community

controls

Exclusive-type

paedophilia

Attracted to males:

9 paedophiles

12 teleiophiles

None VBM GM reductions in

paedophiles:

Cerebellum L/R*, Inferior

frontal gyrus L/R*,

Cingulate gyrus L/R*,

Posterior cingulate gyrus

L*, Insula L/R*, Precuneus

L/R, Parahippocampal

gyrus L/R*, Superior

temporal gyrus L/R,

Middle temporal gyrus R,

Putamen L/R*

(Amygdala L/R in

unpublished re-analysis)

p < .05 FDR

corrected for whole

brain

*Additionally

p < .05 FWE

corrected within

ROIs

Cantor et al. (2008) 44 CSO, outpatient

(paedo- &

hebephilic)

53 NSO, outpatient

Unknown Unknown VBM/MM WM reductions in paedo-

and hebephiles:

Superior fronto-occipital

fasciculus L, Arcuate

fasciculus R

p < .05 FDR

corrected for whole

brain

Cantor & Blanchard

(2012)

19 paedophilic CSO,

outpatient

49 hebephilic CSO,

outpatient

47 NSO, outpatient

Unknown Unknown MM WM reductions in paedo-

and hebephiles in bilateral

temporal (p = .04) and

parietal lobes (p = .06)

p < .05 uncorrected

(2 models)

Poeppl et al. (2013) 9 CSO, inpatient

11 NSO, inpatient

Exclusivity of age

preference

unknown

Attracted to males:

7 paedophiles

0 teleiophiles

None VBM GM reduction in

paedophiles:

Amygdala R

p < .05 FWE

corrected within

ROIs

Annotations: MRI magnetic resonance imaging, CSO child sex offender, NSO non-sex offender, VBM voxel-based morphometry, MM manual morphometry, ROI region of

interest, L/R left/right, GM grey matter, WM white matter, FWE familywise error correction, FDR false discovery rate.

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–23 9

17 offenders with structural abnormalities. Eher et al. (2000)speculated that the observed multi-locus alterations might lead toviolent behaviour by interfering with social information proces-sing. Although the study’s findings were interesting, the reportedresults are unspecific and the localization of anatomical abnor-malities remains unclear. Furthermore, conclusions regarding thepaedophilic subgroup are impossible (although this was not themain aim of the investigation), because paedophilic CSOs wereanalysed jointly with CSOs without paedophilia. Last, a controlgroup was missing.

Further MRI studies appeared from 2007 onwards. These usedhigher spatial resolution (Eher et al. (2000) employed a T2-weighted spin-echo imaging sequence in axial plane with a slicethickness of 5 mm at 0.5 Tesla, while subsequent studies utilizedT1-weighted 3-dimensional sequences with a maximum slicethickness of 1.5 mm at 1.5 Tesla), more sophisticated quantitativeanalysis methods and focused investigation of well-definedpaedophilic samples (diagnosed by structured clinical procedures).To date, five such studies have been published (summarized inTable 2), with three of them conducted with German samples andtwo stemming from Canada, with the latter two relying on thesame data set. Overall 61 paedophilic (and 49 hebephilic men;Cantor and Blanchard, 2012) and 103 teleiophilic men were

included in these studies. In four of the investigations voxel-basedmorphometry (VBM) was used for data analysis. Two studiesadditionally employed traditional morphometry; one study used itexclusively. In the following sections we will review the resultsconcerning group differences between paedophiles and teleio-philes from these studies (see Fig. 3 for a summary ofmethodological details).

The first published study by Schiltz et al. (2007) analysed MRIdata of 15 paedophilic sex offenders recruited from a forensicclinic, and 15 community controls using VBM and manualmorphometry. Six of the paedophile patients had committedoffences exclusively against girls, three exclusively boys, and sixagainst both sexes. Further sample characteristics were notreported, but as Schiltz et al. (2007) analysed data from the samesample as Walter et al. (2007) (see Section 3.2.2.2 and Tables 2 and4), it can be concluded that at least 13 of the 15 patients wereexclusively oriented towards children and did not receivemedication (Walter, personal communication). The VBM resultswere restricted to four predefined regions, known to be associatedwith the regulation of sexual function: (1) The left and (2) rightamygdala, (3) the bilateral septal region and the bed nucleus striaeterminalis as well as the (4) hypothalamus and the substantiainnominata. The authors employed a significance level of p < .05,

Fig. 3. Relevant methodological specifics of MRI studies. See refs. (Ashburner and Friston, 2000; Genovese et al., 2002; Kriegeskorte et al., 2009).

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–2310

corrected for multiple comparisons within these regions of interest(ROIs). VBM and manual morphometry exhibited a reduction ofright amygdala volume accompanied by an enlargement of theright temporal horn in paedophilic offenders. While manualmorphometry showed a similar effect for the left amygdala, thiscould not be confirmed by VBM. VBM did reveal volume reductionsin all other ROIs. Schiltz et al. (2007) suggested that neurodevelop-mental problems cause the abnormalities, proposing that adysfunction of the structures implicated might interfere withsexual maturation. They further speculated that a devaluation ofinfantile sexual interest, which would usually develop duringpuberty, might not occur (Freund and Kuban, 1993).

The second study was published by Schiffer et al. (2007),applied VBM and compared 18 paedophilic inpatients with 24controls. The sample did not differ significantly in age,

handedness, and gender orientation. In both groups, 50% ofparticipants were exclusively attracted to males, while the other50% were exclusively attracted to females. The paedophilicpatients were exclusively attracted to prepubescent children andthey were not medicated. The authors applied both whole brain(thresholded at p < .05, false discovery rate correction, FDR) aswell as ROI analyses (p < .05, familywise error correction, FWE)carried out if an a priori ROI was significant at an uncorrectedthreshold of p < .001 and a cluster extent of k � 100 voxels) totheir data. Assuming a relation of paedophilia to obsessive-compulsive spectrum disorders, Schiffer et al. (2007) predictedassociations within the frontrostriatal, limbic system, insulo-opercular segments, and cerebellum. The whole brain analysisyielded grey matter reductions in paedophilic patients in thebilateral orbitofrontal cortex, insula, ventral striatum (putamen),

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–23 11

cingulate, precuneus, parahippocampal gyrus, superior temporalgyrus, cerebellum, left posterior cingulate, and the right medialtemporal gyrus. Of the 15 ROI analyses carried out additionally,only an effect in the left parahippocampal gyrus would remainstatistically significant at p < .05 FWE if one applied Bonferronicorrection (for the 15 separate tests). Consistent with theirhypothesis, the authors interpreted their results as evidence forrelatedness of paedophilia with the obsessive-compulsivespectrum. In addition, in an unpublished post hoc analyses ofthe data, Schiffer (personal communication) confirmed ROI-corrected (p < .05 FWE) volume reductions within the bilateralamygdala, consistent with the results of Schiltz et al. (2007).

The third German study in which data of paedophilic patientswere analysed with VBM was published by Poeppl and colleaguesin 2013. They compared nine unmedicated paedophilic CSOs with11 non-sexual offenders (NSOs, who had mainly committedproperty offences). Importantly, as both groups were recruitedfrom forensic high security hospitals, the authors controlled forpotential effects of forensic inpatient status. Seven of thepaedophilic patients were attracted to males but none of thecontrols, which limits interpretability of the results. Moreover,information regarding the exclusivity of paedophilic interest islacking and the paedophilic group was significantly older than theNSOs. The authors applied whole brain analyses and small volumecorrections for all regions in which Schiltz et al. (2007) and Schifferet al. (2007) found grey matter reductions at a FWE correctedsignificance level of p < .05. The only region for which Poeppl et al.(2013) replicated grey matter reductions in was the rightamygdala, although this finding would not reach the requiredsignificance threshold if corrected for the number of ROI analyses,as the authors remark themselves. The authors concluded that ananatomical reduction of amygdala volume may not directly causepaedophilia. Instead, in line with Schiltz et al. (2007), theysuggested that the observed abnormality might be evidence for adeficient developmental differentiation of this structure. Further,this aberrant differentiation could result in the non-initiation of adevaluation process of infantile erotic interest.

In addition to the three German studies described above, Cantoret al. (2008) examined a Canadian sample of 44 CSOs who eitherconfirmed paedophilic interest in a diagnostic interview, showed astronger phallometric response to photos of children compared toadults or (when phallometry was not available or unusable) hadcommitted at least one sexual offence against a child below the ageof 14. Hence, although the collection of phallometric data is astrength of this study, the diagnostic heuristic leaves thepossibility that non-paedophilic offenders might have beenincluded here, since children below the age of 14 might very wellhave reached puberty and because there may be other reasons thanpaedophilia to molest children (see Section 1.3). In the offendergroup, 91% of men had molested girls and 32% had molested boys.No further information regarding sexual preference or medicationwere given. The control group consisted of 53 non-paedophilicNSOs, who did not differ from the patient sample in age,intelligence, years of education, and handedness. A majordifference to the other studies is that subjects were notincarcerated but on probation or parole. In addition to VBM, theauthors manually parcellated 39 regions for which they testedgroup differences combined in four models (for cortical andsubcortical grey matter, white matter, and cerebrospinal fluid) tocircumvent multiple testing. Only whole brain analyses correctedfor FDR were performed. With both techniques, no groupdifferences in CSF or grey matter were observable, which standsin contrast to the three German reports. Instead, manualmorphometry pointed to temporal and parietal white matterdeficiencies in the CSO group. Consistent with this, VBM showedthat especially two regions were involved here:

‘‘The larger region followed the superior fronto-occipitalfasciculus; it ran along the dorsal border of the caudatenucleus, extending posteriorly toward the occipital pole andextending anteriorly to terminate primarily in the middlefrontal gyrus. The anterior extension appeared also to terminatein two other, weaker clusters, one in the frontal operculum andone in the opercular part of the inferior frontal gyrus. [. . .] Thesecond region occurred only in the right hemisphere, followingthe arcuate fasciculus from the parietal opercular region to thetemporal opercula, wrapping around the posterior extension ofthe Sylvian fissure and descending to the inferior temporal andfusiform gyri’’ (Cantor et al., 2008, p. 137).

In addition, a phallometric paedophilia index score correlatedwith brain regions that largely overlapped with the areas revealedby the manual and voxel-based morphometry analyses (see alsoSection 3.3 and Tables 2 and 7). This study had some majormethodological strengths like the large sample, availability ofphallometric data, stringent statistics, and the inclusion of a NSOcontrol group. However, the results were limited by the possibilitythat hebephilic subjects might have been included in the data set; alimitation which led to a reanalysis by Cantor and Blanchard(2012).

The reanalysis, based on phallometric data or self-report,classified subjects as paedophilic if there was evidence for sexualinterest in children below 10 years of age, hebephilic for interest inchildren between 11 and 14 years and teleiophilic if both thephallometric response as well as self-report confirmed interest inmen and women older than 17 years, and no sexual offencesagainst minors were known. Accordingly, 19 subjects wereclassified as paedophilic (as opposed to 44 in the originalanalysis), 49 as hebephilic, and 47 as teleiophilic. There was nodifferences in age or years of education between these groups. Theanalyses were restricted to a manual morphometric examinationof those regions for which significant reductions were foundpreviously (Cantor et al., 2008), namely the white matter portionsof bilateral temporal and parietal lobes. The analyses showed nodifferences between paedophilic and hebephilic subjects fortemporal white matter but reduced volumes in both groupscompared to teleiophilic men. Group differences for parietalregions had a similar pattern, although these were onlymarginally significant (p = .06). Therefore, this reanalysis showedcomparable white matter abnormalities in paedophilia andhebephilia, although the spatial resolution here was low. Cantoret al. (2008) suggested that the observed white matter reductionscould be indicative of diminished connectivity between regionsinvolved in the processing of sexual arousal. However, connec-tivity analyses (techniques to investigate the interaction ofdifferent brain regions) or diffusion tensor imaging (DTI; AnMRI technique which allows inferences on white matter structureby measuring the diffusion of molecules, especially water) wouldbe needed to support this conclusion.

In summary, there is one structural MRI finding observed inthree of the four published samples. Schiltz et al. (2007), Schiffer(personal communication), and Poeppl et al. (2013) all foundamygdala volume reductions, pointing to disturbances in emo-tional processing of sexual arousal (Redoute et al., 2000; Stoleruet al., 1999). The fact that this finding was replicated twice ispromising, still, it requires further confirmation as the results wereobtained with multiple testing and at least in one case (Poepplet al., 2013) would not withhold statistical correction for these.Aside from this, the available investigations led to ratherheterogeneous results. While the three German studies conductedwith smaller samples found grey matter reductions in varyingbrain structures (Poeppl et al., 2013; Schiffer et al., 2007; Schiltzet al., 2007), studies relying on one Canadian data set showed

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–2312

white matter reductions exclusively (Cantor and Blanchard, 2012;Cantor et al., 2008).

3.2. Functional neuroimaging

3.2.1. PET studies

There are two studies already mentioned (Graber et al., 1982;Hendricks et al., 1988) in which, additionally to CT scans, PET wasemployed to investigate alterations in brain activity in CSOs.Results of both investigations showed reduced cerebral blood flowin the CSO groups. In the study by Hendricks et al. (1988) thisdifference was greater at anterior than posterior sites. In a furtherPET investigation Cohen et al. (2002) compared seven CSOsdiagnosed with non-exclusive paedophilia (attracted to girls) whounderwent an outpatient treatment with seven healthy controls.They used narrative scenarios about sexual contact between a manand either (a) a prepubescent girl, (b) a 30-year-old woman or (c)words from the dictionary being read out loud. During the lastcondition they observed diminished glucose metabolism inpaedophiles within the right inferior temporal gyrus and ventralsuperior frontal gyrus. In addition to no group differences duringthe condition of interest, observed effects were detected via ROIanalyses, of which a total of 120 were conducted. The authorsdiscuss that no effects survived correction for multiple compar-isons. Hence, although the results of Cohen et al. (2002) pointed toregions previously mentioned in case reports, these first resultsremained inconclusive and interpretability suffers from methodo-logical flaws like small sample sizes, unclear diagnoses and/orimprecise localizations.

3.2.2. fMRI studies

There are seven fMRI investigations and four single case reports(three of these primarily studied neural effects of antilibidinalmedication) on sexual arousal processing in paedophilia. A total of87 paedophilic and 100 teleiophilic men have been examined.Eight of these investigations were performed in Germany, two inSwitzerland, and one was conducted in France. Voxel-wiseanalyses over the whole brain were conducted in 10 of the 11studies. In the remaining study analyses were constricted to theamygdala.

In all of these studies erotic pictures were presented in order tocompare their neural processing in paedophilic men and non-paedophilic control groups. Erotic pictures typically were photo-graphs of children or adults, either nude or dressed in bathing suitsor underwear. These were compared to control conditions duringwhich either fully dressed people, people of a non-preferred age orneutral stimuli were shown. Some fMRI paradigms includedcontrol tasks, like pressing a button whenever a certain stimulusappeared on screen to ensure attention of subjects. Furtherinformation on the employed paradigms can be found in Table 4.Studies typically investigated the following questions:

(1) On the intra-group level: Which regions are activated duringvisual sexual stimulation?

(2) On the inter-group level: Are there differences in brain activitybetween paedophiles and control subjects during stimulationwith child and/or adult stimuli?

(3) On the inter-group level: Are there differences in brain activitybetween paedophiles and control subjects when only proces-sing of the respective arousing stimuli is taken into account(children in paedophiles and adults in teleiophiles)?

In the following sections, we will first review the publicationson sexual arousal processing in single cases using fMRI (Section3.2.2.1), before we will turn to studies providing group statistics onthat matter (Section 3.2.2.2). In addition, there are two further

fMRI studies on different psychological processes (responseinhibition and face processing) in paedophilic men, which aredescribed in Section 3.2.2.3.

3.2.2.1. fMRI case reports on sexual arousal processing and neural

effects of LH-RH agonists. To date, four case reports providing dataon sexual arousal processing in paedophilic CSOs have beenpublished (Table 3). All of the findings summarized in thefollowing section have to be taken cautiously because the resultswere acquired from individual subjects that probably showsubstantial inter-individual variability in activation patterns.Furthermore, they differed in their gender orientation, exclusivityof paedophilic preference, and medication status. Also, stimuli andstatistical analysis (such as contrasts and significance levels)varied across studies.

In three of the four fMRI case studies intra-subject contrastswere performed comparing the neural processing of preferred(nude children or children dressed in swimsuits) against non-preferred stimuli (dressed children or nude adults). There is someoverlap in activation of occipital areas, the right prefrontal cortex,anterior cingulate cortex, and superior temporal gyrus (Table 3).Activation of all of these areas have also been observed by groupstudies on paedophilic men (see Section 3.2.2.2 and Table 5).However, only two of these three studies can be compared directly(which is further complicated by imprecise coordinates given inone study; Dreßing et al., 2001). The findings reported by Schifferet al. (2009) were obtained from a patient who was on antilibidinalmedication for three months (while the others were not).Narrowing comparisons to the two remaining studies (Dreßinget al., 2001; Habermeyer et al., 2012) decreases concordantactivation to the fusiform gyrus. This is likely due to high inter-subject variability in brain activity because there is large overlapfor intra-group contrasts across respective studies (see Section3.2.2.2).

Because of the small number of subjects included, most authorsof case reports abstained from making direct comparisons betweenthem with the exception of Moulier et al. (2012). After masking outactivation observed in the control subject from the same contrastas analysed in the paedophilic patient (male children inswimsuits > female children in swimsuits), the patient showedadditional activity within the left calcarine fissure, left anteriorinsula, caudal anterior cingulate, and left cerebellar vermis. Thesefindings show little agreement with results from inter-groupcontrasts (Table 6), although, results of overall group comparisonsin general are quite inconsistent (see Section 3.2.2.2).

Finally, the main focus of three of the fMRI case reports was toinvestigate effects of pharmacological treatment with a long-acting luteinizing hormone-releasing hormone agonist (LH-RH,leuprolide acetate) on neural activation in paedophilia. LH-RHagonists were shown to suppress deviant sexual urges andarousability (Rosler and Witztum, 1998). The report by Schifferet al. (2009) only allows indirect comparisons of the activity foundin the medicated patient with those seen in their previousunmedicated sample (Schiffer et al., 2008b) at best, since he wasscanned only once while medicated. The lack of recruitment of anumber of areas involved in emotional, motivational, andautonomic aspects of sexual arousal (e.g., thalamus, amygdala,insula, substantia nigra, hippocampus, and the rostral anteriorcingulate), which the authors observed in their sample ofunmedicated paedophilic CSOs (Schiffer et al., 2008b), suggestedthat LH-RH agonists might primarily suppress subcortical brainactivity. Two longitudinal studies on LH-RH effects on neuralactivation used longitudinal designs, scanning the patient beforeand some months after the onset of treatment. Partially confirmingthe hypothesis by Schiffer et al. (2009), Moulier et al. (2012) foundthat after five months of leuprolide acetate treatment, activity was

Table 3Summary of fMRI case reports.

Refs. Subjects Treatment/Design Paradigm/Stimuli Main findings

Dreßing et al. (2001) Patient:

� Paedophilia,

attracted to boys

� CSO

� Age: 33 years

Controls (n = 2):

� Teleiophilia,

attracted to women

� Treatment unknown

� Cross-sectional

Passive viewing of women in

bathing suits or underwear, boys in

bathing suits or underwear, control

pictures without subjects or objects

of same colour intensity and

complexity; presented in

alternating blocks (19.2s/block)

� Stronger recruitment of the visual

cortex, brain stem R, ACC, PFC R, basal

ganglia R, OFC R during boys in bathing

suits only in paedophilic patient

� Fus L was stronger recruited during

boys in bathing suits in paedophilic

patient; in controls during photographs

of women

� Stronger recruitment of medial

temporal and left frontal areas in

controls, but not in patient

� Only qualitative comparison of intra-

subject/group contrasts; significance

level unknown

Schiffer et al. (2009) Patient:

� Paedophilia,

attracted to girls

� Exclusive-type

� CSO

� Age: 38.4 years

No control

� Trenantone

(leuprolide acetate)

11.25 mg/3 months

� Cross-sectional

Passive viewing of 7 photographs of

nude girls and 7 of nude women

presented alternating with 7 images

of dressed girls and 7 of dressed

women (38.5 s/image)

� Nude girls > dressed girls: IFG L, ACC

L, STG L, Cuneus R, MOG bil.

� Nude girls > nude women: DLPFC R,

STL L, SPL bil., MOG bil.

� No effects for the contrasts dressed vs.

undressed women and dressed girls vs.

dressed women

� Significance level unknown

Moulier et al. (2012) Patient:

� Paedophilia,

attracted to boys

� CSO

� Age: 46 years

Control:

� Teleiophilia,

attracted to women

� Age: 47 years

� Leuprorelin

(leuprolide acetate)

3.75 mg/4 weeks

� Mianserin

30 mg/day

� Supportive

psychotherapy

� Longitudinal (pre- vs.

on treatment, 5

months)

Passive viewing of photographs of

boys in swimsuits, girls in

swimsuits, dressed girls, women in

swimsuits, dressed women;

presented in separate 35 s runs, each

3 times

Same order of stimulus categories at

second treatment, but different set

of photographs to maintain degree

of novelty

� Boys swimsuits > girls swimsuits

(masked by this contrast in the control

subject): calcarine fissure L (p < .001,

corrected), AI L (p < .05, corrected),

caudal ACC (p < .001, corrected),

cerebellar vermis L (p < .01, corrected)

� All activations disappeared on

treatment ((T1 boys swimsuits > girls

swimsuits) > (T2 boys swimsuits > girls

swimsuits)); no significant changes in

control subject

� Multiple comparison correction

method unknown; ROI analyses in

some comparisons

Habermeyer et al.

(2012)

� Paedophilia,

attracted to boys

� Non-exclusive

type

� CSO

� Age: 43 years

No control

� Lucrin

� (leuprolide acetate)

11.25 mg/3 months

� Longitudinal (pre- vs.

on treatment, 10

months)

Passive viewing of 10 photographs

of boys and 10 of men in bathing

suits presented alternating with 10

images of dressed boys and 10 of

dressed men (38.5 s/image);

Adopted from Schiffer et al. (2008b,

2009)

Same picture set pre- and on

treatment

� Boys bathing suits > boys dressed:

Amy R, Fus R, STG

� Men bathing suits > men dressed:

Amy/PHc R, STG bil., Pre R, MFG R,

MedFG L, occipital R

� Conjunction ((Boys bathing

suits > boys dressed) & (Men bathing

suits > men dressed)): Amy/PHc R

� Nude boys vs. nude men: Lin L

Pre- > On Treatment: Amy R, SFG R,

MedFG L, MFG L, Pre R, STG bil.

� Significance level: p < .005

uncorrected (voxel-level), p < .05

corrected using Montecarlo

simulations (cluster-level)

Annotations: n sub-sample size, CSO child sex offender, s seconds, mg milligramme, L left, R right, ACC anterior cingulate cortex, PFC prefrontal cortex, OFC orbitofrontal cortex,

Fus fusiform gyrus, IFG inferior frontal gyrus, STG superior temporal gyrus, MOG middle occipital gyrus, DLPFC dorsolateral prefrontal cortex, STL superior temporal lobule,

SPL superior parietal lobule, AI anterior insula, Amy amygdala, PHc parahippocampal gyrus, Pre precentral gyrus, MFG middle frontal gyrus, MedFG medial frontal gyrus, Lin

lingual gyrus, SFG superior frontal gyrus, ROI region of interest.

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–23 13

significantly diminished in those areas, which were initiallyactivated more strongly in the patient than in the control (insula,rostral ACC, calcarine fissure, cerebellar vermis). In contrast,Habermeyer et al. (2012) did not replicate any of the regionsnamed by Moulier et al. (2012) in their patient after 10 months oftreatment. Moreover, except for declining activity within theamygdala, and the adjacent parahippocampal gyrus over time,their results mainly pointed to pharmacological effects in frontaland temporal cortical regions.

Comparability of the results are limited by above mentioneddifferences in methodological approaches, and by the fact thatsingle cases were analysed in which activation patterns cannot bereadily generalized. Studies investigating larger groups of

paedophilic patients hold the promise to reveal more insightfuldata. These will be reviewed in the following section.

3.2.2.2. fMRI studies on sexual arousal processing in samples of

paedophilic men. We will now mainly focus on comparability ofthose six (of seven) group fMRI studies reporting similar contrastsfrom whole brain analyses. But first we will briefly outline themain results of one remaining investigation focusing on amygdalaactivity. Sartorius et al. (2008) investigated 10 paedophilic CSOsattracted to boys from a forensic inpatient setting, and 10 controlsattracted to women. Sexual age preference information was notprovided and subjects were unmedicated. Restricting theiranalyses to the bilateral amygdala, they found significantly

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–2314

stronger activity in paedophilic subjects compared to the controlsduring the presentation of child stimuli, but no group effectsduring adult stimuli. Within-group comparisons showed thatamygdala activity was lower during child compared to adultstimuli in controls while the opposite pattern was true forpaedophiles. This study provides further evidence for amygdalaabnormalities, but it neglects potential further effects since wholebrain analyses were not reported. Further, it suffers from smallsample size, lack of differentiation between gender preferences,and missing adequate control for exclusivity of paedophilicpreference.

Six studies were comparable in sample size and methodology.Four investigated forensic inpatient samples and two studiedpatients from outpatient prevention and therapy programmes. Thenumber of included patients ranged from 8 to 24 (Table 4). Note,that the sample investigated by Ponseti et al. (2012) was the onlyone including men who admitted their sexual attraction tochildren by themselves and who were not forced to interventionby legal authorities. Poeppl et al. (2011) were the only ones to use

Table 4Description of functional MRI studies.

Refs. Sample Sexual orientation

Walter et al. (2007) 13 CSO, inpatient

14 community controls

Exclusive-type paedophilia

Gender orientation unknow

Sartorius et al. (2008) 10 CSO, inpatient

10 community controls

Exclusivity of age preference

Paedophiles attracted to boy

Teleiophiles attracted to wo

Schiffer et al. (2008a) 11 CSO, inpatient

10 community controls

Exclusive-type paedophilia

All subjects attracted to mal

Schiffer et al. (2008b) 8 CSO, inpatient

12 community controls

Exclusive-type paedophilia

All subjects attracted to fem

Poeppl et al. (2011) 9 CSO, inpatient

11 NSO, inpatient

Exclusivity of age preference

Attracted to males:

8 paedophiles

0 teleiophiles

Ponseti et al. (2012) 24 outpatient (12 CSO)

32 community controls

17 Exclusive-type paedophil

Attracted to males:

13 paedophiles

14 teleiophiles

Habermeyer et al.

(2013a,b)

8 outpatient (3 CSO)

8 community controls

Exclusive-type paedophilia

All subjects attracted to fem

Annotations: MRI magnetic resonance imaging, CSO child sex offender, NSO non-sex of

NSOs as control group, while all other reports included communitycontrols. At least in five of these studies, patients were free of anymedication or did not take antilibidinal drugs. Characteristics ofsexual orientation like exclusivity or gender orientation werecontrolled for by some, but not all studies. Please refer to Table 4for details.3.2.2.2.1. Intra-group contrasts. Data regarding intra-group con-trasts are available from three studies (Poeppl et al., 2011; Schifferet al., 2008a, 2008b), in which the sexually preferred images werecontrasted with respective control stimuli (which were differentacross studies; Table 4). As can be seen from Table 5, resultscongruently show activations within comparable regions inpaedophiles and teleiophiles that are distributed over allcomponents of the neurophenomenological model (Redouteet al., 2000; Stoleru et al., 1999). A recent preliminary meta-analysis (Polisois-Keating and Joyal, 2013) confirms this picturedemonstrating robust activations in both groups within thefusiform gyrus, occipital cortex, cerebellum, anterior cingulatecortex, and substantia nigra. In paedophilic men, a greater number

Medication Paradigm/Stimuli

n

None 256 erotic (nude adults only), emotional

and neutral photographs shown randomly

(5 s/image); expectancy period (4–6 s)

before 50% of runs; button press required at

appearance of each picture

unknown

s

men

None 500 stimuli, consisting of images of boys,

girls, men and women (wearing swimsuits

or underwear; 15/category; 1 s/photo), 48

target stimuli, 392 neutral non-target

stimuli shown randomly

odd-ball task: button press of forefinger

required on targets, button press of middle

finger required on other stimuli

es

None Passive viewing of 7 photographs of nude

boys and 7 of nude men presented

alternating with 7 images of dressed boys

and 7 of dressed men (38.5 s/image)

ales

none Passive viewing of 7 photographs of nude

girls and 7 of nude women presented

alternating with 7 images of dressed girls

and 7 of dressed women (38.5 s/image)

unknown None 144 pictures of nude males and females

from Tanner stages 1, 3 and 5 and 24

neutral stimuli (scrambled images of nude

people) shown randomly (4 s/image)

Choice reaction time task: A dot appeared

at 12 possible positions with each picture

requiring to press a button corresponding

to the position as quick as possible.

ia No antilibidinal

medication

490 pictures from 14 categories (consisting

of 35 images each): nude adults and

children in whole-body frontal views,

genitals only, or face only (face pictures not

used for analyses), nonsexual pictures

evoking high or low arousal presented in a

pseudorandomized order (1 s/image)

odd-ball task: button press required on

target stimulus (presented 20 times)

ales

Unknown Passive viewing of 50 pictures from 5

categories (consisting of 10 images each):

boys, girls, men and women in bathing

clothes as well as control stimuli (objects)

presented for 0.75 s each; Instruction:

Attentive viewing in preparation of post-

scan recognition task

fender, s seconds.

Table 5Summary of findings from intra-group contrasts in fMRI studies.

Sexually arousing > Control stimuli Preferred > Non-preferred age

Paedophiles Teleiophiles Paedophiles Teleiophiles

Schiffer et al.

(2008a)a,c

Schiffer et al.

(2008b)a,c

Poeppl et al.

(2011)b,c

Schiffer et al.

(2008a)a,c

Schiffer et al.

(2008b)a,c

Schiffer et al.

(2008a)c

Schiffer et al.

(2008b)c

Poeppl et al.

(2011)d

Schiffer et al.

(2008b)c

Poeppl et al.

(2011)d

SFG R

MFGf L/R R R R L R L/R

IFG R L/R R L/R R L/R L

Pre R L/R

Par R

SMA L L

Insf R L/R R L/R

STG L/R R L/R X L/R

MTG L/R L/R L X L/R

ITG L/R R R X

Fuse,f R L R L/R L/R L/R L R

SPLf R R R R R

IPL L L

Pos R R L/R L

Pcu R R R R L/R L R L

PHc L/R L L/R L R L

SOGe R R

MOGe,f L(R L/R L/R L/R L/R X L/R L/R L

IOGf L/R R L/R L L/R L

Cun L R L

Cal R

Lin L

ACCe,f L/R L/R L

MCC L

PCC L/R

HCf L L/R L R

Amye R R L/R R

Cauf R R L/R R L

Tha L L/R L R

SNe,f L/R L R

Put R L/R

GP R R

Cere,f R

MB R

Annotations: SFG superior frontal gyrus, MFG middle frontal gyrus, IFG inferior frontal gyrus, Pre precentral gyrus, Par paracentral lobule, SMA supplementary motor area, Ins

insula, STG superior temporal gyrus, MTG middle temporal gyrus, ITG inferior temporal gyrus, Fus fusiform gyrus, SPL superior parietal lobule, IPL inferior parietal lobule, Pos

postcentral gyrus, Pcu precuneus, PHc parahippocampal gyrus, SOG superior occipital gyrus, MOG middle occipital gyrus, IOG inferior occipital gyrus, Cun cuneus, Cal

calcarine gyrus, Lin lingual gyrus, ACC anterior cingulate cortex, MCC middle cingulate cortex, PCC posterior cingulate cortex, HC hippocampus, Amy Amygdala, Cau caudate,

Tha thalamus, SN substantia nigra, Put putamen, GB globus pallidus, Cer cerebellum, MB midbrain, L/R left/right, X region implicated, but hemisphere not specified.a Contrast: nude children/adults > dressed children/adults.b Contrast: nude children > scrambled pictures of children.c p < .05 corrected for multiple comparisons using False Discovery Rate (FDR).d p < .001 uncorrected.e Meta-analytic support for teleiophiles.f Meta-analytic support for paedophiles by Polisois-Keating and Joyal (2013).

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–23 15

of significantly activated regions were observed with additionalclusters in the middle frontal gyrus, superior parietal lobule,hippocampus, and the insula. In teleiophilic men, amygdalaactivity was observed, which was not detectable in paedophiles.These regions correspond well with results of meta-analyses oncue-induced sexual arousal and the components of the neurophe-nomenological model (Kuhn and Gallinat, 2011; Poeppl et al.,2014).3.2.2.2.2. Inter-group contrasts. There are inconsistencies regardingthe different brain structures implicated when groups arecompared for either child or adult stimuli (Table 6). Only theright medial frontal gyrus (Poeppl et al., 2011; Schiffer et al.,2008a), hippocampus, and thalamus (Poeppl et al., 2011; Schifferet al., 2008b) were repeatedly found to be more strongly activatedin paedophiles compared to teleiophiles for the child stimuli.Comparing activations between groups for the adult stimuli led toa variety of different regions implicated across studies, with onlythe right insula and right cuneus replicated as more activated inteleiophiles (see Table 6; Poeppl et al., 2011; Schiffer et al., 2008b;Walter et al., 2007).

In addition, there are three studies examining groupdifferences during stimulation with the respective preferredphotos (that is: paedophiles[child > control stimuli] < > teleio-teleiophiles[adult > control stimuli]; Poeppl et al., 2011; Schifferet al., 2008a, 2008b). The findings between studies are inconsis-tent, with the only congruency being that two of three studiesfound no stronger activation in teleiophiles compared to paedo-philes (Table 6). In the remaining study stronger activation infrontal regions and the cingulate was observed in teleiophiles(Schiffer et al., 2008b). Investigating brain activity stronger inpaedophiles compared to controls, Schiffer et al. (2008a, 2008b)found (incongruent) effects in frontal regions, while Poeppl et al.(2011) observed increased recruitment of posterior areas (Table 6).The meta-analysis by Polisois-Keating and Joyal (2013) showed nosignificant differences between groups for these contrasts (at aFDR-corrected significance level of p < .05 and a cluster thresholdof k � 200 voxels).

Ponseti et al. (2012) used similar contrasts for the definition ofthe group-discriminative pattern for subsequent pattern analyses(see below). Divided by the sex of the presented stimuli they

Table 6Summary of findings from inter-group contrasts in fMRI studies.

Child stimuli Adult stimuli Preferred stimuli Child>Adult Adult>Child

Paedo>Teleio Teleio>Paedo Paedo>Teleio Teleio>Paedo Paedo>Teleio Teleio>Paedo

Schiffer

et al.

(2008a)a,f

Schiffer

et al.

(2008b)a,f

Poeppl

et al.

(2011)b,h

Walter

et al.

(2007)c,i

Schiffer

et al.

(2008a)a,f

Schiffer

et al.

(2008b)a,f

Poeppl

et al.

(2011)b,h

Schiffer

et al.

(2008a)a,f

Schiffer

et al.

(2008b)a,f

Poeppl

et al.

(2011)b,h

Schiffer

et al.

(2008a)a,f

Schiffer

et al.

(2008b)a,f

Poeppl

et al.

(2011)b,h

Habermeyer

et al.

(2013a,b)d,g

Ponseti

et al.

(2012)e,h

Ponseti

et al.

(2012)f,h

MFG R R L L NO EFFECTS R NO EFFECTS

MiFG R

IFG R R L/R R

Pre L/R

Par L

Ins R R L/R L

STG L/R

MTG R R R

ITG R L/R

Fus L/R R L L L/R

SPL L/R

IPL L

Pos R

Ang R

Pcu L

PHc

MOG L L

Lin L L/R

Cun R R

ACC L/R R L/R L

MCC L R L/R

PCC R L

HC L/R R R

Amy L

Cau R L/R

Tha R L L L

Hyp L

Cer R L/R R

MB R

Annotations: MFG medial frontal gyrus, IFG inferior frontal gyrus, Pre precentral gyrus, Par paracentral lobule, Ins insula, STG superior temporal gyrus, MTG middle temporal gyrus, ITG inferior temporal gyrus, Fus fusiform gyrus, SPL

superior parietal lobule, IPL inferior parietal lobule, Pos postcentral gyrus, Ang angular gyrus, Pcu precuneus, PHc parahippocampal gyrus, MOG middle occipital gyrus, Cun cuneus, Lin lingual gyrus, ACC anterior cingulate cortex,

MCC middle cingulate cortex, PCC posterior cingulate cortex, HC hippocampus, Amy Amygdala, Cau caudate, Tha thalamus, Hyp hypothalamus, Cer cerebellum, MB midbrain, L/R left/right.a Contrast: nude children/adults>dressed children/adults.b Contrast: nude children> scrambled pictures of children.c Contrast: sexually arousing pictures of adults> emotional pictures.d Contrast: nude men/genitals>nude boys/genitals. Contrast: girls>woman in bathing suits.e Contrast: nude women/genitals>nude girls/genitals.f p< .05 corrected for multiple comparisons using False Discovery Rate (FDR).g p< .05 corrected for multiple comparisons using cluster-level correction based on Monte Carlo simulations.h p< .001 uncorrected.i p< .005 uncorrected.

S. M

oh

nk

e et

al.

/ P

rog

ress in

Neu

rob

iolo

gy

12

2 (2

01

4)

1–

23

16

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–23 17

exclusively investigated hyperactivation of controls viewing adultstimuli compared to paedophiles viewing child stimuli andobserved widespread effects located mainly in posterior andsubcortical structures (Table 6). Employing yet another analysisstrategy Habermeyer et al. (2013a) observed a significant 3-way-interaction of group and the within-subject factors age and gender(of presented stimuli) within the right lateral middle frontal gyrus.Paedophiles showed hyperactivation of the right lateral middlefrontal gyrus exclusively during presentation of erotic girl stimuli,while controls showed hypoactivation across all experimentalconditions. More results from between-group contrasts were notreported from this study.

In summary, the available fMRI studies reviewed here showmuch stronger consistencies when focusing on similaritiesbetween teleiophiles and paedophiles, but led to very differentresults for group differences. These incongruencies aggravate clearconclusions and complicate, if not prohibit, classification accordingto the neurophenomenological model. The heterogeneous resultssuggest that the methodological approaches may have beeninappropriate. In contrast, results of first discriminative analysisstrategies look more promising. Walter (2008; Walter et al., 2010)used a stepwise discriminant analysis based on functional regionsin which group differences during either cognitive anticipation orpassive viewing of erotic stimuli were observed (Walter et al.,2007; see Table 4). This showed that groups (n = 13 unmedicatedpaedophilic CSOs, n = 13 teleiophilic controls) could be separatedby neural activity within the dorsal anterior cingulate during theexpectancy period, and hypothalamic activation during stimulusconsummation. However, these results were obtained using asmall size and validation in an independent data set would beessential. Additionally, the findings are limited by the a prioriselection of regions included in the model. Ponseti et al. (2012)used whole-brain fMRI pattern classification in a sample of 24paedophilic men and 32 community controls (Table 4). In thisstudy paedophilic and teleiophilic sexual orientations werediscriminable with a specificity of 100% and sensitivity of 88%.This investigation employed a paradigm (presentation of photos offull frontal nudes as well as genitals only from adults and childrenof both sexes for 1 s) comparable to those used in other studies. Theclassification was based on the calculation of group differences inactivation patterns, computed similarly as in other studies, but wenta step further. As its purpose was the examination of thediscriminative power of such a design, individual statistics (forboys < men and girls < women) were then projected on these groupdifferences to obtain individual expression values representing thedegree to which the activation pattern of a single subject matchedthe group’s brain response. These values were subsequently used forclassification algorithms. Importantly, Ponseti et al. (2012) cross-validated their results to estimate the model’s ability to classifyunknown data. Using the leave-one-out method, the model wasrepeatedly recalculated leaving out one subject at a time. Groupstatistics from the respective remaining sample (n = 55) were usedto calculate the expression value for the left out subject, which wasthen submitted to classification. This procedure was repeated foreach individual subject, so that it had to be performed 56 times.However, validation in a completely independent data set wouldstill be desirable and the validity of the findings is somewhatconstricted by the fact that significance values were not reported forthe group classification. Still, the high accuracy achieved points tothe presence of functional differences between paedophilic andteleiophilic men, and supports the utility of fMRI research in thispopulation. However, it challenges ‘‘classical’’ analysis strategies,which only focus on group differences.

3.2.2.3. fMRI studies on further psychological processes. In additionto the studies reviewed above, there were two more fMRI

investigations on differing psychological processes. In a sampleoverlapping with the one in which Habermeyer et al. (2013a)studied sexual arousal processing, the same group (Habermeyeret al., 2013b) employed a go-/no-go task in order to investigateresponse inhibition. The task consisted of two alternatingconditions: In the ‘‘go’’ condition subjects were required to pressa button whenever a letter was presented on the screen (here only‘M’s were presented). In the ‘‘no-go’’ condition ‘M’s and ‘W’s werepresented in a pseudorandom order with the task being to pressthe button only in response to ‘M’s, but not to ‘W’s. A total of 11paedophiles were recruited from an outpatient cognitive beha-vioural therapy group. These men did not admit their sexualattraction towards children before getting into contact with thelegal system because of sexual offences against children thatinvolved direct physical contact (n = 5) or the use of childpornography (n = 6). They were compared to eight healthycontrols, not differing significantly in age and intelligence. Threeof the paedophiles were attracted to boys, while none of thecontrols were attracted to men. Behaviourally, the paedophilicCSOs showed longer reaction times in the no-go condition and lessaccurate discrimination of stimuli (‘W’ and ‘M’) than controls.However, there was no higher rate of commission errors (thefailure to suppress an inappropriate response) in paedophiles.These results was interpreted as being more indicative ofinattention, rather than impulsivity. In line with this, there wereno group differences in the activation of brain areas typicallyinvolved in response inhibition (anterior insula, anterior anddorsolateral prefrontal cortices, supplementary motor area, andparietal cortices; Wager et al., 2005), but in regions belonging tothe brain’s default mode network (Whitfield-Gabrieli and Ford,2012). A significant interaction effect (group � condition) showedthat paedophiles (compared to controls) exhibited less deactiva-tion of the precuneus and the angular gyrus during the ‘no-go’condition compared to the ‘go’ condition. In addition, activitywithin these regions was significantly correlated with reactiontimes during ‘no-go’. Since the default mode network is usuallyactivated when the brain is at rest, and is implicated in processessuch as self-reflection and mentalizing (thinking about mentalstates of others; Whitfield-Gabrieli and Ford, 2012), the authorsinterpreted that the paedophilic men might have been moreoccupied with these processes (e.g., they might have thought abouttheir socially unwanted sexual preference, because it wascurrently scientifically investigated) rather than focussing theirattention on the cognitively more demanding ‘no-go’ condition.

In a subsequent study Ponseti et al. (2014) studied neural faceprocessing in the sample in which they performed theirclassification analyses based on visual sexual stimuli (Ponsetiet al., 2012; see Table 4). The authors presented photographs offaces of women, men, girls, and boys as well as further arousingpictures. In order to investigate the neural processing of faces ofthe preferred age they contrasted pictures of the preferred typewith those of the preferred sex, but not of the preferred age (e.g., forpaedophiles attracted to boys: boys’ faces vs. men’s faces) for eachgroup of participants (teleiophiles/paedophiles attracted to males/females). Subsequently, they conducted a conjunction analysis onthese contrasts in order to identify brain regions that teleiophilesrecruited more strongly during adult faces compared to child facesand that paedophiles activated more strongly in response to childfaces compared to adult faces. During viewing faces of thepreferred age, paedophiles and teleiophiles activated a networkof face- and sex-sensitive areas comprising the inferior occipitalgyrus, fusiform gyrus, caudate, putamen, sulcus calcarinus, andventrolateral prefrontal cortex. Therefore, in both groups the samenetwork was activated in response to respective sexually preferredfaces. This agrees with the observation that paedophilic andteleiophilic men activate largely comparable brain areas during

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–2318

sexual arousal processing (see Section 3.2.2.2). However, it was notreported whether there were any group differences during faceprocessing.

3.3. Correlational analyses in neuroimaging studies

Most neuroimaging studies also investigated correlationsbetween brain structure/activity in paedophilia and a variety of

Table 7Significant correlative findings from MRI studies.

Refs. Measure

Structural MRI studies

Schiltz et al. (2007)a SVR-20 ‘‘Multiple sexual offence types’’

MSI ‘‘Incestuous child abuse’’

Schiffer et al. (2007)b MMPI-2 ‘‘Obsessiveness’’

MMPI-2 ‘‘Depression’’

Cantor et al. (2008)b Phallometric paedophilia indexc

Poeppl et al. (2013)a SSPI

Age of victims

Functional MRI studies

Walter et al. (2007)a MSI ‘‘Sexual abuse of children’’

(contrast: sexual > emotional arousal)

Schiffer et al. (2008a) Sexual arousal ratings

(contrast: nude > dessed boys)

(contrast: nude > dressed men)

Schiffer et al. (2008b)a Sexual arousal ratings

(contrast: nude > dessed girls)

(contrast: nude > dessed women)

MSI ‘‘Sexual abuse of children’’

(contrast nude > dressed girls)

variables such as: indexes for sexual arousal or paedophilicinterest, offence characteristics (e.g., the number of sexual offencetypes, incestuous child abuse, age of victims), or psychopathology(obsessiveness and depression). The number of different param-eters complicates comparisons of the published findings (Table 7).Nevertheless there are results of interest across studies.

Walter et al. (2007) and Schiffer et al. (2008b) both foundnegative associations between the Multiphasic Sex Inventory (MSI)

Brain area Test statistic

Amygdala R r = .69

Amygdala R r = �.58

Negative correlations

IFG L T = 7.00

SFG R T = 5.44

Putamen L T = 5.37

Putamen R T = 4.73

Cerebellum T = 5.30

Negative correlations

MFG R T = 6.10

MFG L T = 5.06

RG T = 5.39

White matter:

Temporal Lobe R/L r = �.31/�.25

Parietal Lobe R/L r = �.32/�.33

Corpus callosum r = �.19

CSF:

Lateral ventricle R/L r = .19/.22

Insula/Parietal operculum r = �45

DLPFC L (IFG) r = �.64

OFC R (RG) r = .98

Angular L r = .70

Angular R r = .93

Negative correlations

DLPFC R (Precentral) Z = 3.61

DLPFC R (MFG/SFG) Z = 3.30

DLPFC L (SFG) Z = 3.24

occipital L Z = 3.57

Paedophiles:

SFG R r = .68

MiFG L r = .72

ACC R/L r = .84/.83

STG R/L r = .76/.80

MTG R r = .86

Teleiophiles:

Fusiform R r = .68

Fusiform L r = .87

Paedophiles:

FPPFC R (MFG) r = .�67

Fusiform L r = .62

ITG R r = .75

Teleiophiles:

Putamen R r = .62

Paedophiles:

Fusiform R r = .56

Teleiophiles:

OFC R r = �.76

Fusiform R r = .55

Pcu L r = .58

IPL L r = .61

ACC L r = .65

Caudate R r = .59

Thalamus L r = .55

Fusiform L r = .51

OFC L (IFG/MFG) r = �.64/r = �.55

DLPFC L (SFG) r = �.67

DLPFC R (SFG) r = �.45

FPPPFC (SFG) r = �.49

Table 7 (Continued )

Refs. Measure Brain area Test statistic

Poeppl et al. (2011)a Paedophilic preference indexd

(contrast: Tanner 1 > Tanner 5)

Positive correlations

MiFG L T = 9.37

Putamen L T = 6.82

Post-/Precentral L T = 6.81

Negative correlations

Corpus callosum L/R T = 23.94

MTG L T = 10.41

Corpus callosum R T = 9.38

STG L T = 9.03

MTG R T = 8.62

Pcu/SOG R T = 7.84

Angular L T = 7.08

Calcarine/PCC R T = 6.91

Dentate R T = 6.76

PCC/Pcu R T = 6.75

a Correlations observed in paedophile subjects only.b Correlations observed in a combined analyses with paedophile and teleiophile subjects.c Phallometric paedophilia index was calculated by subtracting phallometric responses to adult stimuli from those to child stimuli.d Paedophilic preference index was calculated by subtracting mean response latencies for adult stimuli (Tanner 5) from those for prepubescent stimuli (Tanner 1), SVR-20

sexual violence risk scale-20 (Boer et al., 1997), MSI ‘Multiphasic sex inventory’ (Deegener, 1996), MMPI-2 Minnesota multiphasic personality inventory (Hathaway et al.,

2001), SSPI Screening scale of paedophilic interest (Seto and Lalumiere, 2001), IFG inferior frontal gyrus, MiFG middle frontal gyrus, SFG superior frontal gyrus, RG rectal gyrus,

DLPFC dorsolateral prefrontal cortex, OFC orbitofrontal cortex, ACC anterior cingulate cortex, FPPFC frontopolar prefrontal cortex, MFG medial frontal gyrus, STG superior

temporal gyrus, MTG middle temporal gyrus, ITG inferior temporal gyrus, Pcu Precuneus, SOG Superior occipital gyrus, PCC posterior cingulate cortex, L left, R right.

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–23 19

subscale ‘‘Sexual abuse of children’’ (Deegener, 1996) and bilateraldorsolateral prefrontal cortex activity during sexual arousalprocessing. In both papers it was assumed that the dorsolateralprefrontal cortex modulates vegetative-autonomic components ofarousal processing (Beauregard et al., 2001). This allows for thespeculation that sexual offending could be promoted by decreasedrecruitment of the dorsolateral prefrontal cortex that may entailinsufficient regulation of physical states.

Schiffer et al. (2008a, 2008b) reported the repeated involve-ment of the fusiform gyrus, despite inconsistent correlationsbetween sexual arousal ratings and brain activation betweenpaedophiles (attracted to boys or girls) and teleiophiles (attractedto men or women). The fusiform gyrus is implicated in the neuralprocessing of sexual arousal (Kuhn and Gallinat, 2011; Poepplet al., 2014; Polisois-Keating and Joyal, 2013; Stoleru et al., 2012)and has been consistently observed in intra-group contrasts infMRI studies on paedophilia (see Table 5). It is assumed to beinvolved in processing motivationally relevant stimuli, includingerotic images and is therefore counted in the ‘‘appraisal’’component of the neurophenomenological model (Redouteet al., 2000; Stoleru et al., 1999).

One structural and one functional MRI study employedpaedophilia index scores (operationalized either by the differencein phallometric responses; Cantor et al., 2008; or reaction times;Poeppl et al., 2011; during stimulation with child vs. adult stimuli;Table 7) for correlational analyses. Both studies coincide in findingnegative associations between activity or structure of the corpuscallosum and bilateral temporal white matter and the score forpaedophilic interest. There is also weaker overlap between bothstudies in associations with parietal white matter areas. Theseobservations support the conclusions made by Cantor et al. (2008)in which neural abnormalities might rather be manifested inalterations of connectivity of areas involved in sexual arousalprocessing than with circumscribed grey matter aberrances.Further study is necessary to elucidate the exact roles of brainconnectivity and the functional significance of the dorsolateralprefrontal cortex and fusiform gyrus in this context.

4. Discussion

The heterogeneous results summarized in this review make itdifficult to draw any definitive conclusions on neural correlates of

paedophilia. Although neurological case reports frequently point-ed to pathology of the frontal lobes, temporal lobes, and the basalganglia, these regions seem to be associated with diminishedbehavioural control that may apply to hypersexuality rather thanpaedophilic sexual preference itself. These abnormalities wereobserved in CSOs and although CSA did not occur as a specificconsequence, it was observable in the context of overall increasedsexualized behaviour and reduced impulse control. Hence, thesefindings may be more closely associated with sexual offending,probably provoked by a more general disinhibition rather thanparaphilic interest, per se (see also Mendez and Shapira, 2011).Moreover, the case studies are selective reports, therefore may beinherently biased. This line of research neglects unpublishedfindings as well as further abnormalities that may have remainedundetected due to patients not being systematically investigated.Furthermore, these studies suffer from the lack of distinctionbetween CSO and paedophilia and often subjects were not properlydiagnosed. Nevertheless, they provide preliminary evidence onstructural brain abnormalities underlying inappropriate sexualbehaviour, which is of relevance in paedophilic motivated sexualbehaviour.

Structural neuroimaging studies employing either CT or MRI,generally conducted on diagnosed forensic samples, also led toinconsistent results. Nevertheless, the volume reduction of theamygdala in paedophilic CSOs was observed in three independentVBM studies (Poeppl et al., 2013; Schiltz et al., 2007; Schiffer,personal communication); thus, it is an interesting and promisingresult. Some issues remain that should be addressed in futurereplications of the amygdala association. First, the results wereobtained using numerous separate ROI analyses and, at least in theinvestigation of Poeppl et al. (2013), would not survive correctionfor the number of small volume corrections. Still, the results fromthe three studies consistently demonstrated a large effect size(Cohen’s d = 1.22–1.511); however, each study was in a limitedsample size, therefore it is possible that the effects are inflated.Hence, future analyses should include a well-powered sample toreplicate the result and confirm the true effect size. In addition, it isdoubtable, whether the finding of reduced amygdala volumerepresents an abnormality specific to paedophilia. The amygdalahas frequently been implicated in sexual arousal processing.Stoleru et al. (2012) reported that it was implicated in 35% of fMRIstudies on male sexual arousal and it plays a likely role in

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–2320

emotional appraisal and encoding of reward value. In line with this,Schiltz et al. (2007) and Poeppl et al. (2013) concluded that smalleramygdala volume might indicate a lack of devaluation of infantilesexual interest, which would represent a neurodevelopmentalabnormality. Further support for this comes from Schiltz et al.(2007). It was reported that amygdala volume was negativelycorrelated with exclusive paedophilic offences and incestuous CSA(Table 7). Additionally, a recent meta-analysis shows that althoughdirect comparisons did not yield significant differences inamygdala activity between paedophiles and teleiophiles, activa-tion observable in teleiophiles during sexual arousal processingwas not detectable in paedophiles (Polisois-Keating and Joyal,2013). However, amygdala volume alterations could be apparentfor other reasons. For example, Pardini et al. (2013) reported anassociation between lower amygdala volume and aggression,violence, and psychopathic traits. Instead of affecting sexualpreference, the structural alteration could be linked to factorsunderlying psychopathy such as: aggression, impulsivity, lack ofempathy, and emotional unconcern (Anderson and Kiehl, 2012;Kiehl, 2006). Furthermore, diminished amygdala volume couldalso be a correlate of more general affective symptoms comorbidwith paedophilia, like depressed mood or anxiety. Thus, insummary, there is considerable empirical support for structuralamygdala alterations in paedophilic CSOs, which have beenobserved in three out of five studies (three out of four data sets).Nevertheless, further research on larger samples using stringentstatistical methods are needed to verify this result and to elucidatethe exact role of the amygdala in this context.

The fMRI studies definitively show that there may be moresimilarities than differences between paedophiles and teleiophilesin the functional recruitment of brain areas during visualstimulation with sexually preferred images (Polisois-Keating andJoyal, 2013; Seto, 2008; Schiffer et al., 2008b). Across studies, theintra-group contrasts showed comparable activity of the sexualarousal network in both groups, corresponding to all componentsof the neurophenomenological model of sexual arousal (Redouteet al., 2000; Stoleru et al., 1999). In contrast, group differencesvaried between studies, although the number of investigationsproviding data for comparable contrasts so far is admittedly low, asdifferent paradigms and analysis strategies were used. It isnoteworthy that Schiffer et al. (2008a, 2008b) and Habermeyeret al. (2013a) were the only ones to use correction for multiplecomparisons over the whole brain in their between-group analysesand they still yielded inconsistent results. Hence, althoughstatistical stringency is of course desirable, more concordantresults may have not been reported because of this level ofsignificance being too strict given the small sample sizes.

Given the aforementioned limitations, only cautious interpre-tation can be derived. For instance, in face of several subcorticaland dorsolateral prefrontal minor activations in paedophiles,Walter et al. (2007) speculated that a lack of sexual interest inadults might stem from difficulties in recruiting regions responsi-ble for vegetative-autonomic responses, potentially resulting frominsufficient dorsolateral prefrontal control. However, other reportsdid not support dampened subcortical activity and some foundeven higher subcortical recruitment when child stimuli wereemployed (Poeppl et al., 2011; Sartorius et al., 2008; Schiffer et al.,2008b). Since Walter et al. (2007) exclusively used adult stimulithe minor activations might stem from the fact that paedophileswere less aroused by these photos (although they reportedotherwise, see below). Schiffer et al. (2008b) concluded fromstronger orbitofrontal and general frontal involvement seen inteleiophiles that these regions might underlie altered evaluative

1 Values were calculated based on Z-values reported by both studies using the

formula: d ¼ ð2z=ffiffiffiffi

NpÞ (Cohen, 1992).

and motivational processes as suggested by the neurophenome-nological model (Redoute et al., 2000; Stoleru et al., 1999). Similarto the group’s VBM study (Schiffer et al., 2007), they assumed thatdysfunction of appraisal processes mediated by this region couldbe associated with disturbed stimulus control as seen in (sexual)compulsive behaviour. Indeed, similar results were obtained byPoeppl et al. (2011) as well, but still, it was not consistentlysupported by subsequent studies (see Table 6). Habermeyer et al.(2013a) for example found stronger right orbitofrontal involve-ment only in paedophilic men while these were watching eroticgirl stimuli, interpreting very similarly as Schiffer et al. (2007), thatthis area was involved in evaluating reinforcers, which wouldentail emotional and behavioural regulation. However, besidesinvestigating samples from unequal settings (in- vs. outpatient),the orbitofrontal regions observed in these two studies were notexactly congruent and the effects pointed into different directions,so that these results could represent differing processes.

Other replicated findings from imaging studies includehyperactivation of the cuneus in teleiophiles during photographsof adults (Table 6). This region is not usually found during sexualarousal, but likely implicated in visual processing or inhibitorycontrol (Haldane et al., 2008). Insula activation was moreconsistently observed in studies on male sexual arousal. Thisregion was found to be more strongly recruited by teleiophilic thanpaedophilic men during presentation of adult stimuli (Walter et al.,2007; Poeppl et al., 2011). The insula may play various roles insexual arousal including interoceptive awareness of bodilyprocesses, the mediation of autonomic responses (including penileerection) as well as determination of the affective tone of sexualarousal (Stoleru et al., 2012). Two studies found strongerhippocampal and thalamic activity in paedophiles upon presenta-tion of child images (Schiffer et al., 2008a; Poeppl et al., 2011)pointing to roles in general emotional arousal and reward-dependent action selection (Stoleru et al., 2012). However, asthe same regions were also found to be more active in teleiophilesin other studies using different contrasts, these results should beinterpreted with caution.

The variability of these results might stem from a number offactors, such as: inclusion of differing paedophilic and controlpopulations, insufficient statistical power, divergent operationa-lization, analysis procedures, and differences in the fMRI para-digms. These varied in a number of factors like the stimuli used(nude vs. partly dressed, inclusion of child photographies), numberof runs, instructions given, the inclusion of a task ensuringattention, and/or the duration of stimulus presentation, whichvaried between 0.75 s and 38.5 s (Table 4). In their review on brainimaging of sexual behaviour Georgiadis and Kringelbach (2012)pointed out that there are well dissociable networks associatedwith short vs. long stimulus presentation times. They argued that a‘‘sexual interest network’’, activated by briefly presented stimuli,could primarily be implicated in the evaluation of salience andhedonic value. In contrast, the ‘‘sexual arousal network’’, proces-sing further physiological components of heightened arousal likepenile tumescence or cardiovascular activity, was observable aftermore prolonged stimulus durations. Furthermore, longer presen-tation times likely result in less distinct and more complexprocesses measured as other mind states like emotion regulationor self-referential processing might coincide with sexual arousal(Georgiadis and Kringelbach, 2012; Habermeyer et al., 2013a). Allof the mentioned factors could have led to quite different arousallevels across studies, which limits comparability.

Interpretability of some findings is further complicated bybehavioural ratings of stimuli. Walter et al. (2007) did not findgroup differences in the sexual arousal and emotional intensityratings for the adult stimuli between groups and Schiffer et al.(2008b) found no significant differences between exclusive-type

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–23 21

paedophiles’ rating of girls and women stimuli. On the one handthis could point to response biases in terms of social desirabilityor unreliable responses from forensic samples. On the other handthis could also mean that the stimulus material employed inthese studies was insufficient to produce the aspired groupdifferences.

The inconsistencies in functional imaging studies contrastdiscriminative analyses, showing that paedophiles and teleiophilesvery accurately can be separated based on activation patterns(Ponseti et al., 2012; Walter et al., 2010). In spite of the describeddisagreement in other studies, these results speak in favour of theusefulness of fMRI to investigate paedophilia and point to thepossibility that abnormalities should not be looked for on the levelof isolated brain areas, but would be better characterized on anetwork level. Furthermore, correlative analyses yielded someinteresting first clues on the role of the DLPFC in arousal regulation,implying a relevance in CSO rather than in paedophilic preferenceper se (compare Walter et al., 2007) and suggested the importanceto study brain connectivity in paedophiles in face of replicatedassociations of paedophilic preference with white matter structureand function (Cantor et al., 2008; Cantor and Blanchard, 2012;Poeppl et al., 2011).

Concluding from the literature reviewed above we would like topoint out some methodological suggestions for future studies:

� Larger sample sizes: Most studies published so far have includedvery small samples. These investigations therefore lack sufficientstatistical power to find potential effects. It is of course difficultto collect larger samples of paedophiles, especially from a non-forensic context, but still, this profoundly hampers moresophisticated analyses.� Differentiation between paedophiles who have and those who

have not committed sexual abuse: Most published studies wereconducted in forensic contexts and therefore included paedo-philic CSOs. In contrast, little is known about paedophilic non-offenders. Conceivably, these groups could differ in quite a fewimportant aspects like personality characteristics (e.g., antisocialtendencies), empathic abilities, and/or impulse control (Hansonand Morton-Bourgon, 2005). These variables in turn could beconfounded with differences seen in comparison to teleiophiles.� Control for the recruitment setting: The forensic context or the

in- vs. out-patient status of patients should be accounted for, asthis could also be associated with a range of potentiallyconfounded variables like factors mentioned above or reactivepsychopathological characteristics. Some studies already col-lected respective control groups and this practice shouldcertainly be maintained whenever possible.� Control for aspects of sexual orientation: Important character-

istics like gender orientation or the exclusivity of paedophilicpreference should be controlled for more thoroughly. This hasimportant implications for the reactivity to the employedstimulus material in functional imaging studies as there mightbe little differences in excitability and brain activity to stimuli ofdifferent age groups in non-exclusive paedophilic men. In thesample of Ponseti et al. (2012) for example, 5 of 11 men attractedto girls as opposed to 2 of 13 men attracted to boys werediagnosed with the non-exclusive type. Consequently, theauthors observed more extended brain activation for theboys < men contrast as opposed to the girls < women contrast.While it cannot be stated safely that this is due to the moreprevalent responsiveness to adults in the group attracted tofemales, this remains a likely explanation.� Control for differentiations given by forensic research: Sub-

groups of paedophilia have been proposed based on clinicalpresentation as given by the degree of fixation to child sexualattraction (Cohen and Galynker, 2002), mode of sexual offending

(Knight, 1988), or the degree of admittance to child sexualattraction (Grossman and Cavanaugh, 1990). However, theseclassifications remain controversial as to their utility to predictre-offence risk, which is a central outcome parameter oftherapeutic approaches (Kingston et al., 2007). With the turnof the millennium, forensic research has shifted attention toimprove the prediction of re-offence risk using ‘‘actuarial’’ riskassessment tools or structured clinical judgement, whichintegrate and weigh the proposed classifications. These toolshave shown good accuracy and thereby support the validity ofthe classification into subgroups (Tully et al., 2013). Hence, itwould be interesting to investigate whether neurobiologicalcorrelates can be defined that might validate the proposeddifferentiations.� Control for pharmacological treatment: There are some inves-

tigations, which did not provide information on pharmacologicaltreatment. Needless to say, this could influence brain activity andin the long term brain structure. As paedophilic patients oftenreceive anti-androgenic or psychopharmacological medication,this is an important factor to mention and to account for.� Validation of stimulus sets: There are clues from some functional

imaging studies that the employed stimulus material was notsufficient to show behavioural effects on excitability or reactiontimes (see above). Hence, it should be validated before beingused in the scanner to enable more reliable conclusions.� Deliberate about presentation times: Short as opposed to longer

stimulus durations lead to differences in brain activity as variousprocesses play a role at different temporal stages of sexualarousal. Early evaluative processes, which are more specificallymeasurable with brief presentation times, are followed byphysiological processes and further cognitive elaboration, whichbecome more relevant with prolonged stimulation. Consequent-ly, depending on the process of interest, different presentationtimes might be appropriate.� Focus on brain networks: Studies using traditional fMRI analysis

methods led to very heterogeneous results while a studyfocusing on brain activity patterns show high accuracy in itsattempt to differentiate between paedophiles and teleiophilesbased on these patterns (Ponseti et al., 2012). Also, there issuggestive evidence that abnormalities may particularly pertainto the coupling of relevant brain areas (Cantor et al., 2008; Cantorand Blanchard, 2012; Poeppl et al., 2011). Therefore, it appearspromising to turn to further analysis methods, which not onlyfocus on mere activation differences but allow for theinvestigation of network characteristics and connectivity.� Exploration of correlations with real world behaviour: It is

known that forensic populations tend to be not very accurate inreporting their preferences or behavioural tendencies. It wouldbe of high interest to investigate the prospective validity ofneuroimaging measures to predict behaviour. This might be ofparticular relevance in the context of subjects with paedophiliathat have not yet offended as well as in samples that are onparole or ready to be released.

Taken together, the present evidence from brain lesion andneuroimaging studies in paedophilia is still in its infancy. Casereports point to the relevance of a number of regions, which aremore likely to be implicated in behavioural control than in sexualpreference. Furthermore, controlled neuroimaging studies show aheterogeneous picture and do not allow any firm conclusions to bedrawn about the neurobiological mechanisms underlying paedo-philic preference and behaviour. In fact, this is not very surprisingtaking into account the small number of studies, the small samplesizes, and the difficulty of performing such studies. However, evenin the face of these complicating factors the existing reports haveshown some very encouraging results like a twofold replication of

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–2322

reduced amygdala volume in paedophilic CSOs and the clearfindings of group-discriminative analyses. These show the poten-tial power of neuroimaging to study paedophilia. Nevertheless, thefunctional significance of smaller amygdala volume and alteredprocessing of the sexual arousal network remain to be investigatedby future studies. We have identified factors that might improvefuture studies and hope that a methodologically critical approachwill help to better understand and handle this medically andsocietally relevant condition.

Acknowledgements

This work was supported by the German Ministry for Researchand Education (BMBF 01KR1205A). We thank Miriam Schuler,Andrew Wold, Ilya Veer and Tristram Lett for proof reading andtheir helpful suggestions during the preparation of this manu-script. The authors declare that they have no conflict of interest.

References

Ahlers, C.J., Schaefer, G.A., Mundt, I.A., Roll, S., Englert, H., Willich, S.N., Beier, K.M.,2009. How unusual are the contents of paraphilias? Paraphilia-associatedsexual arousal patterns in a community-based sample of men. J. Sex. Med.8, 1362–1370.

Alanko, K., Salo, B., Mokros, A., Santtila, P., 2013. Evidence for heritability of adultmen’s sexual interest in youth under age 16 from a population-based extendedtwin design. J. Sex. Med. 10, 1090–1099.

Anderson, N.E., Kiehl, K.A., 2012. The psychopath magnetized: insights from brainimaging. Trends Cogn. Sci. 16, 52–60.

Ashburner, J., Friston, K.J., 2000. Voxel-based morphometry – the methods. Neuro-image 11, 805–821.

Beauregard, M., Levesque, J., Bourgouin, P., 2001. Neural correlates of conscious self-regulation of emotion. J. Neurosci. 21, RC165.

Beier, K.M., Amelung, T., Kuhle, L., Grundmann, D., Scherner, G., Neutze, J., 2013.Hebephilie als sexuelle Storung. Fortschr. Neurol. Psychiatr. 81, 128–137.

Berger, C., Mehrhoff, F.W., Beier, K.M., Meinck, H.-M., 2003. Sexuelle delinquenz undmorbus Parkinson. Nervenarzt 74, 370–375.

Berridge, K.C., Robinson, T.E., 1998. What is the role of dopamine in reward: hedonicimpact, reward learning, or incentive salience? Brain Res. Brain Res. Rev. 28,309–369.

Blanchard, R., 2010. The DSM diagnostic criteria for pedophilia. Arch. Sex. Behav. 39,304–316.

Blanchard, R., 2013. A dissenting opinion on DSM-5 pedophilic disorder. Arch. Sex.Behav. 42, 675–678.

Blanchard, R., Barbaree, H.E., Bogaert, A.F., Dickey, R., Klassen, P., Kuban, M.E.,Zucker, K.J., 2000. Fraternal birth order and sexual orientation in pedophiles.Arch. Sex. Behav. 29, 463–478.

Blanchard, R., Christensen, B.K., Strong, S.M., Cantor, J.M., Kuban, M.E., Klassen, P.,Dickey, R., Blak, T., 2002. Retrospective self-reports of childhood accidentscausing unconsciousness in phallometrically diagnosed pedophiles. Arch.Sex. Behav. 31, 511–526.

Blanchard, R., Kuban, M.E., Klassen, P., Dickey, R., Christensen, B.K., Cantor, J.M., Blak,T., 2003. Self-reported head injuries before and after age 13 in pedophilic andnonpedophilic men referred for clinical assessment. Arch. Sex. Behav. 32, 573–581.

Boer, D.P., Hart, S.D., Kropp, P.R., Webster, C.D., 1997. Manual for the Sexual ViolenceRisk – 20: Professional Guidelines for Assessing Risk of Sexual Violence. Insti-tute Against Family Violence, Vancouver, British Columbia.

Burns, J.M., Swerdlow, R.H., 2003. Right orbitofrontal tumor with pedophiliasymptom and constructional apraxia sign. Arch. Neurol. 60, 437–440.

Burton, D.L., Miller, D.L., Shill, C.T., 2002. A social learning theory comparison of thesexual victimization of adolescent sexual offenders and nonsexual offendingmale delinquents. Child Abuse Negl. 26, 893–907.

Cantor, J.M., Blanchard, R., 2012. White matter volumes in pedophiles, hebephiles,and teleiophiles. Arch. Sex. Behav. 41, 749–752.

Cantor, J.M., Blanchard, R., Christensen, B.K., Dickey, R., Klassen, P.E., Beckstead, A.L.,Blak, T., Kuban, M.E., 2004. Intelligence, memory, and handedness in pedophilia.Neuropsychology 18, 3–14.

Cantor, J.M., Kabani, N., Christensen, B.K., Zipursky, R.B., Barbaree, H.E., Dickey, R.,Klassen, P.E., Mikulis, D.J., Kuban, M.E., Blak, T., Richards, B.A., Hanratty, M.K.,Blanchard, R., 2008. Cerebral white matter deficiencies in pedophilic men. J.Psychiatr. Res. 42, 167–183.

Chow, E.W.C., Choy, A.L., 2002. Clinical characteristics and treatment response toSSRI in a female pedophile. Arch. Sex. Behav. 31, 211–215.

Cohen, J., 1992. A power primer. Psychol. Bull. 112, 323–340.Cohen, L.J., Galynker, I.I., 2002. Clinical features of pedophilia and implications for

treatment. J. Psychiatr. Pract. 8, 276–289.Cohen, L.J., Nikiforov, K., Gans, S., Poznansky, O., McGeoch, P., Weaver, C., King, E.G.,

Cullen, K., Galynker, I., 2002. Heterosexual male perpetrators of childhoodsexual abuse: a preliminary neuropsychiatric model. Psychiatr. Q 73, 313–336.

Dandescu, A., Wolfe, R., 2003. Considerations on fantasy use by child molesters andexhibitionists. Sex. Abuse 15, 297–305.

Deegener, G., 1996. Multiphasic Sex Inventory, 2nd ed. Hogrefe, Gottingen.Denov, M.S., 2003. The myth of innocence: sexual scripts and the recognition of

child sexual abuse by female perpetrators. J. Sex Res. 40, 303–314.Devinsky, J., Sacks, O., Devinsky, O., 2010. Kluver-Bucy syndrome, hypersexuality,

and the law. Neurocase 16, 140–145.Dreßing, H., Obergriesser, T., Tost, H., Kaumeier, S., Ruf, M., Braus, D.F., 2001.

Homosexuelle Padophilie und funktionelle Netzwerke. Fortschr. Neurol. Psy-chiatr. 69, 539–544.

Eher, R., Aigner, M., Fruehwald, S., Frottier, P., Gruenhut, C., 2000. Social informationprocessed self-perceived aggression in relation to brain abnormalities in asample of incarcerated sexual offenders. J. Psychol. Human Sex. 11, 37–47.

Fairweather, D.S., 1947. Psychiatric aspects of the post-encephalitic syndrome. Br. J.Psychiatry 93, 201–254.

Freund, K., Kuban, M., 1993. Toward a testable developmental model of pedophilia:the development of erotic age preference. Child Abuse Negl. 17, 315–324.

Fromuth, M.E., Burkhart, B.R., Jones, C.W., 1991. Hidden child molestation: aninvestigation of adolescent perpetrators in a nonclinical sample. J. Interpers.Violence 6, 376–384.

Gaffney, G.R., Lurie, S.F., Berlin, F.S., 1984. Is there familial transmission ofpedophilia? J. Nerv. Ment. Dis. 172, 546–548.

Genovese, C.R., Lazar, N.A., Nichols, T., 2002. Thresholding of statistical maps infunctional neuroimaging using the false discovery rate. Neuroimage 15, 870–878.

Georgiadis, J.R., Kringelbach, M.L., 2012. The human sexual response cycle: brainimaging evidence linking sex to other pleasures. Prog. Neurobiol. 98, 49–81.

Graber, B., Hartmann, K., Coffman, J.a., Huey, C.J., Golden, C.J., 1982. Brain damageamong mentally disordered sex offenders. J. Forensic Sci. 27, 125–134.

Grossman, L.S., Cavanaugh, J.L., 1990. Psychopathology and denial in alleged sexoffenders. J. Nerv. Ment. Dis. 178, 739–744.

Habermeyer, B., Esposito, F., Handel, N., Lemoine, P., Klarhofer, M., Mager, R.,Dittmann, V., Seifritz, E., Graf, M., 2013a. Immediate processing of erotic stimuliin paedophilia and controls: a case control study. BMC Psychiatry 13, 88–96.

Habermeyer, B., Esposito, F., Handel, N., Lemoine, P., Kuhl, H.C., Klarhofer, M., Mager,R., Mokros, A., Dittmann, V., Seifritz, E., Graf, M., 2013b. Response inhibition inpedophilia: an fMRI pilot study. Neuropsychobiology 68, 228–237.

Habermeyer, B., Handel, N., Lemoine, P., Klarhofer, M., Seifritz, E., Dittmann, V., Graf,M., 2012. LH-RH agonists modulate amygdala response to visual sexual stimu-lation: a single case fMRI study in pedophilia. Neurocase 18, 489–495.

Haldane, M., Cunningham, G., Androutsos, C., Frangou, S., 2008. Structural braincorrelates of response inhibition in bipolar disorder I. J. Psychopharmacol. 22,138–143.

Hanson, R.K., Morton-Bourgon, K.E., 2005. The characteristics of persistent sexualoffenders: a meta-analysis of recidivism studies. J. Consult. Clin. Psychol. 73,1154–1163.

Hathaway, S.R., McKinley, J.C., Engel, R.R., 2001. Minnesota-Multiphasic PersonalityInventory 2: MMPI-2. Huber, Bern.

Hendricks, S.E., Fitzpatrick, D.F., Hartmann, K., Quaife, M.A., Stratbucker, R.A.,Graber, B., 1988. Brain structure and function in sexual molesters of childrenand adolescents. J. Clin. Psychiatry 49, 108–112.

Hucker, S., Langevin, R., Wortzman, G., Bain, J., Handy, L., Chambers, J., Wright, S.,1986. Neuropsychological impairment in pedophiles. Can. J. Behav. Sci. 18, 440–448.

Joyal, C.C., Plante-Beaulieu, J., de Chanterac, A., 2014. The neuropsychology of sexualoffenders: a meta-analysis. Sex. Abuse 26, 149–177.

Kassubek, J., Abler, B., Pinkhardt, E.H., 2011. Neural reward processing underdopamine agonists: imaging. J. Neurol. Sci. 310, 36–39.

Kiehl, K.A., 2006. A cognitive neuroscience perspective on psychopathy: evidencefor paralimbic system dysfunction. Psychiatry Res. 142, 107–128.

Kingston, D.A., Firestone, P., Moulden, H.M., Bradford, J.M., 2007. The utility of thediagnosis of pedophilia: a comparison of various classification procedures. Arch.Sex. Behav. 36, 423–436.

Kluver, H., Bucy, P.C., 1939. Preliminary analysis of functions of the temporal lobesin monkeys. Arch. Neurol. Psychiatry 42, 979–1000.

Knight, R.A., 1988. A taxonomic analysis of child molesters. Ann. N. Y. Acad. Sci. 528,2–20.

Kriegeskorte, N., Simmons, W.K., Bellgowan, P.S.F., Baker, C.I., 2009. Circular analy-sis in systems neuroscience: the dangers of double dipping. Nat. Neurosci. 12,535–540.

Kruger, T.H.C., Schiffer, B., 2011. Neurocognitive and personality factors in homo-and heterosexual pedophiles and controls. J. Sex. Med. 8, 1650–1659.

Kuhn, S., Gallinat, J., 2011. A quantitative meta-analysis on cue-induced male sexualarousal. J. Sex. Med. 8, 2269–2275.

Langevin, R., Wortzman, G., Dickey, R., Wright, P., Handy, L., 1988. Neuropsycho-logical impairment in incest offenders. Sex. Abuse 1, 401–415.

Langevin, R., Wortzman, G., Wright, P., Handy, L., 1989. Studies of brain damage anddysfunction in sex offenders. Sex. Abuse 2, 163–179.

Lesniak, R., Szymusik, A., Chrzanowski, R., 1972. Multidirectional disorders of sexualdrive in a case of brain tumour. Forensic Sci. 1, 333–338.

Maletzky, B.M., Steinhauser, C., 2002. A 25-year follow-up of cognitive/behavioraltherapy with 7275 sexual offenders. Behav. Modif. 26, 123–147.

Marshall, W.L., 2008. Are pedophiles treatable? Evidence from North Americanstudies. Seksuologia Pol. 6, 39–43.

Marshall, W.L., Eccles, A., 1993. Pavlovian conditioning processes in adolescent sexoffenders. In: Barbaree, H.E., Marshall, W.L., Hudson, S.M. (Eds.), The JuvenileSex Offender. Guilford Press, New York, USA, pp. 118–142.

S. Mohnke et al. / Progress in Neurobiology 122 (2014) 1–23 23

Marshall, W.L., Marshall, L.E., 2000. The origins of sexual offending. Trauma Vio-lence Abuse 1, 250–263.

Marshall, W.L., Ward, T., Mann, R.E., Moulden, H., Fernandez, Y.M., Serran, G.,Marshall, L.E., 2005. Working positively with sexual offenders. Maximizingthe effectiveness of treatment. J. Interpers. Violence 20, 1096–1114.

Mendez, M., Shapira, J.S., 2011. Pedophilic behavior from brain disease. J. Sex. Med.8, 1092–1100.

Mendez, M.F., Chow, T., Ringman, J., Twitchell, G., Hinkin, C.H., 2000. Pedophilia andtemporal lobe disturbances. J. Neuropsychiatry Clin. Neurosci. 12, 71–76.

Miller, B.L., Cummings, J.L., McIntyre, H., Ebers, G., Grode, M., 1986. Hypersexualityor altered sexual preference following brain injury. J. Neurol. Neurosurg.Psychiatry 49, 867–873.

Mokros, A., Osterheider, M., Nitschke, J., 2012. Padophilie. Pravalenz, Atiologie undDiagnostik. Nervenarzt 83, 355–358.

Moulier, V., Fonteille, V., Pelegrini-Issac, M., Cordier, B., Baron-Laforet, S., Boriasse,E., Durand, E., Stoleru, S., 2012. A pilot study of the effects of gonadotropin-releasing hormone agonist therapy on brain activation pattern in a man withpedophilia. Int. J. Offender Ther. Comp. Criminol. 56, 50–60.

Muller, K., Curry, S., Ranger, R., Briken, P., Bradford, J., Fedoroff, J.P., 2014. Changes insexual arousal as measured by penile plethysmography in men with pedophilicsexual interest. J. Sex. Med. 11, 1221–1229.

Nunes, K.L., Hermann, C.A., Malcom, J.R., Lavoie, K., 2013. Childhood sexual victimi-zation, pedophilic interest, and sexual recidivism. Child Abuse Negl. 37, 703–711.

Oei, N.Y.L., Rombouts, S.A., Soeter, R.P., van Gerven, J.M., Both, S., 2012. Dopaminemodulates reward system activity during subconscious processing of sexualstimuli. Neuropsychopharmacology 37, 1729–1737.

Pardini, D.A., Raine, A., Erickson, K., Loeber, R., 2013. Lower amygdala volume in menis associated with childhood aggression, early psychopathic traits, and futureviolence. Biol. Psychiatry 75, 73–80.

Poeppl, T.B., Langguth, B., Laird, A.R., Eickhoff, S.B., 2014. The functional neuroanat-omy of male psychosexual and physiosexual arousal: a quantitative meta-analysis. Hum. Brain Mapp. 35, 1404–1421.

Poeppl, T.B., Nitschke, J., Dombert, B., Santtila, P., Greenlee, M.W., Osterheider, M.,Mokros, A., 2011. Functional cortical and subcortical abnormalities in pedo-philia: a combined study using a choice reaction time task and fMRI. J. Sex. Med.8, 1660–1674.

Poeppl, T.B., Nitschke, J., Santtila, P., Schecklmann, M., Langguth, B., Greenlee, M.W.,Osterheider, M., Mokros, A., 2013. Association between brain structure andphenotypic characteristics in pedophilia. J. Psychiatr. Res. 47, 678–685.

Polisois-Keating, A., Joyal, C.C., 2013. Functional neuroimaging of sexual arousal: apreliminary meta-analysis comparing pedophilic to non-pedophilic men. Arch.Sex. Behav. 42, 1111–1113.

Ponseti, J., Granert, O., Jansen, O., Wolff, S., Beier, K., Neutze, J., Deuschl, G., Mehdorn,H., Siebner, H., Bosinski, H., 2012. Assessment of pedophilia using hemodynamicbrain response to sexual stimuli. Arch. Gen. Psychiatry 69, 187–194.

Ponseti, J., Granert, O., van Eimeren, T., Jansen, O., Wolff, S., Beier, K., Deuschl, G.,Bosinski, H., Siebner, H., 2014. Human face processing is tuned to sexual agepreferences. Biol. Lett. 10, 20140200.

Potenza, M.N., 2013. Neurobiology of gambling behaviors. Curr. Opin. Neurobiol. 23,660–667.

Rainero, I., Rubino, E., Negro, E., Gallone, S., Galimberti, D., Gentile, S., Scarpini, E.,Pinessi, L., 2011. Heterosexual pedophilia in a frontotemporal dementia patientwith a mutation in the progranulin gene. Biol. Psychiatry 70, e43–e44.

Redoute, J., Stoleru, S., Gregoire, M.-C., Costes, N., Cinotti, L., Lavenne, F., Le Bars, D.,Forest, M.G., Pujol, J.-F., 2000. Brain processing of visual sexual stimuli in humanmales. Hum. Brain Mapp. 11, 162–177.

Regestein, Q.R., Reich, P., 1978. Pedophilia occuring after onset of cognitive ima-pairment. J. Nerv. Ment. Dis. 166, 794–798.

Rosler, A., Witztum, E., 1998. Treatment of men with paraphilia with a long-acting analogue of gonadotropin-releasing hormone. N. Engl. J. Med. 338,416–422.

Salter, D., McMillan, D., Richards, M., Talbot, T., Hodges, J., Bentovim, A., Hastings, R.,Stevenson, J., Skuse, D., 2003. Development of sexually abusive behaviour insexually victimised males: a longitudinal study. Lancet 361, 471–476.

All in-text references underlined in blue are linked to publications on Rese

Sartorius, A., Ruf, M., Kief, C., Demirakca, T., Bailer, J., Ende, G., Henn, F.A., Meyer-Lindenberg, A., Dressing, H., 2008. Abnormal amygdala activation profile inpedophilia. Eur. Arch. Psychiatry Clin. Neurosci. 258, 271–277.

Schacht, J.P., Anton, R.F., Myrick, H., 2013. Functional neuroimaging studies ofalcohol cue reactivity: a quantitative meta-analysis and systematic review.Addict. Biol. 18, 121–133.

Schiffer, B., Gizewski, E., Kruger, T., 2009. Reduced neuronal responsiveness to visualsexual stimuli in a pedophile treated with a long-acting LH-RH agonist. J. Sex.Med. 6, 892–894.

Schiffer, B., Krueger, T., Paul, T., de Greiff, A., Forsting, M., Leygraf, N., Schedlowski,M., Gizewski, E., 2008a. Brain response to visual sexual stimuli in homosexualpedophiles. J. Psychiatry Neurosci. 33, 23–33.

Schiffer, B., Paul, T., Gizewski, E., Forsting, M., Leygraf, N., Schedlowski, M., Kruger,T.H.C., 2008b. Functional brain correlates of heterosexual paedophilia. Neuro-image 41, 80–91.

Schiffer, B., Peschel, T., Paul, T., Gizewski, E., Forsting, M., Leygraf, N., Schedlowski,M., Krueger, T.H.C., 2007. Structural brain abnormalities in the frontostriatalsystem and cerebellum in pedophilia. J. Psychiatr. Res. 41, 753–762.

Schiffer, B., Vonlaufen, C., 2011. Executive dysfunctions in pedophilic and non-pedophilic child molesters. J. Sex. Med. 8, 1975–1984.

Schiltz, K., Witzel, J., Northoff, G., Zierhut, K., Gubka, U., Fellmann, H., Kaufmann, J.,Tempelmann, C., Wiebking, C., Bogerts, B., 2007. Brain pathology in pedophilicoffenders: evidence of volume reduction in the right amygdala and relateddiencephalic structures. Arch. Gen. Psychiatry 64, 737–746.

Schmidt, A.F., Mokros, A., Banse, R., 2013. Is pedophilic sexual preference continous?A taxometric analysis based on direct and indirect measures. Psychol. Assess.25, 1143–1153.

Seto, M.C., 2008. Pedophilia and Sexual Offending Against Children: Theory, Assess-ment, and Intervention. American Psychological Association, Washington, DC.

Seto, M.C., 2012. Is pedophilia a sexual orientation? Arch. Sex. Behav. 41, 231–236.Seto, M.C., Cantor, J.M., Blanchard, R., 2006. Child pornography offenses are a valid

diagnostic indicator of pedophilia. J. Abnorm. Psychol. 115, 610–615.Seto, M.C., Lalumiere, M.L., 2001. A brief screening scale to identify pedophilic

interests among child molesters. Sex. Abuse 13, 15–25.Stoleru, S., Fonteille, V., Cornelis, C., Joyal, C., Moulier, V., 2012. Functional neuro-

imaging studies of sexual arousal and orgasm in healthy men and women: areview and meta-analysis. Neurosci. Biobehav. Rev. 36, 1481–1509.

Stoleru, S., Gregoire, M.-C., Gerard, D., Decety, J., Lafarge, E., Cinotti, L., Lavenne, F., LeBars, D., Vernet-Maury, E., Rada, H., Collet, C., Mazoyer, B., Forest, M.G., Magnin,F., Spira, A., Comar, D., 1999. Neuroanatomical correlates of visually evokedsexual arousal in human males. Arch. Sex. Behav. 28, 1–21.

Tully, R.J., Chou, S., Browne, K.D., 2013. A systematic review on the effectiveness ofsex offender risk assessment tools in predicting sexual recidivism of adult malesex offenders. Clin. Psychol. Rev. 33, 287–316.

Wager, T.D., Sylvester, C.-Y.C., Lacey, S.C., Nee, D.E., Franklin, M., Jonides, J., 2005.Common and unique components of response inhibition revealed by fMRI.Neuroimage 27, 323–340.

Walter, M., 2008. Untersuchung spezifischer Hirnprozesse sexueller Verarbeitung beiGesunden und padophilen Patienten anhand funktioneller Kernspintomographie.(Dissertation)Otto-von-Guericke-Universitat Magdeburg, Germany.

Walter, M., Ponseti, J., Witzel, J., Bogerts, B., 2010. Hirnbiologische Marker in derDiagnostik und Behandlung der Padophilie und ihr Stellenwert fur gesellschaf-tliche Maßnahmen gegen sexuellen Missbrauch von Kindern. Forens. Psychiatr.Psychother. 17, 115–136.

Walter, M., Witzel, J., Wiebking, C., Gubka, U., Rotte, M., Schiltz, K., Bermpohl, F.,Tempelmann, C., Bogerts, B., Heinze, H.J., Northoff, G., 2007. Pedophilia is linkedto reduced activation in hypothalamus and lateral prefrontal cortex duringvisual erotic stimulation. Biol. Psychiatry 62, 698–701.

Weintraub, D., Koester, J., Potenza, M.N., Siderowf, A.D., Stacy, M., Voon, V., Whetteckey,J., Wunderlich, G.R., Lang, A.E., 2010. Impulse control disorders in Parkinson disease:a cross-sectional study of 3090 patients. Arch. Neurol. 67, 589–595.

Whitfield-Gabrieli, S., Ford, J.M., 2012. Default mode network activity and connec-tivity in psychopathology. Annu. Rev. Clin. Psychol. 8, 49–76.

Wright, P., Nobrega, J., Langevin, R., Wortzman, G., 1990. Brain density and sym-metry in pedophilic and sexually aggressive offenders. Sex. Abuse 3, 319–328.

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