EDITORIAL

Brain Connectivity and Applications to Neuropsychology:Introduction to the Special Issue of Neuropsychology Review

Bonnie J. Nagel

Received: 30 January 2014 /Accepted: 4 February 2014 /Published online: 13 February 2014# Springer Science+Business Media New York 2014

In recent years, understanding of human brain functioning hasdramatically been enhanced by neuroimaging techniques.While the field of neuropsychology was once largely in-formed by postmortem and lesion studies, which providedinsight into specific focal brain and behavioral relationships,it is now better appreciated that regions of the brain do notoperate in isolation but rather function as parts of rich inte-grated networks. The work that has most recently contributedto our understanding of network level brain functioning is thatusing analytic techniques to exploit temporal correlations inthe blood oxygen level-dependent (BOLD) response acrossthe brain, otherwise known as functional connectivity. Thisanalysis can be performed while engaged in a task or while atrest. The latter is less bound by the limitations imposed bytraditional task-based functional magnetic resonance imaging(fMRI) studies, in that it does not rely on a particular level orcomparability of task performance and is relatively easy andfast to collect. The amenability of the resting state paradigm tocreative study of a variety of patient populations, even thosewith dementing disorders, has enabled unprecedented expan-sion of knowledge regarding the underlying neurobiology ofmany disease states.

In This Issue

The authors of this special issue detail how functional con-nectivity studies have advanced our understanding of the brainas it relates to selective aspects of neuropsychological func-tioning in normal development and aging, disease states, and

with treatment. We start from an historical perspective bydirecting the reader to the pioneering work of D. O. Hebband his book, The Organization of Behavior, published in1949 [http://krishikosh.egranth.ac.in/bitstream/1/2027513/1/HS1199.pdf; http://deeplearning.cs.cmu.edu/pdfs/Hebb.1949.pdf]. Therein are the theoretical origins of brainconnectivity, described in chapter 4, “The First Stage ofPerception: Growth of the Assembly.” The noting of thischapter sets the stage for the empirical reviews, as Hebbdescribes the notion of cell “assembly,” forming the basis forwhat is now considered functional connectivity. With thisformative chapter, and through the five empirical reviewarticles, this special issue aims to demonstrate the utility offunctional connectivity studies for uncovering theneurobiological underpinnings of disease and behavior, aswell as how these techniques could be used to identifyneurobiological markers of rehabilitation. In addition toreviewing how functional connectivity studies have beenemployed to understand a specific patient population orphenomenon in neuropsychology, each review highlightskey methodological challenges for using this technique tostudy the connectivity of the human brain. Such issuesinclude addressing nuisance signal in the data, pros and consof seed-based versus independent component analysis ap-proaches, whole-brain versus region-of-interest analyses, andanalytic strategies to address network properties as opposed tosimply one-to-one connections (e.g., graph theory). Despitethe preponderance of methodological considerations that con-stitute this type of investigation, the reviews presented hereemphasize the promise of this technique to enhance under-standing of brain and behavior relationships across thelifespan in health and disease.

Park, Wang, and Posner introduce this issue with theirreview on how functional connectivity studies have informedour understanding of the neuropathological bases for attentiondeficit/hyperactivity disorder (ADHD). Findings from these

B. J. Nagel (*)Departments of Psychiatry and Behavioral Neuroscience, OregonHealth & Science University, 3181 SW Sam Jackson Park Road,DC7P, Portland, OR 97239, USAe-mail: nagelb@ohsu.edu

Neuropsychol Rev (2014) 24:1–2DOI 10.1007/s11065-014-9253-x

studies converge on three distinct networks in the brain: thedefault mode network (DMN), active during rest and oftensuppressed during active tasks; a cognitive control network;and both cognitive and affective cortico-striato-thalamo-corti-cal circuitry. Overall, these studies suggest a lack of typicallyobserved functional segregation between the DMN andcognitive control networks in ADHD, reduced within-DMN connectivity, and atypical connectivity in both cog-nitive and affective cortico-striato-thalamo-cortical loops,the latter of which shows dissociable correlates with ADHDsymptomatology.

Continuing studies on neurodevelopment, Maximo,Cadena, and Kana next explore functional connectivity stud-ies of autism. With the ultimate goal of using functionalconnectivity to identify neurobiological underpinnings of au-tism, and therefore possibly aid diagnosis, studies have dem-onstrated both hypo- and hyper-connectivity in several net-works, with findings of both more short-distance connectivityand attenuated long-distance connectivity across the autisticbrain. In addition, Maximo and colleagues detail studiesshowing parallel aberrations in the structural connectivity ofthe autistic brain, suggesting that the atypical connectivity ofthe brain may be a pathophysiological feature in the neurobi-ology of autism.

Moving into adult populations with a review on brainnetwork abnormalities in schizophrenia and a comprehensiveoverview of analytic techniques, van den Heuvel and Fornitodetail studies of both structural and functional connectivity inschizophrenia, as well as sophisticated graph theory ap-proaches designed to assess features of network integrity. Asis the case with the preceding reviewed populations, schizo-phrenia is associated with widespread connectivity abnormal-ities throughout the brain, including atypical connectivity inDMN, cognitive control, salience, and fronto-limbic net-works. Whereas structural connectivity studies have largelydemonstrated attenuated neuroanatomical connectivity inschizophrenia, functional connectivity studies have shownevidence for both hypo- and hyper-connectivity, with frontalbrain regions most commonly implicated. At a network level,both positive and negative schizophrenic symptoms have beenassociated with lower global network efficiency and lessclustering in the brain, with lower connectivity related topoorer cognitive functioning.

Dennis and Thompson address later stages of the lifespanin their contribution highlighting changes in functional con-nectivity in both normal and pathological aging, includingAlzheimer’s Disease. To examine resting state functional

connectivity in the brain during normal aging and Alzheimer’sDisease, Dennis and Thompson focus on seed-based, inde-pendent components analysis (ICA), and graph theory tech-niques. Not surprisingly, functional connectivity in the braindeclines over the normal aging process with regional variabil-ity, and abnormally fast degradation of connections in theAlzheimer’s Disease state. As is the case with many disorders,one of the networks most implicated in this disease process isthe DMN. Strikingly, while not the focus of the review, theauthors also detail findings from positron emission tomogra-phy (PET) studies showing that regions of the DMN aresusceptible to amyloid plaque deposition, which may be con-tributory in the decline of functional connectivity of thisnetwork.

The final review by Kelly and Castellanos describes howthese neuroimaging methods can be used to study neuralplasticity and recovery more broadly. They note that function-al connectivity is modified by experience and that both prac-tice and training highlight the plasticity of brain networkintegrity. This phenomenon, of particular importance to thefield of neuropsychology as it can help to explain the neuro-biology of brain injury and rehabilitation, can be observedfollowing training on perceptual, motor, and high level cog-nitive tasks. These effects have been observed in numerousbrain networks, and likely reflect increases in network effi-ciency, as well as reorganization and compensation of brainprocesses.

Concluding Comments

As is evident from the work put forth in this special issue,functional connectivity studies have vastly advanced ourknowledge on the neurobiology of development, aging, anddisease and how the brain responds, at a network level, toexperience. Additional work is needed to learn more about thebehavioral and neuropsychological correlates of connectivitypatterns in the brain and to specify how different disease statesare overlapping and dissociable from one another (i.e.,conducting studies across diagnostic categories and continua).One outcome of these pursuits will be to extend the applica-tion of functional connectivity studies to neuropsychologicalassessment and to ground neuroimaging findings in ecologi-cally valid contexts. Even in their infancy, it is clear thatmethods for discovering functional connectivity hold promisefor informing the field of neuropsychology, both at the diag-nostic and treatment level.

2 Neuropsychol Rev (2014) 24:1–2