poster #m177 lack of habituation of mirror neuron activity: study using transcranial magnetic...

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Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1S384 S255 differentially expressed mRNAs that belong to the transforming growth factor beta and the bone morphogenetic proteins signaling pathways, and in the parvalbumin (PV)-immunolabeled neurons from the same region differentially expressed transcripts were associated with WNT, NOTCH and PGE2 signaling and transcription factors such as LHX6, in addition to genes that regulate cell cycle and apoptosis. In the dopamine neurons from the substantia nigra in PD, there was a predominant down-regulation of genes that are involved in PD pathogenesis, such as members of the PARK gene family and genes associated with programmed cell death, mitochondrial dysfunction, neurotransmitter and ion channel receptors, as well as neu- ronal survival mechanisms. In addition to the gene expression proles, we identied a set of differentially expressed miRNAs in both SZ and PD. Enrichment analysis of their predicted targets revealed signaling pathways and gene networks that were also found by the microarrays to be dysreg- ulated raising an interesting possibility that dysfunction of these neurons in SZ or PD may in part be mediated by a concerted dysregulation of gene network functions as a result of the altered expression of miRNAs. Oligodendrocytes from SZ subjects, however, exhibit distinct expression pattern that is consistent with dysregulation of cell cycle events. Discussion: Our data show mostly distinct, but also some overlapping dysfunctional gene and miRNA networks between SZ and late stage PD, and provide a platform for future downstream analyses aiming to understand the molecular processes of individual neuronal dysfunction in psychiatric and neurological disorders. Poster #M177 LACK OF HABITUATION OF MIRROR NEURON ACTIVITY: STUDY USING TRANSCRANIAL MAGNETIC STIMULATION PARADIGMS Hulegar A. Abhishekh 1 , Urvaksh M. Mehta 2 , Rakshathi Basavaraju 2 , Jagadisha Thirthalli 2 , Bangalore Gangadhar 2 1 Bangalore Medical College and Research Institute; 2 National Institute of Mental Health & Neurosciences (NIMHANS) Background: Mirror neurons are specialized aggregation of nerve cells that re during performance of an action as well as during observation of the same action. They are hypothesized to underlie social cognition abilities in both healthy and diseased states. Neuronal habituation refers to decreased ring of neurons due to repeated stimuli. There is little evidence on habit- uation of mirror neurons in humans. In this study we assessed if mirror neurons demonstrated habituation in healthy individuals and patients with schizophrenia. Methods: Fifty-four right handed schizophrenia patients and 45 healthy controls underwent a TMS experiment to assess putative premotor mirror neuron activity (MNA). We used 10 stimuli each of resting motor thresh- old (RMT), motor threshold to elicit 1 millivolt amplitudes of potentials (MT1), short and long interval intracortical inhibition (SICI/LICI) paradigms in random sequence in right rst dorsal interosseous (FDI) muscle. These were applied while the subjects observed a goal-directed action involving the FDI (actual action and its video) and a static image. The difference in the amplitude of the motor evoked potential (MEP) while they observed the static image and the action provided a measure of MNA. Habituation pattern was assessed by analyzing the MEP across each of the 10 trials of individual stimulus paradigms. Results: RMANOVA did not show statistically signicant differences in measures of MNA across trials in RMT, SICI, MT1 and LICI parameters. There was no difference in habituation pattern of MNA across the patient group and healthy individuals. Discussion: This experiment shows lack of habituation pattern in MNA in schizophrenia patients and healthy controls, which is consistent with similar ndings in primate experiments. These results also have implication in designing TMS experiment as increased trials might give more accurate information without being confounded by adaptation phenomenon. Poster #M178 VISUAL HABITUATION IS IMPAIRED IN SCHIZOPHRENIA: A STUDY WITH PATTERN REVERSAL VISUAL EVOKED POTENTIALS Giorgio Di Lorenzo 1 , Fabio Ciabattini 2 , Andrea Daverio 2 , Fabiola Ferrentino 2 , Gianluca Coppola 3 , Cherubino Di Lorenzo 4 , Cinzia Niolu 5 , Francesco Pierelli 6 , Alberto Siracusano 7 , Stefano Seri 8 1 Laboratory of Psychophysiology, Chair of Psychiatry, Department of Systems Medicine, University of Rome; 2 Laboratory of Psychophysiology, Chair of Psychiatry, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; 3 G.B. Bietti Eye Foundation – IRCCS, Dept of Neurophysiology of Vision and Neurophthalmology, Rome, Lazio, Italy; 4 Don Carlo Gnocchi Onlus Foundation, Italy; 5 Chair of Psychiatry, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Lazio, Italy; 6 IRCCS – Neuromed, Pozzilli, Isernia, Italy; 7 Laboratory of Psychophysiology, Chair of Psychiatry, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Lazio, Italy; 8 School of Life and Health Sciences, Wellcome Laboratory for MEG Studies, Aston Brain Centre, Aston University, Birmingham, UK Background: Schizophrenia is characterized by impairment in a wide range of cognitive domains and perceptual modalities including early stages of visual processing. Visual habituation, a reduction of the visual evoked response to sequential presentation of spatially structured stimuli, is a direct measure of visual cortex excitability. As a measure of sensory gating, this phenomenon has been considered as a protective mechanism against over-stimulation. Impaired habituation mechanisms have been suggested to play a key role in the pathophysiology of schizophrenia. We investigated visual habituation with a Pattern-Reversal Visual Evoked Potential (PR-VEP) paradigm to verify whether patients with Schizophrenia (SCZ) showed abnormalities in the evoked response amplitude compared to healthy volunteers (HV). Methods: Thirty-three SCZ (21 men and 12 women; age, mean ±SD: 35.67±10.21), with a clinical and pharmacological stable condition, were selected from an outpatient program. Thirty-three HV (21 men and 12 women; age: 34.91±9.77) was recruited as control group. EEG signal was continuously recorded from a midline occipital electrode. Monocularly full-eld black-and-white checkerboard pattern subtending 15’ of arc was presented, reversing in contrast at 3.1 reversal/s with 100% contrast for 800 consecutive trials. The EEG recording was divided in eight blocks of 100 consecutive trials. The peak latencies of N75, P100 and N145 components as well as the N75-P100 and P100-N145 peak-to-peak amplitudes for each block were measured. As a measure of habituation we used the slope of the linear regression line of the N75-P100 and P100-N145 peak-to-peak amplitudes. Results: Schizophrenia patients had signicantly lower N75-P100 and P100-N145 amplitudes than healthy volunteers in the eight-block PR-VEP grand-average. Repeated measure ANOVA models showed that the N75- P100 and P100-N145 amplitudes for the whole sample decreased between rst and eighth block. There was a signicant difference between healthy volunteers and schizophrenia patients who did not present a reduction in VEP amplitude over the eight blocks. The slope measure conrmed the impaired visual habituation in the schizophrenia patients respect to healthy volunteers. We didn’t nd signicant differences between the two groups in the N75, P100 and N145 latencies in the average response to the 800 stimuli and between the 8 blocks. Discussion: The ndings of this study contribute to the existing evidence of impaired early sensory processing in schizophrenia. One of the possi- ble pathophysiological mechanisms of the visual habituation decit could involve occipital lobe structures regulating neuronal inhibitory/excitatory balance, and in particular of decit in GABA-ergic transmission in the visual cortex. Our data suggests that gating decits in schizophrenia involve multiple sensory domains and visual habituation should be investigated more systematically. Poster #M179 REDUCED THETA BAND RESPONSE TO RELEVANCE IN SCHIZOPHRENIA Alvaro Diez 1 , Alvaro Diez 2 , Alejandro Bachiller 3 , Manuel Martín-Loeches 4 , Pilar Casado 4 , Jesús Poza 3 , Roberto Hornero 3 , Vicente Molina 5 1 Mental Health Sciences Unit - University College London; 2 University College London; 3 University of Valladolid; 4 UCM-ISCIII Center for Human Evolution and Behavior; 5 Hospital Clínico Univ. Valladolid. Spain Background: Alterations in differential processing of relevant versus irrel- evant stimuli may contribute to abnormal salience in schizophrenia. Methods: EEG was recorded and analyzed in both chronic and minimally

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Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384 S255

differentially expressed mRNAs that belong to the transforming growth

factor beta and the bone morphogenetic proteins signaling pathways, and

in the parvalbumin (PV)-immunolabeled neurons from the same region

differentially expressed transcripts were associated with WNT, NOTCH and

PGE2 signaling and transcription factors such as LHX6, in addition to genes

that regulate cell cycle and apoptosis. In the dopamine neurons from the

substantia nigra in PD, there was a predominant down-regulation of genes

that are involved in PD pathogenesis, such as members of the PARK gene

family and genes associated with programmed cell death, mitochondrial

dysfunction, neurotransmitter and ion channel receptors, as well as neu-

ronal survival mechanisms. In addition to the gene expression profiles,

we identified a set of differentially expressed miRNAs in both SZ and PD.

Enrichment analysis of their predicted targets revealed signaling pathways

and gene networks that were also found by the microarrays to be dysreg-

ulated raising an interesting possibility that dysfunction of these neurons

in SZ or PD may in part be mediated by a concerted dysregulation of

gene network functions as a result of the altered expression of miRNAs.

Oligodendrocytes from SZ subjects, however, exhibit distinct expression

pattern that is consistent with dysregulation of cell cycle events.

Discussion: Our data show mostly distinct, but also some overlapping

dysfunctional gene and miRNA networks between SZ and late stage PD, and

provide a platform for future downstream analyses aiming to understand

the molecular processes of individual neuronal dysfunction in psychiatric

and neurological disorders.

Poster #M177

LACK OF HABITUATION OF MIRROR NEURON ACTIVITY: STUDY USING

TRANSCRANIAL MAGNETIC STIMULATION PARADIGMS

Hulegar A. Abhishekh1, Urvaksh M. Mehta2, Rakshathi Basavaraju2,

Jagadisha Thirthalli2, Bangalore Gangadhar2

1Bangalore Medical College and Research Institute; 2National Institute of

Mental Health & Neurosciences (NIMHANS)

Background: Mirror neurons are specialized aggregation of nerve cells that

fire during performance of an action as well as during observation of the

same action. They are hypothesized to underlie social cognition abilities in

both healthy and diseased states. Neuronal habituation refers to decreased

firing of neurons due to repeated stimuli. There is little evidence on habit-

uation of mirror neurons in humans. In this study we assessed if mirror

neurons demonstrated habituation in healthy individuals and patients with

schizophrenia.

Methods: Fifty-four right handed schizophrenia patients and 45 healthy

controls underwent a TMS experiment to assess putative premotor mirror

neuron activity (MNA). We used 10 stimuli each of resting motor thresh-

old (RMT), motor threshold to elicit 1 millivolt amplitudes of potentials

(MT1), short and long interval intracortical inhibition (SICI/LICI) paradigms

in random sequence in right first dorsal interosseous (FDI) muscle. These

were applied while the subjects observed a goal-directed action involving

the FDI (actual action and its video) and a static image. The difference in

the amplitude of the motor evoked potential (MEP) while they observed

the static image and the action provided a measure of MNA. Habituation

pattern was assessed by analyzing the MEP across each of the 10 trials of

individual stimulus paradigms.

Results: RMANOVA did not show statistically significant differences in

measures of MNA across trials in RMT, SICI, MT1 and LICI parameters. There

was no difference in habituation pattern of MNA across the patient group

and healthy individuals.

Discussion: This experiment shows lack of habituation pattern in MNA

in schizophrenia patients and healthy controls, which is consistent with

similar findings in primate experiments. These results also have implication

in designing TMS experiment as increased trials might give more accurate

information without being confounded by adaptation phenomenon.

Poster #M178

VISUAL HABITUATION IS IMPAIRED IN SCHIZOPHRENIA: A STUDY WITH

PATTERN REVERSAL VISUAL EVOKED POTENTIALS

Giorgio Di Lorenzo1, Fabio Ciabattini2, Andrea Daverio2,

Fabiola Ferrentino2, Gianluca Coppola3, Cherubino Di Lorenzo4,

Cinzia Niolu5, Francesco Pierelli6, Alberto Siracusano7, Stefano Seri8

1Laboratory of Psychophysiology, Chair of Psychiatry, Department of Systems

Medicine, University of Rome; 2Laboratory of Psychophysiology, Chair of

Psychiatry, Department of Systems Medicine, University of Rome “Tor Vergata”,

Rome, Italy; 3G.B. Bietti Eye Foundation – IRCCS, Dept of Neurophysiology of

Vision and Neurophthalmology, Rome, Lazio, Italy; 4Don Carlo Gnocchi Onlus

Foundation, Italy; 5Chair of Psychiatry, Department of Systems Medicine,

University of Rome “Tor Vergata”, Rome, Lazio, Italy; 6IRCCS – Neuromed,

Pozzilli, Isernia, Italy; 7Laboratory of Psychophysiology, Chair of Psychiatry,

Department of Systems Medicine, University of Rome “Tor Vergata”, Rome,

Lazio, Italy; 8School of Life and Health Sciences, Wellcome Laboratory for MEG

Studies, Aston Brain Centre, Aston University, Birmingham, UK

Background: Schizophrenia is characterized by impairment in a wide range

of cognitive domains and perceptual modalities including early stages of

visual processing. Visual habituation, a reduction of the visual evoked

response to sequential presentation of spatially structured stimuli, is a

direct measure of visual cortex excitability. As a measure of sensory gating,

this phenomenon has been considered as a protective mechanism against

over-stimulation. Impaired habituation mechanisms have been suggested

to play a key role in the pathophysiology of schizophrenia. We investigated

visual habituation with a Pattern-Reversal Visual Evoked Potential (PR-VEP)

paradigm to verify whether patients with Schizophrenia (SCZ) showed

abnormalities in the evoked response amplitude compared to healthy

volunteers (HV).

Methods: Thirty-three SCZ (21 men and 12 women; age, mean ±SD:

35.67±10.21), with a clinical and pharmacological stable condition, were

selected from an outpatient program. Thirty-three HV (21 men and 12

women; age: 34.91±9.77) was recruited as control group. EEG signal was

continuously recorded from a midline occipital electrode. Monocularly

full-field black-and-white checkerboard pattern subtending 15’ of arc was

presented, reversing in contrast at 3.1 reversal/s with 100% contrast for 800

consecutive trials. The EEG recording was divided in eight blocks of 100

consecutive trials. The peak latencies of N75, P100 and N145 components

as well as the N75-P100 and P100-N145 peak-to-peak amplitudes for each

block were measured. As a measure of habituation we used the slope of

the linear regression line of the N75-P100 and P100-N145 peak-to-peak

amplitudes.

Results: Schizophrenia patients had significantly lower N75-P100 and

P100-N145 amplitudes than healthy volunteers in the eight-block PR-VEP

grand-average. Repeated measure ANOVA models showed that the N75-

P100 and P100-N145 amplitudes for the whole sample decreased between

first and eighth block. There was a significant difference between healthy

volunteers and schizophrenia patients who did not present a reduction in

VEP amplitude over the eight blocks. The slope measure confirmed the

impaired visual habituation in the schizophrenia patients respect to healthy

volunteers. We didn’t find significant differences between the two groups

in the N75, P100 and N145 latencies in the average response to the 800

stimuli and between the 8 blocks.

Discussion: The findings of this study contribute to the existing evidence

of impaired early sensory processing in schizophrenia. One of the possi-

ble pathophysiological mechanisms of the visual habituation deficit could

involve occipital lobe structures regulating neuronal inhibitory/excitatory

balance, and in particular of deficit in GABA-ergic transmission in the

visual cortex. Our data suggests that gating deficits in schizophrenia involve

multiple sensory domains and visual habituation should be investigated

more systematically.

Poster #M179

REDUCED THETA BAND RESPONSE TO RELEVANCE IN SCHIZOPHRENIA

Alvaro Diez1, Alvaro Diez2, Alejandro Bachiller3, Manuel Martín-Loeches4,

Pilar Casado4, Jesús Poza3, Roberto Hornero3, Vicente Molina5

1Mental Health Sciences Unit - University College London; 2University College

London; 3University of Valladolid; 4UCM-ISCIII Center for Human Evolution

and Behavior; 5Hospital Clínico Univ. Valladolid. Spain

Background: Alterations in differential processing of relevant versus irrel-

evant stimuli may contribute to abnormal salience in schizophrenia.

Methods: EEG was recorded and analyzed in both chronic and minimally