Conference Agenda

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Session Overview
Session
Poster Lunch 2: Psychiatry
Time:
Friday, 01/Sep/2017:
12:30pm - 2:30pm

Location: Poster Area

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Presentations

Change of cross frequency coupling by Symptom Provocation in OCD

Masafumi Yoshimura1, Roberto D. Pascual-Marqui1,2, Keiichiro Nishida1, Yuichi Kitaura1, Hiroshi Mii1,3, Yukiko Saito1, Shunichiro Ikeda1,4, Koji Katsura1, Satsuki Ueda1, Shota Minami1, Toshiaki Isotani1,5, Toshihiko Kinoshita1

1Kansai Medical University, Japan; 2The KEY Institute for Brain-Mind Research, Switzerland; 3Setagawa Hospital, Japan; 4University Hospital of Psychiatry Bern, Switzerland; 5Shikoku University, Japan

[Introduction] We investigated the changes in directional cross frequency interactions between theta and alpha oscillations, across six cortical regions, induced by a symptom provocation procedure, in patients with obsessive compulsive disorder (OCD), and in a normal control group.

[Methods] Nine OCD outpatients and nine healthy controls participated in this study. Awake, eyes closed EEG was recorded under conditions (C1) initial rest, (C2) while gently holding a clean paper towel, and (C3) under the instruction to imagine that the towel is repulsively contaminated (symptom provocation, SP). For each condition, signals of cortical electric neuronal activity (i.e. current density) were calculated with sLORETA at medial-prefrontal, precuneus, inferior-parietal, and dorsolateral-prefrontal cortices. Instantaneous amplitudes for the theta (4-8Hz) and alpha (9-14Hz) bands were obtained and used for computing Granger causal directional cross-frequency, cross-cortical interactions.

[Results] The effect of SP was assessed by comparing conditions C2 minus C3. In controls, SP is characterized by a significant increase in mPFC theta due to right fronto-parietal alpha. In contrast, SP in the OCD group mainly displayed alpha-alpha RIPL alpha decrease due to RDLPFC. A direct comparison of OCD and normal controls in the SP condition (C2) showed significant frontal decreases of theta-alpha interactions.

[Discussion] The symptom provocation procedure induced functional changes of cross-frequency connections both in OCD and control mainly involving core right hemisphere network nodes. Functional cross-frequency interactions involving all frontal nodes were decreased in OCD compared to controls during SP. These results support the use of cross-frequency interactions a possible trait marker of OCD.


Effects of Neurexan® on brain regions associated with emotional expectancy

Sarah Alizadeh1, Yan Fan2,3, Anne Kühnel1,2, Luisa Fensky1, Tibor Tar5, Myron Schultz5, Martin Walter1,2,4

1Department of Psychiatry and Psychotherapy, University Tübingen, Tübingen, Germany; 2Clinical Affective Neuroimaging Laboratory, Magdeburg, Germany; 3Department of Psychiatry, CBF, Charité, Berlin, Germany; 4Leibniz Institute for Neurobiology, Magdeburg, Germany; 5Biologische Heilmittel Heel GmbH, Baden-Baden, Germany

Background: Neurexan® is a medicinal product containing four ingredients; passionflower, oats, coffee and zinc valerianate. It has been shown to reduce nervousness, restlessness, acute stress, and insomnia by modulating biological auto-regulating processes. Induced stress sensitizes the amygdala, which increases vigilance and in turn drives the stress response. This is mediated by an amygdala-prefrontal cortex circuit, in which stress impairs the top-down cognitive functions of prefrontal regions, while strengthening the emotional bottom-up responses of the amygdala. We therefore hypothesized that Neurexan® may induce changes in amygdala activation during emotion processing elicited by an emotional expectancy task.

Method: The drug effect was investigated in a randomized, placebo-controlled, double-blind, two-period-crossover clinical trial. The brain response of 37 male subjects to the emotional expectancy paradigm was measured after intake of a single dose of Neurexan® or placebo by 3T functional magnetic resonance imaging. During the task, negative, positive, and neutral IAPS pictures were presented, half of them preceded by visual cues. The visual cues before picture presentation were arrows pointing up (positive picture), down (negative picture) and to the right (neutral picture). The drug effect was assessed with paired t-test comparing drug and placebo condition in the contrast expectancy positive > expectancy negative.

Results: We found amygdala activation in response to expected pictures. Furthermore, we observed significant differences in activation of the left amygdala during the expectancy task under drug compared to placebo condition. The differences in activation are explained by reduced changes in amygdala reactivity modulated by Neurexan® during expectancy of emotional pictures.


Stress-induced changes of amygdala-centered resting state functional connectivity are modified by Neurexan®

Hamidreza Jamalabadi3, Yan Fan1,2, Luisa Fensky3, Anne Kühnel1,3, Vanessa Teckentrup3, Tibor Tar5, Myron Schultz5, Martin Walter1,3,4

1Clinical Affective Neuroimaging Laboratory, Magdeburg, Germany; 2Department of Psychiatry, CBF, Charité, Berlin, Germany; 3Department of Psychiatry and Psychotherapy, University Tübingen, Tübingen, Germany; 4Leibniz Institute for Neurobiology, Magdeburg, Germany; 5Biologische Heilmittel Heel GmbH, Baden-Baden, Germany

Objectives: Neurexan® is a medicinal product containing four ingredients, passionflower, oats, coffee, and zinc valerianate. Neurexan® has been shown to reduce nervousness, restlessness, acute stress, and insomnia. Recent research suggested that it attenuates the neuroendocrine stress response in healthy volunteers. It is known that acute stress initiates changes in functional connectivity (FC) between amygdala and cortical regions. Additionally, changes in amygdala centered resting state functional connectivity (rs-FC) are also associated with trait and pathological anxiety. In the present study, we explored if Neurexan® moderates the effect of acute stress on the amygdala-centered rs-FC and if this is further influenced by trait anxiety or behaviors related to anxiety symptoms.

Methods: Thirty-nine healthy male subjects (age=43.7±9.8) participated in a double-blind, randomized, placebo-controlled, crossover clinical trial employing fMRI imaging. In each scanning session, an 11-min resting state (RS) measurement was performed at two time points: after the intake of a single dose of Neurexan® or placebo (RS1), and after the participants completed the stress task (RS2). Bilateral centromedial (CeA) and basolateral (BLA) subregions of the amygdala were used as seeds to calculate resting state FC maps. The treatment effects were analyzed with whole–brain within–subject ANOVA.

Results: A significant effect of Neurexan® was found on rs-FC between left centromedial amygdala and cortical regions including the left PFC and IFG as well as right centromedial amygdala and precuneus, right IFG and IPL. Furthermore, anxiety measures predicted the Neurexan® effect on stress-induced rs-FC changes from right BLA to vmPFC, left Amygdala, and right IFG.


Effects of Neurexan® on reduced stress responsivity in the autonomic nervous system measured by heart rate variability

Hamidreza Jamalabadi2, Tara Chand2, Sarah Alizadeh2, Myron Schultz4, Martin Walter1,2,3

1Clinical Affective Neuroimaging Laboratory, Magdeburg, Germany; 2Department of Psychiatry and Psychotherapy, University Tübingen, Tübingen, Germany; 3Leibniz Institute for Neurobiology, Magdeburg, Germany; 4Biologische Heilmittel Heel GmbH, Baden-Baden, Germany

Objectives: Cardiovascular function is critical to adaptive behavior and can be measured by heart rate variability (HRV) which is controlled by the Autonomic Nervous System (ANS). Previous studies have shown that the ongoing variability in ANS tone measured by HRV is associated with stress-induced changes in dACC and amygdala functional connectivity. Neurexan®, a medicinal product sold over the counter, contains passionflower, oats, coffee and zinc valerianate. It has been investigated in patients with symptoms related to acute stress, nervousness/restlessness, and insomnia. The previous research suggested attenuated neuroendocrine stress response in healthy volunteers, altered stress reactivity, and lowered amygdala activation after Neurexan® intake. This study explores the effects of Neurexan® on the sympathetic and parasympathetic nervous systems and the stress responsivity in ANS measured by HRV.

Methods: Thirty-nine healthy male subjects participated in a double-blind, randomized, placebo-controlled, two-period crossover study assessing HRV during the scanning sessions. On the first treatment day, half of the participants took Neurexan® (N=20) or placebo (N=19) and vice versa on the second day. The participants performed the ScanSTRESS, which uses arithmetic and mental rotation tasks to induce stress, after intake of Neurexan® or placebo, respectively. Heart rate was continuously measured by photoplethysmography.

Results: To measure the drug effect, we performed paired t-test between drug and placebo conditions during the stress task. We found a significant drug effect in low frequency and high frequency ratio (LF/HF ratio) (p = 0.01; T=-2.5). Under drug LF/HF was significantly reduced compared to placebo, suggesting a dampened stress response.


Visual, auditory and bimodal ERP oddball designs in patients with schizophrenia, schizoaffective disorder and bipolar disorder. Does the use of different oddball tasks have an impact on the P300 component?

Hendrik Kajosch, Kornreich Charles, Steegen Geertje, Cimochowska Agnieszka, Fossion Pierre, Campanella Salvatore

CHU Brugmann, Institut de Psychiatrie, Belgium

The P300 is one of the most investigated event-related potentials (ERPs) in the study of psychiatric disorders. Nevertheless it suffers from a lack of specificity and sensitivity. In previous studies (Campanella et al., 2010; 2012), the application of a more ecological bimodal oddball design has shown an increased sensitivity of the P300 component .

In the present ongoing study we compare the results of a classic oddball design procedure with those of a more ecological bimodal design in three groups of patients presenting schizophrenia (SZ), schizoaffective (SA) and bipolar (BD) disorder matched to a group of healthy controls (HC). Patients were examined at three times: T0: admission at the hospital; T1: before leaving the hospital; and T2: six months after leaving the hospital. Patients were assessed through a structured clinical interview (SCID, ref), and a completion of different clinical evaluation scales (PANSS, Young Mania Scale, Beck, Stai,…). All groups were then confronted to an EEG recording (20 channels, A.N.T. software) during successive oddball tasks.

The objectives of this study are twofold: (1) investigate whether the use of a specific oddball task (visual vs. auditory vs. cross-modal) allowed to enhance the discriminative power of the P300 between psychotic patients and healthy controls; and (2) investigate the correlations between the evolution from To to T2 of the P300 and the evolution of the clinical evaluation of the patient.

Here we would like to present further results of this clinical study, especially those of the group of patients presenting schizophrenia.


Effects of Neurexan® on brain responses to deviant stimuli during an auditory oddball task

Sarah Alizadeh1, Galina Surova2, Hamidreza Jamalabadi1, Myron Schultz4, Martin Walter1,2,3

1Department of Psychiatry and Psychotherapy, University Tübingen, Tübingen, Germany; 2Clinical Affective Neuroimaging Laboratory, Magdeburg, Germany; 3Leibniz Institute for Neurobiology, Magdeburg, Germany; 4Biologische Heilmittel Heel GmbH, Baden-Baden, Germany

Background: Neurexan®, a medicinal product sold over the counter, contains four ingredients; passionflower, oats, coffee and zinc valerianate. Neurexan® has been investigated in patients with symptoms related to acute stress, nervousness/restlessness, and insomnia. The previous research suggested an attenuated neuroendocrine stress response in healthy volunteers induced by Neurexan®. This study further explores the effects of Neurexan® on cognitive performance and attention that can be assessed by the oddball paradigm. It is generally recognized that stress is associated with cognitive impairments. Expecting that Neurexan® reduces the stress level, we hypothesized that subjects in the placebo group would be more susceptible to distraction compared to treatment group.

Methods: In a randomized, placebo-controlled, double-blind, two-period crossover trial, brain responses of 39 healthy, moderately stressed males were measured during an unattended auditory oddball paradigm via 64-channel electroencephalogram (EEG) after intake of a single dose of Neurexan® or placebo. The paradigm consisted of 80% standard tones and two types of deviant tones (10% frequency deviant; 10% duration deviant), presented in a pseudo-randomized order.

Results: Significant effect of Neurexan® on the latency of mismatch negativity decreased latency under treatment) was observed with repeated-measures ANOVA. The main effect of treatment (F(1,37)=4.297, p=.045, η2=.104) and significant treatment x deviant-type interaction (F(1,37)=8.828, p=.005, η2=.193) were found. Further Wilcoxon-test for paired samples showed that reduction of latency was present for the frequency deviant stimuli (z(37)=-2.85, p=.004).

Conclusion: Significant reduction of MMN latency under drug suggests that Neurexan® leads to subtle primary processing changes in term of reaction time.


EEG correlates of the serotonergic hallucinogens as a parameter of assessing translational validity of the serotonergic model of psychosis in rats

Čestmír Vejmola1,2, Filip Tylš1,2, Michaela Lipski1,2, Tomáš Páleníček1,2

1National Institute of Mental Health, Czech Republic; 2Third Faculty of Medicine, Charles University in Prague

Since the discovery of LSD, serotonergic hallucinogens have been used to experimentally model psychosis, even in animals. Its translational validity can be verified by the degree of similarity between various measurable values in both species. Consensus in behavior (disorganization, increased anxiety, occurrence of stereotypical movements) and information processing was already observed. Similarity in the EEG signal between psychotic patients and intoxicated rats has not yet been verified.

The aim of this study was to describe changes in cortical EEG after administration of various serotonergic hallucinogens – psilocin, LSD, mescaline and DOB and compare these results with human data of psychotic patients.

12 rats for each group were implanted with 14 cortical electrodes. EEG was recorded seven days later. After the first ten minutes of recording (baseline), the treatment was applied and recording continued for another 90 minutes. Only signal of selected time segments of behavioral inactivity was evaluated. Quantitative (spectral and coherence) analysis in the Neuroguide program was performed.

EEG power spectral analysis revealed a general decrease in absolute EEG power in all frequency bands in all drug conditions. A common reduction in coherences, especially fronto-temporal in higher frequencies has also been shown.

Serotonergic hallucinogens cause profound electrophysiological changes in the rat brain. The results also revealed some characteristic patterns in the EEG of individual substances. The observed decrease in functional connectivity in rats was also observed in human subjects under the influence of psychedelics and is, in some cases, a common finding in psychotic patients.


Functional Connectivity Embedding for Electrophysiological Models of Induced Psychosis

Vlastimil Koudelka1, Filip Tyls1, Cestmir Vejmola1,2, Martin Brunovsky1,2, Tomas Palenicek1,2, Jiri Horacek1,2

1National Institute of Mental Health, Klecany, Czech Republic; 23rd Faculty of Medicine, Charles University in Prague

Introduction: The presented method deals with changes in human and rats brain functional EEG connectivity conditioned by administration of psilocin (in rats) and psilocybin (in human). The searched similarities between rats and human models are difficult to be found when preserving low-level information e.g. all combinations of connections within all frequency bands in all epochs. Here, we show that unique functional brain clusters coherently modulated by a particular substance are embedded in multi-dimensional space of coherences and can be extracted by appropriate dimensional reduction technique.

Methods: EEG recordings were acquired with respect to pharmacokinetics of psilocin (in rats) and psilocybin (in human). Weighted phase lag indices (WPLI) were calculated at four time epochs after administration. WPLI time differences between epochs were calculated and t-Distributed Stochastic Neighbor embedding (t-SNE) reduced data dimension. A number of clusters was determined by silhouette clustering index and similarities were labeled by k-means algorithm. Surrogate series preserving power spectrum of instantaneous angular frequency in EEG data were generated to statistically address the clustering properties.

Results: Preliminary results of psilocin in rats clearly showed four clusters of connections. Three clusters were localized intra-hemispherically and only one connected both hemispheres together. In human, the psilocybin resulted in two symmetric clusters distributed mostly intra-hemispherically.

Conclusion: Developed method is capable to extract individual (rats or human) and common (rats and human) long term connectivity dynamics induced by drug administration.

This work was supported by the grants GACR 17-23718S, AZV 15-29370A, Progres Q35, and project LO1611 under the NPU I program.


Decreased negative emotion after single-session tDCS on F5 in patients suffering with depression

Keiichiro Nishida1, Yosuke Morishima2, Masafumi Yoshimura1, Koji Katsura1, Satsuki Ueda1, Shunichiro Ikeda1,2, Yousuke Koshikawa1, Azusa Suwa1, Shota Minami1, Ryouhei Ishii3, Roberto Pascual-Maruqui1,4, Toshihiko Kinoshita1

1Department of Neuropsychiatry, Kansai Medical University; 2Division of Systems Neuroscience of Psychopathology, Translational Research Center, University Hospital of Psychiatry, University of Bern; 3Department of Psychiatry, Osaka University Graduate School of Medicine; 4The KEY Institute for Brain-Mind Research, University of Zurich

[Introduction] Transcranial Direct Current Stimulation (tDCS) is getting interests in treatment of psychiatric disorders. As the electrode montage of tDCS defines flow of stimulation current, optimization of an electrode montage is crucial for treatment applications.

The aim of this study is to investigate tDCS effects with different montages in patients with major depression.

[Methods] Eighteen patients and 20 healthy controls (HC) participated. 1 mA tDCS was administered for 20 min either on the DLPFC (F5 EEGelectrode) or medial prefrontal cortex (AFz). Patients and HC received tDCS on one of the site in a randomized order. The Positive and negative affect schedule (PANAS) and State-Trait Anxiety Inventory (STAI) tests were measured before and after tDCS for each session.

[Results] We found that PANAS negative affect scores in the patient group decreased after tDCS only in the F5 stimulation, while no effect in the AFz stimulation condition. No significant tDCS effects were observed in the STAI scores of patients. In controls, there was no significant changes neither in PANAS scores nor STAI scores.

[Conclusion] A previous tDCS study on location of F3 EEG electrode showed no significant changes in PANAS scores in patients with major depression (Wolkenstein and Plewnia, 2013). We consider this discrepancy can be explained by the difference in electrode montages. In conclusion, we argue that the anterior part of the DLPFC could have stronger potency for the treatment of major depression, consistent with subregional difference in treatment efficacy of rTMS on major depression.


White matter correlates of the disorganized speech dimension in schizophrenia

Petra Verena Viher1, Katharina Stegmayer1, Stéphanie Giezendanner1, Andrea Federspiel1, Stephan Bohlhalter2, Roland Wiest3, Werner Strik1, Sebastian Walther1

1University Hospital of Psychiatry, Bern, Switzerland; 2Neurology and Neurorehabilitation Center, Luzerner Kantonsspital, Lucerne, Switzerland; 3Support Center of Advanced Neuroimaging, Institute of Neuroradiology, University of Bern, Switzerland

Background

Disorganized speech has been shown to be related to functional and grey matter abnormalities in schizophrenia. However, the relationship between white matter and disorganized speech is poorly understood. We investigated the association between formal thought disorders (FTDs) and white matter microstructure in 61 patients with schizophrenia spectrum disorders. We hypothesized that FTDs are related to important fibers of the language system such as the uncinate fascicle and superior and inferior longitudinal fascicle.

Methods

The Bern Psychopathology Scale (BPS) organizes schizophrenia symptoms in three neurobiological dimensions, i.e. language, limbic and motor. The BPS was used to rate the dimension of language abnormalities ranging from negative FTDs to positive FTDs. Tract-based spatial statistics (TBSS) was used to study whole brain white matter abnormalities. Fractional anisotropy (FA) values were correlated with the BPS language dimension including age, gender, antipsychotic medication and the motor and affective dimensions of the BPS as covariates.

Results

The TBSS analysis indicated increased FA in left-hemispheric pathways of the language system in patients with negative FTDs; and lower FA values for patients with positive FTDs at p<0.05 (FWE corrected). The fiber tracts associated with FTDs included the left uncinate fascicle, superior and inferior longitudinal fascicle and the inferior fronto-occipital fascicle.

Discussion

We found an association of FTDs in schizophrenia and disturbed WM in language related pathways. Our findings are in line with the literature, linking FTDs in schizophrenia to structural and functional abnormalities in the language system. Thus, altered white matter properties in relevant fiber tracts may represent distinct pathobiology of specific formal thought disorders.


Electrophysiological correlates of functional brain abnormities in major depressive disorder: Microstate analysis on high-density EEG in resting conditions

Alena Damborska1,2, Miralena Tomescu1, Richard Bartecek2, Eliska Honzirkova2, Dominik Drobisz2, Christoph Michel1

1UNIGE, Switzerland; 2Masaryk University, Czech Republic

Objective : The aim of the study was to identify electrophysiological biomarkers of major depressive disorder (MDD) through high-density EEG technique.

Methods: Seven patients suffering from MDD and eight healthy controls underwent EEG recording using 128 or 256 scalp electrodes during eyes closed resting-state conditions. Microstate analysis was performed at individual and group levels. Microstate variants were identified and their parameters such as mean correlation, mean duration, time coverage, and segment count density were evaluated.

Results: Cross-validation criterion used to determine the most dominant topographies revealed six (A-F) microstates. The six microstates across subjects in each group explained more than 80% of global variance. Results of two-way repeated measures ANOVA revealed significant group x microstate interaction for segment count density. Post-hoc test revealed significant group difference for class A microstate, which showed decreased value in MDD patients.

Conclusion: Parameters revealed by microstate analysis are suggested to be possible electrophysiological biomarkers of functional brain abnormities in MDD patients.

The study has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 739939


Investigation of disturbed functional connectivity related to mental disorders using independent component analysis.

Yasuhiro Kawasaki, Kazutaka Ohi, Takamitsu Shimada, Takashi Uehara, Yusuke Nitta, Hiroaki Kihara, Hiroaki Okubo

Department of Neuropsychiatry, Kanazawa Medical University, Japan

Functional magnetic resonance imaging (fMRI) is useful to explore the brain’s functional organization and to examine whether functional organization is altered in patients with mental disorders. Functional connectivity can be defined as the synchrony of neural activity among regions. Areas of the brain which exhibit signal fluctuations correlated in time are assumed to be functionally connected. Independent component analysis allows us to decompose fMRI data into independent and non-Gaussian spatiotemporal components without any use of a reference function or predefined seed voxel. Independent component analysis is extensively applied as an exploratory analysis for the investigation of resting state functional connectivity. To examine the resting-state functional connectivity of mental disorders we evaluated resting-state networks in 20 patients with schizophrenia and 20 healthy participants using 3T MRI scanner. This study was approved by the local ethics committee, and written informed consent was obtained from all participants recruited. Independent component analysis was performed for all data using MELODIC of FSL (FMRIB, Oxford University, UK). Preliminary analysis showed that under each diagnostic grope similar pattern of functional connectivity was observed, however, there was anatomically aberrant activity in patients compared to control. We are planning to conduct deeper analysis of dual regression with increase the number of subject.


Altered EEG spectral power in preterm born adolescents during rest and cognitive performance

Anna-Sophie Rommel1, Sarah-Naomi James1, Grainne McLoughlin1, Daniel Brandeis2,3,4,5, Tobias Banaschewski2, Philip Asherson1, Jonna Kuntsi1

1King's College London, United Kingdom; 2Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany; 3Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland; 4Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; 5Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland

Background: Preterm birth has been associated with an increased risk for ADHD-like behavioural symptoms and cognitive impairments. However, direct comparisons across ADHD and preterm-born samples on neurophysiological measures are limited. The aim of this analysis was to test whether quantitative EEG (QEEG) measures identify differences or similarities in preterm-born adolescents, compared to term-born adolescents with and without ADHD, during resting-state and cognitive task conditions. Methods: We directly compared QEEG activity between 186 preterm-born adolescents, 69 term-born adolescents with ADHD and 135 term-born control adolescents during an eyes-open resting-state condition (EO), which previously discriminated between the adolescents with ADHD and controls, and during a cued continuous performance task (CPT-OX). Results: Absolute delta power was the only frequency range to demonstrate a significant group-by-condition interaction. The preterm group, like the ADHD group, displayed significantly higher delta power during EO, compared to the control group. In line with these findings, parent-rated ADHD symptoms in the preterm group were significantly correlated with delta power during rest. While the preterm and control groups did not differ with regard to absolute delta power during CPT-OX, the ADHD group showed significantly higher absolute delta power compared to both groups. Conclusion: Our results provide evidence for overlapping excess in the absolute delta range in preterm-born adolescents and term-born adolescents with ADHD during rest. During CPT-OX, preterm-born adolescents resembled controls. Increased delta power during rest may be a potential general marker of brain trauma, pathology or neurotransmitter disturbances.


Auditory Sensory Gating in Schizophrenia: relation with cognitive functioning, social cognition, socio-relational functioning

Giorgio Di Lorenzo

University of Rome Tor Vergata, Italy

Auditory Sensory Gating in Schizophrenia: relation with cognitive functioning, social cognition, socio-relational functioning


The neurophysiological effect of EMDR and TF-CBT in PTSD: an EEG study

Giorgio Di Lorenzo

University of Rome Tor Vergata, Italy

The neurophysiological effect of EMDR and TF-CBT in PTSD: an EEG study


Neural Correlates of Semantic Priming in Psychosis

Francilia Zengaffinen1, Stephan Furger1, Antje Stahnke1, Thomas Dierks1, Andrea Federspiel1, Martin Hatzinger2, Thomas König1, Beat Nick2, Charlotte Rapp2, Katharina Stegmayer1, Werner Strik1, Sebastian Walther1, Roland Wiest3, Martina Papmeyer1

1Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland; 2Psychiatric Services Solothurn, Early Detection of Psychosis Clinic, Solothurn, Switzerland; 3University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland

Psychoses are aetiologically complex disorders that affect about 1 − 2% of the population during their lifetime. Psychotic symptoms are thought to represent disturbances in higher-order brain functions that can be grouped according to their dysfunction in one or more of the following three neural brain circuitries: language, affect, motor function. Dysfunction of the neural language brain circuitry has already been linked to disturbances in expressive speech and formal thought disorders. However, it remains currently unknown if the language brain circuitry is only disturbed in psychosis, or if already individuals at familial or clinical high-risk show some extend of aberrancy.

To examine the whole spectrum form health to psychosis, four different subject groups are being examined: healthy controls (HC), first-degree relatives of psychosis patients (REL), a clinical high-risk group (CHR) and psychosis patients (PAT). In total, 120 subjects (30 per group) will complete a lexical priming task during electroencephalography and functional magnetic resonance imaging.

On a behavioural level, we expect to find subtle language dysfunction in the REL and CHR group. Furthermore, we hypothesize that aberrant neural activation patterns are present during the language task in PAT, CHR and REL groups in comparison to HC individuals. Finally, we aim to depict that aberrant neural activation in language - related brain areas is most pronounced in the PAT group and to a lesser extend present in the REL group. With this study, we hope to improve diagnostic strategies, treatments and outcome predictions.


Visual backward masking in siblings of schizophrenia patients: evidence for a compensation mechanism

Janir Ramos da Cruz1,2, Maya Roinishvili3,4, Eka Chkonia4,5, Patrícia Figueiredo2, Michael H. Herzog1

1Laboratory of Psychophysics, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland; 2Institute for Systems and Robotics/Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Portugal; 3Vision Research Laboratory, Beritashvili Centre of Experimental Biomedicine, Tbilisi, Georgia; 4Institute of Cognitive Neurosciences, Agricultural University of Georgia, Tbilisi, Georgia; 5Department of Psychiatry, Tbilisi State Medical University, Tbilisi, Georgia

Visual backward masking (VBM) is a very sensitive endophenotype of schizophrenia. Masking deficits are highly correlated with reduced EEG amplitudes. In VBM, a target stimulus is followed by a mask, which decreases performance on the target. Here, we investigated the neural correlates of VBM in unaffected siblings of schizophrenia patients. We had three conditions: target only and two VBM conditions, with long and short inter-stimulus intervals (ISI). Patients’ performance was impaired, while the siblings performed at the same level as the controls. Interestingly, EEG peak amplitudes were higher in siblings compared to controls, while they were lower in patients relative to controls as previously reported. For siblings, EEG amplitudes were at the same level in all conditions. For controls and patients, EEG peak amplitudes increased with task difficult, e.g., amplitudes in the long ISI condition were lower than in short ISI condition. Our results suggest that unaffected siblings of schizophrenia patients use a compensation mechanism tuning the brain to maximum performance in all conditions. Since siblings are already at the peak of their activations, increasing the task difficulty does not change brain processing.


Emotional Dysregulation – Systems Neuroscience of Affect in Psychosis

Stephan Furger1, Antje Stahnke1, Francilia Zengaffinen1, Thomas Dierks1, Andrea Federspiel1, Martin Hatzinger2, Thomas König1, Beat Nick2, Charlotte Rapp2, Katharina Stegmayer1, Werner Strik1, Sebastian Walther1, Roland Wiest3, Martina Papmeyer1

1Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern Switzerland; 2Psychiatric Services Solothurn, Early Detection of Psychosis Clinic, Solothurn, Switzerland; 3University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland

Despite identical diagnosis, patients with psychosis show a variety of clinical symptoms. Various psychosis symptoms relate to a disturbed perception, experience, regulation or expression of emotions. Previous research indicates that emotional dysregulation may form a distinct psychosis symptom dimension that is linked to aberrant function and structure of the limbic system and its cortico-basal ganglia and cortico-cortical connections. However, the nature of emotional dysregulation in psychosis has not been studied extensively yet. We expect that disturbed affect in psychosis may be best conceptualized as a dimension, that varies with psychosis vulnerability.

Neural activation patterns are investigated using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) from four different subject groups: patients with psychosis, subjects at clinical high-risk for psychosis, first-degree relatives of patients with psychosis and healthy controls. During fMRI and EEG examination, a specifically developed face perception task is being used. The presented stimuli are short animations of faces that vary in certain characteristics: gender (male, female), aesthetic (high, low), head movement (up, down) and gaze direction (direct, averted). Subsequently, all face stimuli are rated with regard to gender, dominance, trustworthiness, aggressiveness, health and attractiveness.

We hypothesize that the four study groups differ in terms of event-related potentials and brain activation patterns in affect-related brain regions. Furthermore, we expect that these differences are being linked to measures of emotionality and emotional processes such as emotion regulation and perception. The expected results will give further insights in the psychopathology of psychosis and might improve future diagnostic and treatment options.


Temporal patterns of EEG microstates during resting-state are correlated with prodromal symptoms in 22q11.2 deletion syndrome: a population at high genetic risk for schizophrenia

Miralena I. Tomescu1, Tonia A. Rihs1, Valeria Kebets2, Maude Schneider3, Stephan Eliez3, Christoph M. Michel1

1Functional Brain Mapping Laboratory, Department of Fundamental Neuroscience, University of Geneva, Geneva, Switzerland; 2Mood Disorders Lab, Department of Neuroscience, University of Geneva, Geneva, Switzerland; 3Office Médico-Pédagogique Research Unit, Department of Psychiatry, University of Geneva, Geneva, Switzerland

We have previously shown that EEG microstates during resting-state have a deviant pattern of temporal presence in a group of adolescents with 22q11.2 deletion syndrome (Tomescu et al., 2014), as well as in a different group of adults diagnosed with schizophrenia (Tomescu et al., 2015). To further explore the relationship between this deviant pattern and the development of schizophrenia, we computed partial least squares correlation (PLSC) between the temporal presence (characterized by the global explained variance (GEV) and duration) of the microstates and the symptoms assessed using the 19 item symptom scale from the structured interview for prodromal syndromes (SIPS, Miller et al., 2003) . The PLSC analysis allowed us to identify patterns of GEV and duration that covary with prodromal symptoms by computing latent variables (LVs), which represent the optimal link between these two modalities (Krishnan et al., 2010). Using permutation testing, we obtained a significant latent variable (5000 iterations, p= 0.03) explaining 62% of the covariance. This LV is characterized by significantly positive loadings of the GEV of microstates A and B and significantly negative loadings of the duration of microstates C and D. These temporal patterns (weighted by the loadings of the latent variable) were negatively correlated with several mostly negative prodromal symptoms, including social anhedonia (r=-0.441, p=0.014), expression of emotion (r=-0.45, p=0.01), experience of emotions and self (r=-0.37 (p=0.04), and disorganized communication (r=-0.36, p=0.050). Thus, temporal patterns of EEG microstates might be related to the severity of prodromal, negative symptoms in the 22q11DS.


Differential ADHD effects on Cognitive Control

Björn Albrecht1, Daniel Brandeis2,3,4,5, Henrik Uebel-von Sandersleben1, Hartmut Heinrich6,7, Hans-Christoph Steinhausen8,9, Aribert Rothenberger1, Tobias Banaschewski2

1Child and Adolescent Psychiatry, University Medical Center Göttingen, Germany; 2Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; 3Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zürich, Zürich, Switzerland; 4Center for Integrative Human Physiology, University of Zürich, Switzerland; 5Neuroscience Center Zurich, University of Zurich and ETH Zurich, Switzerland; 6Department of Child and Adolescent Mental Health, University of Erlangen, Erlangen, Germany; 7Heckscher-Klinik, München, Germany; 8Child and Adolescent Mental Health Centre, Capital Region Psychiatry, Copenhagen, Denmark; 9Clinical Psychology and Epidemiology, Institute of Psychology, University of Basel, Basel, Switzerland

Flexible adaptation to conflicting task demands plays an important role in everyday life and is impaired in many psychiatric disorders. As a prerequisite, cognitive control comes into play when task demands conflict, which may be reflected in brainelectrical activity as enhanced N2 amplitude under conflict (monitoring) in various tasks. Cognitive control may also play a role in Attention Deficit/Hyperactivity Disorder (ADHD), but studies on N2-Enhancement revealed mixed results.

The current study contrasts three task demands tapping conflict monitoring and cognitive control and their relation to ADHD. This was done in a sample of 94 children with ADHD in comparison to 43 Controls, aged 8 to 15 years using a Flanker-Task paradigm by contrasting processing of congruent and incongruent stimuli, and in Continuous Performance Tests by contrasting Go-Nogo demands and processing of additionally presented incongruent stimuli.

All three demands for cognitive control revealed significant N2-Enhancement, but differential ADHD effects thereon: N2-Enhancements in the CPT regarding Go-Nogo and processing of additional incongruent Flankers was similar in ADHD and Controls, while Flanker-Task Congruency revealed medium-sized ADHD effects.

The current results indicate that children with ADHD have medium-sized difficulties with cognitive control during some particular demand (e.g. with Flanker-Task Congruency that requires frequent responding) but not on others (e.g. during response-control in CPTs that require responding in only 10% of all trials). This highlights the importance of clinical studies for understanding cognitive control in different demands, and it may also indicate that moderators like arousal may play an important role for ADHD deficits.


ASD developmental trajectories of resting state EEG powerspectrum

Pilar Garces1, Sarah Baumeister2, Luke Mason3, EU-AIMS LEAP4, Daniel Brandeis3,5, Joerg F. Hipp1

1Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland; 2Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, J5, 68159 Mannheim, Germany; 3Centre for Brain and Cognitive Development, Birkbeck, University of London, Henry Wellcome Building, Malet Street, London, WC1E 7HX, UK; 4see Loth et al, The EU-AIMS Longitudinal European Autism Project (LEAP): Design and methodologies to identify and validate stratification biomarkers for Autism Spectrum Disorders, Molecular Autism.; 5Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zürich, Neumünsterallee 9, 8032 Zürich Switzerland

To generate new treatments for ASD it is critical to understand the deviations in brain function from typically developing controls (TD) and to derive robust biomarkers to quantify those. Resting state EEG is a unique tool to explore non-invasively – and across a broad age range – the dynamics of spontaneous neuronal activity. Here we explored the developmental changes in ASD from childhood to adulthood in resting state EEG powerspectrum in the LEAP dataset of EU-AIMS (www.eu-aims.eu), using n=294 high functioning ASD and TD individuals from 6 to 30 years. More specifically, we investigated the alpha rhythm – the hallmark of resting state EEG, linked to sensory-motor and cognitive processes – and the powerspectrum over frequencies from 1 to 32 Hz at the sensor level and in source space. We quantified developmental trajectories with linear mixed effect models, accounting for confounding factors such as gender, IQ and site. Known typical developmental trajectories were recovered: with increasing age the alpha peak frequency increased, its amplitude decreased, relative power in 2-6Hz decreased and relative power 10-32Hz increased. The developmental changes in the ASD group followed closely that of the TD subjects, and accordingly no significant group effects were found. Additionally, no evidence for increased heterogeneity in ASD was found, since the modeled variances in both groups did not differ significantly. Overall, this indicates that the baseline 1 to 32 Hz power matures in high functioning ASD following a typical developmental trajectory.


Investigation of aberrant white matter structures in the Deficit Subtype of Schizophrenia: A DTI Study

Antonella Amodio1, Mario Quarantelli2, Armida Mucci1, Annarita Vignapiano1, Giulia Maria Giordano1, Alessia Nicita1, Silvana Galderisi1

1Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie 80138 Naples, Italy; 2Biostructure and Bioimaging Institute, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy

Deficit schizophrenia (DS) is characterized by the presence of primary, enduring negative symptoms, and has different course, risk factors and clinical features with respect to non-deficit schizophrenia (ND).

Our aim was to investigate differences in white matter connectivity patterns in subjects with DS compared to ND and healthy controls (HC), using probabilistic analysis of diffusion tensor imaging (DTI) data.

Forty-six subjects with chronic schizophrenia (SCZ) and 35 HC, matched for age and gender, were examined using DTI. SCZ were classified as DS (n=9) or ND (n=37) using the Schedule for the Deficit Syndrome (SDS). Further assessments included the Positive and Negative Syndrome Scale (PANSS) and the MATRICS Consensus Cognitive Battery. Connectivity index (CI, % of the probabilistic streamlines originating from a region that reach a second one) and Fractional Anisotropy (FA) of the connections between bilateral dorso-lateral prefrontal cortex (DLPFC), nucleus accumbens (NAcc), amygdala (AMY) and insular cortex (IC) were examined.

We found a reduced CI between right AMY and DLPFC in SCZ compared to HC (p<0,0044), while there were no differences between DS and ND. DS showed an increased CI from right AMY to dorsal-anterior IC compared to ND (p<0,0036). Finally, in SCZ the FA of right NAcc-DLPFC connections directly correlated with PANSS disorganization dimension (p<0.0031).

These findings confirm previous evidences of distinct neurobiological substrates for different symptom dimensions and clinical subtypes of SCZ. Primary and persistent negative symptoms seem to be related to abnormal connectivity of brain regions involved in guiding goal-directed behavior based on experienced value.


Avolition and white matter abnormalities in schizophrenia: evidence of reduced fractional anisotropy between amygdala and insular cortex.

Antonella Amodio1, Mario Quarantelli2, Armida Mucci1, Annarita Vignapiano1, Giulia Maria Giordano1, Alessia Nicita1, Silvana Galderisi1

1Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie 80138 Naples, Italy; 2Biostructure and Bioimaging Institute, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy

Dysfunction of the reward system is probably related to the avolition/apathy domain of negative symptoms in schizophrenia. In particular, structural and functional abnormalities were reported in key regions within the reward system, including the ventral-tegmental area (VTA), the nucleus accumbens (NAcc), the orbito-frontal cortex (OFC) as well as the amygdala (AMY) and the insular cortex (IC).

Our aim was to investigate the white matter connectivity patterns within these regions in male subjects with schizophrenia, using probabilistic analysis of diffusion tensor imaging (DTI) data.

Thirty male subjects with schizophrenia (SCZ) and 17 male healthy controls (HC) matched for age, underwent DTI. SCZ were evaluated clinically with the Schedule for Deficit Syndrome (SDS), Positive and Negative Syndrome Scale (PANSS) and the MATRICS consensus cognitive battery (MCCB). Pathways connecting the AMY and the NAcc with the OFC and IC were evaluated.

Reduced fractional anisotropy (FA) was observed in left AMY-ventral anterior IC connection (p<0.0048), in SCZ compared to controls. This abnormality was negatively correlated with the avolition/apathy (p<0.0023) but not with the expressive deficit scores. SCZ showed also reduced connectivity indices (% of the probabilistic streamlines originating from a region that reach a second one) between right NAcc and medial OFC as compared to controls (p<0.0001). Finally the left NAcc-dorsal anterior IC connectivity index was negatively correlated with working memory (WM) scores (p<0.0013).

Our results confirm that the avolition/apathy but not the expressive deficit domain is related to reward system abnormalities. Distinct alterations seem to underlie cognitive impairment and avolition/apathy.


Electrophysiological indices of cognitive control and reward processing in schizophrenia

Annarita Vignapiano, Armida Mucci, Giulia Maria Giordano, Antonella Amodio, Silvana Galderisi

Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie 80138 Naples, Italy

Introduction. Abnormalities in cognitive functions and motivation are core aspects of schizophrenia. One of the crucial aspects of cognitive impairment is the disturbance of cognitive control, or the ability to flexibly adjust behavior in accordance with one’s intentions and goals. A large literature has emerged focusing on the anterior N2 as a correlate of cognitive control based on motivational value.

Aims. Given the clinical importance of goal-directed behavior impairments in schizophrenia as a strong predictor of functional outcome, we aimed to study the impact of reward- and avoidance-based motivation on cognitive control using event-related potentials (ERPs).

Method. ERPs were recorded during the execution of the "Monetary Incentive Delay (MID)” task in 34 patients with schizophrenia (SCZ) stabilized on second generation antipsychotics and 22 healthy controls (HC). Negative symptom domains (avolition/apathy and expressive deficit), positive and disorganization dimensions were also assessed in SCZ.

Results. We did not observe any group difference in N2 amplitude or latency. In the HC group, N2 amplitude was significantly larger for anticipation of large punishment than reward and for all incentive conditions than neutral one. Unlike HC, N2 amplitude in SCZ did not discriminate motivational relevance. N2 amplitude was not correlated with psychopathological dimensions in SCZ.

Conclusion. Our results suggest that the discrimination of motivational value appears to be impaired in SCZ, independently of psychopathology. Future studies should be aimed to assess whether distinct subgroups within SCZ, in particular those with deficit features, might be characterized by this abnormality.


Multisensory Integration in Chronic and First Episode Schizophrenia

Justin R Leiter-McBeth, Brian A Coffman, Ali G McCathern, Timothy K Murphy, Sarah M Haigh, Dean F Salisbury

Clinical Neurophysiology Research Laboratory, Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, United States of America

Long-term schizophrenia (Sz) and first episode schizophrenia spectrum (FE) patients have deficits in processing auditory and visual stimuli evidenced by reduced event-related potentials. Multisensory integration (MSI) is the process by which information from multiple modalities are integrated into a coherent percept. Findings from studies of non-linguistic MSI in Sz are equivocal. No studies have assessed MSI in FE. This study examined MSI by presenting 18 first episode matched healthy controls (FEHC), 26 chronic schizophrenia matched healthy controls (SzHC), 21 FE, and 29 Sz with auditory (A), visual (V), and simultaneous audiovisual (AV) stimuli. Auditory stimuli were presented as groups of 4 tones (1 kHz, 50ms, 5ms rise/fall, 330ms SOA, 750ms ITI). Visual stimuli (small blue circle, 50ms) were also presented in groups of 4. AV stimuli were the simultaneous presentation of the A and V stimuli. Participants were asked to sit silently and attend to the stimuli presented. MSI was calculated by subtracting the sum of the unisensory stimuli from the simultaneous audiovisual stimulus [AV – (A+V)]. MSI amplitude was calculated as the average voltage between 95-115ms and 180-190ms at PO9 and PO10, where previous studies have looked for MSI interactions. MSI at 95-115ms was more negative in SzHC (p=.011) compared to Sz, but no group differences were found in FE and FEHC (p=.968). MSI at 180-190ms was not significantly different from controls for Sz or FE. These results suggest that early MSI is impaired in Sz but not FE, and may serve as an indicator of disease progression.


Reduced Mismatch Negativity is Associated with Decreased Heschl’s Gyrus Volume in First Episode Schizophrenia

Anna Shafer1, Brian A Coffman1, Timothy K Murphy1, Sarah M Haigh1, Beatriz Luna2, Dean F Salisbury1

1Clinical Neurophysiology Research Laboratory, Western Psychiatric institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, United States of America; 2Lab of Neurocognitive Development, Department of Psychiatry, University of Pittsburgh School of Medicine, United States of America;

Primary auditory cortex pathophysiology is linked to auditory deficits and auditory verbal hallucinations in schizophrenia. The aim of this study was to replicate associations between reductions in the magnitude of the mismatch negativity (MMN) response during a passive auditory task and reductions in gray matter volume in Heschl’s gyrus in subjects with first-episode schizophrenia (FESz). Participants included 28 FESz and 28 healthy control subjects matched for age, parental socioeconomic status, IQ, sex, and handedness. Freesurfer was used to segment white matter, gray matter, and pial surfaces from T1-weighted structural 3T MRI data (1mm x 1mm x 1mm). Gray matter was measured in left Heschl’s gyrus (containing primary auditory cortex). Pitch-deviant and duration-deviant MMN responses were measured as the averaged amplitude within a 100-ms window at Fz. In FESz, total gray matter volume in Heschl’s gyrus correlated with the magnitude of pitch MMN (rho = -.38, p <.05) and duration MMN (r = -.44, p <.05). There were no significant correlations between MMNs and Heschl’s gray matter volumes in the healthy control group, and the pathological correlations in FESz were significantly different from healthy controls (Fisher Z p <.05). Smaller Heschl’s gyrus in first episode schizophrenia patients is related to a smaller magnitude MMN for both pitch and duration deviants. This pathological relationship between MMN amplitude and Heschl’s gyrus volume in FESz suggests the presence of pre-psychosis gray matter loss in a subset of patients, and may be useful for tracking disease progression and as an outcome measure of successful interventions


Deficits in Attentional Modulation of Auditory Stimuli in First Episode Schizophrenia

Sarah N Fribance, Brian A Coffman, Timothy K Murphy, Sarah M Haigh, Justin R Leiter-McBeth, Dean F Salisbury

Clinical Neurophysiology Research Laboratory, Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, United States of America

The N1 auditory evoked potential is reduced in long-term schizophrenia (Sz) and in the first episode schizophrenia spectrum (FE). N1 is increased by attention, and this modulation is impaired in Sz. It is not known whether FE can modulate N1 by attention. This study examined N1 modulation by attention (Negative Difference; Nd) in FE, early in disease course. Thirteen FE and 11 matched healthy control (HC) participants heard sounds while watching a silent video. Participants heard repetitious tones in a typical AEP task (1k Hz, 50 ms duration, 5 ms rise/fall, 80 dB), spaced 1050 ms to 1550 ms apart. In one condition, participants were told to ignore tones, while in the other condition participants pressed a button to every 7th tone. Continuous EEG was recorded between DC and 104 Hz. After high pass filtering at 0.5 Hz and ICA artifact correction, data were low pass filtered at 20 Hz, epoched, and artifact rejected, and averages constructed. N1 amplitude was calculated as average voltage between 100 ms and 110 ms at Cz. Of primary importance, N1 amplitude was differentially affected by attention between groups (p =0.002). HC showed larger N1 with attention (p =0.01), but FE did not (p =0.27). This may reflect a long-range functional disconnection between cognitive control cortical areas and auditory sensory cortex early in disease course. Clinically, the lack of attention-related Nd in FE suggests it may serve as a sensitive biomarker for the detection of the schizophrenia prodrome among clinical high-risk individuals.


Transcallosal Auditory Connectivity in First Episode Schizophrenia

Yiming Wang1, Brian A Coffman1, Tim K Murphy1, Beatriz Luna2, Fang-Cheng Yeh3, Dean F Salisbury1

1Clinical Neurophysiology Research Laboratory, Western Psychiatric institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, United States of America; 2Lab of Neurocognitive Development, Department of Psychiatry, University of Pittsburgh School of Medicine, United States of America; 3High Definition Fiber Tracking Laboratory,Department of Neurological Surgery, University of Pittsburgh School of Medicine, United States of America

Auditory verbal hallucinations (AVH) are common in schizophrenia and may relate to abnormal connectivity between auditory cortices. We examined transcallosal auditory cortex tracts in 14 AVH+ first-episode schizophrenia patients (FESz), 15 AVH- FESz, and 23 healthy controls with diffusion spectrum imaging (DSI). AVH+ scored at least a 2 on auditory hallucinations, voices commenting, or voices conversing measured with the Scale for the Assessment of Positive Symptoms (SAPS). Groups were matched for age, parental socioeconomic status, education, IQ, gender, and handedness. A deterministic fiber tracking algorithm identified transcallosal auditory fibers, defined as 1000 fibers traversing the posterior third of the corpus callosum and ending bilaterally in Brodmann’s area 22, Heschl’s gyrus, or planum temporale. MANOVA revealed transcallosal auditory cortex connectivity differences between groups (F(6, 94) = 2.34, p = .038) driven by tract volume (F(2, 49) = 3.46, p =.039) and generalized functional anisotropy (gFA, F(2, 49) = 4.77, p = .013). Pairwise t-tests indicated lower gFA and greater tract volume for AVH+ vs AVH- (p’s < .05). Healthy controls trended towards greater gFA (p = .068) vs AVH+ and tract volume (p = .063) vs AVH-. All other comparisons were nonsignificant (p >.1). Reduced fiber tract directionality indicates less efficient transcallosal auditory connectivity in AVH+ FESz; smaller tract volume indicates potential reduced structural auditory cortex connectivity in AVH-. Interhemispheric auditory cortex functional connectivity abnormalities may underlie AVH in schizophrenia even early in disease course while overall structural connectivity differences may affect AVH- individuals. Interhemispheric connectivity differences may underlie symptom-level phenotypes.


Deficits in Rule-Based Deviance Detection in First-Episode Schizophrenia

Sarah M Haigh, Brian A Coffman, Tim K Murphy, Kayla L Ward, Dean F Salisbury

Clinical Neurophysiology Research Laboratory, Western Psychiatric institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, United States of America

Individuals with long-term schizophrenia (SZ) show reductions in simple mismatch negativity (MMN) to infrequent stimulus parameter deviance, and in complex MMN to infrequent pattern deviance. First episode schizophrenia-spectrum individuals (FE) show less reduction of simple MMN. Complex pattern deviance may be more suitable for elucidating subtle deficits in auditory perception at first-episode, and may be more useful for distinguishing between those with and those without schizophrenia. We measured complex MMN to an extra fourth tone amongst standard groups of three tones (1 kHz, 50 ms duration, 5 ms rise/fall, 80 dB, 330 ms SOA, 800 ms ITI) in 23 SZ), and 20 matched healthy controls (HCSZ), and in 21 FE (within 6 months of first-episode), and 20 matched healthy controls (HCFE). Both HCSZ and HCFE produced two complex MMNs: one early ~150 ms after deviant-onset and one late ~400 ms after deviant-onset. SZ showed significant reductions in the late complex MMN (p=.03, d=0.67), as did FE (p=.01, d=0.85). Both individuals with long-term schizophrenia and individuals at their first-break showed impaired complex MMN, specifically later in deviance detection processing. In contrast with simple MMN, complex MMN may be a more sensitive biomarker of the presence of schizophrenia early in disease course. To assess whether complex MMN has greater sensitivity to detect incipient psychosis, both simple MMN and complex MMN will be measured in prodromal individuals.


Systems Neuroscience of Motor Function on the Continuum from Health to Psychosis

Antje Stahnke1, Francilia Zengaffinen1, Stephan Furger1, Thomas Dierks1, Andrea Federspiel1, Martin Hatzinger2, Thomas König1, Beat Nick2, Charlotte Rapp2, Katharina Stegmayer1, Werner Strik1, Peter van Harten3,4, Sebastian Walther1, Roland Wiest5, Martina Papmeyer1

1Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland; 2Psychiatric Services Solothurn, Early Detection of Psychosis Clinic, Solothurn, Switzerland; 3Psychiatric Center, GGz Centraal Innova, Amersfoort, The Netherlands; 4Department of Psychiatry and Psychology, Maastricht University, Maastricht, The Netherlands; 5University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland

Psychotic disorders are highly complex with regard to their symptomatic characteristics and aetiology. About 1-2% of the population are affected by psychosis during their lifetime. Impairments in motor function that occur in psychosis have been associated with aberrant neural activity and structure. It is still unclear whether differences in motor ability in healthy individuals are similarly related to distinct brain activation patterns in motor-related brain areas, suggesting that impairments in psychosis patients are extreme values on a trait continuum. In the present study, we examine the neural underpinnings of motor function on the spectrum from health to psychosis.

We investigate the neural correlates by conducting electroencephalography (EEG) as well as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) in 120 subjects from four different groups: psychosis patients, subjects with a clinical high-risk for psychosis, first-degree relatives of psychosis patients and healthy controls. During MRI and EEG measurement, subjects perform an ankle movement task as well as a biological motion recognition task, using the point light walker paradigm. In addition, physiological markers such as heart rate variability and force variability are recorded.

We hypothesize functional and structural neural abnormalities in the motor areas in relation to the strength of the behavioural disturbances. Our results will provide new insights into the neural basis, as well as the aetiology of motor function in psychosis.


ANALYSIS OF SELECTED QEEG PREDICTORS OF RESPONSE TO TRANSCRANIAL MAGNETIC STIMULATION IN MAJOR DEPRESSION.

Premysl Vlcek, Tomas Novak, Martin Brunovsky, Martin Bareš, Monika Klirova, Anna Bravermanova, Jakub Polak, Barbora Kohutova

National Institute of Mental Health, Klecany, Czech Republic

We used a logistic discriminant analysis (LDA) to determine a QEEG predictive model of response to four-week trial of low-frequency transcranial magnetic stimulation (LF-rTMS) on right prefrontal cortex in patients with major depression who failed to previous antidepressant treatment (N=25). Out of the set of 836 variables generated by the Neuroguide software, we selected 12 significant (p˂0.001) variables using a t-test. This number has been then reduced within LDA by means of a stepwise method on 5 predictors (p˂0.05):alpha asymmetry (ASAL) C3-Cz, ASAL C4-Cz , theta asymmetry (TAS) C4-T4, TAS T3 – T4 and theta peak (TP) C4. The LDA model containing these five variables demonstrated correct classification on 88 %. Furthermore, it shows a good overall model fit based on -2 Log Likelihood (p˂0.001). Sequential and eliminating employment of bootstrapping (N=10000) on the original 12 variables confirmed that the QEEG parameters of TAS T3-T4 (p=0.0001), ASAL2 C4-F8 (p=0.01), ASAL1 C3-Cz (p=0.03), ASAL C3-Cz (p=0.04) demonstrate robust resistancy against bias while keeping a satisfactory level of overall classification. Our findings confirm the ability of QEEG data analysis to create a suitable prediction model. An important part of our model is the T3-T4 predictor, which demonstrates both predictive sensitivity and bias resistance. From our model, it can be concluded that higher temporal theta asymmetry (T3 > T4) indicates a significantly higher chance of therapeutic response to rTMS therapy for pharmaco-resistant depression.

Supported by Czech Science Foundation, grant nr. 17-07070S and Ministry of Health of the Czech Republic, grant nr. 16-31380A.


Avolition and resting state functional connectivity of the VTA in subjects with schizophrenia

Giulia Maria Giordano1, Mario Stanziano2, Michele Papa2, Armida Mucci1, Anna Prinster3, Andrea Soricelli4, Silvana Galderisi1

1Department of Psychiatry, University of Campania "Luigi Vanvitelli", Naples, Italy; 2Laboratory of Neuronal Networks, Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy; 3Biostructure and Bioimaging Institute, National Research Council, Naples, Italy; 4University of Naples ‘Parthenope’ and IRCCS Research Institute SDN, Naples, Italy

Avolition is a key negative symptom of schizophrenia for which there is no effective treatment. It is correlated to poor functional outcome and real life motivation. Dysfunctions of different motivation processes were documented in patients with avolition. Altered connectivity within dopaminergic (DA) cortico-striatal circuits, involved in motivation processes, might underlie most of these dysfunctions. The highest number of DA neurons involved in motivation circuits are located in the ventro-tegmental area (VTA). In light of these observations, our study investigated relationships between the resting-state functional connectivity (RS-FC) of the VTA and avolition.

We used resting state functional magnetic resonance imaging to study RS-FC in 22 healthy controls (HC) and in 26 patients with schizophrenia, treated with second generation antipsychotics only, divided in high (HA=13) and low avolition (LA=13) subgroups. We also assessed the relationships of VTA RS-FC with avolition, assessed using the Schedule for the Deficit Syndrome.

HA patients, in comparison to LA patients and HC, showed significantly reduced VTA RS-FC with the right (R) ventrolateral prefrontal cortex (VLPFC), left (L) VLPFC, R insula (INS), L INS and R lateral occipital complex (LOC). A reduced RS-FC was found for LA patients, with respect to HC, only in L INS and L VLPFC. Significant negative correlations were found between avolition and RS-FC of VTA with R INS, R VLPFC and L INS.

Conclusion. Our findings demonstrate that avolition in schizophrenia is linked to dysconnection of VTA from key cortical regions involved in retrieval of outcome values of actions to motivate behavior.


Acute cannabis effects on cognitive performance and P300 in occasional and chronic cannabis users: an ecologically valid approach

Michaela Viktorinová1,2, Anna Bravermanová1,2, Tomáš Novák1,2, Filip Tylš1,2, Martin Brunovský1,2, Renata Androvičová1,2, Tomáš Páleníček1,2

1National Institute of Mental Health, Klecany, Czech Republic; 2Third Faculty of Medicine, Charles University in Prague

Introduction: Cannabis is the most widely consumed illicit substance with an estimated annual prevalence of 182, 5 million people worldwide in 2014. While the effect of cannabis on cognition has already been investigated, these studies mostly employed intravenously delivered, high doses of Δ-9-THC where participants were unable to influence neither the amount nor the speed of intake. Present study adopted a naturalistic design (subjects using their regular dose of their own cannabis the way they would normally do) focusing on selected cognitive domains and their underlying neurophysiology.

Method: Attention, mental flexibility, psychomotor speed (PEBL battery tasks – TMT, CPT) and P300 (auditory oddball paradigm) were measured 30 minutes after cannabis intoxication in 34 occasional, 31 chronic cannabis users and 30 non-using adults. Phenomenology was objectified by Altered States of Consciousness Scale and Brief Psychiatric Rating Scale. THC and THC-COOH were determined from blood analysis 30 and 60 minutes after cannabis intake.

Results: Although cannabis users had significantly higher APZ and BPRS scores, the groups did not differ in terms of their cognitive performance. Likewise, no between-group differences were observed in terms of P300 amplitude, latency or area under curve. Further analysis only revealed smaller P200 amplitude and shorter N200 latencies in occasional users when compared to non-using controls.

Conclusion: Unimpaired profile of selected cognitive functions both at behavioral and neurophysiological level was an unexpected finding suggesting a possible tolerance to the cognitive-impairing effects of cannabis provided the subjects are able to control the rate of intoxication.


Altered resting-state EEG source functional connectivity in Autism Spectrum Disorder

Giorgio Di Lorenzo

University of Rome Tor Vergata, Italy

Altered resting-state EEG source functional connectivity in Autism Spectrum Disorder


Neurexan® influences stress-induced activity of the anterior cingulate cortex and associated brain regions

Marina Krylova1, Anne Kühnel1,2, Yan Fan3,4, Luisa Fensky1, Vanessa Teckentrup1, Lejla Colic2,3, Myron Schultz5, Martin Walter1,2,3

1University Department of Psychiatry and Psychotherapy, University Tübingen, Tübingen, Germany; 2Clinical Affective Neuroimaging Laboratory, Magdeburg, Germany; 3Leibniz Institute for Neurobiology, Magdeburg, Germany; 4Department of Psychiatry, Charité, CBF, Berlin, Germany; 5Biologische Heilmittel Heel GmbH, Baden-Baden, Germany

Introduction: Neurexan®, a medicinal product sold over the counter (OTC), contains passionflower, oats, coffee and zinc valerianate. Neurexan® has been previously investigated in patients with symptoms related to acute stress, nervousness/restlessness, and insomnia. The underlying neuronal mechanisms that lead to the reduction of those symptoms are less clear. The anterior cingulate cortex (ACC) and the Amygdala are the two areas important in stress reaction. Previous studies showed that especially the dorsal ACC (dACC) influences the generation of autonomic arousal. Additionally, it was found that the dACC is activated under cognitive stress. Thus, the dACC seems to be an important area controlling stress reactivity. We hypothesize Neurexan® to induce changes in the activation of dACC and associated areas during a stress task.

Methods: The treatment effect of a single dose was investigated using a randomized, placebo-controlled, double-blind, two-period-crossover design on thirty-nine healthy males. The stress response was induced using the ScanSTRESS which uses arithmetic tasks as well as mental rotation tasks.

Results&Conclusion: We found higher activation during psychosocial stress (stress > control; rotation and arithmetics together) in the anterior insula, premotor area bilaterally, angular gyrus, occipital lobe, and cerebellum. Paired-t-test analysis showed a significant cluster in the region of interest right dACC for the contrast placebo > drug in rotation stress > rotation control after correcting for multiple testing in the ROI. A single dose of Neurexan® significantly reduces right dACC activation during psychosocial stress compared to placebo.


Effects of Neurexan® on emotional brain response

Marina Krylova1, Anne Kühnel1,2, Vanessa Teckentrup1, Lejla Colic2,3, Yan Fan2,4, Myron Schultz5, Martin Walter1,2,3

1University Department of Psychiatry and Psychotherapy, University Tübingen, Tübingen, Germany; 2Clinical Affective Neuroimaging Laboratory, Magdeburg, Germany; 3Leibniz Institute for Neurobiology, Magdeburg, Germany; 4Department of Psychiatry, Charité, CBF, Berlin, Germany; 5Biologische Heilmittel Heel GmbH, Baden-Baden, Germany

Introduction: Neurexan®, a medicinal product sold over the counter (OTC), contains passionflower, oat, coffee and zinc valerianate. Neurexan® has been investigated in patients with symptoms related to acute stress, nervousness and insomnia. Amygdala is involved in the development of fear and emotional behavior. Acute stress sensitizes the amygdala, thereby increasing vigilance/anxiety, which in turn promotes the stress response. Amygdala reactivity to negative stimuli is a reliable phenotype that closely associates with stress regulation and can be assessed with Hariri paradigm. Furthermore, a linkage between an increased level of stress hormones and increased emotional response to angry faces has been shown in patients with social phobia. Previous investigation suggested an attenuated neuroendocrine stress response in healthy volunteers induced by Neurexan®. Thus, our aim was to further explore the effect of Neurexan® on the emotional brain response in the amygdala.

Methods: In a randomized, placebo-controlled, double-blind, two-period crossover trial brain response to the Hariri task, an emotional paradigm, of 39 healthy, moderate stressed males was measured after intake of a single dose of Neurexan® and placebo control via 3 Tesla fMRI. Data were preprocessed and analyzed in SPM12.

Results&Conclusion: Hariri task was firstly validated for negative emotional faces response. Significant (peak level FWE corrected) bilateral activations of fusiform gyri, amygdalae and prefrontal cortex as well as unilateral activation in right thalamus were confirmed as previously reported. Paired t-test showed a significant reduction of BOLD response to negative faces in the left amygdala (p<0.05) during the Neurexan® session as compared to placebo.


Relation between Cognition and Resting-state EEG source functional connectivity in Schizophrenia

Giorgio Di Lorenzo

University of Rome Tor Vergata, Italy

Relation between Cognition and Resting-state EEG source functional connectivity in Schizophrenia


TIME COURSE OF QUANTITATIVE EEG CHANGES IN AN ANIMAL MODEL OF PSILOCIN-INDUCED PSYCHOSIS

Filip Tyls1,2, Cestmír Vejmola1,2, Vaclava Piorecka1,3, Vlastimil Koudelka1, Tomas Novak1,2, Tomas Palenicek1,2

1National Institute of Mental Health, Czech Republic; 23rd Faculty of Medicine, Charles University in Prague; 3Faculty of Biomedical Engineering, Czech Technical University in Prague

The serotonergic hallucinogen psilocybin and its active metabolite psilocin nowadays receive a lot of attention as a research tool for modeling psychosis. The aim of the study was to assess psilocin-induced changes in quantitative EEG (QEEG) in rats in order to explore the role of different serotonergic receptors in psilocin action.

EEG was recorded in freely moving rats after implantation of 12 active electrodes onto the surface of the cortex. EEG power spectra (local synchronization) and coherence (long projections) were analyzed comparing the drugs’ effect in time to the baseline record. Only EEG traces corresponding to behavioral inactivity were included in the analysis. We used psilocin, selective 5HT receptor antagonists and antipsychotics.

Psilocin generally decreased both EEG absolute spectral power and EEG coherences. The changes in spectral power induced by psilocin were normalized partially by all substances used, mainly in the lower frequency bands. However, only 5HT1A and 5HT2A antagonists partially normalized the psilocin-induced decrease of EEG coherences. The specific QEEG pattern of each substance and the temporal dynamics of QEEG changes will be presented.

Psilocin-induced changes in QEEG in rats are very similar to our human data with psilocybin and are in accordance with the concept of psychosis as a disconnection syndrome. All the specific 5HT antagonists and both antipsychotic drugs specifically affected the EEG spectral power induced by psilocin. Surprisingly, only 5HT1A and 5HT2A antagonists were able to partially reverse psilocin-induced disconnection.

This study was supported by LO1611/NPUI, MICR VI20172020056; Progres Q35; and European Regional Development Fund.


Low-frequency oscillations of Default Mode Network abnormalities in Alzheimer’s Disease

Li Youjun1, Yao Hongxiang2, Lin Pan1, Zheng Liang1, Liu Tian1, Zhou Bo2, Wang Pan2, Zhang Zengqiang2, Wang Luning2, An Ningyu2, Wang Jue1, Zhang Xi2

1Xi'an Jiaotong University, China, People's Republic of; 2Chinese PLA General Hospital, Beijing, China

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with the progressive dysfunction of cognitive ability. Previous research has indicated that the default mode network (DMN) is closely related to cognition and is impaired in Alzheimer’s disease. Because recent studies have shown that different frequency bands represent specific physiological functions, DMN functional connectivity studies of the different frequency bands based on resting state fMRI (RS-fMRI) data may provide new insight into AD pathophysiology. In this study, we explored the functional connectivity based on well-defined DMN regions of interest (ROIs) from the five frequency bands: slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), slow-3 (0.073-0.198 Hz), slow-2 (0.198-0.25 Hz) and low-frequency oscillations (LFO) (0.01-0.08Hz). We found that the altered functional connectivity patterns are mainly in the frequency band of slow-5 and slow-4 and that the decreased connections are long distance, but some relatively short connections are increased. In addition, the functional connectivity fingerprint of the DMN in AD is frequency dependent and differs between the slow-5 and slow-4 bands. Mini-Mental State Examination (MMSE) scores were significantly correlated with the altered functional connectivity patterns in the slow-5 and slow-4 bands. These results indicate that frequency-dependent functional connectivity changes might provide potential biomarkers for AD pathophysiology.


Sensory-motor phase synchronization for deficit of selection of task-relevant information in autism symptom

Masahiro Kawasaki, Eri Miyauchi

University of Tsukuba, Japan

One character of autism spectrum disorder (ASD) is restricted and repetitive patterns of behavior, interests, or activities. The characters are related to the abilities of selection of task-relevant information and inhibition of task-irrelevant information. The abilities are proposed to be related to phase synchronization between the distant motor and sensory areas in human electroencephalography (EEG) studies. It is however, not clear about the relationship of the synchronization with ASD symptoms. To address the issue, we measured EEG data during two types of simple motor-response tasks (an auditory-motor response task (AM) and a single visual-motor response task (VM)) and two types of select-motor-response tasks (an auditory-select-motor response task (ASM) and a single visual-select-motor response task (VSM)). Behavioral results showed that the response time for ASM and VSM tasks was longer than that for the AM and VM tasks. Interestingly, the prolong times were positively correlated with the ASD symptoms. The time-frequency analyses for the EEG data showed that the alpha phases between the motor and visual areas during only the VM and VSM tasks and between the motor and auditory areas in only the AM and ASM tasks. These task-relevant alpha phase synchronizations were decreased in the participants with high scores of the ASD symptoms. These results suggested that the ASD deficits would be associated with the decrements of the alpha synchronizations between the motor areas and the task-relevant sensory areas.


Trust is good, control is better: EEG quality control in a multicenter EEG study of children, adolescents and adults with ADHD

Anna Kaiser1, Martin Holtmann2, Andreas Fallgatter3, Marcel Romanos4, Manfred Döpfner5, Michael Rösler6, Tobias Banaschewski1, Daniel Brandeis1,7,8

1Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany; 2LWL-University Hospital for Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, Ruhr University Bochum, Hamm, Germany; 3Tübingen University Hospital for Psychiatry and Psychotherapy, Tübingen, Germany; 4Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy Hospital Clinic of the University of Würzburg, Würzburg, Germany; 5Child and Adolescent Psychiatry, University of Cologne, Cologne, Germany; 6Institute for Forensic Psychology and Psychiatry, University of the Saarland, Homburg, Germany; 7Department of Child and Adolescent Psychiatry, University of Zürich, Zürich, Switzerland; 8Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland

Quality of the raw data crucially impacts the validity of analyses and interpretation of scientific results obtained from electroencephalography (EEG). Therefore, regular assessments of EEG data quality are essential to ensure that established standards are met, particularly for multicenter studies.

EEG data are collected from N=68 patients within an ongoing multicenter study ESCAlife (involving Bochum, Homburg, Köln, Mainz, Mannheim, Marburg, Oldenburg, Rostock, Tübingen, Würzburg) of children, adolescents and adults (6 - 45 years) with ADHD in the ESCAbrain subproject. Resting state eyes open and eyes closed (4 minutes) EEG data are collected to identify potential predictors of treatment response. The EEG is recorded using a 22-channel EEG cap (Brain Products) and a sampling rate of 256 Hz (DC-70 Hz). As ADHD patients are prone to EEG artifacts, a regular data quality assessment focused on typical artefacts was conducted.

For data processing, the software BrainVision Analyzer (Brain Products) is used. The percentage of artifact-free epochs is calculated for each dataset as an index of data quality. Furthermore, the percentage of blink-artifact-related ICA-components is determined and compared across study centers and participants. Age of the participants, ADHD symptom severity, as well as the different study sites (comprising potentially relevant variables such as the electromagnetic environment, the training, and the experience of the staff with EEG recordings) are explored as relevant factors that might influence data quality.

Finally, corrective actions are discussed that were adopted to improve data quality.

This work was supported by the research consortium on ADHD, ESCA-Life, funded by the German Federal Ministry of Education and Research (FKZ 01EE1408E).


SCP-Neurofeedback and EMG-Biofeedback: Changes in EEG topographies in children with ADHD. Results from a Randomized controlled trial

Pascal-Maurice Aggensteiner1, Daniel Brandeis1,2, Ute Strehl3, Martin Holtmann4

1Central Institute of Mental Health, Medical Faculty Mannheim /Heidelberg University, Germany; 2Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland; 3Institute for Medical Psychology and Behavioral Neurobiology, University of Tuebingen, Tuebingen, Germany; 4LWL-University Hospital for Child and Adolescent Psychiatry, Ruhr-University Bochum, Hamm, Germany

Introduction

The neurophysiological effects of neurofeedback (NF) as a treatment for children with ADHD are still unclear. This randomized controlled trial analysed EEG power spectra before and after 25 sessions of slow-cortical potentials neurofeedback compared to electromyogram (EMG) biofeedback as a semi-active control group.

Methods

Children with ADHD (n=150, age 7-9 y) were randomly assigned to 25 training sessions of SCP- neurofeedback or EMG feedback. The neurofeedback group had to regulate slow EEG activity at Cz, while the EMG-feedback control group had to regulate relative electromyographic activity of the musculus supraspinati. Each training session consisted of three runs with visual feedback and one run without feedback which aims to transfer the learned skills into daily life. EEG power spectra topographies (21 channels) during resting with eyes closed from pre and post-intervention was analysed.

Results

Both interventions showed comparable reductions of theta and alpha activity during the eyes closed condition which was more prominent at central and posterior scalp localisations. A time by group interaction was found for beta frequencies over the central cortex. The EMG control group showed reduced beta power after the training sessions.

Conclusion:

This study provides evidence for nonspecific neurophysiological changes after neurofeedback and EMG training. The general reduction in both groups of theta and alpha power could reflect increased attention although effects of maturation of the brain cannot be excluded. The specific reduction in beta power after EMG biofeedback could be related to a better motor control and inhibition.


The role of the right inferior parietal lobe in sustained anxiety

Matthias Grieder1, Philipp Homan2, Andrea Federspiel1, Claus Kiefer3, Gregor Hasler1

1University Hospital of Psychiatry Bern, Translational Research Center, University of Bern, Switzerland; 2Departments of Psychiatry and Neuroscience, and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 3nstitute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern, Switzerland

Sustained anxiety is a key symptom of anxiety disorders. Its magnitude is related to the activation in the right inferior parietal lobe (rIPL), particularly under the threat of an unpredictable shock, but not under a neutral or predictable shock conditions. The present study investigated the causal role of this relationship.

In a double-blind, placebo-controlled crossover study with 22 healthy subjects, we applied 20 minutes of 1mA cathodal tDCS to the rIPL prior to two recordings of cerebral blood flow (CBF), using ASL-MRI. In between, we applied a threat-of-shock paradigm that comprised three conditions: predictable shocks (P), unpredictable shocks (U), or no electric shocks (N). Based on our previous work, we expected that in the U condition, tDCS reduced CBF in the rIPL and increased anxiety levels relative to sham tDCS. We further examined the CBF time course in neuronal networks that are either hyperactive (AnxNw+) or hypoactive (AnxNw-) in anxiety disorders.

As expected, anxiety levels were higher in the U than the P and N conditions, and tDCS augmented this effect, while sham tDCS did not affect anxiety. Contrary to our predictions, tDCS did not alter CBF in the rIPL. Instead, over the course of the anxiety experiment, CBF increased in both AnxNw+ and AnxNw-. Interestingly, tDCS increased CBF in AnxNw+, but not in AnxNw-.

Taken together, our results suggest that disbalancing the neuronal response to unpredictable threat in anxiety-related networks can reinforce anxiety. Our findings encourage studies to test tDCS to ease anxiety and treat anxiety disorders.


Sigma as a potential predictor for schizotypal personality

Stephanie Andrea Winkelbeiner, Sarah Müller, Stefanie Müller, Kristoffer Fehér, Thomas Dierks, Thomas Koenig, Matthias Grieder

Translational Research Center, University Hospital of Psychiatry, University of Bern

In schizophrenia, deficient sleep-dependent memory consolidation associated with reduced spindle activity contributes to cognitive deficits. Sleep spindles are brief bursts of 11-16Hz synchronous activity during NREM sleep-stage 2 (S2). However, spindle activity has not been investigated in healthy subjects with schizotypal personality traits. Therefore, we explored this relationship with respect to the spindle-frequency sigma and memory performance.

We investigated two hours of early-evening sleep of 20 healthy participants using EEG. Participants completed the Schizotypal Personality Questionnaire (SPQ) and performed an episodic memory task (face-occupation associations) with an immediate baseline recall before sleep and a delayed recall after sleep. Memory performance was defined as the number of correctly remembered associations (hits). Memory consolidation was defined as the difference between hits at delayed recall and baseline. To extract spindle magnitude, a fast Fourier transformation on the S2-data was computed.

Memory performance was not affected by the degree of schizotypal personality, but by the time of recall (before > after sleep). The interaction between schizotypal personality and time of recall failed to reach statistical significance. Yet, analysis revealed an inverse association of sigma amplitude with the SPQ subscales “Social Anxiety” and “No Close Friends”.

Altogether, episodic memory consolidation and performance seem independent of schizotypal personality. Nevertheless, aspects of schizotypal personality are associated with sigma amplitude. Impaired social cognition and skills were found in ultra-high risk patients for psychosis. Therefore, one could speculate about similar neuroplastic mechanisms in subjects with pronounced schizotypal personality traits and patients at risk for developing psychosis.


Pain and Neuroticism: a Trigeminal Pain-Related Evoked Potential Study

Giorgio Di Lorenzo

University of Rome Tor Vergata, Italy

Pain and Neuroticism: a Trigeminal Pain-Related Evoked Potential Study



 
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