Conference Agenda

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Session Overview
Free communications 3: Psychiatric disorders and psychoactive substances
Friday, 01/Sep/2017:
2:30pm - 4:00pm

Location: Room A-003
Uni-S Schanzeneckstrasse 1 3012 Bern

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2:30pm - 2:45pm

D2/D3 Dopamine Receptor Binding with [F-18] Fallypride Correlates of Executive Function in Medication-Naïve Patients with Schizophrenia

Monte Buchsbaum1,5, Nora Vyas2, Douglas Lehrer3, Bradley Christian4, Brian Merrill4, Nicholas Doninger4, Alex DeCastro1, Jogeshwar Mukherjee5

1University of California, San Diego, United States of America; 2Kingston University, London, England; 3Wright State University, Dayton, USA; 4University of Wisconsin-Madison, USA; 5University of California, Irvine

Resting-state 18F-fallypride positron emission tomography was performed on 25 patients (mean(±sd) age: 31.6±12.2) with schizophrenia (20 medication-naïve and 5 previously medicated for a brief period) and 19 age- and sex-matched healthy volunteers (mean(±sd) age: 29.2±9.3).

Two neuropsychological tasks known to activate frontal and temporal lobe function were chosen, specifically the Wisconsin Card Sorting Test (WCST) and the California Verbal Learning Test (CVLT). Magnetic resonance images in standard Talairach position and segmented into gray and white matter were co-registered to the fallypride images, and the AFNI stereotaxic atlas was applied. Selective AFNI regions of interest (ROIs) were calculated from each subject. We calculated product-moment correlation coefficients between each ROI and the brain areas. Patients with schizophrenia showed negative correlations between binding potential and performance on WCST perseverative errors and CVLT learning slope, while healthy volunteers showed better performance with high binding potential in the frontal cortex and right temporal lobe. The healthy volunteers show positive correlations (red/yellow) indicating that high binding potential is associated with better performance. However patients show the reverse (blue) indicating low binding potential is associated with better performance for WCST.

. The positive correlation may be interpreted as less dopamine is associated with better performance in healthy volunteers. However patients with schizophrenia showed the reverse which suggests a compensatory dopamine system response.These results suggest that partial agonist treatment may assist cognitive performance in schizophrenia.

2:45pm - 3:00pm

Aberrant resting state connectivity in the motor system indicates abnormal motor behavior in schizophrenia

Sebastian Walther1, Andrea Federspiel1, Katharina Stegmayer1, Roland Wiest2, Stephan Bohlhalter3, Petra Viher1

1University of Bern, Switzerland; 2Neuroradiology, Inselspital, Bern, Switzerland; 3Neurology and Neurorehabilitation Center, Kantonsspital Luzern, Switzerland

Background: Motor abnormalities are frequent in schizophrenia. Likewise, schizophrenia is faced with structural and functional dysconnectivity. Here, we tested whether resting state connectivity in the motor system would be aberrant in schizophrenia and linked to motor behavior abnormalities.

Method: In total, 46 patients and 44 controls underwent BOLD resting state scans for 8 mins and performed a comprehensive motor battery. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity using CONN. Principal component analyses of motor behavioral data produced four factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). We tested group differences in connectivity as well as correlations betwenn motor factor scores and connectivity values.

Results: Schizophrenia was characterized by hyperconnectivity in three main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity.

Discussion: Altered resting state functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations

3:00pm - 3:15pm

Timing is Everything: Neurophysiology of Rhythm-Based Acoustic Segmentation in the First-Episode Schizophrenia Spectrum

Brian A Coffman, Sarah M Haigh, Tim K Murphy, Justin 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

Dyscoordination of perceptual sequencing systems is central to many cognitive deficits in schizophrenia. This is well-illustrated by neurophysiological deficits in auditory perceptual grouping and segmentation based on rhythmic sequence structure. Here we examine the N2 and auditory sequence potential (ASP) as they relate to network coordination within sensorimotor sequencing systems in participants at the first psychotic episode (FESz). Twenty-three FESz and 23 matched healthy controls (HC) ignored tone groups while watching a silent cartoon. Stimuli comprised 300 groups of three identical tones (1 kHz; 80 dB; 50 ms duration; 330 ms SOA, 800 ms ITI). Beta entrainment, N2, and ASP were measured to standard groups. ASP sources were localized using minimum-norm estimation for individuals with structural MRI (FESz=14; HC=14). ASP was reduced in FESz compared to HC (p<0.05). N2 responses were not significantly reduced (p>0.1). Source analysis revealed that ASP was generated primarily in bilateral primary auditory cortex (A1) and supplementary motor area (SMA). ASP activity in SMA (p<0.001), but not A1 (p>0.1) was reduced for FESz compared to matched controls. Further, coherent beta-band oscillatory activity was entrained to stimulus onset in HC, but not FESz, and this entrainment correlated with ASP activity in A1 and SMA (r’s>0.3). These results suggest that deficits in auditory pattern processing in schizophrenia occur early in the disease course. Reductions in beta entrainment and SMA activity suggest systems-level dysfunction in sensorimotor sequencing networks in FESz. Further work will assess symptom and functioning concomitants in deficits in this fundamental complex perceptual process.

3:15pm - 3:30pm

The effects of psilocybin on the dynamics of EEG changes in human volunteers

Tomas Palenicek1,2, Filip Tyls1,2, Michaela Viktorinova1,2, Jakub Korcak1,2, Anna Bravermanova1, Martin Brunovsky1,2, Jiri Horacek1,2

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

Psilocybin is a serotonergic psychedelic with an agonist activity at 5-HT2A/C and 5-HT1A receptors. It is used as a research tool to study neurobiology of psychosis as well as it is gaining attention as a possible therapeutic tool to treat depression, anxiety and addiction. It has been already shown that psychedelics including psilocybin acutely induce desynchronization of the alpha activity occipitally and disconnection during the peak of intoxication. However understanding of the dynamics of these changes has not been evaluated yet. Therefore the current study focuses on the behavioural and EEG effects of psilocybin at several time points during the 6 hours of intoxication. Twenty volunteers with a balanced gender ratio (10M/10F) have entered the study. Each participant underwent two sessions with oral psilocybin (0.26 mg/kg) or a placebo in a double blinded crossover design. In most of the subjects, psilocybin induced fully psychedelic effects as measured by psychometric scales, the effects peaked between 1-2 h after administration. Decreased current density of the alpha band in the occipital region which diminished over time was the most robust finding. The connectivity analyses showed biphasic effect on overall connectivity indicating two different connectivity states at the peak of intoxication and 6h after the ingestion. Results will be discussed in relation to the potential therapeutic effects of psilocybin. This study was supported by the projects ED2.1.00/03.0078, LO1611/NPU I, MICR VI20172020056, MH CZ - DRO (NIMH-CZ, 00023752) and PROGRES Q35.

3:30pm - 3:45pm

Sustained brain activity during self-reference in bipolar disorder patients

Kallia Apazoglou1, Paolo Cordera2, Patrik Vuilleumier1, Alexandre Dayer1,2, Jean-Michel Aubry2,3, Camille Piguet2,3

1Department of Neuroscience, Faculty of Medicine, University of Geneva, Switzerland; 2Department of Mental Health and Psychiatry, Geneva University Hospital, Switzerland; 3Departement of Psychiatry, Faculty of Medicine, University of Geneva, Switzerland

Aim: Mood disorders patients present difficulties to switch away from negative and self-focused automatic thoughts, which might represent the basis for incapacitating symptoms such as rumination. We aimed to investigate the activity in neural networks when patients have to switch between internally and externally focused attention and correlations with rumination scale.

Method: We compared a group of 20 euthymic bipolar patients and a group of 20 matched heathy controls during a fMRI task where they either rate how they are feeling, or how many letters are in the stimulus, using positive and negative adjectives.

Results: The “externally focused” condition elicited activity in a classical attentional network, and the “internally focused” condition in a network with central activations in medial prefrontal and cingulate regions, validating our paradigm. Bipolar patients showed significantly higher activity than controls in the vmPFC, PCC and parietal cortex, and in particular increased activity in pregenual ACC during the internal trials, which correlated with the tendency to ruminate. Switching from an internal to an external trial revealed higher activity in the entorhinal cortex for patients, especially after a negative trial. Repetition of negative internal trials also showed increased and correlated activity in medial areas.

Conclusion: Patients showed higher activity in medial cortical areas during the internally-focused condition, supporting the notion of an enhancement of self-processing in those patients. Negative valence might additionally trigger more activity in network associated with autobiographic memory and rumination.

3:45pm - 4:00pm

Multimodal Fingerprints of Resting State Networks as assessed by Simultaneous Trimodal MR-PET-EEG Imaging

Shah N.Jon1,2,4,6, Jorge Arrubla1,3, Ravichandran Rajkumar1,3, Ezequiel Fahrrer1, Jörg Mauler1, Elena Rota Kops1, Lutz Tellmann1, Jürgen Scheins1, Frank Boers1, Jürgen Dammers1, Praveen Sripad1, Christoph Lerche1, Langen Karl Joseph1,4,5, Hans Herzog1, Irene Neuner1,3,4

1Institute of Neuroscience and Medicine 4, INM-4, Forschungszentrum Jülich, Germany; 2Institute of Neuroscience and Medicine 11, INM-11, Forschungszentrum Jülich, Germany; 3Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Germany; 4JARA – BRAIN – Translational Medicine, Germany; 5Department of Nuclear Medicine, RWTH Aachen University, Germany; 6Department of Neurology, RWTH Aachen University, Germany

Simultaneous MR-PET-EEG (magnetic resonance imaging - positron emission tomography – electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here for the first time. It enables the assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. Here, we characterize the brain’s default mode network (DMN) in healthy male subjects using multimodal fingerprinting by quantifying energy metabolism via 2- [18F]fluoro-2-desoxy-D-glucose PET (FDG-PET), the inhibition – excitation balance of neuronal activation via magnetic resonance spectroscopy (MRS), its functional connectivity via fMRI and its electrophysiological signature via EEG. The trimodal approach reveals a complementary fingerprint. Neuronal activation within the DMN as assessed with fMRI is positively correlated with the mean standard uptake value of FDG. Electrical source localization of EEG signals shows a significant difference between the dorsal DMN and sensorimotor network in the frequency range of δ, θ, α and β–1, but not with β–2 and β–3. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases.

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