Poster No:
428
Submission Type:
Abstract Submission
Authors:
Nadja Zimmermann1,2,3, Miriam Stüble1,3, Arndt-Lukas Klaassen1, Chantal Michel1, Michael Kaess1,4, Jochen Kindler1, Yosuke Morishima2
Institutions:
1University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland, 2Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland, 3Graduate School for Health Sciences, University of Bern, Bern, Switzerland, 4Department of Child and Adolescent Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany
First Author:
Nadja Zimmermann
University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern|Translational Research Center, University Hospital of Psychiatry, University of Bern|Graduate School for Health Sciences, University of Bern
Bern, Switzerland|Bern, Switzerland|Bern, Switzerland
Co-Author(s):
Miriam Stüble
University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern|Graduate School for Health Sciences, University of Bern
Bern, Switzerland|Bern, Switzerland
Arndt-Lukas Klaassen
University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern
Bern, Switzerland
Chantal Michel
University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern
Bern, Switzerland
Michael Kaess
University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern|Department of Child and Adolescent Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg
Bern, Switzerland|Heidelberg, Germany
Jochen Kindler
University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern
Bern, Switzerland
Yosuke Morishima
Translational Research Center, University Hospital of Psychiatry, University of Bern
Bern, Switzerland
Introduction:
A clinical high-risk (CHR) state for psychosis describes a possibly pre-psychotic state, marked by prodromal symptoms such as impairment of cognition, affect, and social behaviour (Fusar-Poli et al., 2013). Such a state usually precedes the onset of Schizophrenia and other psychotic disorders by several years, but only a fraction of patients classified as CHR convert to a first episode psychosis (De Pablo et al., 2021).
Aberrant connectivity of brain networks has been recognized to lie at the base of psychotic disorders, causing a failure of functional integration on a synaptic level as well as in long-range transmission of signals. This could be a possible cause for psychotic symptoms as well as cognitive deficits observed in psychotic disorders (Stephan et al., 2009)3. Such aberrant structural and functional connectivity has also been observed in patients with a CHR state for psychosis (Andreou & Borgwardt, 2020).
The concurrent use of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) provides opportunities to measure the temporal order of activations of connected cortical areas and their causal interactions in regard to excitatory or inhibitory functioning (Hallet et al., 2017). While there is evidence of abnormal signal propagation (Frantseva et al., 2014) and abnormal synchronized neural oscillations (Ferarelli et al., 2008) in schizophrenic patients measured by TMS-EEG, there is a lack of studies investigating these parameters in a CHR population. Therefore, in the current study, we utilized TMS-EEG to study abnormal neural oscillations in CHR.
Methods:
A total of 43 CHR patients and 57 healthy controls (HC) who completed a psychopathological and neuropsychological assessment as well as an MRI and TMS-EEG session were included in the analysis. Using a neuronavigation system with an individual structural MRI, the left dorsolateral prefrontal cortex (lDLPFC), dorsomedial prefrontal cortex (DMPFC) and left posterior parietal cortex (lPPC) were identified for TMS targets. At each site, single-pulse TMS was applied at both sub- and suprathreshold intensities of the individual Motor threshold and TMS-evoked activity was measured simultaneously with a 64 channel EEG. The acquired EEG data was pre-processed in MATLAB using the EEGLAB toolbox and subsequently analysed with custom scripts. Time-frequency information was extracted by performing Morlet-Wavelet convolution.
Results:
Both groups showed a distinctive distribution of TMS-related theta activity in a fronto-central region after stimulation of all ROIs. In the HC group however, permutation tests revealed significant differences in theta power depending on the site of stimulation. TMS to the left DLPFC stimulation evoked the most amount of power, followed by left PPC and finally DMPFC. In the CHR patients on the other hand, TMS-related power did not vary significantly between stimulation targets and was comparable to HC lDFLPC stimulation.
Conclusions:
In this study, we identified inter-regional heterogeneity in TMS-related theta activity across cortical areas in HC. In contrast, regional differentiation was not observed in CHR, suggesting a loss of functional specialization in CHR patients.
As theta-band oscillatory activity plays a key role in long-range communication between brain networks (Von Stein & Sarnthein, 2000), these regional differences in oscillatory response may represent the organization of connections necessary for functional specialization of cortical regions within healthy brain networks. The absence of such differentiation in CHR could potentially lead to inefficient network communication. These findings provide novel insights into network-level dysfunctions associated with the CHR state for psychosis.
Brain Stimulation:
TMS 2
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
EEG/MEG Modeling and Analysis
Novel Imaging Acquisition Methods:
EEG
Keywords:
Electroencephaolography (EEG)
Psychiatric
Psychiatric Disorders
Schizophrenia
Transcranial Magnetic Stimulation (TMS)
Other - Oscillations; Network dysfunction; Dysconnectivity
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Other
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
No
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Yes
Were any animal research approved by the relevant IACUC or other animal research panel?
NOTE: Any animal studies without IACUC approval will be automatically rejected.
Not applicable
Please indicate which methods were used in your research:
EEG/ERP
Structural MRI
TMS
Neuropsychological testing
For human MRI, what field strength scanner do you use?
3.0T
Which processing packages did you use for your study?
SPM
Other, Please list
-
eeglab, tmseeg, CAT12
Provide references using APA citation style.
1. Andreou, C., & Borgwardt, S. (2020). Structural and functional imaging markers for susceptibility to psychosis. Molecular psychiatry, 25(11), 2773-2785.
2. De Pablo, G. S., Radua, J., Pereira, J., Bonoldi, I., Arienti, V., Besana, F., ... & Fusar-Poli, P. (2021). Probability of transition to psychosis in individuals at clinical high risk: an updated meta-analysis. JAMA psychiatry, 78(9), 970-978.
3. Ferrarelli, F., Massimini, M., Peterson, M. J., Riedner, B. A., Lazar, M., Murphy, M. J., ... & Tononi, G. (2008). Reduced evoked gamma oscillations in the frontal cortex in schizophrenia patients: a TMS/EEG study. American Journal of Psychiatry, 165(8), 996-1005.
4. Frantseva, M., Cui, J., Farzan, F., Chinta, L. V., Perez Velazquez, J. L., & Daskalakis, Z. J. (2014). Disrupted cortical conductivity in schizophrenia: TMS–EEG study. Cerebral Cortex, 24(1), 211-221.
5. Fusar-Poli, P., Borgwardt, S., Bechdolf, A., Addington, J., Riecher-Rössler, A., Schultze-Lutter, F., ... & Yung, A. (2013). The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA psychiatry, 70(1), 107-120.
6. Hallett, M., Di Iorio, R., Rossini, P. M., Park, J. E., Chen, R., Celnik, P., ... & Ugawa, Y. (2017). Contribution of transcranial magnetic stimulation to assessment of brain connectivity and networks. Clinical Neurophysiology, 128(11), 2125-2139.
7. Stephan, K. E., Friston, K. J., & Frith, C. D. (2009). Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophrenia bulletin, 35(3), 509-527.
8. Von Stein, A., & Sarnthein, J. (2000). Different frequencies for different scales of cortical integration: from local gamma to long range alpha/theta synchronization. International journal of psychophysiology, 38(3), 301-313.
No