Pharmacological and electrical modulation of disturbed networks in schizophrenia and the clinical high-risk state for psychosis – Pharmacological modulation of an attentional network in the ketamine model of schizophrenia combined with multimodal EEG/fMRI-DTI imaging
Final Report Abstract
Schizophrenia is a mental disorder that disrupts a person's thoughts, emotions, and behaviour, often leading to an altered perception of reality. This condition is believed to stem from a combination of genetic, neuro chemistry, and environmental factors. One aspect of neuro chemistry involved is an imbalance between excitatory and inhibitory signals in the brain. A crucial player in this process is the N-Methyl-D-Aspartate Receptor (NMDAR). Understanding and measuring how well this receptor functions could be key to developing individual treatments. Our study involves several brain imaging techniques to examine NMDAR functionality during a task that requires attention, including electroencephalography (EEG; which records brain activity with high temporal resolution) and magnetic resonance imaging (MRI; which captures brain activity and structure with high spatial resolution). We use a drug called ketamine on healthy volunteers to mimic the receptor's hypofunction seen in schizophrenia. We aim to measure ketamine’s effects and the benefits of a pretreatment with glycine, which is supposed to enhance NMDAR function. To this end, our study involved 32 participants who after a baseline session were given either glycine or a placebo before receiving ketamine. Our findings demonstrate that ketamine induced schizophrenia-like symptoms and affected brain activity and microstructure. Interestingly, while glycine did not alter the MRI results much, it affected the errors made by participants in the attention task and the corresponding EEG activity after the application of ketamine. This suggests that glycine might help counter some effects of NMDAR hypofunction. In conclusion, our research supports the idea that certain changes in brain activity are linked to NMDAR hypofunction. The observed changes in brain microstructure are surprising and call for further study. Further, our work suggests that monitoring specific brain activity patterns via EEG could offer new insights into how people with schizophrenia might respond to treatments targeting the glutamate system.
Publications
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A Luigi workflow joining individual modules of an MRI processing pipeline
Billah, Tashrif & Bouix, Sylvain
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2024 SIRS conference poster presentation, Toronto: Exploring Neural Correlates of NMDA Receptor Hypofunction through Multimodal Imaging Post-Ketamine Administration: Investigating Markers of Glutamatergic Neurotransmission Modulation
Moritz Nils Haaf
