Modulation of Brain Networks Relevant for Schizophrenia

Abstract

Schizophrenia is a complex neuropsychiatric disorder characterized by disruptions in cognition, perception, and behaviour. Traditional approaches to understanding and treating schizophrenia have primarily focused on categorical diagnostic criteria, often overlooking the underlying neurophysiological mechanisms. In our current research project entitled “Pharmacological and Electrical Modulation of Disturbed Networks in Schizophrenia and the Clinical High-Risk State for Psychosis,” we aimed to identify potential treatment targets for specific symptoms of psychosis and schizophrenia, particularly auditory hallucinations and working memory impairment. Our goal was to advance a symptom-based approach by investigating the role of brain circuits relevant in schizophrenia symptoms and exploring their modulation as a potential therapeutic avenue. To achieve these goals, we carried out a preliminary work to initially investigate these brain networks in healthy participants to assess the feasibility of our approach, with the aim of future translation to patients with psychosis. The current thesis comprises three published studies. The first two studies demonstrate the feasibility of modulating task- and symptom-relevant brain oscillations through cognitive modulation and electrical stimulation techniques in healthy individuals. The third study presents a review on the potential role of transcranial alternating current stimulation (tACS) in psychiatric research. In the first study, we employed a dichotic listening paradigm to examine interhemispheric connectivity in the gamma-band, a frequency known to be altered in individuals experiencing auditory hallucinations. By manipulating attentional control, we successfully induced changes in interhemispheric oscillatory communication, reinforcing the functional role of gamma oscillations in auditory perception and attention. The second study investigated the effects of tACS applied to the dorsolateral prefrontal cortex during a working memory task. Our findings demonstrated that theta-tACS improved reaction times in high-load trials and increased frontal theta power, supporting the notion that non-invasive brain stimulation can enhance cognitive performance through oscillatory entrainment. In the third study, we conducted a systematic search of the literature to assess the broader implications of tACS in psychiatric research. Our analysis highlighted the potential of tACS to modulate pathological brain rhythms associated with psychiatric disorders, including schizophrenia. However, we also emphasized the need for optimized stimulation protocols to achieve consistent and clinically meaningful outcomes. Our findings may contribute to the growing evidence that brain oscillations play a crucial role in cognition and psychopathology. Specifically, we highlight the significance of interhemispheric gamma synchronization in auditory processing and frontal theta oscillations in working memory. These insights may provide promising targets for neuromodulation interventions. Clinically, our results suggest that modulating gamma connectivity could be relevant for treating auditory hallucinations, while theta-tACS may offer a non-invasive approach to improving cognitive deficits in schizophrenia. In conclusion, these results may contribute to the ongoing effort to develop a symptom-based framework for schizophrenia research by demonstrating the functional relevance of brain oscillations and their susceptibility to modulation. Our findings could provide a foundation for future research aimed at refining neuromodulation techniques and translating these insights into clinical applications. While further research is needed to refine stimulation protocols and tailor interventions to patient subgroups, our findings might support the potential of oscillation-based treatments as a promising avenue for mitigating cognitive and perceptual disturbances in schizophrenia.