Mathematical Model Insights into EEG Origin under Transcranial Direct Current Stimulation (tDCS) in the Context of Psychosis.

Abstract

Schizophrenia is a psychotic disease that develops progressively over years with a transition from prodromal to psychotic state associated with a disruption in brain activity. Transcranial Direct Current Stimulation (tDCS), known to alleviate pharmaco-resistant symptoms in patients suffering from schizophrenia, promises to prevent such a psychotic transition. To understand better how tDCS affects brain activity, we propose a neural cortico-thalamo-cortical (CTC) circuit model involving the Ascending Reticular Arousal System (ARAS) that permits to describe major impact features of tDCS, such as excitability for short-duration stimulation and electroencephalography (EEG) power modulation for long-duration stimulation. To this end, the mathematical model relates stimulus duration and Long-Term Plasticity (LTP) effect, in addition to describing the temporal LTP decay after stimulus offset. This new relation promises to optimize future stimulation protocols. Moreover, we reproduce successfully EEG-power modulation under tDCS in a ketamine-induced psychosis model and confirm the N-methyl-d-aspartate (NMDA) receptor hypofunction hypothesis in the etiopathophysiology of schizophrenia. The model description points to an important role of the ARAS and the -rhythm synchronicity in CTC circuit in early-stage psychosis.