Analysis of functional connectivity differences in Schizophrenia groups characterized by M1 receptor polymorphism during the N-Back task with fNIRS

This study focuses on the impact of M1-receptor polymorphism (rs2067477) on functional connectivity patterns of patients with schizophrenia receiving clozapine monotherapy. Although previous work suggested a relationship between M1-receptor polymorphism and cognitive function in schizophrenia, there are contradictory findings. In earlier work, we conducted an fNIRS experiment with treatment resistant schizophrenia patients and observed that the M1-receptor polymorphism did not have an effect on N-back performance; however, significant differences in cortical activity were observed at regions associated with working memory. The current study investigates whether there are differences in the functional connectivity patterns of these patient groups. Wavelet Transform Coherence method was utilized to observe overall and task-level differences in the connectivity profiles of patient groups. The results revealed that wild-type individuals exhibit higher brain activation in task related cortical regions in the prefrontal and premotor cortex, but lower functional connectivity in the fronto-temporal network compared to non-wild-types. These differences indicate the possible role of genetic variations in shaping the neural response to clozapine, with wild-type individuals displaying more efficient neural strategies, whereas non-wild-type individuals rely on broader, less efficient compensatory processes to sustain cognitive performance.