Cerebellar and subcortical interplay in cognitive dysmetria: functional network signatures associate with symptom and trait assessments across schizophrenia, bipolar II, and ADHD patients.

Abstract

Cognitive dysmetria suggests a disorganization of cognitive processes, particularly in relation to the cerebellum's role in coordinating thoughts and actions. This phenomenon has been extensively studied in various psychiatric disorders, including schizophrenia (SCHZ), bipolar disorder II (BIPOL), and attention-deficit/hyperactivity disorder (ADHD). Understanding the relationship between cognitive dysmetria and functional connectivity in these disorders would reveal significant insights into their neurobiological underpinnings. This study explores how distinct and similar functional network connectivity (FNC) patterns between brain regions are associated with clinical symptoms and trait assessments across SCHZ, BIPOL, and ADHD patients by examining both working memory and task-free conditions compared to healthy volunteers (HC). Leveraging an open-source fMRI dataset from the UCLA Consortium for Neuropsychiatric Phenomics, we analyzed FNC patterns across 115 default mode and salience network regions, including cortical, subcortical, and cerebellar regions of interest in 135 participants (39 HC, 27 SCHZ patients, 38 BIPOL patients, and 31 ADHD patients). Abnormal FNC patterns compared to HC were localized to the cerebellar, thalamic, striatal, hippocampal, medial prefrontal and anterior insular cortices. Post-hoc multiple comparison analysis showed abnormal network connectivity predominantly in SCHZ and ADHD patients during rest, while the task condition demonstrated differential effects across all three disorders. Statistical analysis using a factor-by-covariance approach (GLM MANCOVA) suggested that regional functional connectivity was associated with select symptoms and traits pointing to neural signatures underlying psychiatric conditions. Our study suggests that examining and harnessing dysfunctional relationships in subcortical and cerebellar regions could provide a new perspective on the neurobiological basis of psychoses and help improve available treatment strategies.