Functional Connectivity of Corticostriatal Circuitry and Psychosis-like Experiences in the General Community

Abstract

Background: Psychotic symptoms are proposed lie on a continuum, ranging from isolated psychosis-like experiences (PLEs) in non-clinical populations to frank disorder. Here, we investigate neurobiological correlates of this symptomatologic continuum by examining whether functional connectivity of dorsal corticostriatal circuitry, which is disrupted in patients and high-risk individuals, is associated with the severity of subclinical PLEs. Methods: A community sample of 672 adults with no history of psychiatric or neurological illnesses completed a battery of seven questionnaires spanning various PLE domains. Principal component analysis (PCA) estimated major dimensions of PLEs from the questionnaires. PCA dimension scores were then correlated with whole-brain voxelwise functional connectivity (FC) maps of the striatum in a subset of 353 participants who completed a resting-state neuroimaging protocol. Results: PCA identified two dimensions of PLEs accounting for 62.57% of variance in the measures, corresponding to positive and negative PLEs. Reduced FC between the dorsal striatum and prefrontal cortex correlated with higher positive PLEs. Negative PLEs correlated with increased FC between the dorsal striatum and visual and sensorimotor areas.In the ventral corticostriatal system, positive and negative PLEs were both associated with FC between the ventro-rostral putamen and sensorimotor cortices.Conclusions: Consistent with past findings in patients and high-risk individuals, subthreshold positive symptomatology is associated with reduced FC of the dorsal circuit.These findings suggest that the connectivity of this circuit tracks the expression of psychotic phenomena across a broad spectrum of severity, extending from the subclinical domain to clinical diagnosis..

Network controllability in transmodal cortex predicts psychosis spectrum symptoms

“…This failure may be due to the fact that, in our model, the psychosis-negative factor explained less variance in symptom data compared to the psychosis-positive factor (see Table S1), and hence our estimate of negative PS symptoms was perhaps noisier than our estimate of positive PS symptoms. Similar disparities in variance explained between positive and negative psychosis dimensions have also been reported in previous literature using principal component analysis (77). Thus, future work improving the modeling of variance in negative PS symptoms is needed and may yield improved predictive performance in brain-based association studies.…”

“…Here, owing to emergent evidence that the positive and negative aspects of the psychosis spectrum elicit unique effects on the brain (19), we extended the above p-factor model in two ways. First, we included an additional five assessor-rated polytomous items (scored from 0-6, where 0 is ‘absent’ and 6 is ‘severe and psychotic’ or ‘extreme’ from the Scale of Prodromal Symptoms (SOPS) derived from the Structured Interview for Prodromal Syndromes (SIPS (20)) designed to measure the negative/disorganized symptoms of psychosis.…”

Network Controllability in Transmodal Cortex Predicts Positive Psychosis Spectrum Symptoms

“…Hence our estimate of negative PS symptoms was perhaps noisier than our estimate of positive J o u r n a l P r e -p r o o f PS symptoms. Similar disparities in variance explained between positive and negative psychosis dimensions has also been reported in previous literature (73). Thus, future work improving the modeling of variance in negative PS symptoms is needed and may yield improved predictive performance in brain-based association studies.…”

Differentiating the Effect of Medication and Illness on Brain Volume Reductions in First-Episode Psychosis: A Longitudinal, Randomized, Triple-blind, Placebo-controlled MRI Study

“…The function of these circuits is heavily modulated by dopamine, and their disruption is apparent in diagnosed patients 30 , patients’ unaffected first-degree relatives 30 and individuals experiencing an at-risk mental state for psychosis 31 . Functional connectivity within this circuit also correlates with the severity of psychotic-like experiences in non-clinical samples 32 . Thus, one hypothesis that may explain our findings is that altered signalling from the striatum triggers early volumetric loss in the pallidum 29,33 , which subsequently spreads to affect functionally-related prefrontal areas 34,35 .…”