Evaluation of fronto-striatal networks during cognitive control in unmedicated patients with schizophrenia and the effect of antipsychotic medication

Abstract

To understand the mechanism of cognitive control dysfunction in schizophrenia, it is critical to characterize brain function without the confounding effect of medication. It is also important to establish the extent to which antipsychotic medication restores brain function and whether those changes are related to psychosis improvement. Twenty-two patients with schizophrenia, initially unmedicated and after a 6-week course of risperidone, and 20 healthy controls (HC) studied twice, 6 weeks apart, performed an fMRI task. We examined group and longitudinal differences in anterior cingulate cortex (ACC), striatum, and midbrain functional activity during performance of a Stroop color task as well as activity patterns associated with improvement in psychosis symptoms. Unmedicated patients showed reduced functional activity in the ACC, striatum, and midbrain compared to HC. Post hoc contrasts from significant group-by-time interactions indicated that, in patients, drug administration was associated with both activity increases and decreases. In unmedicated patients, greater baseline functional activity in the striatum and midbrain predicted subsequent better treatment response. Greater changes in functional activity in ACC and ventral putamen over the course of 6 weeks positively correlated with better treatment response. Unmedicated patients show reduced activity in brain networks pivotal for cognitive control and medication is associated with functional changes in these regions. These results suggest a mechanism by which antipsychotic medication has a beneficial effect on cognition. Our results also support the notion that treatment response is determined by a combination of the baseline pattern of brain function and by the pharmacological modulation of these regions.

A Longitudinal Multimodal Neuroimaging Study to Examine Relationships Between Resting State Glutamate and Task Related BOLD Response in Schizophrenia

“…Results of Stroop task-based BOLD fMRI signal in off-medication SZ patients and the longitudinal differences after 6 weeks of medication have been previously published ( 63 ). In the SN, off-medication SZ showed significantly less BOLD response in the ACC and insula compared to baseline HC during Stroop task performance.…”

Cognitive control network connectivity differentially disrupted in treatment resistant schizophrenia

“…This finding is supported by evidence that prefrontal-striatal functional connectivity is important for determining treatment response in antipsychotic-naïve patients with psychosis. For example, Cadena et al, 2018 , Cadena et al, 2019 ) reported increased ACC functional activity and functional connectivity between ACC and putamen from baseline to follow-up was associated with better treatment response (decrease in symptoms) following a 6-week course of antipsychotic medication (risperidone) ( Cadena et al, 2018 , Cadena et al, 2019 ). Sarpal et al (2016) also reported that resting-state striatal functional connectivity, including with ACC, was predictive of treatment response following a trial of second generation antipsychotic medication in first episode psychosis ( Sarpal et al, 2015 ).…”

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

“…Other associations with dorsal circuit function and PLE severity implicate areas that are known to be affected by schizophrenia and subthreshold symptomatology. Abnormal structure and function of the ACC are frequently reported in both patients and high-risk individuals (29,(69)(70)(71)(72)(73)(74). Concordantly, ACC dysfunction is linked to a failure to update prior beliefs based on sensory experience, which may induce hallucinations (75).…”