Impaired context processing as a potential marker of psychosis risk state

Abstract

While structural abnormalities of the dorsolateral prefrontal cortex (DLPFC) may pre-date and predict psychosis onset, the relationships between functional deficits, cognitive and psychosocial impairments has yet to be explored in the at-risk period. An established measure of cognitive control (AXCPT) was administered to demographically matched clinical-high-risk (CHR; n=25), first-episode schizophrenia (FE; n=35), and healthy control (HC; n=35) participants during functional magnetic resonance imaging (fMRI) to investigate these relationships. CHR and FE individuals demonstrated impaired context processing and reduced DLPFC activation relative to HC individuals during increased cognitive control demands. FE and CHR individuals’ ability to increase DLPFC activity in response to cognitive control demands was associated with better task performance. Task performance was also associated with severity of disorganization and poverty symptoms in FE participants. These findings support more extensive studies using fMRI to examine the clinical significance of prefrontal cortical functioning in the earliest stages of psychosis.

Neural Dysfunction in Cognitive Control Circuits in Persons at Clinical High-Risk for Psychosis

“…The percentages of CHR individuals in our cohort who had scores equal or lower than 6 on the GFS:S and GSF:R were 43.2 and 44.4%, respectively. These social and role outcomes were similar to those of other CHR cohorts (Carrion et al, 2013) as were our rates of conversion to psychosis and exposure to antipsychotic medications (Niendam et al, 2013;Dandash et al, 2013;Yaakub et al, 2013). One CHR individual was scanned around the time of conversion to psychosis.…”

“…This rate is now considered as typical of prodromal research in general (Niendam et al, 2013;Yaakub et al, 2013;Katsura et al, 2014) and similar to the conversion rates in various consortia, such as the European Prediction of Psychosis Study (Salokangas et al, 2012). These rates reflect a decline in conversion since the time of the original reports in CHR samples (Yung et al, 2007).…”

“…Based on prior studies indicating the presence of abnormal neural processes when performing tasks that place demands on cognitive control (Niendam et al, 2013), and given extensive clinical and developmental considerations that suggest the presence of impaired capacities for processing and resolving conflict in psychotic illness (Luna, 2009), we hypothesized that CHR individuals would present with a neural impairment of conflict processing, an aspect of cognitive control. Mastering the ability to regulate cognitive control flexibly based on changing demands is especially crucial for establishing adaptive, goal-directed behaviors and, thus, for a successful transition from adolescence into adulthood.…”

“…Our primary hypothesis was that CHR individuals would exhibit, when compared with healthy controls, reduced neural activity in DLPFC and dorsal striatum during the processing of conflict (Niendam et al, 2013).…”

Beyond “Cold” Cognition: Exploring Cognitive Control of Emotion as a Risk Factor for Psychosis

“…These self-regulatory processes are reliant on cognitive control mechanisms facilitated by the cingulo-frontalparietal cognitive control network [49,50]. Dysfunction in the cognitive control network, particularly the lateral prefrontal cortex (LPFC), is a well-established neural impairment in schizophrenia [51•] and high-risk populations [52][53][54], and is thought to be a biomarker for psychotic illness [8, 51•]. However, how LPFC dysfunction confers vulnerability and manifests in the core characteristics of psychosis is unknown.…”