The neural underpinnings of cognitive flexibility and their disruption in psychotic illness

Abstract

Schizophrenia (SZ) has long been associated with a variety of cognitive deficits, including reduced cognitive flexibility. More recent findings, however, point to tremendous inter-individual variability among patients on measures of cognitive flexibility/set-shifting. With an eye toward shedding light on potential sources of variability in set-shifting abilities among SZ patients, I examine the neural substrates of underlying probabilistic reversal learning (PRL) - a paradigmatic measure of cognitive flexibility - as well as neuromodulatory influences upon these systems. Finally, I report on behavioral and neuroimaging studies of PRL in SZ patients, discussing the potentially influences of illness profile and antipsychotic medications on cognitive flexibility in SZ.

Keywords: basal ganglia; dopamine; prefrontal cortex; psychosis; serotonin; set-shifting.

Figure 1

(A) Mean percentages of switches occurring × number of trials after a contingency reversal (denoted trial n+x, where x = 1, 2, 3, 4, 5, >5). (B) Scatter plot illustrating systematic relationship, in schizophrenia patients, between psychosis severity ratings and the percentages of stages in which a subject switched back to the previously-better stimulus, before completing the stage. Abbreviations: NC, normal controls; LPS, low-positive-symptom patients; HPS, high-positive-symptom patients, BPRS, Brief Psychiatric Rating Scale.