Load-dependent hyperdeactivation of the default mode network in people with schizophrenia

Schizophrenia is associated with impairment in a range of cognitive functions. Neuroimaging studies have reported lower, but also higher, task-induced activation accompanying impaired performance. Differences in task-load and the ability of people with schizophrenia (PSZ) to stay engaged in the cognitive operations probed appear to underlie such discrepancies. Similarly, task-induced deactivation of the default mode network (DMN) was weaker in PSZ relative to healthy control subjects (HCS) in most studies, but some reported greater deactivation. An inability to stay engaged in the cognitive operations could account for these discrepancies, too, as it would lead to more time off-task and consequently less deactivation of DMN functions. The present study employed a change detection paradigm with small to moderate set sizes (SSs) of 1, 2, and 4 items. Task training prior to fMRI scanning abolished the group difference in no-response trials. Task-positive regions of interest (ROIs) displayed greater activation with increasing SS in both groups. PSZ showed greater activation relative to HCS at SSs 1 and 2. DMN ROIs displayed greater deactivation with increasing SS in PSZ, but not in HCS, and PSZ tended to hyperdeactivate DMN regions at SS 4. No hypodeactivation was observed in PSZ. In conclusion, when minimizing differences in task-engagement, PSZ tend to over-recruit task-positive regions during low-load operations, and hyperdeactivate DMN functions at higher load, perhaps reflecting heightened non-specific vigilance or effort when dealing with cognitive challenges. This speaks against an inability to down-regulate task-independent thought processes as a primary mechanism underlying cognitive impairment in schizophrenia.