Altered Effective Connectivity within an Oculomotor Control Network in Unaffected Relatives of Individuals with Schizophrenia

Abstract

The ability to rapidly stop or change a planned action is a critical cognitive process that is impaired in schizophrenia. The current study aimed to examine whether this impairment reflects familial vulnerability to schizophrenia across two experiments comparing unaffected first-degree relatives to healthy controls. First, we examined performance on a saccadic stop-signal task that required rapid inhibition of an eye movement. Then, in a different sample, we investigated behavioral and neural responses (using fMRI) during a stop-signal task variant that required rapid modification of a prepared eye movement. Here, we examined differences between relatives and healthy controls in terms of activation and effective connectivity within an oculomotor control network during task performance. Like individuals with schizophrenia, the unaffected relatives showed behavioral evidence for more inefficient inhibitory processes. Unlike previous findings in individuals with schizophrenia, however, the relatives showed evidence for a compensatory waiting strategy. Behavioral differences were accompanied by more activation among the relatives in task-relevant regions across conditions and group differences in effective connectivity across the task that were modulated differently by the instruction to exert control over a planned saccade. Effective connectivity parameters were related to behavioral measures of inhibition efficiency. The results suggest that individuals at familial risk for schizophrenia were engaging an oculomotor control network differently than controls and in a way that compromises inhibition efficiency.

Beyond Reactive Inhibition: Unpacking the Multifaceted Nature of Motor Inhibition

“…They interpreted this evidence as suggesting that the ventral striatum enhances visual attention when participants are uncertain whether the subsequent trial will be a go-or a no-go trial, thus providing a plausible example of how proactive mechanisms could operate. Lehet et al [23] completed an elegant study comparing inhibitory control proficiency of the saccadic oculomotor system in unaffected first-degree relatives of schizophrenic individuals with that of healthy people to understand familial vulnerability to schizophrenia. At the behavioral level, the unaffected relatives showed impaired reactive inhibition with respect to controls like schizophrenics.…”