Altered effective connectivity within an oculomotor control network in unaffected relatives of individuals with schizophrenia
Lehet, Matthew; Tso, Ivy F.; Park, Sohee; Neggers, Sebastiaan F.W.; Thompson, Ilse A.; Kahn, Rene S.; Thakkar, Katharine N.
(2021) Brain sciences, volume 11, issue 9
(Article)
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
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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.
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Keywords: Effective connectivity, Endophenotype, Response inhibition, Schizophrenia, General Neuroscience
ISSN: 2076-3425
Publisher: MDPI Multidisciplinary Digital Publishing Institute
Note: Funding Information: Thus, the SEF, FEF, rIFC, caudate, superior colliculus, and thalamus make up a putative saccadic control circuit, which is further supported by anatomical between-region connections. The FEF and SEF are reciprocally connected [105–107], with descending connections to the superior colliculus [108–110], striatum [105,107,111–113], and thalamus [105,107,113,114]. Connections from the striatum and the superior colliculus to cortical oculomotor regions (i.e., the FEF and SEF) pass through the thalamus [115–117] and are themselves reciprocally connected [84,118–120]. Finally, the IFC projects to the caudate [112], and is bidirectionally connected with the SEF [107,121] and thalamus [122], and may thus exert control over saccade plans. This network, which is supported by both physiology and anatomical connections, allows for proactive and reactive control over saccade generation. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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