Altered effective connectivity within an oculomotor control network in individuals with schizophrenia

Lehet, Matthew; Tso, Ivy F.; Neggers, Sebastiaan F. W.; Thompson, Ilse A.; Yao, Beier; Kahn, René S.; Thakkar, Katharine N.

doi:10.1016/j.nicl.2021.102764

Cited by 2 publications

(9 citation statements)

References 134 publications

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“…Bayesian modeling would suggest that longer SSRTs and marginally longer TSRTs among relatives indicate a slower inhibitory process, a failure in initiating an inhibitory process in response to the cue, or both [ 149 ]. Although longer SSRTs/TSRTs in unaffected relatives mirror our findings in individuals with schizophrenia [ 67 , 68 , 69 ], they are inconsistent with previous studies that have not reported significantly longer SSRTs in unaffected relatives using a manual version of the stop-signal task [ 5 , 9 , 60 , 66 , 70 , 71 , 74 ]. Differences between these studies and the current results are potentially explained by response modality [ 150 ].…”

Section: Discussioncontrasting

confidence: 99%

“…Thus, the saccade version of the stop-signal tasks and their variants may provide a more sensitive measure of inhibition that is relevant for the schizophrenia phenotype. In contrast to our findings in individuals with schizophrenia who did not show RT differences relative to healthy controls [ 69 ], unaffected relatives took more time to initiate a response. While this may indicate impairments in saccade generation, this interpretation is not supported by previous literature that reports unimpaired reflexive saccade kinematics in unaffected relatives [ 151 ].…”

Section: Discussioncontrasting

confidence: 99%

“…The behavioral differences between unaffected siblings and healthy controls in experiment 2 were accompanied by the brain activation differences between groups. Consistent with our prior work [ 69 , 99 ], both healthy controls and unaffected siblings showed greater activation in redirect trials as compared to no-step trials in all regions of our oculomotor control network. Unaffected siblings showed more activation than healthy controls across conditions in most ROIs within our network: the SEF, rIFC, caudate, superior colliculus, and thalamus across conditions.…”

Section: Discussionsupporting

confidence: 90%

“…The DCM analyses showed that across groups, the selected oculomotor control network was reliably engaged during the task, which is consistent with a previous study in individuals with schizophrenia [ 69 ]. Furthermore, in HC, several of the mean effective connectivity parameters were related to TSRT, indicating their relevance for efficient control.…”

Section: Discussionsupporting

confidence: 89%

“…This approach to quantifying proactive inhibition has proved fruitful in a variety of clinical populations [ 51 , 52 , 53 , 54 , 55 , 56 ]. Reactive inhibition in the context of the stop-signal was widely studied among individuals with schizophrenia, with slowed SSRT extensively reported in both manual [ 5 , 19 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ] and saccadic [ 10 , 67 , 68 , 69 ] versions of the task; however, see [ 9 , 70 , 71 , 72 , 73 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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