TY - JOUR
T1 - Altered effective connectivity within an oculomotor control network in individuals with schizophrenia
AU - Lehet, Matthew
AU - Tso, Ivy F
AU - Neggers, Sebastiaan F W
AU - Thompson, Ilse A
AU - Yao, Beier
AU - Kahn, René S
AU - Thakkar, Katharine N
N1 - Funding Information:
This work was supported by the National Institutes of Health [Grant numbers: R01 MH112644 (K.N.T.), K23MH108823 (I.F.T.), R01MH122491 (I.F.T.)], a Netherlands Organization for Scientific Research Rubicon grant (K.N.T.), a short- stay fellowship from Utrecht University (K.N.T.), and a University of Utrecht Neuroscience and Cognition grant (S.F.W.N.). We would like the thank Dr. Viabhav Diwadkar for helpful discussions and Dr. Peter Zeidman for helpful advice regarding DCM analyses.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/7/14
Y1 - 2021/7/14
N2 - Rapid inhibition or modification of actions is a crucial cognitive ability, which is impaired in persons with schizophrenia (SZP). Primate neurophysiology studies have identified a network of brain regions that subserves control over gaze. Here, we examine effective connectivity within this oculomotor control network in SZP and healthy controls (HC). During fMRI, participants performed a stop-signal task variant in which they were instructed to saccade to a visual target (no-step trials) unless a second target appeared (redirect trials); on redirect trials, participants were instructed to inhibit the planned saccade and redirect to the new target. We compared functional responses on redirect trials to no-step trials and used dynamic causal modelling (DCM) to examine group differences in network effective connectivity. Behaviorally, SZP were less efficient at inhibiting, which was related to their employment status. Compared to HC, they showed a smaller difference in activity between redirect trials and no-step trials in frontal eye fields (FEF), supplementary eye fields (SEF), inferior frontal cortex (IFC), thalamus, and caudate. DCM analyses revealed widespread group differences in effective connectivity across the task, including different patterns of self-inhibition in many nodes in SZP. Group differences in how effective connectivity was modulated on redirect trials revealed differences between the FEF and SEF, between the SEF and IFC, between the superior colliculus and the thalamus, and self-inhibition within the FEF and caudate. These results provide insight into the neural mechanisms of inefficient inhibitory control in individuals with schizophrenia.
AB - Rapid inhibition or modification of actions is a crucial cognitive ability, which is impaired in persons with schizophrenia (SZP). Primate neurophysiology studies have identified a network of brain regions that subserves control over gaze. Here, we examine effective connectivity within this oculomotor control network in SZP and healthy controls (HC). During fMRI, participants performed a stop-signal task variant in which they were instructed to saccade to a visual target (no-step trials) unless a second target appeared (redirect trials); on redirect trials, participants were instructed to inhibit the planned saccade and redirect to the new target. We compared functional responses on redirect trials to no-step trials and used dynamic causal modelling (DCM) to examine group differences in network effective connectivity. Behaviorally, SZP were less efficient at inhibiting, which was related to their employment status. Compared to HC, they showed a smaller difference in activity between redirect trials and no-step trials in frontal eye fields (FEF), supplementary eye fields (SEF), inferior frontal cortex (IFC), thalamus, and caudate. DCM analyses revealed widespread group differences in effective connectivity across the task, including different patterns of self-inhibition in many nodes in SZP. Group differences in how effective connectivity was modulated on redirect trials revealed differences between the FEF and SEF, between the SEF and IFC, between the superior colliculus and the thalamus, and self-inhibition within the FEF and caudate. These results provide insight into the neural mechanisms of inefficient inhibitory control in individuals with schizophrenia.
KW - Dynamic causal modeling
KW - Effective connectivity
KW - Executive function
KW - Eye movements
KW - Response inhibition
KW - Schizophrenia
KW - Stop-signal task
UR - http://www.scopus.com/inward/record.url?scp=85110261318&partnerID=8YFLogxK
U2 - 10.1016/j.nicl.2021.102764
DO - 10.1016/j.nicl.2021.102764
M3 - Article
C2 - 34284336
SN - 2213-1582
VL - 31
SP - 1
EP - 16
JO - NeuroImage. Clinical
JF - NeuroImage. Clinical
M1 - 102764
ER -