Shuixia Guo1, Wei Zhao1, Haojuan Tao2, Zhening Liu3, Lena Palaniyappan4. 1. College of Mathematics and Computer Science, Key Laboratory of High Performance Computing and Stochastic Information Processing (Ministry of Education of China), Hunan Normal University, Changsha, PR China. 2. Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha, PR China. 3. Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha, PR China. Electronic address: zningl@163.com. 4. Department of Psychiatry, University of Western Ontario, London, Canada; Robarts Research Institute, University of Western Ontario, London, Canada; Lawson Health Research Institute, London, Ontario, Canada; Prevention and Early Intervention Program for Psychoses (PEPP), London Health Sciences Centre, London, Ontario, Canada. Electronic address: lpalaniy@uwo.ca.
Abstract
BACKGROUND: The distributed connectivity among brain regions is in a constant state of flux, even when a subject is at rest. This instability (temporal variability), when optimal, may contribute to efficient cross-network communications. We investigate the role of this variability in the genetic diathesis and symptom expression of schizophrenia. METHODS: Resting state functional MRI data acquired from 116 subjects (28 patients with schizophrenia, 28 siblings and 60 matched healthy controls). Using a sliding-window dynamic connectivity approach, we quantified the variability of whole-brain connectivity (dynamic functional connectivity or dFC) of each of the 90 brain regions obtained using a parcellation scheme that covered all contiguous brain regions of the cerebral cortex. RESULTS: We noted a high degree of instability anchored on the precuneus in patients with schizophrenia compared to both healthy controls (t=3.60, p=0.0005) and unaffected siblings (t=3.61, p=0.001) indicating a role for dFC of precuneus in the clinical expression of schizophrenia. Compared to patients, siblings also showed an increase in medial orbitofrontal but reduced putaminal instability; these latter changes were not seen in patients when compared to controls, indicating a lack of specificity for diathesis or expression related effects. CONCLUSIONS: Instability in the intrinsic connectivity of precuneus, a functional core hub with a major role in task-free self-processing, is likely to be a core substrate of the clinical expression of schizophrenia.
BACKGROUND: The distributed connectivity among brain regions is in a constant state of flux, even when a subject is at rest. This instability (temporal variability), when optimal, may contribute to efficient cross-network communications. We investigate the role of this variability in the genetic diathesis and symptom expression of schizophrenia. METHODS: Resting state functional MRI data acquired from 116 subjects (28 patients with schizophrenia, 28 siblings and 60 matched healthy controls). Using a sliding-window dynamic connectivity approach, we quantified the variability of whole-brain connectivity (dynamic functional connectivity or dFC) of each of the 90 brain regions obtained using a parcellation scheme that covered all contiguous brain regions of the cerebral cortex. RESULTS: We noted a high degree of instability anchored on the precuneus in patients with schizophrenia compared to both healthy controls (t=3.60, p=0.0005) and unaffected siblings (t=3.61, p=0.001) indicating a role for dFC of precuneus in the clinical expression of schizophrenia. Compared to patients, siblings also showed an increase in medial orbitofrontal but reduced putaminal instability; these latter changes were not seen in patients when compared to controls, indicating a lack of specificity for diathesis or expression related effects. CONCLUSIONS: Instability in the intrinsic connectivity of precuneus, a functional core hub with a major role in task-free self-processing, is likely to be a core substrate of the clinical expression of schizophrenia.