The instability of functional connectivity in patients with schizophrenia and their siblings: A dynamic connectivity study

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