TY - JOUR T1 - Fronto-limbic dysconnectivity leads to impaired brain network controllability in young people with bipolar disorder and those at high genetic risk JF - bioRxiv DO - 10.1101/222216 SP - 222216 AU - Jeganathan, Jayson AU - Perry, Alistair AU - Bassett, Danielle S. AU - Roberts, Gloria AU - Mitchell, Philip B. AU - Breakspear, Michael Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/11/20/222216.abstract N2 - Recent investigations have used diffusion-weighted imaging to reveal disturbances in the neurocircuitry that underlies cognitive-emotional control in bipolar disorder (BD) and those at high genetic risk (HR). It has been difficult to quantify how structural changes disrupt the superimposed brain dynamics, leading to the emotional lability that is characteristic of BD. Average controllability is a concept from network control theory that estimates the manner in which local neuronal fluctuations spread from a node or subnetwork to alter the state of the rest of the brain. We used this theory to ask whether structural connectivity deficits previously observed in HR (n=84) individuals, patients with BD (n=38), and age- and- gender-matched controls (n=96) translate to differences in the ability of brain systems to be manipulated between states. Localized impairments in network controllability were seen in the left parahippocampal, middle occipital, superior frontal, and right inferior frontal and precentral gyri in BD and HR groups. Subjects with BD had distributed deficits in a subnetwork containing the left superior and inferior frontal gyri, postcentral gyrus, and insula (p=0.004). HR participants had controllability deficits in a right-lateralized subnetwork involving connections between the dorsomedial and ventrolateral prefrontal cortex, the superior temporal pole, putamen, and caudate nucleus (p=0.008). Between-group controllability differences were attenuated after removal of topological factors by network randomization. Some previously reported differences in network connectivity were not associated with controllability-differences, likely reflecting the contribution of more complex brain network properties. These analyses highlight the potential functional consequences of altered brain networks in BD, and may guide future clinical interventions.HighlightsControl theory estimates how neuronal fluctuations spread from local networks.We compare brain controllability in bipolar disorder and their high-risk relatives.These groups have impaired controllability in networks supporting cognitive and emotional control.Weaker connectivity as well as topological alterations contribute to these changes. ER -