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Fronto-limbic dysconnectivity leads to impaired brain network controllability in young people with bipolar disorder and those at high genetic risk.

ABSTRACT: Recent investigations have used diffusion-weighted imaging to reveal disturbances in the neurocircuitry that underlie cognitive-emotional control in bipolar disorder (BD) and in unaffected siblings or children at high genetic risk (HR). It has been difficult to quantify the mechanism by which 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 extends structural connectivity data to estimate 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 individuals (n?=?84, mean age 22.4), patients with BD (n?=?38, mean age 23.9), and age- and gender-matched controls (n?=?96, mean age 22.6) 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, left middle occipital, left superior frontal, right inferior frontal, and right 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.

SUBMITTER: Jeganathan J

PROVIDER: S-EPMC6051310 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Fronto-limbic dysconnectivity leads to impaired brain network controllability in young people with bipolar disorder and those at high genetic risk.

Jeganathan Jayson J Perry Alistair A Bassett Danielle S DS Roberts Gloria G Mitchell Philip B PB Breakspear Michael M

NeuroImage. Clinical 20180327

Recent investigations have used diffusion-weighted imaging to reveal disturbances in the neurocircuitry that underlie cognitive-emotional control in bipolar disorder (BD) and in unaffected siblings or children at high genetic risk (HR). It has been difficult to quantify the mechanism by which 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 extends stru ...[more]

PMID: 30035004

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Project description:Exposure to early life stress (ELS) is associated with a variety of detrimental psychological and neurodevelopmental effects. Importantly, ELS has been associated with regional alterations and aberrant connectivity in the structure and functioning of brain regions involved in emotion processing and self-regulation, creating vulnerability to mental health problems. However, longitudinal research regarding the impact of ELS on functional connectivity between brain regions in the default mode network (DMN) and fronto-limbic network (FLN), both implicated in emotion-related processes, is relatively scarce. Neuroimaging research on ELS has mostly focused on single nodes or bi-nodal connectivity instead of functional networks. We examined how ELS is associated with connectivity patterns within the DMN and FLN during rest in early adulthood. The participants (n = 86; 47 females) in the current functional magnetic resonance imaging (fMRI) study were young adults (18-21 years old) whose families had participated in a longitudinal study since pregnancy. ELS was assessed both prospectively (parental reports of family relationship problems and mental health problems during pregnancy and infancy) and retrospectively (self-reported adverse childhood experiences). Inter-subject representational similarity analysis (IS-RSA) and multivariate distance matrix regression (MDMR) were used to analyze the association between ELS and the chosen networks. The IS-RSA results suggested that prospective ELS was associated with complex alterations within the DMN, and that retrospective ELS was associated with alterations in the FLN. MDMR results, in turn, suggested that that retrospective ELS was associated with DMN connectivity. Mean connectivity of the DMN was also associated with retrospective ELS. Analyses further showed that ELS-related alterations in the FLN were associated with increased connectivity between the prefrontal and limbic regions, and between different prefrontal regions. These results suggest that exposure to ELS in infancy might have long-lasting influences on functional brain connectivity that persist until early adulthood. Our results also speak for the importance of differentiating prospective and retrospective assessment methods to understand the specific neurodevelopmental effects of ELS.

Project description:ObjectivesAdults with bipolar disorder (BD) display aberrant activation in fronto-limbic neural circuitry during cognitive control. However, fronto-limbic response to cognitive control, and factors destabilizing this circuitry, remain under-studied during the transition from adolescence to young adulthood in BD. Sleep patterns are disturbed in BD, undergo change in adolescence, and support brain function. Among transitional age youth, BD diagnosis and sleep (duration and variability) were tested as predictors of fronto-limbic response to a stressful cognitive control task.MethodsTwo groups of youth (13-22 years old) participated: 15 with BD type I, II or not otherwise specified (NOS) [BD; age 18.1 ± 2.7 years (mean ± standard deviation, SD); 17 female] and 25 healthy controls [CTL; age 19.4 ± 2.7 years (mean ± SD); 17 female]. Sleep was monitored with actigraphy for at least 1 week prior to an adaptive multi-source interference functional magnetic resonance imaging (fMRI) paradigm (a Stroop-like cognitive interference task). Group status and sleep duration (average and intra-individual variability) were examined as predictors of activation in response to incongruent>congruent trials within the bilateral amygdala, anterior cingulate (ACC), ventrolateral prefrontal and dorsolateral prefrontal cortical regions of interest.ResultsThe BD group displayed greater right amygdala activation than the CTL group. Average sleep duration and rostroventral ACC (rvACC) activity were negatively associated in the CTL group, but exhibited a quadratic relationship in the BD group such that short and long sleep were related to greater rvACC activation. Sleep duration variability and dorsal ACC activity were negatively associated in the BD group, and unrelated in the CTL group. Findings remained significant after controlling for age, sex, and mood symptoms.ConclusionsSubjects with BD displayed a hyper-limbic response during cognitive control, and sleep was a source of variability in ACC engagement. Stabilizing sleep may be one avenue for improving cognitive control in BD.

Dataset Information

Fronto-limbic dysconnectivity leads to impaired brain network controllability in young people with bipolar disorder and those at high genetic risk.

Publications

Fronto-limbic dysconnectivity leads to impaired brain network controllability in young people with bipolar disorder and those at high genetic risk.

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