State dependent cortico-amygdala circuit dysfunction in bipolar disorder

Brady, Roscoe O.; Masters, Grace A.; Mathew, Ian T.; Margolis, Allison; Cohen, Bruce M.; Öngür, Döst; Keshavan, Matcheri S.

doi:10.1016/j.jad.2016.04.052

Cited by 76 publications

(48 citation statements)

References 29 publications

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“…Notably, the euthymic state shows hypo-connectivity, while bipolar mania demonstrates connectivity comparable to a HC population. In our prior study, we observed a similar pattern of amygdala connectivity with the HC showing connectivity that was intermediate between bipolar mania and euthymia and we conjectured that the difference between HC and bipolar euthymia may represent a compensatory mechanism rather than a disease process(Brady et al, 2016). Does the dorsal frontal hypoconnectivity in the DMN in euthymia in our current study represent a primary disease process or compensatory state?…”

Section: Discussionmentioning

confidence: 63%

“…Rather, the presented results represent the most prominent and most likely to be reproduced differences between patient groups. As an example of this, our current approach did not identify the ACC-Amygdala disconnectivity in mania that we previously identified in a hypothesis driven examination of amygdala connectivity (Brady et al, 2016). Examining our imaging data after processing in the same method as that publication, we observe that connectivity between the ROIs that most closely correspond to the R amygdala (ROI 155) and the ACC (ROI 22) is different across groups at a p-FDR corrected value of .062 and therefore, while showing a trend consistent with past findings, did not meet the threshold for significance in the current analysis.…”

Section: Discussionmentioning

confidence: 75%

“…Bipolar subjects were recruited as in our previous studies (Brady et al, 2012; Brady et al, 2016; Ongur et al, 2008). Almost all (21/23) of the manic bipolar subjects were recruited from McLean Hospital inpatient units while hospitalized for a manic episode.…”

Section: Methodsmentioning

confidence: 99%

“…A growing body of scientific inquiry has examined changes in neural activity associated with specific cognitive tasks such as emotion and reward processing (reviewed in (Phillips and Swartz, 2014; Strakowski et al, 2012)). Drawing upon these findings from the primarily task-based fMRI literature, we recently examined the “resting state” (rsfMRI) functional connectivity of bipolar mania when compared to bipolar euthymia (Brady et al, 2016). That analysis examined functional connectivity to brain regions selected from a consensus model of the neurobiology of bipolar disorder (Strakowski et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Differential brain network activity across mood states in bipolar disorder

Brady

Tandon

Masters

et al. 2017

Journal of Affective Disorders

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105

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Background This study aimed to identify how the activity of large-scale brain networks differs between mood states in bipolar disorder. The authors measured spontaneous brain activity in subjects with bipolar disorder in mania and euthymia and compared these states to a healthy comparison population. Methods 23 subjects with bipolar disorder type I in a manic episode, 24 euthymic bipolar I subjects, and 23 matched healthy comparison (HC) subjects underwent resting state fMRI scans. Using an existing parcellation of the whole brain, we measured functional connectivity between brain regions and identified significant differences between groups. Results In unbiased whole-brain analyses, functional connectivity between parietal, occipital, and frontal nodes within the dorsal attention network (DAN) were significantly greater in mania than euthymia or HC subjects. In the default mode network (DMN), connectivity between dorsal frontal nodes and the rest of the DMN differentiated both mood state and diagnosis. Limitations The bipolar groups were separate cohorts rather than subjects imaged longitudinally across mood states. Conclusions Bipolar mood states are associated with highly significant alterations in connectivity in two large-scale brain networks. These same networks also differentiate bipolar mania and euthymia from a HC population. State related changes in DAN and DMN connectivity suggest a circuit based pathology underlying cognitive dysfunction as well as activity / reactivity in bipolar mania. Altered activities in neural networks may be biomarkers of bipolar disorder diagnosis and mood state that are accessible to neuromodulation are promising novel targets for scientific investigation and possible clinical intervention.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 75%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Differential brain network activity across mood states in bipolar disorder

Brady

Tandon

Masters

et al. 2017

Journal of Affective Disorders

Self Cite

105

View full text Add to dashboard Cite

show abstract

“…Despite the striking differences in cognition, emotion and behavior between the manic and euthymic states, our understanding of how neurophysiology differs between these mood states is more limited (reviewed in (Salvadore et al, 2010)). To better elucidate the physiology underlying differences in bipolar mood state, we recently utilized resting-state functional magnetic resonance imaging (rsfMRI) to compare differences in functional connectivity between bipolar mania and bipolar euthymia (Brady et al, 2016). In that study we compared two cohorts of subjects, one manic and the other euthymic, and examined whole-brain functional connectivity to several brain regions.…”

Section: Introductionmentioning

confidence: 99%

Bipolar mood state reflected in cortico-amygdala resting state connectivity: A cohort and longitudinal study

Brady

Margolis

Masters

et al. 2017

Journal of Affective Disorders

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Background Using resting-state functional magnetic resonance imaging (rsfMRI), we previously compared cohorts of bipolar I subjects in a manic state to those in a euthymic state to identify mood state-specific patterns of cortico-amygdala connectivity. Our results suggested that mania is reflected in the disruption of emotion regulation circuits. We sought to replicate this finding in a group of subjects with bipolar disorder imaged longitudinally across states of mania and euthymia Methods We divided our subjects into three groups: 26 subjects imaged in a manic state, 21 subjects imaged in a euthymic state, and 10 subjects imaged longitudinally across both mood states. We measured differences in amygdala connectivity between the mania and euthymia cohorts. We then used these regions of altered connectivity to examine connectivity in the longitudinal bipolar group using a within-subjects design. Results Our findings in the mania vs euthymia cohort comparison were replicated in the longitudinal analysis. Bipolar mania was differentiated from euthymia by decreased connectivity between the amygdala and pre-genual anterior cingulate cortex. Mania was also characterized by increased connectivity between amygdala and the supplemental motor area, a region normally anti-correlated to the amygdala in emotion regulation tasks. Limitations Stringent controls for movement effects limited the number of subjects in the longitudinal sample. Conclusions In this first report of rsfMRI conducted longitudinally across mood states, we find that previously observed between-group differences in amygdala connectivity are also found longitudinally within subjects. These results suggest resting state cortico-amygdala connectivity is a biomarker of mood state in bipolar disorder.

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Amygdala subnuclei volume in bipolar spectrum disorders: Insights from diffusion‐based subsegmentation and a high‐risk design

Damme

Alloy

Young

et al. 2020

Human Brain Mapping

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Amygdala abnormalities are widely documented in bipolar spectrum disorders (BSD). Amygdala volume typically is measured after BSD onset; thus, it is not known whether amygdala abnormalities predict BSD risk or relate to the disorder. Additionally, past literature often treated the amygdala as a homogeneous structure, and did not consider its distinct subnuclei and their differential connectivity to other brain regions. To address these issues, we used a behavioral high‐risk design and diffusion‐based subsegmentation to examine amygdala subnuclei among medication‐free individuals with, and at risk for, BSD. The behavioral high‐risk design ( N = 114) included low‐risk ( N = 37), high‐risk ( N = 47), and BSD groups ( N = 30). Diffusion‐based subsegmentation of the amygdala was conducted to determine whether amygdala volume differences related to particular subnuclei. Individuals with a BSD diagnosis showed greater whole, bilateral amygdala volume compared to Low‐Risk individuals. Examination of subnuclei revealed that the BSD group had larger volumes compared to the High‐Risk group in both the left medial and central subnuclei, and showed larger volume in the right lateral subnucleus compared to the Low‐Risk group. Within the BSD group, specific amygdala subnuclei volumes related to time since first episode onset and number of lifetime episodes. Taken together, whole amygdala volume analyses replicated past findings of enlargement in BSD, but did not detect abnormalities in the high‐risk group. Examination of subnuclei volumes detected differences in volume between the high‐risk and BSD groups that were missed in the whole amygdala volume. Results have implications for understanding amygdala abnormalities among individuals with, and at risk for, a BSD.

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State dependent cortico-amygdala circuit dysfunction in bipolar disorder

Cited by 76 publications

References 29 publications

Differential brain network activity across mood states in bipolar disorder

Differential brain network activity across mood states in bipolar disorder

Bipolar mood state reflected in cortico-amygdala resting state connectivity: A cohort and longitudinal study

Amygdala subnuclei volume in bipolar spectrum disorders: Insights from diffusion‐based subsegmentation and a high‐risk design

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