These studies provide measures of tonic functional connectivity, rather than of stimulus-related, phasic functional connectivity, in neural circuits of interest and can thereby identify context-independent functional abnormalities, which potentially represent core functional abnormalities in such circuits in a given disorder. The majority of these studies in bipolar disorder have employed a region-of-interest approach to examine functional connectivity among a priori regions of interest at rest, measuring, for example, correlations between time series of low-frequency fluctuations in activity among these regions. The main finding is abnormally decreased positive or negative (inverse) resting connectivity among frontal, temporal, and subcortical regions in adults with bipolar disorder (
113–
115), which suggests a decoupling of resting connectivity among these regions, although one study reported abnormally increased resting connectivity between the right amygdala and the right ventrolateral prefrontal cortex (
116). Studies focusing on larger-scale networks have reported, in adults with bipolar disorder in different mood states, diverse patterns of abnormally increased resting connectivity in paralimbic and fronto-temporal/paralimbic networks (
117), abnormally decreased connectivity in the medial prefrontal cortex (
118), and abnormal positive resting connectivity between the medial prefrontal cortex and the ventrolateral prefrontal cortex and between the medial prefrontal cortex and the insula, together with abnormal decoupling between the mediodorsal prefrontal cortex and the dorsolateral prefrontal cortex (
119). Other studies have reported reduced global connectivity with the mediodorsal prefrontal cortex and thalamo-cortical disconnectivity in euthymic adults with bipolar disorder with a history of psychosis compared with healthy adults (
115,
120). Recent studies have employed different techniques to examine the amplitude of low-frequency fluctuations and the homogeneity of time series within specific neural regions and have reported increased amplitude of low-frequency fluctuations in fronto-temporal-striatal regions, decreased amplitude of low-frequency fluctuations in left postcentral-parahippocampal regions (
121), and greater regional homogeneity in left fronto-parietal cortices (
122) in depressed adults with bipolar disorder (subtype unspecified) compared with healthy adults.
These studies indicate intrinsic, context-independent abnormalities in adults with bipolar disorder, both in functional connectivity between regions and in the amplitude and homogeneity of low-frequency fluctuations within neural regions, predominantly within fronto-temporal-striatal circuitry. The findings thereby provide some support for our conceptualization of bipolar disorder neural circuitry, but they are highly variable across studies. Furthermore, given the paucity of studies combining resting state with other neuroimaging modalities, it is difficult to determine how these findings relate to the functional and structural abnormalities in neural circuits relevant to bipolar disorder.