Depressive and manic phases in bipolar disorder show opposite constellations of affective, cognitive, and psychomotor symptoms. At a neural level, these may be related to topographical disbalance between large-scale networks, such as the default mode network (DMN) and sensorimotor network (SMN). We investigated topographical patterns of variability in the resting-state signal-measured by fractional SD (fSD) of the BOLD signal-of the DMN and SMN (and other networks) in two frequency bands (Slow5 and Slow4) with their ratio and clinical correlations in depressed (n = 20), manic (n = 20), euthymic (n = 20) patients, and healthy controls (n = 40). After controlling for global signal changes, the topographical balance between the DMN and SMN, specifically in the lowest frequency band, as calculated by the Slow5 fSD DMN/SMN ratio, was significantly increased in depression, whereas the same ratio was significantly decreased in mania. Additionally, Slow5 variability was increased in the DMN and decreased in the SMN in depressed patients, whereas the opposite topographical pattern was observed in mania. Finally, the Slow5 fSD DMN/SMN ratio correlated positively with clinical scores of depressive symptoms and negatively with those of mania. Results were replicated in a smaller independent bipolar disorder sample. We demonstrated topographical abnormalities in frequency-specific resting-state variability in the balance between DMN and SMN with opposing patterns in depression and mania. The Slow5 DMN/SMN ratio was tilted toward the DMN in depression but was shifted toward the SMN in mania. The Slow5 fSD DMN/SMN pattern could constitute a state-biomarker in diagnosis and therapy. bipolar disorder | neuronal variability | default mode network | sensorimotor network B ipolar disorder (BD) type I is a debilitating psychiatric disease with recurrent episodes of depression and mania, characterized by opposite constellations of psychopathological symptoms (1, 2). Typically, depression is characterized by mood biased toward negative affect, cognitive symptoms with thought internally focused: that is, self-focused (which manifests in ruminations) and inhibited psychomotor behavior (which manifests in psychomotor retardation). In contrast, most commonly mania presents mood biased toward positive affect, cognitive symptoms with thought externally focused: that is, environment-focused (which manifests in flight of ideas/ distractibility) and excited psychomotor behavior (which manifests in psychomotor agitation) (1-7). The neural basis underlying such co-occurrence of psychopathological symptoms with opposing constellations in depressive and manic phases of BD, however, remains unclear.Affect, thought, and psychomotor functions can be related to distinct neural networks in the brain's resting state. One central network is the default-mode network (DMN), which was first defined as a group of brain areas consistently showing decrease from baseline state during task-related activity and is indicative of an organization within the brain's ...
