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.

We process and integrate multiple timescales into one meaningful whole. Recent evidence suggests that the brain displays a complex multiscale temporal organization. Different regions exhibit different timescales as described by the concept of intrinsic neural timescales (INT); however, their function and neural mechanisms remains unclear. We review recent literature on INT and propose that they are key for input processing. Specifically, they are shared across different species, i.e., input sharing. This suggests a role of INT in encoding inputs through matching the inputs’ stochastics with the ongoing temporal statistics of the brain’s neural activity, i.e., input encoding. Following simulation and empirical data, we point out input integration versus segregation and input sampling as key temporal mechanisms of input processing. This deeply grounds the brain within its environmental and evolutionary context. It carries major implications in understanding mental features and psychiatric disorders, as well as going beyond the brain in integrating timescales into artificial intelligence.