Contrasting variability patterns in the default mode and sensorimotor networks balance in bipolar depression and mania

Abstract

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 ...

The Role of Intrinsic Brain Functional Connectivity in Vulnerability and Resilience to Bipolar Disorder

“…Reduction in the integrative role of the hippocampus and vmPFC likely leads to impairment in stimuli appraisal and in selecting contextually appropriate responses. Moreover, the reduction of the integrative role of the default-mode network, when considered together with the findings of the sensorimotor network dysconnectivity described above, supports the study by Martino and colleagues (2). They found that the balance between the default-mode and sensorimotor networks activity patterns was altered during acute episodes, favoring the default-mode network in depression and the sensorimotor network in mania.…”

“…Resting-state functional magnetic resonance (rs-fMRI) studies in BD have shown disease mechanisms influence intrinsic connectivity including that of the default-mode, sensorimotor and central executive networks (1–3). Imbalance between the functional connectivity of the sensorimotor and default-mode networks has been directly linked with the clinical expression of bipolar disorder, as illustrated in a recent study that found the sensorimotor and default-mode networks showing opposite variability patterns during depressive and manic episodes (2). …”

Opposing patterns of neuronal variability in the sensorimotor network mediate cyclothymic and depressive temperaments

“…Interestingly what we observe in HC is in line with results of our prior work on BD where we found a shift of the DMN/SMN fSD balance towards the SMN in mania and the opposite in depression (Martino et al, ). Psychomotricity in mania is usually described as increased, unstable, and influenced by external stimuli (as manifested in symptoms like hyperactivity and distractibility).…”

Mapping the brain correlates of borderline personality disorder: A functional neuroimaging meta-analysis of resting state studies

“…These regions are recruited during autobiographical memory, associative memory, semantic and conceptual knowledge, and spatial information that may be associated with altered "disturbed relatedness" factor as well as with the cognitive alterations of BPD (Ruocco, 2005). Altered engagement of the DMN has been reported not only in BPD (Wolf et al, 2011), but also in depression (Sambataro et al, 2014), bipolar disorders (Martino et al, 2016), and schizophrenia (Sambataro et al, 2010) that are disorders with clinical similarities with BPD.…”