A multi-modal investigation of the neurobiology of psychomotor alterations in mania and depression (1/2)

Psychomotor phenomena represent one of the most fundamental dimensions of human behavior and show core alterations in different psychiatric disorders, especially in bipolar disorder (BD), ranging from psychomotor inhibition (e.g., during inhibited depression) to psychomotor excitation (e.g., during mania as well as agitated depression). A dimensional investigation of psychomotor alterations, as recently developed in the Research Domain Criteria (RDoC) matrix, may represent a promising approach to obtain fundamental insights in the neurobiological basis of BD, which to date is still largely unknown. This approach could parse the clinical heterogeneity of BD, as characterized by different phases of illness with complex constellations of different symptoms, which may reflect in the heterogeneity and often inconsistency of the current findings on the neurobiology of this disorder.Following these considerations, the general aim of this project is to comprehensively characterize the neural basis of psychomotor alterations across the various phases of BD, by using a dimensional RDoC-like and multimodal approach. We will collect objective measures of psychomotor activity by using actigraphy, as well as measures of brain functioning, by using both resting-state functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), from a sample of patients affected by BD in each phase of illness (mania, depression, and euthymia), along with healthy controls. In particular, we will investigate: (1) the relationship between psychomotor alterations (as measured by actigraphy) and changes in intrinsic brain activity and its dynamics at a network level in the low-frequency ranges (as measured by resting-state fMRI); (2) the relationship between psychomotor alterations and changes in brain activity in the high-frequency ranges (as measured by EEG); and (3) the relationship between psychomotor changes and abnormal subcortical modulation of brain activity by neurotransmitter-related nuclei (as measured by fMRI).The results from this study will allow to build a pathophysiological model of the psychomotor phenomena in BD, linking changes in neurotransmitter signaling to functional reorganizations of intrinsic brain activity across the full spectrum of frequency ranges (from ultra-slow to gamma), and, finally, to psychopathological alterations at a behavioral level. This, in turn, may help to identify specific biomarkers in BD, critically needed to assist the diagnostic assessment and treatment monitoring. Finally, these scientific findings could provide us with rich information to serve as a basis to translate into new therapeutic applications. The individuation of different subgroup of patients characterized by specific and homogenous alterations at both behavioral and neural levels will help to implement new, individualized, and more effective therapies that have a neuroscientific basis (e.g., non-invasive brain stimulation therapies specifically targeting abnormal oscillation patterns in intrinsic brain activity).