In this study, we will utilize data from 37 infants at high risk of bipolar (biological mother diagnosed with bipolar) which were longitudinally scanned using rsfMRI at 0, 1, and 2 years of age and 142 normal developing controls scanned at the same age intervals. By carrying out a longitudinal study combining advanced neuroimaging and detailed neurobehavioral assessments, the proposed study would be the first to unveil the potential abnormal functional network development associated with bipolar disorder during an unstudied period from neonates through age two. Specifically, we propose to achieve the following two aims.
Aim 1: Characterize the abnormal development of specific functional circuits associated with genetic risk of bipolar and its behavioral correlations during the first two years of life. Various bipolar-related functional circuits associated with emotion, especially those centered at the amygdala, orbitofrontal cortex, insula, temporopolar cortex, and anterior cingulate cortex, will be systematically studied. Moreover, given the reported relevance of motor and cognitive functions in BD, circuits centered at motor-sensory cortices and dorsal lateral prefrontal cortex will also be studied. The longitudinal growth trajectories of the local specialization and long-range integration of all circuits will be delineated and their relationship with different domains of behavior including gross and fine motor, receptive and expressive language, as well as visual spatial working memory will be quantified. We hypothesize: (1) BD-related functional circuits will show abnormal growth trends in infants with a genetically high risk of BD compared with normal controls; (2) functional circuit abnormalities will be significantly associated with corresponding behavioral measurements.
Aim 2: Characterize the abnormal development of whole brain organization properties associated with genetic risk of bipolar and its behavioral correlations during the first two years of life. Building on individual functional circuits, the whole brain operates as an integrated system. Recent developments in quantitatively characterizing the information processing properties of the whole brain system based on graph-theoretical analysis have greatly improved our understanding of normal brain functioning. More importantly, disruptions of such whole brain graph measures have been reported in different brain disorders, including BD. Therefore, we will characterize the potential abnormal development of graph properties associated with genetic risk of BD in this aim.
Overall, the proposed study represents the first step in trying to delineate the brain circuit abnormalities associated with genetic risk for bipolar disorder during infancy. Insights from this study will not only significantly improve our understanding of the developmental pathophysiology of bipolar disorder, but will also provide far-reaching benefits for early identification of risk factors and intervention.