Reduced Functional Connectivity of Prefrontal Regions and Amygdala Within Affect and Working Memory Networks in Pediatric Bipolar Disorder

This study examined whether adolescents with pediatric bipolar disorder (PBD) have abnormal regional functional connectivity in distributed brain networks during an affective working memory task. Adolescents with PBD (n=41) and healthy controls (HC; n=16) performed a two-back functional magnetic resonance imaging working memory task with blocks of either angry or neutral faces. Independent component analysis methodology identified two temporally independent and functionally connected brain networks that showed differential functional connectivity in PBD and HC. Within a network for "affect evaluation and regulation," PBD showed decreased functional connectivity relative to HC in regions involved in emotion processing such as the right amygdala, and in emotion regulation regions such as the right ventrolateral prefrontal cortex (VLPFC), while functional connectivity was increased in emotion evaluation regions such as the bilateral medial PFC. Furthermore, in an "Affective Working Memory Network," PBD exhibited greater connectivity relative to HC in left dorsolateral PFC (DLPFC), caudate, and right VLPFC; and simultaneously reduced connectivity in emotion processing regions, such as the right amygdala, bilateral temporal regions, and the junction of DLPFC/VLPFC, which interfaces affective and cognitive processes. Dysfunction in network engagement in PBD patients illustrates that they are expending greater effort in face emotion evaluation, while being less able to engage affect regulation regions.