Neural model of emotion regulation illustrating possible functional and structural abnormalities in neural systems implicated in voluntary and automatic subprocesses of emotion regulation in adult bipolar disorder. These abnormalities, which appear to be predominantly within the left-sided ventromedial prefrontal cortical regions implicated in automatic emotion regulation, may underlie the mood instability of adult bipolar disorder (BD). For example, functional neuroimaging studies have demonstrated greater subcortical limbic activity (including amygdala, ventral striatum and hippocampus) to emotional stimuli in adult BD relative to healthy individuals during mania,136,147 depression137 and when euthy-mic.139,140,161,162 Studies employing automatic attentional control paradigms show reduced activity predominantly in left-sided ventromedial PFC in BD relative to healthy adults.149,150 Studies employing automatic emotion regulation paradigms also show reduced activity predominantly within left-sided ventromedial prefrontal cortical regions implicated in automatic emotion regulation, both during remission and mania in BD relative to healthy adults.157,159 Structural neuroimaging findings show gray matter structural changes in left OFC, and abnormal integrity and number of white matter fibers connecting left OFC and subcortical limbic regions implicated in emotion processing, in adult BD.112,120,126,131–133 There are more inconsistent findings regarding the roles of lateral and dorsal prefrontal cortical regions implicated in voluntary emotion regulation in adult BD. For example, findings from studies employing voluntary attentional control paradigms per se demonstrate patterns of reduced,143,144 although also increased,145,152 activity in different bilateral lateral and dorsal prefrontal cortical regions in BD vs healthy adults, whereas findings from studies employing voluntary emotion regulation paradigms indicate greater activity in BD than healthy adults bilaterally in these lateral and dorsal prefrontal cortical regions, together with greater activity in bilateral ventromedial prefrontal cortical regions implicated in automatic emotion regulation.140,155 The latter may mediate the voluntary emotion regulatory roles of the previous lateral and dorsal prefrontal cortical regions during voluntary emotion regulation.14 DLPFC, dorsolateral prefrontal cortex; MdPFC, dorsomedial prefrontal cortex; ACG, anterior cingulate gyrus; VLPFC, ventrolateral prefrontal cortex; OFC, orbital frontal cortex; hipp/parahip, hippocampus-parahippocampus region.