An fMRI study of the interface between affective and cognitive neural circuitry in pediatric bipolar disorder

Abstract

The pathophysiology of pediatric bipolar disorder (PBD) impacts both affective and cognitive brain systems. Understanding disturbances in the neural circuits subserving these abilities is critical for characterizing developmental aberrations associated with the disorder and developing improved treatments. Our objective is to use functional neuroimaging with pediatric bipolar disorder patients employing a task that probes the functional integrity of attentional control and affect processing. Ten euthymic unmedicated pediatric bipolar patients and healthy controls matched for age, sex, race, socioeconomic status, and IQ were scanned using functional magnetic resonance imaging. In a pediatric color word matching paradigm, subjects were asked to match the color of a word with one of two colored circles below. Words had a positive, negative or neutral emotional valence, and were presented in 30-s blocks. In the negative affect condition, relative to the neutral condition, patients with bipolar disorder demonstrated greater activation of bilateral pregenual anterior cingulate cortex and left amygdala, and less activation in right rostral ventrolateral prefrontal cortex (PFC) and dorsolateral PFC at the junction of the middle frontal and inferior frontal gyri. In the positive affect condition, there was no reduced activation of PFC or increased amygdala activation. The pattern of reduced activation of ventrolateral PFC and greater amygdala activation in bipolar children in response to negative stimuli suggests both disinhibition of emotional reactivity in the limbic system and reduced function in PFC systems that regulate those responses. Higher cortical cognitive areas such as the dorsolateral PFC may also be adversely affected by exaggerated emotional responsivity to negative emotions. This pattern of functional alteration in affective and cognitive circuitry may contribute to the reduced capacity for affect regulation and behavioral self-control in pediatric bipolar disorder.

Interaction between cognition and emotion in developmental psychopathology: the role of linguistic stimuli

“…This favours the hypothesis that in paediatric BD there is both an enhanced reactivity in the limbic system and a reduced capacity of regulating this response by PFC when negative emotional stimuli are presented. The same pattern of activation was not found in paediatric BD for the positive words and it was not present for the healthy controls, neither in the positive condition nor in the negative condition (Pavuluri et al 2008).…”

The psychoses: Cluster 3 of the proposed meta-structure for DSM-V and ICD-11

“…Other studies using emotional stimuli have revealed a pattern of increased subcortical striatal and limbic activation alongside reduced prefrontal cortex activity in BD (see Green et al 2007). This pattern of activity is also evident in pediatric cases of BD (Dickstein et al 2007 ;Pavuluri et al 2008). In schizophrenia, there is a contrasting pattern of decreased limbic activation and hyperfrontality during emotion processing tasks (e.g.…”

Familial and disease specific abnormalities in the neural correlates of the Stroop Task in Bipolar Disorder

“…We have previously shown that in healthy individuals SCWT performance correlates positively with grey matter volume in the ACC and in the dorsal and ventral PFC; however these structure-function relationships are absent in BD patients (Haldane et al, 2008). Additionally, decreased activation in the VLPFC during the SCWT has been consistently reported in functional magnetic resonance imaging (fMRI) studies of adult (Blumberg et al, 2003;Gruber et al, 2004;Kronhaus et al, 2006;Lagopoulos and Malhi, 2007;Roth et al, 2006) as well as adolescent BD patients (Pavuluri et al, 2008). Therefore current evidence suggests that syndromal expression of BD is reliably associated with dysfunction within brain regions involved in inhibitory control (Aron et al, 2004;Nee et al, 2007;Rubia et al, 2001).…”