A Pharmacological Functional Magnetic Resonance Imaging Study Probing the Interface of Cognitive and Emotional Brain Systems in Pediatric Bipolar Disorder

Mani N Pavuluri,Stephanie A Parnes,John A Sweeney,Jacklynn M Fitzgerald,Alessandra M Passarotti

doi:10.1089/cap.2009.0105

Abstract

This functional magnetic resonance imaging (fMRI) study investigated the effects of pharmacotherapy on brain function underlying affect dysregulation and cognitive function in pediatric bipolar disorder (PBD). Healthy controls (HC) (n=14; mean age =14.1 ± 2.4 years) and unmedicated PBD patients with manic or hypomanic episodes (n=17; mean age =14.3 ± 1.1 years) were matched on intelligence quotient (IQ) and demographic factors. The fMRI studies were performed at baseline and after 14 weeks, during which PBD patients were treated initially with second-generation antipsychotics (SGAs) followed by lamotrigine monotherapy. The pediatric affective color-matching task was used where subjects matched the color of a positive, negative, or neutral word with one of the two colored circles below in each of the trials. There were five blocks of each emotional word type, with 10 trials per block. Behavioral data showed that the PBD group was modestly slower and less accurate than the HC, regardless of condition or treatment status. The blood oxygen level-dependent (BOLD) signal activity was reduced with treatment in the PBD group relative to the HC group during the negative versus neutral condition in bilateral dorsolateral prefrontal cortex (DLPFC), right posterior cingulate gyrus, parahippocampal gyrus, and inferior parietal lobule, but increased in left ventromedial prefrontal cortex (VMPFC). Similarly, during the positive versus neutral condition, the PBD group, relative to HC, showed reduced activity in right DLPFC, precuneus, and inferior parietal lobule and increased activity in the right VMPFC. However, within the PBD group, there was treatment related decrease in VMPFC and DLPFC. Improvement on Young Mania Rating Scale (YMRS) score significantly correlated with the decreased activity in VMPFC within the patient group. Pharmacotherapy in PBD patients led to differential effort with persistently increased activity in the affective regions and decreased activity in the cognitive regions relative to HC, demonstrating altered mechanisms of affective and cognitive systems of brain function, regardless of symptom response.

Highlights

Pediatric bipolar disorder (PBD) is associated with significant affect dysregulation and cognitive dysfunction (Dickstein et al 2004; McClure et al 2005; Pavuluri et al 2006; Dickstein et al 2008; Pavuluri et al 2008)
Another study that examined the influence of emotional challenge on cognitive function, patients with PBD demonstrated decreased activity in right ventromedial prefrontal cortex (VMPFC), ventrolateral prefrontal cortex (VLPFC), and dorsolateral prefrontal cortex (DLPFC; Brodmann area (BA) 9; middle frontal gyrus) and increased activity in limbic regions when compared to healthy controls (HC) (Pavuluri et al 2008)
There are no published treatment studies that simultaneously probed both the affective and cognitive circuitry function in patients, relative to HC. Building on these earlier studies, the current study aimed to examine the effects of pharmacotherapy on both the affective and cognitive neural systems involved in emotion processing during the performance of a cognitive task in patients with PBD, relative to HC

Summary

Introduction

Pediatric bipolar disorder (PBD) is associated with significant affect dysregulation and cognitive dysfunction (Dickstein et al 2004; McClure et al 2005; Pavuluri et al 2006; Dickstein et al 2008; Pavuluri et al 2008). Another study that examined the influence of emotional challenge on cognitive function, patients with PBD demonstrated decreased activity in right VMPFC, VLPFC, and dorsolateral prefrontal cortex (DLPFC; BA 9; middle frontal gyrus) and increased activity in limbic regions when compared to HC (Pavuluri et al 2008). In this latter study, examining the cognitive and affective circuitry interface, euthymic PBD patients and HC performed the cognitive task of matching the color of emotional words with one of the two colored circles below.

Methods

Discussion

Conclusion