A pharmacological functional magnetic resonance imaging study probing the interface of cognitive and emotional brain systems in pediatric bipolar disorder

Abstract

Objective: 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).

Method: 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.

Results: 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.

Conclusions: 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.

FIG. 1.

Trial design of pharmacotherapy. The treatment timeline over the 14 weeks of the study is shown. SGA = Second-generation antipsychotic; Lam = lamotrigine.

FIG. 2.

Pediatric Affective Color Matching Paradigm.

FIG. 3.

Lamotrigine treatment effects. (A) Differences in lamotrigine treatment over time within patients with pediatric bipolar disorder (PBD) (n = 17). The black areas at the top of the head indicate reduced activation for negative versus neutral condition at follow up relative to baseline. VMPFC = Ventromedial prefrontal cortex. (B) Graphic representation of the significant correlation, for the PBD group, between an index of improvement in the Young Mania Rating Scale (YMRS) scores (i.e., ratio between the difference of baseline and follow-up scores) and an index of the decrease in the left VMPFC activity with time. (*) Voxels showing a significant level of activation.

FIG. 4.

Group activation data for each time point and condition. PFC = Prefrontal cortex; DLPFC = dorsolateral prefrontal cortex; PBD = pediatric bipolar disorder; HC = healthy control; TLRC = Talairach coordinates for cluster peak activation. (*) Significant group differences for the cluster.