Striatal dysfunction during failed motor inhibition in children at risk for bipolar disorder
ABSTRACT A better understanding of the neural underpinnings of bipolar disorder (BD) can be obtained by examining brain activity in symptom-free individuals at risk for BD. This study examined the neural correlates of motor inhibition in a sample of symptom-free youths at familial risk for BD.
19 euthymic youths with BD, 13 asymptomatic youths with a first-degree relative with BD, and 21 healthy comparison children completed the stop signal task in a 3 T scanner.
Children at familial risk for BD exhibited increased putamen activation during unsuccessful inhibition that distinguished them from both healthy and BD children. Youths with BD exhibited reduced activation of the right nucleus accumbens during unsuccessful inhibition as compared to the other participant groups.
Striatal activation patterns differ between youths at risk for BD and healthy comparison children during a motor inhibition task.
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ABSTRACT: Impaired response inhibition underlies symptoms and altered functioning in patients with bipolar disorders (BD). The interpretation of fMRI studies requires an accurate estimation of neurocognitive performance, for which individual studies are typically underpowered. Thus, we performed the first combined meta-analysis of fMRI activations and neurocognitive performance in studies investigating response inhibition in BD. We used signed differential mapping to combine anatomical coordinates of activation and standardized differences between means to evaluate neurocognitive performance in 30 fMRI studies of response inhibition comparing controls (n = 667) and patients with BD (n = 635). Relative to controls, BD patients underactivated the right inferior frontal gyrus (rIFG) regardless of current mood state and behavioral performance. Unique to euthymia were cortical hyperactivations (left superior temporal, right middle frontal gyri) combined with subcortical hypoactivations (basal ganglia), whereas unique to mania were subcortical hyperactivations (bilateral basal ganglia), combined with cortical hypoactivations (right inferior and medial frontal gyri). The fMRI changes in euthymia were associated with normal cognitive performance, whereas manic patients committed more errors during response inhibition. The rIFG hypoactivations were congruent with a BD trait, which may underlie the impaired response inhibition in mania. Euthymic BD subjects may compensate for the rIFG hypoactivations by hyperactivations of adjacent cortical areas, yielding comparable performance in inhibitory functions and suggesting possibilities for neuromodulation treatment of these cognitive impairments. The reversal of the activation pattern between mania and euthymia has implications for monitoring of treatment response and identification of imminent relapse.Journal of Psychiatric Research 09/2013; 47(12). DOI:10.1016/j.jpsychires.2013.08.015 · 4.09 Impact Factor
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ABSTRACT: Background: Insight into the neural mechanisms underlying the shared and disparate features of schizophrenia (SZ) and bipolar disorder (BD) is limited. The amygdala and prefrontal cortex (PFC) appear to have crucial roles in SZ and BD, yet abnormalities appear to manifest differently in the 2 disorders. Methods: Eighteen participants with SZ, 18 participants with BD, and 18 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Resting-state functional connectivity (rsFC) between the PFC and the amygdala divided into 3 subregions (the laterobasal, centromedial, and superficial amygdala) was examined using probabilistic anatomic maps. For each participant, rsFC maps of the 3 amygdala subregions were computed and compared across the 3 groups. Results: Compared with the HC group, we found significant differences in rsFC between the amygdala and PFC in the SZ and BD groups. In direct comparison between the SZ and BD groups, distinct patterns of rsFC between the amygdala and PFC were observed, particularly in the superficial amygdala. RsFC between the amygdala and the dorsal lateral PFC was significantly decreased in the SZ group, whereas rsFC between the amygdyala and the ventral PFC was significantly decreased in the BD group. Conclusions: These results strongly suggest dorsal vs ventral PFC differentiation in amygdala-PFC neural system abnormalities between SZ and BD. These regional differences in SZ and BD may give rise to the differences in clinical characteristics observed in SZ and BD, and may implicate potential avenues for differentiating the 2 disorders during early stages of illness.Schizophrenia Bulletin 04/2013; 40(2). DOI:10.1093/schbul/sbt044 · 8.61 Impact Factor
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ABSTRACT: Objectives: Identifying early markers of brain function among those at high risk (HR) for pediatric bipolar disorder (PBD) could serve as a screening measure when children and ado-lescents present with subsyndromal clinical symptoms prior to the conversion to bipolar disorder. Studies on the offspring of patients with bipolar disorder who are genetically at HR have each been limited in establishing a biomarker, while an analytic review in summarizing the findings offers an improvised opportunity toward that goal. Methods: An activation likelihood estimation (ALE) meta-analysis of mixed cognitive and emotional activities using the GingerALE software from the BrainMap Project was com-pleted. The meta-analysis of all fMRI studies contained a total of 29 reports and included PBD, HR, and typically developing (TD) groups. Results:The HR group showed significantly greater activation relative to theTD group in the right DLPFC–insular–parietal–cerebellar regions. Similarly, the HR group exhibited greater activity in the right DLPFC and insula as well as the left cerebellum compared to patients with PBD. Patients with PBD, relative to TD, showed greater activation in regions of the right amygdala, parahippocampal gyrus, medial PFC, left ventral striatum, and cerebellum and lower activation in the right VLPFC and the DLPFC. Conclusion: The HR population showed increased activity, presumably indicating greater compensatory deployment, in relation to both the TD and the PBD, in the key cognition and emotion-processing regions, such as the DLPFC, insula, and parietal cortex. In con-trast, patients with PBD, relative to HR and TD, showed decreased activity, which could indicate a decreased effort in multiple PFC regions in addition to widespread subcortical abnormalities, which are suggestive of a more entrenched disease process.Frontiers in Psychiatry 03/2014; 5. DOI:10.3389/fpsyt.2014.00141