Striatal dysfunction during failed motor inhibition in children at risk for bipolar disorder

Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892-2670, USA.
Progress in Neuro-Psychopharmacology and Biological Psychiatry (Impact Factor: 3.69). 03/2012; 38(2):127-33. DOI: 10.1016/j.pnpbp.2012.02.014
Source: PubMed


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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    • "The biases in affective information processing observed in BD have been linked with altered information processing speed and deficits in verbal memory and response inhibition (Schenkel et al. 2008; Passarotti et al. 2010; Singh et al. 2010; Jacobs et al. 2011; Deveney et al. 2012; Passarotti et al. 2013). In particular, previous studies in BD have consistently shown a robust effect of negative stimuli on cognitive processing (Pavuluri et al. 2008; Passarotti et al. 2011; Pavuluri et al. 2012). "
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    ABSTRACT: Background: Bipolar disorder (BD) is characterized by biased processing of emotional information. However, little research in this area has been conducted in youth with BD and at-risk individuals. The goal of this study was to determine whether children with BD displayed comparable or more severe manifestations of this bias relative to offspring of parents with BD. Materials and methods: The sample (n = 57 children and adolescents) included 18 individuals with BD (age: 13.63 ± 2.99; 8 females), 16 offspring of parents with BD (age: 11.83 ± 2.96; 9 females) and 23 healthy controls (HC) (age: 12.789 ± 3.087; 8 females). All participants performed the Affective Go/No-Go (AGN) and the Rapid Visual Processing (RVP) tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Results: Relative to HC, individuals with BD responded faster to correct trials and committed an elevated number of commission errors across all affective conditions of the AGN task. By contrast, BD offspring showed intact performance accuracy but quicker response times than HC. Post-hoc analyses revealed that this behavioral pattern was observed in BD offspring with mental health problems but not in healthy BD offspring. Overall, mean reaction times and total number of errors in the RVP task were comparable across groups. Conclusions: In line with previous findings, subjects with BD encountered difficulties in processing affective information. The tendency toward faster but accurate responses to affective stimuli observed in BD offspring may be a marker of attentional bias toward affective information and constitute a vulnerability marker for mood disorder.
    Full-text · Article · Oct 2015 · Journal of child and adolescent psychopharmacology
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    • "Interestingly, an adult study including medication-free BD patients (stratify groups by depression, euthymia, and mania episode) performing a negative facial emotion matching task showed greater activations in the putamen in all three BD groups when comparing to controls [52]. Of note, even in symptom-free youths at a familial risk for BD, this difference mentioned above has already occurred, which may indicate that brain functional changes in the putamen is a notably sensitive marker for early stage of BD [53]. Also functional abnormalities in the putamen may be considered as a clinic marker for early identification of PBD. "
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    ABSTRACT: Background Pediatric bipolar disorder (PBD) has attracted increasing attentions due to its high prevalence and great influence on social functions of children and adolescents. However, the pathophysiology underlying PBD remains unclear. In the present study, the resting-state functional magnetic resonance imaging (fMRI) was used to detect abnormalities of baseline brain functions in depressed PBD youth.Methods Seventeen youth with PBD-depression aged 10 - 18 years old and 18 age- and sex-matched normal controls were recruited in this study. The fMRI data under resting state were obtained on a Siemens 3.0 Tesla scanner and were analyzed using the regional homogeneity (ReHo) method. Correlations between the ReHo values of each survived area and the severity of depression symptoms in patients were further analyzed.ResultsAs compared with the control group, PBD-depression patients showed decreased ReHo in the medial frontal gyrus, bilateral middle frontal gyrus and middle temporal gyrus, and the right putamen. Significant negative correlations of the mood and feelings questionnaire scores with mean ReHo values in the medial frontal gyrus and the right middle frontal gyrus in PBD-depression patients were observed.Conclusion Our results suggest that extensive regions with altered baseline brain activities are existed in PBD-depression and these brain regions mainly locate in the fronto-limbic circuit and associated striatal structures. Moreover, the present findings also add to our understanding that there could be unique neuropathophysiological mechanisms underlying PBD-depression.
    Full-text · Article · Aug 2014 · BMC Psychiatry
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    • "Two studies investigated subjects at genetic risk for bipolar disorders (Deveney et al., 2012a; Roberts et al., 2013). Three studies were not included, as they used only ROI and not the whole brain analyses, i.e. (Gruber et al., 2004; Whalley et al., 2011) and (Deveney et al., 2012b) overlapping with (Leibenluft et al., 2007). "
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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.
    Full-text · Article · Sep 2013 · Journal of Psychiatric Research
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