Neural correlates of response inhibition in pediatric bipolar disorder.
ABSTRACT Pediatric bipolar disorder is characterized by core deficits in mood and executive function and commonly co-occurs with attention-deficit/hyperactivity disorder (ADHD). We aimed to examine response inhibition in this population, as an element of executive function, which, if aberrant, may interfere with learning and information processing.
Children (9-18 years) with bipolar I or II disorder (BD, n = 26) and age, gender, and intelligence quotient (IQ) comparable healthy children (HC, n = 22) without any psychopathology were given a standardized Go/NoGo computerized task measuring response inhibition. A whole-brain functional magnetic resonance imaging (MRI) group analysis was performed using statistical parametric mapping software (SPM2) for comparing NoGo to Go epochs.
There were no statistically significant group differences between groups in age, gender, or ethnicity. The BD group had high rates of co-morbid disorders, including 81% with ADHD, 62% with oppositional defiant disorder (ODD), and 46% with anxiety disorders. This BD group had fewer correct responses on Go (84% vs. 96%, T = 3.35, p = 0.002) and overall (85% vs. 94%, T = 4.12, p = 0.0002) trials as compared to the HC group. However, there were no statistically significant group differences in response inhibition on NoGo trials (p = 0.11). In the NoGo-Go contrast, the BD group showed increased neural activation in the right dorsolateral prefrontal cortex (DLPFC) compared to HC (T = 4.21, p < 0.001).
During accurate NoGo but impaired Go trial performance, children with BD showed increased right DLPFC activation versus controls, suggesting increased recruitment of executive control regions for accurate response inhibition. Studies relating these results to mood regulation in pediatric BD are warranted.
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Article: Neural correlates of response inhibition in pediatric bipolar disorder.
SourceAvailable from: Álvaro Frías Ibáñez[Show abstract] [Hide abstract]
ABSTRACT: Background Pediatric bipolar disorder (PBD) has emerged as a field of research in which neuropsychological studies are continuously providing new empirical findings. Despite this, a comprehensive framework for neurocognitive impairments is still lacking, and most of the evidence remains unconnected. We addressed this question through a systematic review of neuropsychological research, with the aim of elucidating the main issues concerning this topic. Method A comprehensive search of databases (PubMed, PsycINFO) was performed. Published manuscripts between 1990 and January 2014 were identified. Overall, 124 studies fulfilled inclusion criteria. Methodological differences between studies required a descriptive review of findings. Results Evidence indicates that verbal/visual-spatial memory, processing speed, working memory, and social cognition are neurocognitive domains impaired in PBD youth. Furthermore, these deficits are greater among those who suffer acute affective symptoms, PBD type I, and/or attention deficit hyperactivity disorder (ADHD) comorbidity. In addition, several neurocognitive deficits imply certain changes in prefrontal cortex activity and are somewhat associated with psychosocial and academic disabilities. Strikingly, these deficits are consistently similar to those encountered in ADHD as well as severe mood dysregulation (SMD). Besides, some neurocognitive impairments appear before the onset of the illness and tend to maintain stable across adolescence. Finally, any therapy has not yet demonstrated to be effective on diminishing these neurocognitive impairments. Limitations More prolonged follow-up studies aimed at delineating the course of treatment and the response to it are warranted. Conclusions Despite noteworthy research on the neurocognitive profile of PBD, our knowledge is still lagging behind evidence from adult counterparts.Journal of Affective Disorders 09/2014; 166:297–306. DOI:10.1016/j.jad.2014.05.025 · 3.71 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
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ABSTRACT: Cognitive control deficits are commonly seen in Depression of Bipolar Disorder (BDd) and Unipolar Major Depressive Disorder (UDd). Because failure to differentiate BDd from UDd has significant clinical consequences we aimed to identify differential patterns of neural activity in BDd versus UDd underlying response inhibition and motor control in adolescents. Functional MRI was used to compare 12 BDd adolescents (mean age= 15.5±1.2) with age- and sex-matched ten UDd and ten healthy control (HC) adolescents during the performance of well-validated Go/NoGo task. NoGo response inhibition versus Go motor control blocks was used in whole-brain analysis and results were corrected for multiple comparisons. There were no significant behavioral or neuroimaging findings between adolescents with BDd and UDd. However, both groups relative to HC showed significantly higher left superior temporal and left caudate activity during the NoGo condition. Moreover, left anterior cingulate (ACC) activity relative to HC was significantly higher only in BDd - not UDd - adolescents during the NoGo condition, and left caudate activity was higher only in UDd - not BDd - adolescents during the Go condition. In addition, several neural regions including dorsolateral prefrontal (DLPFC) were positively correlated with increased reaction time in UDd - not BDd - adolescents. Despite some similarities, neural correlates of depression are different in BDd and UDd relative to HC, and greater recruitment of ACC resources during response inhibition can help distinguish BDd.Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Academie canadienne de psychiatrie de l'enfant et de l'adolescent 02/2014; 23(1):10-9.