Neural Correlates of Response Inhibition in Pediatric Bipolar Disorder

Pediatric Bipolar Disorders Program, Stanford University School of Medicine, Stanford, California 94305-5719, USA.
Journal of child and adolescent psychopharmacology (Impact Factor: 2.93). 02/2010; 20(1):15-24. DOI: 10.1089/cap.2009.0004
Source: PubMed


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[46] = 3.35, p = 0.002) and overall (85% vs. 94%, T[46] = 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[46] = 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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    • "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.
    Journal of child and adolescent psychopharmacology 10/2015; 25(9). DOI:10.1089/cap.2015.0076 · 2.93 Impact Factor
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    • "Regarding cognitive flexibility deficits observed in patients with PBD, an fMRI study found hypoactivation in the caudate among PBD subjects compared to HC youth (Adleman et al., 2011). With respect to response inhibition impairments among PBD youth, research has provided blurred results, either enhanced right DLPFC activation (Singh et al., 2010) or diminished activation in the left VLPFC and in the right anterior cingulate cortex (ACC) (Passarotti et al., 2010c). "
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    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 · 3.38 Impact Factor
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    • "BDII Mixture of mood states Yes Not an exclusion, but details not provided Not provided Yes, current AAO 19.6 (4.0) 8 [4e99] GNG Comparable Welander-Vatn et al., 2013 24 (14) 24 (11) 35.6 (11.3) 34.5 (9.4) BDI Mixture of mood states Yes Yes Not provided Yes, current AAO 23.8 (9.5) Median 6.5 GNG Slower response times and more errors in BD Wessa et al., 2007 17 (7) 17 (6) 44.9 (12.7) 44.9 (11.4) BDI, II Euthymic Yes Yes Not provided No current 21.9 (12.7) Not provided GNG Comparable T. Hajek et al. / Journal of Psychiatric Research 47 (2013) 1955e1966 2003b; Cerullo et al., 2009; Deveney et al., 2012a; Diler et al., 2013; Elliott et al., 2004; Fleck et al., 2011; Frangou, 2012; Hummer et al., 2013; Kaladjian et al., 2009b; Kronhaus et al., 2006; Lagopoulos and Malhi, 2007; Malhi et al., 2005; Mazzola- Pomietto et al., 2009; McIntosh et al., 2008b; Nelson et al., 2007; Passarotti et al., 2010a, 2010b; Pavuluri et al., 2010; Roberts et al., 2013; Roth et al., 2006; Singh et al., 2010; Strakowski et al., 2005, 2008; Townsend et al., 2012; Weathers et al., 2012; Welander-Vatn et al., 2009, 2013; Wessa 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.
    Journal of Psychiatric Research 09/2013; 47(12). DOI:10.1016/j.jpsychires.2013.08.015 · 3.96 Impact Factor
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