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The absence of differences in the deficits of neurocognitive profiles between acutely ill unmedicated patients and euthymic medicated patients suggests that these impairments are trait-like characteristics of pediatric bipolar disorder. The cognitive deficits found in individuals with pediatric bipolar disorder suggest significant involvement of frontal lobe systems supporting working memory and mesial temporal lobe systems supporting verbal memory, regardless of ADHD comorbidity.

Objective-To investigate microstructure of white matter fiber tracts in pediatric bipolar disorder (PBD) and attention deficit hyperactivity disorder (ADHD).Methods-A diffusion tensor imaging (DTI) study was conducted at 3 Tesla on age and IQ-matched children and adolescents with PBD (n=13), ADHD (n=13), and healthy controls (HC) (n=15). Three DTI parameters, fractional anisotropy (FA), apparent diffusion coefficient (ADC), and regional fiber coherence index (r-FCI), were examined in eight fiber tracts: Anterior corona radiata (ACR); anterior limb of the internal capsule (ALIC); superior region of the internal capsule (SRI); posterior limb of the internal capsule (PLIC); superior longitudinal fasciculus (SLF); inferior longitudinal fasciculus (ILF); cingulum (CG); splenium (SP).Results-Significantly lower FA was observed in ACR in both PBD and ADHD relative to HC. In addition, FA and r-FCI values were significantly lower in ADHD relative to PBD and HC in both the ALIC and the SRI. Further, ADC was significantly greater in ADHD relative to both the PBD and HC in ACR, ALIC, PLIC, SRI, CG, ILF, and SLF. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusions-Decreased FA in ACR implies an impaired fiber density or reduced myelination in both PBD and ADHD in this prefrontal tract. These abnormalities, together with the reduced fiber coherence, extended to cortico-bulbar tracts in ADHD. Increased ADC across multiple white matter tracts in ADHD indicates extensive cellular abnormalities with less diffusion restriction in ADHD relative to PBD. NIH Public Access

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The pathophysiology of pediatric bipolar disorder (PBD) impacts both affective and cognitive brain systems. Understanding disturbances in the neural circuits subserving these abilities is critical for characterizing developmental aberrations associated with the disorder and developing improved treatments. Our objective is to use functional neuroimaging with pediatric bipolar disorder patients employing a task that probes the functional integrity of attentional control and affect processing. Ten euthymic unmedicated pediatric bipolar patients and healthy controls matched for age, sex, race, socioeconomic status, and IQ were scanned using functional magnetic resonance imaging. In a pediatric color word matching paradigm, subjects were asked to match the color of a word with one of two colored circles below. Words had a positive, negative or neutral emotional valence, and were presented in 30-s blocks. In the negative affect condition, relative to the neutral condition, patients with bipolar disorder demonstrated greater activation of bilateral pregenual anterior cingulate cortex and left amygdala, and less activation in right rostral ventrolateral prefrontal cortex (PFC) and dorsolateral PFC at the junction of the middle frontal and inferior frontal gyri. In the positive affect condition, there was no reduced activation of PFC or increased amygdala activation. The pattern of reduced activation of ventrolateral PFC and greater amygdala activation in bipolar children in response to negative stimuli suggests both disinhibition of emotional reactivity in the limbic system and reduced function in PFC systems that regulate those responses. Higher cortical cognitive areas such as the dorsolateral PFC may also be adversely affected by exaggerated emotional responsivity to negative emotions. This pattern of functional alteration in affective and cognitive circuitry may contribute to the reduced capacity for affect regulation and behavioral self-control in pediatric bipolar disorder.

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Objective-This fMRI study examined how working memory circuits are affected by face emotion processing in pediatric bipolar disorder (PBD) and attention-deficit hyperactivity disorder (ADHD).Methods-Twenty-three patients with bipolar disorder, 14 patients with ADHD and 19 healthy controls (HC) (mean age = 13.36 ± 2.55) underwent an affective 2-back fMRI task with blocks of happy, angry and neutral faces.Results-For angry vs neutral faces PBD patients, relative to ADHD patients, exhibited increased activation in subgenual anterior cingulate cortex (ACC) and orbitofrontal cortex, and reduced activation in dorsolateral prefrontal cortex (DLPFC) and premotor cortex. Relative to HC the PBD group showed no increased activation and reduced activation at the junction of DLPFC and ventrolateral prefrontal cortex (VLPFC). Relative to HC the ADHD patients exhibited greater activation in DLPFC and reduced activation in ventral and medial PFC, pregenual ACC, striatum and temporo-parietal regions. For happy vs neutral faces, relative to ADHD the PBD group exhibited greater activation in bilateral caudate, and relative to HC it showed increased activation in DLPFC, striatal and parietal regions, and no reduced activation. The ADHD group, compared to HC, showed no reduced activation and increased activation in regions that were under-active for the angry face condition.Conclusions-Relative to the ADHD group the PBD group exhibited greater deployment of the emotion processing circuitry and reduced deployment of working memory circuitry. Commonalities across PBD and ADHD patients, relative to HC, entailed cortico-subcortical activity that is reduced under negative emotional challenge, and increased under positive emotional challenge.