Structural and functional disruption of subcortical limbic structures related with executive function in pediatric bipolar disorder.

BACKGROUND: Impaired cognition has been demonstrated in pediatric bipolar disorder (PBD). The subcortical limbic structures play a key role in PBD. However, alternations of anatomical and functional characteristics of subcortical limbic structures and their relationship with neurocognition of PBD remain unclear. METHODS: Thirty-six PBD type I (PBD-I) (15.36 ± 0.32 years old), twenty PBD type II (PBD-II) (14.80 ± 0.32 years old) and nineteen age-gender matched healthy controls (HCs) (14.16 ± 0.36 years old) were enlisted. Primarily, the volumes of the subcortical limbic structures were obtained and differences in the volumes were evaluated. Then, these structures served as seeds of regions of interest to calculate the voxel-wised functional connectivity (FC). After that, correlation analysis was completed between volumes and FC of brain regions showing significant differences and neuropsychological tests. RESULTS: Compared to HCs, both PBD-I and PBD-II patients showed a decrease in the Stroop color word test (SCWT) and digit span backward test scores. Compared with HCs, PBD-II patients exhibited a significantly increased volume of right septal nuclei, and PBD-I patients presented increased FC of right nucleus accumbens and bilateral pallidum, of right basal forebrain with right putamen and left pallidum. Both the significantly altered volumes and FC were negatively correlated with SCWT scores. SIGNIFICANCE: The study revealed the role of subcortical limbic structural and functional abnormalities on cognitive impairments in PBD patients. These may have far-reaching significance for the etiology of PBD and provide neuroimaging clues for the differential diagnosis of PBD subtypes. CONCLUSIONS: Distinctive features of neural structure and function in PBD subtypes may contribute to better comprehending the potential mechanisms of PBD.

A Multifunctional Additive Based on the Cation-Anion Synergistic Effect for Highly Stable Zinc Metal Anodes.

The Zn dendrite and hydrogen evolution reaction have been a "stubborn illness" for the life span of zinc anodes, which significantly hinders the development of aqueous zinc batteries (AZBs). Herein, considering the ingenious molecular structure, a multifunctional additive based on the synergistic regulation of cations and anions at the interface is designed to promote a dendrite-free and stable Zn anode. Theoretical calculations and characterization results verified that the electrostatic shield effect of the cation, the solvation sheath structure, and the bilayer structural solid electrolyte film (SEI) jointly account for the uniform Zn deposition and side reaction suppression. Ultimately, a remarkably high average Coulombic efficiency (CE) of 99.4% is achieved in the Zn||Cu cell for 300 cycles, and a steady charge/discharge cycling over 3000 and 300 h at 1.0 mA cm-2/1.0 mAh cm-2 and 10 mA cm-2/10 mAh cm-2 is obtained in the Zn||Zn cell. Furthermore, the assembled full battery demonstrates a prolonged cycle life of 2000 cycles.

Increased regional Hurst exponent reflects response inhibition related neural complexity alterations in pediatric bipolar disorder patients during an emotional Go-Nogo task.

Fractal patterns have been shown to change in resting- and task-state blood oxygen level-dependent signals in bipolar disorder patients. However, fractal characteristics of brain blood oxygen level-dependent signals when responding to external emotional stimuli in pediatric bipolar disorder remain unclear. Blood oxygen level-dependent signals of 20 PBD-I patients and 17 age- and sex-matched healthy controls were extracted while performing an emotional Go-Nogo task. Neural responses relevant to the task and Hurst exponent of the blood oxygen level-dependent signals were assessed. Correlations between clinical indices and Hurst exponent were estimated. Significantly increased activations were found in regions covering the frontal lobe, parietal lobe, temporal lobe, insula, and subcortical nuclei in PBD-I patients compared to healthy controls in contrast of emotional versus neutral distractors. PBD-I patients exhibited higher Hurst exponent in regions that involved in action control, such as superior frontal gyrus, inferior frontal gyrus, inferior temporal gyrus, and insula, with Hurst exponent of frontal orbital gyrus correlated with onset age. The present study exhibited overactivation, increased self-similarity and decreased complexity in cortical regions during emotional Go-Nogo task in patients relative to healthy controls, which provides evidence of an altered emotional modulation of cognitive control in pediatric bipolar disorder patients. Hurst exponent may be a fractal biomarker of neural activity in pediatric bipolar disorder.

Immediate visual reproduction negatively correlates with brain entropy of parahippocampal gyrus and inferior occipital gyrus in bipolar II disorder adolescents.

BACKGROUND: Brain entropy reveals complexity and irregularity of brain, and it has been proven to reflect brain complexity alteration in disease states. Previous studies found that bipolar disorder adolescents showed cognitive impairment. The relationship between complexity of brain neural activity and cognition of bipolar II disorder (BD-II) adolescents remains unclear. METHODS: Nineteen BD-II patients (14.63 ±1.57 years old) and seventeen age-gender matched healthy controls (HCs) (14.18 ± 1.51 years old) were enlisted. Entropy values of all voxels of the brain in resting-state functional MRI data were calculated and differences of them between BD-II and HC groups were evaluated. After that, correlation analyses were performed between entropy values of brain regions showing significant entropy differences and clinical indices in BD-II adolescents. RESULTS: Significant differences were found in scores of immediate visual reproduction subtest (VR-I, p = 0.003) and Stroop color-word test (SCWT-1, p = 0.015; SCWT-2, p = 0.004; SCWT-3, p = 0.003) between the two groups. Compared with HCs, BD-II adolescents showed significant increased brain entropy in right parahippocampal gyrus and right inferior occipital gyrus. Besides, significant negative correlations between brain entropy values of right parahippocampal gyrus, right inferior occipital gyrus and immediate visual reproduction subtest scores were observed in BD-II adolescents. CONCLUSIONS: The findings of the present study suggested that the disrupted function of corticolimbic system is related with cognitive abnormality of BD-II adolescents. And from the perspective temporal dynamics of brain system, the current study, brain entropy may provide available evidences for understanding the underlying neural mechanism in BD-II adolescents.

The Different Impact of Depressive or Manic First-episode on Pediatric Bipolar Disorder Patients: Evidence From Resting-state fMRI.

Bipolar disorder may begin as depression or mania, which can affect the treatment and prognosis of bipolar disorder. However, the physiological and pathological differences of pediatric bipolar disorder (PBD) patients with different onset symptoms are not clear. The purpose of this study was to investigate the differences of clinical, cognitive function and intrinsic brain networks in PBD patients with first-episode depression and first-episode mania. A total of 63 participants, including 43 patients and 20 healthy controls, underwent resting-state fMRI scans. PBD patients were classified as first-episode depressive and first-episode manic based on their first-episode symptoms. Cognitive tests were used to measure attention and memory of all participants. Independent component analysis (ICA) was used to extract the salience network (SN), default-mode network (DMN), central executive network (ECN) and limbic network (LN) for each participant. Spearman rank correlation analysis was performed between abnormal activation and clinical and cognitive measures. The results showed that there were differences in cognitive functions such as attention and visual memory between first-episode depression and mania, as well as differences activation in anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), precuneus, inferior parietal cortex and parahippocampus. And significant associations of brain activity with clinical assessments or cognition were found in different patients. In conclusion, we found differential impairments in cognitive and brain network activation in first-episode depressive and first-episode manic PBD patients, and correlations were found between these impairments. These evidences may shed light on the different developmental paths of bipolar disorder.

The disruption of functional connectome gradient revealing networks imbalance in pediatric bipolar disorder.

OBJECTIVE: Pediatric bipolar disorder (PBD) is a psychiatric disorder marked by alteration of brain networks. However, the understanding of these alterations in topological organization still unclear. This study aims to leverage the functional connectome gradient to examine changes in functional network hierarchy in PBD. METHOD: Connectome gradients were used to scrutinize the differences between functional gradient map in PBD patients (n = 68, aged 11 to 18) and healthy controls (HC, n = 37, aged 11 to 18). The association between regional altered gradient scores and clinical factors was examined. We further used Neurosynth to determine the correlation of the cognitive terms with the PBD principal gradient changes. RESULTS: Global topographic alterations were exhibited in the connectome gradient in PBD patients, involving gradient variance, explanation ratio, gradient range, and gradient dispersion in the principal gradient. Regionally, PBD patients revealed that the default mode network (DMN) held the most majority of the brain areas with higher gradient scores, whereas a higher proportion of brain regions with lower gradient scores in the sensorimotor network (SMN). These regional gradient differences exhibited significant correlation with clinical features and meta-analysis terms including cognitive behavior and sensory processing. CONCLUSION: Functional connectome gradient presents a thorough investigation of large-scale networks hierarchy in PBD patients. This exhibited excessive segregation between DMN and SMN supports the theory of imbalance in top-down control and bottom-up in PBD and provides a possible biomarker for diagnostic assessment.

Cortical thickness alterations are associated with astrocytes and excitatory neuron-specific transcriptome signatures in pediatric bipolar disorder.

Bipolar disorder (BD) is a heritable psychiatric disorder with a complex etiology that is often associated with cortical alterations. Morphometric studies in adults with BD are well established; however, few have examined cortical changes in pediatric BD (PBD). Additionally, the correlation between cortical thickness (CT) changes in PBD and gene expression remains elusive. Here, we performed an integrative analysis using neuroimaging data from 58 PBD individuals and the Allen human brain transcriptomic dataset. We applied partial least squares (PLS) regression analysis on structural MRI data and cortical gene expression, enrichment and specific cell type analysis to investigate the genetic correlates of CT alterations in PBD. We found the expression levels of PBD-related genes showed significant spatial correlations with CT differences. Further enrichment and specific cell type analysis revealed that transcriptome signatures associated with cortical thinning were enriched in synaptic signaling, ion channels, astrocytes, and excitatory neurons. Neurodevelopmental patterns of these genes showed significantly increased expression in the cerebellum, cortex, and subcortical regions during the adolescence period. These results highlight neurodevelopmental transcriptional changes could account for most of the observed correlations with CT differences in PBD, which offers a novel perspective to understand biological conceptualization mechanisms for the genetic correlates of CT alterations.

Machine learning algorithm performance evaluation in structural magnetic resonance imaging-based classification of pediatric bipolar disorders type I patients.

The diagnosis based on clinical assessment of pediatric bipolar disorder (PBD) may sometimes lead to misdiagnosis in clinical practice. For the past several years, machine learning (ML) methods were introduced for the classification of bipolar disorder (BD), which were helpful in the diagnosis of BD. In this study, brain cortical thickness and subcortical volume of 33 PBD-I patients and 19 age-sex matched healthy controls (HCs) were extracted from the magnetic resonance imaging (MRI) data and set as features for classification. The dimensionality reduced feature subset, which was filtered by Lasso or f_classif, was sent to the six classifiers (logistic regression (LR), support vector machine (SVM), random forest classifier, naïve Bayes, k-nearest neighbor, and AdaBoost algorithm), and the classifiers were trained and tested. Among all the classifiers, the top two classifiers with the highest accuracy were LR (84.19%) and SVM (82.80%). Feature selection was performed in the six algorithms to obtain the most important variables including the right middle temporal gyrus and bilateral pallidum, which is consistent with structural and functional anomalous changes in these brain regions in PBD patients. These findings take the computer-aided diagnosis of BD a step forward.

Pallidal volume reduction and prefrontal-striatal-thalamic functional connectivity disruption in pediatric bipolar disorders.

BACKGROUND: As a crucial node of the corticolimbic model, the striatum has been demonstrated in modulating emotional cues in pediatric bipolar disorders (PBD), the striatal distinction in structure and function between PBD-I and PBD-II remains unclear. METHODS: MRI data of 36 patients in PBD-I, 22 patients in PBD-II and 19 age-gender matched healthy controls (HCs) were processed. Here, we investigated structural and functional alterations of 8 subregions of striatum (bilateral nucleus accumbens, caudate, putamen and globus pallidus) by analyzing MRI data. RESULTS: We found volume reduction of the right pallidum, the significant positive correlation between the number of episodes and the functional connectivity between left pallidum and right caudate in PBD-I patients, abrupted prefrontal-striatal-thalamic functional connectivity in PBD-I group and decreased functional connectivity in PBD-II relative to HCs and PBD-I. LIMITATIONS: Future studies should enroll more subjects and adopt a longitudinal perspective, which could help to discover striatum structural or functional alterations during subject-specific clinical progress in different states. CONCLUSIONS: Results of the present study confirmed that structural and functional abnormality of striatum may be helpful in identifying PBD clinical types as distinctive biomarkers. The interruptions of the prefrontal-striatal-thalamic circuits may provide advantageous evidence for expounding the role of striatum in bipolar disorders etiology. Thus, potential mechanisms of dysfunction striatum need to be formulated and reconceptualized with multimodal neuroimaging studies in future.

Cell-type-specific genes associated with cortical structural abnormalities in pediatric bipolar disorder.

Background: Pediatric bipolar disorder (PBD) has been proven to be related to abnormal brain structural connectivity, but how the abnormalities in PBD correlate with gene expression is debated. Objective: This study aims at identification of cell-type-specific gene modules based on cortical structural differences in PBD. Methods: Morphometric similarity networks (MSN) were computed as a marker of interareal cortical connectivity based on MRI data from 102 participants (59 patients and 43 controls). Partial least squares (PLS) regression was used to calculate MSN differences related to transcriptomic data in AHBA. The biological processes and cortical cell types associated with this gene expression profile were determined by gene enrichment tools. Results: MSN analysis results demonstrated differences of cortical structure between individuals diagnosed with PBD and healthy control participants. MSN differences were spatially correlated with the PBD-related weighted genes. The weighted genes were enriched for "trans-synaptic signaling" and "regulation of ion transport", and showed significant specific expression in excitatory and inhibitory neurons. Conclusions: This study identified the genes that contributed to structural network aberrations in PBD. It was found that transcriptional changes of excitatory and inhibitory neurons might be associated with abnormal brain structural connectivity in PBD.

Altered spatiotemporal consistency in pediatric bipolar disorder patients with and without psychotic symptoms.

OBJECTIVE: Psychotic symptoms are quite common in patients with pediatric bipolar disorder (PBD) and may affect the symptom severity and prognosis of PBD. However, the potential mechanisms are less well elucidated until now. Thus, the purpose of this study was to investigate the brain functional differences between PBD patients with and without psychotic symptoms. METHOD: A total of 71 individuals including: 27 psychotic PBD (P-PBD), 25 nonpsychotic PBD (NP-PBD), and 19 healthy controls were recruited in the present study. Each subject underwent 3.0 Tesla functional magnetic resonance imaging scan. Four-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was employed to detect the local brain activity changes. Analyses of variance (ANOVA) were used to reveal brain regions with significant differences among three groups groups of individuals, and inter-group comparisons were assessed using post hoc tests. RESULTS: The ANOVA obtained significant among-group FOCA differences in the left triangular inferior frontal gyrus, left supplementary motor area, left precentral gyrus, right postcentral gyrus, right superior occipital gyrus, and right superior frontal gyrus. Compared with the control group, the P-PBD group showed decreased FOCA in the left supplementary motor area and bilateral superior frontal gyrus and showed increased FOCA in the left triangular inferior frontal gyrus. In contrast, the NP-PBD group exhibited decreased FOCA in the right superior occipital gyrus and right postcentral gyrus and showed increased FOCA in the left orbital inferior frontal gyrus. Compared to the NP-PBD group, the P-PBD group showed decreased FOCA in the right superior frontal gyrus. CONCLUSION: The present findings demonstrated that the two groups of PBD patients exhibited segregated brain functional patterns, providing empirical evidence for the biological basis of different clinical outcomes between PBD patients with and without psychotic symptoms.

Increased resting-state brain entropy of parahippocampal gyrus and dorsolateral prefrontal cortex in manic and euthymic adolescent bipolar disorder.

BACKGROUND: Alterations of brain signal complexity may reflect brain functional abnormalities. In adolescent bipolar disorder (ABD) distribution of brain regions showing abnormal complexity in different mood states remains unclear. We aimed to analyze brain entropy (BEN) alteration of functional magnetic resonance imaging (fMRI) signal to observe spatial distribution of complexity in ABD patients, as well as the relationship between this variation and clinical variables. METHODS: Resting-state fMRI data were acquired from adolescents with bipolar disorder (BD) who were in manic (n = 19) and euthymic (n = 20) states, and from healthy controls (HCs, n = 17). The differences in BEN among the three groups, and their associations with clinical variables, were examined. RESULTS: Compared to HCs, manic and euthymic ABD patients showed increased BEN in right parahippocampal gyrus (PHG) and left dorsolateral prefrontal cortex (DLPFC). There was no significant difference of BEN between the manic and the euthymic ABD groups. In manic ABD patients, right PHG BEN exhibited significantly positive relationship with episode times. CONCLUSIONS: Increased BEN in right PHG and left DLPFC in ABD patients may cause dysfunction of corticolimbic circuitry which is important to emotional processing and cognitive control. The positive correlation between PHG BEN and episode times of manic ABD patients further expressed a close association between brain complexity and clinical symptoms. From the perspective of brain temporal dynamics, the present study complements previous findings that have reported corticolimbic dysfunction as an important contributor to the pathophysiology of BD. BEN may provide valuable evidences for understanding the underlying mechanism of ABD.

Shared and specific patterns of structural and functional thalamo-frontal disturbances in manic and euthymic pediatric bipolar disorder.

Bipolar disorder (BD) is clinically defined by alternating depressive and manic episodes with a separated period of euthymia. Thalamo-frontal loop plays vital role in psychotic symptoms, altered motor control and executive difficulties in BD. It remains unclear that structural and functional alterations of thalamo-frontal loop among the different mood states in BD, especially in pediatric BD(PBD).Twenty manic PBD (mPBD), 20 euthymic PBD (ePBD) and 19 healthy controls (HCs) were included in the study. By analyzing the T1 images and fMRI signals, thalamus volume and frontal grey matter cortical thickness were tested, and functional connectivity (FC) between bilateral thalamus and frontal cortex was calculated. Relationship between clinical indices and thalamo-frontal FC was also evaluated in mPBD and ePBD adolescents.Compared to HCs, the cortical thickness of left middle frontal gyrus (MFG), bilateral superior frontal gyrus (SFG) was significantly decreased in both mPBD and ePBD patients, and volume of left thalamus and cortical thickness of right MFG significantly decreased in mPBD patients. Compared to that of the HCs and ePBD subjects, thalamo-frontal hyperconnectivity with MFG was found in mPBD, and compared with that of HCs, thalamo-frontal hypoconnectivity with precentral gyrus/SFG was found in ePBD. In ePBD patients, episode times positively correlated with FC values between thalamus and precentral gyrus.The findings of the present study demonstrate detailed knowledge regarding shared and specific structural and functional disruption in thalamo-frontal loop in mPBD and ePBD subjects. Thalamo-frontal abnormalities reported in adult BD subjects were also observed in adolescent BD patients, and thalamo-frontal dysfunction may be a crucial treatment target in BD.

Functional Connectome Prediction of Anxiety Related to the COVID-19 Pandemic.

OBJECTIVE: Increased anxiety in response to the COVID-19 pandemic has been widely noted. The purpose of this study was to test whether the prepandemic functional connectome predicted individual anxiety induced by the pandemic. METHODS: Anxiety scores from healthy undergraduate students were collected during the severe and remission periods of the pandemic (first survey, February 22-28, 2020, N=589; second survey, April 24 to May 1, 2020, N=486). Brain imaging data and baseline (daily) anxiety ratings were acquired before the pandemic. The predictive performance of the functional connectome on individual anxiety was examined using machine learning and was validated in two external undergraduate student samples (N=149 and N=474). The clinical relevance of the findings was further explored by applying the connectome-based neuromarkers of pandemic-related anxiety to distinguish between individuals with specific mental disorders and matched healthy control subjects (generalized anxiety disorder, N=43; major depression, N=536; schizophrenia, N=72). RESULTS: Anxiety scores increased from the prepandemic baseline to the severe stage of the pandemic and remained high in the remission stage. The prepandemic functional connectome predicted pandemic-related anxiety and generalized to the external sample but showed poor performance for predicting daily anxiety. The connectome-based neuromarkers of pandemic-related anxiety further distinguished between participants with generalized anxiety and healthy control subjects but were not useful for diagnostic classification in major depression and schizophrenia. CONCLUSIONS: These findings demonstrate the feasibility of using the functional connectome to predict individual anxiety induced by major stressful events (e.g., the current global health crisis), which advances our understanding of the neurobiological basis of anxiety susceptibility and may have implications for developing targeted psychological and clinical interventions that promote the reduction of stress and anxiety.

Brain structural alterations in pediatric bipolar disorder patients with and without psychotic symptoms.

BACKGROUND: Bipolar disorder (BD) with psychotic symptoms is a specific phenotype that presents greater risk of relapse and worse outcomes than nonpsychotic BD, however, the underlying mechanisms remain unknown and are less revealed in youth. Thus, the aims of the present study were to investigate brain structural alterations in pediatric bipolar disorder (PBD) patients with and without psychotic symptoms, and specifically to evaluate the impact of psychotic features on gray matter volume (GMV) in PBD patients. METHOD: A total of 73 individuals were recruited into three groups, n = 28, psychotic PBD, P-PBD; n = 26, nonpsychotic PBD, NP-PBD; and n = 19, healthy controls, HC. All participants underwent high-resolution structural magnetic resonance scans. Voxel-based morphometry was used to investigate GMV alterations. Analyses of variance (ANOVA) were performed to obtain brain regions with significant differences among three groups and then post hoc tests were calculated for inter-group comparisons. RESULTS: The ANOVA revealed significant GMV differences among three groups in the bilateral amygdala-hippocampus-parahippocampal complex (AMY-HIS-ParaHIS complex), left superior temporal gyrus (STG), left inferior frontal gyrus (IFG), bilateral putamen (PUT), left precentral gyrus (PG), left supramarginal gyrus (SMG), and right inferior parietal lobule (IPL). Compared with HCs, P-PBD patients showed decreased GMV in the bilateral AMY-HIS-ParaHIS complex, left STG, left IFG, bilateral PUT, and left PG; while NP-PBD patients exhibited decreased GMV in the left IFG, left PG, left SMG, and right IPL. Furthermore, P-PBD patients showed increased GMV in the right IPL when comparing to NP-PBD patients. LIMITATION: The present findings require replication in larger samples and verification in medication free subjects. CONCLUSION: The present findings suggested that psychotic features in PBD were associated with extensive brain structural lesions mainly located in the prefrontal-limbic-striatum circuit, which might represent the pathological basis of more sever symptoms in patients with psychotic PBD.

Disruption of functional and structural networks in first-episode, drug-naïve adolescents with generalized anxiety disorder.

BACKGROUND: Individuals with generalized anxiety disorder (GAD) tend to worry exaggeratedly and uncontrollably about various daily routines. Previous studies have demonstrated that the GAD patients exhibited widespread alternations in both functional networks (FN) and structural networks (SN). However, the simultaneous alternations of the topological organization of FN, SN, as well as their couplings in GAD still remain unknown. METHODS: Using multimodal approach, we constructed FN from resting-state functional magnetic imaging (R-fMRI) data and SN from diffusion magnetic resonance imaging (dMRI) data of 32 adolescent GAD patients and 25 healthy controls (HC). Graph theory analysis was employed to investigate the topological properties of FN, SN, and FN-SN coupling. RESULTS: Compared to HC, the GAD patients showed disruptions in global (i.e., decreased clustering coefficient, global, and local efficiency) and subnetwork (i.e., reduced intermodular connections, rich club, and feeder connections) levels in FN. Abnormal global level properties (i.e., increased characteristic path length and reduced global efficiency) were also observed in SN. Altered FN-SN couplings in normalized characteristic path length and feeder connections were identified in the GAD patients. The identified network measures were correlated with anxiety severity in the GAD patients. LIMITATIONS: The sample size of the current study is small and the cross-sectional nature can not infer causal relationship. CONCLUSIONS: Our findings identified GAD-related topological alternations in both FN and SN, together with the couplings between FN and SN, providing us with a novel perspective for understanding the pathophysiological mechanisms of GAD.

Manic and euthymic states in pediatric bipolar disorder patients during an emotional Go/Nogo task: A functional magnetic resonance imaging study.

BACKGROUND: Neural abnormalities in emotional response inhibition still exist in the euthymic phase of bipolar disorder (BD). Few studies on comparisons of functional magnetic resonance imaging (fMRI) manifestations between different mood phases of pediatric bipolar disorder (PBD) have ever been published. The goal of this study was to explore the differences in neural activities between manic and euthymic PBD during emotional response inhibition. METHODS: Simultaneous imaging of neural activity was recorded during an emotional Go/Nogo paradigm and the effect of emotional response inhibition was analyzed. Neural activities were compared between the three groups. RESULTS: In the presence of emotional versus neutral distractors, both manic and euthymic PBD subjects similarly showed widespreadly increased activities in the cognitive and emotional regulation circuits compared with healthy individuals. Compared with euthymic PBD patients, those with manic PBD exhibited increased activities in the left superior frontal gyrus. Hyperactivity in the left superior frontal, left middle frontal and right inferior frontal gyrus in manic PBD was positively associated with false response errors. CONCLUSION: Increased activity in the left superior frontal gyrus may be characteristic of manic episodes in PBD patients, and such a disparity between manic and euthymic phrases may attribute to more severe emotional dysregulation.

Common and Specific Characteristics of Adolescent Bipolar Disorder Types I and II: A Combined Cortical Thickness and Structural Covariance Analysis.

BACKGROUND: By calculating cortical thickness (CT) and cortical structural covariance (SC), we aimed to investigate cortical morphology and cortical inter-regional correlation alterations in adolescent bipolar disorder type I (BD-I) and type II (BD-II) patients. METHODS: T1-weighted images from 36 BD-I and 22 BD-II patients and 19 healthy controls (HCs) were processed to estimate CT. CT values of the whole brain were compared among three groups. Cortical regions showing CT differences in groups were regarded as seeds for analyzing cortical SC differences between groups. The relationship between CT and clinical indices was further assessed. RESULTS: Both BD groups showed cortical thinning in several frontal and temporal areas vs. HCs, and CT showed no significant difference between two BD subtypes. Compared to HCs, both BD groups exhibited reduced SC connections between left superior frontal gyrus (SFG) and right postcentral gyrus (PCG), left superior temporal gyrus (STG) and right pars opercularis, and left STG and right PCG. Compared with HCs, decreased SC connections between left STG and right inferior parietal gyrus (IPG) and right pars opercularis and right STG were only observed in the BD-I group, and left PCG and left SFG only in the BD-II group. CT of right middle temporal gyrus was negatively correlated with number of episodes in BD-II patients. CONCLUSIONS: Adolescent BD-I and BD-II showed commonly decreased CT while presenting commonly and distinctly declined SC connections. This study provides a better understanding of cortical morphology and cortical inter-regional correlation alterations in BD and crucial insights into neuroanatomical mechanisms and pathophysiology of different BD subtypes.

Altered spatiotemporal consistency of corticolimbic circuitry in euthymic pediatric bipolar disorder.

Bipolar disorder (BD) is a life-threatening illness which clinically defined by an alternating pattern of depressive and manic episodes with a separated period of euthymia. It remains unknown about the consistency of temporal-spatial spontaneous brain activity in euthymic patients, especially in pediatric BD (PBD) patients.Resting-state fMRI signals of sixteen euthymic PBD patients and 16 healthy controls were processed and FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) and functional connectivity were calculated in the present study. Voxel-wised correlation between clinical and cognitive indices and FOCA in PBD was calculated.Compared with healthy subjects, euthymic PBD patients showed worse performance in tests of Stroop Color-Word Test, Digit Span Test and Trail Making Test. Euthymic PBD patients demonstrated increased FOCA in left inferior frontal gyrus, left anterior cingulate cortex and left superior frontal gyrus and decreased FOCA in right orbital frontal gyrus, bilateral precuneus, right superior occipital gyrus and bilateral superior parietal gyrus. Decreased functional connectivities were found between right orbital frontal gyrus and left amygdala, between left superior frontal gyrus and left putamen, and between left superior frontal gyrus and left insula. And increased functional connectivity was found between right superior occipital gyrus and right hippocampus. FOCA of parahippocampal gyrus was negatively correlated with the SCWT-B score in PBD patients.Abnormal spatiotemporal consistency of brain regions of corticolimbic circuitry is possible to contribute to an imbalance between emotional processing and cognitive control in euthymic PBD. The measurement of FOCA measure may provide important clues of understanding PBD.

Alterations of Cognition and Cerebral Ventricle Volume in Manic and Euthymic Pediatric Bipolar Disorder.

Introduction: It remains unknown whether volumetric alterations of ventricles are similar or not in pediatric bipolar disorder (PBD) among different mood states. The present study aims to estimate ventricular volumetric alteration of PBD patients in manic and euthymic status, as well as the relationship between this alteration and cognitive changes. Methods: T1 magnetic resonance images were obtained from 20 manic PBD patients, 21 euthymic PBD patients, and 19 healthy controls (HCs). Ventricular volumes were automatically obtained via FreeSurfer 6.0 software. Ventricular volumes and cognitive indices were compared among the three groups, and the relationship between ventricular volumes and cognitive/clinical indices was analyzed. Results: In contrast to HCs, manic and euthymic PBD patients exhibited decreased cognitive scores of the Stroop color-word test and the digit span subtest. Manic PBD subjects presented enlarged volumes in the bilateral ventricles, third ventricle, and whole ventricles, and euthymic PBD participants displayed increased volumes in the third ventricle, fourth ventricle, and whole ventricles. No significant differences in cognitive performance and ventricular volumes were found between PBD groups. No significant correlation was discovered between ventricular volumes and cognitive/clinical indices in both manic and euthymic PBD patients. Conclusions: No significant differences in cognitive performance and ventricle volume were observed between euthymic and manic PBD groups, which may imply that the alterations are not specific to mood state. It may indicate structural and functional damage of corresponding brain circuits in euthymic PBD patients similar with that of manic PBD, which may provide clues to the diagnosis and treatment of euthymic PBD.