Little is known about the relationship of white matter (WM) fasciculi abnormalities with pathologies of pediatric bipolar disorder (PBD). The aim of the present study was to investigate the abnormalities of WM integrity, characterized by free water elimination (FWE) corrected and superficial WM (SWM) diffusion tensor imaging (DTI) metrics in patients with PBD, and in particular, stratifying groups by psychotic symptoms. DTI data for 27 PBD patients with psychotic symptoms (P-PBD), 25 PBD patients without psychotic symptoms (NP-PBD), and 19 healthy controls (HCs) were examined. The commonly used DTI metrics (FA: fractional anisotropy, MD: mean diffusivity, RD: radial diffusivity, and AD: axial diffusivity), derived using a classical DTI model, a FWE model, and a SWM model, respectively, were computed. The differences in DTI metrics were explored among three groups using tract-based spatial statistics, as well as between-group differences, in regions of interest. In addition, support vector machine (SVM) analyses with leave-one-out cross-validation were applied to verify the capacity of altered WM indices in distinguishing these study groups. Analyses of covariance revealed significant FW-FA differences in three clusters located at the left parietal lobe, left occipital lobe, and right frontal lobe, as well as significant SWM-FA differences in four clusters located at the bilateral occipital lobe, left parietal lobe, and right frontal lobe. As compared with HCs, both groups of PBD patients showed decreased FW-FA and SWM-FA values in aforementioned regions, respectively. Notably, the P-PBD group further exhibited decreased FW-FA and SWM-FA values mainly distributed in the left middle occipital gyrus (MOG) containing fibers from the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and forceps major when compared to the NP-PBD group. Brain regions with altered FW-FA and SWM-FA could effectively discriminate PBD patients from HCs in each SVM analysis. The present study suggested that disrupted WM integrity in the frontal-parietal-occipital regions might be involved in the pathologies of PBD and further WM damage in the left MOG might contribute to the development of psychotic symptoms in PBD.

BACKGROUND:Pediatric bipolar disorder (PBD) with psychotic symptoms may predict more severe impairment in social functioning, but the underlying biological mechanisms remain unclear. The aim of this study was to investigate alterations in subcortical structural volume in PBD with and without psychotic symptoms. METHODS:We recruited 24 psychotic PBD (P-PBD) patients, 24 non-psychotic PBD (NP-PBD) patients, and 18 healthy controls (HCs). All participants underwent scanning with a 3.0 T Siemens Trio scanner. The FreeSurfer 7.4.0 software was employed to calculate the volume of each subcortical structure. An analysis of covariance (ANCOVA) was performed to identify brain regions with significant volume differences among the three groups, and then the inter-group comparisons were calculated. Partial correlation analyses were conducted to identify relationships between subcortical structural volumes and clinical features. Finally, receiver operating characteristic curve (ROC) analysis was employed to verify the capacity to distinguish between P-PBD and NP-PBD, P-PBD and HCs, and NP-PBD and HCs. RESULTS:ANCOVA revealed significant differences in the volumes of bilateral lateral ventricles, third ventricle, left thalamus, and right pallidum among three groups. Compared with HC, the third ventricle volume was increased in both groups of PBD patients, whereas the left thalamus and right pallidum volumes were decreased, and the bilateral lateral ventricles were enlarged in P-PBD patients. In contrast, only the third ventricle showed further enlargement in the group of P-PBD patients compared with NP-PBD patients. Partial correlation analyses revealed that episode times were associated with the third ventricle volume in P-PBD patients. Furthermore, ROC analyses indicated that volume in the left lateral ventricle exhibited the greatest capacity to distinguish between the P-PBD and NP-PBD, and the third ventricle performed best in distinguishing both the P-PBD group from HCs and the NP-PBD group from HCs. The combined metrics demonstrated greater diagnostic value in two-by-two comparisons. CONCLUSION:Current research suggests that PBD with psychotic symptoms may have more extensive lateral and third ventricular volume enlargement. Bilateral lateral ventricles may serve as potential neurobiomarkers to distinguish P- PBD patients from NP-PBD patients.

BackgroundThe thalamus plays a crucial role in sensory processing, emotional regulation, and cognitive functions, and its dysregulation may be implicated in psychosis. The aim of the present study was to examine the differences in thalamic subregional volumes between pediatric bipolar disorder patients with (P-PBD) and without psychotic symptoms (NP-PBD).MethodsParticipants including 28 P-PBD, 26 NP-PBD, and 18 healthy controls (HCs) underwent structural magnetic resonance imaging (sMRI) scanning using a 3.0T MRI scanner. All T1-weighted imaging data were processed by FreeSurfer 7.4.0 software. The volumetric differences of thalamic subregions among three groups were compared by using analyses of covariance (ANCOVA) and post-hoc analyses. Additionally, we applied a standard support vector classification (SVC) model for pairwise comparison among the three groups to identify brain regions with significant volumetric differences.ResultsThe ANCOVA revealed that significant volumetric differences were observed in the left pulvinar anterior (L_PuA) and left reuniens medial ventral (L_MV-re) thalamus among three groups. Post-hoc analysis revealed that patients with P-PBD exhibited decreased volumes in the L_PuA and L_MV-re when compared to the NP-PBD group and HCs, respectively. Furthermore, the SVC model revealed that the L_MV-re volume exhibited the best capacity to discriminate P-PBD from NP-PBD and HCs.ConclusionThe present findings demonstrated that reduced thalamic subregional volumes in the L_PuA and L_MV-re might be associated with psychotic symptoms in PBD.

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.

BackgroundBipolar disorder may begin as depression or mania, which can affect the treatment and prognosis. The physiological and pathological differences among pediatric bipolar disorder (PBD) patients with different onset symptoms are not clear. The aims of the present study were to investigate subcortical structural alterations in PBD patients with first-episode depressive (PBD-FED) and first-episode manic (PBD-FEM).MethodsA total of 59 individuals including 28 PBD-FED, 13 PBD-FEM, and 18 healthy controls (HCs) underwent high-resolution structural magnetic resonance scans. FreeSurfer 7.2 was used to detect changes in subcortical volumes. Simultaneously, thalamic, hippocampal, and amygdala subregion volumes were compared between the three groups.ResultsAnalysis of covariance controlling for age, sex, education, and estimated intracranial volume shows third and fourth ventricle enlargement in patients with PBD. Compared with the PBD-FED and HCs, the PBD-FEM group had reduced gray matter volume in the left thalamus, bilateral hippocampus, and right amygdala. Subsequent subregion analyses showed right cortico-amygdaloid transient, bilateral accessory-basal nucleus, left hippocampal tail, right hippocampal head, and body volume reduction in the PBD-FEM group.ConclusionsThe present findings provided evidence of decreased subcortical structure in PBD-FEM patients, which might present its trait feature.

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.

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.

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.

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.

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.

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.

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.

目的:研究儿童青少年双相障碍抑郁相(PBD-D)患者静息态脑功能的改变,并探讨脑功能改变与患者临床特征的相关性.方法:15例年龄10-18岁的PBD-D患者作为患者组,19例年龄、性别匹配的健康受试者作为健康对照组.对所有受试者采用3.0T西门子磁共振扫描仪采集静息态功能磁共振数据,计算局部脑区神经活动时空四维一致性指标(FOCA).结果:与健康对照相比,PBD-D患者扣带回、左侧额上回、左侧中央前回以及右侧中央后回的FOCA值显著降低;同时,双侧额下回、左侧额中回的FOCA值显著升高.PBD-D患者组左侧额上回的FOCA值与心境和感受问卷(MFQ)的得分呈显著的负相关.结论:PBD-D患者静息状态下存在大脑额-边缘网络的功能异常,并且左侧额上回的功能异常与抑郁发作的严重程度相关.

BackgroundBy 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.MethodsT1-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.ResultsBoth 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.ConclusionsAdolescent 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.

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.

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.

This chapter discusses the fundamentals of porous silicon (PSi) based DNA biosensors. Various surface functionalization approaches are introduced, including surface passivation techniques that can be used to prevent corrosion of the PSi matrix upon DNA hybridization. Several PSi DNA sensor configurations are presented, ranging from single-layer interferometers to on-chip ring resonators, with a focus on performance in terms of sensitivity and limit of detection. Challenges to real-world implementation of PSi DNA biosensors are addressed and important areas of progress in on-chip integration and incorporation of microfluidic channels are highlighted. The chapter ends with an outlook on future point-of-care diagnostic applications.

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.

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.

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.