Brain network deficits in breast cancer patients after early neoadjuvant chemotherapy: A longitudinal MRI study.

Breast cancer (BC) patients who undergo chemotherapy are likely to develop chemotherapy-related cognitive impairment (CRCI). Recent studies of BC patients after chemotherapy have used graph theory to investigate the topological properties of the brain functional connectome. However, little is known about structural morphological networks in BC patients after early neoadjuvant chemotherapy (NAC). Brain morphological network organization in 47 female participants with BC was investigated before and after NAC. Topological properties of brain networks were ascertained based on morphological similarities in regional gray matter using a graph theory approach based on 3D T1-weighted MRI data. Nonparametric permutation testing was used to assess longitudinal-group differences in topological metrics. Compared with BC patients before NAC, BC patients after early NAC showed significantly increased global efficiency (p = .048), decreased path length (p = .033), and abnormal nodal properties and connectivity, mainly located in the central executive network (CEN). The change in the network efficiency of the right caudate was negatively correlated with the change in the Self-Rating Anxiety Scale score (r = -.435, p = .008), and the change in the nodal degree of the left superior frontal gyrus (dorsolateral part) was positively correlated with the change in the Functional Assessment of Cancer Therapy score (r = .547, p = .002). BC participants showed randomization in global properties and dysconnectivity in the CEN after early NAC. NAC may disrupt the cognitive balance of the brain morphological network in individuals with BC.

The impact of age-related hearing loss on structural neuroanatomy: A meta-analysis.

This meta-analysis investigated the association between age-related hearing loss and structural neuroanatomy, specifically changes to gray matter volume. Hearing loss is associated with increased risk of cognitive decline. Hence, understanding the effects of hearing loss in older age on brain health is essential. We reviewed studies which compared older participants with hearing loss (age-related hearing loss: ARHL) to older adults without clinical hearing loss (no-ARHL), on neuroanatomical outcomes, specifically gray matter (GM) volume as measured by magnetic resonance imaging. A total of five studies met the inclusion criteria, three of which were included in an analysis of whole-brain gray matter volume (ARHL group n = 113; no-ARHL group n = 138), and three were included in analyses of lobe-wise gray matter volume (ARHL group n = 139; no-ARHL group n = 162). Effect-size seed-based d mapping software was employed for whole-brain and lobe-wise analysis of gray matter volume. The analysis indicated there was no significant difference between adults with ARHL compared to those with no-ARHL in whole-brain gray matter volume. Due to lacking stereotactic coordinates, the level of gray matter in specific neuroanatomical locations could only be observed at lobe-level. These data indicate that adults with ARHL show increased gray matter atrophy in the temporal lobe only (not in occipital, parietal, or frontal), compared to adults with no-ARHL. The implications for theoretical frameworks of the hearing loss and cognitive decline relationship are discussed in relation to the results. This meta-analysis was pre-registered on PROSPERO (CRD42021265375). Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=265375, PROSPERO CRD42021265375.

Rapid quantification of global brain volumetry and relaxometry in patients with multiple sclerosis using synthetic magnetic resonance imaging.

Background: Early pathologic studies have reported that focal areas of gray lesions in the cortex and other gray matter (GM) regions are important in multiple sclerosis (MS) patients. Quantitative magnetic resonance imaging (qMRI) can provide more specific insight into the disease process, progression, and therapeutic response of MS. The purpose of this study was to quantitatively assess the changes of global GM volumetry and relaxometry information simultaneously in MS patients using synthetic MRI. Methods: All MS patients and healthy controls (HCs) were recruited. The Expanded Disability Status Scale (EDSS) scores were obtained from all patients to evaluate the disability progression. Volumetry and relaxometry of the global brain and regional GM were obtained. The quantitative parameters between MS patients and HCs were compared using an analysis of covariance (ANCOVA). The Pearson correlation assessed the correlations between the quantitative parameters and EDSS, illness duration, education in MS patients. Results: Thirty-five MS patients and fifty-two age-matched HCs were enrolled in this prospective case-control study. The global volumetry including white matter volume (WMV), myelin volume (MYV), and brain parenchymal volume (BPV) were all significantly lower in MS patients (WMV: 613.120±65.388 vs. 579.903±68.432 mL; MYV: 151.883±22.766 vs. 192.457±27.381 mL; BPV: 1,136.771±106.126 vs. 1,276.712±107.368 mL), as well as a higher cerebral spinal fluid volume (CSFV) (241.294±81.805 vs. 177.017±39.729 mL) in MS patients than those in HCs. Similarly, brain parenchymal fraction (BPF) and myelin fraction (MYF) were significantly lower in MS patients (BPF: 82.623±5.368 vs. 87.85±2.392 mL; MYF: 11.034±1.529 vs. 13.231±1.465 mL). For regional GM volumetry, multiple regions of MS patients were significantly smaller than those of HCs (P<0.01, corrected). For regional GM relaxometry, the T1, T2, and PD values of multiple regions showed significant differences. Conclusions: These findings suggest that MS patients had global and regional brain volumetry and relaxometry alterations, and the synthetic MRI-derived parameters may be potentially used as specific quantitative markers for the clinic to improve the understanding of MS.

Rich-Club Organization Disturbances of the Individual Morphological Network in Subjective Cognitive Decline.

Background: Subjective cognitive decline (SCD) was considered to be the preclinical stage of Alzheimer's disease (AD). However, less is known about the altered rich-club organizations of the morphological networks in individuals with SCD. Methods: This study included 53 individuals with SCD and 54 well-matched healthy controls (HC) from the Alzheimer's disease Neuroimaging Initiative (ADNI) database. Individual-level brain morphological networks were constructed by estimating the Jensen-Shannon distance-based similarity in the distribution of regional gray matter volume. Rich-club properties were then detected, followed by statistical comparison. Results: The characteristic rich-club organization of morphological networks (normalized rich-club coefficients > 1) was observed for both the SCD and HC groups under a range of thresholds. The SCD group showed a reduced normalized rich-club coefficient compared with the HC group. The SCD group exhibited the decreased strength and degree of rich-club connections than the HC group (strength: HC = 79.93, SCD = 74.37, p = 0.028; degree: HC = 85.28, SCD = 79.34, p = 0.027). Interestingly, the SCD group showed an increased strength of local connections than the HC group (strength: HC = 1982.16, SCD = 2003.38, p = 0.036). Conclusion: Rich-club organization disturbances of morphological networks in individuals with SCD reveal a distinct pattern between the rich-club and peripheral regions. This altered rich-club organization pattern provides novel insights into the underlying mechanism of SCD and could be used to investigate prevention strategies at the preclinical stage of AD.

Brain Volumetric Measurements in Children With Attention Deficit Hyperactivity Disorder: A Comparative Study Between Synthetic and Conventional Magnetic Resonance Imaging.

Objective: To investigate the profiles of brain volumetric measurements in children with attention deficit hyperactivity disorder (ADHD), and the consistency of these brain volumetric measurements derived from the synthetic and conventional T1 weighted MRI (SyMRI and cT1w MRI). Methods: Brain SyMRI and cT1w images were prospectively collected for 38 pediatric patients with ADHD and 38 healthy children (HC) with an age range of 6-14 years. The gray matter volume (GMV), white matter volume (WMV), cerebrospinal fluid (CSF), non-WM/GM/CSF (NoN), myelin, myelin fraction (MYF), brain parenchyma volume (BPV), and intracranial volume (ICV) were automatically estimated from SyMRI data, and the four matching measurements (GMV, WMV, BPV, ICV) were extracted from cT1w images. The group differences of brain volumetric measurements were performed, respectively, using analysis of covariance. Pearson correlation analysis and interclass correlation coefficient (ICC) were applied to evaluate the association between synthetic and cT1w MRI-derived measurements. Results: As for the brain volumetric measurements extracted from SyMRI, significantly decreased GMV, WMV, BPV, and increased NON volume (p < 0.05) were found in the ADHD group compared with HC; No group differences were found in ICV, CSF, myelin volume and MYF (p > 0.05). With regard to GMV, WMV, BPV, and ICV estimated from cT1w images, the group differences between ADHD and HC were consistent with the results estimated from SyMRI. And these four measurements showed noticeable correlation between the two approaches (r = 0.692, 0.643, 0.898, 0.789, respectively, p < 0.001; ICC values are 0.809, 0.782, 0.946, 0.873, respectively). Conclusion: Our study demonstrated a global brain development disability, but normal whole-brain myelination in children with ADHD. Moreover, our results demonstrated the high consistency of brain volumetric indices between synthetic and cT1w MRI in children, which indicates the high reliability of SyMRI in the child-brain volumetric analysis.

Ultra-high b value DWI in distinguishing fresh gray matter ischemic lesions from white matter ones: a comparative study with routine and high b value DWI.

BACKGROUND: Fresh ischemic lesions (FILs) can occur in both the brain's gray matter (GM) and white matter (WM), with each location signifying a different prognosis for patients. This study aims to investigate the application of ultra-high b value diffusion-weighted imaging (DWI) in distinguishing FILs in these two areas via a comparative study with routine and high b value DWI. METHODS: Multiple b value DWI (b=0, 500, 1,000, 2,000, 4,000, 6,000, 8,000, 10,000 s/mm2) was performed on 47 patients with suspected acute ischemic stroke (AIS). Apparent diffusion coefficient (ADC) maps, including ADC500, ADC1,000, ADC2,000, ADC4,000, ADC6,000, ADC8,000, and ADC10,000, were calculated, and the mean ADC value of the FILs in the GM and WM on each map was obtained by referring to the structural magnetic resonance imaging (MRI). ADC value differences of the FILs in the GM and WM were compared using Mann-Whitney U tests, and receiver operating characteristic (ROC) curves evaluated the diagnostic efficiency of each ADC value in distinguishing FILs in the two areas. RESULTS: In the enrolled 34 patients, 145 FILs were identified, of which 42 involved the GM, 87 the WM, and 16 both the GM and WM. A total of 161 regions were delineated, 58 in the GM and 103 in the WM. The values of FILs in the WM on ADC2,000, ADC4,000, ADC6,000, ADC8,000, and ADC10,000 maps were significantly lower than those in the GM (P=0.007, P<0.001, P<0.001, P<0.001 and P<0.001, respectively), while no significant differences were found on ADC500 and ADC1,000 maps (P=0.427 and P=0.225, respectively). ROC curves demonstrated that the area under the curve (AUC) paralleled the increasing b value, ascending from ADC500 to ADC10,000 (0.538, 0.558, 0.629, 0.766, 0.827, 0.859, 0.872, in that order). CONCLUSIONS: Ultra-high b value DWI is extremely sensitive to the slight diffusion difference between FILs in the GM and the WM. Its sensitivity parallels the increasing b value, indicating its clinical advantage in identifying the microstructure of FILs.

Aberrant Amplitude of Low-Frequency Fluctuation and Degree Centrality within the Default Mode Network in Patients with Vascular Mild Cognitive Impairment.

This study aimed to investigate whole-brain spontaneous activities changes in patients with vascular mild cognitive impairment (VaMCI), and to evaluate the relationships between these brain alterations and their neuropsychological assessments. Thirty-one patients with VaMCI and thirty-one healthy controls (HCs) underwent structural MRI and resting-state functional MRI (rs-fMRI) and neuropsychological assessments. The functional alterations were determined by the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC). The gray matter volume (GMV) changes were analyzed using voxel-based morphometry (VBM). Linear regression analysis was used to evaluate the relationships between the structural and functional changes of brain regions and neuropsychological assessments. The VaMCI group had significantly lower scores in the Montreal Cognitive Assessment (MoCA), and higher scores on the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). Compared to the HCs, the VaMCI group exhibited GM atrophy in the right precentral gyrus (PreCG) and right inferior temporal gyrus (ITG). VaMCI patients further exhibited significantly decreased brain activity within the default mode network (DMN), including the bilateral precuneus (PCu), angular gyrus (AG), and medial frontal gyrus (medFG). Linear regression analysis revealed that the decreased ALFF was independently associated with lower MoCA scores, and the GM atrophy was independently associated with higher HAMD scores. The current finding suggested that aberrant spontaneous brain activity in the DMN might subserve as a potential biomarker of VaMCI, which may highlight the underlying mechanism of cognitive decline in cerebral small vessel disease.

The influence of methadone on cerebral gray matter and functional connectivity.

BACKGROUND: Methadone maintenance treatment (MMT) is widely used for heroin use disorder. Although its curative effect is remarkable, there are problems associated with its use. While previous studies have found that methadone use may have certain effects on cerebral white matter, its effect on gray matter (GM) and its related neural networks is unclear. This study aimed to observe the effects of long-term methadone use on cerebral GM and the changes in related neural networks. METHODS: Patients receiving MMT treatment for heroin use disorder (N=50) were recruited. Longitudinal self-control was adopted, and the voxel-based morphometry (VBM) was used to compare the difference in cerebral GM volume before and after 1 year of methadone use, then we select the brain region where the GM volume changed as the region of interest (ROI), and use the DPARSF software for the whole brain function connection, and the differences in brain function connections before and after 1year MMT treatment were compared. RESULTS: Our results demonstrated that, after 1 year of MMT, patients showed smaller GM volume in the bilateral insula, occipital lingual gyrus, right cingulate gyrus, middle temporal gyrus, left inferior parietal lobule, caudate nucleus, temporal, and occipital regions, and the resting neural network of the brain also changed. CONCLUSIONS: We speculate that long-term methadone use can lead to damage to GM structure and adaptive changes in the neural network of patients with heroin use disorder, mainly involving emotional perception, spatial localization, working memory, and other related functions.

Altered gray matter volume and functional connectivity in patients with herpes zoster and postherpetic neuralgia.

Numerous neuroimaging studies on postherpetic neuralgia (PHN) and herpes zoster (HZ) have revealed abnormalities in brain structure/microstructure and function. However, few studies have focused on changes in gray matter (GM) volume and intrinsic functional connectivity (FC) in the transition from HZ to PHN. This study combined voxel-based morphometry and FC analysis methods to investigate GM volume and FC differences in 28 PHN patients, 25 HZ patients, and 21 well-matched healthy controls (HCs). Compared to HCs, PHN patients exhibited a reduction in GM volume in the bilateral putamen. Compared with HZ patients, PHN patients showed decreased GM volume in the left parahippocampal gyrus, putamen, anterior cingulate cortex, and right caudate and increased GM volume in the right thalamus. However, no regions with significant GM volume changes were found between the HZ and HC groups. Correlation analysis revealed that GM volume in the right putamen was positively associated with illness duration in PHN patients. Furthermore, lower FCs between the right putamen and right middle frontal gyrus/brainstem were observed in PHN patients than in HCs. These results indicate that aberrant GM volumes and FC in several brain regions, especially in the right putamen, are closely associated with chronification from HZ to PHN; moreover, these changes profoundly affect multiple dimensions of pain processing. These findings may provide new insights into the pathophysiological mechanisms of PHN.

Improved neuropathological identification of traumatic brain injury through quantitative neuroimaging and neural network analyses: Some practical approaches for the neurorehabilitation clinician.

BACKGROUND: Quantitative neuroimaging analyses have the potential to provide additional information about the neuropathology of traumatic brain injury (TBI) that more thoroughly informs the neurorehabilitation clinician. OBJECTIVE: Quantitative neuroimaging is typically not covered in the standard radiological report, but often can be extracted via post-processing of clinical neuroimaging studies, provided that the proper volume acquisition sequences were originally obtained. METHODS: Research and commercially available quantitative neuroimaging methods provide region of interest (ROI) quantification metrics, lesion burden volumetrics and cortical thickness measures, degree of focal encephalomalacia, white matter (WM) abnormalities and residual hemorrhagic pathology. If present, diffusion tensor imaging (DTI) provides a variety of techniques that aid in evaluating WM integrity. Using quantitatively identified structural and ROI neuropathological changes are most informative when done from a neural network approach. RESULTS: Viewing quantitatively identifiable damage from a neural network perspective provides the neurorehabilitation clinician with an additional tool for linking brain pathology to understand symptoms, problems and deficits as well as aid neuropsychological test interpretation. All of these analyses can be displayed in graphic form, including3-D image analysis. A case study approach is used to demonstrate the utility of quantitative neuroimaging and network analyses in TBI. CONCLUSIONS: Quantitative neuroimaging may provide additional useful information for the neurorehabilitation clinician.

Second Language Learning in Older Adults: Effects on Brain Structure and Predictors of Learning Success.

It has previously been demonstrated that short-term foreign language learning can lead to structural brain changes in younger adults. Experience-dependent brain plasticity is known to be possible also in older age, but the specific effect of foreign language learning on brain structure in language-and memory-relevant regions in the old brain remains unknown. In the present study, 160 older Swedish adults (65-75 years) were randomized to complete either an entry-level Italian course or a relaxation course, both with a total duration of 11 weeks. Structural MRI scans were conducted before and after the intervention in a subset of participants to test for differential change in gray matter in the two groups in the inferior frontal gyrus, the superior temporal gyrus, and the hippocampus, and in white matter microstructure in the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), fronto-occipital fasciculus, and the hippocampal (HC) section of the cingulum. The study found no evidence for differential structural change following language training, independent of achieved vocabulary proficiency. However, hippocampal volume and associative memory ability before the intervention were found to be robust predictors of vocabulary proficiency at the end of the language course. The results suggest that having greater hippocampal volume and better associative memory ability benefits vocabulary learning in old age but that the very initial stage of foreign language learning does not trigger detectable changes in brain morphometry in old age.

Brain Structural Network Compensation Is Associated With Cognitive Impairment and Alzheimer's Disease Pathology.

BACKGROUND: Structural network alterations in Alzheimer's disease (AD) are related to worse cognitive impairment. The aim of this study was to quantify the alterations in gray matter associated with impaired cognition and their pathological biomarkers in AD-spectrum patients. METHODS: We extracted gray matter networks from 3D-T1 magnetic resonance imaging scans, and a graph theory analysis was used to explore alterations in the network metrics in 34 healthy controls, 70 mild cognitive impairment (MCI) patients, and 40 AD patients. Spearman correlation analysis was computed to investigate the relationships among network properties, neuropsychological performance, and cerebrospinal fluid pathological biomarkers (i.e., Aß, t-tau, and p-tau) in these subjects. RESULTS: AD-spectrum individuals demonstrated higher nodal properties and edge properties associated with impaired memory function, and lower amyloid-ß or higher tau levels than the controls. Furthermore, these compensations at the brain regional level in AD-spectrum patients were mainly in the medial temporal lobe; however, the compensation at the whole-brain network level gradually extended from the frontal lobe to become widely distributed throughout the cortex with the progression of AD. CONCLUSION: The findings provide insight into the alterations in the gray matter network related to impaired cognition and pathological biomarkers in the progression of AD. The possibility of compensation was detected in the structural networks in AD-spectrum patients; the compensatory patterns at regional and whole-brain levels were different and the clinical significance was highlighted.

Focusing on Comorbidity-A Novel Meta-Analytic Approach and Protocol to Disentangle the Specific Neuroanatomy of Co-occurring Mental Disorders.

BACKGROUND: In mental health, comorbidities are the norm rather than the exception. However, current meta-analytic methods for summarizing the neural correlates of mental disorders do not consider comorbidities, reducing them to a source of noise and bias rather than benefitting from their valuable information. OBJECTIVES: We describe and validate a novel neuroimaging meta-analytic approach that focuses on comorbidities. In addition, we present the protocol for a meta-analysis of all major mental disorders and their comorbidities. METHODS: The novel approach consists of a modification of Seed-based d Mapping-with Permutation of Subject Images (SDM-PSI) in which the linear models have no intercept. As in previous SDM meta-analyses, the dependent variable is the brain anatomical difference between patients and controls in a voxel. However, there is no primary disorder, and the independent variables are the percentages of patients with each disorder and each pair of potentially comorbid disorders. We use simulations to validate and provide an example of this novel approach, which correctly disentangled the abnormalities associated with each disorder and comorbidity. We then describe a protocol for conducting the new meta-analysis of all major mental disorders and their comorbidities. Specifically, we will include all voxel-based morphometry (VBM) studies of mental disorders for which a meta-analysis has already been published, including at least 10 studies. We will use the novel approach to analyze all included studies in two separate single linear models, one for children/adolescents and one for adults. DISCUSSION: The novel approach is a valid method to focus on comorbidities. The meta-analysis will yield a comprehensive atlas of the neuroanatomy of all major mental disorders and their comorbidities, which we hope might help develop potential diagnostic and therapeutic tools.

Machine Learning Classification Identifies Cerebellar Contributions to Early and Moderate Cognitive Decline in Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common forms of dementia, marked by progressively degrading cognitive function. Although cerebellar changes occur throughout AD progression, its involvement and predictive contribution in its earliest stages, as well as gray or white matter components involved, remains unclear. We used MRI machine learning-based classification to assess the contribution of two tissue components [volume fraction myelin (VFM), and gray matter (GM) volume] within the whole brain, the neocortex, the whole cerebellum as well as its anterior and posterior parts and their predictive contribution to the first two stages of AD and typically aging controls. While classification accuracy increased with AD stages, VFM was the best predictor for all early stages of dementia when compared with typically aging controls. However, we document overall higher cerebellar prediction accuracy when compared to the whole brain with distinct structural signatures of higher anterior cerebellar contribution to mild cognitive impairment (MCI) and higher posterior cerebellar contribution to mild/moderate stages of AD for each tissue property. Based on these different cerebellar profiles and their unique contribution to early disease stages, we propose a refined model of cerebellar contribution to early AD development.

Type and timing of childhood maltreatment and reduced visual cortex volume in children and adolescents with reactive attachment disorder.

Reactive attachment disorder (RAD) is a severe social functioning disorder associated with early childhood maltreatment where the child displays emotionally withdrawn/inhibited behaviors toward caregivers. Brain regions develop at different rates and regions undergoing rapid change may be particularly vulnerable during these times to stressors or adverse experiences. The aim of this study was to investigate the effect of type and timing of childhood adversities on structural alterations in regional gray matter (GM) volume in maltreated children with RAD. High-resolution magnetic resonance imaging datasets were obtained for children and adolescents with RAD (n = 21; mean age = 12.76 years) and typically developing (TD) control subjects (n = 22; mean age = 12.95 years). Structural images were analyzed using a whole-brain voxel-based morphometry approach and the type and timing of maltreatment, which may be more strongly associated with structural alterations, was assessed using random forest regression with conditional inference trees. Our findings revealed that there is a potential sensitive period between 5 and 7 years of age for GM volume reduction of the left primary visual cortex (BA17) due to maltreatment. We also found that the number of types of maltreatment had the most significant effect on GM volume reduction and that the second most significant variable was exposure to neglect. The present study provides the first evidence showing that type and timing of maltreatment have an important role in inducing structural abnormalities in children and adolescents with RAD.

Gray matter atrophy is associated with functional connectivity reorganization during the Paced Auditory Serial Addition Test (PASAT) execution in Multiple Sclerosis (MS).

BACKGROUND AND PURPOSE: We explored the relationship between gray matter atrophy and reorganization of functional connectivity in multiple sclerosis patients during execution of the Paced Auditory Serial Addition Test (PASAT). MATERIALS AND METHODS: Seventeen patients and 15 healthy controls were selected for the study. Atrophy was determined using voxel-based morphometry, and atrophy-related connectivity changes were assessed using psychophysiological interaction analysis. Group differences, and correlations with PASAT performance and radiological variables were also examined. RESULTS: Gray matter atrophy in MS patients was circumscribed to the bilateral posterior cingulate gyrus/precuneus. Compared with controls, patients showed stronger connectivity between the left posterior cingulate gyrus/precuneus, and the left middle temporal gyrus and left cerebellum. A regression analysis in controls showed a negative correlation between PASAT scores and functional connectivity between: (1) the left posterior cingulate gyrus/precuneus, and left pre/postcentral gyri and left occipital gyrus, and (2) the right posterior cingulate gyrus/precuneus, and bilateral cerebellum and left pre/postcentral gyri. Patients showed a negative correlation between brain parenchymal fraction and functional connectivity between the left posterior cingulate gyrus/precuneus and left cerebellum. CONCLUSION: Patients with early MS and little brain damage presented more connectivity during PASAT execution, which may be interpreted as compensatory processes that help preserve cognitive functions.

Combined analyses of gray matter voxel-based morphometry and white matter tract-based spatial statistics in pediatric bipolar mania.

BACKGROUND: Ample evidence has suggested the presence of gray matter (GM) and white matter (WM) abnormalities in bipolar disorder (BD) patients, including pediatric bipolar disorder (PBD). However, little research has been done in PBD patients that carefully classify the mood states. The aim of the present study is to investigate the brain structural changes in PBD-mania children and adolescents. METHODS: Eighteen children and adolescents with bipolar mania (male/female, 6/12) aged 10-18 years old and 18 age- and sex-matched healthy controls were included in the present study. The 3D T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data were obtained on a Siemens 3.0 T scanner. Voxel-based morphometry (VBM) analysis and tract-based spatial statistics (TBSS) analysis were conducted to compare the gray matter volume and white matter fractional anisotropy (FA) value between patients and controls. Correlations of the MRI data of each survived area with clinical characteristics in PBD patients were further analyzed. RESULTS: As compared with the control group, PBD-mania children showed decreased gray matter volume in the left hippocampus. Meanwhile, significant lower FA value was detected in the right anterior cingulate (AC) in the patient group. No region of increased gray matter volume or FA value was observed in PBD-mania. The hippocampal volume was negatively associated with the Young Mania Rating Scale (YMRS) score when controlling for clinical characteristics in PBD-mania patients, however, there was no significant correlation of FA value of the survived area with illness duration, the onset age, number of episodes, or the YMRS score in PBD-mania patients. LIMITATION: The present outcomes require replication in larger samples and verification in medication free subjects. CONCLUSIONS: Our findings highlighted that extensive brain structural lesions (including GM and WM) were existed in PBD-mania. The widespread occurrence of structural abnormalities mainly located in the anterior limbic network (ALN) which suggested that this network might contribute to emotional and cognitive dysregulations in PBD.