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INTRODUCTION Adults with Down syndrome (DS) accumulate amyloid beta (Aβ) plaques faster and earlier on average than neurotypical adults with sporadic Alzheimer's disease (AD). White matter (WM) microstructure characterized with diffusion tensor imaging (DTI) can indicate underlying architectural changes in longitudinal studies, suggestive of neurodegeneration. This study investigated relationships between DTI and Aβ in DS along the AD continuum. METHODS Using longitudinal amyloid Pittsburgh compound B positron emission tomography, Centiloid (CL) and DTI parameters were examined in 35 adults with DS ages 25 to 57. DTI measures of anisotropy and diffusivity were analyzed using tract‐based spatial statistics and permutation analysis of linear models, testing for significant correlation between the rates of change for CL and DTI. RESULTS All rates of DTI and Aβ changes were significantly related. Significant regions included the corpus callosum, corona radiata, and long‐association fibers. DISCUSSION Aβ burden is associated with widespread longitudinal WM changes in DS. This suggests WM microstructure alterations accompany amyloid accumulation. Highlights A Down syndrome–specific template was created. Longitudinal diffusion tensor imaging (DTI) and amyloid burden rates of change correlate. Longitudinal results show more significant regions than cross‐sectional results. DTI and amyloid changes were found over two timepoints, 3.7 years apart on average. DTI and amyloid‐PET offer greater sensitivity when tracking microstructural changes.

Background Parkinson's disease (PD) is highly heterogeneous reflected by different affected side of body and type of motor symptom. We aim to explore clinical characteristics and underlying brain structure alterations in PD with different predominant sides and motor types. Methods We recruited 161 PD patients and 50 healthy controls (HC). Patients were classified into four subtypes according to their predominant side and motor type: left akinetic/rigid‐dominant (LAR), left tremor‐dominant (LTD), right akinetic/rigid‐dominant (RAR), and right tremor‐dominant (RTD). All participants assessed motor and cognitive performances, then underwent T1‐weighted and diffusion tensor imaging scanning. A general linear model was used to compare neuroimaging parameters among five groups. Results Among four PD subtypes, patients of LAR subtype experienced the worst motor impairment, and only this subtype showed worse cognitive performance compared with HC. Compared with HC and other subtypes, LAR subtype showed a significant reduction in cortical thickness of the right caudal‐anterior‐cingulate gyrus and fractional anisotropy of the right cingulum bundle. Conclusions We demonstrated that LAR subtype had the worst clinical performance, which the severer damage in the right cingulate region might be the underlying mechanism. This study underscores the importance of classifying PD subtypes based on both the side and type of motor symptom for clinical intervention and research to optimize behavioral outcomes in the future. The predominant side and type of motor symptoms contribute to clinical difference in Parkinson's disease. Patients with predominant left‐side akinesia/rigidity subtype performed worst in motor and non‐motor symptoms. The underlying mechanism might be the most severe damage in cingulate region in the right hemisphere.

Purpose Structural changes during depressive episodes in adolescents with major depressive disorder (MDD) remains unclear due to participant heterogeneity, illness chronicity, and medication confounders. This study aimed to explore white matter (WM) microstructural changes in first‐episode, treatment‐naïve adolescents with MDD using an integrated diffusion tensor imaging (DTI) approach. Method We recruited 66 subjects, including 37 adolescents with MDD and 29 healthy controls. Two main DTI techniques, automated fiber quantification (AFQ) and tract‐based spatial statistics (TBSS), were used to analyze fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) in WM tracts. DTI measures were then correlated with the depressive symptoms evaluated by Hamilton Depression Rating Scale scores (HAMD‐17). Findings In AFQ, MDD patients showed significant segmental differences in WM tracts compared to controls, including a negative correlation between SLF AD values and depression severity. TBSS revealed reduced FA in the cingulum, forceps minor, inferior fronto‐occipital fasciculus, inferior longitudinal fasciculus, SLF, and uncinate fasciculus in MDD. Conclusion Our integrated DTI analysis in a unique first‐episode, medication‐naïve cohort revealed microstructural changes in adolescent MDD not previously reported. These findings may provide imaging markers for early detection and enhance our understanding of depression pathology in youth. Microstructure abnormalities of diffusion tensor imaging measures in first‐episode, treatment‐naïve adolescents with major depressive disorder: an integrated AFQ and TBSS study.

Purpose To assess white matter microstructural changes in older long‐term breast cancer survivors 5–15 years post‐chemotherapy treatment. Methods Breast cancer survivors aged 65 years or older who underwent chemotherapy (C+) and who did not undergo chemotherapy (C−) and age‐ and sex‐matched healthy controls (HC) were enrolled at time point 1 (TP1) and followed for 2 years for time point 2 (TP2). All participants underwent brain MRI with diffusion tensor images and neuropsychological (NP) testing with the NIH Toolbox Cognition Battery. Tract‐based spatial statistics (TBSS) analysis was performed on the diffusion tensor images to assess white matter microstructural changes with the fractional anisotropy (FA) parameter. Results There were significant longitudinal alterations in FA within the C+ group over time. The C+ group showed diminished FA in the body and genu of corpus callosum, anterior corona radiate, and external capsule on both the whole brain and region of interest (ROI) based analyses after p < 0.05 family‐wise error (FWE) correction. However, there were no significant group differences between the groups at TP1. Additionally, at TP1, a positive correlation (R = 0.58, p = 0.04) was observed between the FA value of the anterior corona radiata and the crystallized composite score in the C+ group. Conclusions Brain white matter microstructural alterations may be the underlying neural correlates of cognitive changes in older breast cancer survivors who had chemotherapy treatment years ago.

Objective To identify the most prominent and replicable fractional anisotropy (FA) alterations of white matter associated with obsessive‐compulsive disorder (OCD) in tract‐based spatial statistics (TBSS) studies. Methods We reviewed previous TBSS studies (n = 20) in OCD and performed a meta‐analysis (n = 16) of FA differences. Results No between‐group differences in FA were detected in the pooled meta‐analysis. However, reduced FA was identified in the genu and anterior body of corpus callosum (CC) in adult OCD. FA reductions in the anterior body of CC were associated with a later age of onset in adult patients with OCD. For pediatric OCD, decreased FA in earlier adolescence and increased FA in later adolescence were seemingly related to an altered trajectory of brain maturation. Conclusions Absent in the pooled sample but robust in adults, disrupted microstructural organization in the anterior part of CC indicates a bias of deficits toward connections in interhemispheric connections of rostral neocortical regions, which could lead to deficits of interhemispheric communication and thus contribute to cognitive and emotional deficits in adult OCD. The correlation between FA in the anterior body of CC and older illness onset suggests that patients with later adult onset of illness may represent a biologically distinct subgroup. For pediatric OCD, alterations in neurodevelopmental maturation may contribute to inconsistent patterns of FA alteration relative to controls during adolescence. While most studies of OCD have emphasized alterations of within hemisphere fronto‐striatal circuits, these results indicate that between hemisphere connectivity of this circuitry may also represent important pathophysiology of the illness. No between‐group differences in FA were detected in the pooled meta‐analysis. However, reduced FA was identified in the genu and anterior body of corpus callosum (CC) in adult OCD. FA reductions in the anterior body of CC were associated with a later age of onset in adult patients with OCD. For pediatric OCD, decreased FA in earlier adolescence and increased FA in later adolescence is seemingly related to an altered trajectory of brain maturation.

Background Visual deprivation can lead to abnormal and plastic changes in the brain's visual system and other systems. Although the secondary changes of gray matter in patients have been well studied, the study of white matter is rare. In fact, subtle changes in white matter may be revealed by diffusion tensor imaging, and tract‐based spatial statistics can be used to analyze DTI image data. Purpose In the present study, diffusion tensor imaging (DTI) and tract‐based spatial statistics (TBSS) were used to investigate abnormal structural changes in the white matter (WM) of patients with monocular blindness (MB). Methods We recruited 16 healthy controls (HC) (fourteen males and two females) and 16 patients (fifteen males and one female) with right‐eye blindness (without differences in left‐eye vision). All patients were of similar age. Data acquisition was performed using magnetic resonance imaging (MRI) and DTI. Voxel‐based whole brain comparisons of fractional anisotropy (FA) and radial diffusivity (RD) of WM fibers in patients and HC were performed using the TBSS method. The mean FA and RD values for altered brain regions in MB patients were analyzed via the receiver operating characteristic (ROC) curve. Correlation analysis was performed to investigate the relationships between the average FA (RD) value of the whole brain and anxiety score, depression score, and visual function questionnaire score in MB patients. Results In MB patients, the mean FA of the whole brain was decreased versus HC. Moreover, the FA values of the corpus callosum, the corona radiata, the posterior thalamic radiation, and the right retrolenticular part of internal capsule were significantly decreased. In addition, the average RD value of the whole brain in MB patients was higher than that observed in HC. The mean FA and RD values of brain regions were analyzed using the ROC curve, and the results showed that the area under the ROC curve was more accurate. Furthermore, the average FA and RD values of the whole brain were significantly correlated with anxiety score, depression score, and visual function‐related quality of life score. Conclusion DTI and TBSS may be useful in examining abnormal spontaneous alterations in the WM of MB patients. The observed changes in FA and RD values may imply the larvaceous neurological mechanism involved in MB. Diffusion tensor imaging and tract‐based spatial statistics may be useful in examining abnormal spontaneous alterations in the white matter of monocular blindness patients. The observed changes in fractional anisotropy and radial diffusivity values may imply the larvaceous neurological mechanism involved in patients with monocular blindness.

Objective To explore the changes in the cerebral microstructure of patients with noise‐induced hearing loss (NIHL) using diffusion tensor imaging (DTI). Method Overall, 122 patients with NIHL (mild [MP, n = 79], relatively severe patients [including moderate and severe; RSP, n = 32], and undetermined [lost to follow‐up, n = 11]) and 84 healthy controls (HCs) were enrolled. All clinical data, including age, education level, hearing threshold, occupation type, noise exposure time, and some scale scores (including the Mini‐Mental State Examination [MMSE], tinnitus handicap inventory [THI], and Hamilton Anxiety Scale [HAMA]), were collected and analyzed. All participants underwent T1WI3DFSPGR and DTI, and tract‐based spatial statistics and region of interest (ROI) analysis were used for assessment. Results The final sample included 71 MP, 28 RSP, and 75 HCs. The HAMA scores of the three groups were significantly different (p < .05). The noise exposure times, hearing thresholds, and HAMA scores of the MP and RSP were significantly different (p < .05). The noise exposure time was positively correlated with the hearing threshold and negatively correlated with the HAMA scores (p < .05), whereas the THI scores were positively correlated with the hearing threshold (p < .05). DTI analysis showed that all DTI parameters (fractional anisotropy [FA], axial diffusivity [AD], mean diffusivity [MD], and radial diffusivity [RD]) were significantly different in the left inferior longitudinal fasciculus (ILF) and left inferior fronto‐occipital fasciculus (IFOF) for the three groups (p < .05). In addition, the FA values were significantly lower in the bilateral corticospinal tract (CST), right fronto‐pontine tract (FPT), right forceps major, left superior longitudinal fasciculus (temporal part) (SLF), and left cingulum (hippocampus) (C‐H) of the MP and RSP than in those of the HCs (p < .05); the AD values showed diverse changes in the bilateral CST, left IFOF, right anterior thalamic radiation, right external capsule (EC), right SLF, and right superior cerebellar peduncle (SCP) of the MP and RSP relative to those of the HC (p < .05). However, there were no significant differences among the bilateral auditory cortex ROIs of the three groups (p > .05). There was a significant negative correlation between the FA and HAMA scores for the left IFOF/ILF, right FPT, left SLF, and left C‐H for the three groups (p < .05). There was a significant positive correlation between the AD and HAMA scores for the left IFOF/ILF and right EC of the three groups (p < .05). There were significantly positive correlations between the RD/MD and HAMA scores in the left IFOF/ILF of the three groups (p < .05). There was a significant negative correlation between the AD in the right SCP and noise exposure time of the MP and RSP groups (p < .05). The AD, MD, and RD in the left ROI were significantly positively correlated with hearing threshold in the MP and RSP groups (p < .05), whereas FA in the right ROI was significantly positively correlated with the HAMA scores for the three groups (p < .05). Conclusion The changes in the white matter (WM) microstructure may be related to hearing loss caused by noise exposure, and the WM structural abnormalities in patients with NIHL were mainly located in the syndesmotic fibers of the temporooccipital region, which affected the auditory and language pathways. This confirmed that the auditory pathways have abnormal structural connectivity in patients with NIHL.  

Aim Healthy older drivers may be at high risk of fatal traffic accidents. Our recent study showed that volumetric alterations in gray matter in the brain regions within the dorsal attention network (DAN) were strongly related to the risk of unsafe driving in healthy older people. However, the relationship between white matter (WM) structural connectivity and driving ability in healthy older people is still unclear. Methods We used diffusion tensor imaging to examine the association between microstructural alterations in the DAN and the risk of unsafe driving among healthy older people. We enrolled 32 healthy older individuals aged over 65 years and screened unsafe drivers using an on‐road driving test. We then determined the pattern of WM aberrations in unsafe drivers using tract‐based spatial statistics. Results The analysis demonstrated that unsafe drivers had significantly higher axial diffusivity values in nine WM clusters compared with safe drivers. These results were primarily observed bilaterally in the dorsal superior longitudinal fasciculus, which is involved in the DAN. Furthermore, correlation analyses showed that higher axial diffusivity values in the superior longitudinal fasciculus were associated with lower Trail Making Test A scores within unsafe drivers. This result suggests that functionally, WM microstructural alterations in the DAN are associated with attention problems, which may contribute to the risk of unsafe driving among healthy older people. Conclusion Our findings may elucidate the neurobiological mechanisms underlying the increased risk of unsafe driving in healthy older people, potentially facilitating the development of new interventions to prevent fatal accidents.

Background： The ability to predict posttraumatic stress disorder （PTSD） is a critical issue in the management of patients with mild traumatic brain injury （mTBI）, as early medical and rehabilitative interventions may reduce the risks of long-term cognitive changes. The aim of the present study was to investigate how diffusion tensor imaging （DTI） metrics changed in the transition from acute to chronic phases in patients with mTBI and whether the alteration relates to the development of PTSD. Methods： Forty-three patients with mTBI and 22 healthy volunteers were investigated. The patients were divided into two groups： successful recovery （SR, n = 22） and poor recovery （PR, n = 21）, based on neurocognitive evaluation at 1 or 6 months after injury. All patients underwent magnetic resonance imaging investigation at acute （within 3 days）, subacute （10-20 days）, and chronic （1-6 months） phases after injury. Group differences of fractional anisotropy （FA） and mean diffusivity （MD） were analyzed using tract-based spatial statistics （TBSS）. The accuracy of DTI metrics for classifying PTSD was estimated using Bayesian discrimination analysis. Results： TBSS showed white matter （WM） abnormalities in various brain regions. In the acute phase, FA values were higher for PR and SR patients than controls （all P 〈 0.05）. In subacute phase, PR patients have higher mean MD than SR and controls （all P 〈 0.05）. In the chronic phase, lower FA and higher MD were observed in PR compared with both SR and control groups （all P 〈 0.05）. PR and SR groups could be discriminated with a sensitivity of 73%, specificity of 78%, and accuracy of 75.56%, in terms of MD value in subacute phase. Conclusions： Patients with mTBI have multiple abnormalities in various WM regions. DTI metrics change over time and provide a potential indicator at subacute stage for PTSD following mTBI.

Moyamoya disease and cerebrovascular atherosclerotic disease are both chronic ischemic diseases with similar presentations of vascular cognitive impairment. The aim of the present study was to investigate the patterns of microstructural damage associated with vascular cognitive impairment in the two diseases. The study recruited 34 patients with moyamoya disease (age 43.9 ± 9.2 years; 20 men and 14 women, 27 patients with cerebrovascular atherosclerotic disease (age: 44.6 ± 7.6 years; 17 men and 10 women), and 31 normal controls (age 43.6 ± 7.3 years; 18 men and 13 women) from Huashan Hospital of Fudan University in China. Cognitive function was assessed using the Mini-Mental State Examination, long-term delayed recall of Auditory Verbal Learning Test, Trail Making Test Part B, and the Symbol Digit Modalities Test. Single-photon emission-computed tomography was used to examine cerebral perfusion. Voxel-based morphometry and tract-based spatial statistics were performed to identify regions of gray matter atrophy and white matter deterioration in patients and normal controls. The results demonstrated that the severity of cognitive impairment was similar between the two diseases in all tested domains. Patients with moyamoya disease and those with cerebrovascular atherosclerotic disease suffered from disturbed supratentorial hemodynamics. Gray matter atrophy in bilateral middle cingulate cortex and parts of the frontal gyrus was prominent in both diseases, but in general, was more severe and more diffuse in those with moyamoya disease. White matter deterioration was significant for both diseases in the genu and body of corpus callosum, in the anterior and superior corona radiation, and in the posterior thalamic radiation, but in moyamoya disease, it was more diffuse and more severe. Vascular cognitive impairment was associated with regional microstructural damage, with a potential link between, gray and white matter damage. Overall, these results provide insight into the pathophysiological nature of vascular cognitive impairment. This study was approved by the Institutional Review Board in Huashan Hospital, China (approval No. 2014-278). This study was registered with ClinicalTrials.gov on December 2, 2014 with the identifier NCT02305407.