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Abnormal reward sensitivity is a risk factor for psychiatric disorders, including eating disorders such as overeating and binge-eating disorder, but the brain structural mechanisms that underlie it are not completely understood. Here, we sought to investigate the relationship between multimodal whole-brain structural features and reward sensitivity in nonhuman primates. Reward sensitivity was evaluated through behavioral economic analysis in which monkeys (adult rhesus macaques; 7 female, 5 male) responded for sweetened condensed milk (10%, 30%, 56%), Gatorade, or water using an operant procedure in which the response requirement increased incrementally across sessions (i.e., fixed ratio 1, 3, 10). Animals were divided into high (n = 6) or low (n = 6) reward sensitivity groups based on essential value for 30% milk. Multimodal magnetic resonance imaging was used to measure gray matter volume and white matter microstructure. Brain structural features were compared between groups, and their correlations with reward sensitivity for various stimuli was investigated. Animals in the high sensitivity group had greater dorsolateral prefrontal cortex, centromedial amygdaloid complex, and middle cingulate cortex volumes than animals in the low sensitivity group. Furthermore, compared with monkeys in the low sensitivity group, high sensitivity monkeys had lower fractional anisotropy in the left dorsal cingulate bundle connecting the centromedial amygdaloid complex and middle cingulate cortex to the dorsolateral prefrontal cortex, and in the left superior longitudinal fasciculus 1 connecting the middle cingulate cortex to the dorsolateral prefrontal cortex. These results suggest that neuroanatomical variation in prefrontal-limbic circuitry is associated with reward sensitivity. These brain structural features may serve as predictive biomarkers for vulnerability to food-based and other reward-related disorders. [ABSTRACT FROM AUTHOR]

Objective: To identify white matter fiber injury and network changes that may lead to mild cognitive impairment (MCI) progression, then a joint model was constructed based on neuropsychological scales to predict high-risk individuals for Alzheimer's disease (AD) progression among older adults with MCI. Methods: A total of 173 MCI patients were included from the Alzheimer's Disease Neuroimaging Initiative(ADNI) database and randomly divided into training and testing cohorts. Forty-five progressed to AD during a 4-year follow-up period. Diffusion tensor imaging (DTI) techniques extracted relevant DTI quantitative features for each patient. In addition, brain networks were constructed based on white matter fiber bundles to extract network property features. Ensemble dimensionality reduction was applied to reduce both DTI quantitative features and network features from the training cohort, and machine learning algorithms were added to construct white matter signature. In addition, 52 patients from the National Alzheimer's Coordinating Center (NACC) database were used for external validation of white matter signature. A joint model was subsequently generated by combining with scale scores, and its performance was evaluated using data from the testing cohort. Results: Based on multivariate logistic regression, clinical dementia rating and Alzheimer's disease assessment scales (CDRS and ADAS, respectively) were selected as independent predictive factors. A joint model was constructed in combination with the white matter signature. The AUC, sensitivity, and specificity in the training cohort were 0.938, 0.937, and 0.91, respectively, and the AUC, sensitivity, and specificity in the test cohort were 0.905, 0.923, and 0.872, respectively. The Delong test showed a statistically significant difference between the joint model and CDRS or ADAS scores (P < 0.05), yet no significant difference between the joint model and the white matter signature (P = 0.341). Conclusion: The present results demonstrate that a joint model combining neuropsychological scales can be constructed by using machine learning and DTI technology to identify MCI patients who are at high-risk of progressing to AD. [ABSTRACT FROM AUTHOR]

This study aimed to examine the association between past/current sleep duration and macro-/micro-structural brain outcomes and explore whether hypertension or social activity plays a role in such association. Within the UK Biobank, 40 436 dementia-free participants (age 40–70 years) underwent a baseline assessment followed by a brain magnetic resonance imaging (MRI) scan 9 years later. Past (baseline) and current (MRI scans) sleep duration (hours/day) were recorded and classified as short (≤5), intermediate (6–8), and long (≥9). Brain structural volumes and diffusion markers were assessed by MRI scans. Compared with past intermediate sleep, past short sleep was related to smaller cortex volumes (standardized β [95 % CI]: −0.04 [-0.07, −0.02]) and lower regional fractional anisotropy (FA) (−0.08 [-0.13, −0.03]), while past long sleep was related to smaller regional subcortical volumes (standardized β: −0.04 to −0.07 for thalamus, accumbens, and hippocampus). Compared to current intermediate sleep, current short sleep was associated with smaller cortex volumes (−0.03 [-0.05, −0.01]), greater white matter hyperintensities (WMH) volumes (0.04 [0.01, 0.08]), and lower regional FA (−0.07 [-0.11, −0.02]). However, current long sleep was related to smaller total brain (−0.03 [-0.05, −0.02]), grey matter (−0.05 [-0.07, −0.03]), cortex (−0.05 [-0.07, −0.03]), regional subcortical volumes [standardized β: −0.05 to −0.09 for putamen, thalamus, hippocampus, and accumbens]), greater WMH volumes (0.06 [0.03, 0.09]), as well as lower regional FA (−0.05 [-0.09, −0.02]). The association between current long sleep duration and poor brain health was stronger among people with hypertension or low frequency of social activity (all P interaction <0.05). Both past and current short/long sleep are associated with smaller brain volume and poorer white matter health in the brain, especially in individuals with hypertension and low frequency of social activity. Our findings highlight the need to maintain 6–8 h' sleep duration for healthy brain aging. [Display omitted] • Long or short sleep is associated with poorer brain health. • People with hypertension or lack of social activity particularly need healthy sleep to delay brain aging. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Sensory Processing Dysfunction (SPD) is common yet understudied, affecting up to one in six children with 40% experiencing co-occurring challenges with attention. The neural architecture of SPD with Attention Deficit and Hyperactivity Disorder (ADHD) (SPD+ADHD) versus SPD without ADHD (SPD-ADHD) has yet to be explored in diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) has yet to be examined. METHODS: The present study computed DTI and NODDI biophysical model parameter maps of one hundred children with SPD. Global, regional and voxel-level white matter tract measures were analyzed and compared between SPD+ADHD and SPD-ADHD groups. RESULTS: SPD+ADHD children had global WM Fractional Anisotropy (FA) and Neurite Density Index (NDI) that trended lower than SPD-ADHD children, primarily in boys only. Data-driven voxelwise and WM tract-based analysis revealed statistically significant decreases of NDI in boys with SPD+ADHD compared to those with SPD-ADHD, primarily in projection tracts of the internal capsule and commissural fibers of the splenium of the corpus callosum. CONCLUSION: We conclude that WM microstructure is more delayed/disrupted in boys with SPD+ADHD compared to SPD-ADHD, with NODDI showing a larger effect than DTI. This may represent the combined WM pathology of SPD and ADHD, or it may result from a greater degree of SPD WM pathology causing the development of ADHD.

Objectives: The diverse nature of stroke necessitates individualized assessment, presenting challenges to case-control neuroimaging studies. The normative model, measuring deviations from a normal distribution, provides a solution. We aim to evaluate stroke-induced white matter microstructural abnormalities at group and individual levels and identify potential prognostic biomarkers. Methods: Forty-six basal ganglia stroke patients and 46 healthy controls were recruited. Diffusion-weighted imaging and clinical assessment were performed within 7 days after stroke. We used automated fiber quantification to characterize intergroup alterations of segmental diffusion properties along 20 fiber tracts. Then each patient was compared to normative reference (46 healthy participants) by Mahalanobis distance tractometry for 7 significant fiber tracts. Mahalanobis distance-based deviation loads (MaDDLs) and fused MaDDLmulti were extracted to quantify individual deviations. We also conducted correlation and logistic regression analyses to explore relationships between MaDDL metrics and functional outcomes. Results: Disrupted microstructural integrity was observed across the left corticospinal tract, bilateral inferior fronto-occipital fasciculus, left inferior longitudinal fasciculus, bilateral thalamic radiation, and right uncinate fasciculus. The correlation coefficients between MaDDL metrics and initial functional impairment ranged from 0.364 to 0.618 (p<0.05), with the highest being MaDDLmulti. Furthermore, MaDDLmulti demonstrated a significant enhancement in predictive efficacy compared to MaDDL (integrated discrimination improvement [IDI] = 9.62%, p = 0.005) and FA (IDI = 34.04%, p< 0.001) of the left corticospinal tract. Conclusion: MaDDLmulti allows for assessing behavioral disorders and predicting prognosis, offering significant implications for personalized clinical decision- making and stroke recovery. Importantly, our method demonstrates prospects for widespread application in heterogeneous neurological diseases. [ABSTRACT FROM AUTHOR]

• ECHDC3 variants link to WM hyperintensity & insulin resistance. • ECHDC3 -T2DM impact on brain WM microstructures. • ECHDC3 influences T2DM-related memory decline via hippocampus. • ECHDC3 modulates T2DM → right hippocampal FA → memory pathway. ECHDC3 is a risk gene for white matter (WM) hyperintensity and is associated with insulin resistance. This study aimed to investigate whether ECHDC3 variants selectively regulate brain WM microstructures and episodic memory in patients with type 2 diabetes mellitus (T2DM). We enrolled 106 patients with T2DM and 111 healthy controls. A voxel-wise general linear model was employed to explore the interaction effect between ECHDC3 rs11257311 polymorphism and T2DM diagnosis on fractional anisotropy (FA). A linear modulated mediation analysis was conducted to examine the potential of FA value to mediate the influence of T2DM on episodic memory in an ECHDC3 -dependent manner. We observed a noteworthy interaction between genotype and diagnosis on FA in the right inferior temporal WM, right anterior limb of the internal capsule, right frontal WM, and the right hippocampus. Modulated mediation analysis revealed a significant ECHDC3 modulation on the T2DM → right hippocampal FA → short-term memory pathway, with only rs11257311 G risk homozygote demonstrating significant mediation effect. Together, our findings provide evidence of ECHDC3 modulating the effect of T2DM on right hippocampal microstructural impairment and short-term memory decline, which might be a neuro-mechanism for T2DM related episodic memory impairment. [ABSTRACT FROM AUTHOR]

Over the past several years, there has been a surge in blood biomarker studies examining the value of plasma or serum neurofilament light (NfL) as a biomarker of neurodegeneration for Alzheimer's disease. However, there have been limited efforts to combine existing findings to assess the utility of blood NfL as a biomarker of neurodegeneration for Alzheimer's disease. In addition, we still need better insight into the specific aspects of neurodegeneration that are reflected by the elevated plasma or serum concentration of NfL. In this review, we survey the literature on the cross-sectional and longitudinal relationships between blood-based NfL levels and other, neuroimaging-based, indices of neurodegeneration in individuals on the Alzheimer's continuum. Then, based on the biomarker classification established by the FDA-NIH Biomarker Working group, we determine the utility of blood-based NfL as a marker for monitoring the disease status (i.e. monitoring biomarker) and predicting the severity of neurodegeneration in older adults with and without cognitive decline (i.e. a prognostic or a risk/susceptibility biomarker). The current findings suggest that blood NfL exhibits great promise as a monitoring biomarker because an increased NfL level in plasma or serum appears to reflect the current severity of atrophy, hypometabolism and the decline of white matter integrity, particularly in the brain regions typically affected by Alzheimer's disease. Longitudinal evidence indicates that blood NfL can be useful not only as a prognostic biomarker for predicting the progression of neurodegeneration in patients with Alzheimer's disease but also as a susceptibility/risk biomarker predicting the likelihood of abnormal alterations in brain structure and function in cognitively unimpaired individuals with a higher risk of developing Alzheimer's disease (e.g. those with a higher amyloid-β). There are still limitations to current research, as discussed in this review. Nevertheless, the extant literature strongly suggests that blood NfL can serve as a valuable prognostic and susceptibility biomarker for Alzheimer's disease-related neurodegeneration in clinical settings, as well as in research settings. [ABSTRACT FROM AUTHOR]

Background This study aims to investigate the temporal and spatial patterns of structural brain injury related to deep medullary veins (DMVs) damage. Methods and Results This is a longitudinal analysis of the population‐based Shunyi cohort study. Baseline DMVs numbers were identified on susceptibility‐weighted imaging. We assessed vertex‐wise cortex maps and diffusion maps at both baseline and follow‐up using FSL software and the longitudinal FreeSurfer analysis suite. We performed statistical analysis of global measurements and voxel/vertex‐wise analysis to explore the relationship between DMVs number and brain structural measurements. A total of 977 participants were included in the baseline, of whom 544 completed the follow‐up magnetic resonance imaging (age 54.97±7.83 years, 32% men, mean interval 5.56±0.47 years). A lower number of DMVs was associated with a faster disruption of white matter microstructural integrity, presented by increased mean diffusivity and radial diffusion (β=0.0001 and SE=0.0001 for both, P=0.04 and 0.03, respectively), in extensive deep white matter (threshold‐free cluster enhancement P

Children with attention-deficit/hyperactivity disorder (ADHD) demonstrate reduced response inhibition, increased response time variability, and atypical frontal lobe white matter microstructure with emerging evidence of sex differences. This study aims to examine whether frontal lobe white matter microstructure is differentially impacted in ADHD by sex and whether this relates to Go/No-Go (GNG) task performance. Diffusion tensor imaging (DTI) from 187 children (8–12 years), including ADHD (n = 94) and typically developing controls (TD; n = 93). Participants completed three GNG tasks with varying cognitive demands and incentives (standard, cognitive, and motivational). Fractional anisotropy (FA) was examined as an index of white matter microstructure within bilateral frontal lobe regions of interest. Children with ADHD showed reduced FA in primary motor (M1) and supplementary motor area (SMA) regardless of sex. Sex-based dissociation for the effect of diagnosis was observed in medial orbitofrontal cortex (mOFC), with higher FA in girls with ADHD and lower FA in boys with ADHD. Both diagnosis and sex contributed to performance on measures of response inhibition and reaction time (RT) variability, with all children with ADHD demonstrating poorer performance on all GNG tasks, but boys with ADHD demonstrating more impulsivity on standard and motivational behavioral paradigms compared to girls with ADHD. Analyses revealed associations between reduced FA in M1, SMA, and mOFC and increased response inhibition and RT variability with some sex-based differences. These findings provide novel insights regarding the brain basis of ADHD and associated impairments in response inhibition and RT variability, and contribute to our understanding of sexual dimorphic behavioral outcomes. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) patients are at risk for alterations in the cerebral white matter microstructure (WMM) throughout development. It is unclear whether the extent of WMM alterations changes with age, especially during adolescence when the WMM undergoes rapid maturation. We investigated differences in WMM between patients with CHD and healthy controls from childhood until early adulthood in a pooled sample of children, adolescents, and young adults. The association between WMM and EF was assessed. Patients with CHD (N=78) and controls (N=137) between 9 and 32 years of age underwent diffusion tensor imaging and an executive function test-battery. Mean fractional anisotropy (FA) was calculated for each white matter tract. Linear regression tested age and group effects (CHD vs control) and their interaction on FA. Relative Variable Importance (RI) estimated the independent contribution of tract FA, presence of CHD, CHD complexity, and parental education to the variability in EF. Mean FA was lower in patients compared to controls in almost all tracts (p between 0.057 and <0.001). WMM alterations in patients were not different depending on age (all interaction effects p>0.074). Predictors of EF were CHD group (RI=43%), parental education (RI=23%), CHD complexity (RI=10%), FA of the hippocampal cingulum (RI=6%) and FA of the corticospinal tract (RI=6%). The lack of group-FA-interactions indicates that the extent of altered FA remains similar across age. Altered FA is associated with EF impairments. CHD is a chronic disease with cerebral and neurocognitive impairments persisting into adulthood and, thus, long-term follow-up programs may improve overall outcome for this population. [ABSTRACT FROM AUTHOR]

Objective: To determine if there are sex differences in myelin in Parkinson's disease, and whether these explain some of the previously-described sex differences in clinical presentation. Methods: Thirty-three subjects (23 males, 10 females) with Parkinson's disease underwent myelin water fraction (MWF) imaging, an MRI scanning technique of in vivo myelin content. MWF of 20 white matter regions of interest (ROIs) were assessed. Motor symptoms were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS). Principal component analysis, logistic and multiple linear regressions, and t-tests were used to determine which white matter ROIs differed between sexes, the clinical features associated with these myelin changes, and if overall MWF and MWF laterality differed between males and females. Results: Consistent with prior reports, tremor and bradykinesia were more likely seen in females, whereas rigidity and axial symptoms were more likely seen in males in our cohort. MWF of the thalamic radiation, cingulum, cingulum hippocampus, inferior fronto-occipital fasciculi, inferior longitudinal fasciculi, and uncinate were significant in predicting sex. Overall MWF and asymmetry of MWF was greater in males. MWF differences between sexes were associated with tremor symptomatology and asymmetry of motor performance. Conclusion: Sex differences in myelin are associated with tremor and asymmetry of motor presentation. While preliminary, our results suggest that further investigation of the role of biological sex in myelin pathology and clinical presentation in Parkinson's disease is warranted. [ABSTRACT FROM AUTHOR]

Psychomotor disturbance is common in psychotic depression and is associated with relapse. In this analysis, we examined whether white matter microstructure is associated with relapse probability in psychotic depression and, if so, whether white matter microstructure accounts for the association between psychomotor disturbance and relapse. We used tractography to characterize diffusion-weighted MRI data in 80 participants enrolled in a randomized clinical trial that compared efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo in the continuation treatment of remitted psychotic depression. Cox proportional hazard models tested the relationships between psychomotor disturbance (processing speed and CORE score) at baseline, white matter microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) in 15 selected tracts at baseline, and relapse probability. CORE was significantly associated with relapse. Higher mean MD was significantly associated with relapse in the each of the following tracts: corpus callosum, left striato-frontal, left thalamo-frontal, and right thalamo-frontal. CORE and MD were each associated with relapse in the final models. As a secondary analysis with a small sample size, this study was not powered for its aims, and is vulnerable to types I and II statistical errors. Further, the sample size was not sufficient to test the interaction of the independent variables and randomized treatment group with relapse probability. While both psychomotor disturbance and MD were associated with psychotic depression relapse, MD did not account for the relationship between psychomotor disturbance and relapse. The mechanism by which of psychomotor disturbance increases the risk of relapse requires further investigation. Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II); NCT01427608. URL: https://clinicaltrials.gov/ct2/show/NCT01427608. • Psychomotor disturbance (PMD) is common in psychotic depression. • PMD is associated with relapse in this patient group. • We examined whether white matter microstructure (WM) explains this relationship. • Both PMD and WM were associated with relapse in our study group. • However, WM did not account for the relationship between PMD and relapse. [ABSTRACT FROM AUTHOR]

Neuroinflammation and white matter microstructure damage are important causes of cognitive impairment after subarachnoid hemorrhage (SAH). Nod-like receptor protein 3 (NLRP3) plays an important role in neuroinflammation after SAH and may be a potential therapeutic target for treatment of white matter microstructure injury. In this study, we observed whether MCC950, a specific inhibitor of the NLRP3 inflammasome, exerted a therapeutic effect after SAH. The SAH model was induced by endovascular perforation in SpragueDawley rats. MCC950 was injected intraperitoneally 1 h after SAH at a dose of 10 mg/kg. The results showed that MCC950 significantly attenuated white matter microstructure damage in some brain regions, and behavioral experiments confirmed that MCC950 ameliorated cognitive function in rats after SAH, which may provide a new method for the treatment of cognitive dysfunction in SAH patients.

Introduction: Sensory Processing Dysfunction (SPD) is common yet understudied, affecting up to one in six children with 40% experiencing co-occurring challenges with attention. The neural architecture of SPD with Attention Deficit and Hyperactivity Disorder (ADHD) (SPD+ADHD) versus SPD without ADHD (SPD-ADHD) has yet to be explored in diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) has yet to be examined. Methods: The present study computed DTI and NODDI biophysical model parameter maps of one hundred children with SPD. Global, regional and voxel-level white matter tract measures were analyzed and compared between SPD+ADHD and SPD-ADHD groups. Results: SPD+ADHD children had global WM Fractional Anisotropy (FA) and Neurite Density Index (NDI) that trended lower than SPD-ADHD children, primarily in boys only. Data-driven voxelwise and WM tract-based analysis revealed statistically significant decreases of NDI in boys with SPD+ADHD compared to those with SPD-ADHD, primarily in projection tracts of the internal capsule and commissural fibers of the splenium of the corpus callosum. Conclusion: We conclude that WM microstructure is more delayed/disrupted in boys with SPD+ADHD compared to SPD-ADHD, with NODDI showing a larger effect than DTI. This may represent the combined WM pathology of SPD and ADHD, or it may result from a greater degree of SPD WM pathology causing the development of ADHD. [ABSTRACT FROM AUTHOR]

Background: Patients with bipolar disorder (BD) show reduced fractional anisotropy (FA) compared to patients with major depressive disorder (MDD). Little is known about whether these differences are mood state-independent or influenced by acute symptom severity. Therefore, the aim of this study was (1) to replicate abnormalities in white matter microstructure in BD v. MDD and (2) to investigate whether these vary across depressed, euthymic, and manic mood. Methods: In this cross-sectional diffusion tensor imaging study, n = 136 patients with BD were compared to age- and sex-matched MDD patients and healthy controls (HC) (n = 136 each). Differences in FA were investigated using tract-based spatial statistics. Using interaction models, the influence of acute symptom severity and mood state on the differences between patient groups were tested. Results: Analyses revealed a main effect of diagnosis on FA across all three groups (ptfce-FWE = 0.003). BD patients showed reduced FA compared to both MDD (ptfce-FWE = 0.005) and HC (ptfce-FWE < 0.001) in large bilateral clusters. These consisted of several white matter tracts previously described in the literature, including commissural, association, and projection tracts. There were no significant interaction effects between diagnosis and symptom severity or mood state (all ptfce-FWE > 0.704). Conclusions: Results indicated that the difference between BD and MDD was independent of depressive and manic symptom severity and mood state. Disruptions in white matter microstructure in BD might be a trait effect of the disorder. The potential of FA values to be used as a biomarker to differentiate BD from MDD should be further addressed in future studies using longitudinal designs. [ABSTRACT FROM AUTHOR]

Introduction: Hypothyroidism leads to impaired white matter (WM) integrity, associated with cognitive/neuropsychiatric dysfunction. However, the specific segmental abnormalities of the fibers remain unexplored. Therefore, this study aimed to investigate whether the damage of the WM is limited to a specific segment or the entire bundle via diffusion metrics using automated fiber quantification. Methods: A cross-sectional study was conducted on 31 hypothyroid patients and 28 healthy controls. Thyroid-related hormone levels, cognitive/neuropsychiatric function, and diffusion tensor image data were collected and analyzed. Correlation and random forest analyses were also performed. Results: The mean fractional anisotropy (FA) values were reduced at the fiber tract level. The mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were increased in several fiber tracts, i.e., cingulum cingulate (CC), anterior forceps of corpus callosum (CCF_A). Significant correlations were found between cognitive function and diffusion indicators such as the FA value of the left corticospinal tract and arcuate fasciculus (AF), the MD value of left CC, the RD value of left AF, the AD value of left CC, and CCF_A. The widespread microstructure disruption was spread on multiple specific segments of different tracts at the point-wise level. The random forest revealed that the accuracy of recognizing hypothyroid patients was 82.5%, with the anterior component of CCF_A having the most significant contribution. Conclusion: WM microstructural integrity impairments were found in multi-segments of the multiple fiber bundles in hypothyroidism, which might be a potential mechanism of the underlying neurocognitive decline and cerebral impairment. The CCF_A might serve as a neuro biomarker for early warning of cerebral impairment in hypothyroidism. [ABSTRACT FROM AUTHOR]

This study investigated associations between psychological resilience and characteristics of white matter microstructure in pediatric concussion. This is a case control study and a planned substudy of a larger randomized controlled trial. Children with an acute concussion or orthopedic injury were recruited from the emergency department. Participants completed both the Connor–Davidson Resilience Scale 10 and an MRI at 72 h and 4‐weeks post‐injury. The association between resiliency and fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) at both timepoints were examined. We examined whether these associations were moderated by group. The association between resiliency captured at 72 h and diffusion tensor imaging metrics at 4 weeks was also investigated. Clusters were extracted using a significance threshold of threshold‐free cluster enhancement corrected p <.05. A total of 66 children with concussion (median (IQR) age = 12.88 (IQR: 11.80–14.36); 47% female) and 29 children with orthopedic‐injury (median (IQR) age = 12.49 (IQR: 11.18–14.01); 41% female) were included. A negative correlation was identified in the concussion group between 72 h resilience and 72 h FA. Meanwhile, positive correlations were identified in the concussion group with concussion between 72 h resilience and both 72 h MD and 72 h RD. These findings suggest that 72 h resilience is associated with white matter microstructure of the forceps minor, superior longitudinal fasciculus, and anterior thalamic radiation at 72 h post‐concussion. Resilience seems to be associated with neural integrity only in the acute phase of concussion and thus may be considered when researching concussion recovery. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIMS: Even though the Compulsive Sexual Behavior Disorder (CSBD) was added to the ICD-11 under the impulse control category in 2019, its neural mechanisms are still debated. Researchers have noted its similarity both to addiction and to Obssesive-Compulsive Disorder (OCD). The aim of our study was to address this question by investigating the pattern of anatomical brain abnormalities among CSBD patients. METHODS: Reviewing 39 publications on Diffusion Tensor Imaging (DTI) we have identified main abnormalities specific for addictions and OCD. Than we have collected DTI data from 36 heterosexual males diagnosed with CSBD and 31 matched healthy controls. These results were then compared to the addiction and OCD patterns. RESULTS: Compared to controls, CSBD individuals showed significant fractional anisotropy (FA) reduction in the superior corona radiata tract, the internal capsule tract, cerebellar tracts and occipital gyrus white matter. Interestingly, all these regions were also identified in previous studies as shared DTI correlates in both OCD and addiction. DISCUSSION AND CONCLUSIONS: Results of our study suggest that CSBD shares similar pattern of abnormalities with both OCD and addiction. As one of the first DTI study comparing structural brain differences between CSBD, addictions and OCD, although it reveals new aspects of CSBD, it is insufficient to determine whether CSBD resembles more an addiction or OCD. Further research, especially comparing directly individuals with all three disorders may provide more conclusive results.

ObjectiveTo explore the specific alterations of white matter microstructure in children with attention-deficit/hyperactivity disorder (ADHD) by automated fiber quantification (AFQ) and tract-based spatial statistics (TBSS), and to analyze the correlation between white matter abnormality and impairment of executive function.MethodsIn this prospective study, a total of twenty-seven patients diagnosed with ADHD (20 males, 7 females; mean age of 8.89 ± 1.67 years) and twenty-two healthy control (HC) individuals (11 males, 11 females, mean age of 9.82 ± 2.13 years) were included. All participants were scanned with diffusion kurtosis imaging (DKI) and assessed for executive functions. AFQ and TBSS analysis methods were used to investigate the white matter fiber impairment of ADHD patients, respectively. Axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA) of 17 fiber properties were calculated using the AFQ. The mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MDDKI), axial diffusivity (ADDKI), radial diffusivity (RDDKI) and fractional anisotropy (FADKI) of DKI and AD, RD, MD, and FA of diffusion tensor imaging (DTI) assessed the integrity of the white matter based on TBSS. Partial correlation analyses were conducted to evaluate the correlation between white matter abnormalities and clinical test scores in ADHD while taking age, gender, and education years into account. The analyses were all family-wise error rate (FWE) corrected.ResultsADHD patients performed worse on the Behavior Rating Inventory of Executive Function (BRIEF) test (p 0.05, TFCE-corrected). Compared to HC volunteers, the mean AD value of right cingulum bundle (CB_R) fiber tract showed a significantly higher level in ADHD patients following the correction of FWE. As a result of the point-wise comparison between groups, significant alterations (FWE correction, p

IntroductionSensory Processing Dysfunction (SPD) is common yet understudied, affecting up to one in six children with 40% experiencing co-occurring challenges with attention. The neural architecture of SPD with Attention Deficit and Hyperactivity Disorder (ADHD) (SPD+ADHD) versus SPD without ADHD (SPD-ADHD) has yet to be explored in diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) has yet to be examined.MethodsThe present study computed DTI and NODDI biophysical model parameter maps of one hundred children with SPD. Global, regional and voxel-level white matter tract measures were analyzed and compared between SPD+ADHD and SPD-ADHD groups.ResultsSPD+ADHD children had global WM Fractional Anisotropy (FA) and Neurite Density Index (NDI) that trended lower than SPD-ADHD children, primarily in boys only. Data-driven voxelwise and WM tract-based analysis revealed statistically significant decreases of NDI in boys with SPD+ADHD compared to those with SPD-ADHD, primarily in projection tracts of the internal capsule and commissural fibers of the splenium of the corpus callosum.ConclusionWe conclude that WM microstructure is more delayed/disrupted in boys with SPD+ADHD compared to SPD-ADHD, with NODDI showing a larger effect than DTI. This may represent the combined WM pathology of SPD and ADHD, or it may result from a greater degree of SPD WM pathology causing the development of ADHD.

Introduction: Alterations to white matter microstructure as detected by diffusion tensor imaging have been documented in both individuals born with congenital heart disease (CHD) and individuals born preterm. However, it remains unclear if these disturbances are the consequence of similar underlying microstructural disruptions. This study used multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) and neurite orientation dispersion and density imaging (NODDI) to characterize and compare alterations to three specific microstructural elements of white matter - myelination, axon density, and axon orientation - in youth born with CHD or born preterm. Methods: Participants aged 16 to 26 years with operated CHD or born ≤33 weeks gestational age and a group of healthy peers of the same age underwent a brain MRI including mcDESPOT and high angular resolution diffusion imaging acquisitions. Using tractometry, average values of myelin water fraction (MWF), neurite density index (NDI), and orientation dispersion index (ODI) were first calculated and compared between groups for 30 white matter bundles. Afterwards, bundle profiling was performed to further characterize the topology of the detected microstructural alterations. Results: The CHD and preterm groups both presented with widespread bundles and bundle segments with lower MWF, accompanied by some occurrences of lower NDI, relative to controls. While there were no differences in ODI between the CHD and control groups, the preterm group presented with both higher and lower ODI compared to the control group and lower ODI compared to the CHD group. Discussion: While youth born with CHD or born preterm both presented with apparent deficits in white matter myelination and axon density, youth born preterm presented with a unique profile of altered axonal organization. Future longitudinal studies should aim to better understand the emergence of these common and distinct microstructural alterations, which could orient the development of novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Super typhoons can lead to post-traumatic stress disorder (PTSD), which can adversely affect a person's mental health after a disaster. Neuroimaging studies suggest that patients with PTSD may have post-exposure abnormalities of the white matter. However, little is known about these defects, if they are localized to specific regions of the white matter fibers, or whether they may be potential biomarkers for PTSD. Typhoon survivors with PTSD (n = 27), trauma-exposed controls (TEC) (n = 33), and healthy controls (HCs) (n = 30) were enrolled. We used automated fiber quantification (AFQ) to process the participants' DTI and compared diffusion metrics among the three groups. To evaluate diagnostic value, we used support vector machine (SVM) and a random forest (RF) classifier to build a machine learning model. White matter fiber segmentation between the three groups was found to be statistically significant for the fractional anisotropy (FA) value of the right anterior thalamic radiation (ATR) (26—50 nodes) and right uncinate fasciculus (UF) (60—72 nodes) (FDR correction, p < 0.05). By analyzing the characteristics of the machine learning model, the two most important variables were the right ATR and right UF for differentiating PTSD and trauma-exposed controls (TEC) from the healthy controls (HC). In addition, the left cingulum cingulate and left UF were the most critical variables in the differentiation of PTSD and TEC. AFQ with machine learning can localize abnormalities in specific regions of white matter fibers. These regions may be used as a diagnostic biomarker for PTSD. [ABSTRACT FROM AUTHOR]

Objectives: Leveraging a large population-level morphologic, microstructural, and functional neuroimaging dataset, we aimed to elucidate the underlying neurobiology of attention-deficit hyperactivity disorder (ADHD) in children. In addition, we evaluated the applicability of machine learning classifiers to predict ADHD diagnosis based on imaging and clinical information. Methods: From the Adolescents Behavior Cognitive Development (ABCD) database, we included 1,798 children with ADHD diagnosis and 6,007 without ADHD. In multivariate logistic regression adjusted for age and sex, we examined the association of ADHD with different neuroimaging metrics. The neuroimaging metrics included fractional anisotropy (FA), neurite density (ND), mean-(MD), radial-(RD), and axial diffusivity (AD) of white matter (WM) tracts, cortical region thickness and surface areas from T1-MPRAGE series, and functional network connectivity correlations from resting-state fMRI. Results: Children with ADHD showed markers of pervasive reduced microstructural integrity in white matter (WM) with diminished neural density and fiber-tracks volumes - most notable in the frontal and parietal lobes. In addition, ADHD diagnosis was associated with reduced cortical volume and surface area, especially in the temporal and frontal regions. In functional MRI studies, ADHD children had reduced connectivity among default-mode network and the central and dorsal attention networks, which are implicated in concentration and attention function. The best performing combination of feature selection and machine learning classifier could achieve a receiver operating characteristics area under curve of 0.613 (95% confidence interval = 0.580-0.645) to predict ADHD diagnosis in independent validation, using a combination of multimodal imaging metrics and clinical variables. Conclusion: Our study highlights the neurobiological implication of frontal lobe cortex and associate WM tracts in pathogenesis of childhood ADHD. We also demonstrated possible potentials and limitations of machine learning models to assist with ADHD diagnosis in a general population cohort based on multimodal neuroimaging metrics. [ABSTRACT FROM AUTHOR]

Altered white matter (WM) microstructure likely occurs in children with bipolar disorder (BD) with impulsivity representing one of the core features. However, altered WM microstructures and their age-related trendlines in children with BD and those at high-risk of developing BD, as well as correlations of WM microstructures with impulsivity, have been poorly investigated. In this study, diffusion MRI, cognitive, and impulsivity assessments were obtained from children/adolescents diagnosed with BD, offspring of individuals with BD (high-risk BD) and age-matched healthy controls. A novel atlas-based WM skeleton measurement approach was used to quantify WM microstructural integrity with all diffusion-tensor-imaging (DTI) metrics including fractional anisotropy, axial, mean and radial diffusivity to survey entire WM tracts and ameliorate partial volume effects. Among all DTI-derived metric measures, radial diffusivity quantifying WM myelination was found significantly higher primarily in corpus callosum and in the corona radiata in children with BD compared to controls. Distinguished from age-related progressively decreasing diffusivities and increasing fractional anisotropy in healthy controls, flattened age-related trendlines were found in BD group, and intermediate developmental rates were observed in high-risk group. Larger radial diffusivity in the corpus callosum and corona radiata significantly correlated with shorter response times to affective words that indicate higher impulsivity in the BD group, whereas no such correlation was found in the healthy control group. This work corroborates the progressive nature of pediatric BD and suggests that WM microstructural disruption involved in affective regulation and sensitive to impulsivity may serve as a biomarker of pediatric BD progression. • Atlas-based tract- and tract-group-quantification on white matter skeleton was used. • Altered white matter microstructure in pediatric bipolar disorder(BD) was delineated. • Correlations of white matter microstructure to impulsivity in pediatric BD were found. • Flattened microstructural age-related trendlines in children with BD were revealed. • Intermediate developmental rates were observed in high-risk BD group. [ABSTRACT FROM AUTHOR]

IntroductionAlterations to white matter microstructure as detected by diffusion tensor imaging have been documented in both individuals born with congenital heart disease (CHD) and individuals born preterm. However, it remains unclear if these disturbances are the consequence of similar underlying microstructural disruptions. This study used multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) and neurite orientation dispersion and density imaging (NODDI) to characterize and compare alterations to three specific microstructural elements of white matter – myelination, axon density, and axon orientation – in youth born with CHD or born preterm.MethodsParticipants aged 16 to 26 years with operated CHD or born ≤33 weeks gestational age and a group of healthy peers of the same age underwent a brain MRI including mcDESPOT and high angular resolution diffusion imaging acquisitions. Using tractometry, average values of myelin water fraction (MWF), neurite density index (NDI), and orientation dispersion index (ODI) were first calculated and compared between groups for 30 white matter bundles. Afterwards, bundle profiling was performed to further characterize the topology of the detected microstructural alterations.ResultsThe CHD and preterm groups both presented with widespread bundles and bundle segments with lower MWF, accompanied by some occurrences of lower NDI, relative to controls. While there were no differences in ODI between the CHD and control groups, the preterm group presented with both higher and lower ODI compared to the control group and lower ODI compared to the CHD group.DiscussionWhile youth born with CHD or born preterm both presented with apparent deficits in white matter myelination and axon density, youth born preterm presented with a unique profile of altered axonal organization. Future longitudinal studies should aim to better understand the emergence of these common and distinct microstructural alterations, which could orient the development of novel therapeutic approaches.

Visual working memory is critical for goal-directed behavior as it maintains continuity between previous and current visual input. Functional neuroimaging studies have shown that visual working memory relies on communication between distributed brain regions, which implies an important role for long-range white matter connections in visual working memory performance. Here, we characterized the relationship between the microstructure of white matter association tracts and the precision of visual working memory representations. To that purpose, we devised a delayed estimation task which required participants to reproduce visual features along a continuous scale. A sample of 80 healthy adults performed the task and underwent diffusion-weighted MRI. We applied mixture distribution modelling to quantify the precision of working memory representations, swap errors, and guess rates, all of which contribute to observed responses. Latent components of microstructural properties in sets of anatomical tracts were identified by principal component analysis. We found an interdependency between fibre coherence in the bilateral superior longitudinal fasciculus (SLF) I, SLF II, and SLF III, on one hand, and the bilateral inferior fronto-occipital fasciculus (IFOF), on the other, in mediating the precision of visual working memory in a functionally specific manner. We also found that individual differences in axonal density in a network comprising the bilateral inferior longitudinal fasciculus (ILF) and SLF III and right SLF II, in combination with a supporting network located elsewhere in the brain, form a common system for visual working memory to modulate response precision, swap errors, and random guess rates.

Background: The cerebellum is recognized as being involved in neurocognitive and motor functions with communication with extra-cerebellar regions relying on the white matter integrity of the cerebellar peduncles. However, the genetic determinants of cerebellar white matter integrity remain largely unknown. Methods: We conducted a genome-wide association analysis of cerebellar white matter microstructure using diffusion tensor imaging data from 25,415 individuals from UK Biobank. The integrity of cerebellar white matter microstructure was measured as fractional anisotropy (FA) and mean diffusivity (MD). Identification of independent genomic loci, functional annotation, and tissue and cell-type analysis were conducted with FUMA. The linkage disequilibrium score regression (LDSC) was used to calculate genetic correlations between cerebellar white matter microstructure and regional brain volumes and brain-related traits. Furthermore, the conditional/conjunctional false discovery rate (condFDR/conjFDR) framework was employed to identify the shared genetic basis between cerebellar white matter microstructure and common brain disorders. Results: We identified 11 genetic loci (P < 8.3 × 10−9) and 86 genes associated with cerebellar white matter microstructure. Further functional enrichment analysis implicated the involvement of GABAergic neurons and cholinergic pathways. Significant polygenetic overlap between cerebellar white matter tracts and their anatomically connected or adjacent brain regions was detected. In addition, we report the overall genetic correlation and specific loci shared between cerebellar white matter microstructural integrity and brain-related traits, including movement, cognitive, psychiatric, and cerebrovascular categories. Conclusions: Collectively, this study represents a step forward in understanding the genetics of cerebellar white matter microstructure and its shared genetic etiology with common brain disorders.

ObjectiveWhite matter (WM) microstructural changes are increasingly recognized as a mechanism of age-related cognitive differences. This study examined the associations between patterns of WM microstructure and cognitive performance on the University of California, San Francisco (UCSF) Brain Health Assessment (BHA) subtests of memory (Favorites), executive functions and speed (Match), and visuospatial skills (Line Orientation) within a sample of older adults.MethodFractional anisotropy (FA) in WM tracts and BHA performance were examined in 84 older adults diagnosed as neurologically healthy (47), with mild cognitive impairment (19), or with dementia (18). The relationships between FA and subtest performances were evaluated using regression analyses. We then explored whether regional WM predicted performance after accounting for variance explained by global FA.ResultsMemory performance was associated with FA of the fornix and the superior cerebellar peduncle; and executive functions and speed, with the body of the corpus callosum. The fornix-memory association and the corpus callosum-executive association remained significant after accounting for global FA. Neither tract-based nor global FA was associated with visuospatial performance.ConclusionsMemory and executive functions are associated with different patterns of WM diffusivity. Findings add insight into WM alterations underlying age- and disease-related cognitive decline.

IntroductionObesity has become a global public health issue, which impacts general health and the brain. Associations between obesity and white matter microstructure measured using diffusion tensor imaging have been under reviewed, despite a relatively large number of individual studies. Our objective was to determine the association between obesity and white matter microstructure in a large general population sample.MethodsWe analyzed location of brain white matter changes in obesity using the Anisotropic Effect Size Seed-based d Mapping (AES-SDM) method in a voxel-based meta-analysis, with validation in a region of interest (ROI) effect size meta-analysis. Our sample included 21 742 individuals from 51 studies.ResultsThe voxel-based spatial meta-analysis demonstrated reduced fractional anisotropy (FA) with obesity in the genu and splenium of the corpus callosum, middle cerebellar peduncles, anterior thalamic radiation, cortico-spinal projections, and cerebellum. The ROI effect size meta-analysis replicated associations between obesity and lower FA in the genu and splenium of the corpus callosum, middle cerebellar peduncles. Effect size of obesity related brain changes was small to medium.DiscussionOur findings demonstrate obesity related brain white matter changes are localized rather than diffuse. Better understanding the brain correlates of obesity could help identify risk factors, and targets for prevention or treatment of brain changes.

The opioid epidemic is an ongoing public health crisis, and children born following prenatal opioid exposure (POE) have increased risk of long-term cognitive and behavioral sequelae. Clinical studies have identified reduced gray matter volume and abnormal white matter microstructure in children with POE but impacts on whole-brain functional brain connectivity (FC) have not been reported. To define effects of POE on whole brain FC and white matter injury in adult animals, we performed quantitative whole-brain structural and functional MRI. We used an established rat model of POE in which we have previously reported impaired executive function in adult rats analogous to persistent neurocognitive symptoms described in humans with POE. Pregnant Sprague-Dawley rat dams received continuous methadone (12 mg/kg/day) vs. saline infusion for 28 days via osmotic mini-pumps, exposing rats to pre- and postnatal opioid until weaning. At young adult age (P60), POE and saline exposed offspring underwent in vivo MRI included diffusion tensor imaging and functional MRI (fMRI). Results indicate that fractional anisotropy (FA) was decreased in adult animals with POE [n = 11] compared to animals that received saline [n = 9] in major white matter tracts, including the corpus callosum (p 1). Taken together, these data confirm POE reduces brainwide functional connectivity as well as microstructural integrity of major white matter tracts. Altered neural circuitry, dysregulated network refinement, and diffuse network dysfunction have been implicated in executive function deficits that are common in children with POE. FC may serve as a translatable biomarker in children with POE.

Hypertension has been well recognized as a risk factor for cognitive impairment and dementia. Although the underlying mechanisms of hypertension-affected cognitive deterioration are not fully understood, white matter changes (WMCs) seem to play an important role. WMCs include low microstructural integrity and subsequent white matter macrostructural lesions, which are common on brain imaging in hypertensive patients and are critical for multiple cognitive domains. This article provides an overview of the impact of hypertension on white matter microstructural and macrostructural changes and its link to cognitive dysfunction. Hypertension may induce microstructural changes in white matter, especially for the long-range fibers such as anterior thalamic radiation (ATR) and inferior fronto-occipital fasciculus (IFOF), and then macrostructural abnormalities affecting different lobes, especially the periventricular area. Different regions’ WMCs would further exert different effects to specific cognitive domains and accelerate brain aging. As a modifiable risk factor, hypertension might provide a new perspective for alleviating and delaying cognitive impairment.

Background: Peer connections in school classrooms play an important role in social–emotional development and mental health. However, research on the association between children's peer relationships and white matter connections in the brain is scarce. We studied associations between peer relationships in the classroom and white matter structural connectivity in a pediatric population‐based sample. Methods: Bullying and victimization, as well as rejection and acceptance, were assessed in classrooms in 634 children at age 7. White matter microstructure (fractional anisotropy (FA), mean diffusivity (MD)) was measured with diffusion tensor imaging at age 10. We examined global metrics of white matter microstructure and used Tract‐Based Spatial Statistics (TBSS) for voxel‐wise associations. Results: Peer victimization was associated with higher global FA and lower global MD and peer rejection was associated with lower global MD; however, these associations did not remain after multiple testing correction. Voxel‐wise TBSS results for peer victimization and rejection were in line with global metrics both in terms of direction and spatial extent of the associations, with associated voxels (pFWE <.05) observed throughout the brain (including corpus callosum, corona radiata, sagittal stratum and superior longitudinal fasciculi). Conclusions: Although based only on cross‐sectional data, the findings could indicate accelerated white matter microstructure maturation in certain brain areas of children who are victimized or rejected more often. However, repeated measurements are essential to unravel this complex interplay of peer connections, maturation and brain development over time. [ABSTRACT FROM AUTHOR]

• In NMOSD patients, pRNFL and GCC thicknesses correlated with their white matter microstructural integrity. • White matter microstructural changes and retinal structural changes are associated with their clinical outcomes in NMOSD patients. • Retinal imaging of the retinal structure provides evidence of neurodegeneration that may underpin cerebral neurodegeneration in NMOSD. Thinning of retinal thickness seen on optical coherence tomography (OCT) is frequent in patients with neuromyelitis optica spectrum disorder (NMOSD). We explored the association between OCT metrics, MRI measurements and clinical outcomes in NMOSD. 44 NMOSD and 60 controls underwent OCT and MR imaging. Mean peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell complex (GCC) thicknesses were measured. Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) was used to measure the white matter microstructural integrity. In NMOSD patients, Expanded Disability Status Scale (EDSS) was used to quantify disability. Visual acuity (VA) was also performed for all participants. pRNFL thickness was positively associated with mean diffusivity in left posterior thalamic radiation (pp = 0.010) and axial kurtosis in inferior cerebellar peduncle (p = 0.023). Similarly, GCC thickness in NMOSD patients was positively associated with fractional anisotropy in right superior longitudinal fascicules (p = 0. 041) and axial kurtosis of left cerebellar peduncle (p = 0.011). In NMOSD, pRNFL and GCC reflect integrity of clinically relevant white matter structures underlying the value of OCT metrics as markers of neuronaxonal loss and disability. [ABSTRACT FROM AUTHOR]

We aimed to identify important features of white matter microstructures collectively distinguishing individuals with attention-deficit/hyperactivity disorder (ADHD) from those without ADHD using a machine-learning approach. Fifty-one ADHD patients and 60 typically developing controls (TDC) underwent diffusion spectrum imaging at two time points. We evaluated three models to classify ADHD and TDC using various machine-learning algorithms. Model 1 employed baseline white matter features of 45 white matter tracts at Time 1; Model 2 incorporated features from both time points; and Model 3 (main analysis) further included the relative rate of change per year of white matter tracts. The random forest algorithm demonstrated the best performance for classification. Model 1 achieved an area-under-the-curve (AUC) of 0.67. Model 3, incorporating Time 2 variables and relative rate of change per year, improved the performance (AUC = 0.73). In addition to identifying several white matter features at two time points, we found that the relative rate of change per year in the superior longitudinal fasciculus, frontal aslant tract, stria terminalis, inferior fronto-occipital fasciculus, thalamic and striatal tracts, and other tracts involving sensorimotor regions are important features of ADHD. A higher relative change rate in certain tracts was associated with greater improvement in visual attention, spatial short-term memory, and spatial working memory. Our findings support the significant diagnostic value of white matter microstructure and the developmental change rates of specific tracts, reflecting deviations from typical development trajectories, in identifying ADHD. • Machine-learning approaches can distinguish individuals with and without ADHD through white matter analysis. • Annual changes in white matter microstructures enhance diagnostic ability, achieving an AUC of 0.73. • Annual changes in specific white matter tracts are linked to cognitive improvements in ADHD. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) is a serious eating disorder characterized by self-starvation and extreme weight loss. Pseudoatrophic brain changes are often readily visible in individual brain scans, and AN may be a valuable model disorder to study structural neuroplasticity. Structural magnetic resonance imaging studies have found reduced gray matter volume and cortical thinning in acutely underweight patients to normalize following successful treatment. However, some well-controlled studies have found regionally greater gray matter and persistence of structural alterations following long-term recovery. Findings from diffusion tensor imaging studies of white matter integrity and connectivity are also inconsistent. Furthermore, despite the severity of AN, the number of existing structural neuroimaging studies is still relatively low, and our knowledge of the underlying cellular and molecular mechanisms for macrostructural brain changes is rudimentary. We critically review the current state of structural neuroimaging in AN and discuss the potential neurobiological basis of structural brain alterations in the disorder, highlighting impediments to progress, recent developments, and promising future directions. In particular, we argue for the utility of more standardized data collection, adopting a connectomics approach to understanding brain network architecture, employing advanced magnetic resonance imaging methods that quantify biomarkers of brain tissue microstructure, integrating data from multiple imaging modalities, strategic longitudinal observation during weight restoration, and large-scale data pooling. Our overarching objective is to motivate carefully controlled research of brain structure in eating disorders, which will ultimately help predict therapeutic response and improve treatment.

In MRI the transverse relaxation rate, R2 = 1/T2, shows dependence on the orientation of ordered tissue relative to the main magnetic field. In previous studies, orientation effects of R2 relaxation in the mature brain's white matter have been found to be described by a susceptibility-based model of diffusion through local magnetic field inhomogeneities created by the diamagnetic myelin sheaths. Orientation effects in human newborn white matter have not yet been investigated. The newborn brain is known to contain very little myelin and is therefore expected to exhibit a decrease in orientation dependence driven by susceptibility-based effects. We measured R2 orientation dependence in the white matter of human newborns. R2 data were acquired with a 3D Gradient and Spin Echo (GRASE) sequence and fiber orientation was mapped with diffusion tensor imaging (DTI). We found orientation dependence in newborn white matter that is not consistent with the susceptibility-based model and is best described by a model of residual dipolar coupling. In the near absence of myelin in the newborn brain, these findings suggest the presence of residual dipolar coupling between rotationally restricted water molecules. This has important implications for quantitative imaging methods such as myelin water imaging, and suggests orientation dependence of R2 as a potential marker in early brain development.

White matter (WM) alterations have been observed in Huntington disease (HD) but their role in the disease‐pathophysiology remains unknown. We assessed WM changes in premanifest HD by exploiting ultra‐strong‐gradient magnetic resonance imaging (MRI). This allowed to separately quantify magnetization transfer ratio (MTR) and hindered and restricted diffusion‐weighted signal fractions, and assess how they drove WM microstructure differences between patients and controls. We used tractometry to investigate region‐specific alterations across callosal segments with well‐characterized early‐ and late‐myelinating axon populations, while brain‐wise differences were explored with tract‐based cluster analysis (TBCA). Behavioral measures were included to explore disease‐associated brain‐function relationships. We detected lower MTR in patients' callosal rostrum (tractometry: p =.03; TBCA: p =.03), but higher MTR in their splenium (tractometry: p =.02). Importantly, patients' mutation‐size and MTR were positively correlated (all p‐values <.01), indicating that MTR alterations may directly result from the mutation. Further, MTR was higher in younger, but lower in older patients relative to controls (p =.003), suggesting that MTR increases are detrimental later in the disease. Finally, patients showed higher restricted diffusion signal fraction (FR) from the composite hindered and restricted model of diffusion (CHARMED) in the cortico‐spinal tract (p =.03), which correlated positively with MTR in the posterior callosum (p =.033), potentially reflecting compensatory mechanisms. In summary, this first comprehensive, ultra‐strong gradient MRI study in HD provides novel evidence of mutation‐driven MTR alterations at the premanifest disease stage which may reflect neurodevelopmental changes in iron, myelin, or a combination of these. [ABSTRACT FROM AUTHOR]

The beneficial effects of physical activity on neurocognitive functioning in children are considered to be facilitated by physical activity‐induced changes in brain structure and functioning. In this study, we examined the effects of two 14‐week school‐based exercise interventions in healthy children on white matter microstructure and brain activity in resting‐state networks (RSNs) and whether changes in white matter microstructure and RSN activity mediate the effects of the exercise interventions on neurocognitive functioning. A total of 93 children were included in this study (51% girls, mean age 9.13 years). The exercise interventions consisted of four physical education lessons per week, focusing on either aerobic or cognitively demanding exercise and were compared with a control group that followed their regular physical education program of two lessons per week. White matter microstructure was assessed using diffusion tensor imaging in combination with tract‐based spatial statistics. Independent component analysis was performed on resting‐state data to identify RSNs. Furthermore, neurocognitive functioning (information processing and attention, working memory, motor response inhibition, interference control) was assessed by a set of computerized tasks. Results indicated no Group × Time effects on white matter microstructure or RSN activity, indicating no effects of the exercise interventions on these aspects of brain structure and function. Likewise, no Group × Time effects were found for neurocognitive performance. This study indicated that 14‐week school‐based interventions regarding neither aerobic exercise nor cognitive‐demanding exercise interventions influence brain structure and brain function in healthy children. This study was registered in the Netherlands Trial Register (NTR5341). The increase of a sedentary lifestyle among children urges the need to better understand how exercise promotes neurocognitive functioning during development. The beneficial effects of physical activity on neurocognitive functioning in children are considered to be facilitated by physical activity‐induced changes in brain structure and functioning. This randomized controlled trial demonstrates that 14‐week aerobic and cognitively demanding exercise interventions were not sufficient to provoke changes in brain structure and function in healthy children. [ABSTRACT FROM AUTHOR]

Higher physical activity levels are associated with reduced cognitive decline among older adults; however, current understanding of underlying brain mechanisms is limited. This cross-sectional study investigated the relationship between actigraphy-estimated total volume of physical activity (TVPA) and magnetic resonance imaging (MRI) measures of white matter hyperintensities (WMH), and functional and structural brain connectivity, measured by resting-state functional MRI and diffusion tensor imaging. Study participants (N = 156, mean age = 71 years) included 136 with normal cognition and 20 with Mild Cognitive Impairment. Higher TVPA was associated with greater functional connectivity within the default-mode network and greater network modularity (a measure of network specialization), as well as with greater anisotropy and lower radial diffusion in white matter, suggesting better structural connectivity. These associations with functional and structural connectivity were independent of one another and independent of the level of vascular risk, APOE-ε4 status, cognitive reserve, and WMH volume, which were not associated with TVPA. Findings suggest that physical activity is beneficial for brain connectivity among older individuals with varying levels of risk for cognitive decline. [ABSTRACT FROM AUTHOR]

Background: While it is well established that second language (L2) learning success changes with age and across individuals, the underlying neural mechanisms responsible for this developmental shift and these individual differences are largely unknown. We will study the behavioral and neural factors that subserve new grammar and word learning in a large cross-sectional developmental sample. This study falls under the NWO (Nederlandse Organisatie voor Wetenschappelijk Onderzoek [Dutch Research Council]) Language in Interaction consortium (website: https://www.languageininteraction.nl/). Methods: We will sample 360 healthy individuals across a broad age range between 8 and 25 years. In this paper, we describe the study design and protocol, which involves multiple study visits covering a comprehensive behavioral battery and extensive magnetic resonance imaging (MRI) protocols. On the basis of these measures, we will create behavioral and neural fingerprints that capture age-based and individual variability in new language learning. The behavioral fingerprint will be based on first and second language proficiency, memory systems, and executive functioning. We will map the neural fingerprint for each participant using the following MRI modalities: T1‐weighted, diffusion-weighted, resting-state functional MRI, and multiple functional-MRI paradigms. With respect to the functional MRI measures, half of the sample will learn grammatical features and half will learn words of a new language. Combining all individual fingerprints allows us to explore the neural maturation effects on grammar and word learning. Discussion: This will be one of the largest neuroimaging studies to date that investigates the developmental shift in L2 learning covering preadolescence to adulthood. Our comprehensive approach of combining behavioral and neuroimaging data will contribute to the understanding of the mechanisms influencing this developmental shift and individual differences in new language learning. We aim to answer: (I) do these fingerprints differ according to age and can these explain the age-related differences observed in new language learning? And (II) which aspects of the behavioral and neural fingerprints explain individual differences (across and within ages) in grammar and word learning? The results of this study provide a unique opportunity to understand how the development of brain structure and function influence new language learning success. [ABSTRACT FROM AUTHOR]

White matter pathology is common across a wide spectrum of neurological diseases. Characterizing this pathology is important for both a mechanistic understanding of neurological diseases as well as for the development of neuroimaging biomarkers. Although axonal calibers can vary by orders of magnitude, they are tightly regulated and related to neuronal function, and changes in axon calibers have been reported in several diseases and their models. In this study, we utilize the impact acceleration model of traumatic brain injury (IA-TBI) to assess early and late changes in the axon diameter distribution (ADD) of the mouse corticospinal tract using Airyscan and electron microscopy. We find that axon calibers follow a lognormal distribution whose parameters significantly change after injury. While IA-TBI leads to 30% loss of corticospinal axons by day 7 with a bias for larger axons, at 21 days after injury we find a significant redistribution of axon frequencies that is driven by a reduction in large-caliber axons in the absence of detectable degeneration. We postulate that changes in ADD features may reflect a functional adaptation of injured neural systems. Moreover, we find that ADD features offer an accurate way to discriminate between injured and non-injured mice. Exploring injury-related ADD signatures by histology or new emerging neuroimaging modalities may offer a more nuanced and comprehensive way to characterize white matter pathology and may also have the potential to generate novel biomarkers of injury. [ABSTRACT FROM AUTHOR]

Motor adaptations to the microgravity environment during spaceflight allow astronauts to perform adequately in this unique environment. Upon return to Earth, this adaptation is no longer appropriate and can be disruptive for mission critical tasks. Here, we measured if metrics derived from MRI scans collected from astronauts can predict motor performance post-flight. Structural and diffusion MRI scans from 14 astronauts collected before launch, and motor measures (balance performance, speed of recovery from fall, and tandem walk step accuracy) collected pre-flight and post-flight were analyzed. Regional measures of gray matter volume (motor cortex, paracentral lobule, cerebellum), myelin density (motor cortex, paracentral lobule, corticospinal tract), and white matter microstructure (corticospinal tract) were derived as a-priori predictors. Additional whole-brain analyses of cortical thickness, cerebellar gray matter, and cortical myelin were also tested for associations with post-flight and pre-to-post-flight motor performance. The pre-selected regional measures were not significantly associated with motor behavior. However, whole-brain analyses showed that paracentral and precentral gyri thickness significantly predicted recovery from fall post-spaceflight. Thickness of vestibular and sensorimotor regions, including the posterior insula and the superior temporal gyrus, predicted balance performance post-flight and pre-to-post-flight decrements. Greater cortical thickness pre-flight predicted better performance post-flight. Regional thickness of somatosensory, motor, and vestibular brain regions has some predictive value for post-flight motor performance in astronauts, which may be used for the identification of training and countermeasure strategies targeted for maintaining operational task performance. [ABSTRACT FROM AUTHOR]

Background: Observational studies have reported changes in the brain white matter (WM) microstructure in patients with inflammatory bowel disease (IBD); however, it remains uncertain whether the relationship between them is causative. The aim of this study is to reveal the potential causal relationship between IBD and WM microstructure through a bidirectional two-sample Mendelian randomization (MR) analysis., Methods: We extracted genome-wide association study (GWAS) summary statistics for IBD and WM microstructure from published GWASs. Two-sample MR analysis was conducted to explore the bidirectional causal associations between IBD and WM microstructure, followed by a series of sensitivity analyses to assess the robustness of the results., Results: Although forward MR analysis results showed no evidence of causality from microstructural WM to IBD, reverse MR showed that genetically predicted IBD, consisting of ulcerative colitis and Crohn's disease, has a significant causal effect on the orientation dispersion index (OD) of the right tapetum (β = -0.029, 95% CI = -0.045 to -0.013, p = 3.63 × 10 -4 ). Further sensitivity analysis confirmed the robustness of the association., Conclusion: Our results suggested the potentially causal association of IBD with reduced OD in the right tapetum., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Maternal adverse childhood experiences (ACEs) are robust predictors of mental health for both the exposed individual and the next generation; however, the pathway through which such intergenerational risk is conferred remains unknown. The current study evaluated the association between maternal ACEs and infant brain development, including an a priori focus on circuits implicated in emotional and sensory processing., Methods: The sample included 101 mother-infant dyads from a longitudinal study. Maternal ACEs were assessed with the Adverse Childhood Questionnaire dichotomized into low (0 or 1) and high (≥2) groups. White matter microstructure, as indexed by fractional anisotropy (FA), was assessed using structural magnetic resonance imaging in infants (41.6-46.0 weeks' postconceptional age) within a priori tracts (the cingulum, fornix, uncinate, inferior frontal occipital fasciculus, and inferior longitudinal fasciculus). Exploratory analyses were also conducted across the whole brain., Results: High maternal ACEs (≥2) were associated with decreased infant left inferior longitudinal fasciculus (ILF) FA (F(1,94) = 7.78, p < .006) relative to infants of low ACE mothers. No group difference was observed within the right ILF following correction for multiple comparisons (F(1,95) = 4.29, p < .041). Follow-up analyses within the left ILF demonstrated associations between high maternal ACEs and increased left radial diffusivity (F(1,95) = 5.10, p < .006). Exploratory analyses demonstrated preliminary support for differences in visual processing networks (e.g., optic tract) as well as additional circuits less frequently examined in the context of early life adversity exposure (e.g., corticothalamic tract)., Conclusions: Maternal ACEs predict neural circuit development of the inferior longitudinal fasciculus. Findings suggest that early developing sensory circuits within the infant brain are susceptible to maternal adverse childhood experiences and may have implications for the maturation of higher-order emotional and cognitive circuits., Competing Interests: Declaration of competing interest CNE was an investigator for a multisite clinical trial conducted by Sage Therapeutics. She is also a consultant to EmbarkNeuro, Skyland Trail, and Health Rhythms and a member of the scientific advisory board of Babyscripts. No funding or involvement from these entities was used to support the current work, and all views expressed are solely those of the authors. All other authors have no conflicts of interest or relevant disclosures., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Recent evidence suggests an association of air pollution exposure with brain development, but evidence on white matter microstructure in children is scarce. We investigated how air pollution exposure during pregnancy and childhood impacts longitudinal development of white matter microstructure throughout adolescence., Methods: Our study population consisted of 4,108 participants of Generation R, a large population-based birth cohort from Rotterdam, the Netherlands. Residential air pollution exposure to 14 air pollutants during pregnancy and childhood was estimated with land-use regression models. Diffusion tensor images were obtained around age 10 and 14, resulting in a total of 5,422 usable scans (n=3,082 for wave 1 and n=2,340 for wave 2; n= 1,314 for participants with data on both waves). We calculated whole-brain fractional anisotropy (FA) and mean diffusivity (MD) and performed single- and multi-pollutant analyses using mixed effects models adjusted for life-style and socioeconomic status variables., Results: Higher exposure to PM 2.5 during pregnancy, and PM 10 , PM 2.5 , PM 2.5-10 , and NO X during childhood was associated with a consistently lower whole-brain FA throughout adolescence (e.g. - 0.07×10 -2 FA [95%CI -0.12; -0.02] per 1 standard deviation higher PM 2.5 exposure during pregnancy). Higher exposure to silicon (Si) in PM 2.5 and oxidative potential of PM 2.5 during pregnancy, and PM 2.5 during childhood was associated with an initial higher MD followed by a faster decrease in MD throughout adolescence (e.g. - 0.02×10 -5 mm 2 /s MD [95%CI -0.03; -0.00] per year of age per 1 standard deviation higher Si exposure during pregnancy). Results were comparable when performing the analysis in children with complete data on the outcome for both neuroimaging assessments., Conclusions: Exposure to several pollutants was associated with a consistently lower whole-brain FA throughout adolescence. The association of few pollutants with whole-brain MD at baseline attenuated throughout adolescence. These findings suggest both persistent and age-limited associations of air pollution exposure with white matter microstructure., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024. Published by Elsevier Inc.)

Objective: Posttraumatic headache (PTH) represents the most common acute and persistent postconcussive symptom (PCS) in children after concussion, yet there remains a lack of valid and objective biomarkers to facilitate risk stratification and early intervention in this patient population. Fixel-based analysis of diffusion-weighted imaging, which overcomes constraints of traditional diffusion tensor imaging analyses, can improve the sensitivity and specificity of detecting white matter changes postconcussion. The aim of this study was to investigate whole-brain and tract-based differences in white matter morphology, including fiber density (FD) and fiber bundle cross-section (FC) area in children with PCSs and PTH at 2 weeks after concussion., Methods: This prospective longitudinal study recruited children aged 5-18 years who presented to the emergency department of a tertiary pediatric hospital with a concussion sustained within the previous 48 hours. Participants underwent diffusion-weighted MRI at 2 weeks postinjury. Whole-brain white matter statistical analysis was performed at the level of each individual fiber population within an image voxel (fixel) to compute FD, FC, and a combined metric (FD and bundle cross-section [FDC]) using connectivity-based fixel enhancement. Tract-based Bayesian analysis was performed to examine FD in 23 major white matter tracts., Results: Comparisons of 1) recovered (n = 27) and symptomatic (n = 16) children, and those with 2) PTH (n = 13) and non-PTH (n = 30; overall mean age 12.99 ± 2.70 years, 74% male) found no fiber-specific white matter microstructural differences in FD, FC, or FDC at 2 weeks postconcussion, when adjusting for age and sex (family-wise error rate corrected p value > 0.05). Tract-based Bayesian analysis showed evidence of no effect of PTH on FD in 10 major white matter tracts, and evidence of no effect of recovery group on FD in 3 white matter tracts (Bayes factor < 1/3)., Conclusions: Using whole-brain fixel-wise and tract-based analyses, these findings indicate that fiber-specific properties of white matter microstructure are not different between children with persisting PCSs compared with recovered children 2 weeks after concussion. These data extend the limited research on white matter fiber-specific morphology while overcoming limitations inherent to traditional diffusion models. Further validation of our findings with a large-scale cohort is warranted.

Objective: This study examined the association of lifetime experiences, measured by a cognitive reserve (CR) composite score composed of years of education, literacy, and vocabulary measures, to level and rate of change in white matter microstructure, as assessed by diffusion tensor imaging (DTI) measures. We also examined whether the relationship between the proxy CR composite score and white matter microstructure was modified by participant age, APOE -ε4 genetic status, and level of vascular risk. Methods: A sample of 192 non-demented (n = 166 cognitively normal, n = 26 mild cognitive impairment) older adults [mean age = 70.17 (SD = 8.5) years] from the BIOCARD study underwent longitudinal DTI (mean follow-up = 2.5 years, max = 4.7 years). White matter microstructure was quantified by fractional anisotropy (FA) and radial diffusivity (RD) values in global white matter tracts and medial temporal lobe (MTL) white matter tracts. Results: Using longitudinal linear mixed effect models, we found that FA decreased over time and RD increased over time in both the global and MTL DTI composites, but the rate of change in these DTI measures was not related to level of CR. However, there were significant interactions between the CR composite score and age for global RD in the full sample, and for global FA, global RD, and MTL RD among those with normal cognition. These interactions indicated that among participants with a lower baseline age, higher CR composite scores were associated with higher FA and lower RD values, while among participants with higher age at baseline, higher CR composite scores were associated with lower FA and higher RD values. Furthermore, these relationships were not modified by APOE -ε4 genotype or level of vascular risk. Conclusion: The association between level of CR and DTI measures differs by age, suggesting a possible neuroprotective effect of CR among late middle-aged adults that shifts to a compensatory effect among older adults. [ABSTRACT FROM AUTHOR]

Background: Children with trigonocephaly are at risk for neurodevelopmental disorders. The aim of this study is to investigate white matter properties of the frontal lobes in young, unoperated patients with metopic synostosis as compared to healthy controls using diffusion tension imaging (DTI).Methods: Preoperative DTI data sets of 46 patients with trigonocephaly with a median age of 0.49 (interquartile range: 0.38) years were compared with 21 controls with a median age of 1.44 (0.98) years. White matter metrics of the tracts in the frontal lobe were calculated using FMRIB Software Library (FSL). The mean value of tract-specific fractional anisotropy (FA) and mean diffusivity (MD) were estimated for each subject and compared to healthy controls. By linear regression, FA and MD values per tract were assessed by trigonocephaly, sex, and age.Results: The mean FA and MD values in the frontal lobe tracts of untreated trigonocephaly patients, younger than 3 years, were not significantly different in comparison to controls, where age showed to be a significant associated factor.Conclusions: Microstructural parameters of white matter tracts of the frontal lobe of patients with trigonocephaly are comparable to those of controls aged 0-3 years. [ABSTRACT FROM AUTHOR]