Social network size, empathy, and white matter: A diffusion tensor imaging (DTI) study.

Social networks are fundamental for social interactions, with the social brain hypothesis positing that the size of the neocortex evolved to meet social demands. However, the role of fractional anisotropy (FA) in white matter (WM) tracts relevant to mentalizing, empathy, and social networks remains unclear. In this study, we investigated the relationships between FA in brain regions associated with social cognition (superior longitudinal fasciculus (SLF), cingulum (CING), uncinate fasciculus, inferior fronto-occipital fasciculus), social network characteristics (diversity, size, complexity), and empathy (cognitive, affective). We employed diffusion tensor imaging, tract-based spatial statistics, and mediation analyses to examine these associations. Our findings revealed that increased social network size was positively correlated with FA in the left SLF. Further, our mediation analysis showed that lower FA in left CING was associated with increased social network size, mediated by cognitive empathy. In summary, our findings suggest that WM tracts involved in social cognition play distinct roles in social network size and empathy, potentially implicating affective brain regions. In conclusion, our findings offer new perspectives on the cognitive mechanisms involved in understanding others' mental states and experiencing empathy within supportive social networks, with potential implications for understanding individual differences in social behavior and mental health.

Effect of Xiaoyaosan on brain volume and microstructure diffusion changes to exert antidepressant-like effects in mice with chronic social defeat stress.

Objective: Depression is a prevalent mental disorder characterized by persistent negative mood and loss of pleasure. Although there are various treatment modalities available for depression, the rates of response and remission remain low. Xiaoyaosan (XYS), a traditional Chinese herbal formula with a long history of use in treating depression, has shown promising effects. However, the underlying mechanism of its therapeutic action remains elusive. The aim of this study is to investigate the neuroimaging changes in the brain associated with the antidepressant-like effects of XYS. Methods: Here, we combined voxel-based morphometry of T2-weighted images and voxel-based analysis on diffusion tensor images to evaluate alterations in brain morphometry and microstructure between chronic social defeat stress (CSDS) model mice and control mice. Additionally, we examined the effect of XYS treatment on structural disruptions in the brains of XYS-treated mice. Furthermore, we explored the therapeutic effect of 18ß-glycyrrhetinic acid (18ß-GA), which was identified as the primary compound present in the brain following administration of XYS. Significant differences in brain structure were utilized as classification features for distinguishing mice with depression model form the controls using a machine learning method. Results: Significant changes in brain volume and diffusion metrics were observed in the CSDS model mice, primarily concentrated in the nucleus accumbens (ACB), primary somatosensory area (SSP), thalamus (TH), hypothalamus (HY), basomedical amygdala nucleus (BMA), caudoputamen (CP), and retrosplenial area (RSP). However, both XYS and 18ß-GA treatment prevented disruptions in brain volume and diffusion metrics in certain regions, including bilateral HY, right SSP, right ACB, bilateral CP, and left TH. The classification models based on each type of neuroimaging feature achieved high accuracy levels (gray matter volume: 76.39%, AUC=0.83; white matter volume: 76.39%, AUC=0.92; fractional anisotropy: 82.64%, AUC=0.9; radial diffusivity: 76.39%, AUC=0.82). Among these machine learning analyses, the right ACB, right HY, and right CP were identified as the most important brain regions for classification purposes. Conclusion: These findings suggested that XYS can prevent abnormal changes in brain volume and microstructure within TH, SSP, ACB, and CP to exert prophylactic antidepressant-like effects in CSDS model mice. The neuroimaging features within these regions demonstrate excellent performance for classifying CSDS model mice from controls while providing valuable insights into the antidepressant effects of XYS.

Explainable artificial intelligence on safe balance and its major determinants in stroke patients.

This study develops explainable artificial intelligence for predicting safe balance using hospital data, including clinical, neurophysiological, and diffusion tensor imaging properties. Retrospective data from 92 first-time stroke patients from January 2016 to June 2023 was analysed. The dependent variables were independent mobility scores, i.e., Berg Balance Scales with 0 (45 or below) vs. 1 (above 45) measured after three and six months, respectively. Twenty-nine predictors were included. Random forest variable importance was employed for identifying significant predictors of the Berg Balance Scale and testing its associations with the predictors, including Berg Balance Scale after one month and corticospinal tract diffusion tensor imaging properties. Shapley Additive Explanation values were calculated to analyse the directions of these associations. The random forest registered a higher or similar area under the curve compared to logistic regression, i.e., 91% vs. 87% (Berg Balance Scale after three months), 92% vs. 92% (Berg Balance Scale after six months). Based on random forest variable importance values and rankings: (1) Berg Balance Scale after three months has strong associations with Berg Balance Scale after one month, Fugl-Meyer assessment scale, ipsilesional corticospinal tract fractional anisotropy, fractional anisotropy laterality index and age; (2) Berg Balance Scale after six months has strong relationships with Fugl-Meyer assessment scale, Berg Balance Scale after one month, ankle plantar flexion muscle strength, knee extension muscle strength and hip flexion muscle strength. These associations were positive in the SHAP summary plots. Including Berg Balance Scale after one month, Fugl-Meyer assessment scale or ipsilesional corticospinal tract fractional anisotropy in the random forest will increase the probability of Berg Balance Scale after three months being above 45 by 0.11, 0.08, or 0.08. In conclusion, safe balance after stroke strongly correlates with its initial motor function, Fugl-Meyer assessment scale, and ipsilesional corticospinal tract fractional anisotropy. Diffusion tensor imaging information aids in developing explainable artificial intelligence for predicting safe balance after stroke.

Development of white matter in young adulthood: The speed of brain aging and its relationship with changes in fractional anisotropy.

White matter (WM) development has been studied extensively, but most studies used cross-sectional data, and to the best of our knowledge, none of them considered the possible effects of biological (vs. chronological) age. Therefore, we conducted a longitudinal multimodal study of WM development and studied changes in fractional anisotropy (FA) in the different WM tracts and their relationship with cortical thickness-based measures of brain aging in young adulthood. A total of 105 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort underwent magnetic resonance imaging (MRI) at the age of 23-24, and the age of 28-30 years. At both time points, FA in the different WM tracts was extracted using the JHU atlas, and brain age gap estimate (BrainAGE) was calculated using the Neuroanatomical Age Prediction using R (NAPR) model based on cortical thickness maps. Changes in FA and the speed of cortical brain aging were calculated as the difference between the respective variables in the late vs. early 20s. We demonstrated tract-specific increases as well as decreases in FA, which indicate that the WM microstructure continues to develop in the third decade of life. Moreover, the significant interaction between the speed of cortical brain aging, tract, and sex on mean FA revealed that a greater speed of cortical brain aging in young adulthood predicted greater decreases in FA in the bilateral cingulum and left superior longitudinal fasciculus in young adult men. Overall, these changes in FA in the WM tracts in young adulthood point out the protracted development of WM microstructure, particularly in men.

Role of diffusion tensor imaging in the evaluation of white matter integrity in idiopathic intracranial hypertension.

OBJECTIVES: To determine whether idiopathic intracranial hypertension (IIH) may affect white matter integrity and optic pathways by using diffusion tensor imaging (DTI) and to correlate the DTI metrics with intracranial pressure (ICP). METHODS: This study is a retrospective case-control study. A total of 42 patients who underwent lumbar puncture and those with elevated ICP, meeting the diagnostic criteria for IIH, were included in the study. All patients had supportive magnetic resonance imaging findings for the diagnosis of IIH. The headache control group comprised 36 patients who presented to the Neurology Department with infrequent episodic tension-type headache, had a normal neurologic examination, and had clinical and radiological findings suggestive of normal ICP. For each patient with IIH, clinical findings and ophthalmological measurements were recorded. The apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) values were calculated using a region of interest-based method in different white matter tracts and optic pathways and compared. RESULTS: A total of 42 patients diagnosed with IIH (three males, 39 females), with a mean (standard deviation [SD] age of 38.1 (8.9) years), and 36 headache controls (10 males, 26 females, mean [SD] age; 38.1 [9.4] years) were included in the study. The mean (SD) body mass index (BMI) of the patients with IIH was 25.2 (1.9) kg/m2, and the mean (SD) BMI of the headache controls was 23.3 (1.5) kg/m2 (p < 0.001). Decreased FA values and increased RD values in the cingulum were detected in patients with IIH compared to the headache controls (p = 0.003, Cohen's d = 0.681; p = 0.002 Cohen's d = -0.710). Decreased AD values in the left and right superior cerebellar peduncle and increased ADC values in the middle cerebellar peduncle were detected in patients with IIH compared to the headache controls (p < 0.001, Cohen's d = 0.961; p = 0.009, Cohen's d = 0.607; p = 0.015, Cohen's d = -0.564). Increased ADC and RD values and decreased FA values in optic nerve were detected in patients with IIH (p = 0.010, Cohen's d = -0.603; p = 0.004, Cohen's d = -0.676; p = 0.015 Cohen's d = 0.568). A positive correlation was found between the cerebrospinal fluid pressure and ADC values of the left and right superior and left inferior longitudinal fasciculus, genu of the corpus callosum, and right optic radiation (r = 0.43, p = 0.005; r = 0.31, p = 0.044; r = 0.39, p = 0.010; r = 0.35, p = 0.024; r = 0,41, p = 0.007). There was a positive correlation between the retinal nerve fiber layer thickness and the ADC values of the optic nerve (r = 0.32, p = 0.039). CONCLUSIONS: Intracranial hypertension can be associated with deteriorated DTI values, which might be interpreted as a sign of impaired white matter microstructural integrity in many brain regions beyond the periventricular white matter. Pressure-induced edema and axonal degeneration may be the potential underlying mechanisms of this microstructural damage.

No significant alteration in white matter microstructure in first-degree relatives of patients with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is characterized by structural alteration within white matter tissues of cortico-striato-thalamo-cortical, temporal and occipital circuits. However, the presence of microstructural changes in the white matter tracts of unaffected first-degree relatives of patients with OCD as a vulnerability marker remains unclear. Therefore, here, diffusion-tensor magnetic resonance imaging (DTI) data were obtained from 29 first-degree relatives of patients with OCD and 59 healthy controls. We investigated the group differences in FA using whole-brain analysis (DTI analysis). For additional regions of interest (ROI) analysis, we focused on the posterior thalamic radiation and sagittal stratum, shown in recent meta-analysis of patients with OCD. In both whole-brain and ROI analyses, using a strict statistical threshold (family-wise error rate [FWE] corrected p<.05 for whole-brain analyses, and p<.0125 (0.05/4) with Bonferroni correction for ROI analyses), we found no significant group differences in FA. Subtle reductions were observed in the anterior corona radiata, forceps minor, cingulum bundle, and corpus callosum only when a lenient statistical was applied (FWE corrected p<.20). These findings suggest that alterations in the white matter microstructure of first-degree relatives, as potential vulnerability markers for OCD, are likely subtle.

Locus coeruleus microstructural integrity is associated with vigilance vulnerability to sleep deprivation.

Insufficient sleep compromises cognitive performance, diminishes vigilance, and disrupts daily functioning in hundreds of millions of people worldwide. Despite extensive research revealing significant variability in vigilance vulnerability to sleep deprivation, the underlying mechanisms of these individual differences remain elusive. Locus coeruleus (LC) plays a crucial role in the regulation of sleep-wake cycles and has emerged as a potential marker for vigilance vulnerability to sleep deprivation. In this study, we investigate whether LC microstructural integrity, assessed by fractional anisotropy (FA) through diffusion tensor imaging (DTI) at baseline before sleep deprivation, can predict impaired psychomotor vigilance test (PVT) performance during sleep deprivation in a cohort of 60 healthy individuals subjected to a rigorously controlled in-laboratory sleep study. The findings indicate that individuals with high LC FA experience less vigilance impairment from sleep deprivation compared with those with low LC FA. LC FA accounts for 10.8% of the variance in sleep-deprived PVT lapses. Importantly, the relationship between LC FA and impaired PVT performance during sleep deprivation is anatomically specific, suggesting that LC microstructural integrity may serve as a biomarker for vigilance vulnerability to sleep loss.

Impact of excessive abdominal obesity on brain microstructural abnormality in schizophrenia.

Significant evidence links obesity and schizophrenia (SZ), but the brain associations are still largely unclear. 48 people with SZ were divided into two subgroups: patients with lower waist circumference (SZ-LWC: n = 24) and patients with higher waist circumference (SZ-HWC: n = 24). Healthy controls (HC) were included for comparison (HC: n = 27). Using tract-based spatial statistics, we compared fractional anisotropy (FA) of the whole-brain white matter skeleton between these three groups (SZ-LWC, SZ-HWC, HC). Using Free Surfer, we compared whole-brain cortical thickness and the selected subcortical volumes between the three groups. FA of widespread white matter and the mean cortical thickness in the right temporal lobe and insular cortex were significantly lower in the SZ-HWC group than in the HC group. The FA of regional white matter was significantly lower in the SZ-LWC group than in the HC group. There were no significant differences in mean subcortical volumes between the groups. Additionally, the cognitive performances were worse in the SZ-HWC group, who had more severe triglycerides elevation. This study provides evidence for microstructural abnormalities of white matter, cortical thickness and neurocognitive deficits in SZ patients with excessive abdominal obesity.

A longitudinal MRI analysis reveals altered brain connectivity and microstructural changes in a transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by progressive cognitive decline and neuropathological changes, yet the underlying neurobiological mechanisms remain elusive. Here, we employed a multimodal longitudinal neuroimaging approach, using anatomical and functional sequences on a high field magnetic resonance imaging (MRI) preclinical scanner, to investigate alterations in brain connectivity and white matter microstructure in a transgenic mouse model of AD (J20) when compared to wild-type (WT) littermates. Functional connectivity analysis revealed distinct network disruptions in J20 mice, primarily involving connections between posterior and anterior brain regions; importantly, a significant interaction between group and age highlighted an exacerbation of these connectivity changes with advancing age in J20 mice. In addition, significant reductions in fractional anisotropy (FA) were observed in the corpus callosum of J20 mice compared to WT, indicative of microstructural alterations consistent with white matter pathology. The observed alterations in brain connectivity and microstructure provide valuable insights into the spatiotemporal processes underlying AD-related decline and underscore the utility of multimodal neuroimaging in elucidating the neurobiological substrates of AD pathology in animal models.

Diffusion tensor metrics, motor and non-motor symptoms in de novo Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons' degeneration of the substantia nigra, presenting with motor and non-motor symptoms. We hypothesized that altered diffusion metrics are associated with clinical symptoms in de novo PD patients. METHODS: Fractional Anisotropy (FA) and Mean (MD), Axial (AD), and Radial Diffusivity (RD) were assessed in 55 de novo PD patients (58.62 ± 9.85 years, 37 men) and 55 age-matched healthy controls (59.92 ± 11.25 years, 34 men). Diffusion-weighted images and clinical variables were collected from the Parkinson's Progression Markers Initiative study. Tract-based spatial statistics were used to identify white matter (WM) changes, and fiber tracts were localized using the JHU-WM tractography atlas. Motor and non-motor symptoms were evaluated in patients. RESULTS: We observed higher FA values and lower RD values in patients than controls in various fiber tracts (p-TFCE < 0.05). No significant MD or AD difference was observed between groups. Diffusion metrics of several regions significantly correlated with non-motor (state and trait anxiety and daytime sleepiness) and axial motor symptoms in the de novo PD group. No correlations were observed between diffusion metrics and other clinical symptoms evaluated. CONCLUSION: Our findings suggest microstructural changes in de novo PD fiber tracts; however, limited associations with clinical symptoms reveal the complexity of PD pathology. They may contribute to understanding the neurobiological changes underlying PD and have implications for developing targeted interventions. However, further longitudinal research with larger cohorts and consideration of confounding factors are necessary to elucidate the underlying mechanisms of these diffusion alterations in de novo PD.

Comparative analysis of brain age prediction using structural and diffusion MRIs in neonates.

Using machine learning techniques to predict brain age from multimodal data has become a crucial biomarker for assessing brain development. Among various types of brain imaging data, structural magnetic resonance imaging (sMRI) and diffusion magnetic resonance imaging (dMRI) are the most commonly used modalities. sMRI focuses on depicting macrostructural features of the brain, while dMRI reveals the orientation of major white matter fibers and changes in tissue microstructure. However, their differential capabilities in reflecting newborn age and clinical implications have not been systematically studied. This study aims to explore the impact of sMRI and dMRI on brain age prediction. Comparing predictions based on T2-weighted(T2w) and fractional anisotropy (FA) images, we found their mean absolute errors (MAE) in predicting infant age to be similar. Exploratory analysis revealed for T2w images, areas such as the cerebral cortex and ventricles contribute most significantly to age prediction, whereas FA images highlight the cerebral cortex and regions of the main white matter tracts. Despite both modalities focusing on the cerebral cortex, they exhibit significant region-wise differences, reflecting developmental disparities in macro- and microstructural aspects of the cortex. Additionally, we examined the effects of prematurity, gender, and hemispherical asymmetry of the brain on age prediction for both modalities. Results showed significant differences (p<0.05) in age prediction biases based on FA images across gender and hemispherical asymmetry, whereas no significant differences were observed with T2w images. This study underscores the differences between T2w and FA images in predicting infant brain age, offering new perspectives for studying infant brain development and aiding more effective assessment and tracking of infant development.

Effect of worry, depressed affect, and sensitivity to environmental stress owing to neurotic personality on MRI markers of cerebral small vessel disease: A univariable and multivariable Mendelian randomization study.

OBJECTIVE: Neuroticism was found to be associated with cerebral small vessel disease (CSVD) in observational studies. We aimed to explore the causal relationship between distinct components of neuroticism and CSVD. METHODS: Two-sample mendelian randomization (MR) study was conducted to explore the bidirectional causal relationships between three genetically distinct subclusters of neuroticism (depressed affect, worry, and sensitivity to environmental stress and adversity [SESA]) and MRI markers of CSVD using publicly available genome-wide association studies (GWAS) data. Inverse variance weighted (IVW) method was used for the primary causal estimates. Alternative MR approaches and extensive sensitivity analyses were conducted to ensure the robustness of the findings. Multivariable MR (MVMR) analysis was used to estimate the direct causal effects with adjustment of other known risk factors for CSVD. RESULTS: Genetically determined SESA was significantly associated with reduced fractional anisotropy (FA) (beta: -1.94, 95%CI: -3.04 to -0.84, p=5.29e-4), and associated with increased mean diffusivity (MD) (beta=1.55, 95%CI: 0.29 to 2.81, p=0.016) and white matter hyperintensities (WMH) (beta=0.25, 95% CI: 0.03 to 0.47, p=0.029) at the nominally significant level. MVMR analysis suggested the significant associations remained significant after accounting for body mass index (BMI), smoking, alcohol drinking, type 2 diabetes (T2D), hypertension, and depression. The other two neuroticism subclusters (depressed affect and worry) didn't have significant causal effects on the MRI markers. In the reverse MR analysis with the MRI markers as exposures, no significant associations were found. CONCLUSION: This study supported the casual role of SESA in the development of CSVD. Further research to explore the underlying mechanism are warranted.

Maternal adverse childhood experiences and infant visual-limbic white matter development.

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.

Leptin bioavailability and markers of brain atrophy and vascular injury in the middle age.

INTRODUCTION: We investigated the associations of leptin markers with cognitive function and magnetic resonance imaging (MRI) measures of brain atrophy and vascular injury in healthy middle-aged adults. METHODS: We included 2262 cognitively healthy participants from the Framingham Heart Study with neuropsychological evaluation; of these, 2028 also had available brain MRI. Concentrations of leptin, soluble leptin receptor (sOB-R), and their ratio (free leptin index [FLI]), indicating leptin bioavailability, were measured using enzyme-linked immunosorbent assays. Cognitive and MRI measures were derived using standardized protocols. RESULTS: Higher sOB-R was associated with lower fractional anisotropy (FA, ß = -0.114 ± 0.02, p < 0.001), and higher free water (FW, ß = 0.091 ± 0.022, p < 0.001) and peak-width skeletonized mean diffusivity (PSMD, ß = 0.078 ± 0.021, p < 0.001). Correspondingly, higher FLI was associated with higher FA (ß = 0.115 ± 0.027, p < 0.001) and lower FW (ß = -0.096 ± 0.029, p = 0.001) and PSMD (ß = -0.085 ± 0.028, p = 0.002). DISCUSSION: Higher leptin bioavailability was associated with better white matter (WM) integrity in healthy middle-aged adults, supporting the putative neuroprotective role of leptin in late-life dementia risk. HIGHLIGHTS: Higher leptin bioavailability was related to better preservation of white matter microstructure. Higher leptin bioavailability during midlife might confer protection against dementia. Potential benefits might be even stronger for individuals with visceral obesity. DTI measures might be sensitive surrogate markers of subclinical neuropathology.

Improved cognition and preserved hippocampal fractional anisotropy in subjects undergoing carotid endarterectomy "CEA preserves cognition & hippocampal structure".

OBJECTIVES: A growing body of data indicates that extracranial carotid artery disease (ECAD) can contribute to cognitive impairment. However, there have been mixed reports regarding the benefit of carotid endarterectomy (CEA) as it relates to preserving cognitive function. In this work, diffusion magnetic resonance imaging (dMRI) and neurocognitive testing are used to provide insight into structural and functional brain changes that occur in subjects with significant carotid artery stenosis, as well as changes that occur in response to CEA. MATERIALS AND METHODS: The study design was a prospective, non-randomized, controlled study that enrolled patients with asymptomatic carotid stenosis. Thirteen subjects had severe ECAD (≥70% stenosis in at least one carotid artery) and were scheduled to undergo surgery. Thirteen had asymptomatic ECAD with <70% stenosis, therefore not requiring surgery. All subjects underwent neurocognitive testing using the Montreal Cognitive Assessment test (MoCA) and high angular resolution, multi-shell diffusion magnetic resonance imaging (dMRI) of the brain at baseline and at four-six months follow-up. Changes in MoCA scores as well as in Fractional anisotropy (FA) along the hippocampus were compared at baseline and follow-up. RESULTS: At baseline, FA was significantly lower along the ipsilateral hippocampus in subjects with severe ECAD compared to subjects without severe ECAD. MoCA scores were lower in these individuals, but this did not reach statistical significance. At follow-up, MoCA scores increased significantly in subjects who underwent CEA and remained statistically equal in control subjects that did not have CEA. FA remained unchanged in the CEA group and decreased in the control group. CONCLUSIONS: This study suggests that CEA improves cognition and preserves hippocampal white matter structure compared to control subjects not undergoing CEA.

Additive effects of mild head trauma, blast exposure, and aging within white matter tracts: A novel Diffusion Tensor Imaging analysis approach.

Existing diffusion tensor imaging (DTI) studies of neurological injury following high-level blast exposure (hlBE) in military personnel have produced widely variable results. This is potentially due to prior studies often not considering the quantity and/or recency of hlBE, as well as co-morbidity with non-blast head trauma (nbHT). Herein, we compare commonly used DTI metrics: fractional anisotropy and mean, axial, and radial diffusivity, in Veterans with and without history of hlBE and/or nbHT. We use both the traditional method of dividing participants into 2 equally weighted groups and an alternative method wherein each participant is weighted by quantity and recency of hlBE and/or nbHT. While no differences were detected using the traditional method, the alternative method revealed diffuse and extensive changes in all DTI metrics. These effects were quantified within 43 anatomically defined white matter tracts, which identified the forceps minor, middle corpus callosum, acoustic and optic radiations, fornix, uncinate, inferior fronto-occipital and inferior longitudinal fasciculi, and cingulum, as the pathways most affected by hlBE and nbHT. Moreover, additive effects of aging were present in many of the same tracts suggesting that these neuroanatomical effects may compound with age.

Association among internalizing problems, white matter integrity, and social difficulties in children with autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by social difficulties and often accompanied by internalizing and externalizing problems, which are frequently overlooked. Here, we examined and compared fractional anisotropy (FA) between 79 children with ASD (aged 4-7.8 years) and 70 age-, gender-, and handedness- matched typically developing controls (TDCs, aged 3-7.2 years). We aimed to explore the relationship among social difficulties, internalizing and externalizing problems, and brain structural foundation (characterized by white matter integrity). Compared with the TDCs, the children with ASD exhibited more severe internalizing and externalizing problems, which were positively correlated with social difficulties. Reduced FA values were observed in specific white matter tracts that integrate a fronto-temporal-occipital circuit. In particular, the FA values within this circuit were negatively correlated with internalizing problems and SRS-TOTAL scores. Mediation analysis revealed that internalizing problems mediated the relationship between the FA values in the left middle longitudinal fasciculus (L-MdLF) and corpus callosum forceps major (CCM) and social difficulties in children with ASD. These findings contribute to our understanding of social difficulties, internalizing and externalizing problems, and white matter integrity in children with ASD and highlight internalizing problems as a mediator between social difficulties and white matter integrity.

The Role of Diffusion Tensor Imaging in CNS Tuberculosis.

Background and objective Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a significant global health concern, with India being a hotspot for the disease burden. Central nervous system (CNS) tuberculosis, though comprising a smaller proportion of total TB cases, is associated with significant morbidity and mortality. This study aimed to explore the utility of diffusion tensor imaging (DTI) in assessing the microstructural changes in white matter tracts associated with CNS tuberculosis. Materials and methods This study was conducted over two years at the All India Institute of Medical Sciences, Rishikesh. We employed a cross-sectional observational design and included patients with definite or highly probable tuberculous meningitis, alongside healthy controls. Results Our findings revealed a significant reduction in fractional anisotropy (FA) values in various white matter tracts of patients with CNS tuberculosis compared to healthy individuals. This reduction in FA correlated with the severity of tuberculous meningitis, particularly in the corpus callosum. Additionally, DTI highlighted distinct patterns of white matter involvement around intraparenchymal lesions, suggesting potential implications for clinical outcomes. The study emphasizes the utility of FA values in grading disease severity and prognosticating treatment outcomes in CNS tuberculosis. Conclusions Overall, this study provides valuable insights into the microstructural alterations in white matter tracts associated with CNS tuberculosis, highlighting the potential of DTI in early diagnosis, grading disease severity, and monitoring treatment response. We believe these findings will pave the way for further research to optimize the clinical management of this debilitating disease.

Polygenic susceptibility for multiple sclerosis is associated with working memory in low-performing young adults.

BACKGROUND: Multiple sclerosis (MS) is a complex disease with substantial heritability estimates. Besides typical clinical manifestations such as motor and sensory deficits, MS is characterized by structural and functional brain abnormalities, and by cognitive impairment such as decreased working memory (WM) performance. OBJECTIVES: We investigated the possible link between the polygenic risk for MS and WM performance in healthy adults (18-35 years). Additionally, we addressed the relationship between polygenic risk for MS and white matter fractional anisotropy (FA). METHODS: We generated a polygenic risk score (PRS) of MS susceptibility and investigated its association with WM performance in 3282 healthy adults (two subsamples, N1 = 1803, N2 = 1479). The association between MS-PRS and FA was studied in the second subsample. MS severity PRS associations were also investigated for the WM and FA measurements. RESULTS: MS-PRS was significantly associated with WM performance within the 10% lowest WM-performing individuals (p = 0.001; pFDR = 0.018). It was not significantly associated with any of the investigated FA measurements. MS severity PRS was significantly associated with brain-wide mean FA (p = 0.041) and showed suggestive associations with additional FA measurements. CONCLUSIONS: By identifying a genetic link between MS and WM performance this study contributes to the understanding of the genetic complexity of MS, and hopefully to the possible identification of molecular pathways linked to cognitive deficits in MS. It also contributes to the understanding of genetic associations with MS severity, as these associations seem to involve distinct biological pathways compared to genetic variants linked to the overall risk of developing MS.

Effects of Multimodal Physical Therapy on Pain, Disability, H-reflex, and Diffusion Tensor Imaging Parameters in Patients With Lumbosacral Radiculopathy Due to Lumbar Disc Herniation: A Preliminary Trial.

Background Lumbosacral radiculopathy (LSR) due to lumbar disc herniation (LDH) is a condition caused by mechanical compression of nerve roots. Various physical therapy interventions have been proposed for the conservative management of LSR due to LDH. However, the study of physical therapy interventions in a multimodal form is lacking. Additionally, the effect of physical therapy on diffusion tensor imaging (DTI) parameters of the compressed nerve root has not been studied. This study aimed to investigate the effects of multimodal physical therapy (MPT) on pain, disability, soleus H-reflex, and DTI parameters of the compressed nerve root in patients with chronic unilateral LSR due to LDH. Methods A prospective preliminary pre-post clinical trial with a convenience sample was conducted. A total of 14 patients with chronic unilateral LSR due to paracentral L4-L5 or L5-S1 LDH were recruited for the study. Participants received a total of 18 sessions of a six-week MPT program that consisted of electrophysical agents, manual therapy interventions, and core stability exercises. Electrophysical agents involved interferential current and hot pack. Manual therapy interventions included myofascial release, side posture positional distraction, passive spinal rotation mobilization, and high-velocity low-amplitude manipulation. Visual analog scale (VAS), Roland-Morris Disability Questionnaire (RMDQ), soleus H-reflex amplitude, side-to-side amplitude (H/H) ratio, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) of the compressed nerve root were measured at baseline and post-intervention. Results There were significant improvements in VAS, RMDQ, H/H ratio, FA, and ADC of the compressed nerve root. Furthermore, significant improvement was found in the affected side compared with the contralateral side in H-reflex amplitude. Conclusions The observations of this preliminary trial suggest that MPT is a successful intervention in patients with chronic unilateral LSR due to LDH. Regarding DTI parameters of the compressed nerve root, FA increased and ADC decreased. Future studies with a control group, large sample sizes, and longer follow-up periods are needed.