Longitudinal white matter microstructural changes in pediatric mild traumatic brain injury: An A‐CAP study

In the largest sample studied to date, white matter microstructural trajectories and their relation to persistent symptoms were examined after pediatric mild traumatic brain injury (mTBI). This prospective, longitudinal cohort study recruited children aged 8–16.99 years with mTBI or mild orthopedic injury (OI) from five pediatric emergency departments. Children''s pre‐injury and 1‐month post‐injury symptom ratings were used to classify mTBI with or without persistent symptoms. Children completed diffusion‐weighted imaging at post‐acute (2–33 days post‐injury) and chronic (3 or 6 months via random assignment) post‐injury assessments. Mean diffusivity (MD) and fractional anisotropy (FA) were derived for 18 white matter tracts in 560 children (362 mTBI/198 OI), 407 with longitudinal data. Superior longitudinal fasciculus FA was higher in mTBI without persistent symptoms relative to OI, d (95% confidence interval) = 0.31 to 0.37 (0.02, 0.68), across time. In younger children, MD of the anterior thalamic radiations was higher in mTBI with persistent symptoms relative to both mTBI without persistent symptoms, 1.43 (0.59, 2.27), and OI, 1.94 (1.07, 2.81). MD of the arcuate fasciculus, −0.58 (−1.04, −0.11), and superior longitudinal fasciculus, −0.49 (−0.90, −0.09) was lower in mTBI without persistent symptoms relative to OI at 6 months post‐injury. White matter microstructural changes suggesting neuroinflammation and axonal swelling occurred chronically and continued 6 months post injury in children with mTBI, especially in younger children with persistent symptoms, relative to OI. White matter microstructure appears more organized in children without persistent symptoms, consistent with their better clinical outcomes.     

Diffusion tensor imaging of white matter and correlates to eye movement control and psychometric testing in children with prenatal alcohol exposure

Prenatal alcohol exposure (PAE) can cause central nervous system dysfunction and widespread structural anomalies as detected by magnetic resonance imaging (MRI). This study focused on diffusion tensor imaging (DTI) of white matter in a large sample of PAE participants that allowed us to examine correlations with behavioral outcomes. Participants were confirmed PAE (n = 69, mean age = 12.5 ± 3.2 years) or typically developing control children (n = 67, mean age = 12.1 ± 3.2 years) who underwent brain MRI, eye movement tasks, and psychometric tests. A semi‐automated tractography method extracted fractional anisotropy (FA) and mean diffusivity (MD) values from 15 white matter tracts. The PAE group displayed decreased FA compared with controls in multiple tracts including 3 corpus callosum regions, right corticospinal tract, and 3 left hemisphere tracts connecting to the frontal lobe (cingulum, uncinate fasciculus, and superior longitudinal fasciculus). Significant group by sex interactions were found for the genu, left superior longitudinal fasciculus, and the left uncinate, with females in the PAE group exhibiting lower FA compared with control females. Correlations were found between DTI and eye movement measures in the control group, but these same relationships were absent in the PAE group. In contrast, no correlations were found between DTI and any of the psychometric tests used in this study. These findings support the hypothesis that measures of eye movement control may be valuable functional biomarkers of the brain injury induced by PAE as these tasks reveal group differences that appear to be linked to deficits in white matter integrity in the brain. Hum Brain Mapp 38:444–456, 2017. © 2016 Wiley Periodicals, Inc.     

Linear and curvilinear correlations of brain white matter volume,fractional anisotropy,and mean diffusivity with age using voxel‐based and region‐of‐interest analyses in 246 healthy children

In this study, we examined linear and curvilinear correlations of fractional anisotropy (FA), mean diffusivity (MD), and white matter volume with age by using brain structural and diffusion‐tensor magnetic resonance imaging (MRI) in a large number of healthy children and voxel‐based morphometry (VBM) and region‐of‐interest (ROI) analyses. We collected data by brain structural MRI in 246 healthy children, aged 5–18 years. FA and MD images were normalized using the normalization parameter of the corresponding structural MRI. Next, we analyzed the correlations between FA and age and between MD and age by estimating linear and logarithmic functions. We also analyzed the correlation between white matter volume and age by linear, quadratic, and cubic functions. Correlations between FA and age and between MD and age showed exponential trajectories in most ROIs in boys and girls, except for several fibers, such as the corpus callosum connecting the bilateral rectal gyri in boys. The correlation between white matter volume and age showed significant positive linear trajectories in most ROIs in boys and girls, except for a few fibers, such as the bilateral uncinate fasciculus. Additionally, maturational rates differed among major fibers, and in girls, the left superior longitudinal fasciculus, which connects the frontal and temporal lobes, showed a slower rate of maturation than other fibers. Our results may help to clarify the mechanisms of normal brain maturation from the viewpoint of brain white matter. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Different brain profiles in children with prenatal alcohol exposure with or without early adverse exposures

Prenatal alcohol exposure (PAE) can alter brain development and impact mental health outcomes, and often occurs in conjunction with postnatal adversity (e.g., maltreatment). However, it is unclear how postnatal adverse exposures may moderate mental health and brain outcomes in children with PAE. T1‐weighted and diffusion magnetic resonance imaging were obtained from 66 participants aged 7–16 years. Twenty‐one participants had PAE and adverse postnatal exposures (PAE+), 12 had PAE without adverse postnatal exposures (PAE?), and 33 were age‐ and gender‐matched controls unexposed to either prenatal alcohol or postnatal adversity. Internalizing and externalizing mental health symptoms were assessed using the Behavioral Assessment System for Children II, Parent‐Rating Scale. ANCOVAs were used to compare mental health symptoms, limbic and prefrontal cortical volumes, and diffusion parameters of cortico‐limbic white matter tracts between groups, and to assess brain‐mental health relationships. Both PAE groups had worse externalizing behavior (higher scores) than controls. The PAE? group had lower fractional anisotropy (FA) in the bilateral cingulum and left uncinate fasciculus, and smaller volumes in the left anterior cingulate cortex than controls and the PAE+ group. The PAE? group also had higher mean diffusivity (MD) in the left uncinate than the PAE+ group, and smaller right anterior cingulate and superior frontal gyrus volumes than controls. These findings show different brain structure and mental health symptom profiles in children with PAE with and without postnatal adversity, highlighting the need to consider adverse postnatal exposures in individuals with PAE.     

Age‐related topographic map of magnetic resonance diffusion metrics in neonatal brains

Accelerated maturation of brain parenchyma close to term‐equivalent age leads to rapid changes in diffusion‐weighted imaging (DWI) and diffusion tensor imaging (DTI) metrics of neonatal brains, which can complicate the evaluation and interpretation of these scans. In this study, we characterized the topography of age‐related evolution of diffusion metrics in neonatal brains. We included 565 neonates who had MRI between 0 and 3 months of age, with no structural or signal abnormality—including 162 who had DTI scans. We analyzed the age‐related changes of apparent diffusion coefficient (ADC) values throughout brain and DTI metrics (fractional anisotropy [FA] and mean diffusivity [MD]) along white matter (WM) tracts. Rate of change in ADC, FA, and MD values across 5 mm cubic voxels was calculated. There was significant reduction of ADC and MD values and increase of FA with increasing gestational age (GA) throughout neonates'' brain, with the highest temporal rates in subcortical WM, corticospinal tract, cerebellar WM, and vermis. GA at birth had significant effect on ADC values in convexity cortex and corpus callosum as well as FA/MD values in corpus callosum, after correcting for GA at scan. We developed online interactive atlases depicting age‐specific normative values of ADC (ages 34–46 weeks), and FA/MD (35–41 weeks). Our results show a rapid decrease in diffusivity metrics of cerebral/cerebellar WM and vermis in the first few weeks of neonatal age, likely attributable to myelination. In addition, prematurity and low GA at birth may result in lasting delay in corpus callosum myelination and cerebral cortex cellularity.     

White matter deficits mediate effects of prenatal alcohol exposure on cognitive development in childhood

Fetal alcohol spectrum disorders comprise the spectrum of cognitive, behavioral, and neurological impairments caused by prenatal alcohol exposure (PAE). Diffusion tensor imaging (DTI) was performed on 54 children (age 10.1 ± 1.0 years) from the Cape Town Longitudinal Cohort, for whom detailed drinking histories obtained during pregnancy are available: 26 with full fetal alcohol syndrome (FAS) or partial FAS (PFAS), 15 nonsyndromal heavily exposed (HE), and 13 controls. Using voxelwise analyses, children with FAS/PFAS showed significantly lower fractional anisotropy (FA) in four white matter (WM) regions and higher mean diffusivity (MD) in seven; three regions of FA and MD differences (left inferior longitudinal fasciculus (ILF), splenium, and isthmus) overlapped, and the fourth FA cluster was located in the same WM bundle (right ILF) as an MD cluster. HE children showed lower FA and higher MD in a subset of these regions. Significant correlations were observed between three continuous alcohol measures and DTI values at cluster peaks, indicating that WM damage in several regions is dose dependent. Lower FA in the regions of interest was attributable primarily to increased radial diffusivity rather than decreased axonal diffusivity, suggesting poorer axon packing density and/or myelination. Multiple regression models indicated that this cortical WM impairment partially mediated adverse effects of PAE on information processing speed and eyeblink conditioning. Hum Brain Mapp 37:2943–2958, 2016. © 2016 Wiley Periodicals, Inc .     

Spatiotemporal changes in diffusivity and anisotropy in fetal brain tractography

Population averaged diffusion atlases can be utilized to characterize complex microstructural changes with less bias than data from individual subjects. In this study, a fetal diffusion tensor imaging (DTI) atlas was used to investigate tract‐based changes in anisotropy and diffusivity in vivo from 23 to 38 weeks of gestational age (GA). Healthy pregnant volunteers with typically developing fetuses were imaged at 3 T. Acquisition included structural images processed with a super‐resolution algorithm and DTI images processed with a motion‐tracked slice‐to‐volume registration algorithm. The DTI from individual subjects were used to generate 16 templates, each specific to a week of GA; this was accomplished by means of a tensor‐to‐tensor diffeomorphic deformable registration method integrated with kernel regression in age. Deterministic tractography was performed to outline the forceps major, forceps minor, bilateral corticospinal tracts (CST), bilateral inferior fronto‐occipital fasciculus (IFOF), bilateral inferior longitudinal fasciculus (ILF), and bilateral uncinate fasciculus (UF). The mean fractional anisotropy (FA) and mean diffusivity (MD) was recorded for all tracts. For a subset of tracts (forceps major, CST, and IFOF) we manually divided the tractograms into anatomy conforming segments to evaluate within‐tract changes. We found tract‐specific, nonlinear, age related changes in FA and MD. Early in gestation, these trends appear to be dominated by cytoarchitectonic changes in the transient white matter fetal zones while later in gestation, trends conforming to the progression of myelination were observed. We also observed significant (local) heterogeneity in within‐tract developmental trajectories for the CST, IFOF, and forceps major.     

Volume changes and brain‐behavior relationships in white matter and subcortical gray matter in children with prenatal alcohol exposure

Children with prenatal alcohol exposure (PAE) may have cognitive, behavioral and brain abnormalities. Here, we compare rates of white matter and subcortical gray matter volume change in PAE and control children, and examine relationships between annual volume change and arithmetic ability, behavior, and executive function. Participants (n = 75 PAE/64 control; age: 7.1–15.9 years) each received two structural magnetic resonance scans, ～2 years apart. Assessments included Wechsler Intelligence Scale for Children (WISC‐IV), the Child Behavior Checklist and the Behavior Rating Inventory of Executive Function. Subcortical white and gray volumes were extracted for each hemisphere. Group volume differences were tested using false discovery rate (q < 0.05). Analyses examined group‐by‐age interactions and group‐score interactions for correlations between change in volume and raw behavioral scores. Results showed that subjects with PAE had smaller volumes than control subjects across the brain. Significant group‐score interactions were found in temporal and parietal regions for WISC arithmetic scores and in frontal and parietal regions for behavioral measures. Poorer cognitive/ behavioral outcomes were associated with larger volume increases in PAE, while control subjects generally showed no significant correlations. In contrast with previous results demonstrating different trajectories of cortical volume change in PAE, our results show similar rates of subcortical volume growth in subjects with PAE and control subjects. We also demonstrate abnormal brain‐behavior relationships in subjects with PAE, suggesting different use of brain resources. Our results are encouraging in that, due to the stable volume differences, there may be an extended window of opportunity for intervention in children with PAE. Hum Brain Mapp 36:2318–2329, 2015. © 2015 Wiley Periodicals, Inc.     

Both brain size and biological sex contribute to variation in white matter microstructure in middle‐aged healthy adults

Whether head size and/or biological sex influence proxies of white matter (WM) microstructure such as fractional anisotropy (FA) and mean diffusivity (MD) remains controversial. Diffusion tensor imaging (DTI) indices are also associated with age, but there are large discrepancies in the spatial distribution and timeline of age‐related differences reported. The aim of this study was to evaluate the associations between intracranial volume (ICV), sex, and age and DTI indices from WM in a population‐based study of healthy individuals (n = 812) aged 50–66 in the Nord‐Trøndelag health survey. Semiautomated tractography and tract‐based spatial statistics (TBSS) analyses were performed on the entire sample and in an ICV‐matched sample of men and women. The tractography results showed a similar positive association between ICV and FA in all major WM tracts in men and women. Associations between ICV and MD, radial diffusivity and axial diffusivity were also found, but to a lesser extent than FA. The TBSS results showed that both men and women had areas of higher and lower FA when controlling for age, but after controlling for age and ICV only women had areas with higher FA. The ICV matched analysis also demonstrated that only women had areas of higher FA. Age was negatively associated with FA across the entire WM skeleton in the TBSS analysis, independent of both sex and ICV. Combined, these findings demonstrated that both ICV and sex contributed to variation in DTI indices and emphasized the importance of considering ICV as a covariate in DTI analysis.     

Age‐dependent white matter disruptions after military traumatic brain injury: Multivariate analysis results from ENIGMA brain injury

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age‐related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non‐negative matrix factorization (NMF) is a data‐driven approach that detects covarying patterns (components) within high‐dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self‐reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta‐Analysis) Military Brain Injury working group. Regressions were used to examine TBI‐ and mTBI‐related associations in NMF‐derived components while adjusting for age, sex, post‐traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age‐dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q < 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age‐dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans.     

Abnormal white matter integrity in young children with autism

This study investigated white matter integrity in young children with autism using diffusion tensor imaging (DTI). Twenty-two children with autism, mean age 3:2 years, and 32 controls, mean age 3:4 years, participated in the study. Tract-based spatial statistics (TBSS) revealed white matter abnormalities in several distinct clusters within the genu and body of the corpus callosum (CC), left superior longitudinal fasciculus (SLF) and right and left cingulum (Cg). TBSS-VOIs analysis was performed in the clusters where differences in fractional anisotropy (FA) were detected to investigate the relationship between changes in FA and diffusivity indices. In all VOIs, increase in FA was caused by a decrease in radial diffusivity (Dr), while no changes in axial diffusivity (Da) or mean diffusivity (MD) were observed. Tractography analysis was applied to further study the CC, SLF, and Cg. Witelson parcellation scheme was used for the CC. Significant increase in FA was seen in children with autism in the mid-body of the CC as well as in the left Cg. It is suggested that such abnormal white matter integrity in young children with autism may adversely affect connectivity between different brain regions and may be linked to some of the behavioral impairments apparent in autism.     

White matter microstructure shows sex differences in late childhood: Evidence from 6797 children

Sex differences in white matter microstructure have been robustly demonstrated in the adult brain using both conventional and advanced diffusion‐weighted magnetic resonance imaging approaches. However, sex differences in white matter microstructure prior to adulthood remain poorly understood; previous developmental work focused on conventional microstructure metrics and yielded mixed results. Here, we rigorously characterized sex differences in white matter microstructure among over 6000 children from the Adolescent Brain Cognitive Development study who were between 9 and 10 years old. Microstructure was quantified using both the conventional model—diffusion tensor imaging (DTI)—and an advanced model, restriction spectrum imaging (RSI). DTI metrics included fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). RSI metrics included normalized isotropic, directional, and total intracellular diffusion (N0, ND, NT). We found significant and replicable sex differences in DTI or RSI microstructure metrics in every white matter region examined across the brain. Sex differences in FA were regionally specific. Across white matter regions, boys exhibited greater MD, AD, and RD than girls, on average. Girls displayed increased N0, ND, and NT compared to boys, on average, suggesting greater cell and neurite density in girls. Together, these robust and replicable findings provide an important foundation for understanding sex differences in health and disease.     

Developmental trajectories of white matter structure in children with and without reading impairments

Left temporal-parietal white matter structure is consistently associated with reading abilities in children. A small number of longitudinal studies show that development of this area over time is altered in children with impaired reading. However, it remains unclear how brain developmental patterns relate to specific reading skills such as fluency, which is a critical part of reading comprehension. Here, we examined white matter development trajectories in children with dysfluent reading (20 dysfluent and inaccurate readers, 36 dysfluent and accurate readers) compared to non-impaired readers (n = 14) over 18 months. We found typical age-related increases of fractional anisotropy (FA) in bilateral temporal-parietal areas in non-impaired readers, but a lack of similar changes in dysfluent readers. We also found steeper decreases of mean diffusivity (MD) in the right corona radiata and left uncinate fasciculus in dysfluent inaccurate readers compared to dysfluent accurate readers. Changes in diffusion parameters were correlated with changes in reading scores over time. These results suggest delayed white matter development in dysfluent readers, and show maturational differences between children with different types of reading impairment. Overall, these results highlight the importance of considering developmental trajectories, and demonstrate that the window of plasticity may be different for different children.     

Modulation of network centrality and gray matter microstructure using multi‐session brain stimulation and memory training

Neural mechanisms of behavioral improvement induced by repeated transcranial direct current stimulation (tDCS) combined with cognitive training are yet unclear. Previously, we reported behavioral effects of a 3‐day visuospatial memory training with concurrent anodal tDCS over the right temporoparietal cortex in older adults. To investigate intervention‐induced neural alterations we here used functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) datasets available from 35 participants of this previous study, acquired before and after the intervention. To delineate changes in whole‐brain functional network architecture, we employed eigenvector centrality mapping. Gray matter alterations were analyzed using DTI‐derived mean diffusivity (MD). Network centrality in the bilateral posterior temporooccipital cortex was reduced after anodal compared to sham stimulation. This focal effect is indicative of decreased functional connectivity of the brain region underneath the anodal electrode and its left‐hemispheric homolog with other “relevant” (i.e., highly connected) brain regions, thereby providing evidence for reorganizational processes within the brain''s network architecture. Examining local MD changes in these clusters, an interaction between stimulation condition and training success indicated a decrease of MD in the right (stimulated) temporooccipital cluster in individuals who showed superior behavioral training benefits. Using a data‐driven whole‐brain network approach, we provide evidence for targeted neuromodulatory effects of a combined tDCS‐and‐training intervention. We show for the first time that gray matter alterations of microstructure (assessed by DTI‐derived MD) may be involved in tDCS‐enhanced cognitive training. Increased knowledge on how combined interventions modulate neural networks in older adults, will help the development of specific therapeutic interventions against age‐associated cognitive decline.     

The cortical regions and white matter tracts underlying auditory comprehension in patients with primary brain tumor

The comprehension of spoken language is one of the most essential language functions in humans. However, the neurological underpinnings of auditory comprehension remain under debate. Here we used multi‐modal neuroimaging analyses on a group of patients with low‐grade gliomas to localize cortical regions and white matter tracts responsible for auditory language comprehension. Region‐of‐interests and voxel‐level whole‐brain analyses showed that cortical areas in the posterior temporal lobe are crucial for language comprehension. The fiber integrity assessed with diffusion tensor imaging of the arcuate fasciculus and the inferior longitudinal fasciculus was strongly correlated with both auditory comprehension and the grey matter volume of the inferior temporal and middle temporal gyri. Together, our findings provide direct evidence for an integrated network of auditory comprehension whereby the superior temporal gyrus and sulcus, the posterior parts of the middle and inferior temporal gyri serve as auditory comprehension cortex, and the arcuate fasciculus and the inferior longitudinal fasciculus subserve as crucial structural connectivity. These findings provide critical evidence on the neural underpinnings of language comprehension.     

Stability of associations between neuroticism and microstructural asymmetry of the cingulum during late childhood and adolescence: Insights from a longitudinal study with up to 11 waves

Adolescence is characterized by significant brain development and marks a period of the life span with an increased incidence of mood disorders, especially in females. The risk of developing mood disorders is also higher in individuals scoring high on neuroticism, a personality trait characterized by a tendency to experience negative and anxious emotions. We previously found in a cross‐sectional study that neuroticism is associated with microstructural left–right asymmetry of the fronto‐limbic white matter involved in emotional processing, with opposite effects in female and male adolescents. We now have extended this work collecting longitudinal data in 76 typically developing children and adolescents aged 7–18 years, including repeated MRI sampling up to 11 times. This enabled us, for the first time, to address the critical question, whether the association between neuroticism and frontal‐limbic white matter asymmetry changes or remains stable across late childhood and adolescence. Neuroticism was assessed up to four times and showed good intraindividual stability and did not significantly change with age. Conforming our cross‐sectional results, females scoring high on neuroticism displayed increased left–right cingulum fractional anisotropy (FA), while males showed decreased left–right cingulum FA asymmetry. Despite ongoing age‐related increases in FA in cingulum, the association between neuroticism and cingulum FA asymmetry was already expressed in females in late childhood and remained stable across adolescence. In males, the association appeared to become more prominent during adolescence. Future longitudinal studies need to cover an earlier age span to elucidate the time point at which the relationship between neuroticism and cingulum FA asymmetry arises.     

White matter developmental trajectories associated with persistence and recovery of childhood stuttering

Stuttering affects the fundamental human ability of fluent speech production, and can have a significant negative impact on an individual's psychosocial development. While the disorder affects about 5% of all preschool children, approximately 80% of them recover naturally within a few years of stuttering onset. The pathophysiology and neuroanatomical development trajectories associated with persistence and recovery of stuttering are still largely unknown. Here, the first mixed longitudinal diffusion tensor imaging (DTI) study of childhood stuttering has been reported. A total of 195 high quality DTI scans from 35 children who stutter (CWS) and 43 controls between 3 and 12 years of age were acquired, with an average of three scans per child, each collected approximately a year apart. Fractional anisotropy (FA), a measure reflecting white matter structural coherence, was analyzed voxel‐wise to examine group and age‐related differences using a linear mixed‐effects (LME) model. Results showed that CWS exhibited decreased FA relative to controls in the left arcuate fasciculus, underlying the inferior parietal and posterior temporal areas, and the mid body of corpus callosum. Further, white matter developmental trajectories reflecting growth rate of these tract regions differentiated children with persistent stuttering from those who recovered from stuttering. Specifically, a reduction in FA growth rate (i.e., slower FA growth with age) in persistent children relative to fluent controls in the left arcuate fasciculus and corpus callosum was found, which was not evident in recovered children. These findings provide first glimpses into the possible neural mechanisms of onset, persistence, and recovery of childhood stuttering. Hum Brain Mapp 38:3345–3359, 2017. © 2017 Wiley Periodicals, Inc.     

Individual differences in interoceptive accuracy and prediction error in motor functional neurological disorders: A DTI study

In motor functional neurological disorders (mFND), relationships between interoception (a construct of high theoretical relevance to its pathophysiology) and neuroanatomy have not been previously investigated. This study characterized white matter in mFND patients compared to healthy controls (HCs), and investigated associations between fiber bundle integrity and cardiac interoception. Voxel‐based analysis and tractography quantified fractional anisotropy (FA) in 38 mFND patients compared to 38 HCs. Secondary analyses compared functional seizures (FND‐seiz; n = 21) or functional movement disorders (n = 17) to HCs. Network lesion mapping identified gray matter origins of implicated fiber bundles. Within‐group mFND analyses investigated relationships between FA, heartbeat tracking accuracy and interoceptive trait prediction error (discrepancies between interoceptive accuracy and self‐reported bodily awareness). Results were corrected for multiple comparisons, and all findings were adjusted for depression and trait anxiety. mFND and HCs did not show any between‐group interoceptive accuracy or FA differences. However, the FND‐seiz subgroup compared to HCs showed decreased integrity in right‐lateralized tracts: extreme capsule/inferior fronto‐occipital fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, and thalamic/striatum to occipital cortex projections. These alterations originated predominantly from the right temporoparietal junction and inferior temporal gyrus. In mFND patients, individual differences in interoceptive accuracy and interoceptive trait prediction error correlated with fiber bundle integrity originating from the insula, temporoparietal junction, putamen and thalamus among other regions. In this first study investigating brain‐interoception relationships in mFND, individual differences in interoceptive accuracy and trait prediction error mapped onto multimodal integration‐related fiber bundles. Right‐lateralized limbic and associative tract disruptions distinguished FND‐seiz from HCs.     

Association between white matter microstructure and cognitive function in patients with methamphetamine use disorder

Methamphetamine use disorder (MUD) has been associated with broad neurocognitive impairments. While the cognitive impairments of MUD have been demonstrated, the neuropathological underpinnings remain inadequately understood. To date, the published human diffusion tensor imaging (DTI) studies involving the correlation between diffusion parameters and neurocognitive function in MUD are limited. Hence, the present study aimed to examine the association between cognitive performance and white matter microstructure in patients with MUD. Forty‐five patients with MUD and 43 healthy controls (HCs) completed their demographic information collection, cognitive assessments, and DTI imaging. DTI images were preprocessed to extract fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of various fiber tracts. Univariate tests were used to examine group differences in cognitive assessments and DTI metrics. Linear regression was used to examine the relationship between these two metrics. The results revealed that patients with MUD had lower subset scores of the MATRICS Consensus Cognitive Battery (MCCB), which reflects five cognitive domains: processing speed, attention, verbal learning, visual learning, problem‐solving. Patients with MUD also had significantly higher AD, MD, and RD values of the left superior longitudinal fasciculus than HCs. Furthermore, the RD value of the left superior longitudinal fasciculus was a significant predictor of processing speed and problem‐solving ability, as shown by the digit‐symbol coding test and NAB‐Mazes scores, respectively. Findings extended our understanding of white matter microstructure that is related to neurocognitive deficits in MUD and provided potential targets for the prevention and treatment of this chronic disorder.     

Gray and white matter asymmetries in healthy individuals aged 21-29 years: a voxel-based morphometry and diffusion tensor imaging study

The hemispheres of the human brain are functionally and structurally asymmetric. The study of structural asymmetries provides important clues to the neuroanatomical basis of lateralized brain functions. Previous studies have demonstrated age-related changes in morphology and diffusion properties of brain tissue. In this study, we simultaneously explored gray and white matter asymmetry using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) in 109 young healthy individuals (58 females and 51 males). To eliminate the potential confounding effects of aging and handedness, we restricted the study to right-handed subjects aged 21-29 years. VBM and voxel-based analysis of fractional anisotropy (FA) maps derived from DTI revealed a number of gray matter volume asymmetries (including the right frontal and left occipital petalias and leftward asymmetry of the planum temporale) and white matter FA asymmetries (including leftward asymmetry of the arcuate fasciculus, cingulum, and corticospinal tract). There was no significant effect of sex on gray and white matter asymmetry. Leftward volume asymmetry of the planum temporale and leftward FA asymmetry of the arcuate fasciculus were simultaneously demonstrated. Post hoc analysis showed that the gray matter volume of the planum temporale and FA of the arcuate fasciculus were positively related (Pearson correlation coefficient, 0.43; P < 0.0001). The results of our study demonstrate gray and white matter asymmetry in right-handed healthy young adults and suggest that leftward volume asymmetry of the planum temporale and leftward FA asymmetry of the arcuate fasciculus may be related.