Regional Fractional Anisotropy Research Articles

A Site-Wise Reliability Analysis of the ABCD Diffusion Fractional Anisotropy and Cortical Thickness: Impact of Scanner Platforms.

The Adolescent Brain and Cognitive Development (ABCD) project is the largest study of adolescent brain development. ABCD longitudinally tracks 11,868 participants aged 9-10 years from 21 sites using standardized protocols for multi-site MRI data collection and analysis. While the multi-site and multi-scanner study design enhances the robustness and generalizability of analysis results, it may also introduce nonbiological variances including scanner-related variations, subject motion, and deviations from protocols. ABCD imaging data were collected biennially within a period of ongoing maturation in cortical thickness and integrity of cerebral white matter. These changes can bias the classical test-retest methodologies, such as intraclass correlation coefficients (ICC). We developed a site-wise adaptive ICC (AICC) to evaluate the reliability of imaging-derived phenotypes while accounting for ongoing brain development. AICC iteratively estimates the population-level age-related brain development trajectory using a weighted mixed model and updates age-corrected site-wise reliability until convergence. We evaluated the test-retest reliability of regional fractional anisotropy (FA) measures from diffusion tensor imaging and cortical thickness (CT) from structural MRI data for each site. The mean AICC for 20 FA tracts across sites was 0.61 ± 0.19, lower than the mean AICC for CT in 34 regions across sites, 0.76 ± 0.12. Remarkably, sites using Siemens scanners consistently showed significantly higher AICC values compared with those using GE/Philips scanners for both FA (AICC = 0.71 ± 0.12 vs. 0.46 ± 0.17, p < 0.001) and CT (AICC = 0.80 ± 0.10 vs. 0.69 ± 0.11, p < 0.001). These findings demonstrate site-and-scanner related variations in data quality and underscore the necessity for meticulous data curation in subsequent association analyses.

Diffusion and functional MRI reveal microstructural and network connectivity impairment in adult-onset neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder lacking reliable neuroimaging biomarkers. This study aimed to evaluate microstructural and functional connectivity alterations using diffusion kurtosis imaging (DKI) and resting-state fMRI (rs-fMRI), and to investigate their diagnostic potential as biomarkers. Twenty-three patients with NIID and 40 matched healthy controls (HCs) were recruited. Firstly, gray matter (GM) and white matter (WM) changes were assessed by voxel-based analysis (VBA) and tract-based spatial statistics (TBSS). Then we explored modifications in brain functional networks connectivity by independent component analysis. And the relationship between the altered DKI parameters and neuropsychological evaluation was analyzed. Finally, a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of different gray matter and white matter parameters. Compared with the HCs, NIID patients showed reduced mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK), and kurtosis fractional anisotropy (KFA) values in deep gray matter regions. Significantly decreased MK, RK, AK, KFA and fractional anisotropy (FA), and increased mean diffusivity (MD) values were observed in extensive white matter fiber tracts. Notable alterations in functional connectivity were also detected. Among all DKI parameters, the diagnostic efficiency of AK in GM and FA in WM regions was the highest. Adult-onset NIID patients exhibited altered microstructure and functional network connectivity. Our findings suggest that DKI parameters may serve as potential imaging biomarkers for diagnosing adult-onset NIID.

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.

Noninvasive Evaluation of Acupuncture-Induced Cortical Plasticity in Advanced Rehabilitation of Facial Paralysis.

Facial paralysis (FP), which resulted from head and neck cancer resection, significantly impacts patients' quality of life. Traditional assessments rely on subjective evaluations and electromyography, whereas functional magnetic resonance imaging offers a noninvasive alternative for enhanced rehabilitation. Acupuncture has shown promise in promoting cerebral cortex reorganization, yet the precise relationship between acupuncture-induced structural and functional changes remains unclear, necessitating further investigation into therapeutic mechanisms. Fifty-five patients afflicted with FP underwent evaluations using voxel-mirrored homotopic connectivity (VMHC) and tract-based spatial statistics and were divided into the acupuncture intervention group (n = 35) and pseudo intervention group (n = 20). Comparative analyses of metrics pre and postintervention were conducted to delineate therapy-induced modifications in acupuncture intervention. The postacupuncture effect between groups to verify the necessity of accurate positioning for the rehabilitation of FP. Patients with FP showed deficits in VMHC in regions of the postcentral, precentral, and parietal areas. Corpus callosum and internal capsule showed significantly increased fractional anisotropy of the white matter skeleton in tract-based spatial statistics after treatment. Comparison postintervention results between groups exhibited deficits in VMHC and increased fractional anisotropy in regions of the corpus callosum in the acupuncture intervention group. Early acupuncture intervention may suppress cortical hyperactivation and restore interhemispheric inhibition across the corpus callosum to inhibit maladaptive structural plasticity. Precise acupoint localization is crucial for effective therapy, highlighting the potential of postacupuncture cortical space data for refining therapeutic strategies.

A site-wise reliability analysis of the ABCD diffusion fractional anisotropy and cortical thickness: impact of scanner platforms.

The Adolescent Brain and Cognitive Development (ABCD) project is the largest study of adolescent brain development. ABCD longitudinally tracks 11,868 participants aged 9-10 years from 21 sites using standardized protocols for multi-site MRI data collection and analysis. While the multi-site and multi-scanner study design enhances the robustness and generalizability of analysis results, it may also introduce non-biological variances including scanner-related variations, subject motion, and deviations from protocols. ABCD imaging data were collected biennially within a period of ongoing maturation in cortical thickness and integrity of cerebral white matter. These changes can bias the classical test-retest methodologies, such as intraclass correlation coefficients (ICC). We developed a site-wise adaptive ICC (AICC) to evaluate the reliability of imaging-derived phenotypes while accounting for ongoing brain development. AICC iteratively estimates the population-level age-related brain development trajectory using a weighted mixed model and updates age-corrected site-wise reliability until convergence. We evaluated the test-retest reliability of regional fractional anisotropy (FA) measures from diffusion tensor imaging and cortical thickness (CT) from structural MRI data for each site. The mean AICC for 20 FA tracts across sites was 0.61±0.19, lower than the mean AICC for CT in 34 regions across sites, 0.76±0.12. Remarkably, sites using Siemens scanners consistently showed significantly higher AICC values compared to those using GE/Philips scanners for both FA (AICC=0.71±0.12 vs 0.46±0.17, p<0.001) and CT (AICC=0.80±0.10 vs 0.69±0.11, p<0.001). These findings demonstrate site-and-scanner related variations in data quality and underscore the necessity for meticulous data curation in subsequent association analyses.

Association of past and current sleep duration with structural brain differences: A large population-based study from the UK Biobank

ObjectiveThis 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. MethodsWithin 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. ResultsCompared 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 Pinteraction <0.05). ConclusionsBoth 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.

The covariant structural and functional neuro-correlates of cognitive impairments in patients with end-stage renal diseases.

Cognitive impairment (CI) is a common complication of end-stage renal disease (ESRD) that is associated with structural and functional changes in the brain. However, whether a joint structural and functional alteration pattern exists that is related to CI in ESRD is unclear. In this study, instead of looking at brain structure and function separately, we aim to investigate the covariant characteristics of both functional and structural aspects. Specifically, we took the fusion analysis approach, namely, multimodal canonical correlation analysis and joint independent component analysis (mCCA+jICA), to jointly study the discriminative features in gray matter volume (GMV) measured by T1-weighted (T1w) MRI, fractional anisotropy (FA) in white matter measured by diffusion MRI, and the amplitude of low-frequency fluctuation (ALFF) measured by blood oxygenation-level-dependent (BOLD) MRI in 78 ESRD patients versus 64 healthy controls (HCs), followed by a mediation effect analysis to explore the relationship between neuroimaging findings, cognitive impairments and uremic toxins. Two joint group-discriminative independent components (ICs) were found to show covariant abnormalities across FA, GMV, and ALFF (all p < 0.05). The most dominant joint IC revealed associative patterns of alterations of GMV (in the precentral gyrus, occipital lobe, temporal lobe, parahippocampal gyrus, and hippocampus), alterations of ALFF (in the precuneus, superior parietal gyrus, and superior occipital gyrus), and of white matter FA (in the corticospinal tract and inferior frontal occipital fasciculus). Another significant IC revealed associative alterations of GMV (in the dorsolateral prefrontal and orbitofrontal cortex) and FA (in the forceps minor). Moreover, the brain changes identified by FA and GMV in the above-mentioned brain regions were found to mediate the negative correlation between serum phosphate and mini-mental state examination (MMSE) scores (all p < 0.05). The mCCA+jICA method was demonstrated to be capable of revealing covariant abnormalities across neuronal features of different types in ESRD patients as contrasted to HCs, and joint brain changes may play an important role in mediating the relationship between serum toxins and CIs in ESRD. Our results show the mCCA+jICA fusion analysis approach may provide new insights into similar neurobiological studies.

Diffusion tensor imaging and plasma immunological biomarker panel in a rat traumatic brain injury (TBI) model and in human clinical TBI.

Neuroinflammatory reactions play a significant role in the pathology and long-term consequences of traumatic brain injury (TBI) and may mediate salutogenic processes that white matter integrity. This study aimed to investigate the relationship between inflammatory markers and white matter integrity following TBI in both a rat TBI model and clinical TBI cases. In the rat model, blood samples were collected following a controlled cortical impact (CCI) to assess a panel of inflammatory markers; MR-based diffusion tensor imaging (DTI) was employed to evaluate white matter integrity 60 days post-injury. 15 clinical TBI patients were similarly assessed for a panel of inflammatory markers and DTI post-intensive care unit discharge. Blood samples from healthy controls were used for comparison of the inflammatory markers. Time-dependent elevations in immunological markers were observed in TBI rats, with a correlation to preserved fractional anisotropy (FA) in white matter. Specifically, TBI-induced increased plasma levels of IL-1β, IL-6, G-CSF, CCL3, CCL5, and TNF-α were associated with higher white matter integrity, as measured by FA. Clinical cases had similar findings: elevated inflammatory markers (relative to controls) were associated with preservation of FA in vulnerable white matter regions. Inflammatory markers in post-TBI plasma samples are ambivalent with respect to prediction of favourable outcome versus a progression to more pervasive pathology and morbidity.

Diffusion in the corpus callosum predicts persistence of clinical symptoms after mild traumatic brain injury, a multi-scanner study.

Mild traumatic brain injuries (mTBIs) comprise 80% of all TBI, but conventional MRI techniques are often insensitive to the subtle changes and injuries produced in a concussion. Diffusion tensor imaging (DTI) is one of the most sensitive MRI techniques for mTBI studies with outcome and symptom associations described. The corpus callosum (CC) is one of the most studied fiber tracts in TBI and mTBI, but the comprehensive post-mTBI symptom relationship has not fully been explored. This is a retrospective observational study of how quantitative DTI data of the CC and its sub-regions may relate to clinical presentation of symptoms and timing of resolution of symptoms in patients diagnosed with uncomplicated mTBI. DTI and clinical data were obtained retrospectively from 446 (mean age 42 years, range 13-82) civilian patients. From patient medical charts, presentation of the following common post-concussive symptoms was noted: headache, balance issues, cognitive deficits, fatigue, anxiety, depression, and emotional lability. Also recorded was the time between injury and a visit to the physician when improvement or resolution of a particular symptom was reported. FA values from the total CC and 3 subregions of the CC (genu or anterior, mid body, and splenium or posterior) were obtained from hand tracing on the Olea Sphere v3.0 SP12 free-standing workstation. DTI data was obtained from 8 different 3T MRI scanners and harmonized via ComBat harmonization. The statistical models used to explore the association between regional Fractional Anisotropy (FA) values and symptom presentation and time to symptom resolution were logistic regression and interval-censored semi-parametric Cox proportional hazard models, respectively. Subgroups related to age and timing of first scan were also analyzed. Patients with the highest FA in the total CC (p = 0.01), anterior CC (p < 0.01), and mid-body CC (p = 0.03), but not the posterior CC (p = 0.91) recovered faster from post-concussive cognitive deficits. Patients with the highest FA in the posterior CC recovered faster from depression (p = 0.04) and emotional lability (p = 0.01). There was no evidence that FA in the CC or any of its sub-regions was associated with symptom presentation or with time to resolution of headache, balance issues, fatigue, or anxiety. Patients with mTBI under 40 had higher FA in the CC and the anterior and mid-body subregions (but not the posterior subregion: p = 1.00) compared to patients 40 or over (p ≤ 0.01). There was no evidence for differences in symptom presentation based on loss of consciousness (LOC) or sex (p ≥ 0.18). This study suggests that FA of the CC has diagnostic and prognostic value for clinical assessment of mTBI in a large diverse civilian population, particularly in patients with cognitive symptoms.

Microstructural Organization of Distributed White Matter Associated With Fine Motor Control in US Service Members With Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is the most common form of brain injury. While most individuals recover from mTBI, roughly 20% experience persistent symptoms, potentially including reduced fine motor control. We investigate relationships between regional white matter organization and subcortical volumes associated with performance on the Grooved Pegboard (GPB) test in a large cohort of military Service Members and Veterans (SM&Vs) with and without a history of mTBI(s). Participants were enrolled in the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. SM&Vs with a history of mTBI(s) (n = 847) and without mTBI (n = 190) underwent magnetic resonance imaging and the GPB test. We first examined between-group differences in GPB completion time. We then investigated associations between GPB performance and regional structural imaging measures (tractwise diffusivity, subcortical volumes, and cortical thickness) in SM&Vs with a history of mTBI(s). Lastly, we explored whether mTBI history moderated associations between imaging measures and GPB performance. SM&Vs with mTBI(s) performed worse than those without mTBI(s) on the non-dominant hand GPB test at a trend level (p < 0.1). Higher fractional anisotropy (FA) of tracts including the posterior corona radiata, superior longitudinal fasciculus, and uncinate fasciculus were associated with better GPB performance in the dominant hand in SM&Vs with mTBI(s). These findings support that the organization of several white matter bundles are associated with fine motor performance in SM&Vs. We did not observe that mTBI history moderated associations between regional FA and GPB test completion time, suggesting that chronic mTBI may not significantly influence fine motor control.

Association of Olfaction and Microstructural Integrity of Brain Tissue in Community-Dwelling Adults: Atherosclerosis Risk in Communities Neurocognitive Study.

Research on olfaction and brain neuropathology may help understand brain regions associated with normal olfaction and dementia pathophysiology. To identify early regional brain structures affected in poor olfaction, we examined cross-sectional associations of microstructural integrity of the brain with olfaction in the Atherosclerosis Risk in Communities Neurocognitive Study. Participants were selected from a prospective cohort study of community-dwelling adults; selection criteria included the following: evidence of cognitive impairment, participation in a previous MRI study, and a random sample of cognitively normal participants. Microstructural integrity was measured by 2 diffusion tensor imaging (DTI) measures, fractional anisotropy (FA) and mean diffusivity (MD), and olfaction by a 12-item odor identification test at the same visit. Higher FA and MD values indicate better and worse microstructural integrity, respectively, and higher odor identification scores indicate better olfaction. We used brain region-specific linear regression models to examine associations between DTI measures and olfaction, adjusting for potential confounders. Among 1,418 participants (mean age 76 ± 5 years, 41% male, 21% Black race, 59% with normal cognition), the mean olfaction score was 9 ± 2.3. Relevant to olfaction, higher MD in the medial temporal lobe (MTL) regions, namely the hippocampus (β -0.79 [95% CI -0.94 to -0.65] units lower olfaction score per 1 SD higher MD), amygdala, entorhinal area, and some white matter (WM) tracts connecting to these regions, was associated with olfaction. We also observed associations with MD and WM FA in multiple atlas regions that were not previously implicated in olfaction. The associations between MD and olfaction were particularly stronger in the MTL regions among individuals with mild cognitive impairment (MCI) compared with those with normal cognition (e.g., βhippocampus -0.75 [95% CI -1.02 to -0.49] and -0.44 [95% CI -0.63 to -0.26] for MCI and normal cognition, respectively, p interaction = 0.004). Neuronal microstructural integrity in multiple brain regions, particularly the MTL (the regions known to be affected in early Alzheimer disease), is associated with odor identification ability. Differential associations in the MTL regions among cognitively normal individuals compared with those with MCI may reflect the earlier vs later effects of the dementia pathogenesis. It is likely that some of the associated regions may not have any functional relevance to olfaction.

White matter alterations in mild cognitive impairment revealed by meta-analysis of diffusion tensor imaging using tract-based spatial statistics.

The neuropathological mechanism of mild cognitive impairment (MCI) remains unclarified. Diffusion tensor imaging (DTI) studies revealed white matter (WM) microarchitecture alterations in MCI, but consistent findings and conclusions have not yet been drawn. The present coordinate-based meta-analysis (CBMA) of tract-based spatial statistics (TBSS) studies aimed to identify the most prominent and robust WM abnormalities in patients with MCI. A systematic search of relevant studies was conducted through January 2022 to identify TBSS studies comparing fractional anisotropy (FA) between MCI patients and healthy controls (HC). We used the seed-based d mapping (SDM) software to achieve the CBMA and analyze regional FA alterations in MCI. Meta-regression analysis was subsequently applied to explore the potential associations between clinical variables and FA changes. MCI patients demonstrated significantly decreased FA in widely distributed areas in the corpus callosum (CC), including the genu, body, and splenium of the CC, as well as one cluster in the left striatum. FA in the body of the CC and in three clusters in the splenium of the CC was negatively associated with the mean age. Additionally, FA in the genu of the CC and in three clusters in the splenium of the CC had negative correlations with the MMSE scores. Disrupted integrities of the CC and left striatum might play vital roles in the process of cognitive decline. These findings enhanced our understanding of the neural mechanism underlying WM neurodegeneration in MCI and provided perspectives for the early detection and intervention of dementia.Registration number: CRD42022235716.

Altered white matter integrity in euthymic children with bipolar disorder: A tract-based spatial statistical analysis of diffusion tensor imaging

Pediatric Bipolar Disorder (BD) is a serious mental illness that affects children and adolescents, characterized by episodes of mania, depression, and mixed episodes. Recent studies have suggested that abnormalities in the white matter (WM) may be a contributing factor. The neuropathogenesis of BD in children is not well-described, and research in this area is limited. Euthymic phase is a period in which clinical symptoms are present but not severe enough to significantly impact mood and daily behavior. In order to better understand the WM changes associated with BD in children, this study utilized Diffusion Tensor Imaging (DTI), to investigate alterations in WM microstructure. 20 confirmed euthymic BD children (aged 7–16) and 20 typically developing children were included in the study. DTI scans were obtained using a 3 T Magnetom Skyra and were analyzed using tract-based spatial statistics (TBSS) to examine changes in fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). Results showed that compared to the healthy control group, the euthymic BD group exhibited increased FA, AD, RD, and MD values in several brain regions, including the thalamus, precentral corticospinal tract, and superior longitudinal fasciculus. Conversely, decreased values were observed in the body of the corpus callosum and inferior fronto-occipital fasciculus. These findings suggest that alterations in WM microstructure are a hallmark of pediatric bipolar disorder. These findings provide important insights into the brain changes associated with pediatric bipolar disorder and open the door for new avenues of research.

What lies beneath: White matter microstructure in pediatric myalgic encephalomyelitis/chronic fatigue syndrome using diffusion MRI.

Recent studies in adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest that changes in brain white matter microstructural organization may correlate with core ME/CFS symptoms, and represent a potential biomarker of disease. However, this has yet to be investigated in the pediatric ME/CFS population. We examined group differences in macrostructural and microstructural white matter properties, and their relationship with clinical measures, between adolescents recently diagnosed with ME/CFS and healthy controls. Forty-eight adolescents (25 ME/CFS, 23 controls, mean age 16 years) underwent brain diffusion MRI, and a robust multi-analytic approach was used to evaluate white and gray matter volume, regional brain volume, cortical thickness, fractional anisotropy, mean/axial/radial diffusivity, neurite dispersion and density, fiber density, and fiber cross section. From a clinical perspective, adolescents with ME/CFS showed greater fatigue and pain, poorer sleep quality, and poorer performance on cognitive measures of processing speed and sustained attention compared with controls. However, no significant group differences in white matter properties were observed, with the exception of greater white matter fiber cross section of the left inferior longitudinal fasciculus in the ME/CFS group compared with controls, which did not survive correction for intracranial volume. Overall, our findings suggest that white matter abnormalities may not be predominant in pediatric ME/CFS in the early stages following diagnosis. The discrepancy between our null findings and white matter abnormalities identified in the adult ME/CFS literature could suggest that older age and/or longer illness duration influence changes in brain structure and brain-behavior relationships that are not yet established in adolescence.

The correlation between changes in gray matter microstructure and cerebral blood flow in Alzheimer's disease.

To investigate the relationship between changes in cerebral blood flow (CBF) and gray matter (GM) microstructure in Alzheimer's disease (AD) and mild cognitive impairment (MCI). A recruited cohort of 23 AD patients, 40 MCI patients, and 37 normal controls (NCs) underwent diffusional kurtosis imaging (DKI) for microstructure evaluation and pseudo-continuous arterial spin labeling (pCASL) for CBF assessment. We investigated the differences in diffusion- and perfusion-related parameters across the three groups, including CBF, mean diffusivity (MD), mean kurtosis (MK), and fractional anisotropy (FA). These quantitative parameters were compared using volume-based analyses for the deep GM and surface-based analyses for the cortical GM. The correlation between CBF, diffusion parameters, and cognitive scores was assessed using Spearman coefficients, respectively. The diagnostic performance of different parameters was investigated with k-nearest neighbor (KNN) analysis, using fivefold cross-validation to generate the mean accuracy (mAcc), mean precision (mPre), and mean area under the curve (mAuc). In the cortical GM, CBF reduction primarily occurred in the parietal and temporal lobes. Microstructural abnormalities were predominantly noted in the parietal, temporal, and frontal lobes. In the deep GM, more regions showed DKI and CBF parametric changes at the MCI stage. MD showed most of the significant abnormalities among all the DKI metrics. The MD, FA, MK, and CBF values of many GM regions were significantly correlated with cognitive scores. In the whole sample, the MD, FA, and MK were associated with CBF in most evaluated regions, with lower CBF values associated with higher MD, lower FA, or lower MK values in the left occipital lobe, left frontal lobe, and right parietal lobe. CBF values performed best (mAuc = 0.876) for distinguishing the MCI from the NC group. Last, MD values performed best (mAuc = 0.939) for distinguishing the AD from the NC group. Gray matter microstructure and CBF are closely related in AD. Increased MD, decreased FA, and MK are accompanied by decreased blood perfusion throughout the AD course. Furthermore, CBF values are valuable for the predictive diagnosis of MCI and AD. GM microstructural changes are promising as novel neuroimaging biomarkers of AD.

Altered White Matter Integrity in ADHD Revealed by Meta-analysis of Tract-based Spatial Statistics

Objective: We conducted an updated coordinate-based meta-analysis (CBMA) to determine the most prominent and robust white matter (WM) abnormalities in ADHD based on tract-based spatial statistics (TBSS) findings. Method: The seed-based d mapping (SDM) software was applied to compare regional fractional anisotropy (FA) alterations in ADHD. Subgroup meta-analyses in the pure ADHD without comorbidity subgroup, the children and adolescents subgroup, and the adults subgroup were also explored, respectively. Meta-regression analysis was subsequently used to examine potential correlations between demographics and FA changes. Results: Only one cluster in the splenium of corpus callosum (CC) exhibited age-related FA decrease in ADHD individuals in the pooled meta-analysis. The adults ADHD subgroup revealed two clusters with reduced FA lied in the splenium and body of CC. Conclusion: This updated CBMA confirmed the WM abnormalities in the splenium of CC in ADHD, and improved our understanding of the pathogenesis of this neurodevelopmental disorder.

Clinical significance of fractional anisotropy in cerebral white matter regional vulnerability caused by carbon monoxide poisoning: A systematic review and meta-analysis

Carbon monoxide poisoning (COP) can lead to various cerebral white matter (WM) lesions across different disease phases and clinical manifestations, and fractional anisotropy (FA) of diffusion tensor imaging has been widely applied to investigate WM injury in these patients. Here we conducted a systematic review and meta-analysis to investigate the utility of FA in evaluating the regional vulnerability of WM injury caused by COP and explore differences between different disease phases and patient subtypes. We systematically searched PubMed, Medline, Scopus and reference lists of appropriate publications to identify relevant studies. Eight studies with 217 patients with COP and 207 healthy controls (HCs) were included. Eight regions of interest were available to investigate regional vulnerability. The results showed the most significant decrease in FA in orbitofrontal subcortical regions. Comparisons of different disease phases revealed lower FA in the centrum semiovale and corpus callosum in the acute phase, while in the chronic phase, only FA in the centrum semiovale remained significantly decreased. Analysis of different patient subtypes showed that the FA values in the splenium of the corpus callosum were significantly decreased in the patients with delayed neurologic sequelae (DNS) but not in the mixed population (with and without DNS). In conclusion, this meta-analysis highlights the frontal-subcortical regional vulnerability in COP. FA changes in the corpus callosum across different disease phases reflect alterations in underlying microstructures. Extended corpus callosum injury involving the splenium could be an imaging biomarker of the occurrence of DNS.

Childhood trauma is associated with altered white matter microstructural organization in schizophrenia.

It has been reported that childhood trauma (CT) is associated with reductions in fractional anisotropy (FA) in individuals with schizophrenia (SZ). Here, we hypothesized that SZ with high levels of CT will show the greatest reductions in FA in frontolimbic and frontoparietal regions compared to healthy controls (HC) with high trauma levels and participants with no/low levels of CT. Thirty-seven SZ and 129 HC with CT experience were dichotomized into groups of 'none/low' or 'high' levels. Participants underwent diffusion-weighted MRI, and Tract-based spatial statistics were employed to assess the main effect of diagnosis, main effect of CT severity irrespective of diagnosis, and interaction between diagnosis and CT severity. SZ showed FA reductions in the corpus callosum and corona radiata compared to HC. Irrespective of a diagnosis, high CT levels (n=48) were related to FA reductions in frontolimbic and frontoparietal regions compared to those with none/low levels of CT (n=118). However, no significant interaction between diagnosis and high levels of CT was found (n=13). Across all participants, we observed effects of CT on late developing frontolimbic and frontoparietal regions, suggesting that the effects of CT severity on white matter organization may be independent of schizophrenia.

Sex differences, asymmetry, and age-related white matter development in infants and 5-year-olds as assessed with tract-based spatial statistics.

The rapid white matter (WM) maturation of first years of life is followed by slower yet long-lasting development, accompanied by learning of more elaborate skills. By the age of 5 years, behavioural and cognitive differences between females and males, and functions associated with brain lateralization such as language skills are appearing. Diffusion tensor imaging (DTI) can be used to quantify fractional anisotropy (FA) within the WM and increasing values correspond to advancing brain development. To investigate the normal features of WM development during early childhood, we gathered a DTI data set of 166 healthy infants (mean 3.8 wk, range 2-5 wk; 89 males; born on gestational week 36 or later) and 144 healthy children (mean 5.4 years, range 5.1-5.8 years; 76 males). The sex differences, lateralization patterns and age-dependent changes were examined using tract-based spatial statistics (TBSS). In 5-year-olds, females showed higher FA in wide-spread regions in the posterior and the temporal WM and more so in the right hemisphere, while sex differences were not detected in infants. Gestational age showed stronger association with FA values compared to age after birth in infants. Additionally, child age at scan associated positively with FA around the age of 5 years in the body of corpus callosum, the connections of which are important especially for sensory and motor functions. Lastly, asymmetry of WM microstructure was detected already in infants, yet significant changes in lateralization pattern seem to occur during early childhood, and in 5-year-olds the pattern already resembles adult-like WM asymmetry.

Gray and white matter abnormalities in major depressive disorder patients and its associations with childhood adversity

ObjectiveEarly life stress of childhood adversity (CA) may result in major depressive disorder (MDD) by sensitizing individuals to proximal stressors in life events. The neurobiological changes that underlie adult depression may result from the absence of proper care and supervision of caregivers. We aimed to find both gray and white matter abnormalities in MDD patients, who reported the experiences of CA. MethodsThe present study examined cortical alterations in 54 patients with MDD and 167 healthy controls (HCs) using voxel-based morphology and fractional anisotropy (FA) tract-based spatial statistics (TBSS). Both patients and HCs were administered the self-questionnaire clinical scale (the Korean translation of the Childhood Trauma Questionnaire CTQK). Pearson's correlation analysis was performed to find the associations between FA and CTQK. ResultsThe MDD group showed a significant decrease in gray matter (GM) in the left rectus at both the cluster and peak levels after family-wise error correction. The TBSS results showed significantly reduced FA in widespread regions, including the corpus callosum (CC), superior corona radiata, cingulate gyrus, and superior longitudinal fasciculus. The CA was negatively correlated with the FA in CC and crossing pontine tract. ConclusionOur findings demonstrated GM atrophy and white matter (WM) connectivity changes in patients with MDD. The major findings of the widespread FA reduction in WM provided the evidence of brain alterations in MDD. We further propose that the WM would be vulnerable to emotional, physical, and sexual abuse in early childhood during the brain development.