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Sleep deprivation influences several critical functions, yet how it affects human brain white matter (WM) is not well understood. The aim of the present work was to investigate the effect of 32 hours of sleep deprivation on WM microstructure compared to changes observed in a normal sleep-wake cycle (SWC). To this end, we utilised diffusion weighted imaging (DWI) including the diffusion tensor model, diffusion kurtosis imaging and the spherical mean technique, a novel biophysical diffusion model. 46 healthy adults (23 sleep deprived vs 23 with normal SWC) underwent DWI across four time points (morning, evening, next day morning and next day afternoon, after a total of 32 hours). Linear mixed models revealed significant group × time interaction effects, indicating that sleep deprivation and normal SWC differentially affect WM microstructure. Voxel-wise comparisons showed that these effects spanned large, bilateral WM regions. These findings provide important insight into how sleep deprivation affects the human brain.

The degree to which genetic factors influence brain connectivity is beginning to be understood. Large-scale efforts are underway to map the profile of genetic effects in various brain regions. The NIH-funded Human Connectome Project (HCP) is providing data valuable for analyzing the degree of genetic influence underlying brain connectivity revealed by state-of-the-art neuroimaging methods. We calculated the heritability of the fractional anisotropy (FA) measure derived from diffusion tensor imaging (DTI) reconstruction in 481 HCP subjects (194/287 M/F) consisting of 57/60 pairs of mono- and dizygotic twins, and 246 siblings. FA measurements were derived using (Enhancing NeuroImaging Genetics through Meta-Analysis) ENIGMA DTI protocols and heritability estimates were calculated using the SOLAR-Eclipse imaging genetic analysis package. We compared heritability estimates derived from HCP data to those publicly available through the ENIGMA-DTI consortium, which were pooled together from five-family based studies across the US, Europe, and Australia. FA measurements from the HCP cohort for eleven major white matter tracts were highly heritable (h2=0.53–0.90, p<10−5), and were significantly correlated with the joint-analytical estimates from the ENIGMA cohort on the tract and voxel-wise levels. The similarity in regional heritability suggests that the additive genetic contribution to white matter microstructure is consistent across populations and imaging acquisition parameters. It also suggests that the overarching genetic influence provides an opportunity to define a common genetic search space for future gene-discovery studies. Uniquely, the measurements of additive genetic contribution performed in this study can be repeated using online genetic analysis tools provided by the HCP ConnectomeDB web application. •Data from 488 HCP subjects were processed using ENIGMA-DTI protocols.•Heritability in HCP sample was compared to ENIGMA-DTI joint-analytical estimates.•Estimates from HCP and ENIGMA-DTI were highly correlated.•Genetic contribution to white matter integrity is consistent across populations.•Defines common genetic search space for future gene-discovery studies

Although free‐water diffusion reconstruction for diffusion‐weighted imaging (DWI) data can be applied to both single‐shell and multishell data, recent finding in synthetic data suggests that the free‐water indices from single‐shell acquisition should be interpreted with care, as they are heavily influenced by initialization parameters and cannot discriminate between free‐water and mean diffusivity modifications. However, whether using a longer multishell acquisition protocol significantly improve reconstruction for real human MRI data is still an open question. In this study, we compare canonical diffusion tensor imaging (DTI), single‐shell and multishell free‐water imaging (FW) indices derived from a short, clinical compatible diffusion protocol (b = 500 s/mm2, b = 1,000 s/mm2, 32 directions each) on their power to predict brain age. Age was chosen as it is well‐known to be related to widespread modification of the white matter and because brain‐age estimation has recently been found to be relevant to several neurodegenerative diseases. We used a previously developed and validated data‐driven whole‐brain machine learning pipeline to directly compare the precision of brain‐age estimates in a sample of 89 healthy males between 20 and 85 years old. We found that multishell FW outperform DTI indices in estimating brain age and that multishell FW, even when using low (500 ms2) b‐values secondary shell, outperform single‐shell FW. Single‐shell FW led to lower brain‐age estimation accuracy even of canonical DTI indices, suggesting that single‐shell FW indices should be used with caution. For all considered reconstruction algorithms, the most discriminant indices were those measuring free diffusion of water in the white matter. Multishell but not single‐shell free‐water diffusion imaging predicts brain age better than canonical diffusion imaging. Multishell free‐water in isolation performs similarly to more complex models including FA, MD, RD and AD.

Mindfulness meditation training (MMT) reliably reduces stress and anxiety while also improving attention. The primary aim of this study was to investigate the relationship between MMT, stress and anxiety reduction, and its impact upon improvements in attention on the behavioral and neuronal levels. As a second aim, we sought to explore any relationship between MMT, attention, and modified states of mind such as flow. 118 healthy, meditation-naïve, participants were either assigned to a 31-day, web-based, MMT or an active control, health training (HT). Participants underwent functional magnetic resonance imaging while performing the attention network test (ANT) to assess functional and behavioural attentional changes, diffusion tensor imaging (DTI) to assess microstructural neuronal changes and completed relevant questionnaires to explore changes in psychological outcomes. Results confirmed a reduction in perceived stress and anxiety levels in the MMT group and significant improvements in the overall reaction time during the ANT, albeit no specific effects on the attentional components were observed. No statistically significant changes were found in the HT group. Interestingly, a significant group-by-time interaction was seen in flow experience. Functional data exhibited an increased activity in the superior frontal gyrus, posterior cingulate cortex, and right hippocampus during the alerting condition of the ANT after the MMT; decreased stress and trait anxiety were significantly correlated with the activation in the right hippocampus, and increased flow was also significantly correlated with all the aforementioned areas. DTI data showed increased fractional anisotropy values in the right uncinate fasciculus indicating white matter microarchitecture improvement between the right hippocampus and frontal areas of the brain. This study, therefore, demonstrates the effectiveness of web-based MMT on overall well-being and attentional performance, while also providing insight into the relationship between psychological outcomes, attention, and neuroplastic changes.

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

Background Traditional neuromodulation strategies show promise in enhancing cognitive abilities in bipolar disorder (BD) but remain suboptimal. This study introduces a novel multimodal neurostimulation (MNS) protocol to improve therapeutic outcomes. Methods The novel MNS protocol used individualized diffusion tensor imaging (DTI) data to identify fiber tracts between the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex. The highest structural connectivity point is selected as the individualized stimulation site, which is then targeted using a combination of optimized transcranial alternating current stimulation (tACS) and robot-assisted navigated repetitive transcranial magnetic stimulation (rTMS). A double-blind randomized controlled trial was conducted to investigate the clinical efficacy of this innovative neuromodulation approach on cognitive abilities in stable-phase BD patients. One hundred BD patients were randomly assigned to four groups: group A (active tACS-active rTMS (MNS protocol)), group B (sham tACS-active rTMS), group C (active tACS-sham rTMS), and group D (sham tACS-sham rTMS). Participants underwent 15 sessions over 3 weeks. Cognitive assessments (THINC integrated tool) were conducted at baseline (week 0) and post-treatment (week 3). Results Sixty-six participants completed all 15 sessions. Group A (MNS protocol) showed superior improvements in Spotter CRT, TMT, and DSST scores compared to other groups at week 3. Only group A exhibited significant activation in the left frontal region post-MNS intervention. The novel MNS protocol was well tolerated, with no significant side effects observed. Conclusions The study indicates that DTI-guided multimodal neurostimulation mode significantly improves cognitive impairments and is safe for stable-phase BD patients. Trial registration ClinicalTrials.gov identifier: NCT05964777.

Purpose We assessed diffusion tensor imaging (DTI) metric changes of the corpus callosum and cingulum correlated to postprocedural ischemic lesion load (ILL) and cognitive performance in transcatheter aortic valve replacement (TAVR). Methods TAVR subjects had DTI post-TAVR (≤ 8 days) and at 6 months (78 participants, males 56%, age 78.8 years ± 6.3) and four neurocognitive tests (pre-TAVR, post-TAVR, 6 months, 1 year). DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD)) were calculated for 7 regions: corpus callosum (genu, body, splenium) and cingulum (cingulate gyrus, parahippocampal cingulum bilaterally). DTI metrics post-TAVR and at 6 months were compared with Student’s t -test ( p  < 0.0071) and ANOVA covarying for sex, ILL ( p  < 0.05) with post hoc analysis of ILL groups ( p  < 0.0167). Repeated-measures linear mixed-effect model ( p  < 0.05) was performed to investigate the effect of time and ILL on cognition. Results At 6 months, significant decrease of the following DTI metrics was detected: AD (genu, body, splenium, right parahippocampal cingulum: p  ≤ 0.0046); MD (body, both cingulate gyri: p  ≤ 0.0050); RD (left cingulate gyrus: p  = 0.0021); FA (splenium: p  < 0.0001). ANOVA confirmed significant effect of female sex on AD + MD reduction (body, right cingulate gyrus) and AD reduction (left cingulate gyrus) ( p  ≤ 0.0254). Significant negative effect of ILL on some DTI metric changes was found (AD + MD-body: p  ≤ 0.0050; MD-left cingulate gyrus: p  = 0.0087). Cognitive performance remained stable with significant negative correlation of ILL and retrograde memory and visual scores ( p  ≤ 0.0483). Conclusion Significant effect of TAVR on cerebral microstructural integrity was found with reduced diffusivities opposite to the trends reported in various neurodegenerative conditions/ageing, notably in women and lower ILL, and with preserved/improved cognition. Trial registration number. NCT02826200 at ClinicalTrials.gov; date of registration: 07. July 2016.

•The fractional anisotropy of the exFAT region is left-lateralized in the 3T sample.•The AFQ analyses detected a coherent set of laterality differences.•The ML models showed a high agreement with the AFQ analyses.•The dissection study showed converging evidence of crossing fibers along exFAT.•An hemispheric-dependent exFAT microstructural fingerprint has been detected. The Extended Frontal Aslant Tract (exFAT) is a recently described tractography-based extension of the Frontal Aslant Tract connecting Broca’s territory to both supplementary and pre-supplementary motor areas, and more anterior prefrontal regions. In this study, we aim to characterize the microstructural properties of the exFAT trajectories as a means to perform a laterality analysis to detect interhemispheric structural differences along the tracts using the Human Connectome Project (HCP) dataset. To that end, the bilateral exFAT was reconstructed for 3T and 7T HCP acquisitions in 120 randomly selected subjects. As a complementary exploration of the exFAT anatomy, we performed a white matter dissection of the exFAT trajectory of two ex-vivo left hemispheres that provide a qualitative assessment of the tract profiles. We assessed the lateralization structural differences in the exFAT by performing: (i) a laterality comparison between the mean microstructural diffusion-derived parameters for the exFAT trajectories, (ii) a laterality comparison between the tract profiles obtained by applying the Automated Fiber Quantification (AFQ) algorithm, and (iii) a cross-validated Machine Learning (ML) classifier analysis using single and combined tract profiles parameters for single-subject classification. The mean microstructural diffusion-derived parameter comparison showed statistically significant differences in mean FA values between left and right exFATs in the 3T sample. The diffusion parameters studied with the AFQ technique suggest that the inferiormost half of the exFAT trajectory has a hemispheric-dependent fingerprint of microstructural properties, with an increased measure of tissue hindrance in the orthogonal plane and a decreased measure of orientational dispersion along the main tract direction in the left exFAT compared to the right exFAT. The classification accuracy of the ML models showed a high agreement with the magnitude of those differences.

Introduction The current multi-center, randomized, double-blind study was conducted among children with cerebral palsy (CP) to assess the safety and efficacy of umbilical cord blood mononuclear cell (UCB-MNC). We performed the diffusion tensor imaging to assess the changes in the white matter structure. Methods Males and females aged 4 to 14 years old with spastic CP were included. Eligible participants were allocated in 4:1 ratio to be in the experimental or control groups; respectively. Individuals who were assigned in UCB-MNC group were tested for human leukocyte antigen (HLA) and fully-matched individuals were treated with UCB-MNCs. A single dose (5 × 10 6 /kg) UCB-MNCs were administered via intrathecal route in experimental group. The changes in gross motor function measure (GMFM)-66 from baseline to one year after treatment were the primary endpoints. The mean changes in modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also evaluated and compared between groups. The mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR) were the secondary endpoints. Adverse events were safety endpoint. Results There were 72 included individuals (36 cases in each group). The mean GMFM-66 scores increased in experimental group; compared to baseline (+ 9.62; 95%CI: 6.75, 12.49) and control arm (β: 7.10; 95%CI: 2.08, 12.76; Cohen’s d: 0.62) and mean MAS reduced in individuals treated with UCB-MNCs compared to the baseline (-0.87; 95%CI: -1.2, -0.54) and control group (β: -0.58; 95%CI: -1.18, -0.11; Cohen’s d: 0.36). The mean PEDI scores and mean CP-QoL scores in two domains were higher in the experimental group compared to the control. The imaging data indicated that mean FA increased and MD decreased in participants of UCB-MNC group indicating improvements in white matter structure. Lower back pain, headaches, and irritability were the most common adverse events within 24 h of treatment that were related to lumbar puncture. No side effects were observed during follow-up. Conclusions This trial showed that intrathecal injection of UCB-MNCs were safe and effective in children with CP. Trial Registration The study was registered with ClinicalTrials.gov ( NCT03795974 ).

Objectives To investigate whether DTI allows assessment of renal impairment and pathology in patients with chronic glomerulonephritis. Materials and methods Seventy-five patients and 20 healthy volunteers were enrolled in this study. Renal function and kidney biopsies were evaluated. For DTI, a respiratory-triggered coronal EPI sequence was performed (TR, 1400 ms; TE, 76 ms; diffusion direction, 6; NEX, 4; b values, 0 and 600 s/mm2; slices thickness, 6 mm, with no intersection gap). Renal ADC and FA values were calculated and compared between the groups. Correlations between ADC/FA and histopathology were evaluated. Results ADC values decreased with increased stages. ADC differences in renal parenchyma at different disease stages were found, with the exception of the control group compared with stage 1 patients; similar results were obtained for FA. ADC values in the cortex and medulla in stage 1-3 patients were both statistically different, similar to the FA values. A significant negative correlation was found between the percentage of glomerulosclerosis and FA in the renal cortex ( r  = -0.74), similar to the degree of tubulointerstitial fibrosis with FA in the medulla ( r  = -0.76). Conclusions ADC and FA values are correlated with the degree of renal impairment, the percentage of glomerulosclerosis, and area of interstitial fibrosis. Key Points • DTI can be used to assess renal function impairment in patients with chronic glomerulonephritis . • ADC and FA values were correlated with tubulointerstitial fibrosis and glomerulosclerosis . • Identification of renal impairment is helpful for timely treatment . • DTI can be used for non-invasive assessment of renal pathology .