White Matter Integrity Research Articles

The effect of live music therapy on white matter microstructure in very preterm infants – A randomized controlled trial

ObjectiveMusic therapy (MT) is proposed to enrich the acoustic environment of very preterm infants (VPT) on the neonatal intensive care unit during a vulnerable period of brain development. The objective of this study was to investigate the effect of MT on the white matter (WM) microstructure. It is hypothesized that MT affects WM integrity in VPT. MethodsRandomized controlled trial enrolling infants born <32 weeks’ gestation. Infants were randomized to MT or standard care. Live MT was provided twice weekly from the second postnatal week onwards by a trained music therapist. At term equivalent age, participants underwent a cranial magnetic resonance imaging scan including sequences for diffusion tensor imaging analysis. Differences in WM microstructure were assessed using tract based spatial statistics with fractional anisotropy. ResultsOf 80 infants enrolled, 42 were eligible for diffusion tensor imaging analysis (MT: n = 22, standard care: n = 20). While primary tract based spatial statistics analysis revealed no significant differences between groups, post hoc analysis with uncorrected p-values and a significance threshold of p < 0.01 revealed significant fractional anisotropy differences in several WM tracts including the bilateral superior longitudinal fasciculus, the left forceps minor and left fasciculus uncinatus, the corpus callosum, the left external capsule, and the right corticospinal tract. ConclusionPost hoc analysis results suggest an effect of MT on WM integrity in VPT. Larger studies including long-term outcome are necessary to confirm these effects of MT on WM microstructure and to assess its impact on clinical neurodevelopment. Clinical trial registrationClinical trial number DRKS00025753.

Premenopausal bilateral oophorectomy and brain white matter brain integrity in later-life.

Premenopausal bilateral oophorectomy (PBO) is associated with later-life cognition, but the underlying brain changes remain unclear. We assessed the impact of PBO and PBO age on white matter integrity. Female participants with regional diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA) and mean diffusivity (MD) were included (22 with PBO<40 years; 43 with PBO 40-45 years; 39 with PBO 46-49 years; 907 referents without PBO<50 years). Linear regression models adjusted for age and apolipoprotein E (APOE) genotype. Females with PBO<40 years, compared to referents, had lower FA and higher MD in the anterior corona radiata, genu of the corpus collosum, inferior fronto-occipital fasciculus, superior occipital, and superior temporal white matter. Females who underwent PBO between 45 and 49 also had some changes in white matter integrity. Females who underwent PBO<40 years had reduced white matter integrity across multiple regions in later-life. These results are important for females considering PBO for noncancerous conditions. Females with premenopausal bilateral oophorectomy (PBO)<40 years had lower FA versus referents. Females with PBO<40 years had higher MD in many regions versus referents. Adjusting for estrogen replacement therapy use did not attenuate results. Females with PBO 45-49 years also had some white matter changes versus referents.

Greater cortical thinning and microstructural integrity loss in myotonic dystrophy type 1 compared to myotonic dystrophy type 2

BackgroundMyotonic dystrophy is a multisystem disorder characterized by widespread organic involvement including central nervous system symptoms. Although myotonic dystrophy disease types 1 (DM1) and 2 (DM2) cover a similar spectrum of symptoms, more pronounced clinical and brain alterations have been described in DM1. Here, we investigated brain volumetric and white matter alterations in both disease types and compared to healthy controls (HC).MethodsMRI scans were obtained from 29 DM1, 27 DM2, and 56 HC. We assessed macro- and microstructural brain changes by surface-based analysis of cortical thickness of anatomical images and tract-based spatial statistics of fractional anisotropy (FA) obtained by diffusion-weighted imaging, respectively. Global MRI measures were related to clinical and neuropsychological scores to evaluate their clinical relevance.ResultsCortical thickness was reduced in both patient groups compared to HC, showing similar patterns of regional distribution in DM1 and DM2 (occipital, temporal, frontal) but more pronounced cortical thinning for DM1. Similarly, FA values showed a widespread decrease in DM1 and DM2 compared to HC. Interestingly, FA was significantly lower in DM1 compared to DM2 within most parts of the brain.ConclusionComparisons between DM1 and DM2 indicate a more pronounced cortical thinning of grey matter and a widespread reduction in microstructural integrity of white matter in DM1. Future studies are required to unravel the underlying and separating mechanisms for the disease courses of the two types and their neuropsychological symptoms.

Perinatal influences on academic achievement and the developing brain: a scoping systematic review.

In this PRISMA-compliant systematic review, we identify and synthesize the findings of research in which neuroimaging and assessments of achievement have been used to examine the relationships among aspects of developmental programming, neurodevelopment, and achievement in reading and mathematics. Forty-seven studies met inclusion criteria. The majority examined the impact of prematurity (n = 32) and prenatal alcohol exposure (n = 13). Several prematurity studies reported a positive correlation between white-matter integrity of callosal fibers and executive functioning and/or achievement, and white matter properties were consistently associated with cognitive and academic performance in preterm and full-term children. Volumetric studies reported positive associations between academic and cognitive abilities and white and gray matter volume in regions such as the insula, putamen, and prefrontal lobes. Functional MRI studies demonstrated increased right-hemispheric language processing among preterm children. Altered activation of the frontoparietal network related to numerical abilities was also reported. Prenatal alcohol exposure studies reported alterations in white matter microstructure linked to deficits in cognitive functioning and academic achievement, including mathematics, reading, and vocabulary skills. Volumetric studies reported reductions in cerebral, cerebellar, and subcortical gray matter volumes associated with decreased scores on measures of executive functioning, attention, working memory, and academic performance. Functional MRI studies demonstrated broad, diffuse activation, reduced activation in canonical regions, and increased activation in non-canonical regions during numeric tasks. A preponderance of studies linked prematurity and prenatal alcohol exposure to altered neurodevelopmental processes and suboptimal academic achievement. Limitations and recommendations for future research are discussed. Identifier: DOI 10.17605/OSF.IO/ZAN67.

Microglia protect against age-associated brain pathologies

Microglia are brain-resident macrophages that contribute to central nervous system (CNS) development, maturation, and preservation. Here, we examine the consequences of permanent microglial deficiencies on brain aging using the Csf1rΔFIRE/ΔFIRE mouse model. In juvenile Csf1rΔFIRE/ΔFIRE mice, we show that microglia are dispensable for the transcriptomic maturation of other brain cell types. By contrast, with advancing age, pathologies accumulate in Csf1rΔFIRE/ΔFIRE brains, macroglia become increasingly dysregulated, and white matter integrity declines, mimicking many pathological features of human CSF1R-related leukoencephalopathy. The thalamus is particularly vulnerable to neuropathological changes in the absence of microglia, with atrophy, neuron loss, vascular alterations, macroglial dysregulation, and severe tissue calcification. We show that populating Csf1rΔFIRE/ΔFIRE brains with wild-type microglia protects against many of these pathological changes. Together with the accompanying study by Chadarevian and colleagues1, our results indicate that the lifelong absence of microglia results in an age-related neurodegenerative condition that can be counteracted via transplantation of healthy microglia.

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.

Sex, racial, and APOE-ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease.

The effects of sex, race, and Apolipoprotein E (APOE) - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized. Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.06 ± 9.75) with 9,671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex, race, and APOE-ε4 carrier status. Sex differences in FAFWcorr in association and projection tracts, racial differences in FAFWcorr in projection tracts, and APOE-ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. There are prominent differences in white matter microstructure by sex, race, and APOE-ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted.

Longitudinal associations of reproductive factors and exogeneous estrogens with neuroimaging biomarkers of Alzheimer's disease and cerebrovascular disease.

Female-specific reproductive factors and exogeneous estrogen use are associated with cognition in later life. However, the underlying mechanisms are not understood. The present study aimed to investigate the effect of reproductive factors on neuroimaging biomarkers of Alzheimer's disease (AD) and cerebrovascular pathologies. We evaluated 389 females (median age of 71.7 years) enrolled in the Mayo Clinic Study of Aging with reproductive history data and longitudinal magnetic resonance imaging (MRI) scans. We used linear mixed effect models to examine the associations between reproductive factors and changes in neuroimaging measures. Ever hormonal contraception (HC) use was longitudinally associated with higher fractional anisotropy across the corpus callosum, lower white matter hyperintensity (WMH) volume, and greater cortical thickness in an AD meta-region of interest (ROI). The initiation of menopausal hormone therapy (MHT)>5 years post menopause was associated with higher WMH volume. HC use and initiation of MHT>5 years post menopause were generally associated with neuroimaging biomarkers of cerebrovascular pathologies. Hormonal contraception use was associated with better brain white matter (WM) integrity. Initiation of menopausal hormone therapy>5 years post menopause was associated with worsening brain WM integrity. Hormonal contraception use was associated with greater cortical thickness. Ages at menarche and menopause and number of pregnancies were not associated with imaging measures. There were few associations between reproductive factors or exogenous estrogens and amyloid or tau PET.

A Pilot Study Investigating the Use of Serum Glial Fibrillary Acidic Protein to Monitor Changes in Brain White Matter Integrity After Repetitive Head Hits During a Single Collegiate Football Game.

Repetitive head hits (RHHs) in sports and military settings are increasingly recognized as a risk factor for adverse neurological outcomes, but they are not currently tracked. Blood-based biomarkers of concussion have recently been shown to increase after nonconcussive RHHs during a single sporting contest, raising the possibility that they could be used in real time to monitor the brain's early response to repeated asymptomatic head hits. To test this hypothesis, we measured GFAP in serum immediately before (T0), immediately after (T1) and 45 min (T2) after a single collegiate football game in 30 athletes. Glial fibrillary acidic protein (GFAP) changes were correlated with three measures of head impact exposure (number of hits, total linear acceleration, and total rotational acceleration captured by helmet impact sensors) and to changes in brain white matter (WM) integrity, estimated by regional changes in fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging from 24 h before (T1) to 48 h after (T3) the game. To account for the potentially confounding effects of physical exertion on GFAP, correlations were adjusted for kilocalories of energy expended during the game measured by wearable body sensors. All 30 participants were male with a mean age of 19.5 ± 1.2 years. No participant had a concussion during the index game. We observed a significant increase in GFAP from T0 to T1 (mean 79.69 vs. 91.95 pg/mL, p = 0.008) and from T0 to T2 (mean 79.69 vs. 99.21 pg/mL, p < 0.001). WM integrity decreased in multiple WM regions but was statistically significant in the right fornix (mean % FA change -1.43, 95% confidence interval [CI]: -2.20, -0.66). T0 to T2 increases in GFAP correlated with reduced FA in the left fornix, right fornix, and right medical meniscus and with increased MD in the right fornix (r-values ranged from 0.59 to 0.61). Adjustment for exertion had minimal effect on these correlations. GFAP changes did not correlate to head hit exposure, but after adjustment for exertion, T0 to T2 increases correlated with all three hit metrics (r-values ranged from 0.69 to 0.74). Thus, acute elevations in GFAP after a single collegiate football game of RHHs correlated with in-game head hit exposure and with reduced WM integrity 2 days later. These results suggest that GFAP may be a biologically relevant indicator of the brain's early response to RHHs during a single sporting event. Developing tools to measure the neurological response to RHHs on an individual level has the potential to provide insight into the heterogeneity in adverse outcomes after RHH exposure and for developing effective and personalized countermeasures. Owing to the small sample size, these findings should be considered preliminary; validation in a larger, independent cohort is necessary.

Alzheimer’s-linked axonal changes accompany elevated antidromic action potential failure rate in aged mice

Alzheimer’s disease (AD) affects both grey and white matter (WM), but considerably more is known about the former. Interestingly, WM disruption has been consistently observed and thoroughly described using imaging modalities, particularly MRI which has shown WM functional disconnections between the hippocampus and other brain regions during AD pathogenesis when early neurodegeneration and synapse loss are also evident. Nonetheless, high-resolution structural and functional analyses of WM during AD pathogenesis remain scarce. Given the importance of the myelinated axons in the WM for conveying information across brain regions, such studies will provide valuable information on the cellular drivers and consequences of WM disruption that contribute to the characteristic cognitive decline of AD. Here, we employed a multi-scale approach to investigate hippocampal WM disruption during AD pathogenesis and determine whether hippocampal WM changes accompany the well-documented grey matter losses. Our data indicate that ultrastructural myelin disruption is elevated in the alveus in human AD cases and increases with age in 5xFAD mice. Unreliable action potential propagation and changes to sodium channel expression at the node of Ranvier co-emerged with this deterioration. These findings provide important insight to the neurobiological substrates and functional consequences of decreased WM integrity and are consistent with the notion that hippocampal disconnection contributes to cognitive changes in AD.

Dolphin CONTINUE: a multi-center randomized controlled trial to assess the effect of a nutritional intervention on brain development and long-term outcome in infants born before 30 weeks of gestation

BackgroundPreterm born infants are at risk for brain injury and subsequent developmental delay. Treatment options are limited, but optimizing postnatal nutrition may improve brain- and neurodevelopment in these infants. In pre-clinical animal models, combined supplementation of docosahexaenoic acid (DHA), choline, and uridine-5-monophosphate (UMP) have shown to support neuronal membrane formation. In two randomized controlled pilot trials, supplementation with the investigational product was associated with clinically meaningful improvements in cognitive, attention, and language scores. The present study aims to assess the effect of a similar nutritional intervention on brain development and subsequent neurodevelopmental outcome in infants born very and extremely preterm.MethodsThis is a randomized, placebo-controlled, double-blinded, parallel-group, multi-center trial. A total of 130 infants, born at less than 30 weeks of gestation, will be randomized to receive a test or control product between term-equivalent age and 12 months corrected age (CA). The test product is a nutrient blend containing DHA, choline, and UMP amongst others. The control product contains only fractions of the active components. Both products are isocaloric powder supplements which can be added to milk and solid feeds. The primary outcome parameter is white matter integrity at three months CA, assessed using diffusion-tensor imaging (DTI) on MRI scanning. Secondary outcome parameters include volumetric brain development, cortical thickness, cortical folding, the metabolic and biochemical status of the brain, and product safety. Additionally, language, cognitive, motor, and behavioral development will be assessed at 12 and 24 months CA, using the Bayley Scales of Infant Development III and digital questionnaires (Dutch version of the Communicative Development Inventories (N-CDI), Ages and Stages Questionnaire 4 (ASQ-4), and Parent Report of Children’s Abilities – Revised (PARCA-R)).DiscussionThe investigated nutritional intervention is hypothesized to promote brain development and subsequent neurodevelopmental outcome in preterm born infants who have an inherent risk of developmental delay. Moreover, this innovative study may give rise to new treatment possibilities and improvements in routine clinical care.Trial registrationWHO International Clinical Trials Registry: NL-OMON56181 (registration assigned October 28, 2021).

Divergent functional connectivity changes associated with white matter hyperintensities

Age-related white matter hyperintensities are a common feature and are known to be negatively associated with structural integrity, functional connectivity, and cognitive performance. However, this has yet to be fully understood mechanistically. We analyzed multiple MRI modalities acquired in 465 non-demented individuals from the Swedish BioFINDER study including 334 cognitively normal and 131 participants with mild cognitive impairment. White matter hyperintensities were automatically quantified using fluid-attenuated inversion recovery MRI and parameters from diffusion tensor imaging were estimated in major white matter fibre tracts. We calculated fMRI resting state-derived functional connectivity within and between predefined cortical regions structurally linked by the white matter tracts. How change in functional connectivity is affected by white matter lesions and related to cognition (in the form of executive function and processing speed) was explored. We examined the functional changes using a measure of sample entropy. As expected hyperintensities were associated with disrupted structural white matter integrity and were linked to reduced functional interregional lobar connectivity, which was related to decreased processing speed and executive function. Simultaneously, hyperintensities were also associated with increased intraregional functional connectivity, but only within the frontal lobe. This phenomenon was also associated with reduced cognitive performance. The increased connectivity was linked to increased entropy (reduced predictability and increased complexity) of the involved voxels’ blood oxygenation level-dependent signal. Our findings expand our previous understanding of the impact of white matter hyperintensities on cognition by indicating novel mechanisms that may be important beyond this particular type of brain lesions.

Mapping the interplay of atrial fibrillation, brain structure, and cognitive dysfunction.

Atrial fibrillation (AF) is associated with an elevated risk of cognitive impairment and dementia. Understanding the cognitive sequelae and brain structural changes associated with AF is vital for addressing ensuing health care needs. We examined 1335 stroke-free individuals with AF and 2683 matched controls using neuropsychological assessments and multimodal neuroimaging. The analysis revealed that individuals with AF exhibited deficits in executive function, processing speed, and reasoning, accompanied by reduced cortical thickness, elevated extracellular free-water content, and widespread white matter abnormalities, indicative of small vessel pathology. Notably, brain structural differences statistically mediated the relationship between AF and cognitive performance. Integrating a comprehensive analysis approach with extensive clinical and magnetic resonance imaging data, our study highlights small vessel pathology as a possible unifying link among AF, cognitive decline, and abnormal brain structure. These insights can inform diagnostic approaches and motivate the ongoing implementation of effective therapeutic strategies. Highlights We investigated neuropsychological and multimodal neuroimaging data of 1335 individuals with atrial fibrillation (AF) and 2683 matched controls. Our analysis revealed AF-associated deficits in cognitive domains of attention, executive function, processing speed, and reasoning. Cognitive deficits in the AF group were accompanied by structural brain alterations including reduced cortical thickness and gray matter volume, alongside increased extracellular free-water content as well as widespread differences of white matter integrity. Structural brain changes statistically mediated the link between AF and cognitive performance, emphasizing the potential of structural imaging markers as a diagnostic tool in AF-related cognitive decline.

Abolishing UCHL1's hydrolase activity exacerbates ischemia-induced axonal injury and functional deficits in mice.

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a neuronal protein important in maintaining axonal integrity and motor function and may be important in the pathogenesis of many neurological disorders. UCHL1 may ameliorate acute injury and improve recovery after cerebral ischemia. In the current study, the hypothesis that UCHL1's hydrolase activity underlies its effect in maintaining axonal integrity and function is tested after ischemic injury. Hydrolase activity was inhibited by treatment with a UCHL1 hydrolase inhibitor or by employing knockin mice bearing a mutation in the hydrolase active site (C90A). Ischemic injury was induced by oxygen-glucose deprivation (OGD) in brain slice preparations and by transient middle cerebral artery occlusion (tMCAO) surgery in mice. Hydrolase activity inhibition increased restoration time and decreased the amplitude of evoked axonal responses in the corpus callosum after OGD. Mutation of the hydrolase active site exacerbated white matter injury as detected by SMI32 immunohistochemistry, and motor deficits as detected by beam balance and cylinder testing after tMCAO. These results demonstrate that UCHL1 hydrolase activity ameliorates white matter injury and functional deficits after acute ischemic injury and support the hypothesis that UCHL1 activity plays a significant role in preserving white matter integrity and recovery of function after cerebral ischemia.

Mediating role of right superior corona microstructural changes in linking attentional control and trait anxiety among youth with childhood maltreatment.

This study explores the neural correlates between attentional control and trait anxiety among youth with a history of childhood maltreatment. Using diffusion tensor imaging, we investigated the microstructural integrity of brain white matter, particularly focusing on the right superior corona radiata (SCA-R). A total of 173 university students with experiences of childhood maltreatment underwent behavioral assessments using the Attentional Control Scale and trait anxiety measurements via the Spielberger State-Trait Anxiety Inventory. Our analysis found significant correlations between fractional anisotropy values in the SCA-R and trait anxiety levels, controlled for age and sex. Notably, SCA-R fractional anisotropy values partially mediated the relationship between attentional control and trait anxiety, suggesting a potential pathway through which attentional control could mitigate trait anxiety. These insights highlight attentional control as a potential mitigating factor against trait anxiety, particularly noting the partial mediation role of the SCA-R. Importantly, this study is descriptive and correlative, highlighting associations rather than causal relationships among the variables studied. These findings enhance our understanding of the neural mechanisms underlying anxiety in individuals with a history of childhood maltreatment.

The impact of alcohol and tobacco on the white matter integrity during adolescence and young adulthood neurodevelopment

The impact of alcohol and tobacco on the white matter integrity during adolescence and young adulthood neurodevelopment

Multimodal dementia identification using lifestyle and brain lesions, a machine learning approach

Dementia diagnosis often relies on expensive and invasive neuroimaging techniques that limit access to early screening. This study proposes an innovative approach for facilitating early dementia screening by estimating diffusion tensor imaging (DTI) measures using accessible lifestyle and brain imaging factors. Conventional DTI analysis, though effective, is often hindered by high costs and limited accessibility. To address this challenge, fuzzy subtractive clustering identified 14 influential variables from the Lifestyle for Brain Health and Brain Atrophy and Lesion Index frameworks, encompassing demographics, medical conditions, lifestyle factors, and structural brain markers. A multilayer perceptron (MLP) neural network was developed using these selected variables to predict fractional anisotropy (FA), a DTI metric reflecting white matter integrity and cognitive function. The MLP model achieved promising results, with a mean squared error of 0.000 878 on the test set for FA prediction, demonstrating its potential for accurate DTI estimation without costly neuroimaging techniques. The FA values in the dataset ranged from 0 to 1, with higher values indicating greater white matter integrity. Thus, a mean squared error of 0.000 878 suggests that the model’s predictions were highly accurate compared to the observed FA values. This multifactorial approach aligns with the current understanding of dementia’s complex etiology influenced by various biological, environmental, and lifestyle factors. By integrating readily available data into a predictive model, this method enables widespread, cost-effective screening for early dementia risk assessment. The proposed accessible screening tool could facilitate timely interventions, preventive strategies, and efficient resource allocation in public health programs, ultimately improving patient outcomes and caregiver burden.

Age-related Differences in Response Inhibition Are Mediated by Frontoparietal White Matter but Not Functional Activity.

Healthy older adults often exhibit lower performance but increased functional recruitment of the frontoparietal control network during cognitive control tasks. According to the cortical disconnection hypothesis, age-related changes in the microstructural integrity of white matter may disrupt inter-regional neuronal communication, which in turn can impair behavioral performance. Here, we use fMRI and diffusion-weighted imaging to determine whether age-related differences in white matter microstructure contribute to frontoparietal over-recruitment and behavioral performance during a response inhibition (go/no-go) task in an adult life span sample (n = 145). Older and female participants were slower (go RTs) than younger and male participants, respectively. However, participants across all ages were equally accurate on the no-go trials, suggesting some participants may slow down on go trials to achieve high accuracy on no-go trials. Across the life span, functional recruitment of the frontoparietal network within the left and right hemispheres did not vary as a function of age, nor was it related to white matter fractional anisotropy (FA). In fact, only frontal FA and go RTs jointly mediated the association between age and no-go accuracy. Our results therefore suggest that frontal white matter cortical "disconnection" is an underlying driver of age-related differences in cognitive control, and white matter FA may not fully explain functional task-related activation in the frontoparietal network during the go/no-go task. Our findings add to the literature by demonstrating that white matter may be more important for certain cognitive processes in aging than task-related functional activation.

White matter integrity and functional connectivity of the default mode network in acute stroke are associated with cognitive outcome three months post-stroke

BackgroundKnowledge about factors that are associated with post-stroke cognitive outcome is important to identify patients with high risk for impairment. We therefore investigated the associations of white matter integrity and functional connectivity (FC) within the brain's default-mode network (DMN) in acute stroke patients with cognitive outcome three months post-stroke. MethodsPatients aged between 18 and 85 years with an acute symptomatic MRI-proven unilateral ischemic middle cerebral artery infarction, who had received reperfusion therapy, were invited to participate in this longitudinal study. All patients underwent brain MRI within 24–72 h after symptom onset, and participated in a neuropsychological assessment three months post-stroke. We performed hierarchical regression analyses to explore the incremental value of baseline white matter integrity and FC beyond demographic, clinical, and macrostructural information for cognitive outcome. ResultsThe study cohort comprised 34 patients (mean age: 64 ± 12 years, 35% female). The initial median National Institutes of Health Stroke Scale (NIHSS) score was 10, and significantly improved three months post-stroke to a median NIHSS = 1 (p < .001). Nonetheless, 50% of patients showed cognitive impairment three months post-stroke. FC of the non-lesioned anterior cingulate cortex of the affected hemisphere explained 15% of incremental variance for processing speed (p = .007), and fractional anisotropy of the non-lesioned cingulum of the affected hemisphere explained 13% of incremental variance for cognitive flexibility (p = .033). ConclusionsWhite matter integrity and functional MRI markers of the DMN in acute stroke explain incremental variance for post-stroke cognitive outcome beyond demographic, clinical, and macrostructural information.

Diffusion tensor imaging from past to present: A bibliometric analysis with trending topics and global productivity during 1980–2022

AbstractDiffusion tensor imaging (DTI) provides increasing opportunities for clinicians. As bibliometric studies define trends of novel modality applications, this study on DTI analyzed global productivity, most prolific institutions, and research areas. Articles obtained from the Web of Science (WoS) database were analyzed with the VOSviewer program, biblioshiny library in the R studio software bibliometrix package, exponential smoothing estimator, and with the SPSS (Version: 22.0) statistical software. In descending order, the United States, China, and Germany were the top 3 countries publishing DTI research. In descending order, the top 3 most productive institutions were California, Harvard and Johns Hopkins University. Trend topics include traumatic brain injury, tract‐based spatial statistics, fractional anisotropy, prognosis, machine learning, autism, white matter integrity and microstructure and Parkinson's disease. According to the estimations, 345 DTI articles will be published in 2025 (95% CI: 254–437). This study indicates the ever‐growing employment of DTI in clinical and basic sciences.