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Precisely how the anatomical structure of the brain gives rise to a repertoire of complex functions remains incompletely understood. A promising manifestation of this mapping from structure to function is the dependency of the functional activity of a brain region on the underlying white matter architecture. Here, we review the literature examining the macroscale coupling between structural and functional connectivity, and we establish how this structure-function coupling (SFC) can provide more information about the underlying workings of the brain than either feature alone. We begin by defining SFC and describing the computational methods used to quantify it. We then review empirical studies that examine the heterogeneous expression of SFC across different brain regions, among individuals, in the context of the cognitive task being performed, and over time, as well as its role in fostering flexible cognition. Last, we investigate how the coupling between structure and function is affected in neurological and psychiatric conditions, and we report how aberrant SFC is associated with disease duration and disease-specific cognitive impairment. By elucidating how the dynamic relationship between the structure and function of the brain is altered in the presence of neurological and psychiatric conditions, we aim to not only further our understanding of their aetiology but also establish SFC as a new and sensitive marker of disease symptomatology and cognitive performance. Overall, this Review collates the current knowledge regarding the regional interdependency between the macroscale structure and function of the human brain in both neurotypical and neuroatypical individuals., (© 2024. Springer Nature Limited.)

Background: There is a critical need for neuroimaging markers of brain integrity to monitor effects of modifiable lifestyle factors on brain health. This observational, cross-sectional study assessed relationships between brain microstructure and sleep, physical fitness, and cognition in healthy older adults., Methods: Twenty-three adults aged 60 and older underwent whole-brain multi-shell diffusion imaging, comprehensive cognitive testing, polysomnography, and exercise testing. Neurite Orientation Dispersion and Density Imaging (NODDI) was used to quantify neurite density (NDI) and orientation dispersion (ODI). Diffusion tensor imaging (DTI) was used to quantify axial diffusivity (AxD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD). Relationships between sleep efficiency (SE), time and percent in N3 sleep, cognitive function, physical fitness (VO 2 peak) and the diffusion metrics in regions of interest and the whole brain were evaluated., Results: Higher NDI in bilateral white and gray matter was associated with better executive functioning. NDI in the right anterior cingulate and adjacent white matter was positively associated with language skills. Higher NDI in the left posterior corona radiata was associated with faster processing speed. Physical fitness was positively associated with NDI in the left precentral gyrus and corticospinal tract. N3 % was positively associated with NDI in the left caudate and right pre- and postcentral gyri. Higher ODI in the left putamen and adjacent white matter was associated with better executive function., Conclusion: NDI and ODI derived from NODDI are potential neuroimaging markers for associations between brain microstructure and modifiable risk factors in aging. If these associations are observable in clinical samples, NODDI could be incorporated into clinical trials assessing the effects of modifiable risk factors on brain integrity in aging and neurodegenerative diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Structural connectivity (SC) between distant regions of the brain support synchronized function known as functional connectivity (FC) and give rise to the large-scale brain networks that enable cognition and behavior. Understanding how SC enables FC is important to understand how injuries to SC may alter brain function and cognition. Previous work evaluating whole-brain SC-FC relationships showed that SC explained FC well in unimodal visual and motor areas, but only weakly in association areas, suggesting a unimodal-heteromodal gradient organization of SC-FC coupling. However, this work was conducted in group-averaged SC/FC data. Thus, it could not account for inter-individual variability in the locations of cortical areas and white matter tracts. We evaluated the correspondence of SC and FC within three highly sampled healthy participants. For each participant, we collected 78 min of diffusion-weighted MRI for SC and 360 min of resting state fMRI for FC. We found that FC was best explained by SC in visual and motor systems, as well as in anterior and posterior cingulate regions. A unimodal-to-heteromodal gradient could not fully explain SC-FC coupling. We conclude that the SC-FC coupling of the anterior-posterior cingulate circuit is more similar to unimodal areas than to heteromodal areas., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Attention is a heterogeneous function theoretically divided into different systems. While functional magnetic resonance imaging (fMRI) has extensively characterized their functioning, the role of white matter in cognitive function has gained recent interest due to diffusion-weighted imaging advancements. However, most evidence relies on correlations between white matter properties and behavioral or cognitive measures. This study used a new method that combines the signal from distant voxels of fMRI images using the probability of structural connection given by high-resolution normative tractography. We analyzed three fMRI datasets with a visual perceptual task and three attentional manipulations: phasic alerting, spatial orienting, and executive attention. The phasic alerting network engaged temporal areas and their communication with frontal and parietal regions, with left hemisphere dominance. The orienting network involved bilateral fronto-parietal and midline regions communicating by association tracts and interhemispheric fibers. The executive attention network engaged a broad set of brain regions and white matter tracts connecting them, with a particular involvement of frontal areas and their connections with the rest of the brain. These results partially confirm and extend previous knowledge on the neural substrates of the attentional system, offering a more comprehensive understanding through the integration of structure and function., (© 2024. The Author(s).)

Table tennis training has been employed as an exercise treatment to enhance cognitive brain functioning in patients with mental illnesses. However, research on its underlying mechanisms remains limited. In this study, we investigated functional and structural changes in large-scale brain regions between 20 table tennis players (TTPs) and 21 healthy controls (HCs) using 7-Tesla magnetic resonance imaging (MRI) techniques. Compared with those of HCs, TTPs exhibited significantly greater fractional anisotropy (FA) and axial diffusivity (AD) values in multiple fiber tracts. We used the locations with the most significant structural changes in white matter as the seed areas and then compared static and dynamic functional connectivity (sFC and dFC). Brodmann 11, located in the orbitofrontal cortex, showed altered dFC values to large-scale brain regions, such as the occipital lobe, thalamus, and cerebellar hemispheres, in TTPs. Brodmann 48, located in the temporal lobe, showed altered dFC to the parietal lobe, frontal lobe, cerebellum, and occipital lobe. Furthermore, the AD values of the forceps minor (Fmi) and right anterior thalamic radiations (ATRs) were negatively correlated with useful field of view (UFOV) test scores in TTPs. Our results suggest that table tennis players exhibit a unique pattern of dynamic neural activity, this provides evidence for potential mechanisms through which table tennis interventions can enhance attention and other cognitive functions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sustained attention is important for maintaining cognitive function and autonomy during ageing, yet older people often show reductions in this domain. The role of the underlying neurobiology is not yet well understood, with most neuroimaging studies primarily focused on fMRI. Here, we utilise sMRI to investigate the relationships between age, structural brain volumes and sustained attention performance. Eighty-nine healthy older adults (50-84 years, M age 65.5 (SD=8.4) years, 74 f) underwent MRI brain scanning and completed two sustained attention tasks: a rapid visual information processing (RVP) task and sustained attention to response task (SART). Independent hierarchical linear regressions demonstrated that greater volumes of white matter hyperintensities (WMH) were associated with worse RVP_A' performance, whereas greater grey matter volumes were associated with better RVP_A' performance. Further, greater cerebral white matter volumes were associated with better SART_d' performance. Importantly, mediation analyses revealed that both grey and white matter volumes completely mediated the relationship between ageing and sustained attention. These results explain disparate attentional findings in older adults, highlighting the intervening role of brain structure., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Functional coactivation between human brain regions is partly explained by white matter connections; however, how the structure-function relationship varies by function remains unclear. Here, we reference large data repositories to compute maps of structure-function correspondence across hundreds of specific functions and brain regions. We use natural language processing to accurately predict structure-function correspondence for specific functions and to identify macroscale gradients across the brain that correlate with structure-function correspondence as well as cortical thickness. Our findings suggest structure-function correspondence unfolds along a sensory-fugal organizational axis, with higher correspondence in primary sensory and motor cortex for perceptual and motor functions, and lower correspondence in association cortex for cognitive functions. Our study bridges neuroscience and natural language to describe how structure-function coupling varies by region and function in the brain, offering insight into the diversity and evolution of neural network properties., (© 2024. The Author(s).)

Motor imagery is a higher-order cognitive brain function that mentally simulates movements without performing the actual physical one. Although motor imagery has attracted the interest of many researchers, and mental practice utilizing motor imagery has been widely used in sports training and post-stroke rehabilitation, neural bases that determine individual differences in motor imagery ability are not well understood. In this study, using controllability of motor imagery (CMI) test that can objectively evaluate individual ability to manipulate one's imaginary postures, we examined structural and functional features characterizing the brains of individuals with higher controllability of motor imagery, by analyzing T1-weighted structural MRI data obtained from 89 participants and functional MRI data obtained from 28 of 89 participants. The higher CMI test scorers had larger volume in the bilateral superior frontoparietal white matter regions. The CMI test activated the bilateral dorsal premotor cortex (PMD) and superior parietal lobule (SPL); specifically, the left PMD and/or the right SPL enhanced functional coupling with the visual body, somatosensory, and motor/kinesthetic areas in the higher scorers. Hence, controllability of motor imagery is higher for those who well-develop superior frontoparietal network, and for those whose this network accesses these sensory areas to predict the expected multisensory experiences during motor imagery. This study elucidated for the first time the structural and functional features characterizing the brains of individuals with higher controllability of motor imagery, and advanced understanding of individual differences in motor imagery ability., (© 2024. The Author(s).)

The macroscale connectome is the network of physical, white-matter tracts between brain areas. The connections are generally weighted and their values interpreted as measures of communication efficacy. In most applications, weights are either assigned based on imaging features-e.g. diffusion parameters-or inferred using statistical models. In reality, the ground-truth weights are unknown, motivating the exploration of alternative edge weighting schemes. Here, we explore a multi-modal, regression-based model that endows reconstructed fiber tracts with directed and signed weights. We find that the model fits observed data well, outperforming a suite of null models. The estimated weights are subject-specific and highly reliable, even when fit using relatively few training samples, and the networks maintain a number of desirable features. In summary, we offer a simple framework for weighting connectome data, demonstrating both its ease of implementation while benchmarking its utility for typical connectome analyses, including graph theoretic modeling and brain-behavior associations., (© 2024. The Author(s).)

The brain is responsive to an ever-changing environment, enabling the organism to learn and change behavior accordingly. Efforts to understand the underpinnings of this plasticity have almost exclusively focused on the functional and underlying structural changes that neurons undergo at neurochemical synapses. What has received comparatively little attention is the involvement of activity-dependent myelination in such plasticity and the functional output of circuits controlling behavior. The traditionally held view of myelin as a passive insulator of axons is changing to one of lifelong changes in myelin, modulated by neuronal activity and experience. We review the nascent evidence of the functional role of myelin plasticity in strengthening circuit functions that underlie learning and behavior.

Multiple studies have reported a significant dependence of the effective transverse relaxation rate constant (R 2 ) and the phase of gradient-echo based (GRE) signal on the orientation of white matter fibres in the human brain. It has also been hypothesized that magnetic susceptibility, as obtained by single-orientation quantitative susceptibility mapping (QSM), exhibits such a dependence. In this study, we investigated this hypothesized relationship in a cohort of healthy volunteers. We show that R * follows the predicted orientation dependence consistently across white matter regions, whereas the apparent magnetic susceptibility is related differently to fibre orientation across the brain and often in a complex non-monotonic manner. In addition, we explored the effect of fractional anisotropy measured by diffusion-weighted MRI on the strength of the orientation dependence and observed only a limited influence in many regions. However, with careful consideration of such an impact and the limitations imposed by the ill-posed nature of the dipole inversion process, it is possible to study magnetic susceptibility anisotropy in specific brain regions with a single orientation acquisition.2 * follows the predicted orientation dependence consistently across white matter regions, whereas the apparent magnetic susceptibility is related differently to fibre orientation across the brain and often in a complex non-monotonic manner. In addition, we explored the effect of fractional anisotropy measured by diffusion-weighted MRI on the strength of the orientation dependence and observed only a limited influence in many regions. However, with careful consideration of such an impact and the limitations imposed by the ill-posed nature of the dipole inversion process, it is possible to study magnetic susceptibility anisotropy in specific brain regions with a single orientation acquisition., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier Inc.)

Myelin, a lipid membrane that wraps axons, enabling fast neurotransmission and metabolic support to axons, is conventionally thought of as a static structure that is set early in development. However, recent evidence indicates that in the central nervous system (CNS), myelination is a protracted and plastic process, ongoing throughout adulthood. Importantly, myelin is emerging as a potential modulator of neuronal networks, and evidence from human studies has highlighted myelin as a major player in shaping human behavior and learning. Here we review how myelin changes throughout life and with learning. We discuss potential mechanisms of myelination at different life stages, explore whether myelin plasticity provides the regenerative potential of the CNS white matter, and question whether changes in myelin may underlie neurological disorders., (© 2021. Springer Nature America, Inc.)

Diffusion MRI has provided the neuroimaging community with a powerful tool to acquire in-vivo data sensitive to microstructural features of white matter, up to 3 orders of magnitude smaller than typical voxel sizes. The key to extracting such valuable information lies in complex modelling techniques, which form the link between the rich diffusion MRI data and various metrics related to the microstructural organization. Over time, increasingly advanced techniques have been developed, up to the point where some diffusion MRI models can now provide access to properties specific to individual fibre populations in each voxel in the presence of multiple "crossing" fibre pathways. While highly valuable, such fibre-specific information poses unique challenges for typical image processing pipelines and statistical analysis. In this work, we review the "Fixel-Based Analysis" (FBA) framework, which implements bespoke solutions to this end. It has recently seen a stark increase in adoption for studies of both typical (healthy) populations as well as a wide range of clinical populations. We describe the main concepts related to Fixel-Based Analyses, as well as the methods and specific steps involved in a state-of-the-art FBA pipeline, with a focus on providing researchers with practical advice on how to interpret results. We also include an overview of the scope of all current FBA studies, categorized across a broad range of neuro-scientific domains, listing key design choices and summarizing their main results and conclusions. Finally, we critically discuss several aspects and challenges involved with the FBA framework, and outline some directions and future opportunities., (Copyright © 2021. Published by Elsevier Inc.)

Brain age can be estimated using different Magnetic Resonance Imaging (MRI) modalities including diffusion MRI. Recent studies demonstrated that white matter (WM) tracts that share the same function might experience similar alterations. Therefore, in this work, we sought to investigate such issue focusing on five WM bundles holding that feature that is Association, Brainstem, Commissural, Limbic and Projection fibers, respectively. For each tract group, we estimated brain age for 15,335 healthy participants from United Kingdom Biobank relying on diffusion MRI data derived endophenotypes, Bayesian ridge regression modeling and 10 fold-cross validation. Furthermore, we estimated brain age for an Ensemble model that gathers all the considered WM bundles. Association analysis was subsequently performed between the estimated brain age delta as resulting from the six models, that is for each tract group as well as for the Ensemble model, and 38 daily life style measures, 14 cardiac risk factors and cardiovascular magnetic resonance imaging features and genetic variants. The Ensemble model that used all tracts from all fiber groups (FG) performed better than other models to estimate brain age. Limbic tracts based model reached the highest accuracy with a Mean Absolute Error (MAE) of 5.08, followed by the Commissural ([Formula: see text]), Association ([Formula: see text]), and Projection ([Formula: see text]) ones. The Brainstem tracts based model was the less accurate achieving a MAE of 5.86. Accordingly, our study suggests that the Limbic tracts experience less brain aging or allows for more accurate estimates compared to other tract groups. Moreover, the results suggest that Limbic tract leads to the largest number of significant associations with daily lifestyle factors than the other tract groups. Lastly, two SNPs were significantly (p value [Formula: see text]) associated with brain age delta in the Projection fibers. Those SNPs are mapped to HIST1H1A and SLC17A3 genes., (© 2021. The Author(s).)

Visually appreciable white matter (WM) changes have been described in obstructive sleep apnea (OSA). However, few data exist on the involvement of silent WM abnormalities. This prospective study investigated the microstructural integrity of normal-appearing white matter (NAWM) in male OSA patients before and after continuous positive airway pressure (CPAP) treatment, using a neuroimaging approach. Magnetic resonance imaging (MRI) was acquired from 32 participants (16 severe never-treated OSA and 16 controls). Diffusion tensor imaging (DTI) and Tract-Based Spatial Statistics (TBSS) were used to assess the microstructural NAWM changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). In order to evaluate the efficacy of the therapy, OSA patients underwent MRI evaluations at baseline and after 3 months of treatment (follow-up). CPAP treatment significantly increased the FA in NAWM of the brain stem, corpus callosum and bilateral internal capsule of OSA patients at follow-up compared to baseline (p < 0.05, TFCE-corrected). OSA patients also showed increases in AD in the corpus callosum, superior corona radiata, and internal capsule of the right hemisphere (p < 0.05, TFCE-corrected) after CPAP treatment. A significant negative correlation was found between the FA of the corona radiata, corpus callosum, internal capsule, limbic structures, and neuropsychological scores at follow-up evaluation. No significant differences were found in MD and RD of NAWM in our patients after treatment. Our results demonstrate that FA and AD of NAWM in major tracts such as the corpus callosum and the internal capsule increased significantly after CPAP treatment, as a potential beneficial effect of ventilatory therapy. The recovery of NAWM alterations might also be related to the improvement in the neurocognitive profile, suggesting that nonclearly visible WM alterations may contribute to the physiopathology of OSA-related cognitive impairment., (© 2021 Wiley Periodicals LLC.)

Background: Physical activity (PA) has been shown to modulate the detrimental effect of carrying the apolipoprotein-E epsilon 4 (APOE-ɛ4) allele on brain structure. However, the current literature mainly provides cross-sectional data, and longitudinal studies investigating the interaction between genotype and PA on white matter (WM) integrity are lacking., Objectives: We investigated both the cross-sectional and the longitudinal interactive effects of APOE-ɛ4 and PA on WM integrity in older adults., Methods: Fractional anisotropy, as well as axial, radial, and mean diffusivity, extracted from brain diffusion tensor imaging (DTI) were used to assess WM integrity in non-demented older adults. They were categorized according to their APOE-ɛ4 status (carriers vs. non-carriers), and their level of total (TPA), moderate to vigorous (MVPA) and light (LPA) PA were assessed using a questionnaire. Mixed model regressions were performed to test the interactive effects of APOE-ɛ4 status and PA on WM integrity at baseline and over a 3-year follow-up., Results: 190 subjects with a mean age 74.5 years (SD = 3.9) were examined. Despite a lack of cross-sectional associations, sensitivity analyses revealed that, in the carrier group only, higher levels of LPA, but not MVPA, were mainly associated with higher axial and mean diffusivity values over time., Conclusions: This study partially confirms the previously reported interactive associations between PA, APOE-ɛ4 genotype and WM integrity, supporting the hypothesis that PA may protect against fiber loss in WM tracts containing crossing fibers. Future studies assessing sedentary behaviors in addition to PA could bring relevant contributions to the field. CLINICAL TRIAL REGISTRATION NUMBER FROM CLINICALTRIALS.GOV: NCT00672685., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Recent evidence indicates that both cardiovascular fitness and gross motor skill performance are related to enhanced neurocognitive functioning in children by influencing brain structure and functioning. This study investigates the role of white matter microstructure in the relationship of both cardiovascular fitness and gross motor skills with neurocognitive functioning in healthy children. In total 92 children (mean age 9.1 years, range 8.0-10.7) were included in this study. Cardiovascular fitness and gross motor skill performance were assessed using performance-based tests. Neurocognitive functioning was assessed using computerized tests (working memory, inhibition, interference control, information processing, and attention). Diffusion tensor imaging was used in combination with tract-based spatial statistics to assess white matter microstructure as defined by fractional anisotropy (FA), axial and radial diffusivity (AD, RD). The results revealed positive associations of both cardiovascular fitness and gross motor skills with neurocognitive functioning. Information processing and motor response inhibition were associated with FA in a cluster located in the corpus callosum. Within this cluster, higher cardiovascular fitness and better gross motor skills were both associated with greater FA, greater AD, and lower RD. No mediating role was found for FA in the relationship of both cardiovascular fitness and gross motor skills with neurocognitive functioning. The results indicate that cardiovascular fitness and gross motor skills are related to neurocognitive functioning as well as white matter microstructure in children. However, this study provides no evidence for a mediating role of white matter microstructure in these relationships., (© 2021 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Urbanicity has been suggested to affect cognition, but the underlying mechanism remains unknown. We examined whether epigenetic modification (DNA methylation, DNAm), and brain white matter fiber integrity (fractional anisotropy, FA) or local spontaneous brain function activity (regional homogeneity, ReHo) play roles in the association between childhood urbanicity and cognition based on 497 healthy Chinese adults. We found significant correlation between childhood urbanicity and better cognitive performance. Multiset canonical correlation analysis (mCCA) identified an intercorrelated DNAm-FA-ReHo triplet, which showed significant pairwise correlations (DNAm-FA: Bonferroni-adjusted P, Pbon = 4.99E-03, rho = 0.216; DNAm-ReHo: Pbon = 4.08E-03, rho = 0.239; ReHo-FA: Pbon = 1.68E-06, rho = 0.328). Causal mediation analysis revealed that 1) ReHo mediated 10.86% childhood urbanicity effects on the speed of processing and 2) childhood urbanicity alters ReHo through DNA methylation in the cadherin and Wnt signaling pathways (mediated effect: 48.55%). The mediation effect of increased ReHo in the superior temporal gyrus underlying urbanicity impact on a better speed of processing was further validated in an independent cohort. Our work suggests a mediation role for ReHo, particularly increased brain activity in the superior temporal gyrus, in the urbanicity-associated speed of processing., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: Airline pilot is a highly specialized profession that requires to response quickly and accurately in the presence of a wide variety of visual information. Although functional imaging studies have employed virtual simulation to identify brain areas that underlie various flying-related tasks, little is known about the specific patterns of structural plasticity in the airline pilot's brain., Materials and Methods: In this study, we examined differences of gray matter and white matter volumes between 42 airline pilots and 39 non-pilots by using voxel-based morphometry, and further assessed the association between magnitude of structural alterations and flight time in the pilots., Results: We found significantly increased white matter volume in the cuneus area in the pilot group compared to the non-pilot group (p <  0.05, FWE corrected). Using a relaxed threshold, it was also observed that the pilots had increased gray matter volume in the lingual gyrus, inferior frontal gyrus, supramarginal gyrus, cuneus, and postcentral gyrus, and increased white matter volume in the postcentral area (p <  0.001, uncorrected). Moreover, the pilots' flight time was positively correlated with gray matter volume in the postcentral gyrus and white matter volume in the cuneus area (p <  0.001, uncorrected)., Conclusions: The morphological changes in specific visual and sensorimotor areas may provide airline pilots with neural efficiency in the visuo-motor processing related to flight., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Opposing genetic and cultural-social explanations for the origin of language are currently the focus of much discussion. One of the functions linked to the longitudinal fascicle is language, which links Wernicke's area and Broca's area in the brain, and its size should indicate the brain increase in the evolution. Sapajus is a New World primate genus with high cognition and advanced tool use similar to that of chimpanzees. A study of the gross anatomy of the longitudinal fascicle of Sapajus using Kingler's method found it to differ from other studied primates, such as macaques and chimpanzees, mainly because its fibers join the cingulate fascicle. As in other non-human primates, the longitudinal fascicle of Sapajus does not reach the temporal lobe, which could indicate a way of separating these fascicles to increase white matter in relation to individual function. The study of anatomical structures seems very promising for understanding the basis of the origin of language. Indeed, socio-historical-cultural philosophy affirms the socio-cultural origin of speech, although considering the anatomical structures behind it working as a functional system., Competing Interests: The authors have declared that no competing interests exist.

Understanding the neurophysiology underlying neonatal responses to noxious stimulation is central to improving early life pain management. In this neonatal multimodal MRI study, we use resting-state and diffusion MRI to investigate inter-individual variability in noxious-stimulus evoked brain activity. We observe that cerebral haemodynamic responses to experimental noxious stimulation can be predicted from separately acquired resting-state brain activity (n = 18). Applying this prediction model to independent Developing Human Connectome Project data (n = 215), we identify negative associations between predicted noxious-stimulus evoked responses and white matter mean diffusivity. These associations are subsequently confirmed in the original noxious stimulation paradigm dataset, validating the prediction model. Here, we observe that noxious-stimulus evoked brain activity in healthy neonates is coupled to resting-state activity and white matter microstructure, that neural features can be used to predict responses to noxious stimulation, and that the dHCP dataset could be utilised for future exploratory research of early life pain system neurophysiology.

Background: Stress exposure as well as psychiatric disorders are often associated with abnormalities in brain structure or connectivity. The co-chaperone FK506-binding protein 51 (FKBP51) is a regulator of the stress system and is associated with a risk to develop stress-related mental illnesses., Purpose: To assess the effect of a general FKBP51 knockout on brain structure and connectivity in male mice., Study Type: Animal study., Animal Model: Two cohorts of FKBP51 knockout (51KO) and wildtype (WT) mice. The first cohort was comprised of n = 18 WT and n = 17 51KOs; second cohort n = 10 WT and n = 9 51KOs., Field Strength/sequence: 9.4T/3D gradient echo (VBM), DTI-EPI (DTI)., Assessment: Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). For VBM, all procedures were executed in SPM12. DTI: FMRIB Software Library (FSL) Tract Based Statistics (TBSS) were integrated within DTI-TK, allowing the creation of a mean FA skeleton. A voxelwise statistical analysis was applied between WT and 51KO mice., Statistical Test: Volumetric differences were collected at a threshold of P < 0.005, and only clusters surviving a familywise error correction on the cluster level (pFWE, cluster <0.05) were further considered. VBM data were analyzed using a two-sample t-test. The Threshold Free Cluster Enhancement (TFCE) method was used to derive uncorrected-P statistical results at a P-level of 0.01., Results: The structural analysis revealed two clusters of significantly larger volumes in the hypothalamus, periaqueductal gray, and dorsal raphe region of WT animals. DTI measurements, however, demonstrated statistically higher fractional anisotropy (FA) values for 51KO animals in locations including the anterior commissure, fornix, and posterior commissure/superior colliculus commissure region., Data Conclusion: This study used in vivo structural MRI and DTI to demonstrate that a lack of FKBP51 leads to alterations in brain architecture and connectivity in male mice. These findings are of particular translational relevance for our understanding of the neuroanatomy underlying the interaction of FKBP5 genetic status, stress susceptibility, and psychiatric disorders., Level of Evidence: 1 TECHNICAL EFFICACY STAGE: 1., (© 2020 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC. on behalf of International Society for Magnetic Resonance in Medicine.)

Accurate knowledge of adult human brain volume (BV) is critical for studies of aging- and disease-related brain alterations, and for monitoring the trajectories of neural and cognitive functions in conditions like Alzheimer's disease and traumatic brain injury. This scoping meta-analysis aggregates normative reference values for BV and three related volumetrics-gray matter volume (GMV), white matter volume (WMV) and cerebrospinal fluid volume (CSFV)-from typically-aging adults studied cross-sectionally using magnetic resonance imaging (MRI). Drawing from an aggregate sample of 9473 adults, this study provides (A) regression coefficients β describing the age-dependent trajectories of volumetric measures by sex within the range from 20 to 70 years based on both linear and quadratic models, and (B) average values for BV, GMV, WMV and CSFV at the representative ages of 20 (young age), 45 (middle age) and 70 (old age). The results provided synthesize ~20 years of brain volumetrics research and allow one to estimate BV at any age between 20 and 70. Importantly, however, such estimates should be used and interpreted with caution because they depend on MRI hardware specifications (e.g. scanner manufacturer, magnetic field strength), data acquisition parameters (e.g. spatial resolution, weighting), and brain segmentation algorithms. Guidelines are proposed to facilitate future meta- and mega-analyses of brain volumetrics.

We propose a novel approach for processing diffusion MRI tractography datasets using the sparse closest point transform (SCPT). Tractography enables the 3D geometry of white matter pathways to be reconstructed; however, algorithms for processing them are often highly customized, and thus, do not leverage the existing wealth of machine learning (ML) algorithms. We investigated a vector-space tractography representation that aims to bridge this gap by using the SCPT, which consists of two steps: first, extracting sparse and representative landmarks from a tractography dataset, and second transforming curves relative to these landmarks with a closest point transform. We explore its use in three typical tasks: fiber bundle clustering, simplification, and selection across a population. The clustering algorithm groups fibers from single whole-brain datasets using a non-parametric k-means clustering algorithm, with performance compared with three alternative methods and across four datasets. The simplification algorithm removes redundant curves to improve interactive visualization, with performance gauged relative to random subsampling. The selection algorithm extracts bundles across a population using a one-class Gaussian classifier derived from an atlas prototype, with performance gauged by scan-rescan reliability and sensitivity to normal aging, as compared to manual mask-based selection. Our results demonstrate how the SCPT enables the novel application of existing vector-space ML algorithms to create effective and efficient tools for tractography processing. Our experimental data is available online, and our software implementation is available in the Quantitative Imaging Toolkit.

We present an exploratory cross-sectional analysis of the effect of season and weather on Freesurfer-derived brain volumes from a sample of 3,279 healthy individuals collected on two MRI scanners in Hartford, CT, USA over a 15 year period. Weather and seasonal effects were analyzed using a single linear regression model with age, sex, motion, scan sequence, time-of-day, month of the year, and the deviation from average barometric pressure, air temperature, and humidity, as covariates. FDR correction for multiple comparisons was applied to groups of non-overlapping ROIs. Significant negative relationships were found between the left- and right- cerebellum cortex and pressure (t = -2.25, p = 0.049; t = -2.771, p = 0.017). Significant positive relationships were found between left- and right- cerebellum cortex and white matter between the comparisons of January/June and January/September. Significant negative relationships were found between several subcortical ROIs for the summer months compared to January. An opposing effect was observed between the supra- and infra-tentorium, with opposite effect directions in winter and summer. Cohen's d effect sizes from monthly comparisons were similar to those reported in recent psychiatric big-data publications, raising the possibility that seasonal changes and weather may be confounds in large cohort studies. Additionally, changes in brain volume due to natural environmental variation have not been reported before and may have implications for weather-related and seasonal ailments., Competing Interests: The authors have declared that no competing interests exist.

Ultrasound-(US) emitting sources are highly present in modern human environments (e.g., movement sensors, electric transformers). US affecting humans or even posing a health hazard remains understudied. Hence, ultrasonic (22.4 kHz) vs. sham devices were installed in participants' bedrooms, and active for 28 nights. Somatic and psychiatric symptoms, sound-sensitivity, sleep quality, executive function, and structural MRI were assessed pre-post. Somatization (possible nocebo) and phasic alertness increased significantly in sham, accuracy in a flexibility task decreased significantly in the verum condition (indicating hastier responses). Effects were not sustained after p-level adjustment. Exploratory voxel-based morphometry (VBM) revealed regional grey matter (rGMV) but no regional white matter volume changes in verum (relative to placebo). rGMV increased in bilateral cerebellum VIIb/Crus II and anterior cingulate (BA24). There were rGMV decreases in two bilateral frontal clusters: in the middle frontal gyri/opercular part of inferior frontal gyrus (BA46, 44), and the superior frontal gyri (BA4 ,6, 8). No brain-behavior-links were identified. Given the overall pattern of results, it is suggested that ultrasound may particularly induce regional gray matter decline in frontal areas, however with yet unclear behavioral consequences. Given the localization of clusters, candidate behavioral variables for follow-up investigation are complex motor control/coordination, stress regulation, speech processing, and inhibition tasks.Trial registration: The trial was registered at NIH www.clinicaltrials.gov , trial identifier: NCT03459183, trial name: SonicBrain01, full trial protocol available here: https://clinicaltrials.gov/ct2/show/NCT03459183 .

Subconcussive hits to the head and physical fitness both have been associated with alterations in white matter (WM) microstructure in partly overlapping areas of the brain. The aim of the present study was to determine whether WM damage associated with repeated exposure to subconcussive hits to the head in university level contact sports athletes is modulated by high levels of fitness. To this end, 72 students were recruited: 24 athletes practicing a varsity contact sport (A-CS), 24 athletes practicing a varsity non-contact sport (A-NCS), and 24 healthy non-athletes (NA). Participants underwent a magnetic resonance imaging session that included diffusion-weighted imaging. Between-groups, statistical analyses were performed with diffusion tensor imaging measures extracted by tractometry of sections of the corpus callosum and the corticospinal tract. Most significant effects were found in A-NCS who exhibited higher fractional anisotropy (FA) values than A-CS in almost all segments of the corpus callosum and in the corticospinal tract. The A-NCS also showed higher FA compared with NA in the anterior regions of the corpus callosum and the corticospinal tracts. No group difference was found between the A-CS and the NA groups. These data suggest that repeated subconcussive hits to the head lead to anisotropic changes in the WM that may counteract the beneficial effects associated with high levels of fitness.

Understanding the development of white matter microstructure in the general population is an imperative precursor to identifying its involvement in psychopathology. Previous studies have reported changes in white matter microstructure associated with age and different developmental patterns between boys and girls. Handedness has also been related to white matter in adults. Motor performance, tightly dependent on overall neuronal myelination, has been related to the corpus callosum. However, the association between motor performance and global white matter microstructure has not been reported in the literature. In general, these age, sex, handedness, and motor performance associations have been observed using small and poorly representative samples. We examined the relationships between age, sex, handedness, and motor performance, measured with a finger tapping task, and white matter microstructure in the forceps major and minor and in 5 tracts bilaterally (cingulum, corticospinal, inferior and superior longitudinal fasciculi, and uncinate) in a population-based sample of 3031 children between 8 and 12 years of age. Diffusion tensor imaging (DTI) data were acquired using a single, study-dedicated 3 Tesla scanner. We extracted and quantified features of white matter microstructure for each tract. We computed global DTI metrics by combining scalar values across multiple tracts into single latent factors using a confirmatory factor analysis. The adjusted linear regression models indicated that age was associated with global fractional anisotropy (FA), global mean diffusivity (MD), and almost all the tracts. Further, girls showed lower global MD than boys, while FA values differed by tract, and no age-sex interactions were found. No differences were observed in white matter microstructure between right- and left-handed children. We observed that FA in forceps major was associated with right-hand finger tapping performance. White matter FA in association tracts was only related to motor function before multiple testing correction. Our findings do not provide evidence for a relationship between finger tapping task performance and global white matter microstructure., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Inc.)

Diffusion MRI techniques are used widely to study the characteristics of the human brain connectome in vivo. However, to resolve and characterise white matter (WM) fibres in heterogeneous MRI voxels remains a challenging problem typically approached with signal models that rely on prior information and constraints. We have recently introduced a 5D relaxation-diffusion correlation framework wherein multidimensional diffusion encoding strategies are used to acquire data at multiple echo-times to increase the amount of information encoded into the signal and ease the constraints needed for signal inversion. Nonparametric Monte Carlo inversion of the resulting datasets yields 5D relaxation-diffusion distributions where contributions from different sub-voxel tissue environments are separated with minimal assumptions on their microscopic properties. Here, we build on the 5D correlation approach to derive fibre-specific metrics that can be mapped throughout the imaged brain volume. Distribution components ascribed to fibrous tissues are resolved, and subsequently mapped to a dense mesh of overlapping orientation bins to define a smooth orientation distribution function (ODF). Moreover, relaxation and diffusion measures are correlated to each independent ODF coordinate, thereby allowing the estimation of orientation-specific relaxation rates and diffusivities. The proposed method is tested on a healthy volunteer, where the estimated ODFs were observed to capture major WM tracts, resolve fibre crossings, and, more importantly, inform on the relaxation and diffusion features along with distinct fibre bundles. If combined with fibre-tracking algorithms, the methodology presented in this work has potential for increasing the depth of characterisation of microstructural properties along individual WM pathways., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

A large population of infracortical white matter neurons, or white matter interstitial cells (WMICs), are found within the subcortical white matter of the mammalian telencephalon. We examined WMICs in three species of megachiropterans, Megaloglossus woermanni, Casinycteris argynnis, and Rousettus aegyptiacus, using immunohistochemical and stereological techniques. Immunostaining for neuronal nuclear marker (NeuN) revealed substantial numbers of WMICs in each species-M. woermanni 124,496 WMICs, C. argynnis 138,458 WMICs, and the larger brained R. aegyptiacus having an estimated WMIC population of 360,503. To examine the range of inhibitory neurochemical types we used antibodies against parvalbumin, calbindin, calretinin, and neural nitric oxide synthase (nNOS). The calbindin and nNOS immunostained neurons were the most commonly observed, while those immunoreactive for calretinin and parvalbumin were sparse. The proportion of WMICs exhibiting inhibitory neurochemical profiles was ~26%, similar to that observed in previously studied primates. While for the most part the WMIC population in the megachiropterans studied was similar to that observed in other mammals, the one feature that differed was the high proportion of WMICs immunoreactive to calbindin, whereas in primates (macaque monkey, lar gibbon and human) the highest proportion of inhibitory WMICs contain calretinin. Interestingly, there appears to be an allometric scaling of WMIC numbers with brain mass. Further quantitative comparative work across more mammalian species will reveal the developmental and evolutionary trends associated with this infrequently studied neuronal population., (© 2020 Wiley Periodicals, Inc.)

Most magnetic resonance imaging (MRI) studies investigating the relationship between regional brain myelination or axonal density and aging have relied upon nonspecific methods to probe myelin and axonal content, including diffusion tensor imaging and relaxation time mapping. While these studies have provided pivotal insights into changes in cerebral architecture with aging and pathology, details of the underlying microstructural alterations have not been fully elucidated. In the current study, we used the BMC-mcDESPOT analysis, a direct and specific multicomponent relaxometry method for imaging of myelin water fraction (MWF), a marker of myelin content, and NODDI, an emerging multicomponent diffusion technique, for neurite density index (NDI) imaging, a proxy of axonal density. We investigated age-related differences in MWF and NDI in several white matter brain regions in a cohort of cognitively unimpaired participants over a wide age range. Our results indicate a quadratic, inverted U-shape, relationship between MWF and age in all brain regions investigated, suggesting that myelination continues until middle age followed by a decrease at older ages, in agreement with previous work. We found a similarly complex regional association between NDI and age, with several cerebral structures also exhibiting a quadratic, inverted U-shape, relationship. This novel observation suggests an increase in axonal density until the fourth decade of age followed by a rapid loss at older ages. We also observed that these age-related differences in MWF and NDI vary across different brain regions, as expected. Finally, our study indicates no significant association between MWF and NDI in most cerebral structures investigated, although this association approached significance in a limited number of brain regions, indicating the complementary nature of their information and encouraging further investigation. Overall, we find evidence of nonlinear associations between age and myelin or axonal density in a sample of well-characterized adults, using direct myelin and axonal content imaging methods., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020. Published by Elsevier Inc.)

Brain age is becoming a widely applied imaging-based biomarker of neural aging and potential proxy for brain integrity and health. We estimated multimodal and modality-specific brain age in the Whitehall II (WHII) MRI cohort using machine learning and imaging-derived measures of gray matter (GM) morphology, white matter microstructure (WM), and resting state functional connectivity (FC). The results showed that the prediction accuracy improved when multiple imaging modalities were included in the model (R 2 = 0.30, 95% CI [0.24, 0.36]). The modality-specific GM and WM models showed similar performance (R 2 = 0.22 [0.16, 0.27] and R 2 = 0.24 [0.18, 0.30], respectively), while the FC model showed the lowest prediction accuracy (R 2 = 0.002 [-0.005, 0.008]), indicating that the FC features were less related to chronological age compared to structural measures. Follow-up analyses showed that FC predictions were similarly low in a matched sub-sample from UK Biobank, and although FC predictions were consistently lower than GM predictions, the accuracy improved with increasing sample size and age range. Cardiovascular risk factors, including high blood pressure, alcohol intake, and stroke risk score, were each associated with brain aging in the WHII cohort. Blood pressure showed a stronger association with white matter compared to gray matter, while no differences in the associations of alcohol intake and stroke risk with these modalities were observed. In conclusion, machine-learning based brain age prediction can reduce the dimensionality of neuroimaging data to provide meaningful biomarkers of individual brain aging. However, model performance depends on study-specific characteristics including sample size and age range, which may cause discrepancies in findings across studies., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The ability to effectively suppress motor response tendencies is essential for focused and goal-directed behavior. Here, we tested the hypothesis that developmental improvement in the ability to cancel a motor response is reflected by maturational changes in the white matter underlying the right presupplementary motor area (preSMA) and posterior inferior frontal gyrus (IFG), two cortical key areas of the fronto-basal ganglia "stopping" network. Eighty-eight typically-developing children and adolescents, aged 7-19 years, were longitudinally assessed with the stop-signal task (SST) and diffusion tensor imaging (DTI) of the brain over a period of six years. Participants were examined from two to nine times with an average of 6.6 times, resulting in 576 SST-DTI datasets. We applied tract-based spatial statistics to extract mean fractional anisotropy (FA) from regions-of-interest in the white matter underlying the right IFG (IFG FA ) and right preSMA (preSMA FA ) at each time point. Motor response cancelation performance, estimated with the stop-signal reaction time (SSRT), improved with age. Initially well performing children plateaued around the age of 11 years, while initially poor performers caught up at the age of 13-14 years. White matter microstructure continued to mature across the investigated age range. Males generally displayed linear maturational trajectories, while females displayed more curvilinear trajectories that leveled off around 12-14 years of age. Maturational increases in right preSMA FA but not right IFG FA were associated with developmental improvements in SSRT. This association differed depending on the mean right preSMA FA across the individual maturational trajectory. Children with lower mean right preSMA FA exhibited poorer SSRT performance at younger ages but steeper developmental trajectories of SSRT improvement. Children with higher mean right preSMA FA exhibited flatter trajectories of SSRT improvement along with faster SSRT already at the first assessments. The results suggest that no further improvement in motor response cancellation is achieved once a certain level of maturity in the white matter underlying the right preSMA is reached. Similar dynamics may apply to other behavioral read-outs and brain structures and, thus, need to be considered in longitudinal MRI studies designed to map brain structural correlates of behavioral changes during development., Competing Interests: Declaration of competing interest Hartwig R. Siebner has received honoraria as speaker and ad-hoc consultant from Sanofi Genzyme, Denmark and Novartis, Denmark and as editor-in-chief (NeuroImage Clinical) and senior editor (NeuroImage) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany. The authors declare no potential conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Based on the evidence that meditation is associated with numerous beneficial effects on well-being and reduced stress-related symptoms, mindfulness-based techniques were increasingly implemented into psychotherapeutic programs. However, different meditation styles and the cross-sectional nature of most previous analyses resulted in a great variety of morphometric findings. The present study aims to elucidate cortical reorganization processes and altered axonal integrity caused by short-term meditation training, and benefits from solely using focused attention meditation (FAM)., Methods: 3 T MRI, including T1-MPRAGE and diffusion-weighted sequences, was performed in 27 healthy, meditation naïve participants (age: 43 ± 12.4 years) pre and post FAM meditation training (duration: 7.3 ± 0.4 weeks). Voxel-based morphometry was applied to assess brain changes in gray and white matter. Questionnaires were filled out by the individuals at both time-points to evaluate quality of life and self-awareness deficits., Results: The major findings comprised (i) gray matter increases in the insula, the caudate nucleus and frontal cortices, (ii) decreases in extended parietotemporal regions, the right medial prefrontal cortex and the parahippocampal gyrus, as well as (iii) fractional anisotropy increases of the right hippocampus, the basal ganglia and adjacent regions. Regression analysis revealed an association of specific alterations with reduced levels of state anxiety., Conclusions: FAM training induced a broad range of dynamic brain alterations even within few weeks of training. Interestingly, this cohort revealed more, and partially different patterns of structural gray matter change compared to prior studies. The broad impact on neuronal organization processes may reflect more general outcomes related to health and well-being., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Despite the importance of cortico-striatal circuits to cognition, investigation of age effects on the structural circuitry connecting these regions is limited. The current study examined age effects on frontostriatal white matter connectivity, and identified associations with both executive function performance and dynamic modulation of blood-oxygen-level-dependent (BOLD) activation to task difficulty in a lifespan sample of 169 healthy humans aged 20-94 years. Greater frontostriatal diffusivity was associated with poorer executive function and this negative association strengthened with increasing age. Whole-brain functional magnetic resonance imaging (fMRI) analyses additionally indicated an association between frontostriatal mean diffusivity and BOLD modulation to difficulty selectively in the striatum across 2 independent fMRI tasks. This association was moderated by age, such that younger- and middle-aged individuals showed reduced dynamic range of difficulty modulation as a function of increasing frontostriatal diffusivity. Together these results demonstrate the importance of age-related degradation of frontostriatal circuitry on executive functioning across the lifespan, and highlight the need to capture brain changes occurring in early-to middle-adulthood., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Resting-state functional MRI (RfMRI) analyses have identified two anatomically separable fronto-parietal attention networks in the human brain: a bilateral dorsal attention network and a right-lateralised ventral attention network (VAN). The VAN has been implicated in visuospatial cognition and, thus, potentially in the unilateral spatial neglect associated with right hemisphere lesions. Its parietal, frontal and temporal endpoints are thought to be structurally supported by undefined white matter tracts. We investigated the white matter tract connecting the VAN. We used three approaches to study the structural anatomy of the VAN: (a) independent component analysis on RfMRI (50 subjects), defining the endpoints of the VAN, (b) tractography in the same 50 healthy volunteers, with regions of interest defined by the MNI coordinates of cortical areas involved in the VAN used in a seed-based approach and (c) dissection, by Klingler's method, of 20 right hemispheres, for ex vivo studies of the fibre tracts connecting VAN endpoints. The VAN includes the temporoparietal junction and the ventral frontal cortex. The endpoints of the superior longitudinal fasciculus in its third portion (SLF III) and the arcuate fasciculus (AF) overlap with the VAN endpoints. The SLF III connects the supramarginal gyrus to the ventral portion of the precentral gyrus and the pars opercularis. The AF connects the middle and inferior temporal gyrus and the middle and inferior frontal gyrus. We reconstructed the structural connectivity of the VAN and considered it in the context if the pathophysiology of unilateral neglect and right hemisphere awake brain surgery., (© 2020 Anatomical Society.)

Our main goal was to determine the influence of white matter integrity on the dynamic coupling between brain regions and the individual variability of cognitive performance in older adults. Electroencephalography was recorded while participants performed a task specifically designed to engage working memory and inhibitory processes, and the associations among functional activity, structural integrity, and cognitive performance were assessed. We found that the association between white matter microstructural integrity and cognitive functioning with aging is mediated by time-varying alpha and gamma phase-locking value. Specifically, better preservation of the inferior fronto-occipital fasciculus in older individuals drives faster task-related modulations of alpha and gamma long-range phase-locking value between the inferior frontal gyrus and occipital lobe and lower local phase-amplitude coupling in occipital lobes, which in turn drives better cognitive control performance. Our results help delineate the role of individual variability of white matter microstructure in dynamic synchrony and cognitive performance during normal aging., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Researchers have used direct electrical brain stimulation to treat a range of neurological and psychiatric disorders. However, for brain stimulation to be maximally effective, clinicians and researchers should optimize stimulation parameters according to desired outcomes., Objective: The goal of our large-scale study was to comprehensively evaluate the effects of stimulation at different parameters and locations on neuronal activity across the human brain., Methods: To examine how different kinds of stimulation affect human brain activity, we compared the changes in neuronal activity that resulted from stimulation at a range of frequencies, amplitudes, and locations with direct human brain recordings. We recorded human brain activity directly with electrodes that were implanted in widespread regions across 106 neurosurgical epilepsy patients while systematically stimulating across a range of parameters and locations., Results: Overall, stimulation most often had an inhibitory effect on neuronal activity, consistent with earlier work. When stimulation excited neuronal activity, it most often occurred from high-frequency stimulation. These effects were modulated by the location of the stimulating electrode, with stimulation sites near white matter more likely to cause excitation and sites near gray matter more likely to inhibit neuronal activity., Conclusion: By characterizing how different stimulation parameters produced specific neuronal activity patterns on a large scale, our results provide an electrophysiological framework that clinicians and researchers may consider when designing stimulation protocols to cause precisely targeted changes in human brain activity., Competing Interests: Declaration of competing interest M.K. and D.R. have started a company, Nia Therapeutics, Inc., intended to develop and commercialize brain stimulation therapies for memory restoration. Each of them holds >5% equity interest in Nia. R.E.G. serves as a consultant to Medtronic, which was a subcontractor on the RAM project. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. B.J. receives research funding from NeuroPace and Medtronic not relating to this research. G.W. has rights to receive future royalties from the licensing of brain stimulation technology. Mayo Clinic has a financial interest related to brain stimulation technology, and is co-owner of Cadence Neuroscience Inc, the development of which has been assisted by G.W. The remaining authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The aim of the study was explore how the white matter structure changes and obsessive-compulsive disorder (OCD) symptom dimensions are related. We recruited 46 untreated adult patients with OCD, and 46 healthy controls matched for gender, age, and education. The patients were classified according to symptom dimensions assessed by the four-factor model. Diffusion tensor imaging (DTI) was employed to evaluate brain structural alterations in patients with OCD, and DTI data were processed using voxel-based morphometry (VBM) analysis. In comparison with healthy controls, there was a significant decreased fractional anisotropy of patients with OCD in several white matter regions of the cingulate gyrus and left inferior frontal gyrus. When stratified by symptom dimensions, patients presenting with the contamination/cleaning dimension had significantly lower fractional anisotropy in the white matter areas of the right insula and the left thalamus than the healthy controls. Whereas harm/checking symptom dimension patients exhibited a significant decrease of fractional anisotropy in the white matter regions of the right hippocampus. Our study has clear implications for the idea that OCD can be seen as a heterogeneous disorder, and symptom dimensions in patients with OCD are relevant to various white matter alterations patterns.

Declining auditory spatial processing is hypothesized to contribute to the difficulty older adults have detecting, locating, and selecting a talker from among others in noisy listening environments. Though auditory spatial processing has been associated with several cortical structures, little is known regarding the underlying white matter architecture or how age-related changes in white matter microstructure may affect it. The arcuate fasciculus is a target for understanding age-related differences in auditory spatial attention based on normative spatial attention findings in humans. Similarly, animal and human clinical studies suggest that the corpus callosum plays a role in the cross-hemispheric integration of auditory spatial information important for spatial localization and attention. The current investigation used diffusion imaging to examine the extent to which age-group differences in the identification of spatially cued speech were accounted for by individual differences in the white matter microstructure of the right arcuate fasciculus and the corpus callosum. Higher right arcuate and callosal fractional anisotropy (FA) predicted better segregation and identification of spatially cued speech across younger and older listeners. Further, individual differences in callosal microstructure mediated age-group differences in auditory spatial processing. Follow-up analyses suggested that callosal tracts connecting left and right pre-frontal and posterior parietal cortex are particularly important for auditory spatial processing. The results are consistent with previous work in animals and clinical human samples and provide a cortical mechanism to account for age-related deficits in auditory spatial processing. Further, the results suggest that both intrahemispheric and interhemispheric mechanisms are involved in auditory spatial processing., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study examined within-subject differences among three fluid abilities that decline with age: reasoning, episodic memory and processing speed, compared with vocabulary, a crystallized ability that is maintained with age. The data were obtained from the Reference Ability Neural Network (RANN) study from which 221 participants had complete behavioral data for all 12 cognitive tasks, three per ability, along with fMRI and diffusion weighted imaging data. We used fMRI task activation to guide white matter tractography, and generated mean percent signal change in the regions associated with the processing of each ability along with diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), for each cognitive ability. Qualitatively brain regions associated with vocabulary were more localized and lateralized to the left hemisphere whereas the fluid abilities were associated with brain activations that were more distributed across the brain and bilaterally situated. Using continuous age, we observed smaller correlations between MD and age for white matter tracts connecting brain regions associated with the vocabulary ability than that for the fluid abilities, suggesting that vocabulary white matter tracts were better maintained with age. Furthermore, after multiple comparisons correction and accounting for age, education, and sex, the mean percent signal change for episodic memory showed positive associations with behavioral performance. Overall, the vocabulary ability may be better maintained with age due to the more localized brain regions involved, which places smaller reliance on long distance white matter tracts for signal transduction. These results support the hypothesis that functional activation and white matter structures underlying the vocabulary ability contribute to the ability's greater resistance against aging., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Measuring fibre dispersion in white matter with diffusion magnetic resonance imaging (MRI) is limited by an inherent degeneracy between fibre dispersion and microscopic diffusion anisotropy (i.e., the diffusion anisotropy expected for a single fibre orientation). This means that estimates of fibre dispersion rely on strong assumptions, such as constant microscopic anisotropy throughout the white matter or specific biophysical models. Here we present a simple approach for resolving this degeneracy using measurements that combine linear (conventional) and spherical tensor diffusion encoding. To test the accuracy of the fibre dispersion when our microstructural model is only an approximation of the true tissue structure, we simulate multi-compartment data and fit this with a single-compartment model. For such overly simplistic tissue assumptions, we show that the bias in fibre dispersion is greatly reduced (~5x) for single-shell linear and spherical tensor encoding data compared with single-shell or multi-shell conventional data. In in-vivo data we find a consistent estimate of fibre dispersion as we reduce the b-value from 3 to 1.5 ms/μm 2 , increase the repetition time, increase the echo time, or increase the diffusion time. We conclude that the addition of spherical tensor encoded data to conventional linear tensor encoding data greatly reduces the sensitivity of the estimated fibre dispersion to the model assumptions of the tissue microstructure., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Cognitive control and incentive sensitivity are related to overeating and obesity. Optimal white matter integrity is relevant for an efficient interaction among reward-related brain regions. However, its relationship with sensitivity to incentives remains controversial. The aim of this study was to assess the incentive sensitivity and its relationship to white matter integrity in normal-weight and overweight groups. Seventy-six young adults participated in this study: 31 were normal-weight (body mass index [BMI] 18.5 to < 25.0 kg/m2, 14 females) and 45 were overweight (BMI ≥ 25.0 kg/m2, 22 females). Incentive sensitivity was assessed using an antisaccade task that evaluates the effect of incentives (neutral, reward, and loss avoidance) on cognitive control performance. Diffusion tensor imaging studies were performed to assess white matter integrity. The relationship between white matter microstructure and incentive sensitivity was investigated through tract-based spatial statistics. Behavioral antisaccade results showed that normal-weight participants presented higher accuracy (78.0 vs. 66.7%, p = 0.01) for loss avoidance incentive compared to overweight participants. Diffusion tensor imaging analysis revealed a positive relationship between fractional anisotropy and loss avoidance accuracy in the normal-weight group (p < 0.05). No relationship reached significance in the overweight group. These results support the hypothesis that white matter integrity is relevant for performance in an incentivized antisaccade task., Competing Interests: The authors have declared that no competing interests exist.

Understanding how the anatomy of the human brain constrains and influences the formation of large-scale functional networks remains a fundamental question in neuroscience. Here, given measured brain activity in gray matter, we interpolate these functional signals into the white matter on a structurally-informed high-resolution voxel-level brain grid. The interpolated volumes reflect the underlying anatomical information, revealing white matter structures that mediate the interaction between temporally coherent gray matter regions. Functional connectivity analyses of the interpolated volumes reveal an enriched picture of the default mode network (DMN) and its subcomponents, including the different white matter bundles that are implicated in their formation, thus extending currently known spatial patterns that are limited within the gray matter only. These subcomponents have distinct structure-function patterns, each of which are differentially observed during tasks, demonstrating plausible structural mechanisms for functional switching between task-positive and -negative components. This work opens new avenues for the integration of brain structure and function, and demonstrates the collective mediation of white matter pathways across short and long-distance functional connections., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

A diverse set of white matter connections supports seamless transitions between cognitive states. However, it remains unclear how these connections guide the temporal progression of large-scale brain activity patterns in different cognitive states. Here, we analyze the brain's trajectories across a set of single time point activity patterns from functional magnetic resonance imaging data acquired during the resting state and an n-back working memory task. We find that specific temporal sequences of brain activity are modulated by cognitive load, associated with age, and related to task performance. Using diffusion-weighted imaging acquired from the same subjects, we apply tools from network control theory to show that linear spread of activity along white matter connections constrains the probabilities of these sequences at rest, while stimulus-driven visual inputs explain the sequences observed during the n-back task. Overall, these results elucidate the structural underpinnings of cognitively and developmentally relevant spatiotemporal brain dynamics.

The mapping of human brain connections is still an on going task. Unlike deep white matter (DWM), which has been extensively studied and well documented, superficial white matter (SWM) has been often left aside. Improving our understanding of the SWM is an important goal for a better understanding of the brain network and its relation to several pathologies. The shape and localization of these short bundles present a high variability across subjects. Furthermore, the small diameter of most superficial bundles and partial volume effects induced by their proximity to the cortex leads to complex tratography issues. Therefore, the mapping of SWM bundles and the use of the resulting atlases for clinical studies requiere dedicated methodologies that are reviewed in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mental health problems often emerge in adolescence and are associated with reduced gray matter thickness or volume in the prefrontal cortex (PFC) and limbic system and reduced fractional anisotropy (FA) and increased mean diffusivity (MD) of white matter linking these regions. However, few studies have investigated whether internalizing and externalizing behavior are associated with brain structure in children and adolescents without mental health disorders, which is important for understanding the progression of symptoms. 67 T1-weighted and diffusion tensor imaging datasets were obtained from 48 typically developing participants aged 6-16 years (37M/30F; 19 participants had two visits). Volume was calculated in the prefrontal and limbic structures, and diffusion parameters were assessed in limbic white matter. Linear mixed effects models were used to compute associations between brain structure and internalizing and externalizing behavior, assessed using the Behavioral Assessment System for Children (BASC-2) Parent Rating Scale. Internalizing behavior was positively associated with MD of the bilateral cingulum. Gender interactions were found in the cingulum, with stronger positive relationships between MD and internalizing behavior in females. Externalizing behavior was negatively associated with FA of the left cingulum, and the left uncinate fasciculus showed an age-behavior interaction. No relationships between behavior and brain volumes survived multiple comparison correction. These results show altered limbic white matter FA and MD related to sub-clinical internalizing and externalizing behavior and further our understanding of neurological markers that may underlie risk for future mental health disorders.

The hub-and-spoke semantic representation theory posits that semantic knowledge is processed in a neural network, which contains an amodal hub, the sensorimotor modality-specific regions, and the connections between them. The exact neural basis of the hub, regions and connectivity remains unclear. Semantic dementia could be an ideal lesion model to construct the semantic network as this disease presents both amodal and modality-specific semantic processing (e.g. colour) deficits. The goal of the present study was to identify, using an unbiased data-driven approach, the semantic hub and its general and modality-specific semantic white matter connections by investigating the relationship between the lesion degree of the network and the severity of semantic deficits in 33 patients with semantic dementia. Data of diffusion-weighted imaging and behavioural performance in processing knowledge of general semantic and six sensorimotor modalities (i.e. object form, colour, motion, sound, manipulation and function) were collected from each subject. Specifically, to identify the semantic hub, we mapped the white matter nodal degree value (a graph theoretical index) of the 90 regions in the automated anatomical labelling atlas with the general semantic abilities of the patients. Of the regions, only the left fusiform gyrus was identified as the hub because its structural connectivity strength (i.e. nodal degree value) could significantly predict the general semantic processing of the patients. To identify the general and modality-specific semantic connections of the semantic hub, we separately correlated the white matter integrity values of each tract connected with the left fusiform gyrus, with the performance for general semantic processing and each of six semantic modality processing. The results showed that the hub region worked in concert with nine other regions in the semantic memory network for general semantic processing. Moreover, the connection between the hub and the left calcarine was associated with colour-specific semantic processing. The observed effects could not be accounted for by potential confounding variables (e.g. total grey matter volume, regional grey matter volume and performance on non-semantic control tasks). Our findings refine the neuroanatomical structure of the semantic network and underline the critical role of the left fusiform gyrus and its connectivity in the network., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Word learning plays a central role in language development and is a key predictor for later academic success. The underlying neural basis of successful word learning in children is still unknown. Here, we took advantage of the opportunity afforded by diffusion-weighted magnetic resonance imaging to investigate neural plasticity in the white matter of typically developing preschool children as they learn words. We demonstrate that after 3 weeks of word learning, children showed significantly larger increases of fractional anisotropy (FA) in the left precentral white matter compared to two control groups. Average training accuracy was correlated with FA change in the white matter underlying the left dorsal postcentral gyrus, with children who learned more slowly showing larger FA increases in this region. Moreover, we found that the status of white matter in the left middle temporal gyrus, assumed to support semantic processes, is predictive for early stages of word learning. Our findings provide the first evidence for white matter plasticity following word learning in preschool children. The present results on learning novel words in children point to a key involvement of the left fronto-parietal fiber connection, known to be implicated in top-down attention as well as working memory. While working memory and attention have been discussed to participate in word learning in children, our training study provides evidence that the neural structure supporting these cognitive processes plays a direct role in word learning.

In this study, we examined a large sample of 231 generally healthy older adults across 4 years with regard to several brain anatomical measures (volumes of total grey matter volume: GM, normal appearing white matter: NAWM, lateral ventricle: LV, and white matter hypointensities: WMH) and psychometric intelligence (verbal and non-verbal). The dataset comprised four measurement occasions (baseline, 1-, 2-, and 4-year follow-ups). With this longitudinal data set, we evaluated level-level, level-change, and change-change relationships between the anatomical and psychometric measures using latent growth curve models. Our analyses indicate that GM and NAWM decreased significantly over the course of 4 years with annual percent changes of - 0.73% and - 0.79%, respectively. WMH and LV volumes increase with annual percent changes of 7.3% and 4%, respectively. Verbal and nonverbal IQ measures remained stable in our sample. In addition, we uncovered evidence for level-level and -change associations between several of the brain anatomical measures. With regard to brain-IQ associations, we observed a positive level-level association for GM and NAWM, indicating that participants with larger brain volumes demonstrate higher IQ measures. No substantial evidence was identified for level- or change-change associations between any of the brain metrics and the IQ measures. Taken together, these results suggest that while healthy older adults demonstrated age-related neuroanatomical decline over a time span of 4 years, these degenerative changes are not necessarily linked to simultaneous cognitive deterioration.