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In adults, individual differences in procedural learning (PL) are associated with white matter organization within the basal ganglia-cerebellar circuit. However, no research has examined whether this circuitry is related to individual differences in PL during childhood. Here, 28 children (M age  = 10.00 ± 2.31, 10 female) completed the serial reaction time (SRT) task to measure PL, and underwent structural magnetic resonance imaging (MRI). Fixel-Based Analysis was performed to extract specific measures of white matter fiber density (FD) and fiber cross-section (FC) from the superior cerebellar peduncles (SCP) and the striatal premotor tracts (STPMT), which underlie the fronto-basal ganglia-cerebellar system. These fixel metrics were correlated with the 'rebound effect' from the SRT task - a measure of PL proficiency which compares reaction times associated with generating a sequence, to random trials. While no significant associations were observed at the fixel level, a significant positive association was observed between average FD in the right SCP and the rebound effect, with a similar trend observed in the left SCP. No significant effects were detected in the STPMT. Our results indicate that, like in adults, microstructure of the basal ganglia-cerebellar circuit may explain individual differences in childhood PL., 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 The Author(s). Published by Elsevier Inc. 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.)

Human brain gray matter (GM) has usually been clustered into multiple functional networks. The white matter (WM) fiber bundles are known to interconnect these networks simultaneously, engaging in numerous cognitive functions. However, the exact interconnections between GM and WM are still unclear, whether functional signals in WM rewires GM community organization remains to be explored. In this study, we divided brain functional connections into three types by using edge-centric method, including intra-GM, intra-WM and GM-WM connections, and calculated the edge community evaluation indexes for quantifying GM community engagement. The results showed that the involvement of WM significantly enhanced community entropy in the heteromodal system, while the sensory-attention system remained barely changed. In addition, delta community entropy showed a significant correlation with clinical cognitive scale. Our results suggested that WM rewired GM community organization, enhancing the community engagement of brain regions in the heteromodal system. This involvement was observed to be disrupted in disease groups. Our study revealed that considering the functional signals of GM and WM simultaneously could better understand the brain's functional organization., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest relevant to this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

White matter (WM) functional activity has been reliably detected through functional magnetic resonance imaging (fMRI). Previous studies have primarily examined WM bundles as unified entities, thereby obscuring the functional heterogeneity inherent within these bundles. Here, for the first time, we investigate the function of sub-bundles of a prototypical visual WM tract-the optic radiation (OR). We use the 7T retinotopy dataset from the Human Connectome Project (HCP) to reconstruct OR and further subdivide the OR into sub-bundles based on the fiber's termination in the primary visual cortex (V1). The population receptive field (pRF) model is then applied to evaluate the retinotopic properties of these sub-bundles, and the consistency of the pRF properties of sub-bundles with those of V1 subfields is evaluated. Furthermore, we utilize the HCP working memory dataset to evaluate the activations of the foveal and peripheral OR sub-bundles, along with LGN and V1 subfields, during 0-back and 2-back tasks. We then evaluate differences in 2bk-0bk contrast between foveal and peripheral sub-bundles (or subfields), and further examine potential relationships between 2bk-0bk contrast and 2-back task d-prime. The results show that the pRF properties of OR sub-bundles exhibit standard retinotopic properties and are typically similar to the properties of V1 subfields. Notably, activations during the 2-back task consistently surpass those under the 0-back task across foveal and peripheral OR sub-bundles, as well as LGN and V1 subfields. The foveal V1 displays significantly higher 2bk-0bk contrast than peripheral V1. The 2-back task d-prime shows strong correlations with 2bk-0bk contrast for foveal and peripheral OR fibers. These findings demonstrate that the blood oxygen level-dependent (BOLD) signals of OR sub-bundles encode high-fidelity visual information, underscoring the feasibility of assessing WM functional activity at the sub-bundle level. Additionally, the study highlights the role of OR in the top-down processes of visual working memory beyond the bottom-up processes for visual information transmission. Conclusively, this study innovatively proposes a novel paradigm for analyzing WM fiber tracts at the individual sub-bundle level and expands understanding of OR function., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

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).)

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., (© 2024 Massachusetts Institute of Technology.)

We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions., Competing Interests: Competing interests statement:The authors declare no competing interest.

The sulco-gyral pattern is a qualitative feature of the cortical anatomy that is determined in utero, stable throughout lifespan and linked to brain function. The intraparietal sulcus (IPS) is a nodal associative brain area, but the relation between its morphology and cognition is largely unknown. By labelling the left and right IPS of 390 healthy participants into two patterns, according to the presence or absence of a sulcus interruption, here we demonstrate a strong association between the morphology of the right IPS and performance on memory and language tasks. We interpret the results as a morphological advantage of a sulcus interruption, probably due to the underlying white matter organization. The right-hemisphere specificity of this effect emphasizes the neurodevelopmental and plastic role of sulcus morphology in cognition prior to lateralisation processes. The results highlight a promising area of investigation on the relationship between cognitive performance, sulco-gyral pattern and white matter bundles., (© 2024. The Author(s).)

Functional MRI (fMRI) enables evaluation of language cortical organization and plays a central role in surgical planning. Diffusion Tensor Imaging (DTI) or Tractography, allows evaluation of the white matter fibers involved in language. Unlike fMRI, DTI does not rely on the patient's cooperation. In monolinguals, there is a significant correlation between the lateralization of language on fMRI and on DTI. Our objective is to delineate the arcuate fasciculus (AF) in right- and left-handed trilinguals and determine if the AF laterality on DTI is correlated to language lateralization on fMRI. 15 right and 15 left-handed trilingual volunteers underwent fMRI and DTI. Laterality Index was determined on fMRI (fMRI-LI). Mean Diffusivity, Fractional Anisotropy (FA), Number of Fibers, Fiber Length, Fiber Volume and Laterality Index (DTI-LI) of the AF were calculated on DTI. 28 of the 30 subjects presented a bilateral AF. Most subjects (52%) were found to have a bilateral language lateralization of the AF on DTI. Only 4 subjects had bilateral lateralization of language on fMRI. The right AF demonstrated lower diffusivity than the left AF in the total participants, the right-handed, and the left-handed subjects. FA, Volume and Length of the AF were not significantly different between the two hemispheres. No correlation was found between the DTI-LI of the AF and the fMRI-LI. A prominent role of the right AF and a bilateral structural organization of the AF was present in our multilingual population regardless of their handedness. While in prior studies DTI was able to determine language lateralization in monolingual subjects, this was not possible in trilingual highly educated subjects., (© 2021. The Author(s).)

Ultra-High Field (UHF) MRI provides a significant increase in Signal-to-Noise Ratio (SNR) and gains in contrast weighting in several functional and structural acquisitions. Unfortunately, an increase in field strength also induces non-uniformities in the transmit field (B1+) that can compromise image contrast non-uniformly. The MPRAGE is one of the most common T1 weighted (T1w) image acquisitions for structural imaging. It provides excellent contrast between gray and white matter and is widely used for brain segmentation. At 7T, the signal non-uniformities tend to complicate this and therefore, the self-bias-field corrected MP2RAGE is often used there. In both MPRAGE and MP2RAGE, more homogeneous image contrast can be achieved with adiabatic pulses, like the TR-FOCI inversion pulse, or special pulse design on parallel transmission systems, like Universal Pulses (UP). In the present study, we investigate different strategies to improve the bias-field for MPRAGE at 7T, comparing the contrast and GM/WM segmentability against MP2RAGE. The higher temporal efficiency of MPRAGE combined with the potential of the user-friendly UPs was the primary motivation for this MPRAGE-MP2RAGE comparison. We acquired MPRAGE data in six volunteers, adding a k-space shutter to reduce scan time, a kt-point UP approach for homogeneous signal excitation, and a TR-FOCI pulse for homogeneous inversion. Our results show remarkable signal contrast improvement throughout the brain, including regions of low B1 + such as the cerebellum. The improvements in the MPRAGE were largest following the introduction of the UPs. In addition to the CNR, both SNR and GM/WM segmentability were also assessed. Among the MPRAGEs, the combined strategy (UP + TR-FOCI) yielded highest SNR and showed highest spatial similarity between GM segments to the MP2RAGE. Interestingly, the distance between gray and white matter peaks in the intensity histograms did not increase, as better pulses and higher SNR especially benefitted the (cerebellar) gray matter. Overall, the gray-white matter contrast from MP2RAGE is higher, with higher CNR and higher intensity peak distances, even when scaled to scan time. Hence, the extra acquisition time for MP2RAGE is justified by the improved segmentability., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

White matter deterioration is associated with cognitive impairment in healthy aging and Alzheimer's disease. It is critical to identify interventions that can slow down white matter deterioration. So far, clinical trials have failed to demonstrate the benefits of aerobic exercise on the adult white matter using diffusion Magnetic Resonance Imaging. Here, we report the effects of a 6-month aerobic walking and dance interventions (clinical trial NCT01472744) on white matter integrity in healthy older adults (n = 180, 60-79 years) measured by changes in the ratio of calibrated T1- to T2-weighted images (T1w/T2w). Specifically, the aerobic walking and social dance interventions resulted in positive changes in the T1w/T2w signal in late-myelinating regions, as compared to widespread decreases in the T1w/T2w signal in the active control. Notably, in the aerobic walking group, positive change in the T1w/T2w signal correlated with improved episodic memory performance. Lastly, intervention-induced increases in cardiorespiratory fitness did not correlate with change in the T1w/T2w signal. Together, our findings suggest that white matter regions that are vulnerable to aging retain some degree of plasticity that can be induced by aerobic exercise training. In addition, we provided evidence that the T1w/T2w signal may be a useful and broadly accessible measure for studying short-term within-person plasticity and deterioration in the adult human white matter., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

In recent years, the field of functional neuroimaging has moved away from a pure localisationist approach of isolated functional brain regions to a more integrated view of these regions within functional networks. However, the methods used to investigate functional networks rely on local signals in grey matter and are limited in identifying anatomical circuitries supporting the interaction between brain regions. Mapping the brain circuits mediating the functional signal between brain regions would propel our understanding of the brain's functional signatures and dysfunctions. We developed a method to unravel the relationship between brain circuits and functions: The Functionnectome. The Functionnectome combines the functional signal from fMRI with white matter circuits' anatomy to unlock and chart the first maps of functional white matter. To showcase this method's versatility, we provide the first functional white matter maps revealing the joint contribution of connected areas to motor, working memory, and language functions. The Functionnectome comes with an open-source companion software and opens new avenues into studying functional networks by applying the method to already existing datasets and beyond task fMRI., (© 2021. The Author(s).)

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.)

Brain activation mapping using functional magnetic resonance imaging (fMRI) has been extensively studied in brain gray matter (GM), whereas in large disregarded for probing white matter (WM). This unbalanced treatment has been in part due to controversies in relation to the nature of the blood oxygenation level-dependent (BOLD) contrast in WM and its detectability. However, an accumulating body of studies has provided solid evidence of the functional significance of the BOLD signal in WM and has revealed that it exhibits anisotropic spatio-temporal correlations and structure-specific fluctuations concomitant with those of the cortical BOLD signal. In this work, we present an anisotropic spatial filtering scheme for smoothing fMRI data in WM that accounts for known spatial constraints on the BOLD signal in WM. In particular, the spatial correlation structure of the BOLD signal in WM is highly anisotropic and closely linked to local axonal structure in terms of shape and orientation, suggesting that isotropic Gaussian filters conventionally used for smoothing fMRI data are inadequate for denoising the BOLD signal in WM. The fundamental element in the proposed method is a graph-based description of WM that encodes the underlying anisotropy observed across WM, derived from diffusion-weighted MRI data. Based on this representation, and leveraging graph signal processing principles, we design subject-specific spatial filters that adapt to a subject's unique WM structure at each position in the WM that they are applied at. We use the proposed filters to spatially smooth fMRI data in WM, as an alternative to the conventional practice of using isotropic Gaussian filters. We test the proposed filtering approach on two sets of simulated phantoms, showcasing its greater sensitivity and specificity for the detection of slender anisotropic activations, compared to that achieved with isotropic Gaussian filters. We also present WM activation mapping results on the Human Connectome Project's 100-unrelated subject dataset, across seven functional tasks, showing that the proposed method enables the detection of streamline-like activations within axonal bundles., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests in regards to the subject matter discussed in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Language is the most commonly described lateralised cognitive function, relying more on the left hemisphere compared to the right hemisphere in over 90% of the population. Most research examining the structure-function relationship of language lateralisation only included people showing a left language hemisphere dominance. In this work, we applied a state-of-the-art "fixel-based" analysis approach, allowing statistical analysis of white matter micro- and macrostructure on a fibre-specific level in a sample of participants with left and right language dominance (LLD and RLD). Both groups showed a similar extensive pattern of white matter lateralisation including a comparable leftwards lateralisation of the arcuate fasciculus, regardless of their functional language lateralisation. These results suggest that lateralisation of language functioning and the arcuate fasciculus are driven by independent biases. Finally, a significant group difference of lateralisation was detected in the forceps minor, with a leftwards lateralisation in LLD and rightwards lateralisation for the RLD group., (Copyright © 2021. Published by Elsevier Inc.)

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.

The indispensability of visual working memory (VWM) in human daily life suggests its importance in higher cognitive functions and neurological diseases. However, despite the extensive research efforts, most findings on the neural basis of VWM are limited to a unimodal context (either structure or function) and have low generalization. To address the above issues, this study proposed the usage of multimodal neuroimaging in combination with machine learning to reveal the neural mechanism of VWM across a large cohort (N = 547). Specifically, multimodal magnetic resonance imaging features extracted from voxel-wise amplitude of low-frequency fluctuations, gray matter volume, and fractional anisotropy were used to build an individual VWM capacity prediction model through a machine learning pipeline, including the steps of feature selection, relevance vector regression, cross-validation, and model fusion. The resulting model exhibited promising predictive performance on VWM (r = .402, p < .001), and identified features within the subcortical-cerebellum network, default mode network, motor network, corpus callosum, anterior corona radiata, and external capsule as significant predictors. The main results were then compared with those obtained on emotional regulation and fluid intelligence using the same pipeline, confirming the specificity of our findings. Moreover, the main results maintained well under different cross-validation regimes and preprocess strategies. These findings, while providing richer evidence for the importance of multimodality in understanding cognitive functions, offer a solid and general foundation for comprehensively understanding the VWM process from the top down., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Adequate cerebral blood flow (CBF) is essential to a healthy central nervous system (CNS). Previous work suggests that CBF differs between men and women, and declines with age and certain pathologies, but a highly controlled systematic study across a wide age range, and incorporating white matter (WM) regions, has not been undertaken. Here, we investigate age- and sex-related differences in CBF in gray matter (GM) and WM regions in a cohort ( N = 80) of cognitively unimpaired individuals over a wide age range. In agreement with literature, we find that GM regions exhibited lower CBF with age. In contrast, WM regions exhibited higher CBF with age in various cerebral regions. We attribute this new finding to increased oligodendrocyte metabolism to maintain myelin homeostasis in the setting of increased myelin turnover with age. Further, consistent with prior studies, we found that CBF was higher in women than in men in all brain structures investigated. Our work provides new insights into the effects of age and sex on CBF. In addition, our results provide reference CBF values for the standard ASL protocol recommended by the ISMRM Perfusion Study Group and the European ASL in Dementia consortium. Thus, these results provide a foundation for further investigations of CNS perfusion in a variety of settings, including aging, cerebrovascular diseases, and dementias.

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.)

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.

Displacement Encoding with Stimulated Echoes (DENSE) has recently shown potential for measuring cardiac-induced cerebral volumetric strain in the human brain. As such, it may provide a powerful tool for investigating the cerebral small vessels. However, further development and validation are necessary. This study aims, first, to validate a retrospectively-gated implementation of the DENSE method for assessing brain tissue pulsations as a physiological marker, and second, to use the acquired measurements to explore intracranial volume dynamics. We acquired repeated measurements of cerebral volumetric strain in 8 healthy subjects, and internally validated these measurements by comparing them to spinal CSF stroke volumes obtained in the same scan session. Peak volumetric strain was found to be highly repeatable between scan sessions. First/second measured peak volumetric strains were: (6.4 ​± ​1.7)x10 -4 /(6.7 ​± ​1.6)x10 -4 for whole brain, (9.5 ​± ​2.5)x10 -4 /(9.6 ​± ​2.4)x10 -4 for grey matter, and (4.4 ​± ​1.7)x10 -4 /(4.1 ​± ​0.8)x10 -4 for white matter. Grey matter showed significantly higher peak strain (p ​< ​0.001) and earlier time-to-peak strain (p ​< ​0.02) than white matter. An approximately linear relationship was found between CSF and brain tissue volume pulsations over the cardiac cycle (mean slope and R 2 of 0.88 ​± ​0.23 and 0.89 ​± ​0.07, respectively). The close similarity between CSF and brain tissue volume pulsations implies limited contributions from large intracranial vessel pulsations, providing further evidence for venous compression as an additional mechanism for maintaining stable intracranial pressures over the cardiac cycle. Cerebral pulsatility showed consistent inter-subject peak values in healthy subjects, and was strongly correlated to CSF stroke volumes. These results strengthen the potential of brain tissue volumetric strain as a means for investigating the intracranial dynamics of the ageing brain in normal or diseased states., Competing Interests: Declaration of competing interest The authors have no conflict of interests to disclose., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The structural and functional organization of brain networks subserving basic daily activities (i.e. language, visuo-spatial cognition, movement, semantics, etc.) are not completely understood to date. Here, we report the first probabilistic cortical and subcortical atlas of critical structures mediating human brain functions based on direct electrical stimulation (DES), a well-validated tool for the exploration of cerebral processing and for performing safe surgical interventions in eloquent areas., Methods: We collected 1162 cortical and 659 subcortical DES responses during testing of 16 functional domains in 256 patients undergoing awake surgery. Spatial coordinates for each functional response were calculated, and probability distributions for the entire patient cohort were mapped onto a standardized three-dimensional brain template using a multinomial statistical analysis. In addition, matching analyses were performed against prior established anatomy-based cortical and white matter (WM) atlases., Results: The probabilistic maps for each functional domain were provided. The topographical analysis demonstrated a wide spatial distribution of cortical functional responses, while subcortical responses were more restricted, localizing to known WM pathways. These DES-derived data showed reliable matching with existing cortical and WM atlases as well as recent neuroimaging and neurophysiological data., Conclusions: We present the first integrated and comprehensive cortical-subcortical atlas of structures essential for humans' neural functions based on highly-specific DES mapping during real-time neuropsychological testing. This novel atlas can serve as a complementary tool for neuroscientists, along with data obtained from other modalities, to improve and refine our understanding of the functional anatomy of critical brain networks., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Preclinical imaging studies offer a unique access to the rat brain, allowing investigations that go beyond what is possible in human studies. Unfortunately, these techniques still suffer from a lack of dedicated and standardized neuroimaging tools, namely brain templates and descriptive atlases. Here, we present two rat brain MRI templates and their associated gray matter, white matter and cerebrospinal fluid probability maps, generated from ex vivo [Formula: see text]-weighted images (90 µm isotropic resolution) and in vivo T 2 -weighted images (150 µm isotropic resolution). In association with these templates, we also provide both anatomical and functional 3D brain atlases, respectively derived from the merging of the Waxholm and Tohoku atlases, and analysis of resting-state functional MRI data. Finally, we propose a complete set of preclinical MRI reference resources, compatible with common neuroimaging software, for the investigation of rat brain structures and functions.

Declarative memory is supported by distributed brain networks in which the medial-temporal lobes (MTLs) and pFC serve as important hubs. Identifying the unique and shared contributions of these regions to successful memory performance is an active area of research, and a growing literature suggests that these structures often work together to support declarative memory. Here, we present data from a context-dependent relational memory task in which participants learned that individuals belonged in a single room in each of two buildings. Room assignment was consistent with an underlying contextual rule structure in which male and female participants were assigned to opposite sides of a building and the side assignment switched between buildings. In two experiments, neural correlates of performance on this task were evaluated using multiple neuroimaging tools: diffusion tensor imaging (Experiment 1), magnetic resonance elastography (Experiment 1), and functional MRI (Experiment 2). Structural and functional data from each individual modality provided complementary and consistent evidence that the hippocampus and the adjacent white matter tract (i.e., fornix) supported relational memory, whereas the ventromedial pFC/OFC (vmPFC/OFC) and the white matter tract connecting vmPFC/OFC to MTL (i.e., uncinate fasciculus) supported memory-guided rule use. Together, these data suggest that MTL and pFC structures differentially contribute to and support contextually guided relational memory.

A major challenge in neuroscience is understanding how brain function emerges from the connectome. Most current methods have focused on quantifying functional connectomes in gray-matter (GM) signals obtained from functional magnetic resonance imaging (fMRI), while signals from white-matter (WM) have generally been excluded as noise. In this study, we derived a functional connectome from WM resting-state blood-oxygen-level-dependent (BOLD)-fMRI signals from a large cohort (n = 488). The WM functional connectome exhibited weak small-world topology and nonrandom modularity. We also found a long-term (i.e., over 10 months) topological reliability, with topological reproducibility within different brain parcellation strategies, spatial distance effect, global and cerebrospinal fluid signals regression or not. Furthermore, the small-worldness was positively correlated with individuals' intelligence values (r = .17, p corrected = .0009). The current findings offer initial evidence using WM connectome and present additional measures by which to uncover WM functional information in both healthy individuals and in cases of clinical disease., (© 2019 Wiley Periodicals, Inc.)

The aim of this study is to characterise the stiffness of white and grey matter in paediatric subjects using magnetic resonance elastography (MRE) and to determine whether these properties change throughout normal development. MRE was performed using a clinical 3T MRI scanner at three frequencies (30, 40 and 60 Hz) on 36 healthy paediatric subjects aged between 7 and 18 years (19 F) and 11 adults aged 23-44 years (6 F). Anatomical and diffusion tensor imaging was also collected. The stiffness quantified as the magnitude of the complex shear modulus (G*), fractional anisotropy (FA), mean diffusivity (MD) and volume of white and grey matter were calculated. One-way analysis of variance and Tukey's multiple comparison tests were used to compare data in age groups separated into children (7-12 years), adolescents (13-18 years) and adults (18+ years), and Spearman's correlations were performed for paediatric data. White and grey matter stiffness for each frequency and their frequency dependence was found to be very similar in paediatric and adult subjects (p > 0.05 all variables). No significant correlations were found when comparing G* with age, FA, MD or volume. Adult G*, FA, MD and volume values were within range of others reported in the literature. Paediatric white and grey matter stiffness values are similar to those of adults. We conclude that clinically, adult values can be used as a baseline measure in paediatric brain MRE.

The cerebral arteries are difficult to reproduce from first principles, featuring interwoven territories, and intricate layers of grey and white matter with differing metabolic demand. The aim of this study was to identify the ideal configuration of arteries required to sustain an entire brain hemisphere based on minimisation of the energy required to supply the tissue. The 3D distribution of grey and white matter within a healthy human brain was first segmented from magnetic resonance images. A novel simulated annealing algorithm was then applied to determine the optimal configuration of arteries required to supply brain tissue. The model was validated through comparison of this ideal, entirely optimised, brain vasculature with the structure and properties of real arteries. This analysis established that the human cerebral vasculature is highly optimised; closely resembling the most energy efficient arrangement of vessels. In addition to local adherence to fluid dynamical optimisation principles, the optimised vasculature reproduced expected brain perfusion territories, featuring well-defined boundaries between anterior, middle and posterior regions. This validated brain vascular model and algorithm can be used for patient-specific modelling of stroke and cerebral haemodynamics, identification of sub-optimal conditions associated with vascular disease, and optimising vascular structures for tissue engineering applications and artificial organ design.

This study examined the long-term effects of being born very-low-birth-weight (VLBW, <1500 g) on adult cerebral structural development using a multi-method neuroimaging approach. The New Zealand VLBW study cohort comprised 413 individuals born VLBW in 1986. Of the 338 who survived to discharge, 229 were assessed at age 27-29 years. Of these, 150 had a 3 T MRI scan alongside 50 healthy term-born controls. The VLBW group included 53/57 participants born <28 weeks gestation. MRI analyses included: a) structural MRI to assess grey matter (GM) volume and cortical thickness; b) arterial spin labelling (ASL) to quantify GM perfusion; and c) diffusion tensor imaging (DTI) to measure white matter (WM) integrity. Compared to controls, VLBW adults had smaller GM volumes within frontal, temporal, parietal and occipital cortices, bilateral cingulate gyri and left caudate, as well as greater GM volumes in frontal, temporal and occipital areas. Thinner cortex was observed within frontal, temporal and parietal cortices. VLBW adults also had less GM perfusion within limited temporal areas, bilateral hippocampi and thalami. Finally, lower fractional anisotropy (FA) and axial diffusivity (AD) within principal WM tracts was observed in VLBW subjects. Within the VLBW group, birthweight was positively correlated with GM volume and perfusion in cortical and subcortical regions, as well as FA and AD across numerous principal WM tracts. Between group differences within temporal cortices were evident across all imaging modalities, suggesting that the temporal lobe may be particularly susceptible to disruption in development following preterm birth. Overall, findings reveal enduring and pervasive effects of preterm birth on brain structural development, with individuals born at lower birthweights having greater long-term neuropathology., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Disentangling the heterogeneity of brain aging in cognitively normal older adults is challenging, as multiple co-occurring pathologic processes result in diverse functional and structural changes. Capitalizing on machine learning methods applied to magnetic resonance imaging data from 400 participants aged 50 to 96 years in the Baltimore Longitudinal Study of Aging, we constructed normative cross-sectional brain aging trajectories of structural and functional changes. Deviations from typical trajectories identified individuals with resilient brain aging and multiple subtypes of advanced brain aging. We identified 5 distinct phenotypes of advanced brain aging. One group included individuals with relatively extensive structural and functional loss and high white matter hyperintensity burden. Another subgroup showed focal hippocampal atrophy and lower posterior-cingulate functional coherence, low white matter hyperintensity burden, and higher medial-temporal connectivity, potentially reflecting high brain tissue reserve counterbalancing brain loss that is consistent with early stages of Alzheimer's disease. Other subgroups displayed distinct patterns. These results indicate that brain changes should not be measured seeking a single signature of brain aging but rather via methods capturing heterogeneity and subtypes of brain aging. Our findings inform future studies aiming to better understand the neurobiological underpinnings of brain aging imaging patterns., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Importance: Risk of stroke and brain atrophy in later life relate to levels of cardiovascular risk in early adulthood. However, it is unknown whether cerebrovascular changes are present in young adults., Objective: To examine relationships between modifiable cardiovascular risk factors and cerebrovascular structure, function, and white matter integrity in young adults., Design, Setting, and Participants: A cross-sectional observational study of 125 young adults (aged 18-40 years) without clinical evidence of cerebrovascular disease. Data collection was completed between August 2014 and May 2016 at the University of Oxford, United Kingdom. Final data collection was completed on May 31, 2016., Exposures: The number of modifiable cardiovascular risk factors at recommended levels, based on the following criteria: body mass index (BMI) <25; highest tertile of cardiovascular fitness and/or physical activity; alcohol consumption <8 drinks/week; nonsmoker for >6 months; blood pressure on awake ambulatory monitoring <130/80 mm Hg; a nonhypertensive diastolic response to exercise (peak diastolic blood pressure <90 mm Hg); total cholesterol <200 mg/dL; and fasting glucose <100mg/dL. Each risk factor at the recommended level was assigned a value of 1, and participants were categorized from 0-8, according to the number of risk factors at recommended levels, with higher numbers indicating healthier risk categories., Main Outcomes and Measures: Cerebral vessel density, caliber and tortuosity, brain white matter hyperintensity lesion count. In a subgroup (n = 52), brain blood arrival time and cerebral blood flow assessed by brain magnetic resonance imaging (MRI)., Results: A total of 125 participants, mean (SD) age 25 (5) years, 49% women, with a mean (SD) score of 6.0 (1.4) modifiable cardiovascular risk factors at recommended levels, completed the cardiovascular risk assessment and brain MRI protocol. Cardiovascular risk factors were correlated with cerebrovascular morphology and white matter hyperintensity count in multivariable models. For each additional modifiable risk factor categorized as healthy, vessel density was greater by 0.3 vessels/cm3 (95% CI, 0.1-0.5; P = .003), vessel caliber was greater by 8 μm (95% CI, 3-13; P = .01), and white matter hyperintensity lesions were fewer by 1.6 lesions (95% CI, -3.0 to -0.5; P = .006). Among the 52 participants with available data, cerebral blood flow varied with vessel density and was 2.5 mL/100 g/min higher for each healthier category of a modifiable risk factor (95% CI, 0.16-4.89; P = .03)., Conclusions and Relevance: In this preliminary study involving young adults without clinical evidence of cerebrovascular disease, a greater number of modifiable cardiovascular risk factors at recommended levels was associated with higher cerebral vessel density and caliber, higher cerebral blood flow, and fewer white matter hyperintensities. Further research is needed to verify these findings and determine their clinical importance.

Functional magnetic resonance imaging (fMRI) acquisitions include a great deal of individual variability. This individuality often generates obstacles to the efficient use of databanks from multiple subjects. Although recent studies have suggested that inter-regional connectivity reflects individuality, conventional three-dimensional (3D) registration methods that calibrate inter-subject variability are based on anatomical information about the gray matter shape (e.g., T1-weighted). Here, we present a new registration method focusing more on the white matter structure, which is directly related to the connectivity in the brain, and apply it to subject-transfer brain decoding. Our registration method based on diffusion tensor imaging (DTI) transferred functional maps of each individual to a common anatomical space, where a decoding analysis of multi-voxel patterns was performed. The decoder trained on functional maps from other individuals in the common space showed a transfer decoding accuracy comparable to that of an individual decoder trained on single-subject functional maps. The DTI-based registration allowed more precise transformation of gray matter boundaries than a well-established T1-based method. These results suggest that the DTI-based registration is a promising tool for standardization of the brain functions, and moreover, will allow us to perform 'zero-shot' learning of decoders which is profitable in brain machine interface scenes.

Functional connectivity density mapping (FCDM) is a newly developed data-driven technique that quantifies the number of local and global functional connections for each voxel in the brain. In this study, we evaluated reproducibility, sensitivity, and specificity of both local functional connectivity density (lFCD) and global functional connectivity density (gFCD). We compared these metrics using the human connectome project (HCP) compatible high-resolution (2 mm isotropic, TR = 0.8 s) multiband (MB), and more typical, lower resolution (3.5 mm isotropic, TR = 2.0 s) single-band (SB) resting state functional MRI (rs-fMRI) acquisitions. Furthermore, in order to be more clinically feasible, only rs-fMRI scans that lasted seven minutes were tested. Subjects were scanned twice within a two-week span. We found sensitivity and specificity increased and reproducibility either increased or did not change for the MB compared to the SB acquisitions. The MB scans also showed improved gray matter/white matter contrast compared to the SB scans. The lFCD and gFCD patterns were similar across MB and SB scans and confined predominantly to gray matter. We also observed a strong spatial correlation of FCD between MB and SB scans indicating the two acquisitions provide similar information. These findings indicate high-resolution MB acquisitions improve the quality of FCD data, and seven minute rs-fMRI scan can provide robust FCD measurements.

Detection of functional magnetic resonance imaging (fMRI) activation in white matter has been increasingly reported despite historically being controversial. Much of the development work to-date has used high-field 4 T MRI and specialized pulse sequences. In the current study, we utilized conventional 3 T MRI and a commonly applied gradient-echo-planar imaging sequence to evaluate white matter (WM) fMRI sensitivity within a common framework. Functional WM activity was replicated in target regions of interest within the corpus callosum, at the group and individual levels. As expected there was a reduction in overall WM activation sensitivity. Individual analyses revealed that 8 of the 13 individuals showed white matter activation, showing a lower percentage of individuals with WM activation detected. Importantly, WM activation results were sensitive to analyses that applied alternate hemodynamic response functions, with an increase in the group level cluster when hemodynamic response function (HRF) onset slope was reduced. The findings supported the growing evidence that WM activation is detectable, with activation levels are closer to thresholds used for routine 3T MRI studies. Optimization factors, such as the HRF model, appear to be important to further enhance the characterization of WM activity in fMRI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Global signal regression is a controversial processing step for resting-state functional magnetic resonance imaging, partly because the source of the global blood oxygen level-dependent (BOLD) signal remains unclear. On the one hand, nuisance factors such as motion can readily introduce coherent BOLD changes across the whole brain. On the other hand, the global signal has been linked to neural activity and vigilance levels, suggesting that it contains important neurophysiological information and should not be discarded. Any widespread pattern of coordinated activity is likely to contribute appreciably to the global signal. Such patterns may include large-scale quasiperiodic spatiotemporal patterns, known also to be tied to performance on vigilance tasks. This uncertainty surrounding the separability of the global BOLD signal from concurrent neurological processes motivated an examination of the global BOLD signal's spatial distribution. The results clarify that although the global signal collects information from all tissue classes, a diverse subset of the BOLD signal's independent components contribute the most to the global signal. Further, the timing of each network's contribution to the global signal is not consistent across volunteers, confirming the independence of a constituent process that comprises the global signal.

We have reported reliable changes in behavior, brain structure, and function in 24 healthy right-handed adults who practiced a finger-thumb opposition sequence task with their left hand for 10 min daily, over 4 weeks. Here, we extend these findings by using diffusion MRI to investigate white-matter changes in the corticospinal tract, basal-ganglia, and connections of the dorsolateral prefrontal cortex. Twenty-three participant datasets were available with pre-training and post-training scans. Task performance improved in all participants (mean: 52.8%, SD: 20.0%; group P < 0.01 FWE) and widespread microstructural changes were detected across the motor system of the "trained" hemisphere. Specifically, region-of-interest-based analyses of diffusion MRI (n = 22) revealed significantly increased fractional anisotropy (FA) in the right caudate nucleus (4.9%; P < 0.05 FWE), and decreased mean diffusivity in the left nucleus accumbens (-1.3%; P < 0.05 FWE). Diffusion MRI tractography (n = 22), seeded by sensorimotor cortex fMRI activation, also revealed increased FA in the right corticospinal tract (mean 3.28%; P < 0.05 FWE) predominantly reflecting decreased radial diffusivity. These changes were consistent throughout the entire length of the tract. The left corticospinal tract did not show any changes. FA also increased in white matter connections between the right middle frontal gyrus and both right caudate nucleus (17/22 participants; P < 0.05 FWE) and right supplementary motor area (18/22 participants; P < 0.05 FWE). Equivalent changes in FA were not seen in the left (non-trained) hemisphere. In combination with our functional and structural findings, this study provides detailed, multifocal evidence for widespread neuroplastic changes in the human brain resulting from motor training. Hum Brain Mapp 38:4302-4312, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Population studies of brain function with resting-state functional magnetic resonance imaging (rs-fMRI) largely rely on the accurate inter-subject registration of functional areas. This is typically achieved through registration of the corresponding T1-weighted MR images with more structural details. However, accumulating evidence has suggested that such strategy cannot well-align functional regions which are not necessarily confined by the anatomical boundaries defined by the T1-weighted MR images. To mitigate this problem, various registration algorithms based directly on rs-fMRI data have been developed, most of which have utilized functional connectivity (FC) as features for registration. However, most of the FC-based registration methods usually extract the functional features only from the thin and highly curved cortical grey matter (GM), posing a great challenge in accurately estimating the whole-brain deformation field. In this paper, we demonstrate that the additional useful functional features can be extracted from brain regions beyond the GM, particularly, white-matter (WM) based on rs-fMRI, for improving the overall functional registration. Specifically, we quantify the local anisotropic correlation patterns of the blood oxygenation level-dependent (BOLD) signals, modeled by functional correlation tensors (FCTs), in both GM and WM. Functional registration is then performed based on multiple components of the whole-brain FCTs using a multichannel Large Deformation Diffeomorphic Metric Mapping (mLDDMM) algorithm. Experimental results show that our proposed method achieves superior functional registration performance, compared with other conventional registration methods.

Background: Current computational neuroanatomy focuses on morphological measurements of the brain using standard magnetic resonance imaging (MRI) techniques. In comparison quantitative MRI (qMRI) typically provides a better tissue contrast and also greatly improves the sensitivity and specificity with respect to the microstructural characteristics of tissue., Objective: Current methodological developments in qMRI are presented, which go beyond morphology because this provides standardized measurements of the microstructure of the brain. The concept of in-vivo histology is introduced, based on biophysical modelling of qMRI data (hMRI) for determination of quantitative histology-like markers of the microstructure., Results: The qMRI metrics can be used as direct biomarkers of the microstructural mechanisms driving observed morphological findings. The hMRI metrics utilize biophysical models of the MRI signal in order to determine 3‑dimensional maps of histology-like measurements in the white matter., Conclusion: Non-invasive brain tissue characterization using qMRI or hMRI has significant implications for both scientific and clinical applications. Both approaches improve the comparability across sites and time points, facilitate multicenter and longitudinal studies as well as standardized diagnostics. The hMRI is expected to shed new light on the relationship between brain microstructure, function and behavior both in health and disease. In the future hMRI will play an indispensable role in the field of computational neuroanatomy.

Alterations in iron concentration in certain deep gray matter regions are known to occur in aging and several clinical conditions. In vivo measurements of R 2 ∗ transverse relaxation rates and quantitative susceptibility mapping (QSM) have been shown to be strongly correlated with iron concentration in tissue, but their calculation requires the acquisition of a multi-echo gradient recalled echo sequence (MGRE). In the current study, we examined the feasibility of approximating R 2 ∗ rates using metrics derived from fMRI-EPI and T 2 -weighted FLAIR images, which are widely available. In a sample of 40 healthy subjects, we obtained these metrics (v EPI and v FLAIR ), as well as R 2 ∗ rates and QSM estimates, and found significant correlations between v EPI and v FLAIR and R 2 ∗ rates in several subcortical gray matter regions known to accumulate iron, but not in a control corticospinal white matter region. These relationships were preserved after referencing v EPI and v FLAIR with respect to the values in the control region. Effect sizes (above 0.5 for some of the regions, particularly the largest ones) were calculated and put in relation to those of the correlation between QSM and R 2 ∗ rates. We propose that the metrics described here may be applied, possibly in a retrospective fashion, to analyze datasets with available EPI or T 2 -weighted FLAIR scans (and lacking a MGRE sequence), to devise new hypotheses regarding links between iron concentration in brain tissue and other variables of interest., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Despite the relationship between brain structure and function being of fundamental interest in cognitive neuroscience, the relationship between the brain's white matter, measured using fractional anisotropy (FA), and the functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) response is poorly understood. A systematic review of literature investigating the association between FA and fMRI BOLD response was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed and Web of Knowledge databases were searched up until 22.04.2016 using a predetermined set of search criteria. The search identified 363 papers, 28 of which met the specified inclusion criteria. Positive relationships were mainly observed in studies investigating the primary sensory and motor systems and in resting state data. Both positive and negative relationships were seen in studies using cognitive tasks. This systematic review suggests that there is a relationship between FA and the fMRI BOLD response and that the relationship is task and region dependent. Behavioural and/or clinical variables were shown to be essential in interpreting the relationships between imaging measures. The results highlight the heterogeneity in the methods used across papers in terms of fMRI task, population investigated and data analysis techniques. Further investigation and replication of current findings are required before definitive conclusions can be drawn., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Voxel-based morphometry has been used to investigate the associations between regional gray and white matter volume and cognitive function. The manuscript introduces these studies' methods, cautions, results, and problems related to the reports of the results. In many studies of ours that investigating these associations using the huge sample size and robust statistics, the associations were weak and wide spread in the brain. These patterns of results suggest the difficulty in finding the specific neural bases that underlie individual cognitive functions through VBM.

The capacity to imagine situations that have already happened or fictitious events that may take place in the future is known as mental time travel (MTT). Studies have shown that MTT is an important aspect of spontaneous thought, yet we lack a clear understanding of how the neurocognitive architecture of the brain constrains this element of human cognition. Previous functional magnetic resonance imaging (MRI) studies have shown that MTT involves the coordination between multiple regions that include mesiotemporal structures such as the hippocampus, as well as prefrontal and parietal regions commonly associated with the default mode network (DMN). The current study used a multimodal neuroimaging approach to identify the structural and functional brain organisation that underlies individual differences in the capacity to spontaneously engage in MTT. Using regionally unconstrained diffusion tractography analysis, we found increased diffusion anisotropy in right lateralised temporo-limbic, corticospinal, inferior fronto-occipital tracts in participants who reported greater MTT. Probabilistic connectivity mapping revealed a significantly higher connection probability of the right hippocampus with these tracts. Resting-state functional MRI connectivity analysis using the right hippocampus as a seed region revealed greater functional coupling to the anterior regions of the DMN with increasing levels of MTT. These findings demonstrate that the interactions between the hippocampus and regions of the cortex underlie the capacity to engage in MTT, and support contemporary theoretical accounts that suggest that the integration of the hippocampus with the DMN provides the neurocognitive landscape that allows us to imagine distant times and places., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Despite the wide applications of functional magnetic resonance imaging (fMRI) to mapping brain activation and connectivity in cortical gray matter, it has rarely been utilized to study white-matter functions. In this study, we investigated the spatiotemporal characteristics of fMRI data within the white matter acquired from humans both in the resting state and while watching a naturalistic movie. By using independent component analysis and hierarchical clustering, resting-state fMRI data in the white matter were de-noised and decomposed into spatially independent components, which were further assembled into hierarchically organized axonal fiber bundles. Interestingly, such components were partly reorganized during natural vision. Relative to resting state, the visual task specifically induced a stronger degree of temporal coherence within the optic radiations, as well as significant correlations between the optic radiations and multiple cortical visual networks. Therefore, fMRI contains rich functional information about the activity and connectivity within white matter at rest and during tasks, challenging the conventional practice of taking white-matter signals as noise or artifacts., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To determine how cardiovascular risk is associated with working memory task performance and task-related suppression of default-mode network (DMN) activity in cognitively intact older adults., Design: A cross-sectional functional magnetic resonance imaging study of older adults with cardiovascular risk factors., Setting: Rotman Research Institute, Baycrest Health Sciences., Participants: Thirty older adults with cardiovascular risk factors., Measurements: Participants provided health information and a blood sample, and underwent functional magnetic resonance imaging during a working memory task and during a breath-hold task to assess cerebrovascular reactivity., Results: Higher plasma low-density lipoprotein cholesterol (LDL-C) was associated with poorer working memory task performance (P = 0.008) and reduced task-related DMN suppression (P = 0.005). A composite index of cardiovascular risk, the Framingham General Cardiovascular Risk Profile, showed no associations with task performance or task-related DMN suppression. These findings were independent of white matter burden and cerebrovascular reactivity and thus cannot be accounted for by individual differences in neurovascular health., Conclusion: These findings suggest a deleterious effect of elevated LDL-C on working memory task performance and task-related DMN suppression in older adults with cardiovascular risk. The relations between the Framingham General Cardiovascular Risk Profile, cognitive task performance, and DMN function require further study., (© 2016 The Authors. The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.)

Resting state functional magnetic resonance imaging (rsfMRI) has been widely used to measure functional connectivity between cortical regions of the brain. However, there have been minimal reports of bold oxygenation level dependent (BOLD) signals in white matter, and even fewer attempts to detect resting state connectivity. Recently, there has been growing evidence that suggests that reliable detection of white matter BOLD signals may be possible. We have previously shown that nearest neighbor inter-voxel correlations of resting state BOLD signal fluctuations in white matter are anisotropic and can be represented by a functional correlation tensor, but the biophysical origins of these signal variations are not clear. We aimed to assess whether MRI signal fluctuations in white matter vary for different baseline levels of neural activity. We performed imaging studies on live squirrel monkeys under different levels of isoflurane anesthesia at 9.4T. We found 1) the fractional power (0.01-0.08Hz) in white matter was between 60 to 75% of the level in gray matter; 2) the power in both gray and white matter low frequencies decreased monotonically in similar manner with increasing levels of anesthesia; 3) the distribution of fractional anisotropy values of the functional tensors in white matter were significantly higher than those in gray matter; and 4) the functional tensor eigenvalues decreased with increasing level of anesthesia. Our results suggest that as anesthesia level changes baseline neural activity, white matter signal fluctuations behave similarly to those in gray matter, and functional tensors in white matter are affected in parallel., (Published by Elsevier Inc.)

Quantitative magnetic resonance imaging (qMRI) aims to quantify tissue parameters by eliminating instrumental bias. We describe qMRI theory, simulations, and software designed to estimate proton density (PD), the apparent local concentration of water protons in the living human brain. First, we show that, in the absence of noise, multichannel coil data contain enough information to separate PD and coil sensitivity, a limiting instrumental bias. Second, we show that, in the presence of noise, regularization by a constraint on the relationship between T1 and PD produces accurate coil sensitivity and PD maps. The ability to measure PD quantitatively has applications in the analysis of in-vivo human brain tissue and enables multisite comparisons between individuals and across instruments. Hum Brain Mapp 37:3623-3635, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Progress in magnetic resonance imaging (MRI) now makes it possible to identify the major white matter tracts in the living human brain. These tracts are important because they carry many of the signals communicated between different brain regions. MRI methods coupled with biophysical modeling can measure the tissue properties and structural features of the tracts that impact our ability to think, feel, and perceive. This review describes the fundamental ideas of the MRI methods used to identify the major white matter tracts in the living human brain.

Gait is a complex sequence of movements, requiring cooperation of many brain areas, such as the motor cortex, somatosensory cortex, and cerebellum. However, it is unclear which connecting white matter tracts are essential for communication across brain areas to facilitate proper gait. Using diffusion tensor imaging, we investigated associations of microstructural organization in 14 brain white matter tracts with gait, among 2330 dementia- and stroke-free community-dwelling individuals. Gait was assessed by electronic walkway and summarized into Global Gait, and 7 gait domains. Higher white matter microstructure associated with higher Global Gait, Phases, Variability, Pace, and Turning. Microstructure in thalamic radiations, followed by association tracts and the forceps major, associated most strongly with gait. Hence, in community-dwelling individuals, higher white matter microstructure associated with better gait, including larger strides, more single support, less stride-to-stride variability, and less turning steps. Our findings suggest that intact thalamocortical communication, cortex-to-cortex communication, and interhemispheric visuospatial integration are most essential in human gait., (Copyright © 2016 Elsevier Inc. All rights reserved.)