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Objective: In tasks involving new visuospatial information, we rely on working memory, supported by a distributed brain network. We investigated the dynamic interplay between brain regions, including cortical and white matter structures, to understand how neural interactions change with different memory loads and trials, and their subsequent impact on working memory performance., Methods: Patients undertook a task of immediate spatial recall during intracranial EEG monitoring. We charted the dynamics of cortical high-gamma activity and associated functional connectivity modulations in white matter tracts., Results: Elevated memory loads were linked to enhanced functional connectivity via occipital longitudinal tracts, yet decreased through arcuate, uncinate, and superior-longitudinal fasciculi. As task familiarity grew, there was increased high-gamma activity in the posterior inferior-frontal gyrus (pIFG) and diminished functional connectivity across a network encompassing frontal, parietal, and temporal lobes. Early pIFG high-gamma activity was predictive of successful recall. Including this metric in a logistic regression model yielded an accuracy of 0.76., Conclusions: Optimizing visuospatial working memory through practice is tied to early pIFG activation and decreased dependence on irrelevant neural pathways., Significance: This study expands our knowledge of human adaptation for visuospatial working memory, showing the spatiotemporal dynamics of cortical network modulations through white matter tracts., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The neurobiological underpinnings of action-related episodic memory and how enactment contributes to efficient memory encoding are not well understood. We examine whether individual differences in level (n = 338) and 5-year change (n = 248) in the ability to benefit from motor involvement during memory encoding are related to gray matter (GM) volume, white matter (WM) integrity, and dopamine-regulating genes in a population-based cohort (age range = 25-80 years). A latent profile analysis identified 2 groups with similar performance on verbal encoding but with marked differences in the ability to benefit from motor involvement during memory encoding. Impaired ability to benefit from enactment was paired with smaller HC, parahippocampal, and putamen volume along with lower WM microstructure in the fornix. Individuals with reduced ability to benefit from encoding enactment over 5 years were characterized by reduced HC and motor cortex GM volume along with reduced WM microstructure in several WM tracts. Moreover, the proportion of catechol-O-methyltransferase-Val-carriers differed significantly between classes identified from the latent-profile analysis. These results provide converging evidence that individuals with low or declining ability to benefit from motor involvement during memory encoding are characterized by low and reduced GM volume in regions critical for memory and motor functions along with altered WM microstructure., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

We examined the number, distribution, and immunoreactivity of the infracortical white matter neuronal population, also termed white matter interstitial cells (WMICs), throughout the telencephalic white matter of an adult female chimpanzee. Staining for neuronal nuclear marker (NeuN) revealed WMICs throughout the infracortical white matter, these cells being most numerous and dense close to the inner border of cortical layer VI, decreasing significantly in density with depth in the white matter. Stereological analysis of NeuN-immunopositive cells revealed an estimate of approximately 137.2 million WMICs within the infracortical white matter of the chimpanzee brain studied. Immunostaining revealed subpopulations of WMICs containing neuronal nitric oxide synthase (nNOS, approximately 14.4 million in number), calretinin (CR, approximately 16.7 million), very few WMICs containing parvalbumin (PV), and no calbindin-immunopositive neurons. The nNOS, CR, and PV immunopositive WMICs, possibly all inhibitory neurons, represent approximately 22.6% of the total WMIC population. As the white matter is affected in many cognitive conditions, such as schizophrenia, autism, epilepsy, and also in neurodegenerative diseases, understanding these neurons across species is important for the translation of findings of neural dysfunction in animal models to humans. Furthermore, studies of WMICs in species such as apes provide a crucial phylogenetic context for understanding the evolution of these cell types in the human brain., (© 2021 Wiley Periodicals LLC.)

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.)

The corpus callosum (CC), the anterior (AC), and the posterior (PC) commissures are the principal axonal fiber bundle pathways that allow bidirectional communication between the brain hemispheres. Here, we used the Allen mouse brain connectivity atlas and high-resolution diffusion-weighted MRI (DWI) to investigate interhemispheric fiber bundles in C57bl6/J mice, the most commonly used wild-type mouse model in biomedical research. We identified 1) commissural projections from the primary motor area through the AC to the contralateral hemisphere; and 2) intrathalamic interhemispheric fiber bundles from multiple regions in the frontal cortex to the contralateral thalamus. This is the first description of direct interhemispheric corticothalamic connectivity from the orbital cortex. We named these newly identified crossing points thalamic commissures. We also analyzed interhemispheric connectivity in the Balb/c mouse model of dysgenesis of the corpus callosum (CCD). Relative to C57bl6/J, Balb/c presented an atypical and smaller AC and weaker interhemispheric corticothalamic communication. These results redefine our understanding of interhemispheric brain communication. Specifically, they establish the thalamus as a regular hub for interhemispheric connectivity and encourage us to reinterpret brain plasticity in CCD as an altered balance between axonal reinforcement and pruning., (Published by Oxford University Press 2021.)

Objective: In order to evaluate the clinical utility even under general anesthesia, the present study aimed to clarify the effect of anesthesia on the cortico-cortical evoked potentials (CCEPs)., Methods: We analyzed 14 patients' data in monitoring the integrity of the dorsal language pathway by using CCEPs both under general anesthesia with propofol and remifentanil and awake condition, with the main aim of clarifying the effect of anesthesia on the distribution and waveform of CCEPs., Results: The distribution of larger CCEP response sites, including the locus of the maximum CCEP response site, was marginally affected by anesthesia. With regard to similarity of waveforms, the mean waveform correlation coefficient indicated a strong agreement. CCEP N1 amplitude increased by an average of 25.8% from general anesthesia to waking, except three patients. CCEP N1 latencies had no correlation in changes between the two conditions., Conclusions: We demonstrated that the distribution of larger CCEP responses was marginally affected by anesthesia and that the CCEP N1 amplitude had tendency to increase from general anesthesia to the awake condition., Significance: The CCEP method provides the efficiency of intraoperative monitoring for dorsal language white matter pathway even under general anesthesia., Competing Interests: Declaration of Competing Interest Department of Epilepsy, Movement Disorders and Physiology (Kyoto University Graduate School of Medicine) is the Industry-Academic Collaboration Courses, supported by Eisai Co., Ltd., NIHON KOHDEN CORPORATION, Otsuka Pharmaceutical Co., and UCB Japan Co., Ltd., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by 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.

During the second and third trimesters of human gestation, rapid neurodevelopment is underpinned by fundamental processes including neuronal migration, cellular organization, cortical layering, and myelination. In this time, white matter growth and maturation lay the foundation for an efficient network of structural connections. Detailed knowledge about this developmental trajectory in the healthy human fetal brain is limited, in part, due to the inherent challenges of acquiring high-quality MRI data from this population. Here, we use state-of-the-art high-resolution multishell motion-corrected diffusion-weighted MRI (dMRI), collected as part of the developing Human Connectome Project (dHCP), to characterize the in utero maturation of white matter microstructure in 113 fetuses aged 22 to 37 wk gestation. We define five major white matter bundles and characterize their microstructural features using both traditional diffusion tensor and multishell multitissue models. We found unique maturational trends in thalamocortical fibers compared with association tracts and identified different maturational trends within specific sections of the corpus callosum. While linear maturational increases in fractional anisotropy were seen in the splenium of the corpus callosum, complex nonlinear trends were seen in the majority of other white matter tracts, with an initial decrease in fractional anisotropy in early gestation followed by a later increase. The latter is of particular interest as it differs markedly from the trends previously described in ex utero preterm infants, suggesting that this normative fetal data can provide significant insights into the abnormalities in connectivity which underlie the neurodevelopmental impairments associated with preterm birth., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

The mismatch negativity (MMN) is an event related brain potential (ERP) elicited by unpredicted sounds presented in a sequence of repeated auditory stimuli. The neural sources of the MMN have been previously attributed to a fronto-temporo-parietal network which crucially overlaps with the so-called auditory dorsal stream, involving inferior and middle frontal, inferior parietal, and superior and middle temporal regions. These cortical areas are structurally connected by the arcuate fasciculus (AF), a three-branch pathway supporting the feedback-feedforward loop involved in auditory-motor integration, auditory working memory, storage of acoustic templates, as well as comparison and update of those templates. Here, we characterized the individual differences in the white-matter macrostructural properties of the AF and explored their link to the electrophysiological marker of passive change detection gathered in a melodic multifeature MMN-EEG paradigm in 26 healthy young adults without musical training. Our results show that left fronto-temporal white-matter connectivity plays an important role in the pre-attentive detection of rhythm modulations within a melody. Previous studies have shown that this AF segment is also critical for language processing and learning. This strong coupling between structure and function in auditory change detection might be related to life-time linguistic (and possibly musical) exposure and experiences, as well as to timing processing specialization of the left auditory cortex. To the best of our knowledge, this is the first time in which the relationship between neurophysiological (EEG) and brain white-matter connectivity indexes using DTI-tractography are studied together. Thus, the present results, although still exploratory, add to the existing evidence on the importance of studying the constraints imposed on cognitive functions by the underlying structural connectivity., (Copyright © 2021. Published by Elsevier Inc.)

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.)

We aimed to link macro- and microstructure measures of brain white matter obtained from diffusion MRI with effective connectivity measures based on a propagation of cortico-cortical evoked potentials induced with intrasurgical direct electrical stimulation. For this, we compared streamline lengths and log-transformed ratios of streamlines computed from presurgical diffusion-weighted images, and the delays and amplitudes of N1 peaks recorded intrasurgically with electrocorticography electrodes in a pilot study of 9 brain tumor patients. Our results showed positive correlation between these two modalities in the vicinity of the stimulation sites (Pearson coefficient 0.54±0.13 for N1 delays, and 0.47±0.23 for N1 amplitudes), which could correspond to the neural propagation via U-fibers. In addition, we reached high sensitivities (0.78±0.07) and very high specificities (0.93±0.03) in a binary variant of our comparison. Finally, we used the structural connectivity measures to predict the effective connectivity using a multiple linear regression model, and showed a significant role of brain microstructure-related indices in this relation., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Over the last 15 years, research on canid cognition has revealed that domestic dogs possess a surprising array of complex sociocognitive skills pointing to the possibility that the domestication process might have uniquely altered their brains; however, we know very little about how evolutionary processes (natural or artificial) might have modified underlying neural structure to support species-specific behaviors. Evaluating the degree of cortical folding (i.e., gyrification) within canids may prove useful, as this parameter is linked to functional variation of the cerebral cortex. Using quantitative magnetic resonance imaging to investigate the impact of domestication on the canine cortical surface, we compared the gyrification index (GI) in 19 carnivore species, including six wild canid and 13 domestic dog individuals. We also explored correlations between global and local GI with brain mass, cortical thickness, white and gray matter volume and surface area. Our results indicated that GI values for domestic dogs are largely consistent with what would be expected for a canid of their given brain mass, although more variable than that observed in wild canids. We also found that GI in canids is positively correlated with cortical surface area, cortical thickness and total cortical gray matter volumes. While we found no evidence of global differences in GI between domestic and wild canids, certain regional differences in gyrification were observed., (© 2020 Wiley Periodicals LLC.)

The frontal cortex and temporal lobes together regulate complex learning and memory capabilities. Here, we collected resting-state functional and diffusion-weighted MRI data before and after male rhesus macaque monkeys received extensive training to learn novel visuospatial discriminations (reward-guided learning). We found functional connectivity changes in orbitofrontal, ventromedial prefrontal, inferotemporal, entorhinal, retrosplenial, and anterior cingulate cortices, the subicular complex, and the dorsal, medial thalamus. These corticocortical and thalamocortical changes in functional connectivity were accompanied by related white matter structural alterations in the uncinate fasciculus, fornix, and ventral prefrontal tract: tracts that connect (sub)cortical networks and are implicated in learning and memory processes in monkeys and humans. After the well-trained monkeys received fornix transection, they were impaired in learning new visuospatial discriminations. In addition, the functional connectivity profile that was observed after the training was altered. These changes were accompanied by white matter changes in the ventral prefrontal tract, although the integrity of the uncinate fasciculus remained unchanged. Our experiments highlight the importance of different communication relayed among corticocortical and thalamocortical circuitry for the ability to learn new visuospatial associations (learning-to-learn) and to make reward-guided decisions. SIGNIFICANCE STATEMENT Frontal neural networks and the temporal lobes contribute to reward-guided learning in mammals. Here, we provide novel insight by showing that specific corticocortical and thalamocortical functional connectivity is altered after rhesus monkeys received extensive training to learn novel visuospatial discriminations. Contiguous white matter fiber pathways linking these gray matter structures, namely, the uncinate fasciculus, fornix, and ventral prefrontal tract, showed structural changes after completing training in the visuospatial task. Additionally, different patterns of functional and structural connectivity are reported after removal of subcortical connections within the extended hippocampal system, via fornix transection. These results highlight the importance of both corticocortical and thalamocortical interactions in reward-guided learning in the normal brain and identify brain structures important for memory capabilities after injury., (Copyright © 2020 the authors.)

The Imperial Academy of Medicine of Paris met in the spring of 1865 to discuss the localization of speech. One of the participants was Maximien Parchappe (1800-1866), an alienist whose research interests lay in the cerebral cortex. This article addresses Maximien Parchappe's concept that the cognitive elements of language-such as the translation of thoughts into words, the will to express them, and the means to do so-reside within the cortical gray matter, and that they are integrated through white-matter fibers. In so doing, Parchappe anticipated Carl Wernicke's linking of the posterior aspects of the dominant frontal and temporal lobes in verbal expression, and Jules Dejerine's linking of the angular gyrus and Wernicke's area in the understanding of written language. Functional imaging has revived interest in language as a network of neuronal aggregates and has given new relevance to Parchappe's concept of the functional organization of language.

Determining the anatomical source of brain activity non-invasively measured from EEG or MEG sensors is challenging. In order to simplify the source localization problem, many techniques introduce the assumption that current sources lie on the cortical surface. Another common assumption is that this current flow is orthogonal to the cortical surface, thereby approximating the orientation of cortical columns. However, it is not clear which cortical surface to use to define the current source locations, and normal vectors computed from a single cortical surface may not be the best approximation to the orientation of cortical columns. We compared three different surface location priors and five different approaches for estimating dipole vector orientation, both in simulations and visual and motor evoked MEG responses. We show that models with source locations on the white matter surface and using methods based on establishing correspondences between white matter and pial cortical surfaces dramatically outperform models with source locations on the pial or combined pial/white surfaces and which use methods based on the geometry of a single cortical surface in fitting evoked visual and motor responses. These methods can be easily implemented and adopted in most M/EEG analysis pipelines, with the potential to significantly improve source localization of evoked responses., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Fluid intelligence (Gf) is the innate ability of an individual to respond to complex and unexpected situations. Although some studies have considered that the multiple-demand (MD) system of the brain was the biological foundation for Gf, further characterization of their relationships in the context of aging is limited. The present study hypothesized that the structural metrics of the MD system, including cortical thickness, cortical volumes, and white matter (WM) tract integrity, was the brain correlates for Gf across the adult life span. Partial correlation analysis was performed to investigate whether the MD system could still explain Gf independent of the age effect. Moreover, the partial correlations between Gf and left/right structural metrics within the MD regions were compared to test whether the correlations displayed distinct lateralization., Methods: The participants were recruited from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) databank, comprising the images of 603 healthy participants aged 18-88 years acquired on a 3-T system. The MRI data included high-resolution T1-weighted and diffusion-weighted images, from which gray matter and WM structural metrics of the MD system were analyzed, respectively. The structural metrics of gray matter were quantified in terms of cortical volume/thickness of five pairs of cortical regions, and those of WM were quantified in terms of the mean axial diffusivity (D A ), radial diffusivity (D R ), mean diffusivity (D M ), and generalized fractional anisotropy (GFA) on five pairs of tracts. Partial correlation controlling for age and sex effects, was performed to investigate the associations of Gf scores with the mean D A , D R , D M and GFA of all tracts in the MD system, those of left and right hemispheric tracts, and those of each tract. Fisher's exact test was used to compare the partial correlations between left and right MD regions., Results: The linear relationship between cortical volumes and Gf was evident across all levels of the MD system even after controlling for age and sex. For the WM integrity, diffusion indices including D A , D R , D M and GFA displayed linear relationships with Gf scores at various levels of the MD system. Among the 10 WM tracts connecting the MD regions, bilateral superior longitudinal fasciculus I and bilateral frontal aslant tracts exhibited the strongest and significant associations. Our results did not show significant inter-hemispheric differences in the associations between structural metrics of the MD system and Gf., Conclusion: Our results demonstrate significant associations between Gf and both cortical volumes and tract integrity of the MD system across the adult lifespan in a population-based cohort. We found that the association remained significant in the entire adult lifespan despite simultaneous decline of Gf and the MD system. Our results suggest that the MD system might be a structural underpinning of Gf and support the fronto-parietal model of cognitive aging. However, we did not find hemispheric differences in the Gf-MD correlations, not supporting the hemi-aging hypothesis., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Humans show great interindividual variability in the degree they engage in social relationship. The neural basis of this variability is still poorly understood, particularly in children. In this study, we aimed to investigate the neural basis of interindividual variability in the first step of social behavior, that is social perception, in typically developing children. For that purpose, we first used eye-tracking to objectively measure eye-gaze processing during passive visualization of social movie clips in 24 children and adolescents (10.5 ± 2.9 y). Secondly, we correlated eye-tracking data with measures of fractional anisotropy, an index of white matter microstructure, obtained using diffusion tensor imaging MRI. The results showed a large interindividual variability in the number of fixations to the eyes of characters during visualization of social scenes. In addition, whole-brain analysis showed a significant positive correlation between FA and number of fixations to the eyes,mainly in the temporal part of the superior longitudinal fasciculi bilaterally, adjacent to the posterior superior temporal cortex. Our results indicate the existence of a neural signature associated with the interindividual variability in social perception in children, contributing for better understanding the neural basis of typical and atypical development of a broader social expertise.

Human cognition and behavior emerge from neuronal interactions on a brain structural architecture. The convergence (or divergence) between functional dynamics and structural connectivity (SC) and their relationship with cognition are still a pivotal question about the brain. We focused on the information processing speed (IPS), assessed by the Symbol Digit Modalities Test (SDMT), once delayed IPS underlies attention deficits in various clinical conditions. We hypothesize that the SC constrains but does not determine functional connectivity, and such a relationship is related to the cognitive performance. Blood oxygenation level-dependent and diffusion tensor images of healthy young volunteers were acquired in a 3T magnetic resonance imaging machine. Activation maps included the left and right middle frontal gyri, left superior parietal lobule, left precuneus, left inferior frontal gyrus (IFG), right cuneus, left lingual gyrus, and left declive. A network involving such regions and signal propagation from visual, through cognitive, up to motor regions was proposed. Random effects Bayesian model selection showed that the top-down connections have the highest expected and exceedance probabilities. Moreover, all pairs of task-related regions were connected by at least one tract, except for the left declive with the left IFG. The interactions between the right cuneus with left declive were related to the interindividual variability in SDMT performance. Altogether, our findings suggest that the IPS functional network is related to the highest SDMT scores when its effective endogenous connections are suppressed to the detriment of modulation caused by the experimental conditions, with the underlying structure providing low diffusion environments.

In the white matter of the human cerebrum, the majority of cortico-cortical fibers are of short range, connecting neighboring cortical areas. U-fibers represent connections between neighboring areas and are located in the white matter immediately deep to the cerebral cortex. Using gyrencephalic carnivore ferrets, here we investigated the neurochemical, anatomical and developmental features of U-fibers. We demonstrate that U-fibers were derived from neighboring cortical areas in ferrets. U-fiber regions in ferrets were intensely stained with Gallyas myelin staining and Turnbull blue iron staining. We further found that U-fibers were derived from neurons in both upper and lower layers in neighboring areas of the cerebral cortex and that U-fibers were formed later than axons in the deep white matter during development. Our findings shed light on the fundamental features of U-fibers in the gyrencephalic cerebral cortex. Because genetic manipulation techniques for ferrets are now available, ferrets should be an important option for investigating the development, functions and pathophysiological changes of U-fibers.

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.)

Cortical atrophy and degraded axonal health have been shown to coincide during normal aging; however, few studies have examined these measures together. To lend insight into both the regional specificity and the relative timecourse of structural degradation of these tissue compartments across the adult lifespan, we analyzed gray matter (GM) morphometry (cortical thickness, surface area, volume) and estimates of white matter (WM) microstructure (fractional anisotropy, mean diffusivity) using traditional univariate and more robust multivariate techniques to examine age associations in 186 healthy adults aged 20-94 years old. Univariate analysis of each tissue type revealed that negative age associations were largest in frontal GM and WM tissue and weaker in temporal, cingulate, and occipital regions, representative of not only an anterior-to-posterior gradient, but also a medial-to-lateral gradient. Multivariate partial least squares correlation (PLSC) found the greatest covariance between GM and WM was driven by the relationship between WM metrics in the anterior corpus callosum and projections of the genu, anterior cingulum, and fornix; and with GM thickness in parietal and frontal regions. Surface area was far less susceptible to age effects and displayed less covariance with WM metrics, while regional volume covariance patterns largely mirrored those of cortical thickness. Results support a retrogenesis-like model of aging, revealing a coupled relationship between frontal and parietal GM and the underlying WM, which evidence the most protracted development and the most vulnerability during healthy aging., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

The physiological basis of resilience to age-associated and AD-typical neurodegenerative pathology is still not well understood. So far, the established resilience factor intelligence has been shown to be associated with white matter network global efficiency, a key constituent of which are highly connected hubs. However, hub properties have also been shown to be impaired in AD. Individual predisposition or vulnerability of hub properties may thus modulate the impact of pathology on cognitive outcome and form part of the physiological basis of resilience. 85 cognitively normal elderly subjects and patients with MCI with DWI, MRI and AV45-PET scans were included from ADNI. We reconstructed the global WM networks in each subject and characterized hub-properties of GM regions using graph theory by calculating regional betweenness centrality. Subsequently, we investigated whether regional GM volume (GMV) and structural WM connectivity (WMC) of more hub-like regions was more associated with resilience, quantified as cognitive performance independent of amyloid burden, tau and WM lesions. Subjects with higher resilience showed higher increased regional GMV and WMC in more hub-like compared to less hub-like GM-regions. Additionally, this association was in some instances further increased at elevated amounts of brain pathology. Higher GMV and WMC of more hub-like regions may contribute more to resilience compared to less hub-like regions, reflecting their increased importance to brain network efficiency, and may thus form part of the neurophysiological basis of resilience. Future studies should investigate the factors leading to higher GMV and WMC of hubs in non-demented elderly with higher resilience.

Hand preference is a striking example of functional lateralization, with 90% of the population preferentially using their right hand. However, the search for brain structural correlates of this lateralization has produced inconsistent results. While large-scale neuroimaging studies using automated methods have largely failed to find local anatomical asymmetries associated with hand preference, other studies identifying specific motor regions have been able to find local morphological and functional differences. The present study looked at brain asymmetries in the brain's motor system using established cortical landmarks to identify the somatomotor hand region and extracted regional volumes of subcortical and cerebellar regions. Our results showed a strong left-right asymmetry in the cortical hand region, with weaker asymmetries appearing in the striatum and cerebellar white matter. Such asymmetries were much more pronounced in right-handers, whereas much weaker or absent lateralizing effects were observed in left-handed subjects. This study demonstrates the importance of local landmarks in studying individual anatomical differences. More generally, establishing structural correlates of hand preference is important, as this could further establish the origins of cerebral lateralization.

Because the white matter of the cerebral cortex contains axons that connect distant neurons in the cortical gray matter, the relationship between the volumes of the 2 cortical compartments is key for information transmission in the brain. It has been suggested that the volume of the white matter scales universally as a function of the volume of the gray matter across mammalian species, as would be expected if a global principle of wiring minimization applied. Using a systematic analysis across several mammalian clades, here we show that the volume of the white matter does not scale universally with the volume of the gray matter across mammals and is not optimized for wiring minimization. Instead, the ratio between volumes of gray and white matter is universally predicted by the same equation that predicts the degree of folding of the cerebral cortex, given the clade-specific scaling of cortical thickness, such that the volume of the gray matter (or the ratio of gray to total cortical volumes) divided by the square root of cortical thickness is a universal function of total cortical volume, regardless of the number of cortical neurons. Thus, the very mechanism that we propose to generate cortical folding also results in compactness of the white matter to a predictable degree across a wide variety of mammalian species., Competing Interests: The authors declare no conflict of interest.

The aims of this study were to determine which cognitive control functions are most sensitive to cross-sectional age differences and to identify neural features in different neuroimaging modalities that associated cognitive control function across the adult lifespan. We employed a joint independent component analysis (jICA) approach to obtain common networks among three different brain-imaging modalities (i.e., structural MRI, resting-state functional MRI, and diffusion tensor imaging) in relation to the cognitive control function. We differentiated three distinct cognitive constructs: one common (across inhibition, shifting, and updating) and two specific (shifting, updating) factors. These common/specific constructs were transformed from three original performance indexes: (a) stop-signal reaction time, (b) switch-cost, and (c) performance sensitivity collected from 156 individuals aged 20 to 78 years old. The current results show that the cross-sectional age difference is associated with a wide spread of brain degeneration that is not limited to the frontal region. Crucially, these findings suggest there are some common and distinct joined multimodal components that correlate with the psychological constructs of common and discrete cognitive control functions, respectively. To support current findings, other fusion ICA models were also analyzed including, parallel ICA (para-ICA) and multiset canonical correlation analysis with jICA (mCCA + jICA). Dynamic interactions among these brain features across different brain modalities could serve as possible developmental mechanisms associated with these age effects., (© 2019 Wiley Periodicals, Inc.)

Background: Multiple sclerosis (MS) has both an inflammatory and a neurodegenerative component, with gray matter (GM) atrophy being an important contributor to disability. Optical coherence tomography (OCT) may serve as a prognostic tool for neuroaxonal health by measuring ganglion cell inner plexiform layer (GCIPL) thickness. There is a paucity of literature regarding the effects of race on pathobiology of MS, as racial minorities are underrepresented in research studies., Objective: The aim of this paper is to compare the correlation between GM fraction (GMF) and GCIPL thickness in Caucasian Americans with MS (CAMS) and African Americans with MS (AAMS)., Methods: Fifty-nine patients with relapsing-remitting multiple sclerosis (RRMS) were included. Using a cross-sectional design, we compared the OCT (GCIPL thickness) and MRI (GMF) data of 32 CAMS and 27 AAMS patients., Results: No significant correlation was observed between GMF and GCIPL in our study group (p = 0.127, r = 0.148). CAMS exhibited a significant correlation between these measures (p = 0.0004, r = 0.434), while in AAMS these measures did not correlate significantly (p = 0.187, r = -0.201)., Conclusion: GCIPL might be a sensitive biomarker predicting GM atrophy and disability in CAMS, but not in AAMS. Larger studies are needed to investigate reliable biomarkers across races. Inclusion of AAMS in research studies is necessary to shed more light on the pathobiology of MS., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To what extent are levels of cognitive expertise reflected in differential structural connectivity of the brain? We addressed this question by analyzing the white matter brain structure of experts (mathematicians) versus non-experts (non-mathematicians) using probabilistic tractography. Having mathematicians and non-mathematicians as participant groups enabled us to directly compare profiles of structural connectivity arising from individual levels of expertise in mathematics. Tracking from functional seed regions activated during the processing of complex arithmetic formulas revealed an involvement of various fiber bundles such the inferior fronto-occipital fascicle, arcuate fasciculus/superior longitudinal fasciculus (AF/SLF), cross-hemispheric connections of frontal lobe areas through the corpus callosum and cortico-subcortical connectivity via the bilateral thalamic radiation. With the aim of investigating expertise-dependent structural connectivity, the streamline density was correlated with the level of expertise, defined by automaticity of processing complex mathematics. The results showed that structural integrity of the AF/SLF was higher in individuals with higher automaticity, while stronger cortico-thalamic connectivity was associated with lower levels of automaticity. Therefore, we suggest that expertise in the domain of mathematics is reflected in plastic changes of the brain's white matter structure, possibly reflecting a general principle of cognitive expertise.

It has been recently found that the human dorso-central insular cortex contributes to the execution and recognition of the affective component of hand actions, most likely through modulation of the activity of the parieto-frontal circuits. While the anatomical connections between the hand representation of the insula and, the parietal and frontal regions controlling reaching/grasping actions is well assessed in the monkey, it is unknown the existence of a homolog circuit in humans. In the present study, we performed a multifiber tractography investigation to trace the tracts possibly connecting the insula to the parieto-frontal circuits by locating seeds in the parietal, premotor, and prefrontal nodes of the reaching/grasping network, in both humans and monkeys. Results showed that, in both species, the insula is connected with the cortical action execution/recognition circuit by similar white matter tracts, running in parallel to the third branch of the superior longitudinal fasciculus and the anterior segment of the arcuate fasciculus., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Accurate estimates of the BOLD hemodynamic response function (HRF) are crucial for the interpretation and analysis of event-related functional MRI data. To date, however, there have been no comprehensive measurements of the HRF in white matter (WM) despite increasing evidence that BOLD signals in WM change after a stimulus. We performed an event-related cognitive task (Stroop color-word interference) to measure the HRF in selected human WM pathways. The task was chosen in order to produce robust, distributed centers of activity throughout the cortex. To measure the HRF in WM, fiber tracts were reconstructed between each pair of activated cortical areas. We observed clear task-specific HRFs with reduced magnitudes, delayed onsets and prolonged initial dips in WM tracts compared with activated grey matter, thus calling for significant changes to current standard models for accurately characterizing the HRFs in WM and for modifications of standard methods of analysis of functional imaging data.

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.)

Cerebrovascular reactivity (CVR) is a measure of vascular response to a vasoactive stimulus, and can be used to assess the health of the brain vasculature. In this current study we used different analyses of BOLD fMRI responses to CO 2 to provide a number of metrics including ramp and step CVR, speed of response and transfer function analysis (TFA). 51 healthy control volunteers between the ages of 18-85 (26 males) were recruited and scanned at 3T field strength. Atlases reflecting voxel-wise means and standard deviations were compiled to assess possible differences in these metrics between four age cohorts. Testing was carried out using an automated computer-controlled gas blender to induce hypercapnia in a step and ramp paradigm, and monitoring end-tidal partial pressures of CO 2 (P ET CO 2 ) and O 2 (P ET O 2 ). No significant differences were found for resting P ET CO 2 values between cohorts. Ramp CVR decreased significantly with age in white matter frontal regions comprising the ACA-MCA watershed area, a finding that may be indicative of age related changes. Similarly, TFA showed that gain was reduced in the left white matter ACA-MCA watershed area as well as the posterior and anterior cingulate cortex, and superior frontal gyrus in the oldest compared to youngest cohort. These findings, detailing changes in cerebrovascular regulation in the healthy aging brain should prove useful in mapping areas of dysregulated blood flow in individuals with vascular risk factors especially those at risk for developing vascular dementia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The insula is a multimodal sensory integration structure that, in addition to serving as a gateway between somatosensory areas and limbic structures, plays a crucial role in autonomic nervous system function. While anatomical studies following the development of the insula have been conducted, currently, no studies have been published in human fetuses tracking the development of neuronal migration or of white matter tracts in the cortex. In this study, we aimed to follow the neuronal migration and subsequent maturation of axons in and around the insula in human fetal ages. Using high-angular resolution diffusion magnetic resonance imaging tractography, major white matter pathways to/from the insula and its surrounding operculum were identified at a number of time points during human gestation. Pathways likely linked to neuronal migration from the ventricular zone to the inferior frontal gyrus, superior temporal region, and the insular cortex were detected in the earliest gestational age studied (15 GW). Tractography reveals neuronal migration to areas surrounding the insula occurred at different time points. These results, in addition to demonstrating key time points for neuronal migration, suggest that neurons and axonal fiber pathways underlying the insula and its surrounding gyri mature differentially despite their relationship during cortical folding.

The organization of the human insular cortex has traditionally been considered as an anterior-posterior dichotomy, where anterior and posterior subdivisions have unique structural and functional connections. However, recent functional neuroimaging research proposes a tripartite organization where insular subdivisions have both unique and overlapping functional profiles. Studies examining unique profiles show that the dorsal anterior insula (dAI) has connections with frontal areas supporting higher-level cognitive processes, the ventral anterior insula (vAI) has connections with limbic areas supporting affective processes, and the posterior insula (PI) has connections with sensorimotor areas supporting interoceptive processes. Studies examining overlapping profiles demonstrate that all 3 subdivisions can also have similar functional profiles. The structural organization supporting a functional tripartite insula organization presenting with overlapping and unique connections is currently unknown. We used a large HARDI diffusion magnetic resonance imaging (MRI) dataset (n = 199) to demonstrate novel visualizations of insula white matter tracts supporting a tripartite structure-function insula organization. Overlapping connections of all 3 insula subdivisions consisted of association pathways (inferior fronto-occipital fasciculus, uncinate fasciculus, arcuate fasciculus) while unique connections included the corona radiata, subcortical-cortical tracts, and horizontal and u-shaped tracts. These results generally support a tripartite structure-function organization of the insular cortex, with subdivisions that exhibit both overlapping and unique connectivity profiles.

Understanding how knowledge is represented in the human brain is a fundamental challenge in neuroscience. To date, most of the work on this topic has focused on knowledge representation in cortical areas and debated whether knowledge is represented in a distributed or localized fashion. Fang and colleagues provide evidence that brain connections and the white matter supporting such connections might play a significant role. The work opens new avenues of investigation, breaking through disciplinary boundaries across network neuroscience, computational neuroscience, cognitive science, and classical lesion studies.

The subcortical white matter (SWM) has been traditionally considered as a site for passive-neutral-information transfer through cerebral cortex association and projection fibers. Yet, the presence of subcortical neuronal and glial "interstitial" cells expressing immunolabelled neurotransmitters/neuromodulators and synaptic vesicular proteins, and recent immunohistochemical and electrophysiological observations on the rat visual cortex as well as interactive regulation of myelinating processes support the possibility that SWM nests subcortical, regionally variable, distributed neuronal-glial circuits, that could influence information transfer. Their hypothetical involvement in regulating the timing and signal transfer probability at the SWM axonal components ought to be considered and experimentally analysed. Thus, the "interstitial" neuronal cells-associated with local glial cells-traditionally considered to be vestigial and functionally inert under normal conditions, they may well turn to be critical in regulating information transfer at the SWM.

Understanding events requires interplaying cognitive processes arising in neural networks whose organisation and connectivity remain subjects of controversy in humans. In the present study, by combining diffusion tensor imaging and functional interaction analysis, we aim to provide new insights on the organisation of the structural and functional pathways connecting the multiple nodes of the identified semantic system -shared by vision and language (Jouen et al., 2015). We investigated a group of 19 healthy human subjects during experimental tasks of reading sentences or seeing pictures. The structural connectivity was realised by deterministic tractography using an algorithm to extract white matter fibers terminating in the selected regions of interest (ROIs) and the functional connectivity by independent component analysis to measure correlated activities among these ROIs. The major connections link ventral neural stuctures including the parietal and temporal cortices through inferior and middle longitudinal fasciculi, the retrosplenial and parahippocampal cortices through the cingulate bundle, and the temporal and prefrontal structures through the uncinate fasciculus. The imageability score provided when the subject was reading a sentence was significantly correlated with the factor of anisotropy of the left parieto-temporal connections of the middle longitudinal fasciculus. A large part of this ventrally localised structural connectivity corresponds to functional interactions between the main parietal, temporal and frontal nodes. More precisely, the strong coactivation both in the anterior temporal pole and in the region of the temporo-parietal cortex suggests dual and cooperating roles for these areas within the semantic system. These findings are discussed in terms of two semantics-related sub-systems responsible for conceptual representation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Essential language sites and the arcuate fasciculus (AF) have been extensively researched. However, the relationship between them remains insufficiently studied, especially in healthy people. Navigated transcranial magnetic stimulation (nTMS) is increasingly used in language mapping. While enjoying the advantage of non-invasiveness, it is also capable of inducing a virtual lesion in the brain. Thus, it offers the possibility of using the virtual-lesion method to study the healthy brain. This study combined nTMS and diffusion tensor imaging (DTI) tractography to investigate the relationship between essential language sites and the AF in 30 healthy right-handed volunteers. A total of 143 essential language sites were identified using nTMS, and a total of 175 AF terminations were identified using DTI tractography. Sixty-six sites had a direct correlation with the AF, accounting for 46% of the total essential language sites. Forty-seven AF terminations harbored essential language sites, accounting for 27% of the total AF terminations. Upon data rendering to the cortical parcellation system, a region-related heterogeneity of the correlation rate was found. This study provides the first data on the relationship between essential language sites and the AF in healthy adults.

Objective: We determined if transcranial color-coded Doppler derived hemodynamics are associated with MRI-based cerebral blood flow (CBF) in regions clinically important to dementia in healthy middle-aged adults., Approach: In 30 subjects (18m/12f; age  =  52  ±  1 years), blood flow velocity (BFV) and cerebrovascular conductance (CVC) were measured with transcranial color-coded Doppler (TCCD) at the middle cerebral artery (MCA) and cerebral blood flow (CBF) was assessed with arterial spin labeled perfusion MRI., Main Results: BFV and CVC were associated with hippocampus (r  =  0.58 and r  =  0.61, both p  <  0.01) and occipitoparietal (r  =  0.50 and r  =  0.58, both p  <  0.01) CBF. CVC was further associated with posterior cingulate CBF (r  =  0.58 p  <  0.01). Independent of age and sex, BFV and CVC were associated with hippocampus (r  =  0.59 and r  =  0.55, both p  <  0.003) and occipitoparietal (r  =  0.50 and r  =  0.57, both p  <  0.01) CBF. CVC was independently associated with posterior cingulate CBF (r  =  0.38, p  =  0.049)., Significance: TCCD-measured BFV and CVC of the MCA are indicators of cerebral perfusion to clinically valuable brain regions in healthy middle-aged adults. TCCD may not be a good indicator of blood flow to cerebral white matter.

The neural foundations underlying semantic processing have been extensively investigated, highlighting a pivotal role of the ventral stream. However, although studies concerning the involvement of the left ventral route in verbal semantics are proficient, the potential implication of the right ventral pathway in non-verbal semantics has been to date unexplored. To gain insights on this matter, we used an intraoperative direct electrostimulation to map the structures mediating the non-verbal semantic system in the right hemisphere. Thirteen patients presenting with a right low-grade glioma located within or close to the ventral stream were included. During the 'awake' procedure, patients performed both a visual non-verbal semantic task and a verbal (control) task. At the cortical level, in the right hemisphere, we found non-verbal semantic-related sites (n = 7 in 6 patients) in structures commonly associated with verbal semantic processes in the left hemisphere, including the superior temporal gyrus, the pars triangularis, and the dorsolateral prefrontal cortex. At the subcortical level, we found non-verbal semantic-related sites in all but one patient (n = 15 sites in 12 patients). Importantly, all these responsive stimulation points were located on the spatial course of the right inferior fronto-occipital fasciculus (IFOF). These findings provide direct support for a critical role of the right IFOF in non-verbal semantic processing. Based upon these original data, and in connection with previous findings showing the involvement of the left IFOF in non-verbal semantic processing, we hypothesize the existence of a bilateral network underpinning the non-verbal semantic system, with a homotopic connectional architecture.

Cortical network activity correlates with vigilance state: Deep sleep is characterized by slow, synchronized oscillations, whereas desynchronized, stochastic discharge is typical of the waking state. Neuropeptides, such as orexin and substance P but also neurotensin (NT), promote arousal. Relatively little is known about if NT can directly affect the cortical network, and if so, through which mechanisms and cellular targets. Here, we addressed these issues using rat in vitro cortex preparations. Following NT application specifically to deeper layers, slow oscillation activity was attenuated with a significant reduction in UP state frequency. The cortical response to thalamic stimulation exhibited enhanced temporal precision in the presence of NT, consistent with the transition in vivo from sleep to wakefulness. These changes were associated with a relative shift toward inhibition in the excitation/inhibition balance. Whole-cell recordings from layer 6 revealed presynaptically driven NT-induced inhibition of pyramidal neurons and excitation of fast-spiking interneurons. Deeper in the cortex, neurons within the white matter (WM) were strongly depolarized by NT application. The colocalization of NT and tyrosine hydroxylase immunoreactivities in deep layer fibers throughout the cortical mantle indicates mediation via dopaminergic systems. These data suggest a cortical mechanism for NT-induced wakefulness and support a role for WM neurons in state control., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Human brain imaging revealed that the brain can undergo structural plasticity following new learning experiences. Most magnetic resonance imaging (MRI) uncovered morphometric alternation in cortical density after the long-term training of weeks to months. A recent diffusion tensor imaging (DTI) study has found changes in diffusion indices after 2 h of training, primarily in the hippocampus. However, whether a short learning experience can induce microstructural changes in the neocortex is still unclear. Here, we used diffusion MRI, a method sensitive to tissue microstructure, to study cortical plasticity. To attain cortical involvement, we used a short language task (under 1 h) of introducing new lexical items (flower names) to the lexicon. We have found significant changes in diffusivity in cortical regions involved in language and reading (inferior frontal gyrus, middle temporal gyrus, and inferior parietal lobule). In addition, the difference in the values of diffusivity correlated with the lexical learning rate in the task. Moreover, significant changes were found in white matter tracts near the cortex, and the extent of change correlated with behavioral measures of lexical learning rate. These findings provide first evidence of short-term cortical plasticity in the human brain after a short language learning task. It seems that short training of less than an hour of high cognitive demand can induce microstructural changes in the cortex, suggesting a rapid time scale of neuroplasticity and providing additional evidence of the power of MRI to investigate the temporal and spatial progressions of this process.

High education, as a proxy of cognitive reserve (CR), has been associated with cognitive advantage amongst old adults and may operate through neuroprotective and/or compensation mechanisms. In neuromaging studies, indirect evidences of neuroprotection can be inferred from positive relationships between CR and brain integrity measures. In contrast, compensation allows high CR elders to sustain greater brain damage. We included 100 cognitively normal old-adults and investigated the associations and interactions between education, speed of processing (SP), memory and two brain integrity measures: cortical thickness (CTh) of gray matter (GM) and fractional anisotropy (FA) in the white matter (WM). High education was associated with better cognitive performance, enlarged CTh in frontal lobe areas and reduced measures of FA in several areas. Better SP performance in higher educated subjects was related to more preserved GM and WM, while memory status amongst high educated elders was better explained by a putative compensatory mechanism and independently from cerebrovascular risk indicators. Moreover, we analyzed the direct effect of age on measures of brain integrity and found a stronger negative effect on WM than in CTh, which was accentuated amongst the high CR sample. Our study suggests that the cognitive advantage associated to high education among healthy aging is related to the coexistence of both neuroprotective and compensatory mechanisms. In particular, high educated elders seem to have greater capacity to counteract a more abrupt age impact on WM integrity.

Early fMRI studies suggested that brain areas processing self-related and other-related information were highly overlapping. Hypothesising functional localisation of the cortex, researchers have tried to locate "self-specific" and "other-specific" regions within these overlapping areas by subtracting suspected confounding signals in task-based fMRI experiments. Inspired by recent advances in whole-brain dynamic modelling, we instead explored an alternative hypothesis that similar spatial activation patterns could be associated with different processing modes in the form of different synchronisation patterns. Combining an automated synthesis of fMRI data with a presumption-free diffusion spectrum image (DSI) fibre-tracking algorithm, we isolated a network putatively composed of brain areas and white matter tracts involved in self-other processing. We sampled synchronisation patterns from the dynamical systems of this network using various combinations of physiological parameters. Our results showed that the self-other processing network, with simulated gamma-band activity, tended to stabilise at a number of distinct synchronisation patterns. This phenomenon, termed "multistability," could serve as an alternative model in theorising the mechanism of processing self-other information.

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.)

Objective: Although aging is associated with alterations of both activity/rest cycle and brain structure, few studies have evaluated associations between these processes. The aim of this study was to examine relationship between activity/rest cycle quality and brain structural integrity in aging subjects by exploring both grey and white matter compartments., Material and Methods: Fifty-eight elderly subjects (76±0.5 years; 41% female) without dementia, sleep disorders and medications were included in the analysis. Actigraphy was used to measure parameters of activity/rest cycle (24-h amplitude, 24-h fragmentation and 24-h stability) and sleep (total sleep time and sleep fragmentation) over a minimal period of 5 days. Whole brain linear regression analyses were performed on grey matter volumes maps using voxel based morphometry and on white matter integrity using tract based statistics analyses., Results: A lower 24-h amplitude and a higher sleep fragmentation were independently associated with a reduction of white matter integrity in models including age and gender as covariates. The association between 24-h amplitude and white matter integrity decreased but remained significant in a model accounted for sleep fragmentation, indicating a specific effect of 24-h cycle disturbances. No association with grey matter volumes was observed., Conclusion: In elderly, not only sleep but also 24-h cycle disturbances were associated with altered structural connectivity. This alteration of structural backbone networks related to activity/rest cycle disturbances in aging might constitute a cerebral frailty factor for the development of cognitive impairment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Research in the macaque monkey suggests that cortical areas with similar microstructure are more likely to be connected. Here, we examine this link in the human cerebral cortex using 2 magnetic resonance imaging (MRI) measures: quantitative  T1 maps, which are sensitive to intracortical myelin content and provide an in vivo proxy for cortical microstructure, and resting-state functional connectivity. Using ultrahigh-resolution MRI at 7 T and dedicated image processing tools, we demonstrate a systematic relationship between T1-based intracortical myelin content and functional connectivity. This effect is independent of the proximity of areas. We employ nonlinear dimensionality reduction to characterize connectivity components and identify specific aspects of functional connectivity that are linked to myelin content. Our results reveal a consistent spatial pattern throughout different analytic approaches. While functional connectivity and myelin content are closely linked in unimodal areas, the correspondence is lower in transmodal areas, especially in posteromedial cortex and the angular gyrus. Our findings are in agreement with comprehensive reports linking histologically assessed microstructure and connectivity in different mammalian species and extend them to the human cerebral cortex in vivo., (© The Author 2017. Published by Oxford University Press.)

Diffusion tensor imaging (DTI) tractography and functional magnetic resonance imaging (fMRI) are powerful techniques to elucidate the anatomical and functional aspects of brain connectivity. However, integrating these approaches to describe the precise link between structure and function within specific brain circuits remains challenging. In this study, a novel DTI-fMRI integration method is proposed, to provide the topographical characterization and the volumetric assessment of the functional and anatomical connections within the language circuit. In a group of 21 healthy elderly subjects (mean age 68.5 ± 5.8 years), the volume of connection between the cortical activity elicited by a verbal fluency task and the cortico-cortical fiber tracts associated with this function are mapped and quantified. An application of the method to a case study in neuro-rehabilitation context is also presented. Integrating structural and functional data within the same framework, this approach provides an overall view of white and gray matter when studying specific brain circuits.

Little is known about the white matter integrity of cerebellar-cortical pathways in individuals with dyslexia. Building on previous findings of decreased volume in the anterior lobe of the cerebellum, we utilized novel cerebellar segmentation procedures and probabilistic tractography to examine tracts that connect the anterior lobe of the cerebellum and cortical regions typically associated with reading: the temporoparietal (TP), occipitotemporal (OT), and inferior frontal (IF) regions. The sample included 29 reading impaired children and 27 typical readers. We found greater fractional anisotropy (FA) for the poor readers in tracts connecting the cerebellum with TP and IF regions relative to typical readers. In the OT region, FA was greater for the older poor readers, but smaller for the younger ones. This study provides evidence for discrete, regionally-bound functions of the cerebellum and suggests that projections from the anterior cerebellum appear to have a regulatory effect on cortical pathways important for reading., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Fast cancellation or switching of action plans is a critical cognitive function. Rapid signal transmission is key for quickly executing and inhibiting responses, and the structural integrity of connections between brain regions plays a crucial role in signal transmission speed. In this study, we used the search-step task, which has been used in nonhuman primates to measure dynamic alteration of saccade plans, in combination with functional and diffusion-weighted MRI. Functional MRI results were used to identify brain regions involved in the reactive control of gaze. Probabilistic tractography was used to identify white matter pathways connecting these structures, and the integrity of these connections, as indicated by fractional anisotropy (FA), was correlated with search-step task performance. Average FA from tracts between the right frontal eye field (FEF) and both right supplementary eye field (SEF) and the dorsal striatum were associated with faster saccade execution. Average FA of connections between the dorsal striatum and both right SEF and right inferior frontal cortex (IFC) as well as between SEF and IFC predicted the speed of inhibition. These relationships were largely behaviorally specific, despite the correlation between saccade execution and inhibition. Average FA of connections between the IFC and both SEF and the dorsal striatum specifically predicted the speed of inhibition, and connections between the FEF and SEF specifically predicted the speed of execution. In addition, these relationships were anatomically specific; correlations were observed after controlling for global FA. These data suggest that networks supporting saccade initiation and inhibition are at least partly dissociable. Hum Brain Mapp 37:2811-2822, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Psychological studies showed the quantity of reading habit affects the development of their reading skills, various language skills, and knowledge. However, despite a vast amount of literature, the effects of reading habit on the development of white matter (WM) structures critical to language and reading processes have never been investigated. In this study, we used the fractional anisotropy (FA) measure of diffusion tensor imaging to measure WM microstructural properties and examined cross-sectional and longitudinal correlations between reading habit and FA of the WM bundles in a large sample of normal children. In both cross-sectional and longitudinal analyses, we found that greater strength of reading habit positively affected FA in the left arcuate fasciculus (AF), in the left inferior fronto-occipital fasciculus (IFOF), and in the left posterior corona radiata (PCR). Consistent with previous studies, we also confirmed the significance or a tendency for positive correlation between the strength of reading habit and the Verbal Comprehension score in cross-sectional and longitudinal analyses. These cross-sectional and longitudinal findings indicate that a healthy reading habit may be directly or indirectly associated with the advanced development of WM critical to reading and language processes. Future intervention studies are needed to determine the causal effects of reading habits on WM in normal children., (Copyright © 2016 Elsevier Inc. All rights reserved.)