Cortical mapping of callosal connections in healthy young adults.

The corpus callosum (CC) is the principal white matter bundle supporting communication between the two brain hemispheres. Despite its importance, a comprehensive mapping of callosal connections is still lacking. Here, we constructed the first bidirectional population-based callosal connectional atlas between the midsagittal section of the CC and the cerebral cortex of the human brain by means of diffusion-weighted imaging tractography. The estimated connectional topographic maps within this atlas have the most fine-grained spatial resolution, demonstrate histological validity, and were reproducible in two independent samples. This new resource, a complete and comprehensive atlas, will facilitate the investigation of interhemispheric communication and come with a user-friendly companion online tool (CCmapping) for easy access and visualization of the atlas.

Latent disconnectome prediction of long-term cognitive-behavioural symptoms in stroke.

Stroke significantly impacts the quality of life. However, the long-term cognitive evolution in stroke is poorly predictable at the individual level. There is an urgent need to better predict long-term symptoms based on acute clinical neuroimaging data. Previous works have demonstrated a strong relationship between the location of white matter disconnections and clinical symptoms. However, rendering the entire space of possible disconnection-deficit associations optimally surveyable will allow for a systematic association between brain disconnections and cognitive-behavioural measures at the individual level. Here we present the most comprehensive framework, a composite morphospace of white matter disconnections (disconnectome) to predict neuropsychological scores 1 year after stroke. Linking the latent disconnectome morphospace to neuropsychological outcomes yields biological insights that are available as the first comprehensive atlas of disconnectome-deficit relations across 86 scores-a Neuropsychological White Matter Atlas. Our novel predictive framework, the Disconnectome Symptoms Discoverer, achieved better predictivity performances than six other models, including functional disconnection, lesion topology and volume modelling. Out-of-sample prediction derived from this atlas presented a mean absolute error below 20% and allowed personalize neuropsychological predictions. Prediction on an external cohort achieved an R2 = 0.201 for semantic fluency. In addition, training and testing were replicated on two external cohorts achieving an R2 = 0.18 for visuospatial performance. This framework is available as an interactive web application (http://disconnectomestudio.bcblab.com) to provide the foundations for a new and practical approach to modelling cognition in stroke. We hope our atlas and web application will help to reduce the burden of cognitive deficits on patients, their families and wider society while also helping to tailor future personalized treatment programmes and discover new targets for treatments. We expect our framework's range of assessments and predictive power to increase even further through future crowdsourcing.

Callosal Fiber Length Scales with Brain Size According to Functional Lateralization, Evolution, and Development.

Brain size significantly impacts the organization of white matter fibers. Fiber length scaling, the degree to which fiber length varies according to brain size, was overlooked. We investigated how fiber lengths within the corpus callosum, the most prominent white matter tract, vary according to brain size. The results showed substantial variation in length scaling among callosal fibers, replicated in two large healthy cohorts (∼2000 human subjects, including both sexes). The underscaled callosal fibers mainly connected the precentral gyrus and parietal cortices, whereas the overscaled callosal fibers mainly connected the prefrontal cortices. The variation in such length scaling was biologically meaningful: larger scaling corresponded to larger neurite density index but smaller fractional anisotropy values; cortical regions connected by the callosal fibers with larger scaling were more lateralized functionally as well as phylogenetically and ontogenetically more recent than their counterparts. These findings highlight an interaction between interhemispheric communication and organizational and adaptive principles underlying brain development and evolution.SIGNIFICANCE STATEMENT Brain size varies across evolution, development, and individuals. Relative to small brains, the neural fiber length in large brains is inevitably increased, but the degree of such increase may differ between fiber tracts. Such a difference, if it exists, is valuable for understanding adaptive neural principles in large versus small brains during evolution and development. The present study showed a substantial difference in the length increase between the callosal fibers that connect the two hemispheres, replicated in two large healthy cohorts. Together, our study demonstrates that reorganization of interhemispheric fibers length according to brain size is intrinsically related to fiber composition, functional lateralization, cortical myelin content, and evolutionary and developmental expansion.

Neural dissociation of visual attention span and phonological deficits in developmental dyslexia: A hub-based white matter network analysis.

It has been suggested that developmental dyslexia may have two dissociable causes-a phonological deficit and a visual attention span (VAS) deficit. Yet, neural evidence for such a dissociation is still lacking. This study adopted a data-driven approach to white matter network analysis to explore hubs and hub-related networks corresponding to VAS and phonological accuracy in a group of French dyslexic children aged from 9 to 14 years. A double dissociation in brain-behavior relations was observed. Structural connectivity of the occipital-parietal network surrounding the left superior occipital gyrus hub accounted for individual differences in dyslexic children's VAS, but not in phonological processing accuracy. In contrast, structural connectivity of two networks: the temporal-parietal-occipital network surrounding the left middle temporal gyrus hub and the frontal network surrounding the left medial orbital superior frontal gyrus hub, accounted for individual differences in dyslexic children's phonological processing accuracy, but not in VAS. Our findings provide evidence in favor of distinct neural circuits corresponding to VAS and phonological deficits in developmental dyslexia. The study points to connectivity-constrained white matter subnetwork dysfunction as a key principle for understanding individual differences of cognitive deficits in developmental dyslexia.

Unravelling the Neural Basis of Spatial Delusions After Stroke.

OBJECTIVE: Knowing explicitly where we are is an interpretation of our spatial representations. Reduplicative paramnesia is a disrupting syndrome in which patients present a firm belief of spatial mislocation. Here, we studied the largest sample of patients with delusional misidentifications of space (ie, reduplicative paramnesia) after stroke to shed light on their neurobiology. METHODS: In a prospective, cumulative, case-control study, we screened 400 patients with acute right-hemispheric stroke. We included 64 cases and 233 controls. First, lesions were delimited and normalized. Then, we computed structural and functional disconnection maps using methods of lesion-track and network-mapping. The maps were compared, controlling for confounders. Second, we built a multivariate logistic model, including clinical, behavioral, and neuroimaging data. Finally, we performed a nested cross-validation of the model with a support-vector machine analysis. RESULTS: The most frequent misidentification subtype was confabulatory mislocation (56%), followed by place reduplication (19%), and chimeric assimilation (13%). Our results indicate that structural disconnection is the strongest predictor of the syndrome and included 2 distinct streams, connecting right fronto-thalamic and right occipitotemporal structures. In the multivariate model, the independent predictors of reduplicative paramnesia were the structural disconnection map, lesion sparing of right dorsal fronto-parietal regions, age, and anosognosia. Good discrimination accuracy was demonstrated (area under the curve = 0.80 [0.75-0.85]). INTERPRETATION: Our results localize the anatomic circuits that may have a role in the abnormal spatial-emotional binding and in the defective updating of spatial representations underlying reduplicative paramnesia. This novel data may contribute to better understand the pathophysiology of delusional syndromes after stroke. ANN NEUROL 2021;89:1181-1194.

Imaging evolution of the primate brain: the next frontier?

Evolution, as we currently understand it, strikes a delicate balance between animals' ancestral history and adaptations to their current niche. Similarities between species are generally considered inherited from a common ancestor whereas observed differences are considered as more recent evolution. Hence comparing species can provide insights into the evolutionary history. Comparative neuroimaging has recently emerged as a novel subdiscipline, which uses magnetic resonance imaging (MRI) to identify similarities and differences in brain structure and function across species. Whereas invasive histological and molecular techniques are superior in spatial resolution, they are laborious, post-mortem, and oftentimes limited to specific species. Neuroimaging, by comparison, has the advantages of being applicable across species and allows for fast, whole-brain, repeatable, and multi-modal measurements of the structure and function in living brains and post-mortem tissue. In this review, we summarise the current state of the art in comparative anatomy and function of the brain and gather together the main scientific questions to be explored in the future of the fascinating new field of brain evolution derived from comparative neuroimaging.

Post-stroke deficit prediction from lesion and indirect structural and functional disconnection.

Behavioural deficits in stroke reflect both structural damage at the site of injury, and widespread network dysfunction caused by structural, functional, and metabolic disconnection. Two recent methods allow for the estimation of structural and functional disconnection from clinical structural imaging. This is achieved by embedding a patient's lesion into an atlas of functional and structural connections in healthy subjects, and deriving the ensemble of structural and functional connections that pass through the lesion, thus indirectly estimating its impact on the whole brain connectome. This indirect assessment of network dysfunction is more readily available than direct measures of functional and structural connectivity obtained with functional and diffusion MRI, respectively, and it is in theory applicable to a wide variety of disorders. To validate the clinical relevance of these methods, we quantified the prediction of behavioural deficits in a prospective cohort of 132 first-time stroke patients studied at 2 weeks post-injury (mean age 52.8 years, range 22-77; 63 females; 64 right hemispheres). Specifically, we used multivariate ridge regression to relate deficits in multiple functional domains (left and right visual, left and right motor, language, spatial attention, spatial and verbal memory) with the pattern of lesion and indirect structural or functional disconnection. In a subgroup of patients, we also measured direct alterations of functional connectivity with resting-state functional MRI. Both lesion and indirect structural disconnection maps were predictive of behavioural impairment in all domains (0.16 < R2 < 0.58) except for verbal memory (0.05 < R2 < 0.06). Prediction from indirect functional disconnection was scarce or negligible (0.01 < R2 < 0.18) except for the right visual field deficits (R2 = 0.38), even though multivariate maps were anatomically plausible in all domains. Prediction from direct measures of functional MRI functional connectivity in a subset of patients was clearly superior to indirect functional disconnection. In conclusion, the indirect estimation of structural connectivity damage successfully predicted behavioural deficits post-stroke to a level comparable to lesion information. However, indirect estimation of functional disconnection did not predict behavioural deficits, nor was a substitute for direct functional connectivity measurements, especially for cognitive disorders.

Subspecialization within default mode nodes characterized in 10,000 UK Biobank participants.

The human default mode network (DMN) is implicated in several unique mental capacities. In this study, we tested whether brain-wide interregional communication in the DMN can be derived from population variability in intrinsic activity fluctuations, gray-matter morphology, and fiber tract anatomy. In a sample of 10,000 UK Biobank participants, pattern-learning algorithms revealed functional coupling states in the DMN that are linked to connectivity profiles between other macroscopical brain networks. In addition, DMN gray matter volume was covaried with white matter microstructure of the fornix. Collectively, functional and structural patterns unmasked a possible division of labor within major DMN nodes: Subregions most critical for cortical network interplay were adjacent to subregions most predictive of fornix fibers from the hippocampus that processes memories and places.

Mapping the principal gradient onto the corpus callosum.

Gradients capture some of the variance of the resting-state functional magnetic resonance imaging (rsfMRI) signal. Amongst these, the principal gradient depicts a functional processing hierarchy that spans from sensory-motor cortices to regions of the default-mode network. While the cortex has been well characterised in terms of gradients little is known about its underlying white matter. For instance, comprehensive mapping of the principal gradient on the largest white matter tract, the corpus callosum, is still missing. Here, we mapped the principal gradient onto the midsection of the corpus callosum using the 7T human connectome project dataset. We further explored how quantitative measures and variability in callosal midsection connectivity relate to the principal gradient values. In so doing, we demonstrated that the extreme values of the principal gradient are located within the callosal genu and the posterior body, have lower connectivity variability but a larger spatial extent along the midsection of the corpus callosum than mid-range values. Our results shed light on the relationship between the brain's functional hierarchy and the corpus callosum. We further speculate about how these results may bridge the gap between functional hierarchy, brain asymmetries, and evolution.

Reading music and words: The anatomical connectivity of musicians' visual cortex.

Musical score reading and word reading have much in common, from their historical origins to their cognitive foundations and neural correlates. In the ventral occipitotemporal cortex (VOT), the specialization of the so-called Visual Word Form Area for word reading has been linked to its privileged structural connectivity to distant language regions. Here we investigated how anatomical connectivity relates to the segregation of regions specialized for musical notation or words in the VOT. In a cohort of professional musicians and non-musicians, we used probabilistic tractography combined with task-related functional MRI to identify the connections of individually defined word- and music-selective left VOT regions. Despite their close proximity, these regions differed significantly in their structural connectivity, irrespective of musical expertise. The music-selective region was significantly more connected to posterior lateral temporal regions than the word-selective region, which, conversely, was significantly more connected to anterior ventral temporal cortex. Furthermore, musical expertise had a double impact on the connectivity of the music region. First, music tracts were significantly larger in musicians than in non-musicians, associated with marginally higher connectivity to perisylvian music-related areas. Second, the spatial similarity between music and word tracts was significantly increased in musicians, consistently with the increased overlap of language and music functional activations in musicians, as compared to non-musicians. These results support the view that, for music as for words, very specific anatomical connections influence the specialization of distinct VOT areas, and that reciprocally those connections are selectively enhanced by the expertise for word or music reading.

Anchoring the human olfactory system within a functional gradient.

Margulies et al. (2016) demonstrated the existence of at least five independent functional connectivity gradients in the human brain. However, it is unclear how these functional gradients might link to anatomy. The dual origin theory proposes that differences in cortical cytoarchitecture originate from two trends of progressive differentiation between the different layers of the cortex, referred to as the hippocampocentric and olfactocentric systems. When conceptualising the functional connectivity gradients within the evolutionary framework of the Dual Origin theory, the first gradient likely represents the hippocampocentric system anatomically. Here we expand on this concept and demonstrate that the fifth gradient likely links to the olfactocentric system. We describe the anatomy of the latter as well as the evidence to support this hypothesis. Together, the first and fifth gradients might help to model the Dual Origin theory of the human brain and inform brain models and pathologies.

Impact of literacy on the functional connectivity of vision and language related networks.

Learning to read leads to functional and structural changes in cortical brain areas related to vision and language. Previous evidence suggests that the Visual Word Form Area (VWFA), a region devoted to the recognition of letter strings in literate persons, acts as an interface between both systems. While different studies have performed univariate analyses to study the effects of literacy on brain function, little is known about its impact on whole functional networks, especially when literacy is acquired during adulthood. We investigated functional connectivity in three groups of adults with different literacy status: illiterates, ex-illiterates (i.e., who learned to read during adulthood), and literates (i.e., who learned to read in childhood). We used a data-driven, multivariate whole brain approach (Independent Component Analysis [ICA]) combined with a region of interest (ROI) analysis in order to explore the functional connectivity of the VWFA with four ICA networks related to vision and language functions. ICA allowed for the identification of four networks of interest: left fronto-parietal, auditory, medial visual and lateral visual functional networks, plus a control right fronto-parietal network. We explored the effects literacy on the connectivity between the VWFA and these networks, trying furthermore to disentangle the roles of reading proficiency and age of acquisition (i.e., literacy status) in these changes. Results showed that functional connectivity between the VWFA and the left fronto-parietal and lateral visual networks increased and decreased, respectively, with literacy. Moreover, the functional coupling of the VWFA and the auditory network decreased with literacy. This study provides novel insights in the mechanisms of reading acquisition and brain plasticity, putting to light the emergence of the VWFA as a bridge between language and vision. Further studies are required to characterize the interplay of proficiency and age of reading acquisition, and its relevance to models of brain plasticity across lifespan.

The role of diffusion MRI in neuroscience.

Diffusion-weighted imaging has pushed the boundaries of neuroscience by allowing us to examine the white matter microstructure of the living human brain. By doing so, it has provided answers to fundamental neuroscientific questions, launching a new field of research that had been largely inaccessible. We briefly summarize key questions that have historically been raised in neuroscience concerning the brain's white matter. We then expand on the benefits of diffusion-weighted imaging and its contribution to the fields of brain anatomy, functional models and plasticity. In doing so, this review highlights the invaluable contribution of diffusion-weighted imaging in neuroscience, presents its limitations and proposes new challenges for future generations who may wish to exploit this powerful technology to gain novel insights.

Two critical brain networks for generation and combination of remote associations.

Recent functional imaging findings in humans indicate that creativity relies on spontaneous and controlled processes, possibly supported by the default mode and the fronto-parietal control networks, respectively. Here, we examined the ability to generate and combine remote semantic associations, in relation to creative abilities, in patients with focal frontal lesions. Voxel-based lesion-deficit mapping, disconnection-deficit mapping and network-based lesion-deficit approaches revealed critical prefrontal nodes and connections for distinct mechanisms related to creative cognition. Damage to the right medial prefrontal region, or its potential disrupting effect on the default mode network, affected the ability to generate remote ideas, likely by altering the organization of semantic associations. Damage to the left rostrolateral prefrontal region and its connections, or its potential disrupting effect on the left fronto-parietal control network, spared the ability to generate remote ideas but impaired the ability to appropriately combine remote ideas. Hence, the current findings suggest that damage to specific nodes within the default mode and fronto-parietal control networks led to a critical loss of verbal creative abilities by altering distinct cognitive mechanisms.

Structural Variability Across the Primate Brain: A Cross-Species Comparison.

A large amount of variability exists across human brains; revealed initially on a small scale by postmortem studies and, more recently, on a larger scale with the advent of neuroimaging. Here we compared structural variability between human and macaque monkey brains using grey and white matter magnetic resonance imaging measures. The monkey brain was overall structurally as variable as the human brain, but variability had a distinct distribution pattern, with some key areas showing high variability. We also report the first evidence of a relationship between anatomical variability and evolutionary expansion in the primate brain. This suggests a relationship between variability and stability, where areas of low variability may have evolved less recently and have more stability, while areas of high variability may have evolved more recently and be less similar across individuals. We showed specific differences between the species in key areas, including the amount of hemispheric asymmetry in variability, which was left-lateralized in the human brain across several phylogenetically recent regions. This suggests that cerebral variability may be another useful measure for comparison between species and may add another dimension to our understanding of evolutionary mechanisms.

Frontoparietal Tracts Linked to Lateralized Hand Preference and Manual Specialization.

Humans show a preference for using the right hand over the left for tasks and activities of everyday life. While experimental work in non-human primates has identified the neural systems responsible for reaching and grasping, the neural basis of lateralized motor behavior in humans remains elusive. The advent of diffusion imaging tractography for studying connectional anatomy in the living human brain provides the possibility of understanding the relationship between hemispheric asymmetry, hand preference, and manual specialization. In this study, diffusion tractography was used to demonstrate an interaction between hand preference and the asymmetry of frontoparietal tracts, specifically the dorsal branch of the superior longitudinal fasciculus, responsible for visuospatial integration and motor planning. This is in contrast to the corticospinal tract and the superior cerebellar peduncle, for which asymmetry was not related to hand preference. Asymmetry of the dorsal frontoparietal tract was also highly correlated with the degree of lateralization in tasks requiring visuospatial integration and fine motor control. These results suggest a common anatomical substrate for hand preference and lateralized manual specialization in frontoparietal tracts important for visuomotor processing.

Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer's disease.

INTRODUCTION: The longitudinal trajectories of functional brain dynamics and the impact of genetic risk factors in individuals at risk for Alzheimer's disease are poorly understood. METHODS: In a large-scale monocentric cohort of 224 amyloid stratified individuals at risk for Alzheimer's disease, default mode network (DMN) resting state functional connectivity (FC) was investigated between two serial time points across 2 years. RESULTS: Widespread DMN FC changes were shown in frontal and posterior areas, as well as in the right hippocampus. There were no cross-sectional differences, however, apolipoprotein E ε4 (APOE Îµ4) carriers demonstrated slower increase in FC in frontal lobes. There was no impact of individual brain amyloid load status. DISCUSSION: For the first time, we demonstrated that the pleiotropic biological effect of the APOE ε4 allele impacts the dynamic trajectory of the DMN during aging. Dynamic functional biomarkers may become useful surrogate outcomes for the development of preclinical targeted therapeutic interventions.

Different patterns of confabulation in left visuo-spatial neglect.

Confabulating patients produce statements and actions that are unintentionally incongruous to their history, background, present and future situation. Here we present the very unusual case of a patient with right hemisphere damage and signs of left visual neglect, who, when presented with visual stimuli, confabulated both for consciously undetected and for consciously detected left-sided details. Advanced anatomical investigation suggested a disconnection between the parietal and the temporal lobes in the right hemisphere. A disconnection between the ventral cortical visual stream and the dorsal fronto-parietal networks in the right hemisphere may contribute to confabulatory behaviour by restricting processing of left-sided stimuli to pre-conscious stages in the ventral visual stream.

Vocabulary growth rate from preschool to school-age years is reflected in the connectivity of the arcuate fasciculus in 14-year-old children.

The acquisition of language involves the functional specialization of several cortical regions. Connectivity between these brain regions may also change with the development of language. Various studies have demonstrated that the arcuate fasciculus was essential for language function. Vocabulary learning is one of the most important skills in language acquisition. In the present longitudinal study, we explored the influence of vocabulary development on the anatomical properties of the arcuate fasciculus. Seventy-nine Chinese children participated in this study. Between age 4 and age 10, they were administered the same vocabulary task repeatedly. Following a previous study, children's vocabulary developmental trajectories were clustered into three subgroups (consistently good, catch-up, consistently poor). At age 14, diffusion tensor imaging data were collected. Using ROI-based tractography, the anterior, posterior and direct segments of the bilateral arcuate fasciculus were delineated in each child's native space. Group comparisons showed a significantly reduced fractional anisotropy in the left arcuate fasciculus of children in the consistently poor group, in particular in the posterior and direct segments of the arcuate fasciculus. No group differences were observed in the right hemisphere, nor in the left anterior segment. Further regression analyses showed that the rate of vocabulary development, rather than the initial vocabulary size, was a specific predictor of the left arcuate fasciculus connectivity.

Rostro-caudal Architecture of the Frontal Lobes in Humans.

The nature of the inputs and outputs of a brain region defines its functional specialization. The frontal portion of the brain is essential for goal-directed behaviors, however, the biological basis for its functional organization is unknown. Here, exploring structural connectomic properties, we delineated 12 frontal areas, defined by the pattern of their white matter connections. This result was highly reproducible across neuroimaging centers, acquisition parameters, and participants. These areas corresponded to regions functionally engaged in specific tasks, organized along a rostro-caudal axis from the most complex high-order association areas to the simplest idiotopic areas. The rostro-caudal axis along which the 12 regions were organized also reflected a gradient of cortical thickness, myelination, and cell body density. Importantly, across the identified regions, this gradient of microstructural features was strongly associated with the varying degree of information processing complexity. These new anatomical signatures shed light onto the structural organization of the frontal lobes and could help strengthen the prediction or diagnosis of neurodevelopmental and neurodegenerative disorders.