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Contains fulltext : 281742.pdf (Publisher’s version ) (Open Access) Cognitive functional neuroimaging has been around for over 30 years and has shed light on the brain areas relevant for reading. However, new methodological developments enable mapping the interaction between functional imaging and the underlying white matter networks. In this study, we used such a novel method, called the disconnectome, to decode the reading circuitry in the brain. We used the resulting disconnection patterns to predict a typical lesion that would lead to reading deficits after brain damage. Our results suggest that white matter connections critical for reading include fronto-parietal U-shaped fibres and the vertical occipital fasciculus (VOF). The lesion most predictive of a reading deficit would impinge on the left temporal, occipital, and inferior parietal gyri. This novel framework can systematically be applied to bridge the gap between the neuropathology of language and cognitive neuroscience. 12 p.

Contains fulltext : 292574.pdf (Publisher’s version ) (Open Access) 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. 16 p.

Item does not contain fulltext There is more to brain connections than the mere transfer of signals between brain regions. Behavior and cognition emerge through cortical area interaction. This requires integration between local and distant areas orchestrated by densely connected networks. Brain connections determine the brain’s functional organization. The imaging of connections in the living brain has provided an opportunity to identify the driving factors behind the neurobiology of cognition. Connectivity differences between species and among humans have furthered the understanding of brain evolution and of diverging cognitive profiles. Brain pathologies amplify this variability through disconnections and, consequently, the disintegration of cognitive functions. The prediction of long-term symptoms is now preferentially based on brain disconnections. This paradigm shift will reshape our brain maps and challenge current brain models. 6 p.

Thirty years of functional neuroimaging have been accumulating a wealth of evidence of the intricate relationship between structure and function. However, potential overlap, independence, granularity of and gaps between functions remain poorly understood at the global level. In this study, we extracted the latent structure of the current brain-cognition knowledge and revealed its organisational structure. This knowledge has been derived from the most comprehensive meta-analytic fMRI database (Neurosynth) that was used to compute a two-dimensional embedding space – the brain-cognition space – capturing the relationship between brain functions as we know it. The structure of the space allowed us to test the degree of logic in the relationship between functions statistically – a rationality index – and to predict the activation pattern of new and still undetermined functions. The organisation and predictive framework defined by the brain-cognition space will foster the investigation of novel functions and guide the exploration of the fabric of human cognition.

Over the past two decades, the study of resting-state functional magnetic resonance imaging (fMRI) has revealed the existence of multiple brain areas displaying synchronous functional blood oxygen level-dependent signals (BOLD) - resting-state networks (RSNs). The variation in functional connectivity between the different areas of a resting-state network or between multiple networks, have been extensively studied and linked to cognitive states and pathologies. However, the white matter connections supporting each network remain only partially described. In this work, we developed a data-driven method to systematically map the white and grey matter contributing to resting-state networks. Using the Human Connectome Project, we generated an atlas of 30 resting-state networks, each with two maps: white matter and grey matter. By integrating structural and functional neuroimaging data, this method builds an atlas that unlocks the joint anatomical exploration of white and grey matter to resting-state networks. The method also allows highlighting the overlap between networks, which revealed that most (89%) of the brain's white matter is shared amongst multiple networks, with 16% shared by at least 7 resting-state networks. These overlaps, especially the existence of regions shared by numerous networks, suggest that white matter lesions in these areas might strongly impact the correlations and the communication within resting-state networks. We provide an open-source software to explore the joint contribution of white and grey matter to RSNs and facilitate the study of the impact of white matter damage on RSNs.Competing Interest StatementThe authors have declared no competing interest.

Strong right-hand preference on the population level is a uniquely human feature, although its neural basis is still not clearly defined. Recent behavioural and neuroimaging literature suggests that hand preference may be related to the orchestrated function and size of fronto-parietal white matter tracts bilaterally. Lesions to these tracts induced during tumour resection may provide an opportunity to test this hypothesis. In the present study, a cohort of seventeen neurosurgical patients with left hemisphere brain tumours were recruited to investigate whether resection of certain white matter tracts affects the choice of hand selected for the execution of a goal-directed task (assembly of jigsaw puzzles). Patients performed the puzzles, but also tests for basic motor ability, selective attention and visuo-constructional ability, preoperatively and one month after surgery. An atlas-based disconnectome analysis was conducted to evaluate whether resection of tracts was significantly associated with changes in hand selection. Diffusion tractography was also used to dissect fronto-parietal tracts (the superior longitudinal fasciculus) and the corticospinal tract. Results showed a shift in hand selection despite the absence of any motor or cognitive deficits, which was significantly associated with frontal and parietal resections rather than other lobes. In particular, the shift in hand selection was significantly associated with the resection of dorsal rather than ventral fronto-parietal white matter connections. Dorsal white matter pathways contribute bilaterally to control of goal-directed hand movements. We show that unilateral lesions, that may unbalance the cooperation of the two hemispheres, can alter the choice of hand selected to accomplish movements.

Item does not contain fulltext Understanding human white matter development is vital to characterize typical brain organization and developmental neurocognitive disorders. In this issue of Neuron, Nazeri and colleagues identify different parts of white matter in the neonatal brain and show their maturational trajectories in line with microstructural feature development. 4 p.

Item does not contain fulltext In 2016, the University of Bordeaux ran a competition within the local neuroscience community to find a name for its new neuroscience building. The name of Paul Broca, who was born nearby in 1824, was chosen in honour of his origins and his contributions to neuroscience. Recently, however, a debate has been ignited about the appropriateness of this choice, given Broca's endorsement of physiological anthropology. At a time when academic institutions worldwide are revising their curricula to better reflect the contributions of previously overlooked groups, how should we respond when the views of the 'founding fathers' of neurology clash with those of society today? 'Here are eight instances in which the lesion was in the posterior third of the third frontal convolution. This number seems to me to be sufficient to give strong presumptions. And the most remarkable thing is that in all the patients the lesion was on the left side. I do not dare draw conclusions from this'. (Broca, 1863) Paul Broca was initially hesitant in 1863, but 2 years later, he was confident that 'nous parlons avec l’hémisphère gauche' (we speak with the left hemisphere) and narrowed it down to the troisième circonvolution frontale (today known as the inferior frontal gyrus). This work revolutionized neuroscience in the 1860s and led not only to Broca's name becoming an eponym for this brain area, but also laid the foundations for new theories (e.g. localizationism, cerebral dominance and asymmetry), methods (lesion-symptom mapping), and disciplines (neurobiology of language, aphasiology). 4 p.

Contains fulltext : 284388.pdf (Publisher’s version ) (Open Access) Motricity is the most commonly affected ability after a stroke. While many clinical studies attempt to predict motor symptoms at different chronic time points after a stroke, longitudinal acute-to-chronic studies remain scarce. Taking advantage of recent advances in mapping brain disconnections, we predict motor outcomes in 62 patients assessed longitudinally two weeks, three months, and one year after their stroke. Results indicate that brain disconnection patterns accurately predict motor impairments. However, disconnection patterns leading to impairment differ between the three-time points and between left and right motor impairments. These results were cross-validated using resampling techniques. In sum, we demonstrated that while some neuroplasticity mechanisms exist changing the structure-function relationship, disconnection patterns prevail when predicting motor impairment at different time points after stroke. 14 p.

Language is a unique trait of the human species, of which the genetic architecture remains largely unknown. Through language disorders studies, many candidate genes were identified. However, such complex and multifactorial trait is unlikely to be driven by only few genes and case-control studies, suffering from a lack of power, struggle to uncover significant variants. In parallel, neuroimaging has significantly contributed to the understanding of structural and functional aspects of language in the human brain and the recent availability of large scale cohorts like UK Biobank have made possible to study language via image-derived endophenotypes in the general population. Because of its strong relationship with task-based fMRI activations and its easiness of acquisition, resting-state functional MRI have been more popularised, making it a good surrogate of functional neuronal processes. Taking advantage of such a synergistic system by aggregating effects across spatially distributed traits, we performed a multivariate genome-wide association study (mvGWAS) between genetic variations and resting-state functional connectivity (FC) of classical brain language areas in the inferior frontal (pars opercularis, triangularis and orbitalis), temporal and inferior parietal lobes (angular and supramarginal gyri), in 32,186 participants from UK Biobank. Twenty genomic loci were found associated with language FCs, out of which three were replicated in an independent replication sample. A locus in 3p11.1, regulating EPHA3 gene expression, is found associated with FCs of the semantic component of the language network, while a locus in 15q14, regulating THBS1 gene expression is found associated with FCs of the perceptualmotor language processing, bringing novel insights into the neurobiology of language.

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

The frontal lobe is central to distinctive aspects of human cognition and behavior. Some comparative studies link this to a larger frontal cortex and even larger frontal white matter in humans compared with other primates, yet others dispute these findings. The discrepancies between studies could be explained by limitations of the methods used to quantify volume differences across species, especially when applied to white matter connections., The frontal lobe is central to distinctive aspects of human cognition and behavior. Some comparative studies link this to a larger frontal cortex and even larger frontal white matter in humans compared with other primates, yet others dispute these findings. The discrepancies between studies could be explained by limitations of the methods used to quantify volume differences across species, especially when applied to white matter connections. In this study, we used a novel tractography approach to demonstrate that frontal lobe networks, extending within and beyond the frontal lobes, occupy 66% of total brain white matter in humans and 48% in three monkey species: vervets (Chlorocebus aethiops), rhesus macaque (Macaca mulatta) and cynomolgus macaque (Macaca fascicularis), all male. The simian–human differences in proportional frontal tract volume were significant for projection, commissural, and both intralobar and interlobar association tracts. Among the long association tracts, the greatest difference was found for tracts involved in motor planning, auditory memory, top-down control of sensory information, and visuospatial attention, with no significant differences in frontal limbic tracts important for emotional processing and social behaviour. In addition, we found that a nonfrontal tract, the anterior commissure, had a smaller volume fraction in humans, suggesting that the disproportionally large volume of human frontal lobe connections is accompanied by a reduction in the proportion of some nonfrontal connections. These findings support a hypothesis of an overall rearrangement of brain connections during human evolution. SIGNIFICANCE STATEMENT Tractography is a unique tool to map white matter connections in the brains of different species, including humans. This study shows that humans have a greater proportion of frontal lobe connections compared with monkeys, when normalized by total brain white matter volume. In particular, tracts associated with language and higher cognitive functions are disproportionally larger in humans compared with monkeys, whereas other tracts associated with emotional processing are either the same or disproportionally smaller. This supports the hypothesis that the emergence of higher cognitive functions in humans is associated with increased extended frontal connectivity, allowing human brains more efficient cross talk between frontal and other high-order associative areas of the temporal, parietal, and occipital lobes.

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

International audience; Clinical neuroscience research relying on animal models brought valuable translational insights into the function and pathologies of the human brain. The anatomical, physiological, and behavioural similarities between humans and mammals have prompted researchers to study cerebral mechanisms at different levels to develop and test new treatments. The vast majority of biomedical research uses rodent models, which are easily manipulable and have a broadly resembling organisation to the human nervous system but cannot satisfactorily mimic some disorders. For these disorders, macaque monkeys have been used as they have a more comparable central nervous system. Still, this research has been hampered by limitations, including high costs and reduced samples. This review argues that a squirrel monkey model might bridge the gap by complementing translational research from rodents, macaque, and humans. With the advent of promising new methods such as ultrasound imaging, tool miniaturisation, and a shift towards open science, the squirrel monkey model represents a window of opportunity that will potentially fuel new translational discoveries in the diagnosis and treatment of brain pathologies.

Contains fulltext : 250627.pdf (Publisher’s version ) (Open Access) Inter-individual differences can inform treatment procedures and-if accounted for-have the potential to significantly improve patient outcomes. However, when studying brain anatomy, these inter-individual variations are commonly unaccounted for, despite reports of differences in gross anatomical features, cross-sectional, and connectional anatomy. Brain connections are essential to facilitate functional organization and, when severed, cause impairments or complete loss of function. Hence, the study of cerebral white matter may be an ideal compromise to capture inter-individual variability in structure and function. We reviewed the wealth of studies that associate cognitive functions and clinical symptoms with individual tracts using diffusion tractography. Our systematic review indicates that tractography has proven to be a sensitive method in neurology, psychiatry, and healthy populations to identify variability and its functional correlates. However, the literature may be biased, as the most commonly studied tracts are not necessarily those with the highest sensitivity to cognitive functions and pathologies. Additionally, the hemisphere of the studied tract is often unreported, thus neglecting functional laterality and asymmetries. Finally, we demonstrate that tracts, as we define them, are not correlated with one, but multiple cognitive domains or pathologies. While our systematic review identified some methodological caveats, it also suggests that tract-function correlations might still be a promising tool in identifying biomarkers for precision medicine. They can characterize variations in brain anatomy, differences in functional organization, and predicts resilience and recovery in patients. 16 p.

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.

Available online 30 April 2021. Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress. The present manuscript is part of a growing community effort to collate Brainhack-related insights and expertise into a Jupyter Book (http://brainhack.org/brainhack_jupyter_book/) that will serve as a centralized set of resources for the community; we acknowledge all the individuals who contributed and will make ongoing contributions to these resources. A pre-print version of the present manuscript is available as part of the Jupyter Book. Moreover, we would like to acknowledge all Brainhack organizers, supporters, presenters, and participants for their contribution to growing and maintaining this community. The benefits described in this manuscript would not be possible without them. We also thank all institutions, labs, and organizations who have helped this community grow, meet in stimulating environments, and add an excellent educational resource pool and agenda. With an expanding community, Brainhack’s support network keeps growing, and we thank all labs and individual researchers for their dedication and expertise offered to this community (see http://brainhack.org/brainhack_jupyter_book/acknowledgments.html for a full list of individual acknowledgments; an updated list will be maintained in the Jupyter Book). Grants and funding bodies: This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 867458 awarded to Julia M. Huntenburg; from ANR-19-DATA-0025 NeuroWebLab for Katja Heuer, Roberto Toro, and Nicholas Traut; and from NIH K00MH122372 for Stephanie Noble. The Brainhack Community member list and contributions of the different authors are detailed at http://brainhack.org/brainhack_jupyter_book/contributors.html. Our crediting system is described here: http://brainhack.org/brainhack_jupyter_book/neuroview_authorship-agreement.html.

Contains fulltext : 217200.pdf (Publisher’s version ) (Closed access) Nonhuman primate neuroimaging is on the cusp of a transformation, much in the same way its human counterpart was in 2010, when the Human Connectome Project was launched to accelerate progress. Inspired by an open data-sharing initiative, the global community recently met and, in this article, breaks through obstacles to define its ambitions. 4 p.

ObjectiveTo combine MRI-based cortical morphometry and diffusion white matter tractography to describe the anatomical correlates of repetition deficits in patients with primary progressive aphasia (PPA).MethodsThe traditional anatomical model of language identifies a network for word repetition that includes Wernicke and Broca regions directly connected via the arcuate fasciculus. Recent tractography findings of an indirect pathway between Wernicke and Broca regions suggest a critical role of the inferior parietal lobe for repetition. To test whether repetition deficits are associated with damage to the direct or indirect pathway between both regions, tractography analysis was performed in 30 patients with PPA (64.27 ± 8.51 years) and 22 healthy controls. Cortical volume measurements were also extracted from 8 perisylvian language areas connected by the direct and indirect pathways.ResultsCompared to healthy controls, patients with PPA presented with reduced performance in repetition tasks and increased damage to most of the perisylvian cortical regions and their connections through the indirect pathway. Repetition deficits were prominent in patients with cortical atrophy of the temporo-parietal region with volumetric reductions of the indirect pathway.ConclusionsThe results suggest that in PPA, deficits in repetition are due to damage to the temporo-parietal cortex and its connections to Wernicke and Broca regions. We therefore propose a revised language model that also includes an indirect pathway for repetition, which has important clinical implications for the functional mapping and treatment of neurologic patients.

See Forkel and de Schotten (doi:10.1093/brain/awaa060) for a scientific commentary on this article. Establishing the functional necessity of a neural substrate requires the study of discrete — usually structural — lesions. Jha et al. present a new approach, employing localised metabolic lesions associated with focal epilepsy to derive novel functional anatomical maps of cognition and affect in the human brain., In theory the most powerful technique for functional localization in cognitive neuroscience, lesion-deficit mapping is in practice distorted by unmodelled network disconnections and strong ‘parasitic’ dependencies between collaterally damaged ischaemic areas. High-dimensional multivariate modelling can overcome these defects, but only at the cost of commonly impracticable data scales. Here we develop lesion-deficit mapping with metabolic lesions—discrete areas of hypometabolism typically seen on interictal 18F-fluorodeoxyglucose PET imaging in patients with focal epilepsy—that inherently capture disconnection effects, and whose structural dependence patterns are sufficiently benign to allow the derivation of robust functional anatomical maps with modest data. In this cross-sectional study of 159 patients with widely distributed focal cortical impairments, we derive lesion-deficit maps of a broad range of psychological subdomains underlying affect and cognition. We demonstrate the potential clinical utility of the approach in guiding therapeutic resection for focal epilepsy or other neurosurgical indications by applying high-dimensional modelling to predict out-of-sample verbal IQ and depression from cortical metabolism alone.

Strong right-hand preference on the population level is a uniquely human feature, although the neural basis for this is still not clearly defined. Recent behavioural and neuroimaging literature suggests that hand preference may be related to the orchestrated function and size of fronto-parietal white matter tracts bilaterally. Lesions to these tracts induced during tumour resection may provide an opportunity to test this hypothesis. In the present study, a cohort of seventeen neurosurgical patients with left hemisphere brain tumours were recruited to investigate whether resection of certain white matter tracts affects the choice of hand selected for the execution of a goal-directed task (assembly of jigsaw puzzles). Patients performed the puzzles, but also tests for basic motor ability, selective attention and visuo-constructional ability, preoperatively and one month after surgery. Diffusion tractography of fronto-parietal tracts (the superior longitudinal fasciculus) and the corticospinal tract were performed, to evaluate whether resection of tracts was significantly associated with changes in hand selection. A complementary atlas-based disconnectome analysis was also conducted. Results showed a shift in hand selection despite the absence of any motor or cognitive deficits, which was significantly associated with patients with frontal and parietal resections, compared with those with resections in other lobes. In particular, this effect was significantly associated with the resection of dorsal fronto-parietal white matter connections, but not with the ventral fronto-parietal tract. Dorsal white matter pathways contribute bilaterally, with specific lateralised competencies, to control of goal-directed hand movements. We show that unilateral lesions, by unbalancing the cooperation of the two hemispheres, can alter the choice of hand selected to accomplish movements.

The field of neuroanatomy of language is moving forward at a fast pace. This progression is partially due to the development of diffusion tractography, which has been used to describe white matter connections in the living human brain. For the field of neurolinguistics, this advancement is timely and important for two reasons. First, it allows clinical researchers to liberate themselves from neuroanatomical models of language derived from animal studies. Second, for the first time, it offers the possibility of testing network correlates of neurolinguistic models directly in the human brain. This chapter introduces the reader to general principles of diffusion imaging and tractography. Examples of its applications to normal language and its disorders will be used to explicate its potentials and limitations.

International audience

Human behavioral asymmetries are commonly studied in the context of structural cortical and connectional asymmetries. Within this framework, Sreenivasan and Sridharan (1) provide intriguing evidence of a relationship between visual asymmetries and the lateralization of superior colliculi connections—a phylogenetically older mesencephalic structure. Specifically, response facilitation for cued locations (i.e., choice bias) in the contralateral hemifield was associated with differences in the connectivity of the superior colliculus. Given that the superior colliculus has a structural homolog—the optic tectum—which can be traced across all Vertebrata, these results may have meaningful evolutionary ramifications. Even the oldest vertebrates display asymmetries in visually guided … [↵][1]1To whom correspondence may be addressed. Email: patrick.friedrich{at}rub.de. [1]: #xref-corresp-1-1

Patients with anosognosia for hemiplegia after right-hemisphere stroke deny the existence of contralesional motor deficits. Besharati et al. show that such patients are impaired in social cognition tasks requiring 3 rd person perspective-taking. A reduced ability to disengage from the 1 st person perspective may explain the patients’ reduced bodily self-awareness., Following right-hemisphere damage, a specific disorder of motor awareness can occur called anosognosia for hemiplegia, i.e. the denial of motor deficits contralateral to a brain lesion. The study of anosognosia can offer unique insights into the neurocognitive basis of awareness. Typically, however, awareness is assessed as a first person judgement and the ability of patients to think about their bodies in more ‘objective’ (third person) terms is not directly assessed. This may be important as right-hemisphere spatial abilities may underlie our ability to take third person perspectives. This possibility was assessed for the first time in the present study. We investigated third person perspective taking using both visuospatial and verbal tasks in right-hemisphere stroke patients with anosognosia ( n = 15) and without anosognosia ( n = 15), as well as neurologically healthy control subjects ( n = 15). The anosognosic group performed worse than both control groups when having to perform the tasks from a third versus a first person perspective. Individual analysis further revealed a classical dissociation between most anosognosic patients and control subjects in mental (but not visuospatial) third person perspective taking abilities. Finally, the severity of unawareness in anosognosia patients was correlated to greater impairments in such third person, mental perspective taking abilities (but not visuospatial perspective taking). In voxel-based lesion mapping we also identified the lesion sites linked with such deficits, including some brain areas previously associated with inhibition, perspective taking and mentalizing, such as the inferior and middle frontal gyri, as well as the supramarginal and superior temporal gyri. These results suggest that neurocognitive deficits in mental perspective taking may contribute to anosognosia and provide novel insights regarding the relation between self-awareness and social cognition.

Patients with stroke offer a unique window into understanding human brain function. Mapping stroke lesions poses several challenges due to the complexity of the lesion anatomy and the mechanisms causing local and remote disruption on brain networks. In this prospective longitudinal study, we compare standard and advanced approaches to white matter lesion mapping applied to acute stroke patients with aphasia. Eighteen patients with acute left hemisphere stroke were recruited and scanned within two weeks from symptom onset. Aphasia assessment was performed at baseline and six-month follow-up. Structural and diffusion MRI contrasts indicated an area of maximum overlap in the anterior external/extreme capsule with diffusion images showing a larger overlap extending into posterior perisylvian regions. Anatomical predictors of recovery included damage to ipsilesional tracts (as shown by both structural and diffusion images) and contralesional tracts (as shown by diffusion images only). These findings indicate converging results from structural and diffusion lesion mapping methods but also clear differences between the two approaches in their ability to identify predictors of recovery outside the lesioned regions., Highlights • Lesion mapping methods determine different lesion extents and associated outcomes. • Voxel-based methods are sensitive to lesions associated with aphasia recovery. • Diffusion data can reveal anatomical predictors of recovery beyond the lesion.

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.

The parietal lobe has a unique place in the human brain. Anatomically, it is at the crossroad between the frontal, occipital, and temporal lobes, thus providing a middle ground for multimodal sensory integration. Functionally, it supports higher cognitive functions that are characteristic of the human species, such as mathematical cognition, semantic and pragmatic aspects of language, and abstract thinking. Despite its importance, a comprehensive comparison of human and simian intraparietal networks is missing. In this study, we used diffusion imaging tractography to reconstruct the major intralobar parietal tracts in twenty-one datasets acquired invivo from healthy human subjects and eleven exvivo datasets from five vervet and six macaque monkeys. Three regions of interest (post-central gyrus, superior parietal lobule and inferior parietal lobule) were used to identify the tracts. Surface projections were reconstructed for both species and results compared to identify similarities or differences in tract anatomy (i.e., trajectories and cortical projections). In addition, post-mortem dissections were performed in a human brain. The largest tract identified in both human and monkey brains is a vertical pathway between the superior and inferior parietal lobules. This tract can be divided into an anterior (supramarginal gyrus) and a posterior (angular gyrus) component in both humans and monkey brains. The second prominent intraparietal tract connects the post-central gyrus to both supramarginal and angular gyri of the inferior parietal lobe in humans but only to the supramarginal gyrus in the monkey brain. The third tract connects the post-central gyrus to the anterior region of the superior parietal lobule and is more prominent in monkeys compared to humans. Finally, short U-shaped fibres in medial and lateral aspects of the parietal lobe were identified in both species. A tract connecting the medial parietal cortex to the lateral inferior parietal cortex was observed in the monkey brain only. Our findings suggest a consistent pattern of intralobar parietal connections between humans and monkeys with some differences for those areas that have cytoarchitectonically distinct features in humans. The overall pattern of intraparietal connectivity supports the special role of the inferior parietal lobule in cognitive functions characteristic of humans.

Stroke-induced aphasia is associated with adverse effects on quality of life and the ability to return to work. For patients and clinicians the possibility of relying on valid predictors of recovery is an important asset in the clinical management of stroke-related impairment. Age, level of education, type and severity of initial symptoms are established predictors of recovery. However, anatomical predictors are still poorly understood. In this prospective longitudinal study, we intended to assess anatomical predictors of recovery derived from diffusion tractography of the perisylvian language networks. Our study focused on the arcuate fasciculus, a language pathway composed of three segments connecting Wernicke’s to Broca’s region (i.e. long segment), Wernicke’s to Geschwind’s region (i.e. posterior segment) and Broca’s to Geschwind’s region (i.e. anterior segment). In our study we were particularly interested in understanding how lateralization of the arcuate fasciculus impacts on severity of symptoms and their recovery. Sixteen patients (10 males; mean age 60 ± 17 years, range 28–87 years) underwent post stroke language assessment with the Revised Western Aphasia Battery and neuroimaging scanning within a fortnight from symptoms onset. Language assessment was repeated at 6 months. Backward elimination analysis identified a subset of predictor variables (age, sex, lesion size) to be introduced to further regression analyses. A hierarchical regression was conducted with the longitudinal aphasia severity as the dependent variable. The first model included the subset of variables as previously defined. The second model additionally introduced the left and right arcuate fasciculus (separate analysis for each segment). Lesion size was identified as the only independent predictor of longitudinal aphasia severity in the left hemisphere [beta = −0.630, t(−3.129), P = 0.011]. For the right hemisphere, age [beta = −0.678, t(–3.087), P = 0.010] and volume of the long segment of the arcuate fasciculus [beta = 0.730, t(2.732), P = 0.020] were predictors of longitudinal aphasia severity. Adding the volume of the right long segment to the first-level model increased the overall predictive power of the model from 28% to 57% [F(1,11) = 7.46, P = 0.02]. These findings suggest that different predictors of recovery are at play in the left and right hemisphere. The right hemisphere language network seems to be important in aphasia recovery after left hemispheric stroke.

International audience; Last year was the 150th anniversary of Paul Broca's landmark case report on speech disorder that paved the way for subsequent studies of cortical localization of higher cognitive functions. However, many complex functions rely on the activity of distributed networks rather than single cortical areas. Hence, it is important to understand how brain regions are linked within large-scale networks and to map lesions onto connecting white matter tracts. To facilitate this network approach we provide a synopsis of classical neurological syndromes associated with frontal, parietal, occipital, temporal and limbic lesions. A review of tractography studies in a variety of neuropsychiatric disorders is also included. The synopsis is accompanied by a new atlas of the human white matter connections based on diffusion tensor tractography freely downloadable on http://www.natbrainlab.com. Clinicians can use the maps to accurately identify the tract affected by lesions visible on conventional CT or MRI. The atlas will also assist researchers to interpret their group analysis results. We hope that the synopsis and the atlas by allowing a precise localization of white matter lesions and associated symptoms will facilitate future work on the functional correlates of human neural networks as derived from the study of clinical populations. Our goal is to stimulate clinicians to develop a critical approach to clinico-anatomical correlative studies and broaden their view of clinical anatomy beyond the cortical surface in order to encompass the dysfunction related to connecting pathways.

The occipital and frontal lobes are anatomically distant yet functionally highly integrated to generate some of the most complex behaviour. A series of long associative fibres, such as the fronto-occipital networks, mediate this integration via rapid feed-forward propagation of visual input to anterior frontal regions and direct top–down modulation of early visual processing.Despite the vast number of anatomical investigations a general consensus on the anatomy of fronto-occipital connections is not forthcoming. For example, in the monkey the existence of a human equivalent of the ‘inferior fronto-occipital fasciculus’ (iFOF) has not been demonstrated. Conversely, a ‘superior fronto-occipital fasciculus’ (sFOF), also referred to as ‘subcallosal bundle’ by some authors, is reported in monkey axonal tracing studies but not in human dissections.In this study our aim is twofold. First, we use diffusion tractography to delineate the in vivo anatomy of the sFOF and the iFOF in 30 healthy subjects and three acallosal brains. Second, we provide a comprehensive review of the post-mortem and neuroimaging studies of the fronto-occipital connections published over the last two centuries, together with the first integral translation of Onufrowicz's original description of a human fronto-occipital fasciculus (1887) and Muratoff's report of the ‘subcallosal bundle’ in animals (1893).Our tractography dissections suggest that in the human brain (i) the iFOF is a bilateral association pathway connecting ventro-medial occipital cortex to orbital and polar frontal cortex, (ii) the sFOF overlaps with branches of the superior longitudinal fasciculus (SLF) and probably represents an ‘occipital extension’ of the SLF, (iii) the subcallosal bundle of Muratoff is probably a complex tract encompassing ascending thalamo-frontal and descending fronto-caudate connections and is therefore a projection rather than an associative tract.In conclusion, our experimental findings and review of the literature suggest that a ventral pathway in humans, namely the iFOF, mediates a direct communication between occipital and frontal lobes. Whether the iFOF represents a unique human pathway awaits further ad hoc investigations in animals.

Introduction The atlas by Heinrich Sachs (1892) provided an accurate description of the intralobar fibres of the occipital lobe, with a detailed representation of the short associative tracts connecting different parts of the lobe. Little attention has been paid to the work of Sachs since its publication. In this study, we present the results of the dissection of three hemispheres, performed according to the Klingler technique (1935). Our anatomical findings are then compared to the original description of the occipital fibres anatomy as detailed by Sachs. Methods Three hemispheres were dissected according to Klingler's technique (1935). Specimens were fixed in 10% formalin and frozen at −15 °C for two weeks. After defreezing, dissection of the white matter fibres was performed with blunt dissectors. Coronal sections were obtained according to the cuts originally described by Sachs. In addition, medial to lateral and lateral to medial dissection of the white matter of the occipital lobe was also performed. Results A network of short association fibres was demonstrated in the occipital lobe, comprising intralobar association fibres and U-shaped fibres, which are connecting neighbouring gyri. Lateral to the ventricles, longitudinal fibres of the stratum sagittale were also identified that are arranged as external and internal layers. Fibres of the forceps major were also found to be in direct contact with the ventricular walls. We were able to replicate all tracts originally described by Sachs. In addition, a previously unrecognised tract, connecting the cuneus to the lingual gyrus, was identified. This tract corresponds to the “sledge runner”, described in tractography studies. Conclusions The occipital lobe shows a rich network of intralobar fibres, arranged around the ventricular wall. Good concordance was observed between the Klingler dissection technique and the histological preparations of Sachs.

International audience; Right hemisphere dominance for visuospatial attention is characteristic for most humans, but its anatomical basis remains unknown. We report the first evidence in humans for a larger parieto-frontal network in the right than left hemisphere; and a significant correlation between the degree of anatomical lateralization and asymmetry of performance on visuospatial tasks. Our results suggest that hemispheric specialization is associated with an unbalanced speed of visuospatial processing.

Looking for a friend in the crowd, avoiding a sudden danger or contemplating a work of art are some examples of actions based on the efficiency of our visuo-spatial attention system. The specialization of the right brain hemisphere for visuo-spatial attention is a characteristic of most humans, but its anatomical basis remains largely unknown. Our study is the first to report in humans the existence of a bilateral parieto-frontal network whose hemispheric lateralization predicts the degree of specialization of the right hemisphere for visuo-spatial attention. Our results also suggest that this specialization is associated with an unbalanced speed of visuo-spatial processing between the two hemispheres. This lateralization may be predictive of visuo-spatial recovery in patients with lesions of parieto-frontal networks.

Functional neuroimaging supports the hypothesis that auditory verbal hallucinations (AVH) in schizophrenia result from altered functional connectivity between perisylvian language regions, although the extent to which AVH are also associated with an altered tract anatomy is less clear.Twenty-eight patients with schizophrenia subdivided into 17 subjects with a history of AVH and 11 without a history of hallucinations and 59 age- and IQ-matched healthy controls were recruited. The number of streamlines, fractional anisotropy (FA), and mean diffusivity were measured along the length of the arcuate fasciculus and its medial and lateral components.Patients with schizophrenia had bilateral reduction of FA relative to controls in the arcuate fasciculi (p.001). Virtual dissection of the subcomponents of the arcuate fasciculi revealed that these reductions were specific to connections between posterior temporal and anterior regions in the inferior frontal and parietal lobe. Also, compared with controls, the reduction in FA of these tracts was highest, and bilateral, in patients with AVH, but in patients without AVH, this reduction was reported only on the left.These findings point toward a supraregional network model of AVH in schizophrenia. They support the hypothesis that there may be selective vulnerability of specific anatomical connections to posterior temporal regions in schizophrenia and that extensive bilateral damage is associated with a greater vulnerability to AVH. If confirmed by further studies, these findings may advance our understanding of the anatomical factors that are protective against AVH and predictive of a treatment response.

Nat. Neurosci. 14, 1245–1246 (2011); published online 18 September 2011; corrected after print 13 October 2011 In the version of this article initially published, the institute identifier was omitted from the INSERM affiliation of author Michel Thiebaut de Schotten. The correct affiliation should read Unite Mixte de Recherche (UMR) S 975.

The nineteenth century witnessed some of the greatest neuroanatomists of all times. Amongst them is the largely forgotten Heinrich Sachs, a student of Carl Wernicke in Breslau. Sachs was a German neurologist, born in 1863 in Halberstadt a town in the German state of Saxony-Anhalt and the capital of the district of Harz. Despite his upbringing in a lower-income background, he was able to study medicine in Berlin where he graduated in 1885 with his doctoral thesis on amyotrophic lateral sclerosis. Thereafter, Sachs practised as a physician for some years before starting his specialisation within Carl Wernicke’s laboratory at the University Hospital of Breslau [1]. Sachs habilitated in 1897 in Psychiatry and Neurology with his work on the accruement of spatial perception through sensory impressions [2]. The most comprehensive information accessible today originates from Sachs’ personal files, which contain his signature (Fig. 1). These files enclose a reply to the demand of the principal of the royal university acting upon order of the royal ministry, which insisted that professors of their universities disclose their personal and professional relations. In this document, Sachs stated that his confession was Jewish-protestant and as a remark added that he was also working as specialist registrar at the hospital for accidents and emergencies. This position was to influence one of his last publications on traumatic neurosis [3]. Fig. 1 Sachs’ signature as shown in his private files from 1897 and a frontal section through the right occipital lobe shown as schematic representation of the white matter arrangement (taken from his atlas [4, 5]). Anatomical labels identify the following ... Sachs was married with one child. His wife was brought up within an established merchant family in Breslau and their daughter was the poet Lessie Sachs (1897–1942) who emigrated to the US during the Nazi era. In 1892 Sachs published the first part of a white matter atlas, which was dedicated to the investigation of the anatomy of the human brain. This endeavour was devoted to the study of the connectional anatomy of the occipital lobe and the adjacent temporal and parietal lobes [4]. Carl Wernicke expressed his deep appreciation and enthusiasm for this work within the preface. This wonderful elaborate effort demonstrated white matter connections within the occipital lobe (intralobar U-shaped fibres) in parallel to trajectories reaching adjacent cortices (interlobar association pathways). Sachs highlighted the importance of studying anatomy in the healthy brain prior to examining pathological, embryological or animal specimens. He further claimed that to establish a trajectory of a neuronal pathway a minimum of two methods was required to partially overcome the shortcomings inherent to each method [4]. His remarkable atlas has recently been translated [5] and replicated using the Klingler method [6]. Of note, it was also within this work that Sachs argued that the origin of the “superior fronto-occipital fasciculus” derived from callosal fibres, which were unable to transverse the hemispheric midline [7, 8]. Owing to this observation, it was recently suggested that the “Probst bundle” (the alternative name used for the superior fronto-occipital fasciculus) be renamed as the “Sachs-Probst bundle” [7]. Sachs was, however, not the first to publish this observation [8]. His name has been adopted for other pathways and structures in the brain including the fasciculus occipitalis transversus of Vialet and Sachs [6]. Beyond his detailed anatomical interest, Sachs was captivated by the structural- functional relationships in the brain and attempted to use his anatomical knowledge to explain behaviour. Being a neurologist and a student of Wernicke, he repeatedly scrutinised anatomical models of aphasia [9, 10]. Sachs sternly critiqued the schematic models as oversimplified and highlighted the importance of the white matter connections between cortical regions: “The doctrine presented here had already been subjected to substantial criticism by Freud in 1892. Nevertheless due to its convenience, simplicity and apparent tangibility it withstood the critique. […] It should be highlighted that for Wernicke the content centre [Begriffszentrum] has never been anything else but the entire cortex. His choice of the term “transcortical” does not reflect an entity outside the brain, such as the soul, but was dedicated to the fibre pathways which are interconnecting cortical areas”. Of contemporary interest is his closing paragraph [9]: “The question of utmost interest is whether the right hemisphere, which is identical to the left in its anatomy, can functionally compensate when the language centres, and in particular the sensory language centre [superior temporal gyrus], in the left hemisphere are damaged. This compensation is possible and does occur if an illness affects a child within its first years of life”. In his habilitation on the accruement of spatial perception Sachs dichotomised all sensory impressions into simple and complex inputs. The first group consists of taste, olfaction and thermoception. These perceptions can occur in different qualities with altered intensities and elicit distinct feelings; yet, no spatial or temporal relations are experienced or encoded in memory. In contrast, auditory, visual, and haptic inputs require relations. For example, auditory input necessitates the recognition of tones (simple input) in parallel with the relation between them, i.e. harmonies and melodies (complex input). Sachs believed that simple perception is innate whereas complex perception is acquired and thus a higher brain function which reaches beyond passive sensations. For Heinrich Sachs, the brain was the master and the body was the emissary: “The function of the nervous system is to orchestrate the functions of all individual organs […]. This unique purpose of the nervous system to coordinate all other parts of the body to produce a unified action is represented in its form. It is made of nothing but a net of fibres. At times these fibres are propagating to the body and are in contact with all other organs. Other fibres combine as big tangles to form nerve centres in which the regulation of the bodily functions is performed”. Sachs died aged 65 years in Breslau in 1928. The circumstances and causes of his death are not currently known.