Publications

Abstract

Ambiguity surrounds the existence and morphology of the human forniceal commissure. We combine advanced in-vivo tractography, multidirectional ex-vivo fiber dissection, and multiplanar histological analysis to characterize this structure’s anatomy. Across all 178 subjects, in-vivo fiber dissection based on the Human Connectome Project 7 T MRI data identifies no interhemispheric connections between the crura fornicis. Multidirectional ex-vivo fiber dissection under the operating microscope demonstrates the psalterium as a thin soft-tissue membrane spanning between the right and left crus fornicis, but exposes no commissural fibers. Multiplanar histological analysis with myelin and Bielchowsky silver staining, however, visualizes delicate cruciform fibers extending between the crura fornicis, enclosed by connective tissue, the psalterium. The human forniceal commissure is therefore much more delicate than previously described and presented in anatomical textbooks. This finding is consistent with the observed phylogenetic trend of a reduction of the forniceal commissure in non-human primates compared to non-primate eutherian mammals.

Abstract

Attention is a core cognitive function that filters and selects behaviourally relevant information in the environment. The cortical mapping of attentional systems identified two segregated networks that mediate stimulus-driven and goal-driven processes, the Ventral and the Dorsal Attention Networks (VAN, DAN). Deep brain electrophysiological recordings, behavioral data from phylogenetic distant species, and observations from human brain pathologies challenge purely corticocentric models. Here, we used advanced methods of functional alignment applied to resting-state functional connectivity analyses to map the subcortical architecture of the Ventral and Dorsal Attention Networks. Our investigations revealed the involvement of the pulvinar, the superior colliculi, the head of caudate nuclei, and a cluster of brainstem nuclei relevant to both networks. These nuclei are densely connected structural network hubs, as revealed by diffusion-weighted imaging tractography. Their projections establish interrelations with the acetylcholine nicotinic receptor as well as dopamine and serotonin transporters, as demonstrated in a spatial correlation analysis with a normative atlas of neurotransmitter systems. This convergence of functional, structural, and neurochemical evidence provides a comprehensive framework to understand the neural basis of attention across different species and brain diseases.

Abstract

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 pre-
viously overlooked groups, how should we respond when the views of the ‘founding fathers’ of neurology
clash with those of society today?

Abstract

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.

Abstract

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.

Abstract

Lesion symptom mapping has revolutionized our understanding of the functioning of the human brain. Associating damaged voxels in the brain with loss of function has created a map of the brain that identifies critical areas. While these methods have significantly advanced our understanding, recent improvements have identified the need for multivariate and multimodal methods to map hidden lesions and damage to white matter networks beyond the lesion voxels. This article reviews the evolution of lesion-symptom mapping from single case studies to the human disconnectome.

Abstract

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.

Abstract

Inter-individual differences can inform treatment procedures and - if accounted for - can improve patient outcomes. However, when studying brain anatomy, these variations are largely unaccounted for. Brain connections are essential to mediate brain functional organization and, when severed, cause functional impairments. Here we reviewed the wealth of studies that associate functions and clinical symptoms with connections using tractography. Our results indicate that tractography is a sensitive method in healthy and clinical conditions to identify variability and its functional correlates. While our review identified some methodological caveats, it also suggests that tract-function correlations might be a promising biomarker for precision medicine.

Abstract

Understanding human white matter development is vital to characterize typical brain organization and developmental neurocognitive disorders. In this issue of Neuron, Nazeri and colleagues1 identify different parts of white matter in the neonatal brain and show their maturational trajectories in line with microstructural feature development.

Abstract

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 (tbfMRI) activations and its easiness of acquisition, resting-state functional MRI (rsfMRI) 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 perceptual-motor language processing, bringing novel insights into the neurobiology of language.

Abstract

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.

Abstract

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.

Abstract

Social factors play a crucial role in the advancement of science. New findings are discussed and theories emerge through social interactions, which usually take place within local research groups and at academic events such as conferences, seminars, or workshops. This system tends to amplify the voices of a select subset of the community—especially more established researchers—thus limiting opportunities for the larger community to contribute and connect. Brainhack (https://brainhack.org/) events (or Brainhacks for short) complement these formats in neuroscience with decentralized 2- to 5-day gatherings, in which participants from diverse backgrounds and career stages collaborate and learn from each other in an informal setting. The Brainhack format was introduced in a previous publication (Cameron Craddock et al., 2016; Figures 1A and 1B). It is inspired by the hackathon model (see glossary in Table 1), which originated in software development and has gained traction in science as a way to bring people together for collaborative work and educational courses. Unlike many hackathons, Brainhacks welcome participants from all disciplines and with any level of experience—from those who have never written a line of code to software developers and expert neuroscientists. Brainhacks additionally replace the sometimes-competitive context of traditional hackathons with a purely collaborative one and also feature informal dissemination of ongoing research through unconferences.

Abstract

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.

Abstract

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.

Abstract

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 in vivo from healthy human subjects and eleven ex vivo datasets from five vervet and six macaque monkeys. Three regions of interest (postcentral 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 postcentral gyrus to both supramarginal and angular gyri of the inferior parietal lobule in humans but only to the supramarginal gyrus in the monkey brain. The third tract connects the postcentral 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 the 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.