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Functional coactivation between human brain regions is partly explained by white matter connections; however, how the structure-function relationship varies by function remains unclear. Here, we reference large data repositories to compute maps of structure-function correspondence across hundreds of specific functions and brain regions. We use natural language processing to accurately predict structure-function correspondence for specific functions and to identify macroscale gradients across the brain that correlate with structure-function correspondence as well as cortical thickness. Our findings suggest structure-function correspondence unfolds along a sensory-fugal organizational axis, with higher correspondence in primary sensory and motor cortex for perceptual and motor functions, and lower correspondence in association cortex for cognitive functions. Our study bridges neuroscience and natural language to describe how structure-function coupling varies by region and function in the brain, offering insight into the diversity and evolution of neural network properties., (© 2024. The Author(s).)

The central sulcus divides the primary motor and somatosensory cortices in many anthropoid primate brains. Differences exist in the surface area and depth of the central sulcus along the dorso-ventral plane in great apes and humans compared to other primate species. Within hominid species, there are variations in the depth and aspect of their hand motor area, or knob, within the precentral gyrus. In this study, we used post-image analyses on magnetic resonance images to characterize the central sulcus shape of humans, chimpanzees (Pan troglodytes), gorillas (Gorilla gorilla), and orangutans (Pongo pygmaeus and Pongo abelii). Using these data, we examined the morphological variability of central sulcus in hominids, focusing on the hand region, a significant change in human evolution. We show that the central sulcus shape differs between great ape species, but all show similar variations in the location of their hand knob. However, the prevalence of the knob location along the dorso-ventral plane and lateralization differs between species and the presence of a second ventral motor knob seems to be unique to humans. Humans and orangutans exhibit the most similar and complex central sulcus shapes. However, their similarities may reflect divergent evolutionary processes related to selection for different positional and habitual locomotor functions., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The capacity to learn enabled the human species to adapt to various challenging environmental conditions and pass important achievements on to the next generation. A growing body of research suggests links between neocortical folding properties and numerous aspects of human behavior, but their impact on enhanced human learning capacity remains unexplored. Here we leverage three training cohorts to demonstrate that higher levels of premotor cortical folding reliably predict individual long-term learning gains in a challenging new motor task, above and beyond initial performance differences. Individual folding-related predisposition to motor learning was found to be independent of cortical thickness and intracortical microstructure, but dependent on larger cortical surface area in premotor regions. We further show that learning-relevant features of cortical folding occurred in close spatial proximity to practice-induced structural brain plasticity. Our results suggest a link between neocortical surface folding and human behavioral adaptability., (© 2024. The Author(s).)

The frontal aslant tract (FAT) connects the supplementary motor area (SMA) with the pars opercularis. Its role in language and its implications in glioma surgery remain under discussion. We present an anatomosurgical study of three cases with surgical resolution. Three patients with gliomas in the left frontal lobe were operated on using an awake patient protocol with cortical and subcortical mapping techniques, conducting motor and language evaluations. Tractography was performed using DSI Studio software. All three patients showed intraoperative language inhibition through subcortical stimulation of the FAT. Resection involving the FAT correlated with language deficits in all cases and movement initiation deficits in two cases. All patients recovered from their deficits at six months postoperatively. In conclusion, the tract has been successfully reconstructed, showing both anatomical and functional complexity, supporting the idea of its mapping and preservation in glioma surgery. Future interdisciplinary studies are necessary to determine the transient or permanent nature of the deficits.

Introduction: Felids have evolved a specialized suite of morphological adaptations for obligate carnivory. Although the musculoskeletal anatomy of the Felidae has been studied extensively, the comparative neuroanatomy of felids is relatively unexplored. Little is known about how variation in the cerebral anatomy of felids relates to species-specific differences in sociality, hunting strategy, or activity patterns., Methods: We quantitatively analyzed neuropil variation in the prefrontal, primary motor, and primary visual cortices of six species of Felidae (Panthera leo, Panthera uncia, Panthera tigris, Panthera leopardus, Acinonyx jubatus, Felis sylvestris domesticus) to investigate relationships with brain size, neuronal cell parameters, and select behavioral and ecological factors. Neuropil is the dense, intricate network of axons, dendrites, and synapses in the brain, playing a critical role in information processing and communication between neurons., Results: There were significant species and regional differences in neuropil proportions, with African lion, cheetah, and tiger having more neuropil in all three cortical regions in comparison to the other species. Based on regression analyses, we find that the increased neuropil fraction in the prefrontal cortex supports social and behavioral flexibility, while in the primary motor cortex, this facilitates the neural activity needed for hunting movements. Greater neuropil fraction in the primary visual cortex may contribute to visual requirements associated with diel activity patterns., Conclusion: These results provide a cross-species comparison of neuropil fraction variation in the Felidae, particularly the understudied Panthera, and provide evidence for convergence of the neuroanatomy of Panthera and cheetahs., (© 2024 S. Karger AG, Basel.)

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations 1,2 , despite evidence for concentric functional zones 3 and maps of complex actions 4 . Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action 5 and physiological control 6 , arousal 7 , errors 8 and pain 9 . This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions 4 and connectivity to internal organs 10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate-isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement., (© 2023. The Author(s).)

BACKGROUND [color=black]The precentral knob of the precentral gyrus is the original site for hand somatotopy in the corticospinal tract, and it is considered an important target for neuromodulation. However, little is known about the anatomical location of the precentral knob for easy clinical use. This study aimed to describe the use of an optical tracking brain navigator to identify the anatomical location of the precentral knob in the precentral gyrus in normal subjects. [/color] MATERIAL AND METHODS [color=black]Twenty healthy right-handed subjects were enrolled for this study. The locations of target and surface points in each subject were determined using a brain navigator. The target and surface points were defined as the precentral knob and the area of the scalp in the vertical direction from the target point, respectively. Then, by placing a marked 1-cm grid on each subject's head, the horizontal and vertical distances from the midline central (Cz) were measured using the point marker.[/color] RESULTS [color=black]The average distance from Cz to the location of the precentral knob in the horizontal direction was 30.75 mm in the right hemisphere, 31.25 mm in the left hemisphere, and 31.00 mm in both hemispheres. The average distance from Cz to the location of the precentral knob in the vertical direction was -12.75 mm in the right hemisphere, -14.50 mm in the left hemisphere, and -13.62 mm in both hemispheres. [/color] CONCLUSIONS [color=black]This study showed that the anatomical location of the precentral knob in normal subjects could be identified using a brain navigator and this method may be used clinically for patients requiring neuromodulation.[/color].

The widely used rubber hand illusion (RHI) paradigm provides insight into how the brain manages conflicting multisensory information regarding bodily self-consciousness. Previous functional neuroimaging studies have revealed that the feeling of body ownership is linked to activity in the premotor cortex, the intraparietal areas, the occipitotemporal cortex, and the insula. The current study investigated whether the individual differences in the sensation of body ownership over a rubber hand, as measured by subjective report and the proprioceptive drift, are associated with structural brain differences in terms of cortical thickness in 67 healthy young adults. We found that individual differences measured by the subjective report of body ownership are associated with the cortical thickness in the somatosensory regions, the temporo-parietal junction, the intraparietal areas, and the occipitotemporal cortex, while the proprioceptive drift is linked to the premotor area and the anterior cingulate cortex. These results are in line with functional neuroimaging studies indicating that these areas are indeed involved in processes such as cognitive-affective perspective taking, visual processing of the body, and the experience of body ownership and bodily awareness. Consequently, these individual differences in the sensation of body ownership are pronounced in both functional and structural differences., (© 2022. The Author(s).)

Short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) occur when the motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS) is reduced by the delivery of a preceding peripheral nerve stimulus. The intra-individual variability in SAI and LAI is considerable, and the influence of sample demographics (e.g., age and biological sex) and testing context (e.g., time of day) is not clear. There are also no established normative values for these measures, and their reliability varies from study-to-study. To address these issues and facilitate the interpretation of SAI and LAI research, we pooled data from studies published by our lab between 2014 and 2020 and performed several retrospective analyses. Patterns in the depth of inhibition with respect to age, biological sex and time of testing were investigated, and the relative reliability of measurements from studies with repeated baseline SAI and LAI assessments was examined. Normative SAI and LAI values with respect to the mean and standard deviation were also calculated. Our data show no relationship between the depth of inhibition for SAI and LAI with either time of day or age. Further, there was no significant difference in SAI or LAI between males and females. Intra-class correlation coefficients (ICC) for repeated measurements of SAI and LAI ranged from moderate (ICC = 0.526) to strong (ICC = 0.881). The mean value of SAI was 0.71 ± 0.27 and the mean value of LAI was 0.61 ± 0.34. This retrospective study provides normative values, reliability estimates, and an exploration of demographic and testing influences on these measures as assessed in our lab. To further facilitate the interpretation of SAI and LAI data, similar studies should be performed by other labs that use these measures., Competing Interests: The authors have declared that no competing interests exist.

Objective: The setting of external ventricular drainage (EVD) is one of the most frequent procedures in the neurosurgical practice. However, complication risks of this procedure may grow from 5% to 39%. The number of publications concerning the advancement of ventricular drainage setting technique and complication risks identification is increasing year after year. We posed a question on the dependence of complication risks and catheter setting accuracy on the different factors of routine practice of the N. N. Burdenko National Medical Research Center for neurosurgery within the scope of this work., Methods: The data on patients whose EVD was set in the premotor area in 2019 were collected retrospectively. The surgeons were divided into 3 groups according to their experience valued in years., Results: The result of drainage setting was considered satisfactory if its end was in the frontal horn or body of the ipsilateral ventricle. Generally, 122 patients passed EVD placement during 2019. According to computed tomography scans of the brain, the drainage position was satisfactory in 85 patients (75.9%) and unsatisfactory in 27 patients (24.1%)., Conclusions: The procedures were performed by surgeons with <2 years of experience in 16.1% of cases, 2-5 years of experience in 25% of cases, and >5 years of experience in 58.9% of cases. The complication risk and accuracy of drainage setting do not depend on surgeon experience, type of bone access, and position in the premotor area., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Full-length SMART-seq 1 single-cell RNA sequencing can be used to measure gene expression at isoform resolution, making possible the identification of specific isoform markers for different cell types. Used in conjunction with spatial RNA capture and gene-tagging methods, this enables the inference of spatially resolved isoform expression for different cell types. Here, in a comprehensive analysis of 6,160 mouse primary motor cortex cells assayed with SMART-seq, 280,327 cells assayed with MERFISH 2 and 94,162 cells assayed with 10x Genomics sequencing 3 , we find examples of isoform specificity in cell types-including isoform shifts between cell types that are masked in gene-level analysis-as well as examples of transcriptional regulation. Additionally, we show that isoform specificity helps to refine cell types, and that a multi-platform analysis of single-cell transcriptomic data leveraging multiple measurements provides a comprehensive atlas of transcription in the mouse primary motor cortex that improves on the possibilities offered by any single technology., (© 2021. The Author(s).)

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted 1 . Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture., (© 2021. The Author(s).)

Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain 1-3 . With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas-containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities-is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions 4 . We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis., (© 2021. The Author(s).)

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals 1 . Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations., (© 2021. The Author(s).)

Cortical neurons exhibit extreme diversity in gene expression as well as in morphological and electrophysiological properties 1,2 . Most existing neural taxonomies are based on either transcriptomic 3,4 or morpho-electric 5,6 criteria, as it has been technically challenging to study both aspects of neuronal diversity in the same set of cells 7 . Here we used Patch-seq 8 to combine patch-clamp recording, biocytin staining, and single-cell RNA sequencing of more than 1,300 neurons in adult mouse primary motor cortex, providing a morpho-electric annotation of almost all transcriptomically defined neural cell types. We found that, although broad families of transcriptomic types (those expressing Vip, Pvalb, Sst and so on) had distinct and essentially non-overlapping morpho-electric phenotypes, individual transcriptomic types within the same family were not well separated in the morpho-electric space. Instead, there was a continuum of variability in morphology and electrophysiology, with neighbouring transcriptomic cell types showing similar morpho-electric features, often without clear boundaries between them. Our results suggest that neuronal types in the neocortex do not always form discrete entities. Instead, neurons form a hierarchy that consists of distinct non-overlapping branches at the level of families, but can form continuous and correlated transcriptomic and morpho-electrical landscapes within families., (© 2020. The Author(s).)

A mammalian brain is composed of numerous cell types organized in an intricate manner to form functional neural circuits. Single-cell RNA sequencing allows systematic identification of cell types based on their gene expression profiles and has revealed many distinct cell populations in the brain 1,2 . Single-cell epigenomic profiling 3,4 further provides information on gene-regulatory signatures of different cell types. Understanding how different cell types contribute to brain function, however, requires knowledge of their spatial organization and connectivity, which is not preserved in sequencing-based methods that involve cell dissociation. Here we used a single-cell transcriptome-imaging method, multiplexed error-robust fluorescence in situ hybridization (MERFISH) 5 , to generate a molecularly defined and spatially resolved cell atlas of the mouse primary motor cortex. We profiled approximately 300,000 cells in the mouse primary motor cortex and its adjacent areas, identified 95 neuronal and non-neuronal cell clusters, and revealed a complex spatial map in which not only excitatory but also most inhibitory neuronal clusters adopted laminar organizations. Intratelencephalic neurons formed a largely continuous gradient along the cortical depth axis, in which the gene expression of individual cells correlated with their cortical depths. Furthermore, we integrated MERFISH with retrograde labelling to probe projection targets of neurons of the mouse primary motor cortex and found that their cortical projections formed a complex network in which individual neuronal clusters project to multiple target regions and individual target regions receive inputs from multiple neuronal clusters., (© 2021. The Author(s).)

Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization 1-5 . First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties., (© 2021. The Author(s).)

High-frequency repeated transcranial magnetic stimulation (HF-rTMS) is a safe non-invasive neuromodulatory technique and there is a body of evidence shows that it can modulate plasticity in different brain areas. One of the most interesting application of HF-rTMS is the modulation of plasticity in primary motor cortex (M1) to promote recovery after brain injuries. However, the underlying mechanism by which HF-rTMS modulates motor cortex plasticity remain to be investigated. In this study, we investigated the effects of HF-rTMS treatment on morphological plasticity of pyramidal neurons in layer II/III (L2/3) of the primary motor cortex in mice. Our results show that the treatment did not increase anxiety in mice in the open field test and the elevated plus-maze test. Treated mice displayed increased total spine density in apical and basal dendrites, with a predominance of thin spines. The treatment also increased dendritic complexity, as assessed by Sholl analysis at both apical and basal dendrites. Collectively, the results show that HF-rTMS induced remarkable changes in dendritic complexity in primary motor cortex L2/3 connections which may strengthen corticocortical connections increasing integration of information across cortical areas. The data support the use of HF-rTMS as a circuit-targeting neuromodulation strategy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The dorso-posterior parietal cortex (DPPC) is a major node of the grasp/manipulation control network. It is assumed to act as an optimal forward estimator that continuously integrates efferent outflows and afferent inflows to modulate the ongoing motor command. In agreement with this view, a recent per-operative study, in humans, identified functional sites within DPPC that: (i) instantly disrupt hand movements when electrically stimulated; (ii) receive short-latency somatosensory afferences from intrinsic hand muscles. Based on these results, it was speculated that DPPC is part of a rapid grasp control loop that receives direct inputs from the hand-territory of the primary somatosensory cortex (S1) and sends direct projections to the hand-territory of the primary motor cortex (M1). However, evidence supporting this hypothesis is weak and partial. To date, projections from DPPC to M1 grasp zone have been identified in monkeys and have been postulated to exist in humans based on clinical and transcranial magnetic studies. This work uses diffusion-MRI tractography in two samples of right- (n = 50) and left-handed (n = 25) subjects randomly selected from the Human Connectome Project. It aims to determine whether direct connections exist between DPPC and the hand control sectors of the primary sensorimotor regions. The parietal region of interest, related to hand control (hereafter designated DPPC hand ), was defined permissively as the 95% confidence area of the parietal sites that were found to disrupt hand movements in the previously evoked per-operative study. In both hemispheres, irrespective of handedness, we found dense ipsilateral connections between a restricted part of DPPC hand and focal sectors within the pre and postcentral gyrus. These sectors, corresponding to the hand territories of M1 and S1, targeted the same parietal zone (spatial overlap > 92%). As a sensitivity control, we searched for potential connections between the angular gyrus (AG) and the pre and postcentral regions. No robust pathways were found. Streamline densities identified using AG as the starting seed represented less than 5 % of the streamline densities identified from DPPC hand . Together, these results support the existence of a direct sensory-parietal-motor loop suited for fast manual control and more generally, for any task requiring rapid integration of distal sensorimotor signals., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

Premotor circuits in the brainstem project to pools of orofacial motoneurons to execute essential motor action such as licking, chewing, breathing, and in rodent, whisking. Previous transsynaptic tracing studies only mapped orofacial premotor circuits in neonatal mice, but the adult circuits remain unknown as a consequence of technical difficulties. Here, we developed a three-step monosynaptic transsynaptic tracing strategy to identify premotor neurons controlling vibrissa, tongue protrusion, and jaw-closing muscles in the adult mouse. We registered these different groups of premotor neurons onto the Allen mouse brain common coordinate framework (CCF) and consequently generated a combined 3D orofacial premotor atlas, revealing unique spatial organizations of distinct premotor circuits. We further uncovered premotor neurons that simultaneously innervate multiple motor nuclei and, consequently, are likely to coordinate different muscles involved in the same orofacial motor actions. Our method for tracing adult premotor circuits and registering to Allen CCF is generally applicable and should facilitate the investigations of motor controls of diverse behaviors., Competing Interests: JT, JP, JL, SL, PT, BH, SZ, DK, BF, FW No competing interests declared, (© 2021, Takatoh et al.)

Neurophysiological and anatomical data suggest the existence of several functionally distinct regions in the lower arcuate sulcus and adjacent postarcuate convexity of the macaque monkey. Ventral premotor F5c lies on the postarcuate convexity and consists of a dorsal hand-related and ventral mouth-related field. The posterior bank of the lower arcuate contains two additional premotor F5 subfields at different anterior-posterior levels, F5a and F5p. Anterior to F5a, area 44 has been described as a dysgranular zone occupying the deepest part of the fundus of the inferior arcuate. Finally, area GrFO occupies the most rostral portion of the fundus and posterior bank of inferior arcuate and extends ventrally onto the frontal operculum. Recently, data-driven exploratory approaches using resting-state fMRI data have been suggested as a promising non-invasive method for examining the functional organization of the primate brain. Here, we examined to what extent partitioning schemes derived from data-driven clustering analysis of resting-state fMRI data correspond with the proposed organization of the fundus and posterior bank of the macaque arcuate sulcus, as suggested by invasive architectonical, connectional and functional investigations. Using a hierarchical clustering analysis, we could retrieve clusters corresponding to the dorsal and ventral portions of F5c on the postarcuate convexity, F5a and F5p at different antero-posterior locations on the posterior bank of the lower arcuate, area 44 in the fundus, as well as part of area GrFO in the most anterior portion of the fundus. Additionally, each of these clusters displayed distinct whole-brain functional connectivity, in line with previous anatomical tracer and seed-based functional connectivity investigations of F5/44 subdivisions. Overall, our data suggests that hierarchical clustering analysis of resting-state fMRI data can retrieve a fine-grained level of cortical organization that resembles detailed parcellation schemes derived from invasive functional and anatomical investigations., (Copyright © 2020. Published by Elsevier Inc.)

Transcranial direct-current stimulation (tDCS) is a non-invasive brain stimulation technique consisting in the application of weak electric currents on the scalp. Although previous studies have demonstrated the clinical value of tDCS for modulating sensory, motor, and cognitive functions, there are still huge gaps in the knowledge of the underlying physiological mechanisms. To define the immediate impact as well as the after effects of tDCS on sensory processing, we first performed electrophysiological recordings in primary somatosensory cortex (S1) of alert mice during and after administration of S1-tDCS, and followed up with immunohistochemical analysis of the stimulated brain regions. During the application of cathodal and anodal transcranial currents we observed polarity-specific bidirectional changes in the N1 component of the sensory-evoked potentials (SEPs) and associated gamma oscillations. On the other hand, 20 min of cathodal stimulation produced significant after-effects including a decreased SEP amplitude for up to 30 min, a power reduction in the 20-80 Hz range and a decrease in gamma event related synchronization (ERS). In contrast, no significant changes in SEP amplitude or power analysis were observed after anodal stimulation except for a significant increase in gamma ERS after tDCS cessation. The polarity-specific differences of these after effects were corroborated by immunohistochemical analysis, which revealed an unbalance of GAD 65-67 immunoreactivity between the stimulated versus non-stimulated S1 region only after cathodal tDCS. These results highlight the differences between immediate and after effects of tDCS, as well as the asymmetric after effects induced by anodal and cathodal stimulation.

Long-term hearing loss in postlingually deaf (PD) adults may lead to brain structural changes that affect the outcomes of cochlear implantation. We studied 94 PD patients who underwent cochlear implantation and 37 patients who were MRI-scanned within 2 weeks after the onset of sudden hearing loss and expected with minimal brain structural changes in relation to deafness. Compared with those with sudden hearing loss, we found lower gray matter (GM) probabilities in bilateral thalami, superior, middle, inferior temporal cortices as well as the central cortical regions corresponding to the movement and sensation of the lips, tongue, and larynx in the PD group. Among these brain areas, the GM in the middle temporal cortex showed negative correlation with disease duration, whereas the other areas displayed positive correlations. Left superior, middle temporal cortical, and bilateral thalamic GMs were the most accurate predictors of post-cochlear implantation word recognition scores (mean absolute error [MAE] = 10.1, r = .82), which was superior to clinical variables used (MAE: 12.1, p < .05). Using the combined brain morphological and clinical features, we achieved the best prediction of the outcome (MAE: 8.51, r = .90). Our findings suggest that the cross-modal plasticity allowing the superior temporal cortex and thalamus to process other modal sensory inputs reverses the initially lower volume when deafness becomes persistent. The middle temporal cortex processing higher-level language comprehension shows persistent negative correlations with disease duration, suggesting this area's association with degraded speech comprehensions due to long-term deafness. Morphological features combined with clinical variables might play a key role in predicting outcomes of cochlear implantation., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: The corpus callosotomy (CCT) has been reported as an effective procedure to alleviate drop attacks. However, the extent of CCT remains debatable. Classical studies suggest that motor fibers traverse mainly through the anterior half of the corpus callosum (CC), although recent diffusion tensor imaging studies described that motor fibers crossed the CC in a more posterior location, emphasizing the posterior midbody and the isthmus., Methods: Cortical and subcortical structures were examined in 30 hemispheres prepared for white matter fiber dissection. Dissections were carried out under surgical magnification to trace fibers originating from the primary motor cortex and their course through the CC. The distance of the most anterior and posterior motor fibers to the tip of the genu were measured, and the extent of CCT enabling disconnection of all motor fibers was calculated., Results: Motor fibers coursed through the posterior half of the CC in the majority of hemispheres, mainly locating in posterior midbody and the isthmus. Callosal fibers should be interrupted to an average of 61% ± 0.07% point of the CC to reach the anterior limit of motor fibers and to an average of 69% ± 0.07% point to include posterior limit of motor fibers. Motor fibers were extending until the posterior one third of the CC in 22 specimens., Conclusions: Anterior-half CCT did not include all motor fibers in any specimen. Anterior two thirds CCT disrupted all motor fibers in one fourth of the cases. Our findings suggest that an ideal CCT should extend to the posterior midbody and isthmus of the CC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Projections of small regions (domains) of primary motor cortex (M1), premotor cortex (PMC) and posterior parietal cortex (PPC) to the striatum of squirrel monkeys were revealed by restricted injections of anterograde tracers. As many as 8 classes of action-specific domains can be identified in PPC, as well as in PMC and M1, and some have been identified for injections by the action evoked by 0.5 s trains of electrical microstimulation. Injections of domains in all three cortical regions labeled dense patches of terminations in the matrix of the ipsilateral putamen, while providing sparse or no projections to corresponding regions of the contralateral putamen. When two or three of these domains were injected with different tracers, projection fields in the putamen were highly overlapped for injections in functionally matched domains across cortical areas, but were highly segregated for injections placed in functionally mismatched domains. While not all classes of domains were studied, the results suggest that the striatum potentially has separate representations of eight or more classes of actions that receive inputs from domains in three or more cortical regions in sensorimotor cortex. The overlap/segregation of cortico-striatal projections correlates with the strength of cortico-cortical connections between injected motor areas., (Copyright © 2020. Published by Elsevier Ltd.)

The Extended Frontal Aslant Tract (exFAT) is a recently described tractography-based extension of the Frontal Aslant Tract connecting Broca's territory to both supplementary and pre-supplementary motor areas, and more anterior prefrontal regions. In this study, we aim to characterize the microstructural properties of the exFAT trajectories as a means to perform a laterality analysis to detect interhemispheric structural differences along the tracts using the Human Connectome Project (HCP) dataset. To that end, the bilateral exFAT was reconstructed for 3T and 7T HCP acquisitions in 120 randomly selected subjects. As a complementary exploration of the exFAT anatomy, we performed a white matter dissection of the exFAT trajectory of two ex-vivo left hemispheres that provide a qualitative assessment of the tract profiles. We assessed the lateralization structural differences in the exFAT by performing: (i) a laterality comparison between the mean microstructural diffusion-derived parameters for the exFAT trajectories, (ii) a laterality comparison between the tract profiles obtained by applying the Automated Fiber Quantification (AFQ) algorithm, and (iii) a cross-validated Machine Learning (ML) classifier analysis using single and combined tract profiles parameters for single-subject classification. The mean microstructural diffusion-derived parameter comparison showed statistically significant differences in mean FA values between left and right exFATs in the 3T sample. The diffusion parameters studied with the AFQ technique suggest that the inferiormost half of the exFAT trajectory has a hemispheric-dependent fingerprint of microstructural properties, with an increased measure of tissue hindrance in the orthogonal plane and a decreased measure of orientational dispersion along the main tract direction in the left exFAT compared to the right exFAT. The classification accuracy of the ML models showed a high agreement with the magnitude of those differences., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The human motor cortex comprises a microcircuit of five interconnected layers with different cell types. In this Review, we use a layer-specific and cell-specific approach to integrate physiological accounts of this motor cortex microcircuit with the pathophysiology of neurodegenerative diseases affecting motor functions. In doing so we can begin to link motor microcircuit pathology to specific disease stages and clinical phenotypes. Based on microcircuit physiology, we can make future predictions of axonal loss and microcircuit dysfunction. With recent advances in high-resolution neuroimaging we can then test these predictions in humans in vivo, providing mechanistic insights into neurodegenerative disease.

Although motor cortex is integral in driving physical exertion, how its inherent properties influence decisions to exert is unknown. In this study, we examined how anatomical properties of motor cortex are related to participants' subjective valuations of effort and their decisions to exert effort. We used computational modeling to characterize participants' subjective valuation of physical effort during an effort-based decision-making task in which they made choices about exerting different levels of hand-grip exertion. We also acquired structural MRI data from these participants and extracted anatomical measures of each individual's hand knob, the region of motor cortex recruited during hand-grip exertion. We found that individual participants' cortical thickness of hand knob was associated with their effort-based decisions regarding hand exertion. These data provide evidence that the anatomy of an individual's motor cortex is an important factor in decisions to engage in physical activity. NEW & NOTEWORTHY How effortful a task feels is an integral aspect of human decision-making that influences choices to engage in physical activity. We show that properties of motor cortex (the brain region responsible for physical exertion) are related to assessments of effort and decisions to exert. These findings provide a link between the anatomical properties of motor cortex and the cognitive function of effort-based choice.

The caudal forelimb area (CFA) of the mouse cortex is essential in many forelimb movements, and diverse types of GABAergic interneuron in the CFA are distinct in the mediation of cortical inhibition in motor information processing. However, their long-range inputs remain unclear. In the present study, we combined the monosynaptic rabies virus system with Cre driver mouse lines to generate a whole-brain map of the inputs to three major inhibitory interneuron types in the CFA. We discovered that each type was innervated by the same upstream areas, but there were quantitative differences in the inputs from the cortex, thalamus, and pallidum. Comparing the locations of the interneurons in two sub-regions of the CFA, we discovered that their long-range inputs were remarkably different in distribution and proportion. This whole-brain mapping indicates the existence of parallel pathway organization in the forelimb subnetwork and provides insight into the inhibitory processes in forelimb movement to reveal the structural architecture underlying the functions of the CFA.

Decades after the motor homunculus was first proposed, it is still unknown how different body parts are intermixed and interrelated in human motor cortical areas at single-neuron resolution. Using multi-unit recordings, we studied how face, head, arm, and leg movements are represented in the hand knob area of premotor cortex (precentral gyrus) in people with tetraplegia. Contrary to traditional expectations, we found strong representation of all movements and a partially "compositional" neural code that linked together all four limbs. The code consisted of (1) a limb-coding component representing the limb to be moved and (2) a movement-coding component where analogous movements from each limb (e.g., hand grasp and toe curl) were represented similarly. Compositional coding might facilitate skill transfer across limbs, and it provides a useful framework for thinking about how the motor system constructs movement. Finally, we leveraged these results to create a whole-body intracortical brain-computer interface that spreads targets across all limbs., Competing Interests: Declaration of Interests J.M.H. is a consultant for Neuralink Inc., Proteus Biomedical, and Boston Scientific and serves on the medical advisory board of Enspire DBS. K.V.S. is a consultant for Neuralink and is on the scientific advisory boards of CTRL-Labs, MIND-X, Inscopix, and Heal. All other authors have no competing interests. The MGH Translational Research Center has a clinical research support agreement with Neuralink, Paradromics, and Synchron, for which L.R.H. provides consultative input., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The human brain coordinates a wide variety of motor activities. On a large scale, the cortical motor system is topographically organized such that neighboring body parts are represented by neighboring brain areas. This homunculus-like somatotopic organization along the central sulcus has been observed using neuroimaging for large body parts such as the face, hands and feet. However, on a finer scale, invasive electrical stimulation studies show deviations from this somatotopic organization that suggest an organizing principle based on motor actions rather than body part moved. It has not been clear how the action-map organization principle of the motor cortex in the mesoscopic (sub-millimeter) regime integrates into a body map organization principle on a macroscopic scale (cm). Here we developed and applied advanced mesoscopic (sub-millimeter) fMRI and analysis methodology to non-invasively investigate the functional organization topography across columnar and laminar structures in humans. Compared to previous methods, in this study, we could capture locally specific blood volume changes across entire brain regions along the cortical curvature. We find that individual fingers have multiple mirrored representations in the primary motor cortex depending on the movements they are involved in. We find that individual digits have cortical representations up to 3 ​mm apart from each other arranged in a column-like fashion. These representations are differentially engaged depending on whether the digits' muscles are used for different motor actions such as flexion movements, like grasping a ball or retraction movements like releasing a ball. This research provides a starting point for non-invasive investigation of mesoscale topography across layers and columns of the human cortex and bridges the gap between invasive electrophysiological investigations and large coverage non-invasive neuroimaging., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background Resting-state functional MRI holds substantial potential for clinical application, but limitations exist in current understanding of how tumors exert local effects on resting-state functional MRI readings. Purpose To investigate the association between tumors, tumor characteristics, and changes in resting-state connectivity, to explore neurovascular uncoupling as a mechanism underlying these changes, and to evaluate seeding methodologies as a clinical tool. Materials and Methods Institutional review board approval was obtained for this HIPAA-compliant observational retrospective study of patients with glioma who underwent MRI and resting-state functional MRI between January 2016 and July 2017. Interhemispheric symmetry of connectivity was assessed in the hand motor region, incorporating tumor position, perfusion, grade, and connectivity generated from seed-based correlation. Statistical analysis was performed by using one-tailed t tests, Wilcoxon rank sum tests, one-way analysis of variance, Pearson correlation, and Spearman rank correlation, with significance at P < .05. Results Data in a total of 45 patients with glioma (mean age, 51.3 years ± 14.3 [standard deviation]) were compared with those in 10 healthy control subjects (mean age, 50.3 years ± 17.2). Patients showed loss of symmetry in measures of hand motor resting-state connectivity compared with control subjects ( P < .05). Tumor distance from the ipsilateral hand motor (IHM) region correlated with the degree ( R = 0.38, P = .01) and strength ( R = 0.33, P = .03) of resting-state connectivity. In patients with World Health Organization grade IV glioblastomas 40 mm or less from the IHM region, loss of symmetry in strength of resting-state connectivity was correlated with tumor perfusion ( R = 0.74, P < .01). In patients with gliomas 40 mm or less from the IHM region, seeding the nontumor hemisphere yielded less asymmetric hand motor resting-state connectivity than seeding the tumor hemisphere (connectivity seeded:contralateral = 1.34 nontumor vs 1.38 tumor hemisphere seeded; P = .03, false discovery rate threshold = 0.01). Conclusion Hand motor resting-state connectivity was less symmetrical in a tumor distance-dependent manner in patients with glioma. Differences in resting-state connectivity may be false-negative results driven by a neurovascular uncoupling mechanism. Seeding from the nontumor hemisphere may attenuate asymmetry in patients with tumors near ipsilateral hand motor cortices. © RSNA, 2020 Online supplemental material is available for this article.

Current noninvasive methods to detect structural plasticity in humans are mainly used to study long-term changes. Diffusion magnetic resonance imaging (MRI) was recently proposed as a novel approach to reveal gray matter changes following spatial navigation learning and object-location memory tasks. In the present work, we used diffusion MRI to investigate the short-term neuroplasticity that accompanies motor sequence learning. Following a 45-min training session in which participants learned to accurately play a short sequence on a piano keyboard, changes in diffusion properties were revealed mainly in motor system regions such as the premotor cortex and cerebellum. In a second learning session taking place immediately afterward, feedback was given on the timing of key pressing instead of accuracy, while participants continued to learn. This second session induced a different plasticity pattern, demonstrating the dynamic nature of learning-induced plasticity, formerly thought to require months of training in order to be detectable. These results provide us with an important reminder that the brain is an extremely dynamic structure. Furthermore, diffusion MRI offers a novel measure to follow tissue plasticity particularly over short timescales, allowing new insights into the dynamics of structural brain plasticity., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

The primate frontal lobe processes diverse motor information in parallel through multiple motor-related areas. For example, the supplementary motor area (SMA) is mainly involved in internally-triggered movements, whereas the premotor cortex (PM) is highly responsible for externally-guided movements. The primary motor cortex (M1) deals with both aspects of movements to execute a single motor behavior. To elucidate how the cortical motor system is structured to process a variety of information, the laminar distribution patterns of signals were examined between SMA and M1, or PM and M1 in macaque monkeys by using dual anterograde tract-tracing. Dense terminal labeling was observed in layers 1 and upper 2/3 of M1 after one tracer injection into SMA, another tracer injection into the dorsal division of PM resulted in prominent labeling in the deeper portion of layer 2/3. Weaker labeling was also visible in layer 5 in both cases. On the other hand, inputs from M1 terminated in both the superficial and the deep layers of SMA and PM. The present data indicate that distinct types of motor information are arranged in M1 in a layer-specific fashion to be orchestrated through a microcircuit within M1.

The effectiveness of transcranial direct current stimulation (tDCS) placed over the motor hotspot (thought to represent the primary motor cortex (M1)) to modulate motor network excitability is highly variable. The premotor cortex-particularly the dorsal premotor cortex (PMd)-may be a promising alternative target to reliably modulate motor excitability, as it influences motor control across multiple pathways, one independent of M1 and one with direct connections to M1. This double-blind, placebo-controlled preliminary study aimed to differentially excite motor and premotor regions using high-definition tDCS (HD-tDCS) with concurrent functional magnetic resonance imaging (fMRI). HD-tDCS applied over either the motor hotspot or the premotor cortex demonstrated high inter-individual variability in changes on cortical motor excitability. However, HD-tDCS over the premotor cortex led to a higher number of responders and greater changes in local fMRI-based complexity than HD-tDCS over the motor hotspot. Furthermore, an analysis of individual motor hotspot anatomical locations revealed that, in more than half of the participants, the motor hotspot is not located over anatomical M1 boundaries, despite using a canonical definition of the motor hotspot. This heterogeneity in stimulation site may contribute to the variability of tDCS results. Altogether, these preliminary findings provide new considerations to enhance tDCS reliability.

The basal ganglia are critical for the control of motor behaviors and for reinforcement learning. Here, we demonstrate in rats that primary and secondary motor areas (M1 and M2) make functional synaptic connections in the globus pallidus (GP), not usually thought of as an input site of the basal ganglia. Morphological observation revealed that the density of axonal boutons from motor cortices in the GP was 47% and 78% of that in the subthalamic nucleus (STN) from M1 and M2, respectively. Cortical excitation of GP neurons was comparable to that of STN neurons in slice preparations. FoxP2-expressing arkypallidal neurons were preferentially innervated by the motor cortex. The connection probability of cortico-pallidal innervation was higher for M2 than M1. These results suggest that cortico-pallidal innervation is an additional excitatory input to the basal ganglia, and that it can affect behaviors via the cortex-basal ganglia-thalamus motor loop., Competing Interests: FK, ST, KK, FF No competing interests declared, (© 2019, Karube et al.)

High-resolution tract tracing and stereology were used to study the terminal organization of the corticospinal projection (CSP) from the ventral (v) and dorsal (d) regions of the lateral premotor cortex (LPMC) to spinal levels C5-T1. The LPMCv CSP originated from the postarcuate sulcus region, was bilateral, sparse, and primarily targeted the dorsolateral and ventromedial sectors of contralateral lamina VII. The convexity/lateral part of LPMCv did not project below C2. Thus, very little LPMCv corticospinal output reaches the cervical enlargement. In contrast, the LPMCd CSP was 5× more prominent in terminal density. Bilateral terminal labeling occurred in the medial sectors of lamina VII and adjacent lamina VIII, where propriospinal neurons with long-range bilateral axon projections reside. Notably, lamina VIII also harbors axial motoneurons. Contralateral labeling occurred in the lateral sectors of lamina VII and the dorsomedial quadrant of lamina IX, noted for harboring proximal upper limb flexor motoneurons. Segmentally, the CSP to contralateral laminae VII and IX preferentially innervated C5-C7, which supplies shoulder, elbow, and wrist musculature. In contrast, terminations in axial-related lamina VIII were distributed bilaterally throughout all cervical enlargement levels, including C8 and T1. These findings demonstrate the LPMCd CSP is structured to influence axial and proximal upper limb movements, supporting Kuypers conceptual view of the LPMCd CSP being a major component of the medial motor control system. Thus, distal upper extremity control influenced by LPMC, including grasping and manipulation, must occur through indirect neural network connections such as corticocortical, subcortical, or intrinsic spinal circuits., (© 2019 Wiley Periodicals, Inc.)

Background: Non-invasive brain stimulation (NIBS) is increasingly used as a probe of function and therapeutics in experimental neuroscience and neurorehabilitation. Scalp-to-cortex distance (SCD), as a key parameter, has been shown to potentially impact on the electric field. This study aimed to examine the region-specific SCD and its relationship with cognitive function in the context of age-related brain atrophy., Methods: We analyzed the SCD and cortical thickness (CT) of left primary motor cortex (M1) in 164 cognitively normal (CN) adults and 43 dementia patients drawn from the Open Access Series of Imaging Studies (OASIS). The degree of brain atrophy was measured by the volume of ventricular system. Computational head model was developed to simulate the impact of SCD on the electric field., Results: Increased SCD of left M1 was only found in dementia patients (P < .001). When considering CT, the ratio of SCD to CT (F = 27.41, P < .001) showed better differential value than SCD. The SCD of left M1 was associated with worse global cognition (r = -.207, P = .011) and enlarged third ventricle (r = .241, P < .001). The electric field was consequently reduced with the increased SCD across cognitively normal elderly and dementia groups., Conclusions: Scalable distance measures, including SCD and CT, are markedly correlated with reduced electric field in dementia patients. The findings suggest that it is important to be aware of region-specific distance measures when conducting NIBS-based rehabilitation in individuals with brain atrophy., (© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Neurons form bona fide synapses with oligodendrocyte precursor cells (OPCs), but the circuit context of these neuron to OPC synapses remains incompletely understood. Using monosynaptically-restricted rabies virus tracing of OPC afferents, we identified extensive afferent synaptic inputs to OPCs residing in secondary motor cortex, corpus callosum, and primary somatosensory cortex of adult mice. These inputs primarily arise from functionally-interconnecting cortical areas and thalamic nuclei, illustrating that OPCs have strikingly comprehensive synaptic access to brain-wide projection networks. Quantification of these inputs revealed excitatory and inhibitory components that are consistent in number across brain regions and stable in barrel cortex despite whisker trimming-induced sensory deprivation., Competing Interests: CM, BY, KC, SS, MM No competing interests declared, (© 2019, Mount et al.)

Prior expectations of movement instructions can promote preliminary action planning and influence choices. We investigated how action priors affect action-goal encoding in premotor and parietal cortices and if they bias subsequent free choice. Monkeys planned reaches according to visual cues that indicated relative probabilities of two possible goals. On instructed trials, the reach goal was determined by a secondary cue respecting these probabilities. On rarely interspersed free-choice trials without instruction, both goals offered equal reward. Action priors induced graded free-choice biases and graded frontoparietal motor-goal activity, complementarily in two subclasses of neurons. Down-regulating neurons co-encoded both possible goals and decreased opposite-to-preferred responses with decreasing prior, possibly supporting a process of choice by elimination. Up-regulating neurons showed increased preferred-direction responses with increasing prior, likely supporting a process of computing net likelihood. Action-selection signals emerged earliest in down-regulating neurons of premotor cortex, arguing for an initiation of selection in the frontal lobe., Competing Interests: LS, AG No competing interests declared, (© 2019, Suriya-Arunroj and Gail.)

Newly learned motor skills are initially labile and then consolidated to permit retention. The circuits that enable the consolidation of motor memories remain uncertain. Most work to date has focused on primary motor cortex, and although there is ample evidence of learning-related plasticity in motor cortex, direct evidence for its involvement in memory consolidation is limited. Learning-related plasticity is also observed in somatosensory cortex, and accordingly, it may also be involved in memory consolidation. Here, by using transcranial magnetic stimulation (TMS) to block consolidation, we report the first direct evidence that plasticity in somatosensory cortex participates in the consolidation of motor memory. Participants made movements to targets while a robot applied forces to the hand to alter somatosensory feedback. Immediately following adaptation, continuous theta-burst transcranial magnetic stimulation (cTBS) was delivered to block retention; then, following a 24-hour delay, which would normally permit consolidation, we assessed whether there was an impairment. It was found that when mechanical loads were introduced gradually to engage implicit learning processes, suppression of somatosensory cortex following training almost entirely eliminated retention. In contrast, cTBS to motor cortex following learning had little effect on retention at all; retention following cTBS to motor cortex was not different than following sham TMS stimulation. We confirmed that cTBS to somatosensory cortex interfered with normal sensory function and that it blocked motor memory consolidation and not the ability to retrieve a consolidated motor memory. In conclusion, the findings are consistent with the hypothesis that in adaptation learning, somatosensory cortex rather than motor cortex is involved in the consolidation of motor memory., Competing Interests: The authors have declared that no competing interests exist.

Motor cortical beta activity (13-30 Hz) is a hallmark signature of healthy and pathological movement, but its behavioural relevance remains unclear. Using high-precision magnetoencephalography (MEG), we show that during the classical event-related desynchronisation (ERD) and event-related synchronisation (ERS) periods, motor cortical beta activity in individual trials (n > 12,000) is dominated by high amplitude, transient, and infrequent bursts. Beta burst probability closely matched the trial-averaged beta amplitude in both the pre- and post-movement periods, but individual bursts were spatially more focal than the classical ERS peak. Furthermore, prior to movement (ERD period), beta burst timing was related to the degree of motor preparation, with later bursts resulting in delayed response times. Following movement (ERS period), the first beta burst was delayed by approximately 100 milliseconds when an incorrect response was made. Overall, beta burst timing was a stronger predictor of single trial behaviour than beta burst rate or single trial beta amplitude. This transient nature of motor cortical beta provides new constraints for theories of its role in information processing within and across cortical circuits, and its functional relevance for behaviour in both healthy and pathological movement., Competing Interests: The authors have declared that no competing interests exist.

Cortico-basal ganglia-thalamocortical loops are largely conceived as parallel circuits that process limbic, associative, and sensorimotor information separately. Whether and how these functionally distinct loops interact remains unclear. Combining genetic and viral approaches, we systemically mapped the limbic and motor cortico-basal ganglia-thalamocortical loops in rodents. Despite largely closed loops within each functional domain, we discovered a unidirectional influence of the limbic over the motor loop via ventral striatum-substantia nigra (SNr)-motor thalamus circuitry. Slice electrophysiology verifies that the projection from ventral striatum functionally inhibits nigro-thalamic SNr neurons. In vivo optogenetic stimulation of ventral or dorsolateral striatum to SNr pathway modulates activity in medial prefrontal cortex (mPFC) and motor cortex (M1), respectively. However, whereas the dorsolateral striatum-SNr pathway exerts little impact on mPFC, activation of the ventral striatum-SNr pathway effectively alters M1 activity. These results demonstrate an open cortico-basal ganglia loop whereby limbic information could modulate motor output through ventral striatum control of M1., Competing Interests: SA, JS, HL, XY, MI, PC, JW, TR, XJ No competing interests declared, (© 2019, Aoki et al.)

Premotor neurons play a fundamental role in transforming physical properties of observed objects, such as size and shape, into motor plans for grasping them, hence contributing to "pragmatic" affordance processing. Premotor neurons can also contribute to "semantic" affordance processing, as they can discharge differently even to pragmatically identical objects depending on their behavioural relevance for the observer (i.e. edible or inedible objects). Here, we compared the response of monkey ventral premotor area F5 neurons tested during pragmatic (PT) or semantic (ST) visuomotor tasks. Object presentation responses in ST showed shorter latency and lower object selectivity than in PT. Furthermore, we found a difference between a transient representation of semantic affordances and a sustained representation of pragmatic affordances at both the single neuron and population level. Indeed, responses in ST returned to baseline within 0.5 s whereas in PT they showed the typical sustained visual-to-motor activity during Go trials. In contrast, during No-go trials, the time course of pragmatic and semantic information processing was similar. These findings suggest that premotor cortex generates different dynamics depending on pragmatic and semantic information provided by the context in which the to-be-grasped object is presented.

Learning has been associated with changes in the brain at every level of organization. However, it remains difficult to establish a causal link between specific changes in the brain and new behavioral abilities. We establish that new neural activity patterns emerge with learning. We demonstrate that these new neural activity patterns cause the new behavior. Thus, the formation of new patterns of neural population activity can underlie the learning of new skills., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Individual differences in educational attainment are linked to differences in intelligence, and predict important social, economic, and health outcomes. Previous studies have found common genetic factors that influence educational achievement, cognitive performance and total brain volume (i.e., brain size). Here, in a large sample of participants from the UK Biobank, we investigate the shared genetic basis between educational attainment and fine-grained cerebral cortical morphological features, and associate this genetic variation with a related aspect of cognitive ability. Importantly, we execute novel statistical methods that enable high-dimensional genetic correlation analysis, and compute high-resolution surface maps for the genetic correlations between educational attainment and vertex-wise morphological measurements. We conduct secondary analyses, using the UK Biobank verbal-numerical reasoning score, to confirm that variation in educational attainment that is genetically correlated with cortical morphology is related to differences in cognitive performance. Our analyses relate the genetic overlap between cognitive ability and cortical thickness measurements to bilateral primary motor cortex as well as predominantly left superior temporal cortex and proximal regions. These findings extend our understanding of the neurobiology that connects genetic variation to individual differences in educational attainment and cognitive performance., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The laminar organization of the motor cortex of the sheep and other large domestic herbivores received scarce attention and is generally considered homologous to that of rodents and primates. Thickness of the cortex, subdivision into layers and organization are scarcely known. In the present study, we applied different modern morphological, mathematical and image-analyses techniques to the study of the motor area that controls movements of the forelimb in the sheep. The thickness of the cortex resulted comparable to that of other terrestrial Cetartiodactyls (but thicker than in marine Cetartiodactyls of similar body mass). The laminar organization showed marked development of layer 1, virtual absence of layer 4, and image analysis suggested prevalence of large irregular neural cells in the deeper layers. Diffusion tensor imaging revealed robust projections from the motor cortex to the pyramids in the brainstem, and well evident tracts descending to the tegmentum of the mesencephalon and dorsal pons. Our data contrast the general representation of the motor system of this species, considered to be predominantly based on extra-pyramidal tracts that originate from central pattern generators in the brainstem.

Based on architectonic, tract-tracing or functional criteria, the rostral portion of ventral premotor cortex in the macaque monkey, also termed area F5, has been divided into several subfields. Cytoarchitectonical investigations suggest the existence of three subfields, F5c (convexity), F5p (posterior) and F5a (anterior). Electrophysiological investigations have suggested a gradual dorso-ventral transition from hand- to mouth-dominated motor fields, with F5p and ventral F5c strictly related to hand movements and mouth movements, respectively. The involvement of F5a in this respect, however, has received much less attention. Recently, data-driven resting-state fMRI approaches have also been used to examine the presence of distinct functional fields in macaque ventral premotor cortex. Although these studies have suggested several functional clusters in/near macaque F5, so far the parcellation schemes derived from these clustering methods do not completely retrieve the same level of F5 specialization as suggested by aforementioned invasive techniques. Here, using seed-based resting-state fMRI analyses, we examined the functional connectivity of different F5 seeds with key regions of the hand and face/mouth parieto-frontal-insular motor networks. In addition, we trained monkeys to perform either hand grasping or ingestive mouth movements in the scanner in order to compare resting-state with task-derived functional hand and mouth motor networks. In line with previous single-cell investigations, task-fMRI suggests involvement of F5p, dorsal F5c and F5a in the execution of hand grasping movements, while non-communicative mouth movements yielded particularly pronounced responses in ventral F5c. Corroborating with anatomical tracing data of macaque F5 subfields, seed-based resting-state fMRI suggests a transition from predominant functional correlations with the hand-motor network in F5p to mostly mouth-motor network functional correlations in ventral F5c. Dorsal F5c yielded robust functional correlations with both hand- and mouth-motor networks. In addition, the deepest part of the fundus of the inferior arcuate, corresponding to area 44, displayed a strikingly different functional connectivity profile compared to neighboring F5a, suggesting a different functional specialization for these two neighboring regions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The corpus callosum (CC) is the largest white matter structure of the brain and offers the structural basis for an intense interaction between both cerebral hemispheres. Especially with respect to the interaction of both motor cortices it shows a differentiated somatotopic organization. Neuropathological processes are often reflected in structural alterations of the CC and a spatially precise description of structures for the healthy brain is essential for further differentiation of structural damage in patients. We performed a fine-grained parcellation of the CC on 1065 diffusion-weighted data sets of the Human Connectome Project. Interhemispheric tractograms between interhemispherically corresponding functional subdivisions of the primary motor cortex (M1; Brainnetome Atlas) were calculated, transformed into a common space, averaged and thresholded, to be assessed for localization, fractional anisotropy (FA) and mean diffusivity (MD). Spatially distinct CC regions for each functional M1 subdivision (lower and upper limbs, head/face, tongue/larynx) were identified and will be available as anatomical masks. Non-parametrical statistics for the average FA and MD values showed significant differences between all callosal regions. The newly proposed callosal regions allow for a precise differentiation of M1-M1 motor connectivity and the structural integrity of these tracts. Availability of masked regions in a common space will help to better understand inter-hemispherical callosal connectivity in patients or healthy volunteers.

The cortical area within the human primary motor cortex (M1) that hosts the representation of the hand and fingers is known as the 'hand-knob' and is essential for voluntary hand movement. The anatomo-functional heterogeneity described within the monkey primary motor cortex (M1) in a rostro-caudal direction suggests an internal subdivision in two sectors originating different systems of connections to the spinal cord. Direct investigation of the human hand-knob has been prevented, so far, by methodological constraints. The unique setting of brain tumour resection with the brain mapping technique in awake patients enables direct electrophysiological investigation of the functional properties of the human hand-knob. Motor-evoked potentials (MEPs) elicited by Direct Electrical Stimulation (DES) at high frequency (HF-DES) delivered along the hand-knob in rostro-caudal direction, i.e., from the central to the precentral sulcus, were recorded from the hand/arm muscles in patients at rest. The sites located near the precentral sulcus identified with HF-DES were then stimulated with low-frequency DES (LF-DES) during a hand manipulation task (HMt) to assess whether DES affected task execution. From the stimulated sites, corticofugal projections and U-shaped tracts connecting with adjacent gyri were traced using diffusion tensor and spherical deconvolution tractography. Analysis of MEPs showed a rostro-caudal gradient of cortical excitability along the hand-knob (the rostral sector being less excitable). Stimulation of rostral sites during the HMt impaired the task by inducing dysfunctional recruitment or, alternatively, suppression of distal muscles. Diffusion tractography showed different patterns of rostro-caudal connectivity for the U-shaped tracts. Overall data suggests, in humans, the anatomo-functional subdivision of the human hand-knob in two sectors, possibly subserving different roles in motor control., (Copyright © 2019 Elsevier Ltd. All rights reserved.)