Search

Human machine interfaces are increasingly designed to reduce our reliance on the dominantly used senses of vision and audition. Many emerging technologies are attempting to convey complex spatiotemporal information via tactile percepts shown to be effective in the visual domain, such as shape and motion. Despite the intuitive appeal of touch as a method of feedback, we do not know to what extent the hand can substitute for the retina in this way. Here we ask whether the tactile system can be used to perceive complex whole hand motion stimuli, and whether it exhibits the same kind of established perceptual biases as reported in the visual domain. Using ultrasound stimulation, we were able to project complex moving dot percepts onto the palm in mid-air, over 30cm above an emitter device. We generated dot kinetogram stimuli involving motion in three different directional axes (‘Horizontal’, ‘Vertical’, and ‘Oblique’) on the ventral surface of the hand. We found clear evidence that participants were able to discriminate tactile motion direction. Furthermore, there was a marked directional bias in motion perception: participants were better and more confident at discriminating motion in the vertical and horizontal axes of the hand, compared to those stimuli moving obliquely. This pattern directly mirrors the perceptional biases that have been robustly reported in the visual field, termed the ‘Oblique Effect’. These data show the existence of biases in motion perception that transcend sensory modality. Furthermore, we extend the Oblique Effect to a whole hand scale, using motion stimuli presented on the broad and relatively low acuity surface of the palm, away from the densely innervated and much studied fingertips. These findings also highlight targeted ultrasound stimulation as a versatile means by which to convey potentially complex spatial and temporal information without the need for a user to wear or touch a device. This ability is particularly attractive as a potential feedback mechanism for application in contact-free human machine interfaces.

Key points Massive irreparable rotator cuff tear was used as a model to study the impact of chronic pain and motor impairment on the motor systems of the human brain using magnetic resonance imaging.Patients show markers of lower grey/white matter integrity and lower functional connectivity compared with control participants in regions responsible for movement and the perception of visual movement and body shape.An independent cohort of patients showed relative deficits in the perception of visual motion and hand laterality compared with an age‐matched control group.These data support the hypothesis that the structure and function of the motor control system differs in patients who have experienced chronic motor impairment.This work also raises a new hypothesis, supported by neuroimaging and behaviour, that a loss of motor function could also be associated with off‐target effects, namely a reduced ability to perceive motion and body form. Abstract Changes in the way we move can induce changes in the brain, yet we know little of such plasticity in relation to musculoskeletal diseases. Here we use massive irreparable rotator cuff tear as a model to study the impact of chronic motor impairment and pain on the human brain. Cuff tear destabilises the shoulder, impairing upper‐limb function in overhead and load‐bearing tasks. We used neuroimaging and behavioural testing to investigate how brain structure and function differed in cuff tear patients and controls (imaging: 21 patients, age 76.3 ± 7.68; 18 controls, age 74.9 ± 6.59; behaviour: 13 patients, age 75.5 ± 10.2; 11 controls, age 73.4 ± 5.01). We observed lower grey matter density and cortical thickness in cuff tear patients in the postcentral gyrus, inferior parietal lobule, temporal‐parietal junction and the pulvinar – areas implicated in somatosensation, reach/grasp and body form perception. In patients we also observed lower functional connectivity between the motor network and the middle temporal visual cortex (MT), a region involved in visual motion perception. Lower white matter integrity was observed in patients in the inferior fronto‐occipital/longitudinal fasciculi. We investigated the cognitive domains associated with the brain regions identified. Patients exhibited relative impairment in visual body judgements and the perception of biological/global motion. These data support our initial hypothesis that cuff tear is associated with differences in the brain's motor control regions in comparison with unaffected individuals. Moreover, our combination of neuroimaging and behavioural data raises a new hypothesis that chronic motor impairment is associated with an altered perception of visual motion and body form., Key points Massive irreparable rotator cuff tear was used as a model to study the impact of chronic pain and motor impairment on the motor systems of the human brain using magnetic resonance imaging.Patients show markers of lower grey/white matter integrity and lower functional connectivity compared with control participants in regions responsible for movement and the perception of visual movement and body shape.An independent cohort of patients showed relative deficits in the perception of visual motion and hand laterality compared with an age‐matched control group.These data support the hypothesis that the structure and function of the motor control system differs in patients who have experienced chronic motor impairment.This work also raises a new hypothesis, supported by neuroimaging and behaviour, that a loss of motor function could also be associated with off‐target effects, namely a reduced ability to perceive motion and body form.

Whilst considerable progress has been made in using ultra-high field fMRI to study brain function at fine spatial resolution, methods are generally optimized at a single site and do not translate to studies where multiple sites are required for sufficient subject recruitment. With a recent increase in installations of human 7 T systems, there is now the opportunity to establish a framework for multi-site 7 T fMRI studies. However, an understanding of the inter-site variability of fMRI measurements is required for datasets to be combined across sites. To address this, we employ a hand digit localization task and compare across-site and within-site reproducibility of 7 T fMRI to a hand digit localization task which requires fine spatial resolution to resolve individual digit representations. As part of the UK7T Network “Travelling Heads” study, 10 participants repeated the same hand digit localization task at five sites with whole-body 7T MRI systems to provide a measure of inter-site variability. A subset of the participants (2 per site) performed repeated sessions at each site for measurement of intra-site reproducibility. Dice’s overlap coefficient was used to assess reproducibility, with hand region inter-site Dice = 0.70±0.04 significantly lower than intrasite Dice = 0.76±0.06, with similar trends for the individual digit maps. Although slightly lower than intra-site reproducibility, the inter-site reproducibility results are consistent with previous single site reproducibility measurements, providing evidence that multi-site 7 T fMRI studies are feasible. These results can be used to inform sample size calculations for future multi-site somatomotor mapping studies.

Hand movements are controlled by neuronal networks in primary motor cortex (M1). The organising principle in M1 does not follow an anatomical body map, but rather a distributed representational structure in which motor primitives are combined to produce motor outputs. Both electrophysiological recordings in primates and human imaging data suggest that M1 encodes kinematic features of movements, such as joint position and velocity. However, M1 exhibits well-documented sensory responses to cutaneous and proprioceptive stimuli, raising questions regarding the origins of kinematic motor representations: are they relevant in top-down motor control, or are they an epiphenomenon of bottom-up sensory feedback during movement? Moreover, to what extent is information related to muscle activity encoded in motor cortex? Here we provide evidence for spatially and temporally distinct encoding of kinematic and muscle information in human M1 during the production of a wide variety of naturalistic hand movements. Using a powerful combination of high-field fMRI and MEG, a spatial and temporal multivariate representational similarity analysis revealed encoding of kinematic information from data glove recordings in more caudal regions of M1, over 200ms before movement onset. In contrast, patterns of muscle activity from EMG were encoded in more rostral motor regions later in the cycle of movement. Our spatial and temporal analysis provide compelling evidence that top-down control of dexterous movement engages kinematic representations in caudal regions of M1 prior to movement production; an area with direct cortico-motorneuronal connections. Muscle information encoded more rostrally in M1 was engaged later, suggestive of involvement in bottom-up signalling.

Key points The ability to learn new motor skills is supported by plasticity in the structural and functional organisation of the primary motor cortex in the human brain.Changes inhibitory to signalling by GABA are thought to be crucial in inducing motor cortex plasticity.This study used magnetic resonance spectroscopy (MRS) to quantify the concentration of GABA in human motor cortex during a period of motor learning, as well as during a period of movement and a period at rest.We report evidence for a reduction in the MRS‐measured concentration of GABA specific to learning. Further, the GABA concentration early in the learning task was strongly correlated with the magnitude of subsequent learning: higher GABA concentrations were associated with poorer learning.The results provide initial insight into the neurochemical correlates of cortical plasticity associated with motor learning, specifically relevant in therapeutic efforts to induce cortical plasticity during recovery from stroke. Abstract The ability to learn novel motor skills is a central part of our daily lives and can provide a model for rehabilitation after a stroke. However, there are still fundamental gaps in our understanding of the physiological mechanisms that underpin human motor plasticity. The acquisition of new motor skills is dependent on changes in local circuitry within the primary motor cortex (M1). This reorganisation has been hypothesised to be facilitated by a decrease in local inhibition via modulation of the neurotransmitter GABA, but this link has not been conclusively demonstrated in humans. Here, we used 7 T magnetic resonance spectroscopy to investigate the dynamics of GABA concentrations in human M1 during the learning of an explicit, serial reaction time task. We observed a significant reduction in GABA concentration during motor learning that was not seen in an equivalent motor task lacking a learnable sequence, nor during a passive resting task of the same duration. No change in glutamate was observed in any group. Furthermore, M1 GABA measured early in task performance was strongly correlated with the degree of subsequent learning, such that greater inhibition was associated with poorer subsequent learning. This result suggests that higher levels of cortical inhibition may present a barrier that must be surmounted in order to achieve an increase in M1 excitability, and hence encoding of a new motor skill. These results provide strong support for the mechanistic role of GABAergic inhibition in motor plasticity, raising questions regarding the link between population variability in motor learning and GABA metabolism in the brain., Key points The ability to learn new motor skills is supported by plasticity in the structural and functional organisation of the primary motor cortex in the human brain.Changes inhibitory to signalling by GABA are thought to be crucial in inducing motor cortex plasticity.This study used magnetic resonance spectroscopy (MRS) to quantify the concentration of GABA in human motor cortex during a period of motor learning, as well as during a period of movement and a period at rest.We report evidence for a reduction in the MRS‐measured concentration of GABA specific to learning. Further, the GABA concentration early in the learning task was strongly correlated with the magnitude of subsequent learning: higher GABA concentrations were associated with poorer learning.The results provide initial insight into the neurochemical correlates of cortical plasticity associated with motor learning, specifically relevant in therapeutic efforts to induce cortical plasticity during recovery from stroke.

Experience-dependent reorganisation of functional maps in the cerebral cortex is well described in the primary sensory cortices. However, there is relatively little evidence for such cortical reorganisation over the short-term. Using human somatosensory cortex as a model, we investigated the effects of a 24 hr gluing manipulation in which the right index and right middle fingers (digits 2 and 3) were adjoined with surgical glue. Somatotopic representations, assessed with two 7 tesla fMRI protocols, revealed rapid off-target reorganisation in the non-manipulated fingers following gluing, with the representation of the ring finger (digit 4) shifted towards the little finger (digit 5) and away from the middle finger (digit 3). These shifts were also evident in two behavioural tasks conducted in an independent cohort, showing reduced sensitivity for discriminating the temporal order of stimuli to the ring and little fingers, and increased substitution errors across this pair on a speeded reaction time task. DOI: http://dx.doi.org/10.7554/eLife.17280.001, eLife digest The areas of the brain that receive inputs from our senses have a map-like structure. In an area called the visual cortex this map represents our field of vision; in the auditory cortex, it represents the range of different tones we can hear. The sense of touch is processed in the somatosensory cortex: an area of the brain that is organised around a map of the body, with adjacent regions of the cortex representing adjacent regions of the body. The clear structure of these brain regions makes them ideal for exploring how the organisation of the brain changes over time. How quickly can changes to the touch inputs that the brain receives cause the map in the somatosensory cortex to reorganise? Can these effects be produced in just 24 hours? And would this remapping affect how we perceive touch? To investigate these questions, Kolasinski et al. glued together the right index and right middle fingers of healthy human volunteers. This separated the middle and ring fingers: a pair that usually move together due to the anatomical structure of the hand. Functional magnetic resonance imaging of the brain’s activity revealed that within 24 hours of the gluing, the brain’s representation of the ring finger moved away from that of the middle finger, and towards the representation of the little finger. A perceptual judgment task mirrored this finding: after 24 hours of gluing, the participants became better at distinguishing between the middle and ring fingers and worse at distinguishing between the ring and little fingers. This is a powerful demonstration of the human brain’s potential to adapt and reorganise rapidly to changes to sensory inputs. The sense of touch declines gradually with age and may also be reduced as a result of disease such as stroke. A long-term challenge is to understand how the sensory regions of the brain change during this loss of sensation. Further research could then investigate how to maintain the structure of the cortical map to prolong or restore high quality touch sensation. DOI: http://dx.doi.org/10.7554/eLife.17280.002

Vitamin D and its metabolites have pleomorphic roles in both nervous system health and disease. Animal models have been paramount in contributing to our knowledge and understanding of the consequences of vitamin D deficiency on brain development and its implications for adult psychiatric and neurological diseases. The conflation of in vitro, ex vivo, and animal model data provide compelling evidence that vitamin D has a crucial role in proliferation, differentiation, neurotrophism, neuroprotection, neurotransmission, and neuroplasticity. Vitamin D exerts its biological function not only by influencing cellular processes directly, but also by influencing gene expression through vitamin D response elements. This review highlights the epidemiological, neuropathological, experimental and molecular genetic evidence implicating vitamin D as a candidate in influencing susceptibility to a number of psychiatric and neurological diseases. The strength of evidence varies for schizophrenia, autism, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and is especially strong for multiple sclerosis.

Little is known about the emergence of structural asymmetry of white matter tracts during early brain development. We examined whether and when asymmetry in diffusion parameters of limbic and association white matter pathways emerged in humans in 23 brains ranging from 15 gestational weeks (GW) up to 3 years of age (11 ex vivo and 12 in vivo cases) using high-angular resolution diffusion imaging tractography. Age-related development of laterality was not observed in a limbic connectional pathway (cingulum bundle or fornix). Among the studied cortico-cortical association pathways (inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus, and arcuate fasciculus), only the ILF showed development of age-related laterality emerging as early as the second trimester. Comparisons of ages older and younger than 40 GW revealed a leftward asymmetry in the cingulum bundle volume and a rightward asymmetry in apparent diffusion coefficient and leftward asymmetry in fractional anisotropy in the ILF in ages older than 40 GW. These results suggest that morphometric asymmetry in cortical areas precedes the emergence of white matter pathway asymmetry. Future correlative studies will investigate whether such asymmetry is anatomically/genetically driven or associated with functional stimulation.

Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional anatomical connectivity to the spread of multiple sclerosis pathology in a ‘tract-specific’ pattern. Furthermore, the persisting relationship between metrics from post-mortem diffusion-weighted magnetic resonance imaging and histological measures from fixed tissue further validates the potential of imaging for future neuropathological studies.

The hand area of the primary somatosensory cortex contains detailed finger topography, thought to be shaped and maintained by daily life experience. Here we utilise phantom sensations and ultra high-field neuroimaging to uncover preserved, though latent, representation of amputees’ missing hand. We show that representation of the missing hand’s individual fingers persists in the primary somatosensory cortex even decades after arm amputation. By demonstrating stable topography despite amputation, our finding questions the extent to which continued sensory input is necessary to maintain organisation in sensory cortex, thereby reopening the question what happens to a cortical territory once its main input is lost. The discovery of persistent digit topography of amputees’ missing hand could be exploited for the development of intuitive and fine-grained control of neuroprosthetics, requiring neural signals of individual digits. DOI: http://dx.doi.org/10.7554/eLife.15292.001, eLife digest The brain has a remarkable ability to adapt to changes in circumstances. But what happens to the brain when it loses a key source of input, for example, following the amputation of a limb? A region of the brain known as primary somatosensory cortex processes sensory inputs from all over the body. The more sensitive an area of the body is, the more fine-grained its representation is in the cortex. For example, the hand is represented with a highly detailed map, with each finger represented seperately. The brain is thought to require ongoing sensory signals from the body to maintain these detailed representations in the cortex. Indeed, textbooks typically state that the brain will ‘overwrite’ its representation of a body part if input from that area no longer arrives. According to this view, people who have lost a hand should show little or no activity in the area of primary somatosensory cortex that used to represent it. However, many people who have had a limb amputated continue to experience vivid sensations of the missing limb long after its loss. When asked to move their so-called ‘phantom’ limb, these individuals report being able to feel the movement. Kikkert, Kolasinski et al. now show, using advanced imaging techniques, that the brains of individuals with phantom hands continue to represent the missing hand several decades after its loss. Indeed, asking the subjects to move individual fingers of their phantom hand activates fine-grained representations of those fingers, similar to those seen in two-handed controls. By showing that the brain ‘remembers’ an amputated hand, Kikkert, Kolasinski et al. demonstrate that ongoing sensory input is not required to maintain representations of the body in somatosensory cortex. This, in turn, offers new hope for developing prosthetic limbs that are under direct brain control. If the brain continues to represent individual fingers many years after their loss, it should be possible to exploit those pathways to achieve intuitive fine-grained control of artificial fingers. DOI: http://dx.doi.org/10.7554/eLife.15292.002

Corticogenesis is underpinned by a complex process of subcortical neuroproliferation, followed by highly orchestrated cellular migration. A greater appreciation of the processes involved in human fetal corticogenesis is vital to gaining an understanding of how developmental disturbances originating in gestation could establish a variety of complex neuropathology manifesting in childhood, or even in adult life. Magnetic resonance imaging modalities offer a unique insight into anatomical structure, and increasingly infer information regarding underlying microstructure in the human brain. In this study we applied a combination of high-resolution structural and diffusion-weighted magnetic resonance imaging to a unique cohort of three post-mortem fetal brain specimens, aged between 19 and 22 post-conceptual weeks. Specifically, we sought to assess patterns of diffusion coherence associated with subcortical neuroproliferative structures: the pallial ventricular/subventricular zone and subpallial ganglionic eminence. Two distinct three-dimensional patterns of diffusion coherence were evident: a clear radial pattern originating in ventricular/subventricular zone, and a tangentio-radial patterns originating in ganglionic eminence. These patterns appeared to regress in a caudo-rostral and lateral-ventral to medial-dorsal direction across the short period of fetal development under study. Our findings demonstrate for the first time distinct patterns of diffusion coherence associated with known anatomical proliferative structures. The radial pattern associated with dorsopallial ventricular/subventricular zone and the tangentio-radial pattern associated with subpallial ganglionic eminence are consistent with reports of radial-glial mediated neuronal migration pathways identified during human corticogenesis, supported by our prior studies of comparative fetal diffusion MRI and histology. The ability to assess such pathways in the fetal brain using MR imaging offers a unique insight into three-dimensional trajectories beyond those visualized using traditional histological techniques. Our results suggest that ex-vivo fetal MRI is a potentially useful modality in understanding normal human development and various disease processes whose etiology may originate in aberrant fetal neuronal migration.

Multiple sclerosis (MS) is a chronic inflammatory neurological condition characterised by both focal and diffuse neurodegeneration and demyelination throughout the central nervous system. However, associations between these individual pathological processes remain poorly defined. Here we present a highly novel combination of whole brain post-mortem diffusion and structural MRI with quantitative histology to assess patterns of MS pathology. Two white matter tracts and their associated grey matter structures were assessed in nine fixed whole brains on the basis of their documented involvement in MS: that running from lateral geniculate nucleus to primary visual cortex, and from mediodorsal nucleus of the thalamus to prefrontal cortex. Cortical thickness was correlated significantly with both tract myelination and thalamic nucleus cell density within the anatomically distinct tract structures. Such correlations were not observed between these markers of neurodegeneration across the two tract types. In addition, diffusion MRI metrics in all tracts were correlated significantly with histologically defined levels of tract myelination. These data demonstrate for the first time the potential relevance of functional anatomical connectivity to the spread of MS pathology in a “tract-specific” pattern. Furthermore, the persisting relationship between metrics from post-mortem diffusion-weighted MRI and tissue microstructure in fixed samples validates the exciting potential of this imaging modality for future neuropathological studies.