Prediction of post-stroke motor recovery benefits from measures of sub-acute widespread network damages.

Following a stroke in regions of the brain responsible for motor activity, patients can lose their ability to control parts of their body. Over time, some patients recover almost completely, while others barely recover at all. It is known that lesion volume, initial motor impairment and cortico-spinal tract asymmetry significantly impact motor changes over time. Recent work suggested that disabilities arise not only from focal structural changes but also from widespread alterations in inter-regional connectivity. Models that consider damage to the entire network instead of only local structural alterations lead to a more accurate prediction of patients' recovery. However, assessing white matter connections in stroke patients is challenging and time-consuming. Here, we evaluated in a data set of 37 patients whether we could predict upper extremity motor recovery from brain connectivity measures obtained by using the patient's lesion mask to introduce virtual lesions in 60 healthy streamline tractography connectomes. This indirect estimation of the stroke impact on the whole brain connectome is more readily available than direct measures of structural connectivity obtained with magnetic resonance imaging. We added these measures to benchmark structural features, and we used a ridge regression regularization to predict motor recovery at 3 months post-injury. As hypothesized, accuracy in prediction significantly increased (R 2 = 0.68) as compared to benchmark features (R 2 = 0.38). This improved prediction of recovery could be beneficial to clinical care and might allow for a better choice of intervention

Post-stroke reorganization of transient brain activity characterizes deficits and recovery of cognitive functions

Functional magnetic resonance imaging (fMRI) has been widely employed to study stroke pathophysiology. In particular, analyses of fMRI signals at rest were directed at quantifying the impact of stroke on spatial features of brain networks. However, brain networks have intrinsic time features that were, so far, disregarded in these analyses. In consequence, standard fMRI analysis failed to capture temporal imbalance resulting from stroke lesions, hence restricting their ability to reveal the interdependent pathological changes in structural and temporal network features following stroke. Here, we longitudinally analyzed hemodynamic-informed transient activity in a large cohort of stroke patients (n = 103) to assess spatial and temporal changes of brain networks after stroke. Metrics extracted from the hemodynamic-informed transient activity were replicable within- and between-individuals in healthy participants, hence supporting their robustness and their clinical applicability. While large-scale spatial patterns of brain networks were preserved after stroke, their durations were altered, with stroke subjects exhibiting a varied pattern of longer and shorter network activations compared to healthy individuals. Specifically, patients showed a longer duration in the lateral precentral gyrus and anterior cingulum, and a shorter duration in the occipital lobe and in the cerebellum. These temporal alterations were associated with white matter damage in projection and association pathways. Furthermore, they were tied to deficits in specific behavioral domains as restoration of healthy brain dynamics paralleled recovery of cognitive functions (attention, language and spatial memory), but was not significantly correlated to motor recovery. These findings underscore the critical importance of network temporal properties in dissecting the pathophysiology of brain changes after stroke, thus shedding new light on the clinical potential of time-resolved methods for fMRI analysis

A spinal cord neuroprosthesis for locomotor deficits due to Parkinson’s disease

People with late-stage Parkinson’s disease (PD) often suffer from debilitating locomotor deficits that are resistant to currently available therapies. To alleviate these deficits, we developed a neuroprosthesis operating in closed loop that targets the dorsal root entry zones innervating lumbosacral segments to reproduce the natural spatiotemporal activation of the lumbosacral spinal cord during walking. We first developed this neuroprosthesis in a non-human primate model that replicates locomotor deficits due to PD. This neuroprosthesis not only alleviated locomotor deficits but also restored skilled walking in this model. We then implanted the neuroprosthesis in a 62-year-old male with a 30-year history of PD who presented with severe gait impairments and frequent falls that were medically refractory to currently available therapies. We found that the neuroprosthesis interacted synergistically with deep brain stimulation of the subthalamic nucleus and dopaminergic replacement therapies to alleviate asymmetry and promote longer steps, improve balance and reduce freezing of gait. This neuroprosthesis opens new perspectives to reduce the severity of locomotor deficits in people with PD

Spinal Cord fMRI: A New Window into the Central Nervous System

With the brain, the spinal cord forms the central nervous system. Initially considered a passive relay between the brain and the periphery, the spinal cord is now recognized as being active and plastic. Yet, it remains largely overlooked by the human neuroscience community, in stark contrast with the wealth of research investigating the brain. In this review, we argue that fMRI, traditionally used to image cerebral function, can be extended beyond the brain to help unravel spinal mechanisms involved in human behaviors. To this end, we first outline strategies that have been proposed to tackle the challenges inherent to spinal cord fMRI. Then, we discuss how they have been utilized to provide insights into the functional organization of spinal sensorimotor circuits, highlighting their potential to address fundamental and clinical questions. By summarizing guidelines and applications of spinal cord fMRI, we hope to stimulate and support further research into this promising yet underexplored field.</p

Dynamic functional connectivity of resting-state spinal cord fMRI reveals fine-grained intrinsic architecture

The neuroimaging community has shown tremendous interest in exploring the brain's spontaneous activity using functional magnetic resonance imaging (fMRI). On the contrary, the spinal cord has been largely overlooked despite its pivotal role in processing sensorimotor signals. Only a handful of studies have probed the organization of spinal resting-state fluctuations, always using static measures of connectivity. Many innovative approaches have emerged for analyzing dynamics of brain fMRI, but they have not yet been applied to the spinal cord, although they could help disentangle its functional architecture. Here, we leverage a dynamic connectivity method based on the clustering of hemodynamic-informed transients to unravel the rich dynamic organization of spinal resting-state signals. We test this approach in 19 healthy subjects, uncovering fine-grained spinal components and highlighting their neuroanatomical and physiological nature. We provide a versatile tool, the spinal innovation-driven co-activation patterns (SpiCiCAP) framework, to characterize spinal circuits during rest and task, as well as their disruption in neurological disorders

System for personalized robotic therapy and related methods

The present invention provides an apparatus and a method able to estimate motor improvement in real-time during three-dimensional rehabilitation tasks and to consequently dynamically personalize the therapy.The method can be carried out by a computer program. The use of said apparatus for restoring motor functions in a subject suffering from neuromotor impairment is also within the scope of the invention

How are Muscle Synergies Affected by Electromyography Pre-Processing?

Muscle synergies have been used for decades to explain a variety of motor behaviors, both in humans and animals and, more recently, to steer rehabilitation strategies. However, many sources of variability such as factorization algorithms, criteria for dimensionality reduction and data pre-processing constitute a major obstacle to the successful comparison of the results obtained by different research groups. Starting from the canonical EMG processing we determined how variations in filter cut-off frequencies and normalization methods, commonly found in literature, affect synergy weights and inter-subject similarity (ISS) using experimental data related to a 15-muscles upper-limb reaching task. Synergy weights were not significantly altered by either normalization (maximum voluntary contraction - MVC - or maximum amplitude of the signal - SELF) or band-pass filter ([20-500 Hz] or [50-500] Hz). Normalization did, however, alter the amount of variance explained by a set of synergies, which is a criterion often used for model order selection. Comparing different low-pass (LP) filters (0.5 Hz, 4 Hz, 10 Hz, 20 Hz cut-offs) we showed that increasing the low pass filter cut-off had the effect of decreasing the variance accounted for by a set number of synergies and affected individual muscle contributions. Extreme smoothing (i.e., LP cut-off 0.5 Hz) enhanced the contrast between active and inactive muscles but had an unpredictable effect on the ISS. The results presented here constitute a further step towards a thoughtful EMG pre-processing for the extraction of muscle synergies

Brain imaging of locomotion in neurological conditions

International audienc