Neurostimulation for Stroke Rehabilitation

Neurological injuries such as strokes can lead to important loss in motor function. Thanks to neuronal plasticity, some of the lost functionality may be recovered over time. However, the recovery process is often slow and incomplete, despite the most effective conventional rehabilitation therapies. As we improve our understanding of the rules governing activity-dependent plasticity, neuromodulation interventions are being developed to harness neural plasticity to achieve faster and more complete recovery. Here, we review the principles underlying stimulation-driven plasticity as well as the most commonly used stimulation techniques and approaches. We argue that increased spatiotemporal precision is an important factor to improve the efficacy of neurostimulation and drive a more useful neuronal reorganization. Consequently, closed-loop systems and optogenetic stimulation hold theoretical promise as interventions to promote brain repair after stroke.

Human CA1 and subiculum activity forecast stroke chronicity

ABSTRACTFollowing a stroke, the brain undergoes a process of neuronal reorganization to compensate for structural damage and cope with functionality loss. Increases in stroke-induced neurogenesis rates in the dentate gyrus and neural migration from the hippocampus towards the affected site have been observed, suggesting that the hippocampus is involved in functionality gains and neural reorganization. Despite the observed hippocampal contributions to structural changes, the hippocampal physiology for stroke recovery has been poorly characterized. To this end, we measured resting-state whole-brain activity from non-hippocampal stroke survivors (n=13) during functional MRI scanning. Analysis of multiple hippocampal subregions revealed that the voxel activity of hippocampal readout sites (CA1 and subiculum) forecast the patient’s chronicity stage stronger than early regions of the hippocampal circuit. Furthermore, we observed hemispheric-specific contributions to chronicity forecasting, raising the hypothesis that left and right hippocampus are functionally dissociable during recovery. In addition, we suggest that in contrast with whole-brain analysis, the monitoring of segregated and specialized sub-networks after stroke potentially reveals detailed aspects of stroke recovery. Altogether, our results shed light on the contribution of the subcortical-cortical interplay for neural reorganization and highlight new avenues for stroke rehabilitation.

Spinal Cord Injury

Pain from spinal cord injury (SCI) is one of the pain syndromes that is recalcitrant to treatment. It is often a result of injury associated with mechanical trauma and vascular compromise of the spinal cord parenchyma. SCI pain is associated with substantial impact on the patient’s life, interfering with activities of daily living, effective rehabilitation, and quality of life. The underlying mechanism for the development of SCI pain includes neuronal hyperexcitability, reduced inhibition, neuronal reorganization, and plasticity. The diverse factors associated with SCI pain warrant the need for an interdisciplinary approach tailored to the individual patient. The goals of treatment should encompass four domains: pain management, spinal rehabilitation, psychological treatment, and social and environmental modification.

TMS-induced neuronal plasticity enables targeted remodeling of visual cortical maps

Transcranial magnetic stimulation (TMS) has become a popular clinical method to modify cortical processing. The events underlying TMS-induced functional changes remain, however, largely unknown because current noninvasive recording methods lack spatiotemporal resolution or are incompatible with the strong TMS-associated electrical field. In particular, an answer to the question of how the relatively unspecific nature of TMS stimulation leads to specific neuronal reorganization, as well as a detailed picture of TMS-triggered reorganization of functional brain modules, is missing. Here we used real-time optical imaging in an animal experimental setting to track, at submillimeter range, TMS-induced functional changes in visual feature maps over several square millimeters of the brain’s surface. We show that high-frequency TMS creates a transient cortical state with increased excitability and increased response variability, which opens a time window for enhanced plasticity. Visual stimulation (i.e., 30 min of passive exposure) with a single orientation applied during this TMS-induced permissive period led to enlarged imprinting of the chosen orientation on the visual map across visual cortex. This reorganization was stable for hours and was characterized by a systematic shift in orientation preference toward the trained orientation. Thus, TMS can noninvasively trigger a targeted large-scale remodeling of fundamentally mature functional architecture in early sensory cortex.

Olfactory Loss and Regain: Lessons for Neuroplasticity

For the visual and auditory senses, an array of studies has reported on neuronal reorganization processes after sensory loss. In contrast to this, neuroplasticity has been investigated only scarcely after loss of the olfactory sense. The present review focuses on the current extent of literature on structural and functional neuroplasticity effects after loss, with a focus on magnetic resonance imaging–based studies. We also include findings on the regain of the olfactory sense, for example after successful olfactory training. Existing studies indicate that widespread structural changes beyond the level of the olfactory bulb occur in the brain after loss of the olfactory sense. Moreover, on a functional level, loss of olfactory input not only entails changes in olfaction-related brain regions but also in the trigeminal system. Existing evidence should be strengthened by future longitudinal studies, a more thorough investigation of the neuronal consequences of congenital anosmia, and the application of state-of-the-art neuroimaging methods, such as connectivity analyses and joint analyses of brain structure and function.

A Review on Locomotor Training after Spinal Cord Injury: Reorganization of Spinal Neuronal Circuits and Recovery of Motor Function

Locomotor training is a classic rehabilitation approach utilized with the aim of improving sensorimotor function and walking ability in people with spinal cord injury (SCI). Recent studies have provided strong evidence that locomotor training of persons with clinically complete, motor complete, or motor incomplete SCI induces functional reorganization of spinal neuronal networks at multisegmental levels at rest and during assisted stepping. This neuronal reorganization coincides with improvements in motor function and decreased muscle cocontractions. In this review, we will discuss the manner in which spinal neuronal circuits are impaired and the evidence surrounding plasticity of neuronal activity after locomotor training in people with SCI. We conclude that we need to better understand the physiological changes underlying locomotor training, use physiological signals to probe recovery over the course of training, and utilize established and contemporary interventions simultaneously in larger scale research studies. Furthermore, the focus of our research questions needs to change from feasibility and efficacy to the following: what are the physiological mechanisms that make it work and for whom? The aforementioned will enable the scientific and clinical community to develop more effective rehabilitation protocols maximizing sensorimotor function recovery in people with SCI.

Sensorimotor Cortex Reorganization in Alzheimer's Disease and Metal Dysfunction: A MEG Study

Objective. To verify whether systemic biometals dysfunctions affect neurotransmission in living Alzheimer’s disease (AD) patients.Methods. We performed a case-control study using magnetoencephalography to detect sensorimotor fields of AD patients, at rest and during median nerve stimulation. We analyzed position and amount of neurons synchronously activated by the stimulation in both hemispheres to investigate the capability of the primary somatosensory cortex to reorganize its circuitry disrupted by the disease. We also assessed systemic levels of copper, ceruloplasmin, non-Cp copper (i.e., copper not bound to ceruloplasmin), peroxides, transferrin, and total antioxidant capacity.Results. Patients’ sensorimotor generators appeared spatially shifted, despite no change of latency and strength, while spontaneous activity sources appeared unchanged. Neuronal reorganization was greater in moderately ill patients, while delta activity increased in severe patients. Non-Cp copper was the only biological variable appearing to be associated with patient sensorimotor transmission.Conclusions. Our data strengthen the notion that non-Cp copper, not copper in general, affects neuronal activity in AD.Significance. High plasticity in the disease early stages in regions controlling more commonly used body parts strengthens the notion that physical and cognitive activities are protective factors against progression of dementia.