Changes in functional connectivity of motor zones in the course of treatment with a regent multimodal complex exoskeleton in neurorehabilitation of post-stroke patients

The effect of a treatment course with a Regent multimodal complex exoskeleton (MCE) on the reorganization of cortical locomotor zones was studied in 14 patients with post-stroke hemiparesis, mainly in the chronic stage of the disease. Specific activation zones were identified prior to treatment in the primary sensorimotor and supplementary motor areas and the inferior parietal lobules of both affected and healthy hemispheres by functional magnetic resonance imaging (fMRI) used in a special passive sensorimotor paradigm. After a treatment course with the MCE, temporal characteristics of walking were found to improve, which was accompanied by a decrease in the activation zones of the inferior parietal lobules, especially in the healthy hemisphere, and a significant increase in the activation zones of the primary sensorimotor and supplementary motor areas. Significant changes in intrahemispheric and interhemispheric interactions were revealed by analyzing the functional connectivity of the zones under study before and after a course of treatment with the MCE.     

Evaluation of changes in the cortical gait control in post-stroke patients induced by the use of the “Regent” soft exoskeleton complex (SEC) by navigated transcranial magnetic stimulation

The mechanisms underlying the locomotion recovery in poststroke patients remain unknown. Navigated transcranial magnetic stimulation (nTMS) is a new method to evaluate the functional state of the motor system. Using of the “Regent” soft exoskeleton complex (SEC) allow to correct walking pattern significantly. The aim of this study was to evaluate the capability of nTMS to assess changes in gait cortical control using SEC in poststroke patients. 14 patients of the subcortical stroke (the mean age was 53.0 years, the mean time from stroke onset was 14.2 months) received 10 training sessions with SEC. The patients received nTMS before and after the sessions, as well as they were clinically evaluated by the Fugl–Meyer scale section for lower extremity and a 10-m walk test. Whereas a reliable reduction in the time of walking for 10 m was recorded after the sessions with the application of SEC, the Fugl-Meyer scale assessment remained unchanged. During nTMS, a reduction was recorded in the average latency of evoked motor response from the affected hemisphere, as well as various patterns of changes in the size and localization of cortical representations of the leg muscles. We have concluded that the nTMS method allowed us to identify the individual patterns of changes in the cortical representations of leg muscles as a result of the use of SEC in post-stroke patients with injuries in a group of locomotor system elements, thus identifying not only the fact of the undergoing neuroplastic processes, but also their direction.     

Activation of the sensorimotor cortex with the use of a device for the mechanical stimulation of the plantar support zones

Studies of the control movements mechanisms have been performed in the interest of space medicine were the basis for the development of the concept about the leading role of the support afferent input in the regulation of postural-tonic system of mammals. Introduction of functional magnetic resonance imaging (fMRI) made it possible to investigate in-vivo brain mapping during stimulation of support afferent input. The aim of our study was to investigate brain activation due to mechanical support stimulation of the soles with the special device "Korvit". 12 healthy participants (6 women, 6 men; average age = 28.8 years) were scanned. fMRI protocol for each person consisted of 2 different blocked paradigms: soles stimulation in stance imitation (1) and slow walking imitation (2) modes. The results were analyzed with statistical program SPM5 for each person and then for the whole group. In all our paradigms there was significant (P(correct) < 0.05 for cluster level) activation of primary somatosensory, premotor and dorsolateral cortex, insula. During the stance imitation mode, extensive prefrontal cortex activation was observed; during the slow walking imitation mode there was activation of different primary and secondary sensorimotor cortex areas.     

Specific activation of brain cortical areas in response to stimulation of the support receptors in healthy subjects and patients with focal lesions of the CNS

The space medicine data on the nature of motor disorders suggest an important role of the support inputs in the control of mammalian tonic and postural systems. Progress in functional magnetic resonance tomography (fMRT) makes it possible to perform in vivo analysis of various brain areas during stimulation of the support afferentation. Under these conditions, specific activation of the brain cortical areas was studied in 19 healthy subjects (with the mean age of 38 ± 15.13 years) and 23 patients (with the mean age of 53 ± 9.07 years) with focal CNS lesions (cortical-subcortical ischemic stroke). During scanning of subjects, the support areas of the soles of the feet were stimulated using a block design to simulate slow walking. In healthy subjects, significant activation was recorded (p < 0.05 at the cluster level) in the primary somatosensory cortex, premotor and dorsolateral prefrontal cortex, and insular lobe. In patients that had had a stroke, activation of the locomotion-controlling supraspinal systems clearly depended on the stage of the disease. In patients with a cortical-subcortical stroke, the pattern of contralateral activation of the sensorimotor locomotion predominated during motility rehabilitation.     

Alterations in Cortical Sensorimotor Connectivity following Complete Cervical Spinal Cord Injury: A Prospective Resting-State fMRI Study

Functional magnetic resonance imaging (fMRI) studies have demonstrated alterations during task-induced brain activation in spinal cord injury (SCI) patients. The interruption to structural integrity of the spinal cord and the resultant disrupted flow of bidirectional communication between the brain and the spinal cord might contribute to the observed dynamic reorganization (neural plasticity). However, the effect of SCI on brain resting-state connectivity patterns remains unclear. We undertook a prospective resting-state fMRI (rs-fMRI) study to explore changes to cortical activation patterns following SCI. With institutional review board approval, rs-fMRI data was obtained in eleven patients with complete cervical SCI (>2 years post injury) and nine age-matched controls. The data was processed using the Analysis of Functional Neuroimages software. Region of interest (ROI) based analysis was performed to study changes in the sensorimotor network using pre- and post-central gyri as seed regions. Two-sampled t-test was carried out to check for significant differences between the two groups. SCI patients showed decreased functional connectivity in motor and sensory cortical regions when compared to controls. The decrease was noted in ipsilateral, contralateral, and interhemispheric regions for left and right precentral ROIs. Additionally, the left postcentral ROI demonstrated increased connectivity with the thalamus bilaterally in SCI patients. Our results suggest that cortical activation patterns in the sensorimotor network undergo dynamic reorganization following SCI. The presence of these changes in chronic spinal cord injury patients is suggestive of the inherent neural plasticity within the central nervous system.     

mGluR5 Ablation in Cortical Glutamatergic Neurons Increases Novelty-Induced Locomotion

The group I metabotropic glutamate receptor 5 (mGluR5) has been implicated in the pathology of various neurological disorders including schizophrenia, ADHD, and autism. mGluR5-dependent synaptic plasticity has been described at a variety of neural connections and its signaling has been implicated in several behaviors. These behaviors include locomotor reactivity to novel environment, sensorimotor gating, anxiety, and cognition. mGluR5 is expressed in glutamatergic neurons, inhibitory neurons, and glia in various brain regions. In this study, we show that deleting mGluR5 expression only in principal cortical neurons leads to defective cannabinoid receptor 1 (CB1R) dependent synaptic plasticity in the prefrontal cortex. These cortical glutamatergic mGluR5 knockout mice exhibit increased novelty-induced locomotion, and their locomotion can be further enhanced by treatment with the psychostimulant methylphenidate. Despite a modest reduction in repetitive behaviors, cortical glutamatergic mGluR5 knockout mice are normal in sensorimotor gating, anxiety, motor balance/learning and fear conditioning behaviors. These results show that mGluR5 signaling in cortical glutamatergic neurons is required for precisely modulating locomotor reactivity to a novel environment but not for sensorimotor gating, anxiety, motor coordination, several forms of learning or social interactions.     

Lesions of the Basal forebrain cholinergic system impair task acquisition and abolish cortical plasticity associated with motor skill learning

The contribution of the basal forebrain cholinergic system in mediating plasticity of cortical sensorimotor representations was examined in the context of normal learning. The effects of specific basal forebrain cholinergic lesions upon cortical reorganization associated with learning a skilled motor task were investigated, addressing, for the first time, the functional consequences of blocking cortical map plasticity. Results demonstrate that disrupting basal forebrain cholinergic function disrupts cortical map reorganization and impairs motor learning. Cholinergic lesions do not impair associative fear learning or overall sensorimotor function. These results support the hypothesis that the basal forebrain cholinergic system may be specifically implicated in forms of learning requiring plasticity of cortical representations.     

Driving plasticity in human adult motor cortex is associated with improved motor function after brain injury

Changes in somatosensory input can remodel human cortical motor organization, yet the input characteristics that promote reorganization and their functional significance have not been explored. Here we show with transcranial magnetic stimulation that sensory-driven reorganization of human motor cortex is highly dependent upon the frequency, intensity, and duration of stimulus applied. Those patterns of input associated with enhanced excitability (5 Hz, 75% maximal tolerated intensity for 10 min) induce stronger cortical activation to fMRI. When applied to acutely dysphagic stroke patients, swallowing corticobulbar excitability is increased mainly in the undamaged hemisphere, being strongly correlated with an improvement in swallowing function. Thus, input to the human adult brain can be programmed to promote beneficial changes in neuroplasticity and function after cerebral injury.     

Noradrenergic modulation of tactile responses in rat cortex. Current source-density and unit analyses

This study describes the noradrenergic modulation of tactile afferent information in the sensorimotor cortex of urethane-anesthetized rats. Synaptic and spike responses to a mechanical stimulation of the hand palm were evaluated by means of current source-density analysis and unit activity recording in all cortical layers. Results showed that activation of the locus coeruleus decreased and shortened afferent synaptic excitation in supragranular, but not in deep layers. On the average, unit responses exhibited facilitated latency, moderately increased amplitude, enhanced postexcitatory inhibition and synchronization of responses across layers. The apparent paradox of this global phasic facilitation correlated with a decrease in input synaptic currents was discussed according to hypotheses which might explain its functional significance.     

fMRI responses of the brain during active and passive movements in left-handed subjects

The hemodynamic (magnetic resonance imaging, fMRI, 3T) brain responses were studied in 15 left-handed healthy subjects performing active and passive movements of the dominant and non-dominant hands. Group and individual fMRI responses to the motor load were analyzed. It was found that, during the active movements of dominant and non-dominant hands, the main activation cluster appeared in the preand postcentral gyrus of the contralateral hemisphere and which topographically similar during active and passive movements. The activation cluster of greater volume was identified in these areas; the response was more diffused during the non-dominant hand movements in comparison with the dominant hand. During passive movements, the cortical activation clusters of a smaller volume in comparison with the active movements were found, which was expressed most clearly during the performance of non-dominant hand movements and could reflect the weakening of the control from the cortical structures in these conditions.     

Activation of the sensorimotor cortex using a device for mechanical stimulation of the plantar support zones

Numerous studies on the mechanisms of the motor control carried out in the interests of space medicine resulted in a concept on the leading role of the support afferent input in the regulation of the postural tonic system in mammals. The implementation of functional magnetic resonance imaging (fMRI) has permitted in vivo brain mapping during stimulation of the support afferent input. The goal of this study was to identify activated regions in the brain during mechanical stimulation of the plantar support zones in different modes using a special Korvit simulator. Twelve healthy volunteers (six women and six men) aged from 22 to 42 years were studied using fMRI, each of them was scanned once. The fMRI protocol for each subject consisted of two different blocked paradigms: (1) with the soles of a subject stimulated in an imitated standing mode and (2) with the soles stimulated in an imitation slow-walking mode. The patterns of activation in each mode were analyzed using the SPM5 statistical software package for each subject and for the group as a whole. All the paradigms showed significant activation (p _correct < 0. 05 at the cluster level) in the primary somatosensory, premotor, dorsolateral and prefrontal cortices, as well as in the insula. The involvement of the prefrontal cortex during simulation of standing and a broad involvement of the primary and secondary sensorimotor cortices during simulation of slow walking were found.     

Cortical plasticity in patients with median nerve lesions studied with MEG

We have previously shown age- and time-dependent effects on brain activity in the primary somatosensory cortex (SI), in a functional magnetic resonance imaging (fMRI) study of patients with median nerve injury. Whereas fMRI measures the hemodynamic changes in response to increased neural activity, magnetoencephalography (MEG) offers a more concise way of examining the evoked response, with superior temporal resolution. We therefore wanted to combine these imaging techniques to gain additional knowledge of the plasticity processes in response to median nerve injury. Nine patients with median nerve trauma at the wrist were examined with MEG. The N1 and P1 responses at stimulation of the injured median nerve at the wrist were lower in amplitude compared to the healthy side (p?larger N1 amplitude (p?p?p?increased MEG response amplitude to ulnar nerve stimulation. This can be interpreted as a sign of brain plasticity.     

Enhancing Sensorimotor Activity by Controlling Virtual Objects with Gaze

This fMRI work studies brain activity of healthy volunteers who manipulated a virtual object in the context of a digital game by applying two different control methods: using their right hand or using their gaze. The results show extended activations in sensorimotor areas, not only when participants played in the traditional way (using their hand) but also when they used their gaze to control the virtual object. Furthermore, with the exception of the primary motor cortex, regional motor activity was similar regardless of what the effector was: the arm or the eye. These results have a potential application in the field of the neurorehabilitation as a new approach to generate activation of the sensorimotor system to support the recovery of the motor functions.     

Timing and sequence of brain activity in top-down control of visual-spatial attention

Recent brain imaging studies using functional magnetic resonance imaging (fMRI) have implicated a frontal-parietal network in the top-down control of attention. However, little is known about the timing and sequence of activations within this network. To investigate these timing questions, we used event-related electrical brain potentials (ERPs) and a specially designed visual-spatial attentional-cueing paradigm, which were applied as part of a multi-methodological approach that included a closely corresponding event-related fMRI study using an identical paradigm. In the first 400 ms post cue, attention-directing and control cues elicited similar general cue-processing activity, corresponding to the more lateral subregions of the frontal-parietal network identified with the fMRI. Following this, the attention-directing cues elicited a sustained negative-polarity brain wave that was absent for control cues. This activity could be linked to the more medial frontal–parietal subregions similarly identified in the fMRI as specifically involved in attentional orienting. Critically, both the scalp ERPs and the fMRI-seeded source modeling for this orienting-related activity indicated an earlier onset of frontal versus parietal contribution (∼400 versus ∼700 ms). This was then followed (∼800–900 ms) by pretarget biasing activity in the region-specific visual-sensory occipital cortex. These results indicate an activation sequence of key components of the attentional-control brain network, providing insight into their functional roles. More specifically, these results suggest that voluntary attentional orienting is initiated by medial portions of frontal cortex, which then recruit medial parietal areas. Together, these areas then implement biasing of region-specific visual-sensory cortex to facilitate the processing of upcoming visual stimuli.     

Plasticity of cortical structures under the conditions of neurological deficit accompanied by a disorder of hand movement: Modern approaches to rehabilitation

Reorganization of cortical structures under the conditions of neurological deficit is an important interdisciplinary problem. This problem closely unites neurologists, physiologists, and mathematicians, which makes it possible to develop rehabilitation measures taking into account individual features. Fine hand movements under the conditions of motor pathology are an ideal model for investigation of neuroplasticity.     

Interaction of Motor Training and Intermittent Theta Burst Stimulation in Modulating Motor Cortical Plasticity: Influence of BDNF Val66Met Polymorphism

Cortical physiology in human motor cortex is influenced by behavioral motor training (MT) as well as repetitive transcranial magnetic stimulation protocol such as intermittent theta burst stimulation (iTBS). This study aimed to test whether MT and iTBS can interact with each other to produce additive changes in motor cortical physiology. We hypothesized that potential interaction between MT and iTBS would be dependent on BDNF Val66Met polymorphism, which is known to affect neuroplasticity in the human motor cortex. Eighty two healthy volunteers were genotyped for BDNF polymorphism. Thirty subjects were assigned for MT alone, 23 for iTBS alone, and 29 for MT + iTBS paradigms. TMS indices for cortical excitability and motor map areas were measured prior to and after each paradigm. MT alone significantly increased the motor cortical excitability and expanded the motor map areas. The iTBS alone paradigm also enhanced excitability and increased the motor map areas to a slightly greater extent than MT alone. A combination of MT and iTBS resulted in the largest increases in the cortical excitability, and the representational motor map expansion of MT + iTBS was significantly greater than MT or iTBS alone only in Val/Val genotype. As a result, the additive interaction between MT and iTBS was highly dependent on BDNF Val66Met polymorphism. Our results may have clinical relevance in designing rehabilitative strategies that combine therapeutic cortical stimulation and physical exercise for patients with motor disabilities.     

Neural activation and functional connectivity during motor imagery of bimanual everyday actions

Bimanual actions impose intermanual coordination demands not present during unimanual actions. We investigated the functional neuroanatomical correlates of these coordination demands in motor imagery (MI) of everyday actions using functional magnetic resonance imaging (fMRI). For this, 17 participants imagined unimanual actions with the left and right hand as well as bimanual actions while undergoing fMRI. A univariate fMRI analysis showed no reliable cortical activations specific to bimanual MI, indicating that intermanual coordination demands in MI are not associated with increased neural processing. A functional connectivity analysis based on psychophysiological interactions (PPI), however, revealed marked increases in connectivity between parietal and premotor areas within and between hemispheres. We conclude that in MI of everyday actions intermanual coordination demands are primarily met by changes in connectivity between areas and only moderately, if at all, by changes in the amount of neural activity. These results are the first characterization of the neuroanatomical correlates of bimanual coordination demands in MI. Our findings support the assumed equivalence of overt and imagined actions and highlight the differences between uni- and bimanual actions. The findings extent our understanding of the motor system and may aid the development of clinical neurorehabilitation approaches based on mental practice.     

Human-Robot Interaction: Does Robotic Guidance Force Affect Gait-Related Brain Dynamics during Robot-Assisted Treadmill Walking?

In order to determine optimal training parameters for robot-assisted treadmill walking, it is essential to understand how a robotic device interacts with its wearer, and thus, how parameter settings of the device affect locomotor control. The aim of this study was to assess the effect of different levels of guidance force during robot-assisted treadmill walking on cortical activity. Eighteen healthy subjects walked at 2 km.h^-1 on a treadmill with and without assistance of the Lokomat robotic gait orthosis. Event-related spectral perturbations and changes in power spectral density were investigated during unassisted treadmill walking as well as during robot-assisted treadmill walking at 30%, 60% and 100% guidance force (with 0% body weight support). Clustering of independent components revealed three clusters of activity in the sensorimotor cortex during treadmill walking and robot-assisted treadmill walking in healthy subjects. These clusters demonstrated gait-related spectral modulations in the mu, beta and low gamma bands over the sensorimotor cortex related to specific phases of the gait cycle. Moreover, mu and beta rhythms were suppressed in the right primary sensory cortex during treadmill walking compared to robot-assisted treadmill walking with 100% guidance force, indicating significantly larger involvement of the sensorimotor area during treadmill walking compared to robot-assisted treadmill walking. Only marginal differences in the spectral power of the mu, beta and low gamma bands could be identified between robot-assisted treadmill walking with different levels of guidance force. From these results it can be concluded that a high level of guidance force (i.e., 100% guidance force) and thus a less active participation during locomotion should be avoided during robot-assisted treadmill walking. This will optimize the involvement of the sensorimotor cortex which is known to be crucial for motor learning.     

A Resting-State Functional Magnetic Resonance Imaging Study of Acute Carbon Monoxide Poisoning in Humans

The objective of this study was to evaluate the brain function characteristics of carbon monoxide poisoning patients using resting-state functional magnetic resonance imaging (fMRI) method. For this purpose, 12 carbon monoxide poisoning patients and healthy controls were subjected to resting-state fMRI scans separately. A regional homogeneity (ReHo) approach was used to analyze the brain function in carbon monoxide poisoning patients. Compared with control group, the value of ReHo in carbon monoxide poisoning group showed distinct decrease in bilateral superior frontal gyrus, middle frontal gyrus, right cuneus, left middle temporal gyrus, right insula, and cerebellum. Therefore, it was concluded that the brain functions in carbon monoxide poisoning patients were abnormal under the resting-state. The cuneate lobe function may indicate the degree of brain hypoxia and strengthening the cerebellar function training may promote the rehabilitation process.     

Perceiving time to collision activates the sensorimotor cortex

The survival of many animals hinges upon their ability to avoid collisions with other animals or objects, or to precisely control the timing of collisions. Optical expansion provides a compelling impression of object approach and in principle can provide the basis for judgments of time to collision (TTC) [1]. It has been demonstrated that pigeons [2] and houseflies [3] have neural systems that can initiate rapid coordinated actions on the basis of optical expansion. In the case of humans, the linkage between judgments of TTC and coordinated action has not been established at a cortical level. Using functional magnetic resonance imaging (fMRI), we identified superior-parietal and motor-cortex areas that are selectively active during perceptual TTC judgments, some of which are normally involved in producing reach-to-grasp responses. These activations could not be attributed to actual movement of participants. We demonstrate that networks involved in the computational problem of extracting TTC from expansion information have close correspondence with the sensorimotor systems that would be involved in preparing a timed motor response, such as catching a ball or avoiding collision.