Cerebral strokes can disrupt descending commands from motor cortical areas to the spinal cord, which can result in permanent motor deficits of the arm and hand. However, below the lesion, the spinal ...circuits that control movement remain intact and could be targeted by neurotechnologies to restore movement. Here we report results from two participants in a first-in-human study using electrical stimulation of cervical spinal circuits to facilitate arm and hand motor control in chronic post-stroke hemiparesis ( NCT04512690 ). Participants were implanted for 29 d with two linear leads in the dorsolateral epidural space targeting spinal roots C3 to T1 to increase excitation of arm and hand motoneurons. We found that continuous stimulation through selected contacts improved strength (for example, grip force +40% SCS01; +108% SCS02), kinematics (for example, +30% to +40% speed) and functional movements, thereby enabling participants to perform movements that they could not perform without spinal cord stimulation. Both participants retained some of these improvements even without stimulation and no serious adverse events were reported. While we cannot conclusively evaluate safety and efficacy from two participants, our data provide promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke.
Getting Neurorehabilitation Right Krakauer, John W.; Carmichael, S. Thomas; Corbett, Dale ...
Neurorehabilitation and neural repair,
10/2012, Letnik:
26, Številka:
8
Journal Article
Recenzirano
Animal models suggest that a month of heightened plasticity occurs in the brain after stroke, accompanied by most of the recovery from impairment. This period of peri-infarct and remote plasticity is ...associated with changes in excitatory/inhibitory balance and the spatial extent and activation of cortical maps and structural remodeling. The best time for experience and training to improve outcome is unclear. In animal models, very early (<5 days from onset) and intense training may lead to increased histological damage. Conversely, late rehabilitation (>30 days) is much less effective both in terms of outcome and morphological changes associated with plasticity. In clinical practice, rehabilitation after disabling stroke involves a relatively brief period of inpatient therapy that does not come close to matching intensity levels investigated in animal models and includes the training of compensatory strategies that have minimal impact on impairment. Current rehabilitation treatments have a disappointingly modest effect on impairment early or late after stroke. Translation from animal models will require the following: (1) substantial increases in the intensity and dosage of treatments offered in the first month after stroke with an emphasis on impairment; (2) combinational approaches such as noninvasive brain stimulation with robotics, based on current understanding of motor learning and brain plasticity; and (3) research that emphasizes mechanistic phase II studies over premature phase III clinical trials.
Background: Post‐treatment platelet reactivity (PR) is associated with ischemic and bleeding events in patients receiving P2Y12 receptor antagonists.
Objectives: We aimed to study the relationship ...between post‐treatment PR after a 60‐mg loading dose (LD) of prasugrel and 1‐year thrombotic and bleeding events.
Method: Patients were prospectively included in this multicenter study if they had a successful percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and received prasugrel. The platelet reactivity index (PRI) was measured using the Vasodilator‐Stimulated Phosphoprotein index (VASP) after a prasugrel LD. Endpoints included the rate of thrombotic events and bleeding events at 1 year.
Results: Among the 301 patients enrolled, 9 (3%) were lost to follow‐up at 1 year. The rates of thrombotic and bleeding events at 1 year were of 7.5% and 6.8%, respectively. Receiver‐operating curve (ROC) analysis demonstrated an optimal cut‐off value of 53.5% of PRI to predict thrombotic events at 1 year. Using this cut‐off value we observed that patients exhibiting high on‐treatment platelet reactivity (HTPR) had a higher rate of thrombotic events (22.4% vs. 2.9%; P < 0.001). In parallel the optimal cut‐off value of PRI to predict bleeding was 16%. Patients with a PRI ≤ 16% had a higher rate of bleeding events compared with those with a PRI > 16% (15.6% vs. 3.3%; P < 0.001). In multivariate analysis, the PRI predicted both thrombotic and bleeding events (OR: 1.44, 95% confidence interval CI: 1.2–1.72; P < 0.001 and OR: 0.75, 95% CI: 0.59–0.96; P = 0.024 respectively, per 10% increase).
Conclusion: Platelet reactivity measurement after a prasugrel LD predicts both ischemic and bleeding events at 1 year follow‐up for ACS patients undergoing PCI.
Abstract Recovery of motor function in brain and spinal cord disorders is an area of active research that seeks to maximize improvement after an episode of neuronal death or dysfunction. Recovery ...likely results from changes in structure and function of undamaged neurons, and this plasticity is a target for rehabilitative strategies. Sensory and motor function are mapped onto brain regions somatotopically, and these maps have been demonstrated to change in response to experience, particularly in development, but also in adults after injury. The map concept, while appealing, is limited, as the fine structure of the motor representation is not well-ordered somatotopically. But after stroke, the spared areas of the main cortical map for movement appear to participate in representing affected body parts, expanding representation in an experience-dependent manner. This occurs in both animal models and human clinical trials, although one must be cautious in comparing the results of invasive electrophysiological techniques with non-invasive ones such as transcranial magnetic stimulation. Developmental brain disorders, such as cerebral palsy, and embryonic abnormalities, such as dysmelia, demonstrate the potential of the human brain to remap the motor system. Future therapies may be able to use that potential to maximize recovery.
Key points
Muscle weakness after stroke results from damage to corticospinal fibres that structurally and functionally connect cerebral cortex to the spinal cord.
Here, we show an asymmetry in ...corticospinal recruitment of spinal motor neurons that is linked to maximal voluntary output of hand muscles weakened by stroke. Spike timing‐dependent plasticity of synapses between corticospinal and spinal motor neurons transiently reversed recruitment failures in some survivors. These modulatory effects were strongly associated with recruitment asymmetry and hand impairment.
Our findings highlight the functional relevance of spinal motor neuron recruitment by corticospinal inputs and the viability of corticospinal motor neuronal synapses for restoring activation of lower motor neurons after stroke.
Corticospinal input to spinal motor neurons is structurally and functionally altered by hemiparetic stroke. The pattern and extent to which corticospinal recruitment of spinal motor neurons is reorganized and whether such changes are linked to the severity of motor impairments is not well understood. Here, we performed experiments using the triple stimulation technique to quantify corticospinal recruitment of spinal motor neurons serving paretic and non‐paretic intrinsic hand muscles of humans with longstanding motor impairment secondary to stroke (n = 13). We also examined whether recruitment failures could be transiently reversed by strengthening corticospinal–motoneuronal synaptic connectivity via targeted, temporally controlled non‐invasive stimulation to elicit spike timing‐dependent plasticity (STDP). Asymmetries were detected in corticospinal recruitment of spinal motor neurons, central conduction time and motor‐evoked potential (MEP) latency. However, only recruitment asymmetry correlated with maximal voluntary motor output from the paretic hand. STDP‐like effects were observed as an increase in spinal motor neuron recruitment. Control experiments to isolate the locus of plasticity demonstrated a modulation in MEPs elicited by electrical stimulation of primary motor cortex but not F‐wave size or persistence, suggesting that plasticity was mediated through enhanced efficacy of residual corticospinal–motor neuronal synapses. The modulation in recruitment was strongly associated with baseline recruitment asymmetry and impairment severity. Our findings demonstrate that asymmetry in corticospinal recruitment of spinal motor neurons is directly related to impairments experienced by stroke survivors. These recruitment deficits may be partially and transiently reversed by spike timing‐dependent plasticity of synapses between upper and lower motor neurons in the spinal cord, downstream of supraspinal circuits damaged by stroke.
Key points
Muscle weakness after stroke results from damage to corticospinal fibres that structurally and functionally connect cerebral cortex to the spinal cord.
Here, we show an asymmetry in corticospinal recruitment of spinal motor neurons that is linked to maximal voluntary output of hand muscles weakened by stroke. Spike timing‐dependent plasticity of synapses between corticospinal and spinal motor neurons transiently reversed recruitment failures in some survivors. These modulatory effects were strongly associated with recruitment asymmetry and hand impairment.
Our findings highlight the functional relevance of spinal motor neuron recruitment by corticospinal inputs and the viability of corticospinal motor neuronal synapses for restoring activation of lower motor neurons after stroke.
Background. Robot-assisted therapy provides high-intensity arm rehabilitation that can significantly reduce stroke-related upper extremity (UE) deficits. Motor improvement has been shown at the ...joints trained, but generalization to real-world function has not been profound. Objective. To investigate the efficacy of robot-assisted therapy combined with therapist-assisted task training versus robot-assisted therapy alone on motor outcomes and use in participants with moderate to severe chronic stroke-related arm disability. Methods. This was a single-blind randomized controlled trial of two 12-week robot-assisted interventions; 45 participants were stratified by Fugl-Meyer (FMA) impairment (mean 21 ± 1.36) to 60 minutes of robot therapy (RT; n = 22) or 45 minutes of RT combined with 15 minutes therapist-assisted transition-to-task training (TTT; n = 23). The primary outcome was the mean FMA change at week 12 using a linear mixed-model analysis. A subanalysis included the Wolf Motor Function Test (WMFT) and Stroke Impact Scale (SIS), with significance P <.05. Results. There was no significant 12-week difference in FMA change between groups, and mean FMA gains were 2.87 ± 0.70 and 4.81 ± 0.68 for RT and TTT, respectively. TTT had greater 12-week secondary outcome improvements in the log WMFT (−0.52 ± 0.06 vs −0.18 ± 0.06; P = .01) and SIS hand (20.52 ± 2.94 vs 8.27 ± 3.03; P = .03). Conclusion. Chronic UE motor deficits are responsive to intensive robot-assisted therapy of 45 or 60 minutes per session duration. The replacement of part of the robotic training with nonrobotic tasks did not reduce treatment effect and may benefit stroke-affected hand use and motor task performance.
Clinical recovery after stroke can be significant and has been attributed to plastic reorganization and recruitment of novel areas previously not engaged in a given task. As equivocal results have ...been reported in studies using single imaging or electrophysiological methods, here we applied an integrative multimodal approach to a group of well-recovered chronic stroke patients (n = 11; aged 50–81 years) with left capsular lesions. Focal activation during recovered hand movements was assessed with EEG spectral analysis and H215O-PET with EMG monitoring, cortico–cortical connectivity with EEG coherence analysis (cortico–cortical coherence) and corticospinal connectivity with transcranial magnetic stimulation (TMS). As seen from comparisons with age-matched controls, our patients showed enhanced recruitment of the lateral premotor cortex of the lesioned hemisphere Brodmann area (BA) 6, lateral premotor and to a lesser extent primary sensorimotor and parietal cortex of the contralesional hemisphere (CON-H; BA 4 and superior parietal lobule) and left cerebellum (patients versus controls, Z > 3.09). EEG coherence analysis showed that after stroke cortico–cortical connections were reduced in the stroke hemisphere but relatively increased in the CON-H (ANOVA, contrast analysis, P < 0.05), suggesting a shift of functional connectivity towards the CON-H. Nevertheless, fast conducting corticospinal transmission originated exclusively from the lesioned hemisphere. No direct ipsilateral motor evoked potentials (MEPs) could be elicited with TMS over the contralesional primary motor cortex (iM1) in stroke patients. We conclude that (i) effective recovery is based on enhanced utilization of ipsi- and contralesional resources, (ii) basic corticospinal commands arise from the lesioned hemisphere without recruitment of (‘latent’) uncrossed corticospinal tract fibres and (iii) increased contralesional activity probably facilitates control of recovered motor function by operating at a higher-order processing level, similar to but not identical with the extended network concerned with complex movements in healthy subjects.
The default mode of the motor system is a coupling between limbs. However, in some movements, a decoupling is required and thus calls for selection and facilitation/inhibition processes. Here, we ...investigate the relative contribution of recruitment versus selection processes to the overall processing complexity. To this aim we proposed a new multilimb reaction-time task (MUL-RT). Simple, choice and normalized (choice minus simple) RT were analysed together with error rates in thirty-six young adults for 15 coordination modes including all possible configuration of limb recruitment. Simple and normalized RTs were respectively assumed to be indicative of the recruitment and selection processes. Results supported a model of coupling/decoupling interactions respectively reporting weak, intermediate and strong interaction for selecting diagonal, ipsilateral and homologous limbs. Movement laterality (left vs. right) had no effect on selection complexity, whereas selecting upper limbs was less challenging than selecting lower limbs. Results in the different coordination modes suggested that recruitment complexity decreased as follows: 3 limbs = 4 limbs>2 limbs (homologous, ipsilateral and diagonal)>1 limb, and selection complexity as follows: 2 diagonal limbs>3 limbs>2 ipsilateral limbs>1 limb = 2 homologous limbs>4 limbs. Based on these ordinal scales of recruitment and selection complexity, we extrapolated the overall processing complexity of the simple and choice MUL-RT. This method was efficient in reproducing the absolute results we obtained on a ratio scale (ms) and demonstrated that processing complexity in simple RT was mainly governed by the 'recruitment principle' (the more limbs recruited the lower the performance), whereas contributions of recruitment and 'selection principle' (nature of the coordination determines performance) to overall processing complexity were similar in choice RT.
Subjective sensory experiences are constructed by the integration of afferent sensory information with information about the uniquely personal internal cognitive state. The insular cortex is ...anatomically positioned to serve as one potential interface between afferent processing mechanisms and more cognitively oriented modulatory systems. However, the role of the insular cortex in such modulatory processes remains poorly understood. Two individuals with extensive lesions to the insula were examined to better understand the contribution of this brain region to the generation of subjective sensory experiences. Despite substantial differences in the extent of the damage to the insular cortex, three findings were common to both individuals. First, both subjects had substantially higher pain intensity ratings of acute experimental noxious stimuli than age-matched control subjects. Second, when pain-related activation of the primary somatosensory cortex was examined during left- and right-sided stimulation, both individuals exhibited dramatically elevated activity of the primary somatosensory cortex ipsilateral to the lesioned insula in relation to healthy control subjects. Finally, both individuals retained the ability to evaluate pain despite substantial insular damage and no evidence of detectable insular activity. Together, these results indicate that the insula may be importantly involved in tuning cortical regions to appropriately use previous cognitive information during afferent processing. Finally, these data suggest that a subjectively available experience of pain can be instantiated by brain mechanisms that do not require the insular cortex.
Cerebral cortical activity is heavily influenced by interactions with the basal ganglia. These interactions occur via cortico-basal ganglia-thalamo-cortical loops. The putamen is one of the major ...sites of cortical input into basal ganglia loops and is frequently activated during pain. This activity has been typically associated with the processing of pain-related motor responses. However, the potential contribution of putamen to the processing of sensory aspects of pain remains poorly characterized. In order to more directly determine if the putamen can contribute to sensory aspects of pain, nine individuals with lesions involving the putamen underwent both psychophysical and functional imaging assessment of perceived pain and pain-related brain activation. These individuals exhibited intact tactile thresholds, but reduced heat pain sensitivity and widespread reductions in pain-related cortical activity in comparison with 14 age-matched healthy subjects. Using magnetic resonance imaging to assess structural connectivity in healthy subjects, we show that portions of the putamen activated during pain are connected not only with cortical regions involved in sensory-motor processing, but also regions involved in attention, memory and affect. Such a framework may allow cognitive information to flow from these brain areas to the putamen where it may be used to influence how nociceptive information is processed. Taken together, these findings indicate that the putamen and the basal ganglia may contribute importantly to the shaping of an individual subjective sensory experience by utilizing internal cognitive information to influence activity of large areas of the cerebral cortex.
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