Reinforcement Learning Is Impaired in the Sub-acute Post-stroke Period.

Background: Neurorehabilitation approaches are frequently predicated on motor learning principles. However, much is left to be understood of how different kinds of motor learning are affected by stroke causing hemiparesis. Here we asked if two kinds of motor learning often employed in rehabilitation, (1) reinforcement learning and (2) error-based adaptation, are altered at different times after stroke. Methods: In a cross-sectional design, we compared learning in two groups of patients with stroke, matched for their baseline motor execution deficit on the paretic side. The early group was tested within 3 months following stroke (N = 35) and the late group was tested more than 6 months after stroke (N = 30). Two types of task were studied: one based on reinforcement learning and the other on error-based learning. Results: We found that reinforcement learning was impaired in the early but not the late group, whereas error-based learning was unaffected compared to controls. These findings could not be attributed to differences in baseline execution, cognitive impairment, gender, age, or lesion volume and location. Conclusions: The presence of a specific impairment in reinforcement learning in the first 3 months after stroke has important implications for rehabilitation. It might be necessary to either increase the amount of reinforcement feedback given early or even delay onset of certain forms of rehabilitation training, e.g., like constraint-induced movement therapy, and instead emphasize others forms of motor learning in this early time period. A deeper understanding of stroke-related changes in motor learning capacity has the potential to facilitate the development of new, more precise treatment interventions.

No Polarity-specific Modulation of Prefrontal-to-M1 Interhemispheric Inhibition by Transcranial Direct Current Stimulation Over the Lateral Prefrontal Cortex.

The lateral prefrontal cortex (PFC) plays a variety of crucial roles in higher-order cognitive functions. Previous works have attempted to modulate lateral PFC function by applying non-invasive transcranial direct current stimulation (tDCS) and demonstrated positive effects on performance of tasks involving cognitive processes. The neurophysiological underpinning of the stimulation effects, however, remain poorly understood. Here, we explored the neurophysiological after-effects of tDCS over the lateral PFC by assessing changes in the magnitude of interhemispheric inhibition from the lateral PFC to the contralateral primary motor cortex (PFC-M1 IHI). Using a dual-site transcranial magnetic stimulation paradigm, we assessed PFC-M1 IHI before and after the application of tDCS over the right lateral PFC. We conducted a double-blinded, crossover, and counterbalanced design where 15 healthy volunteers participated in three sessions during which they received either anodal, cathodal, and sham tDCS. In order to determine whether PFC-M1 IHI could be modulated at all, we completed the same assessment on a separate group of 15 participants as they performed visuo-motor reaction tasks that likely engage the lateral PFC. The results showed that tDCS over the right lateral PFC did not modulate the magnitude of PFC-M1 IHI, whereas connectivity changed when Go/NoGo decisions were implemented in reactions during the motor tasks. Although PFC-M1 IHI is sensitive enough to be modulated by behavioral manipulations, tDCS over the lateral PFC does not have substantial modulatory effects on PFC to M1 functional connectivity, or at least not to the degree that can be detected with this measure.

Dissociation between abnormal motor synergies and impaired reaching dexterity after stroke.

Most patients with stroke experience motor deficits, usually referred to collectively as hemiparesis. Although hemiparesis is one of the most common and clinically recognizable motor abnormalities, it remains undercharacterized in terms of its behavioral subcomponents and their interactions. Hemiparesis comprises both negative and positive motor signs. Negative signs consist of weakness and loss of motor control (dexterity), whereas positive signs consist of spasticity, abnormal resting posture, and intrusive movement synergies (abnormal muscle co-activations during voluntary movement). How positive and negative signs interact, and whether a common mechanism generates them, remains poorly understood. Here, we used a planar, arm-supported reaching task to assess poststroke arm dexterity loss, which we compared with the Fugl-Meyer stroke scale; a measure primarily reflecting abnormal synergies. We examined 53 patients with hemiparesis after a first-time ischemic stroke. Reaching kinematics were markedly more impaired in patients with subacute (<3 mo) compared to chronic (>6 mo) stroke even for similar Fugl-Meyer scores. This suggests a dissociation between abnormal synergies (reflected in the Fugl-Meyer scale) and loss of dexterity, which in turn suggests different underlying mechanisms. Moreover, dynamometry suggested that Fugl-Meyer scores capture weakness as well as abnormal synergies, in line with these two deficits sharing a neural substrate. These findings have two important implications: First, clinical studies that test for efficacy of rehabilitation interventions should specify which component of hemiparesis they are targeting and how they propose to measure it. Metrics used widely for this purpose may not always be chosen appropriately. For example, as we show here, the Fugl-Meyer score may capture some hemiparesis components (abnormal synergies and weakness) but not others (loss of dexterity). Second, there may be an opportunity to design rehabilitation interventions to address specific subcomponents of hemiparesis.NEW & NOTEWORTHY Motor impairment is common after stroke and comprises reduced dexterity, weakness, and abnormal muscle synergies. Here we report that, when matched on an established synergy and weakness scale (Fugl-Meyer), patients with subacute stroke have worse reaching dexterity than chronic ones. This result suggests that the components of hemiparesis are dissociable and have separable mechanisms and, thus, may require distinct assessments and treatments.

Altered corticomotor latencies but normal motor neuroplasticity in concussed athletes.

Persistent cognitive, affective, and motor symptoms have been associated with sports-related concussions including several neurophysiological changes in the primary motor cortex. In particular, previous research has provided some evidence of altered latencies of the corticomotor pathway and altered motor neuroplasticity. However, to date, no studies have assessed these neurophysiological metrics in a common group of athletes across different phases of injury and recovery. In this study corticomotor latencies and neuroplasticity were assessed in collegiate athletes with or without a history of prior concussion across two different phases of injury: either in an acute state of concussion (within 2 wk of injury) or in a chronic state of concussion (more than 1 yr after injury). Corticomotor latencies were determined by measuring the motor evoked potential (MEP) onset time, and motor neuroplasticity was assessed by measuring MEP amplitudes following application of anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1). We found that concussed athletes had slower corticomotor latencies than nonconcussed athletes, and corticomotor latency was also positively correlated with the number of prior concussions. In contrast, there was no evidence of altered motor neuroplasticity in athletes regardless of concussion history. These findings suggest concussions may lead to permanent changes in the corticospinal tract that are exacerbated by repeated injury.NEW & NOTEWORTHY We are the first to assess corticomotor latencies and motor neuroplasticity in a common group of collegiate athletes across different phases of injury and recovery. We found that the number of concussions an individual sustains negatively impacts corticomotor latencies with a higher number of prior concussions correlating positively with longer latencies. Our findings indicate that concussions may lead to permanent changes in the corticospinal tract that are exacerbated by repeated injury.

Effects of arm weight support on neuromuscular activation during reaching in chronic stroke patients.

To better understand how arm weight support (WS) can be used to alleviate upper limb impairment after stroke, we investigated the effects of WS on muscle activity, muscle synergy expression, and corticomotor excitability (CME) in 13 chronic stroke patients and 6 age-similar healthy controls. For patients, lesion location and corticospinal tract integrity were assessed using magnetic resonance imaging. Upper limb impairment was assessed using the Fugl-Meyer upper extremity assessment with patients categorised as either mild or moderate-severe. Three levels of WS were examined: low = 0, medium = 50 and high = 100% of full support. Surface EMG was recorded from 8 upper limb muscles, and muscle synergies were decomposed using non-negative matrix factorisation from data obtained during reaching movements to an array of 14 targets using the paretic or dominant arm. Interactions between impairment level and WS were found for the number of targets hit, and EMG measures. Overall, greater WS resulted in lower EMG levels, although the degree of modulation between WS levels was less for patients with moderate-severe compared to mild impairment. Healthy controls expressed more synergies than patients with moderate-severe impairment. Healthy controls and patients with mild impairment showed more synergies with high compared to low weight support. Transcranial magnetic stimulation was used to elicit motor-evoked potentials (MEPs) to which stimulus-response curves were fitted as a measure of corticomotor excitability (CME). The effect of WS on CME varied between muscles and across impairment level. These preliminary findings demonstrate that WS has direct and indirect effects on muscle activity, synergies, and CME and warrants further study in order to reduce upper limb impairment after stroke.

Posture interacts with arm weight support to modulate corticomotor excitability to the upper limb.

The use of arm weight support (WS) to optimize movement quality may be an avenue for improved upper limb stroke rehabilitation; however, the underlying neurophysiological effects of WS are not well understood. Rehabilitation exercises may be performed when sitting or standing, but the interaction of posture with WS has not been examined until now. We explored the effect of posture with WS on corticomotor excitability (CME) in healthy adults. Thirteen participants performed static shoulder abduction in two postures (sitting and standing) at three levels of WS (0, 45, and 90 % of full support). Transcranial magnetic stimulation of primary motor cortex was used to elicit motor-evoked potentials (MEPs) in eight upper limb muscles. Stimulus-response (SR) curves were fitted to the MEP data using nonlinear regression. Whole-body posture interacted with WS to influence tonic activity and CME in all muscles examined. SR curve parameters revealed greater CME when standing compared to sitting for upper arm muscles, but lower CME to the shoulder, forearm, and hand. Distal to the shoulder, tonic activity and CME were modulated independent of any explicit differences in task requirements. Overall, these results support a model of integrated upper limb control influenced by whole-body posture and WS. These findings have implications for the application of WS in settings such as upper limb rehabilitation after stroke.

Partial weight support of the arm affects corticomotor selectivity of biceps brachii.

BACKGROUND: Weight support of the arm (WS) can be used in stroke rehabilitation to facilitate upper limb therapy, but the neurophysiological effects of this technique are not well understood. While an overall reduction in muscle activity is expected, the mechanism by which WS may alter the expression of muscle synergies has not been examined until now. We explored the neurophysiological effect of WS on the selectivity of biceps brachii (BB) activation in healthy adults. METHODS: Thirteen participants completed counterbalanced movement tasks in a repeated measures design. Three levels of WS (0, 45, and 90 % of full support) were provided to the arm using a commercial device (Saebo Mobile Arm Support). At each level of WS, participants maintained a flexed shoulder posture while performing rhythmic isometric elbow flexion (BB agonist) or forearm pronation (BB antagonist). Single-pulse transcranial magnetic stimulation of primary motor cortex was used to elicit motor-evoked potentials (MEPs) in BB 100-300 ms before muscle contraction. Baseline muscle activity and MEP amplitude were the primary dependent measures. Effects of movement TASK and SUPPORT LEVEL were statistically analyzed using linear mixed effects models. RESULTS: As expected, with increased support tonic activity was reduced across all muscles. This effect was greatest in the anti-gravity muscle anterior deltoid, and evident in biceps brachii and pronator teres as well. For BB MEP amplitude, TASK and SUPPORT LEVEL, interacted such that for elbow flexion, MEP amplitudes were smaller with incrementally greater WS whereas, for forearm pronation MEP amplitudes were smaller only at high WS. CONCLUSIONS: Weight support of the arm influences corticomotor selectivity of biceps brachii. WS may impact coordination independently of a global reduction in muscle activity. The amount of supportive force applied to the arm influences the neuromechanical control profile for the limb. These findings may inform the application of WS in upper limb stroke rehabilitation.

A neuroanatomical framework for upper limb synergies after stroke.

Muscle synergies describe common patterns of co- or reciprocal activation that occur during movement. After stroke, these synergies change, often in stereotypical ways. The mechanism underlying this change reflects damage to key motor pathways as a result of the stroke lesion, and the subsequent reorganization along the neuroaxis, which may be further detrimental or restorative to motor function. The time course of abnormal synergy formation seems to lag spontaneous recovery that occurs in the initial weeks after stroke. In healthy individuals, motor cortical activity, descending via the corticospinal tract (CST) is the predominant driver of voluntary behavior. When the CST is damaged after stroke, other descending pathways may be up-regulated to compensate. The contribution of these pathways may emerge as new synergies take shape at the chronic stage after stroke, as a result of plasticity along the neuroaxis. The location of the stroke lesion and properties of the secondary descending pathways and their regulation are then critical for shaping the synergies in the remaining motor behavior. A consideration of the integrity of remaining descending motor pathways may aid in the design of new rehabilitation therapies.

Partial weight support differentially affects corticomotor excitability across muscles of the upper limb.

Partial weight support may hold promise as a therapeutic adjuvant during rehabilitation after stroke by providing a permissive environment for reducing the expression of abnormal muscle synergies that cause upper limb impairment. We explored the neurophysiological effects of upper limb weight support in 13 healthy young adults by measuring motor-evoked potentials (MEPs) from transcranial magnetic stimulation (TMS) of primary motor cortex and electromyography from anterior deltoid (AD), biceps brachii (BB), extensor carpi radialis (ECR), and first dorsal interosseous (FDI). Five levels of weight support, varying from none to full, were provided to the arm using a commercial device (Saebo Mobile Arm Support). For each level of support, stimulus-response (SR) curves were derived from MEPs across a range of TMS intensities. Weight support affected background EMG activity in each of the four muscles examined (P < 0.0001 for each muscle). Tonic background activity was primarily reduced in the AD. Weight support had a differential effect on the size of MEPs across muscles. After curve fitting, the SR plateau for ECR increased at the lowest support level (P = 0.004). For FDI, the SR plateau increased at the highest support level (P = 0.0003). These results indicate that weight support of the proximal upper limb modulates corticomotor excitability across the forearm and hand. The findings support a model of integrated control of the upper limb and may inform the use of weight support in clinical settings.