Preliminary evidence indicates that dopamine given by mouth facilitates the learning of motor skills and improves the recovery of movement after stroke. The mechanism of these phenomena is unknown. ...Here, we describe a mechanism by demonstrating in rat that dopaminergic terminals and receptors in primary motor cortex (M1) enable motor skill learning and enhance M1 synaptic plasticity. Elimination of dopaminergic terminals in M1 specifically impaired motor skill acquisition, which was restored upon DA substitution. Execution of a previously acquired skill was unaffected. Reversible blockade of M1 D1 and D2 receptors temporarily impaired skill acquisition but not execution, and reduced long-term potentiation (LTP) within M1, a form of synaptic plasticity critically involved in skill learning. These findings identify a behavioral and functional role of dopaminergic signaling in M1. DA in M1 optimizes the learning of a novel motor skill.
BACKGROUND AND PURPOSE—Assessing upper limb movements poststroke is crucial to monitor and understand sensorimotor recovery. Kinematic assessments are expected to enable a sensitive quantification of ...movement quality and distinguish between restitution and compensation. The nature and practice of these assessments are highly variable and used without knowledge of their clinimetric properties. This presents a challenge when interpreting and comparing results. The purpose of this review was to summarize the state of the art regarding kinematic upper limb assessments poststroke with respect to the assessment task, measurement system, and performance metrics with their clinimetric properties. Subsequently, we aimed to provide evidence-based recommendations for future applications of upper limb kinematics in stroke recovery research.
METHODS—A systematic search was conducted in PubMed, Embase, CINAHL, and IEEE Xplore. Studies investigating clinimetric properties of applied metrics were assessed for risk of bias using the Consensus-Based Standards for the Selection of Health Measurement Instruments checklist. The quality of evidence for metrics was determined according to the Grading of Recommendations Assessment, Development, and Evaluation approach.
RESULTS—A total of 225 studies (N=6197) using 151 different kinematic metrics were identified and allocated to 5 task and 3 measurement system groups. Thirty studies investigated clinimetrics of 62 metricsreliability (n=8), measurement error (n=5), convergent validity (n=22), and responsiveness (n=2). The metrics task/movement time, number of movement onsets, number of movement ends, path length ratio, peak velocity, number of velocity peaks, trunk displacement, and shoulder flexion/extension received a sufficient evaluation for one clinimetric property.
CONCLUSIONS—Studies on kinematic assessments of upper limb sensorimotor function are poorly standardized and rarely investigate clinimetrics in an unbiased manner. Based on the available evidence, recommendations on the assessment task, measurement system, and performance metrics were made with the goal to increase standardization. Further high-quality studies evaluating clinimetric properties are needed to validate kinematic assessments, with the long-term goal to elucidate upper limb sensorimotor recovery poststroke.
CLINICAL TRIAL REGISTRATION—URLhttps://www.crd.york.ac.uk/prospero/. Unique identifierCRD42017064279.
The primary motor cortex (M1) of the rat contains dopaminergic terminals. The origin of this dopaminergic projection and its functional role for movement are obscure. Other areas of cortex receive ...dopaminergic projections from the ventral tegmental area (VTA) of the midbrain, and these projections are involved in learning phenomena. We therefore hypothesized that M1 receives a dopaminergic projection from VTA and that this projection mediates the learning of a motor skill by inducing cellular plasticity events in M1. Retrograde tracing from M1 of Long-Evans rats in conjunction with tyrosine hydroxylase immunohistochemistry identified dopaminergic cell bodies in VTA. Electrical stimulation of VTA induced expression of the immediate-early gene c-fos in M1, which was blocked by intracortical injections of D(1) and D(2) antagonists. Destroying VTA dopaminergic neurons prevented the improvements in forelimb reaching seen in controls during daily training. Learning recovered on administration of levodopa into the M1 of VTA-lesioned animals. Lesioning VTA did not affect performance of an already learned skill, hence, left movement execution intact. These findings provide evidence that dopaminergic terminals in M1 originate in VTA, contribute to M1 plasticity, and are necessary for successful motor skill learning. Because VTA dopaminergic neurons are known to signal rewards, the VTA-to-M1 projection is a candidate for relaying reward information that could directly support the encoding of a motor skill within M1.
Objective
The ‘Early Prediction of Functional Outcome after Stroke’ (EPOS) model was developed to predict the presence of at least some upper limb capacity (Action Research Am Test ARAT ≥10/57) at 6 ...months based on assessments on days 2, 5 and 9 after stroke. External validation of the model is the next step towards clinical implementation. The objective here is to externally validate the EPOS model for upper limb outcome 3 months poststroke in Switzerland and extend the model using an ARAT cut-off at 32 points.
Methods
Data from two prospective longitudinal cohort studies including first-ever stroke patients admitted to a Swiss stroke center were analyzed. The presence of finger extension and shoulder abduction was measured on days 1 and 8 poststroke in Cohort 1, and on days 3 and 9 in Cohort 2. Upper limb capacity was measured 3 months poststroke. Discrimination (area under the curve; AUC) and calibration obtained with the model were determined.
Results
In Cohort 1 (N = 39, median age 74 years), the AUC on day 1 was 0.78 (95%CI 0.61, 0.95) and 0.96 (95%CI 0.90, 1.00) on day 8, using the model of day 5. In Cohort 2 (N = 85, median age 69 years), the AUC was 0.96 (95%CI 0.93, 0.99) on day 3 and 0.89 (95% CI 0.80, 0.98) on day 9. Applying a 32-point ARAT cut-off resulted in an AUC ranging from 0.82 (95%CI 0.68, 0.95; Cohort 1, day 1) to 0.95 (95%CI 0.87, 1.00; Cohort 1, day 8).
Conclusions
The EPOS model was successfully validated in first-ever stroke patients with mild-to-moderate neurological impairments, who were independent before their stroke. Now, its impact on clinical practice should be investigated in this population. Testing the model’s performance in severe (recurrent) strokes and stratification of patients using the ARAT 32-point cut-off is required to enhance the model’s generalizability and potential clinical impact.
Objective
Patients with chronic stroke have been shown to have failure to release interhemispheric inhibition (IHI) from the intact to the damaged hemisphere before movement execution (premovement ...IHI). This inhibitory imbalance was found to correlate with poor motor performance in the chronic stage after stroke and has since become a target for therapeutic interventions. The logic of this approach, however, implies that abnormal premovement IHI is causal to poor behavioral outcome and should therefore be present early after stroke when motor impairment is at its worst. To test this idea, in a longitudinal study, we investigated interhemispheric interactions by tracking patients’ premovement IHI for one year following stroke.
Methods
We assessed premovement IHI and motor behavior five times over a 1‐year period after ischemic stroke in 22 patients and 11 healthy participants.
Results
We found that premovement IHI was normal during the acute/subacute period and only became abnormal at the chronic stage; specifically, release of IHI in movement preparation worsened as motor behavior improved. In addition, premovement IHI did not correlate with behavioral measures cross‐sectionally, whereas the longitudinal emergence of abnormal premovement IHI from the acute to the chronic stage was inversely correlated with recovery of finger individuation.
Interpretation
These results suggest that interhemispheric imbalance is not a cause of poor motor recovery, but instead might be the consequence of underlying recovery processes. These findings call into question the rehabilitation strategy of attempting to rebalance interhemispheric interactions in order to improve motor recovery after stroke. Ann Neurol 2019;85:502–513
(
: Assessing feasibility and initial impact of the Home-Graded Repetitive Arm Supplementary Program combined with in-home accelerometer-based feedback (AH-GRASP) on perceived and actual daily-life ...upper limb (UL) activity in stroke survivors during the chronic phase with good UL motor function but low perceived daily-life activity.
: A 4-week intervention program (4 contact hours, 48 h self-practice) encompassing task-oriented training, behavioral techniques, phone-based support, monitoring, and weekly feedback sessions using wrist-worn accelerometery was implemented using a pre-post double baseline repeated measures design. Feasibility, clinical assessments, patient-reported outcomes, and accelerometer data were investigated.
: Of the 34 individuals approached, nineteen were included (recruitment rate 56%). Two dropped out, one due to increased UL pain (retention rate 89%). Seven (41%) achieved the prescribed exercise target (120 min/day, six days/week). Positive patient experiences and improvements in UL capacity, self-efficacy, and contribution of the affected UL to overall activity (
< 0.05, small to large effect sizes) were observed. Additionally, seven participants (41%) surpassed the minimal clinically important difference in perceived UL activity.
: A home-based UL exercise program with accelerometer-based feedback holds promise for enhancing perceived and actual daily-life UL activity for our subgroup of chronic stroke survivors.
Many stroke survivors experience persisting episodic memory disturbances. Since hippocampal and para-hippocampal areas are usually spared from the infarcted area, alterations of memory processing ...networks remote from the ischemic brain region might be responsible for the observed clinical symptoms. To pinpoint changes in activity of hippocampal connections and their role in post-stroke cognitive impairment, we induced ischemic stroke by occlusion of the middle cerebral artery (MCAO) in adult rats and analyzed the functional and structural consequences using activity-dependent manganese (Mn
) enhanced MRI (MEMRI) along with behavioral and histopathological analysis. MCAO caused stroke lesions of variable extent along with sensorimotor and cognitive deficits. Direct hippocampal injury occurred in some rats, but was no prerequisite for cognitive impairment. In healthy rats, injection of Mn
into the entorhinal cortex resulted in distribution of the tracer within the hippocampal subfields into the lateral septal nuclei. In MCAO rats, Mn
accumulated in the ipsilateral thalamus. Histopathological analysis revealed secondary thalamic degeneration 28 days after stroke. Our findings provide in vivo evidence that remote sensorimotor stroke modifies the activity of hippocampal-thalamic networks. In addition to potentially reversible alterations in signaling of these connections, structural damage of the thalamus likely reinforces dysfunction of hippocampal-thalamic circuitries.
PDF
