Barbara M. Quaney

Post-infarct cortical plasticity and behavioral recovery using concurrent cortical stimulation and rehabilitative training: A feasibility study in primates

Abstract Stroke is often characterized by incomplete recovery and chronic motor impairments. A nonhuman primate model of cortical ischemia was used to evaluate the feasibility of using device-assisted cortical stimulation combined with rehabilitative training to enhance behavioral recovery and cortical plasticity. Following preinfarct training on a unimanual motor task, maps of movement representations in primary motor cortex were derived. Then, an ischemic infarct was produced which destroyed the hand representation. Several weeks later, a second cortical map was derived to guide implantation of a surface electrode over periinfarct motor cortex. After several months of spontaneous recovery, monkeys underwent subthreshold electrical stimulation combined with rehabilitative training for several weeks. Post-therapy behavioral performance was tracked for several additional months. A third cortical map was derived several weeks post-therapy to examine changes in motor representations. Monkeys showed significant improvements in motor performance (success, speed, and efficiency) following therapy, which persisted for several months. Cortical mapping revealed large-scale emergence of new hand representations in peri-infarct motor cortex, primarily in cortical tissue underlying the electrode. Results support the feasibility of using a therapy approach combining peri-infarct electrical stimulation with rehabilitative training to alleviate chronic motor deficits and promote recovery from cortical ischemic injury.

Aerobic exercise improves cognition and motor function poststroke.

Background. Cognitive deficits impede stroke recovery. Aerobic exercise (AEX) improves cognitive executive function (EF) processes in healthy individuals, although the learning benefits after stroke are unknown. Objective. To understand AEX-induced improvements in EF, motor learning, and mobility poststroke. Methods. Following cardiorespiratory testing, 38 chronic stroke survivors were randomized to 2 different groups that exercised 3 times a week (45-minute sessions) for 8 weeks. The AEX group (n = 19; 9 women; 10 men; 64.10 ± 12.30 years) performed progressive resistive stationary bicycle training at 70% maximal heart rate, whereas the Stretching Exercise (SE) group (n = 19; 12 women; 7 men; 58.96 ± 14.68 years) performed stretches at home. Between-group comparisons were performed on the change in performance at “Post” and “Retention” (8 weeks later) for neuropsychological and motor function measures. Results. VO2max significantly improved at Post with AEX (P = .04). AEX also improved motor learning in the less-affected hand, with large effect sizes (Cohen’s d calculation). Specifically, AEX significantly improved information processing speed on the serial reaction time task (SRTT; ie, “procedural motor learning”) compared with the SE group at Post (P = .024), but not at Retention. Also, at Post (P = .038), AEX significantly improved predictive force accuracy for a precision grip task requiring attention and conditional motor learning of visual cues. Ambulation and sit-to-stand transfers were significantly faster in the AEX group at Post (P = .038), with balance control significantly improved at Retention (P = .041). EF measurements were not significantly different for the AEX group. Conclusion. AEX improved mobility and selected cognitive domains related to motor learning, which enhances sensorimotor control after stroke.

Impaired Grip Force Modulation in the Ipsilesional Hand after Unilateral Middle Cerebral Artery Stroke

Understanding grasping control after stroke is important for relearning motor skills. The authors examined 10 individuals (5 males; 5 females; ages 32-86) with chronic unilateral middle cerebral artery (MCA) stroke (4 right lesions; 6 left lesions) when lifting a novel test object using skilled precision grip with their ipsilesional (“unaffected”) hand compared to healthy controls (n = 14; 6 males; 8 females; ages 19-86). All subjects possessed normal range of motion, cutaneous sensation, and proprioception in the hand tested and had no apraxia or cognitive deficits. Subjects lifted the object 10 times at each object weight (260 g, 500 g, 780 g) using a moderately paced self-selected lifting speed. The normal horizontal (“grip”) force and vertical tangential (“lift”) force were separately measured at the thumb and index finger. Regardless of the object weight or stroke location, the stroke group generated greater grip forces at liftoff of the object (≥39%; P ≤ 0.05) and across the dynamic (P ≤ 0.05) and static portions (P ≤ 0.05) of the lifts compared to the healthy group. Peak lift forces were equivalent between groups, suggesting accurate load force information processing occurred. These results warrant further investigation of altered sensorimotor processing or compensatory biomechanical strategies that may lead to inaccurate grip force execution after strokes.

Learning Implicitly: Effects of Task and Severity After Stroke

Background. Disparate results have been reported on the implicit learning ability of adults with stroke. Objective. This study aimed to elucidate the relationships between stroke severity and the task employed to test implicit motor learning. Methods. Twenty-eight patients with chronic stroke were divided according to stroke severity using the Orpington prognostic score into those with mild (n = 16, score < 3.2) or moderate stroke (n = 12, score 3.2-5.0). Seventeen healthy individuals served as matched controls (HC). All participants practiced 2 implicit learning tasks, the Serial Reaction Time (SRT) and Serial Hand Movement (SHM). Results. A group-bytask-by-block interaction (P = .000) demonstrated differences across the experimental factors. Post hoc analyses revealed differences between groups and tasks. Greater change in the speed of responding was exhibited for the SHM than the SRT task by the HC and mild groups; however, the moderate group did not demonstrate a between-task difference. Conclusion. Both stroke severity and motor task influenced the magnitude of implicit learning across acquisition, which suggests for the first time that different tasks may yield disparate implicit learning outcomes in the same population. Additionally, the impact of stroke severity may be important when assessing residual implicit motor learning capability. The combination of these 2 factors helps explain previously reported contradictory findings and may inform future studies.

Visuomotor Training Improves Stroke-Related Ipsilesional Upper Extremity Impairments

Background. Unilateral middle cerebral artery infarction has been reported to impair bilateral hand grasp. Methods. Individuals (5 males and 5 females; age 33-86 years) with chronic unilateral middle cerebral artery stroke (4 right lesions and 6 left lesions) repeatedly lifted a 260-g object. Participants were then trained to lift the object using visuomotor feedback via an oscilloscope that displayed their actual grip force (GF) and a target GF, which roughly matched the physical properties of the object. Results.The subjects failed to accurately modulate the predictive GF when relying on somatosensory information from the previous lifts. Instead, for all the lifts, they programmed excessive GF equivalent to the force used for the first lift. The predictive GF was lowered for lifts following the removal of the visual feedback. The mean difference in predictive GF between the lifts before and after visual training was significant (4.35 ± 0.027 N; P ≤ .001; 95% confidence interval [CI] = 3.80-4.88). After removal of visual feedback, there was also a significant mean difference in the applied predictive GF between the “early” and “late” lifts (0.78 ± 0.029 N; P ≤ .006; 95% CI = 0.22-1.35), demonstrating continued increase in predictive GF accuracy. Conclusion. Predictive or feedforward fingertip force generation is impaired in the ipsilesional hand when lifting a novel object with precision grip. Reacquisition of the motor forces for the grasp of objects is possible after stroke. Potentially, retraining grasp control for the ipsilesional hand may translate to improved function and motor learning within the contralesional hand.

Between-day reliability of upper extremity H-reflexes

H-reflexes are useful for evaluating the group Ia monosynaptic reflex excitability in the lower and upper extremities (UEs). However, there is no established between-day protocol for measuring H-reflex excitability in the UE extensor carpi radialis longus (ECRL). The purpose of this study was to develop a reliable protocol to measure the H-reflex excitability between-days for the ECRL, and the antagonist muscle, the flexor carpi radialis (FCR). H-reflex recruitment curves were recorded from eight healthy young subjects over 3 consecutive days in both muscles. Variables associated with the H-reflex excitability were measured: (a) maximum amplitude (Hmax); (b) gain (HGN); (c) threshold (HTH, visHTH, and sdHTH). All variables were normalized with respect to the M-wave. Within individual muscles, there were no statistically significant differences between-days for the group (p>0.05) and variables showed fair to good reliability (ICC=0.57-0.99). This method of reliably measuring H-reflex excitability within UE muscles will be useful for investigating the effects of pathology and rehabilitation on monosynaptic reflexes.

Retinal image location of hand, fingers, and objects during manual tasks.

Purpose. A new method was developed using the scanning laser ophthalmoscope (SLO) to investigate the effects of central visual loss on eye-hand coordination in manual tasks. Using the SLO, the retinal positions of the hand, fingers, and objects are imaged and recorded while a subject performs a manual task. Method. A video camera images the subject’s hand and objects to be manipulated in the SLO laser-beam raster, producing a video image of a subject’s hand, fingers, and objects on the subject’s retina while the objects are manipulated. A subject with bilateral central scotomas and an age-matched control subject with normal vision traced an ellipse with the index finger, tapped four disks in sequence, and carried out a pattern duplication task with pegs. Retinal positions of the fovea or preferred retinal locus (PRL), fingers, and objects were measured from digitized SLO images. Results. In all tasks, the fovea or PRL was directed to an object or position before the fingers arrived. This lead time was much greater for the scotoma subject than the control subject (∼1400 vs. ∼400 ms, respectively). The scotoma subject was much less accurate in placing the PRL and fingers on objects and required substantially more time for task completion than the control subject. Conclusions. The coordination of foveal fixation and finger placement found with the SLO method was similar to that found by others using eyetracking techniques with visually normal subjects. The presence of a central scotoma and use of a PRL caused marked deterioration in the quality of this coordination. Unlike eyetracking methods, the SLO technique does not require calibration because the positions of the fingers and objects are directly observable on the retina. This method could be useful in studying eye-hand coordination of individuals with scotomas that affect foveal vision.

A pilot study to measure upper extremity H-reflexes following neuromuscular electrical stimulation therapy after stroke

Upper extremity (UE) hemiparesis persists after stroke, limiting hand function. Neuromuscular electrical stimulation (NMES) is an effective intervention to improve UE recovery, although the underlying mechanisms are not fully understood. Our objective was to establish a reliable protocol to measure UE agonist-antagonist forearm monosynaptic reflexes in a pilot study to determine if NMES improves wrist function after stroke. We established the between-day reliability of the H-reflex in the extensor carpi radialis longus (ECRL) and flexor carpi radialis (FCR) musculature for individuals with prior stroke (n=18). The same-day generation of ECRL/FCR H-reflex recruitment curves was well tolerated, regardless of age or UE spasticity. The between-day reliability of the ECRL H-reflex was enhanced above FCR, similar to healthy subjects [20], with the Hmax the most reliable parameter quantified in both muscles. H-reflex and functional measures following NMES show the potential for NMES-induced increases in ECRL Hmax, but confirmation requires a larger clinical study. Our initial results support the safe, easy, and efficacious use of in-home NMES, and establish a potential method to measure UE monosynaptic reflexes after stroke.

A novel device to measure power grip forces in squirrel monkeys

Understanding the neural bases for grip force behaviors in both normal and neurologically impaired animals is imperative prior to improving treatments and therapeutic approaches. The present paper describes a novel device for the assessment of power grip forces in squirrel monkeys. The control of grasping and object manipulation represents a vital aspect of daily living by allowing the performance of a wide variety of complex hand movements. However, following neurological injury such as stroke, these grasping behaviors are often severely affected, resulting in persistent impairments in strength, grip force modulation and kinematic hand control. While there is a significant clinical focus on rehabilitative strategies to address these issues, there exists the need for translational animal models. In the study presented here, we describe a simple grip force device designed for use in non-human primates, which provides detailed quantitative information regarding distal grip force dynamics. Adult squirrel monkeys were trained to exceed a specific grip force threshold, which was rewarded with a food pellet. One of these subjects then received an infarct of the M1 hand representation area. Results suggest that the device provides detailed and reliable information on grip behaviors in healthy monkeys and can detect deficits in grip dynamics in monkeys with cortical lesions (significantly longer release times). Understanding the physiological and neuroanatomical aspects of grasping function following neurological injury may lead to more effective rehabilitative interventions.