Training-induced Recovery Research Articles

Accounting for the valley of recovery during post-stroke rehabilitation training via a model-based analysis of macaque manual dexterity.

True recovery, in which a stroke patient regains the same precise motor skills observed in prestroke conditions, is the fundamental goal of rehabilitation training. However, a transient drop in task performance during rehabilitation training after stroke, observed in human clinical outcome as well as in both macaque and squirrel monkey retrieval data, might prevent smooth transitions during recovery. This drop, i.e., recovery valley, often occurs during the transition from compensatory skill to precision skill. Here, we sought computational mechanisms behind such transitions and recovery. Analogous to motor skill learning, we considered that the motor recovery process is composed of spontaneous recovery and training-induced recovery. Specifically, we hypothesized that the interaction of these multiple skill update processes might determine profiles of the recovery valley. A computational model of motor recovery was developed based on a state-space model of motor learning that incorporates a retention factor and interaction terms for training-induced recovery and spontaneous recovery. The model was fit to previously reported macaque motor recovery data where the monkey practiced precision grip skills after a lesion in the sensorimotor area in the cortex. Multiple computational models and the effects of each parameter were examined by model comparisons based on information criteria and sensitivity analyses of each parameter. Both training-induced and spontaneous recoveries were necessary to explain the behavioral data. Since these two factors contributed following logarithmic function, the training-induced recovery were effective only after spontaneous biological recovery had developed. In the training-induced recovery component, the practice of the compensation also contributed to recovery of the precision grip skill as if there is a significant generalization effect of learning between these two skills. In addition, a retention factor was critical to explain the recovery profiles. We found that spontaneous recovery, training-induced recovery, retention factors, and interaction terms are crucial to explain recovery and recovery valley profiles. This simulation-based examination of the model parameters provides suggestions for effective rehabilitation methods to prevent the recovery valley, such as plasticity-promoting medications, brain stimulation, and robotic rehabilitation technologies.

Spared perilesional V1 activity underlies training-induced recovery of luminance detection sensitivity in cortically-blind patients

Damage to the primary visual cortex (V1) causes homonymous visual-field loss long considered intractable. Multiple studies now show that perceptual training can restore visual functions in chronic cortically-induced blindness (CB). A popular hypothesis is that training can harness residual visual functions by recruiting intact extrageniculostriate pathways. Training may also induce plastic changes within spared regions of the damaged V1. Here, we link changes in luminance detection sensitivity with retinotopic fMRI activity before and after visual discrimination training in eleven patients with chronic, stroke-induced CB. We show that spared V1 activity representing perimetrically-blind locations prior to training predicts the amount of training-induced recovery of luminance detection sensitivity. Additionally, training results in an enlargement of population receptive fields in perilesional V1, which increases blind-field coverage and may support further recovery with subsequent training. These findings uncover fundamental changes in perilesional V1 cortex underlying training-induced restoration of conscious luminance detection sensitivity in CB.

Effects of repetitive transcranial magnetic stimulation on recovery in lower limb muscle strength and gait function following spinal cord injury: a randomized controlled trial

Study designRandomized sham-controlled clinical trial.ObjectivesThe objective of this study is to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) compared to sham stimulation, on the development of lower limb muscle strength and gait function during rehabilitation of spinal cord injury (SCI).SettingSCI rehabilitation hospital in Viborg, Denmark.MethodsTwenty individuals with SCI were randomized to receive rTMS (REAL, n = 11) or sham stimulation (SHAM, n = 9) and usual care for 4 weeks. rTMS (20 Hz, 1800 pulses per session) or sham stimulation was delivered over leg M1 Monday–Friday before lower limb resistance training or physical therapy. Lower limb maximal muscle strength (MVC) and gait function were assessed pre- and post intervention. Lower extremity motor score (LEMS) was assessed at admission and at discharge.ResultsOne individual dropped out due to seizure. More prominent increases in total leg (effect size (ES): 0.40), knee flexor (ES: 0.29), and knee extensor MVC (ES: 0.34) were observed in REAL compared to SHAM; however, repeated-measures ANOVA revealed no clear main effects for any outcome measure (treatment p > 0.15, treatment × time p > 0.76, time p > 0.23). LEMS improved significantly for REAL at discharge, but not for SHAM, and REAL demonstrated greater improvement in LEMS than SHAM (p < 0.02). Similar improvements in gait performance were observed between groups.ConclusionsHigh-frequency rTMS may increase long-term training-induced recovery of lower limb muscle strength following SCI. The effect on short-term recovery is unclear. Four weeks of rTMS, when delivered in conjunction with resistance training, has no effect on recovery of gait function, indicating a task-specific training effect.

Functional MRI of visual cortex predicts training-induced recovery in stroke patients with homonymous visual field defects

Post-chiasmatic damage to the visual system leads to homonymous visual field defects (HVDs), which can severely interfere with daily life activities. Visual Restitution Training (VRT) can recover parts of the affected visual field in patients with chronic HVDs, but training outcome is variable. An untested hypothesis suggests that training potential may be largest in regions with ‘neural reserve’, where cortical responses to visual stimulation do not lead to visual awareness as assessed by Humphrey perimetry—a standard behavioural visual field test. Here, we tested this hypothesis in a sample of twenty-seven hemianopic stroke patients, who participated in an assiduous 80-hour VRT program. For each patient, we collected Humphrey perimetry and wide-field fMRI-based retinotopic mapping data prior to training. In addition, we used Goal Attainment Scaling to assess whether personal activities in daily living improved. After training, we assessed with a second Humphrey perimetry measurement whether the visual field was improved and evaluated which personal goals were attained. Confirming the hypothesis, we found significantly larger improvements of visual sensitivity at field locations with neural reserve. These visual field improvements implicated both regions in primary visual cortex and higher order visual areas. In addition, improvement in daily life activities correlated with the extent of visual field enlargement. Our findings are an important step toward understanding the mechanisms of visual restitution as well as predicting training efficacy in stroke patients with chronic hemianopia.

Dynamic Interaction between Cortico-Brainstem Pathways during Training-Induced Recovery in Stroke Model Rats.

Reorganization of residual descending motor circuits underlies poststroke recovery. We previously clarified a causal relationship between the cortico-rubral tract and intensive limb use-induced functional recovery after internal capsule hemorrhage (ICH). However, other descending tracts, such as the cortico-reticular tract, might also be involved in rehabilitation-induced compensation. To investigate whether rehabilitation-induced recovery after ICH involves a shift in the compensatory circuit from the cortico-rubral tract to the cortico-reticular tract, we established loss of function of the cortico-rubral tract or/and cortico-reticular tract using two sets of viral vectors comprising the Tet-on system and designer receptors exclusively activated by the designer drug system. We used an ICH model that destroyed almost 60% of the corticofugal fibers. Anterograde tracing in rehabilitated rats revealed abundant sprouting of axons from the motor cortex in the red nucleus but not in the medullary reticular formation during the early phase of recovery. This primary contribution of the cortico-rubral tract was demonstrated by its selective blockade, whereas selective cortico-reticular tract silencing had little effect. Interestingly, cortico-rubral tract blockade from the start of rehabilitation induced an obvious increase of axon sprouting in the reticular formation with substantial functional recovery. Additional cortico-reticular tract silencing under the cortico-rubral tract blockade significantly worsened the recovered forelimb function. Furthermore, the alternative recruitment of the cortico-reticular tract was gradually induced by intensive limb use under cortico-rubral tract blockade, in which cortico-reticular tract silencing caused an apparent motor deficit. These findings indicate that individual cortico-brainstem pathways have dynamic compensatory potency to support rehabilitative functional recovery after ICH.SIGNIFICANCE STATEMENT This study aimed to clarify the interaction between the cortico-rubral and the cortico-reticular tract during intensive rehabilitation and functional recovery after capsular stroke. Pathway-selective disturbance by two sets of viral vectors revealed that the cortico-rubral tract was involved in rehabilitation-induced recovery of forelimb function from an early phase after internal capsule hemorrhage, but that the cortico-reticular tract was not. The sequential disturbance of both tracts revealed that the cortico-reticular tract was recruited and involved in rehabilitation-induced recovery when the cortico-rubral tract failed to function. Our data demonstrate a dynamic compensatory action of individual cortico-brainstem pathways for recovery through poststroke rehabilitation.

Segregation of Spontaneous and Training Induced Recovery from Visual Field Defects in Subacute Stroke Patients.

Whether rehabilitation after stroke profits from an early start is difficult to establish as the contributions of spontaneous recovery and treatment are difficult to tease apart. Here, we use a novel training design to dissociate these components for visual rehabilitation of subacute stroke patients with visual field defects such as hemianopia. Visual discrimination training was started within 6 weeks after stroke in 17 patients. Spontaneous and training-induced recoveries were distinguished by training one-half of the defect for 8 weeks, while monitoring spontaneous recovery in the other (control) half of the defect. Next, trained and control regions were swapped, and training continued for another 8 weeks. The same paradigm was also applied to seven chronic patients for whom spontaneous recovery can be excluded and changes in the control half of the defect point to a spillover effect of training. In both groups, field stability was assessed during a no-intervention period. Defect reduction was significantly greater in the trained part of the defect than in the simultaneously untrained part of the defect irrespective of training onset (p = 0.001). In subacute patients, training contributed about twice as much to their defect reduction as the spontaneous recovery. Goal Attainment Scores were significantly and positively correlated with the total defect reduction (p = 0.01), percentage increase reading speed was significantly and positively correlated with the defect reduction induced by training (epoch 1: p = 0.0044; epoch 2: p = 0.023). Visual training adds significantly to the spontaneous recovery of visual field defects, both during training in the early and the chronic stroke phase. However, field recovery as a result of training in this subacute phase was as large as in the chronic phase. This suggests that patients benefited primarily of early onset training by gaining access to a larger visual field sooner.

Pre-training cortical activity preserved after V1 damage predicts sites of training-induced visual recovery

Pre-training cortical activity preserved after V1 damage predicts sites of training-induced visual recovery

Different properties of training-induced visual recovery in sub-acute and chronic stroke patients

Different properties of training-induced visual recovery in sub-acute and chronic stroke patients

Computational rehabilitation of neglect: Using state-space models to understand the recovery mechanisms.

Unilateral spatial neglect is a neuropsychological syndrome often observed in right hemisphere stroke patients. The symptoms differ from subject to subject. A few rehabilitation approaches, e.g. prism adaptation, have demonstrated some effect in reducing the symptoms, but the underlying mechanisms are still largely unclear. Recently, neural models have been proposed to qualitatively describe cortical lesions, the resulting neglect symptoms and the effects of treatment. However, these predictions are qualitative and cannot be used to compare different hypotheses or to interpret symptoms at individual subjects level. Here we propose a computational model of the trial-by-trial dynamics of training-induced recovery from neglect. Neglect is modelled in terms of an impaired internal representation of visual stimuli in the left hemispace. The model assumes that recovery is driven by the mismatch between defective representations of visual stimuli and the corresponding hand positions. The model reproduces the main observations of prism adaptation experiments. Using standard system identification techniques, we fitted the model to data from a rehabilitation trial based on a novel rehabilitation approach based on virtual reality, involving reaching movements within an adaptive environment. Our results suggest that the model can be used to interpret data from individual subjects and to formulate testable hypotheses on the mechanisms of recovery and directions for treatment.

Motor Skills Training Enhances α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor Subunit mRNA Expression in the Ipsilateral Sensorimotor Cortex and Striatum of Rats Following Intracerebral Hemorrhage

We investigated the effects of acrobatic training (AT) on expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits in the sensorimotor cortex and striatum after intracerebral hemorrhage (ICH). Male Wistar rats were divided into 4 groups: ICH without AT (ICH), ICH with AT (ICH + AT), sham operation without AT (SHAM), and sham operation with AT (SHAM + AT). ICH was induced by collagenase injection into the left striatum. The ICH + AT group performed 5 acrobatic tasks daily on days 4-28 post ICH. Forelimb sensorimotor function was evaluated using the forelimb placing test. On days 14 and 29, mRNA expression levels of AMPAR subunits GluR1-4 were measured by real-time reverse transcription-polymerase chain reaction. Forelimb placing test scores were significantly higher in the ICH + AT group than in the ICH group. Expression levels of all AMPAR subunit mRNAs were significantly higher in the ipsilateral sensorimotor cortex of rats in the ICH + AT group than in that of rats in the ICH group on day 29. GluR3 and GluR4 expression levels were reduced in the ipsilateral striatum of rats in the ICH group compared with that of rats in the SHAM group on day 14. These changes may play a critical role in motor skills training-induced recovery after ICH.

Training-induced recovery of fMRI-based motion adaptation signals in V1 damaged humans

Training-induced recovery of fMRI-based motion adaptation signals in V1 damaged humans

Lack of location specificity along the blind field border for training-induced visual recovery after V1 damage in humans

Lack of location specificity along the blind field border for training-induced visual recovery after V1 damage in humans

Training-induced recovery of low-level vision followed by high-level perceptual improvements in an adult with developmental object and face agnosia

Training-induced recovery of low-level vision followed by high-level perceptual improvements in an adult with developmental object and face agnosia

Neurophysiological and Behavioral Effects of tDCS Combined With Constraint-Induced Movement Therapy in Poststroke Patients

Background. Recovery of motor function after stroke may depend on a balance of activity in the neural network involving the affected and the unaffected motor cortices. Objective. To assess whether transcranial direct current stimulation (tDCS) can increase the training-induced recovery of motor functions. Methods. In an exploratory study, 14 patients with chronic stroke and mean Fugl-Meyer Upper Extremity Motor Assessment of 29 (range = 8-50) entered a double-blind sham-controlled study, aimed to investigate neurophysiological and behavioral effects of bihemispheric tDCS (cathodal stimulation of the unaffected motor cortex and anodal stimulation of the affected motor cortex), combined with constraint-induced movement therapy (CIMT). Results. Patients in both groups demonstrated gains on primary outcome measures, that is, Jebsen Taylor Hand Function Test, Handgrip Strength, Motor Activity Log Scale, and Fugl-Meyer Motor Score. Gains were larger in the active tDCS group. Neurophysiological measurements showed a reduction in transcallosal inhibition from the intact to the affected hemisphere and increased corticospinal excitability in the affected hemisphere only in the active tDCS/CIMT group. Such neurophysiological changes correlated with the magnitude of the behavioral gains. Both groups showed a reduction in corticospinal excitability of the unaffected hemisphere. Conclusions. CIMT alone appears effective in modulating local excitability but not in removing the imbalance in transcallosal inhibition. Bihemispheric tDCS may achieve this goal and foster greater functional recovery.

Neural Plasticity After Acquired Brain Injury: Evidence from Functional Neuroimaging

Abstract The reorganization of the adult central nervous system after damage is a relatively new area of investigation. Neuroimaging methods, such as functional magnetic resonance imaging, diffusion tensor imaging, and positron emission tomography, have the ability to identify, in vivo, some of the processes involved in these neuroplastic changes and can help with diagnosis, prognosis, and potentially treatment approaches. In this article, traumatic brain injury and stroke are used as examples in which neural plasticity plays an important role in recovery. Basic concepts related to brain remodeling, including spontaneous reorganization and training-induced recovery, as well as characteristics of reorganization in successful recovery, are reviewed. The microscopic and molecular mechanisms that underlie neural plasticity and neurogenesis are briefly described. Finally, exciting future directions for the evaluation, diagnosis, and treatment of severe brain injury are explored, with an emphasis on how neuroimaging can help to inform these new approaches.

Integrity of the hippocampus and surrounding white matter is correlated with language training success in aphasia

Aphasia after middle cerebral artery (MCA) stroke shows highly variable degrees of recovery. One possible explanation may be offered by the variability of the occlusion location. Branches from the proximal portion of the MCA often supply the mesial temporal lobe including parts of the hippocampus, a structure known to be involved in language learning. Therefore, we assessed whether language recovery in chronic aphasia is dependent on the proximity of the MCA infarct and correlated with the integrity of the hippocampus and its surrounding white matter. Language reacquisition capability was determined after 2weeks of intensive language therapy and 8months after treatment in ten chronic aphasia patients. Proximity of MCA occlusion relative to the internal carotid artery was determined by magnetic resonance imaging (MRI) based on the most proximal anatomical region infarcted. Structural damage to the hippocampus was assessed by MRI-based volumetry, regional microstructural integrity of hippocampus adjacent white matter by fractional anisotropy. Language learning success for trained materials was correlated with the proximity of MCA occlusion, microstructural integrity of the left hippocampus and its surrounding white matter, but not with lesion size, overall microstructural brain integrity and a control region outside of the MCA territory. No correlations were found for untrained language materials, underlining the specificity of our results for training-induced recovery. Our results suggest that intensive language therapy success in chronic aphasia after MCA stroke is critically dependent on damage to the hippocampus and its surrounding structures.

Training-induced plasticity in rats with cervical spinal cord injury: Effects and side effects

We investigated the contribution of corticospinal tract (CST) plasticity to training-induced recovery and side effects following spinal cord injury (SCI). Rats were divided into three lesion groups: a unilateral lesion of the dorsal funiculus, the lateral funiculus or a lesion of the entire dorsolateral quadrant (DLQ). Following surgery, rats were distributed into a training group and an untrained group. Trained rats received rehabilitative training in skilled reaching 6 days a week, starting 4 days post-lesion. Following 6 weeks, all rats were tested in reaching (trained task) and crossing a horizontal ladder (untrained task). We found that trained rats with a lesion involving the dorsal column were significantly better in reaching compared to untrained animals. However, when crossing the horizontal ladder, trained rats made significantly more mistakes than untrained animals. Interestingly, rats with a lateral funiculus lesion did not show either effect. A subsequent ablation of the pyramidal tract (pyramidotomy) in rats with a DLQ-lesion significantly reduced but did not eliminate the reaching success. This spared function suggests that other descending systems contributed to the training-induced recovery. In addition, motor-evoked potentials (MEP) from cortical stimulation could still be evoked after pyramidotomy. Further, blocking synaptic transmission passing through the red nucleus using muscimol did not influence the occurrence of MEP's, suggesting that other descending pathways, like the reticulospinal tract, were involved in functional recovery. In summary, this study demonstrates that training-induced CST plasticity may contribute to recovery of motor function, but may also negatively affect untrained tasks as previously reported.

Pseudo-hallucinations in patients with visual field defects during spontaneous and training-induced recovery

Pseudo-hallucinations in patients with visual field defects during spontaneous and training-induced recovery

Training-induced Recovery of Manual Dexterity after a Lesion in the Motor Cortex

Cerebral injury, such as stroke, cause functional deficits; however some functions can recover with postlesion rehabilitative training. Several recent studies using rodents and monkeys have reported the effects of postlesion training on functional recovery after brain injury. We present herein an overview of recent animal experimental studies on the effects of postlesion motor training on brain plasticity and motor recovery. Our study in the macaque monkey reported the effects of hand motor training on motor recovery after lesioning of the primary motor cortex (M1). In monkeys that had undergone intensive daily training after the lesion, manual dexterity recovered to previous levels. Relatively independent digit movements, including those of precision grip, were restored in the trained monkeys. While hand movements recovered to some extent in the monkeys without postlesion training, these monkeys frequently used alternative grips to grasp a small object instead o f the precision grip. These findings suggest that recovery after M1 lesions includes both training-dependent and training-independent processes, and that recovery of precision grip requires intensive postlesion training. Recent results of both brain imaging and gene expression analyses suggest that functional and structural changes may occur in uninjured motor areas during recovery of hand function after M1 lesions. In particular, our preliminary results suggest that structural changes in ventral premotor cortex neurons may participate in functional compensation of precision grip.

Sensorimotor training promotes functional recovery and somatosensory cortical map reactivation following cervical spinal cord injury

Sensorimotor activity has been shown to play a key role in functional recovery after partial spinal cord injury (SCI). Most studies in rodents have focused on the rehabilitation of hindlimb locomotor functions after thoracic or lumbar SCI, whereas forelimb motor and somatosensory abilities after cervical SCI remain largely uninvestigated, despite the high incidence of such injuries in humans. Moreover, little is known about the neurophysiological substrates of training-induced recovery in supraspinal structures. This study was aimed at evaluating the effects of a training procedure combining both motor and sensory stimulation on behavioral performance and somatosensory cortical map remodeling after cervical (C4-C5) spinal hemisection in rats. This SCI severely impaired both sensory and motor capacities in the ipsilateral limbs. Without training, post-lesion motor capacities gradually improved, whereas forepaw tactile abilities remained impaired. Consistently, no stimulus-evoked responses were recorded within the forepaw representational zone in the primary somatosensory (S1) cortex at 2 months after the SCI. However, our data reveal that with training started from the 7th day post-lesion, a nearly complete recovery (characterized by an early and rapid improvement of motor functions) was associated with a gradual compensation of tactile deficits. Furthermore, the recovery of tactile abilities was correlated with the areal extent of reactivation of S1 cortex forepaw representations. Rehabilitative training promoted post-lesion adaptive plasticity, probably by enhancing endogenous activity within spared spinal and supraspinal circuits and pathways sustaining sensory and motor functions. This study highlights the beneficial effect of sensorimotor training in motor improvement and its critical influence on tactile recovery after SCI.