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. 2008 Aug 22;4(8):e1000133.
doi: 10.1371/journal.pcbi.1000133.

Stroke rehabilitation reaches a threshold

Affiliations

Stroke rehabilitation reaches a threshold

Cheol E Han et al. PLoS Comput Biol. .

Abstract

Motor training with the upper limb affected by stroke partially reverses the loss of cortical representation after lesion and has been proposed to increase spontaneous arm use. Moreover, repeated attempts to use the affected hand in daily activities create a form of practice that can potentially lead to further improvement in motor performance. We thus hypothesized that if motor retraining after stroke increases spontaneous arm use sufficiently, then the patient will enter a virtuous circle in which spontaneous arm use and motor performance reinforce each other. In contrast, if the dose of therapy is not sufficient to bring spontaneous use above threshold, then performance will not increase and the patient will further develop compensatory strategies with the less affected hand. To refine this hypothesis, we developed a computational model of bilateral hand use in arm reaching to study the interactions between adaptive decision making and motor relearning after motor cortex lesion. The model contains a left and a right motor cortex, each controlling the opposite arm, and a single action choice module. The action choice module learns, via reinforcement learning, the value of using each arm for reaching in specific directions. Each motor cortex uses a neural population code to specify the initial direction along which the contralateral hand moves towards a target. The motor cortex learns to minimize directional errors and to maximize neuronal activity for each movement. The derived learning rule accounts for the reversal of the loss of cortical representation after rehabilitation and the increase of this loss after stroke with insufficient rehabilitation. Further, our model exhibits nonlinear and bistable behavior: if natural recovery, motor training, or both, brings performance above a certain threshold, then training can be stopped, as the repeated spontaneous arm use provides a form of motor learning that further bootstraps performance and spontaneous use. Below this threshold, motor training is "in vain": there is little spontaneous arm use after training, the model exhibits learned nonuse, and compensatory movements with the less affected hand are reinforced. By exploring the nonlinear dynamics of stroke recovery using a biologically plausible neural model that accounts for reversal of the loss of motor cortex representation following rehabilitation or the lack thereof, respectively, we can explain previously hard to reconcile data on spontaneous arm use in stroke recovery. Further, our threshold prediction could be tested with an adaptive train-wait-train paradigm: if spontaneous arm use has increased in the "wait" period, then the threshold has been reached, and rehabilitation can be stopped. If spontaneous arm use is still low or has decreased, then another bout of rehabilitation is to be provided.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Experimental setup and model structure.
(A) Experimental setup. (B) Model structure. Solid line: information signal; dashed line: activation signal; dotted line: reward-based (reinforcement) learning; double dotted line: error-based (supervised) learning.
Figure 2
Figure 2. Neuronal population coding and spontaneous use over the workspace for the affected arm.
(A) Neuronal population coding. (B) spontaneous use (B). For (A) and (B): (1) Before stroke, (2) after stroke, (3) after 3,000 free choice trials, and (4) after 1,000 forced used trials followed by 2,000 free choice trials. In (A), each population vector figure shows the desired reach directions (thin black arrows), the neuron activation levels along their preferred directions (thin gray lines), and the resulting population vector (thick black arrows). Note that there are no “votes” for directions corresponding to the lesioned directions in (A.2) and (A.3) but that in (A.4), many neurons have become retuned to yield votes in the lesioned directions. In (B), the pie plots show the probability of using the unaffected right arm to reach to targets arrayed on a circle around the central position. In (B.2) and (B.3), the less affected arm reaches into the lesioned quadrant, but this effect is reversed with therapy (B.4).
Figure 3
Figure 3. Time course of behavioral performance and spontaneous use in the affected range just before stroke, following stroke (“acute stroke”), during rehabilitation, and after rehabilitation (“chronic stroke”).
(A) Directional error, (B) normalized population vector (PV), and (C) spontaneous arm choice. Five different durations of therapy were used (0, 200, 400, 800, or 3,000 trials). The spontaneous arm use is an average selection probability from 10 uniformly distributed desired directions on the affected range. The threshold of effective rehabilitation for this stroke size is shown in the horizontal dotted line of (C). If the rehabilitation leads to performance above this threshold, then a virtuous circle between spontaneous arm use and performance will take place and performances will continue to improve without the need for further rehabilitation.
Figure 4
Figure 4. Changes in spontaneous use following rehabilitation as a function of the number of rehabilitation trials.
We plotted the average slope of spontaneous arm use in the 1,000 trials following rehabilitation as a function of the intensity of therapy. Above 420 trials (with the default parameter set), spontaneous arm use increases after therapy. Below this number of trials, it decreases.
Figure 5
Figure 5. Effect of the number of rehabilitation trials in immediate and follow-up tests.
Directional error (A), normalized population vector (PV) (B), and spontaneous arm use (C) in the immediate and follow-up tests. The directional error performance following few rehabilitation trials worsens after therapy. On the contrary, the directional error performance after sufficient rehabilitation trials improves even after therapy. Similar bistable patterns are shown for the normalized population vector and spontaneous use shown in (B) and (C).
Figure 6
Figure 6. Effect of stroke size.
(A) Number of rehabilitation trials required to reach the effective rehabilitation threshold, as a function of lesion sizes. (B) Normalized population vector (PV) as a function of lesion size in the follow-up test after 800 rehabilitation trials.
Figure 7
Figure 7. Changes in reach precision (standard deviation of directional error) in relation to changes in accuracy (mean of directional error).
(A) Contralateral (affected) arm and (B) ipsilateral (nonaffected) arm. In each panel, the thick solid line corresponds to the changes occurring from just before stroke to the 500th free choice trials following stroke onset. The thin solid line represents additional changes in a no therapy condition (3,000 free choice trials). The dotted line represents additional changes in a therapy condition (1,000 therapy trials followed by 2,000 free choice trials). After stroke, accuracy and variability of the contralateral arm worsened. Following therapy, accuracy improved but with little change in variability. With no therapy, behavioral compensation with the nonaffected arm further developed, resulting in improved accuracy for this arm (B).
Figure 8
Figure 8. Cortical reorganization following stroke.
Reorganization of the affected (left) hemisphere (A) and nonaffected (right) hemisphere (B) after stroke followed by therapy or no therapy. In each panel, histograms of the cells' preferred directions are shown (1) before stroke, (2) after stroke with 500 free choice trials, and (3) after 3,000 free choice trials or (4) after 1,000 forced used training trials and subsequent 2,000 free choice trials. The gray area in (A.2) shows the lesion site. Before the lesion, the left hemisphere contains more neurons with preferred directions in the right workspace, and the right hemisphere contains more neurons for the left workspace because of the bias for workspace preference. Just after lesion, the left hemisphere is affected. If no therapy follows, the size of the affected range increases, and the number of neurons for the fourth quadrant increases in the affected hemisphere (maladaptation) and in the first quadrant in the nonaffected hemispheres (A.3). On the contrary, the number of neurons for the first quadrant in the right hemisphere increases due to compensation. After therapy (1,000 forced use trials followed by 2,000 free choice trials), however, the distributions of directions are similar to the prelesion distribution in both hemispheres.
Figure 9
Figure 9. Cortical reorganization without unsupervised learning.
Reorganization of the affected (left) hemisphere (A) and nonaffected (right) hemisphere (B) after stroke followed by therapy or no therapy. In each panel, histograms of the cells' preferred directions are shown (1) before stroke, (2) after stroke with 500 free choice trials, and (3) after 3,000 free choice trials or (4) after 1,000 forced used training trials and subsequent 2,000 free choice trials. The gray area in (A.2) shows the lesion site.
Figure 10
Figure 10. Learning rates sensitivity analysis.
Effect of the supervised learning rate (A), the unsupervised learning rate (B), and the reinforcement learning rate (C) on directional error after different durations of therapy (200, 400, and 800 therapy trials) followed by 3,000 free choice condition. The default parameters used in simulations are shown with the gray vertical lines.

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