Participant 2 was a 63-year-old right-handed woman 9 months after a stroke localized to the left internal capsule and corona radiata. Lesion volume was 2.1 cm3 (Figure 1A). Sensorimotor Summary: Participant 2 had functional bilateral hot/cold discrimination; touch perception was impaired. Haptic performance and proprioception were impaired in the right hand; weight and texture discrimination was normal bilaterally. Motor testing identified a mild deficit on both objective and self-reported right-hand use (3.6/5.0 on the MAL amount of use; see Table 2).
The participants trained 5 days per week for 2 weeks. Daily sessions lasted 4 hours, and breaks were provided upon request. Both participants completed all 10 days of training. Trainers recorded time on task for each participant on every task. For participants 1 and 2, mean time on task per day was 203 minutes and 215 minutes, mean number of tasks per day was 9.1 and 7.6, while the mean time per task was 22 minutes and 28 minutes, respectively.
The intervention was based on the following principles. Treatment intensity was adapted from constraint-induced movement therapy.67 Tasks were primarily unimanual, based on the concept of forced use,68 but occasionally bimanual (<10%), dependent on participant ability and task structure. To force a sensory demand, most tasks were performed with vision of task objects obscured by a curtain hung between the participant and the activity.69 If obscuring vision resulted in a task being too difficult or vision had no relevance to the task (ie, hot/cold discrimination), the trainer would remove the curtain. A variety of tasks were used (listed in Table 3). They were developed in our laboratory with the goal of requiring sensory discrimination of temperature, weights, textures, shapes, and objects in the context of active exploration with the involved hand9–11 (see Video Abstract in Supplemental Digital Content for an example of task description). Task variety has been associated with maintaining motivation70 and attention.71,72 Moreover, across domains, higher-level sensory processing shares a parietal-prefrontal-premotor network as suggested by evidence from neuroimaging studies.31,73–75 Tasks were progressed in difficulty, on the basis of performance and participant-specific impairments. Tasks were modified, and/or participants were assisted by the trainer when necessary to accommodate for motor impairment. Random verbal feedback was provided by the trainers; participants also used the nonparetic hand and/or vision for feedback. Student physical therapists trained to administer this protocol provided one-on-one or one-on-two guidance to the participants.
Participant 1 had no increase in sensory scores in either hand after training. His WMFT scores met the criteria for minimal clinically important difference (MCID); importantly, the MCID was established in a study of acute stroke.48 His change in the MAL score was not clinically meaningful.47 Imaging Outcomes: Participant 1 had low cortical activation overall, during contralesional, left index brush discrimination at pretest and posttest imaging time points. In a post-minus-pretest contrast of impaired hand brush discrimination statistic parametric maps, participant 1 had a statistically significant increase in activation that peaked in the contralesional precentral and postcentral gyri after training; this resulted from less deactivation in these areas at posttest compared with pretest (see Figure 1B). The diffusion tractography models of the right and left sSTRs for participant 1 are asymmetrical, consistent with attenuation of the right sSTR due to right hemisphere internal capsule stroke. The posttest sSTR models are depicted in Figure 1C; as no significant difference was observed between pretest and posttest, only the posttest sSTR models are shown for both participants. For participant 1, FA and FD values for the left (contralesional) sSTR were stable across imaging time points; whereas at posttest in the right sSTR, FA appears to have increased while FD appears to have decreased (see Table 4). It should be noted that this variability is likely due to the relatively small number of voxels in the right sSTR model. Reliability of DTT has not been established for small white matter projections such as this.64 Brain volume change was +0.4%, which is slightly above the published error rate of this method of 0.2%.66
Participant 2 had a positive change in sensory scores for touch perception, proprioception, and haptic performance, while weight and texture discrimination was in the range of normal at pretest and posttest. Right index finger touch perception improved from a threshold of 0.2 g at pretest to within the range of normal (0.07 g) at posttest.76 Mean normal error for the Wrist Position Sense Test is 11°, while standard error of measurement is 2.8°; 8.4° is considered “genuine change.”34 Participant 2 had a 4.5° decrease in error in the Wrist Position Sense Test after training, which represents a 33% decrease in error and a shift from above normal to below normal error. For healthy older adults, the average number of errors on the Haptic Object Recognition Test is 4.7 ± 2.5.36 Participant 2 decreased from 7 errors at pretest to 1 error at posttest. Following training, the MAL scores for participant 2 approached prestroke levels of use at 4.7/5, change in the MAL scores exceeded the arbitrarily established MCID of 10%.47 WMFT scores also exceeded the MCID.48 Participant 2 had a 29% decrease in time per peg on the Nine-Hole Peg Test and was within the range of normal (18–20 seconds)38 at posttest. Her Box and Blocks Test score was 76% of normal at both time points. Imaging Outcomes: Analysis of post-minus-pretest contrast of brush discrimination for participant 2 indicated a statistically significant increase in activation in clusters, peaking in the left postcentral gyrus (Figure 1B), the supplementary motor area, and in the right inferior frontal gyrus after training. The diffusion tractography models of the right and left sSTRs for participant 2 were symmetrical, FA and FD pre- and posttraining values were stable showing typical variability associated with these measures (Table 4).64 Percentage of brain volume change was 0.17%.
Poststroke tactile sensory dysfunction is common. This article detailed a novel, intensive training program and associated outcome measures, emphasizing sensory discrimination and manual manipulation of objects, which may be a useful framework from which a clinical trial of sensorimotor training after stroke could be designed. During training, the participants were engaged and able to participate at relatively similar levels, as indicated by time on task, despite differences in hand function. Tasks were easily adapted to meet the functional level of each individual and progressed to challenge emerging skills. Furthermore, this study provides an example of extending measurement to neural reorganization of the sensorimotor system that accompanies functional improvement.
Both participants surpassed the MCID in arm function after training, measured by the WMFT. Their recovery paralleled that achieved from motor-focused training paradigms, such as constraint-induced movement therapy.67 It should be noted that the MCID on the WMFT of −19 seconds, referred to here, was established in a study of participants with acute stroke.48 Therefore, caution should be exercised when interpreting the importance of this change for persons with chronic stroke. Sensory recovery was more variable and difficult to evaluate. Participant 2, with initial mild sensory impairment, demonstrated improvement in touch perception, wrist proprioception, and shape discrimination. Participant 1, with severely impaired sensation at pretest, had not improved in sensory measures by posttest. It is possible that the 2-week intervention was not adequate to show change on the sensory measures when impairment is severe. It is also possible that the more severe motor impairment of participant 1 limited the amount of sensory improvement.
This protocol used a variety of behavioral tests to evaluate function. Review of the results and observation regarding their application yielded several key ideas. The Weinstein Enhanced Sensory Test, although easily completed, did not allow sufficient discrimination of touch perception; thus, the Semmes-Weinstein monofilaments are a preferable measure.76 The Haptic Object Recognition Test is very challenging, especially for older adults, because of the cross-modal nature (ie, haptic exploration with visual comparison of unfamiliar objects). It requires visual imagery, perhaps to a greater extent than other shape discrimination measures36; use of another measure of shape discrimination is recommended. The Hand Active Sensation Test discriminates high and low function well but is lengthy to administer; other measures of texture and weight discrimination should be explored. The Wrist Position Sense Test adequately identifies proprioception deficits and was sensitive to change. Finally, our participant with no sensory recovery after training could not discriminate hot and cold. Hot/cold discrimination screening is economical and time-efficient. Future researchers may wish to include temperature discrimination with other measures examined to predict sensory recovery. Motor measures used here were effective in discriminating motor behavior. The largest pre-post test differences were documented using the WMFT and MAL. We included both the Nine-Hole Peg Test and Box and Blocks Test to provide a greater focus on hand and finger function; however, the WMFT seems to differentiate function as effectively as these other measures. In summary, the motor outcome measures used in this case series are expected to capture change due to training in larger studies, using this protocol. Continued evaluation of sensory measures to identify those that provide the best profile of sensory behavior poststroke is recommended.
Participant 1, with severely impaired left-hand sensation and no measurable recovery of sensory function, had low activation overall during left index brush discrimination, and most notably, the ipsilesional right parietal cortex had no activation that met threshold before or after training. This likely reflects impaired perception of the stimulus at both time points. A post-minus-pretest contrast identified significantly greater activation bilaterally; however, the majority of voxels were in the left sensorimotor cortical areas after training, suggesting predominantly contralesional neural reorganization. In the absence of measurable change in sensory function, we suggest that this functional reorganization may represent the effect of practice imagining sensory stimuli.77 However, we cannot rule out the possibility that improved sensory function may have been possible with longer treatment duration or that the posttest activation change might be a precursor for later sensory improvement. Participant 1 had a 0.4% increase in brain volume after training. At just more than the published error rate of 0.2% for the method used, the significance of the increase is difficult to interpret. Overall volume and pattern of activation of participant 2 was within the range of previously published control data at both time points,31 evidence that she perceived the stimulus and was performing the task. A contrast of post-minus-pretest right index brush perception identified statistically significantly greater activation in left ipsilesional sensory cortex (Figure 1B), right inferior frontal gyrus, and left supplementary motor area after training. If the statistical difference in fMRI in these 2 participants is taken as evidence of neural reorganization, these findings are in line with others who report better function is associated with a return to contralateral control, as demonstrated by participant 2, while poorer function is more often associated with ipsilateral and diffuse patterns of activation, as demonstrated by participant 1.13
Diffusion imaging studies suggest white matter remodeling results from training in healthy children,78 adults,79 and elders.80 Animal studies of training-induced white matter remodeling identify time frames as short as 1,81 2,82 and 6 weeks.83 At present, there is limited evidence of white matter remodeling after stroke in humans. A recent cross-sectional study of the microstructure of the corticospinal tract after stroke suggests motor skill recovery relates to the remodeling of both ipsilesional and contralesional corticospinal tracts.84 Network analysis of poststroke white matter suggests that contralesional regions homologous to the lesion are compromised while other regions exhibit positive adaptive changes.85
The participants in this case series have markedly different structural integrity of the sSTR in their lesioned hemisphere. In these 2 participants, ipsilesional sSTR integrity appears to correspond to their level of sensory function. While the sSTRs are nearly symmetrical in participant 2, in participant 1, contralesional sSTR has high FA, FD, and bundle volume values that may reflect contralesional remodeling similar to data from Schaechter et al,84 who suggest evidence of contralesional corticospinal tract remodeling. The small volume of white matter obtained in the right sSTR bundle in participant 1 reflects white matter damage associated with the stroke lesion. Lack of change in sensory function after training in participant 1 points to the possibility that a minimum amount of neural substrate may be necessary for sensory recovery. Given this, it is interesting to consider whether a visuomotor training program with enriched feedback, as described by Quaney et al,86 would have yielded better outcomes for this participant. These ideas are important from a prognostic standpoint; however, additional inquiry is needed to identify the minimum functional activation or substrate required to benefit from sensorimotor or visuomotor training.
The tractography method and diffusion parameters used here did not identify a change in sSTR white matter after training in either participant. The 34% increase in FA in participant 1 is likely an artifact of low reliability associated with measurement of small white matter tracts.64 Importantly, the tractography method and diffusion parameters used here may not be sensitive to white matter reorganization; alternatively, reorganization may have taken place elsewhere in network. These cases highlight questions for future research on poststroke white matter reorganization, including (1) what treatment dose is necessary, (2) where microstructural white matter changes might occur, (3) what diffusion parameters are sensitive enough to identify change, and (4) what time-frame is sufficient?
This study lacked a multiple baseline design, and while the participants were in the chronic phase poststroke, natural recovery cannot be ruled out. Study participants did not have aphasia, apraxia, or neglect. We expect these conditions would affect outcomes of future research. We used different sensory discrimination tasks for fMRI and behavioral testing. Because of incompatibility with the MRI, Hand Active Sensation Test scores were not obtained during functional scanning; instead, we used brush texture discrimination, which reliably identifies sensory discrimination dysfunction in stroke survivors.87 Prior experience with MRI may impact activation at posttest, consistent with the observation of less variability in experienced than MRI naive participants.88 Further research on dose, timing, and duration of training is necessary to generalize this protocol to the greater population of individuals with stroke.
Sensorimotor training, using a protocol focused on manual manipulation and sensory discrimination, may be an effective method for improving sensory and motor function poststroke and bears further evaluation. Additional research is needed to identify best measures of sensory function that are easily applied and span the breadth of tactile sensory behavior. Conversely, the WMFT and MAL effectively measure change from this and other sensorimotor training paradigms.67 Finally, the potential for sensory recovery appears strongly related to the integrity of the sSTR; however, future work must look beyond this large white matter tract for structural change in other components of the sensory discrimination network. It is expected that subsequent evaluation of this protocol, in a large clinical trial, will elucidate the neural reorganization that supports sensorimotor recovery.
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diffusion imaging; fMRI; motor function; neural reorganization; sensory discrimination; sensory function; sensorimotor training; stroke