The Black Box of Technological Outcome Measures: An Example in Duchenne Muscular Dystrophy.

BACKGROUND: Outcome measures for non-ambulant Duchenne muscular dystrophy (DMD) patients are limited, with only the Performance of the Upper Limb (PUL) approved as endpoint for clinical trials. OBJECTIVE: We assessed four outcome measures based on devices developed for the gaming industry, aiming to overcome disadvantages of observer-dependency and motivation. METHODS: Twenty-two non-ambulant DMD patients (range 8.6-24.1 years) and 14 healthy controls (HC; range 9.5-25.4 years) were studied at baseline and 16 patients at 12 months using Leap Motion to quantify wrist/hand active range of motion (aROM) and a Kinect sensor for reached volume with Ability Captured Through Interactive Video Evaluation (ACTIVE), Functional Workspace (FWS) summed distance to seven upper extremity body points, and trunk compensation (KinectTC). PUL 2.0 was performed in patients only. A stepwise approach assessed quality control, construct validity, reliability, concurrent validity, longitudinal change and patient perception. RESULTS: Leap Motion aROM distinguished patients and HCs for supination, radial deviation and wrist flexion (range p = 0.006 to <0.001). Reliability was low and the manufacturer's hand model did not match the sensor's depth images. ACTIVE differed between patients and HCs (p < 0.001), correlated with PUL (rho = 0.76), and decreased over time (p = 0.030) with a standardized response mean (SRM) of -0.61. It was appraised as fun on a 10-point numeric rating scale (median 9/10). PUL decreased over time (p < 0.001) with an SRM of -1.28, and was appraised as fun (median 7/10). FWS summed distance distinguished patients and HCs (p < 0.001), but reliability in patients was insufficient. KinectTC differed between patients and HCs (p < 0.01), but correlated insufficiently with PUL (rho = -0.69). CONCLUSIONS: Only ACTIVE qualified as potential outcome measure in non-ambulant DMD patients, although the SRM was below the commonly used threshold of 0.8. Lack of insight in technological constraints due to intellectual property and software updates made the technology behind these outcome measures a kind of black box that could jeopardize long-term use in clinical development.

Patient-Tailored Augmented Reality Games for Assessing Upper Extremity Motor Impairments in Parkinson's Disease and Stroke.

In clinical practice, upper extremity motor impairments are commonly assessed with disease-specific, subjectively scored and low-resolution rating scales that often do not consider the variations in tasks and environment that are essential aspects of daily life. Augmented reality (AR) systems with contactless tracking of the hand and upper body offer opportunities for objective quantification of motor (dys)function in a challenging, engaging and patient-tailored environment. In this study, we explore the potential of AR for evaluating 1) speed and goal-directedness of movements within the individually determined interaction space, 2) adaptation of hand opening to objects of different sizes, and 3) obstacle avoidance in healthy individuals (N = 10) and two highly prevalent neurological conditions (N = 10 patients with Parkinson's Disease and N = 10 stroke patients). We successfully implemented three AR games to evaluate these key aspects of motor function. As expected, PD patients moved slower than controls and needed more time for task completion. No differences were observed between stroke patients and controls, perhaps because motor impairments in this patient group were relatively mild. Importantly, usability of our AR system was good and considerably improved compared to our previous study due to more natural and patient-tailored interaction. Although our findings testify to the potential of AR for assessing motor impairments in patients with neurological conditions and provide starting points for further improvement, there are still many steps to be taken towards application in clinical practice.

Cognitive-motor interference during goal-directed upper-limb movements.

Research and clinical practice have focused on effects of a cognitive dual-task on highly automated motor tasks such as walking or maintaining balance. Despite potential importance for daily life performance, there are only a few small studies on dual-task effects on upper-limb motor control. We therefore developed a protocol for assessing cognitive-motor interference (CMI) during upper-limb motor control and used it to evaluate dual-task effects in 57 healthy individuals and two highly prevalent neurological disorders associated with deficits of cognitive and motor processing (57 patients with Parkinson's disease [PD], 57 stroke patients). Performance was evaluated in cognitive and motor domains under single- and dual-task conditions. Patterns of CMI were explored to evaluate overall attentional capacity and attention allocation. As expected, patients with neurological deficits showed different patterns of CMI compared to healthy individuals, depending on diagnosis (PD or stroke) and severity of cognitive and/or motor symptoms. Healthy individuals experienced CMI especially under challenging conditions of the motor task. CMI was greater in PD patients, presumably due to insufficient attentional capacity in relation to increased cognitive involvement in motor control. Although no general increase of CMI was observed in stroke patients, correlation analyses suggested that especially patients with severe motor dysfunction experienced CMI. Clinical ratings of cognitive and motor function were weakly associated with CMI, suggesting that CMI reflects a different construct than these unidimensional clinical tests. It remains to be investigated whether CMI is an indicator of difficulties with day-to-day activities.

Manipulation of visual information affects control strategy during a visuomotor tracking task.

Proper understanding of motor control requires insight into the extent and manner in which task performance and control strategy are influenced by various aspects of visual information. We therefore systematically manipulated the visual presentation (i.e., scaling factor and optical flow density) of a visuomotor tracking task without changing the task itself, and investigated the effect on performance, effort, motor control strategy (i.e., anticipatory or corrective steering) and underlying neuromechanical parameters (i.e., intrinsic muscle stiffness and damping, and proprioceptive and visual feedback). Twenty healthy participants controlled the left-right position of a virtual car (by means of wrist rotations in a haptic robot) to track a slightly curved virtual road (presented on a 60" LED screen), while small torque perturbations were applied to the wrist (1.25-20Hz multisine) for quantification of the neuromechanical parameters. This visuomotor tracking task was performed in conditions with low/medium/high scaling factor and low/high optical flow density. Task performance was high in all conditions (tracking accuracy 96.6%-100%); a higher scaling factor was associated with slightly better performance. As expected, participants did adapt their control strategy and the use of proprioceptive and visual feedback in response to changes in the visual presentation. These findings indicate that effects of visual representation on motor behavior should be taken into consideration in designing, interpreting and comparing experiments on motor control in health and disease. In future studies, these insights might be exploited to assess the sensory-motor adaptability in various clinical conditions.

Optical Hand Tracking: A Novel Technique for the Assessment of Bradykinesia in Parkinson's Disease.

BACKGROUND: Evaluation of therapies for Parkinson's disease (PD) may benefit from objective quantification of the separate movement components of bradykinesia (i.e., velocity, amplitude, and rhythm). This study evaluated the sensitivity and reliability of parameters derived from recently available optical hand tracking techniques for patient-friendly, automated quantification of bradykinesia of the upper extremity in PD. METHODS: Fifty-seven patients with PD and 57 healthy individuals (controls) performed repetitive finger tapping (RFT), alternating hand movements (AHM), and alternating forearm movements (AFM). Movement components of bradykinesia (i.e., velocity, frequency, amplitude, hesitations, and halts) were quantified using optical hand tracking. Reliability was quantified using intraclass correlation coefficients in a subgroup of 12 patients with PD and 12 controls (test-retest) and in all 57 controls (intra-trial). RESULTS: RFT and AHM were successfully recorded in 94% of all participants. Movement components differed between patients with PD and controls and were correlated with clinical ratings. Velocity and halt duration appeared to be most useful (i.e., the largest difference between the PD and control groups, good reliability) for the quantification of RFT, whereas frequency appeared to be most useful for the quantification of AHM. Other variables, such as frequency and amplitude of RFT, showed poor test-retest reliability, because they were susceptible to changes in movement strategy. AFM was excluded from the analysis because of problems with hand recognition. CONCLUSION: Novel optical hand tracking techniques yield promising results for patient-friendly quantification of bradykinesia of the upper extremity in PD. Future work should aim to optimize optical hand tracking and reduce susceptibility to changes in strategy.

Evaluation of mirrored muscle activity in patients with Complex Regional Pain Syndrome.

OBJECTIVE: Motor dysfunction in Complex Regional Pain Syndrome (CRPS) has been associated with bilateral changes in central motor processing, suggesting abnormal coupling between the affected and unaffected limb. We evaluated the occurrence of involuntary muscle activity in a limb during voluntary movements of the contralateral limb (i.e., mirror activity) in unilaterally affected patients to examine disinhibition of contralateral motor activity in CRPS. METHODS: Mirror activity was examined during unimanual rhythmic flexion-extension movements of the wrist through in-depth analysis of electromyography recordings from the passive arm in 20 CRPS patients and 40 controls. RESULTS: The number of mirror-epochs was comparable for both arms in both CRPS patients and controls. Mirror-epochs in the affected arm of patients were comparable to those in controls. Mirror-epochs in the unaffected arm were shorter and showed less resemblance (in terms of rhythm and timing) to activity of the homologous muscle in the moving arm compared to mirror-epochs in controls. CONCLUSIONS: No evidence for disinhibition of contralateral motor activity was found during unimanual movement. SIGNIFICANCE: Although motor dysfunction in CRPS has been associated with bilateral changes in cortical motor processing, the present findings argue against disinhibition of interhemispheric projections to homologous muscles in the contralateral limb during unimanual movement.

Motor dysfunction of complex regional pain syndrome is related to impaired central processing of proprioceptive information.

UNLABELLED: Our understanding of proprioceptive deficits in complex regional pain syndrome (CRPS) and its potential contribution to impaired motor function is still limited. To gain more insight into these issues, we evaluated accuracy and precision of joint position sense over a range of flexion-extension angles of the wrist of the affected and unaffected sides in 25 chronic CRPS patients and in 50 healthy controls. The results revealed proprioceptive impairment at both the patients' affected and unaffected sides, characterized predominantly by overestimation of wrist extension angles. Precision of the position estimates was more prominently reduced at the affected side. Importantly, group differences in proprioceptive performance were observed not only for tests at identical percentages of each individual's range of wrist motion but also when controls were tested at wrist angles that corresponded to those of the patient's affected side. More severe motor impairment of the affected side was associated with poorer proprioceptive performance. Based on additional sensory tests, variations in proprioceptive performance over the range of wrist angles, and comparisons between active and passive displacements, the disturbances of proprioceptive performance most likely resulted from altered processing of afferent (and not efferent) information and its subsequent interpretation in the context of a distorted "body schema." PERSPECTIVE: The present results point at a significant role for impaired central processing of proprioceptive information in the motor dysfunction of CRPS and suggest that therapeutic strategies aimed at identification of proprioceptive impairments and their restoration may promote the recovery of motor function in CRPS patients.

Deficient muscle activation in patients with Complex Regional Pain Syndrome and abnormal hand postures: an electromyographic evaluation.

OBJECTIVE: Motor abnormalities in Complex Regional Pain Syndrome (CRPS) are common and often characterized by a restricted active range of motion (AROM) and an increased resistance to passive movements, whereby the affected body part preferably adopts an abnormal posture. The objective of the present study was to obtain a better understanding of the factors that are associated with these abnormal postures and limitations of the AROM, and to investigate whether these motor impairments reflect dystonia. METHODS: We evaluated characteristics of surface EMG of the flexor carpi radialis and extensor carpi radialis muscles during active maintenance of various flexion-extension postures of the wrist of the affected and unaffected side in 15 chronic CRPS patients, and in 15 healthy controls. RESULTS: Deviant joint postures in chronic CRPS - at least in those patients with some range of active movement - were not characterized by sustained muscle contractions, and limitations of the AROM were not attributable to excessive co-contraction. Rather, the agonistic muscle and its antagonist were activated in normal proportions, albeit over a limited range. CONCLUSIONS: The AROM limitations and abnormal postures that are often observed in chronic CRPS patients are not associated with excessive muscle activity and hence do not exhibit the characteristics typical of dystonia. SIGNIFICANCE: We hypothesize that structural alterations in skeletal muscle tissue and pain-induced adaptations of motor function may contribute to the observed motor impairments. Our findings may have important clinical implications, since commonly prescribed treatments are aimed at reducing excessive muscle contraction.

Anchoring in rhythmic in-phase and antiphase visuomotor tracking.

Rhythmic limb movements are often anchored at particular points in the movement cycle. Anchoring may reveal essential task-specific information for motor control. We examined the effect of tracking mode (in-phase, antiphase) and gaze direction (left, right) on anchoring in visuomotor tracking with and without concurrent visual feedback of the hand movement. For in-phase tracking, anchoring was observed at the foveated reversal point whereas for antiphase tracking anchoring was observed at both reversals, suggesting the presence of two reference points instead of one. Anchoring at the foveated reversal reflected gaze anchoring (i.e., coalignment of hand and gaze) while anchoring at the nonfoveated reversal reflected visuomotor synchronization (i.e., the hand was steered to the nonfoveated reversal coincident with a target reversal at the point of gaze). We propose that the number and location of anchor points play a crucial role in the underlying control by providing reference values for error correction processes.

Walking to the beat of different drums: practical implications for the use of acoustic rhythms in gait rehabilitation.

Acoustic rhythms are frequently used in gait rehabilitation, with positive instantaneous and prolonged transfer effects on various gait characteristics. The gait modifying ability of acoustic rhythms depends on how well gait is tied to the beat, which can be assessed with measures of relative timing of auditory-motor coordination. We examined auditory-motor coordination in 20 healthy elderly individuals walking to metronome beats with pacing frequencies slower than, equal to, and faster than their preferred cadence. We found that more steps were required to adjust gait to the beat, the more the metronome rate deviated from the preferred cadence. Furthermore, participants anticipated the beat with their footfalls to various degrees, depending on the metronome rate; the faster the tempo, the smaller the phase advance or phase lead. Finally, the variability in the relative timing between footfalls and the beat was smaller for metronome rates closer to the preferred cadence, reflecting superior auditory-motor coordination. These observations have three practical implications. First, instantaneous effects of acoustic stimuli on gait characteristics may typically be underestimated given the considerable number of steps required to attune gait to the beat in combination with the usual short walkways. Second, a systematic phase lead of footfalls to the beat does not necessarily reflect a reduced ability to couple gait to the metronome. Third, the efficacy of acoustic rhythms to modify gait depends on metronome rate. Gait is coupled best to the beat for metronome rates near the preferred cadence.

Comparing the efficacy of metronome beeps and stepping stones to adjust gait: steps to follow!

Acoustic metronomes and visual targets have been used in rehabilitation practice to improve pathological gait. In addition, they may be instrumental in evaluating and training instantaneous gait adjustments. The aim of this study was to compare the efficacy of two cue types in inducing gait adjustments, viz. acoustic temporal cues in the form of metronome beeps and visual spatial cues in the form of projected stepping stones. Twenty healthy elderly (aged 63.2 ± 3.6 years) were recruited to walk on an instrumented treadmill at preferred speed and cadence, paced by either metronome beeps or projected stepping stones. Gait adaptations were induced using two manipulations: by perturbing the sequence of cues and by imposing switches from one cueing type to the other. Responses to these manipulations were quantified in terms of step-length and step-time adjustments, the percentage correction achieved over subsequent steps, and the number of steps required to restore the relation between gait and the beeps or stepping stones. The results showed that perturbations in a sequence of stepping stones were overcome faster than those in a sequence of metronome beeps. In switching trials, switching from metronome beeps to stepping stones was achieved faster than vice versa, indicating that gait was influenced more strongly by the stepping stones than the metronome beeps. Together these results revealed that, in healthy elderly, the stepping stones induced gait adjustments more effectively than did the metronome beeps. Potential implications for the use of metronome beeps and stepping stones in gait rehabilitation practice are discussed.