optimizing self-exercise scheduling in motor stroke using Challenge Point Framework theory.

An important challenge for technology-assisted self-led rehabilitation is how to automate appropriate schedules of exercise that are responsive to patients' needs, and optimal for learning. While random scheduling has been found to be superior for long-term learning relative to fixed scheduling (Contextual Interference), this method is limited by not adequately accounting for task difficulty, or skill acquisition during training. One method that combines contextual interference with adaptation of the challenge to the skill-level of the player is Challenge Point Framework (CPF) theory. In this pilot study we test whether self-led motor training based upon CPF scheduling achieves faster learning than deterministic, fixed scheduling. Training was implemented in a mobile gaming device adapted for arm disability, allowing for grip and wrist exercises. We tested 11 healthy volunteers and 12 hemiplegic stroke patients in a single-blinded no crossover controlled randomized trial. Results suggest that patients training with CPF-based adaption performed better than those training with fixed conditions. This was not seen for healthy volunteers whose performance was close to ceiling. Further data collection is required to determine the significance of the results.

Motor dexterity and strength depend upon integrity of the attention-control system.

Attention control (or executive control) is a higher cognitive function involved in response selection and inhibition, through close interactions with the motor system. Here, we tested whether influences of attention control are also seen on lower level motor functions of dexterity and strength-by examining relationships between attention control and motor performance in healthy-aged and hemiparetic-stroke subjects (n = 93 and 167, respectively). Subjects undertook simple-tracking, precision-hold, and maximum force-generation tasks, with each hand. Performance across all tasks correlated strongly with attention control (measured as distractor resistance), independently of factors such as baseline performance, hand use, lesion size, mood, fatigue, or whether distraction was tested during motor or nonmotor cognitive tasks. Critically, asymmetric dissociations occurred in all tasks, in that severe motor impairment coexisted with normal (or impaired) attention control whereas normal motor performance was never associated with impaired attention control (below a task-dependent threshold). This implies that dexterity and force generation require intact attention control. Subsequently, we examined how motor and attention-control performance mapped to lesion location and cerebral functional connectivity. One component of motor performance (common to both arms), as well as attention control, correlated with the anatomical and functional integrity of a cingulo-opercular "salience" network. Independently of this, motor performance difference between arms correlated negatively with the integrity of the primary sensorimotor network and corticospinal tract. These results suggest that the salience network, and its attention-control function, are necessary for virtually all volitional motor acts while its damage contributes significantly to the cardinal motor deficits of stroke.

Balancing the playing field: collaborative gaming for physical training.

BACKGROUND: Multiplayer video games promoting exercise-based rehabilitation may facilitate motor learning, by increasing motivation through social interaction. However, a major design challenge is to enable meaningful inter-subject interaction, whilst allowing for significant skill differences between players. We present a novel motor-training paradigm that allows real-time collaboration and performance enhancement, across a wide range of inter-subject skill mismatches, including disabled vs. able-bodied partnerships. METHODS: A virtual task consisting of a dynamic ball on a beam, is controlled at each end using independent digital force-sensing handgrips. Interaction is mediated through simulated physical coupling and locally-redundant control. Game performance was measured in 16 healthy-healthy and 16 patient-expert dyads, where patients were hemiparetic stroke survivors using their impaired arm. Dual-player was compared to single-player performance, in terms of score, target tracking, stability, effort and smoothness; and questionnaires probing user-experience and engagement. RESULTS: Performance of less-able subjects (as ranked from single-player ability) was enhanced by dual-player mode, by an amount proportionate to the partnership's mismatch. The more abled partners' performances decreased by a similar amount. Such zero-sum interactions were observed for both healthy-healthy and patient-expert interactions. Dual-player was preferred by the majority of players independent of baseline ability and subject group; healthy subjects also felt more challenged, and patients more skilled. CONCLUSION: This is the first demonstration of implicit skill balancing in a truly collaborative virtual training task leading to heightened engagement, across both healthy subjects and stroke patients.

Elasticity improves handgrip performance and user experience during visuomotor control.

Passive rehabilitation devices, providing motivation and feedback, potentially offer an automated and low-cost therapy method, and can be used as simple human-machine interfaces. Here, we ask whether there is any advantage for a hand-training device to be elastic, as opposed to rigid, in terms of performance and preference. To address this question, we have developed a highly sensitive and portable digital handgrip, promoting independent and repetitive rehabilitation of grasp function based around a novel elastic force and position sensing structure. A usability study was performed on 66 healthy subjects to assess the effect of elastic versus rigid handgrip control during various visuomotor tracking tasks. The results indicate that, for tasks relying either on feedforward or on feedback control, novice users perform significantly better with the elastic handgrip, compared with the rigid equivalent (11% relative improvement, 9-14% mean range; p < 0.01). Furthermore, there was a threefold increase in the number of subjects who preferred elastic compared with rigid handgrip interaction. Our results suggest that device compliance is an important design consideration for grip training devices.

Democratizing Neurorehabilitation: How Accessible are Low-Cost Mobile-Gaming Technologies for Self-Rehabilitation of Arm Disability in Stroke?

Motor-training software on tablets or smartphones (Apps) offer a low-cost, widely-available solution to supplement arm physiotherapy after stroke. We assessed the proportions of hemiplegic stroke patients who, with their plegic hand, could meaningfully engage with mobile-gaming devices using a range of standard control-methods, as well as by using a novel wireless grip-controller, adapted for neurodisability. We screened all newly-diagnosed hemiplegic stroke patients presenting to a stroke centre over 6 months. Subjects were compared on their ability to control a tablet or smartphone cursor using: finger-swipe, tap, joystick, screen-tilt, and an adapted handgrip. Cursor control was graded as: no movement (0); less than full-range movement (1); full-range movement (2); directed movement (3). In total, we screened 345 patients, of which 87 satisfied recruitment criteria and completed testing. The commonest reason for exclusion was cognitive impairment. Using conventional controls, the proportion of patients able to direct cursor movement was 38-48%; and to move it full-range was 55-67% (controller comparison: p>0.1). By comparison, handgrip enabled directed control in 75%, and full-range movement in 93% (controller comparison: p<0.001). This difference between controllers was most apparent amongst severely-disabled subjects, with 0% achieving directed or full-range control with conventional controls, compared to 58% and 83% achieving these two levels of movement, respectively, with handgrip. In conclusion, hand, or arm, training Apps played on conventional mobile devices are likely to be accessible only to mildly-disabled stroke patients. Technological adaptations such as grip-control can enable more severely affected subjects to engage with self-training software.

Prediction of stroke thrombolysis outcome using CT brain machine learning.

A critical decision-step in the emergency treatment of ischemic stroke is whether or not to administer thrombolysis - a treatment that can result in good recovery, or deterioration due to symptomatic intracranial haemorrhage (SICH). Certain imaging features based upon early computerized tomography (CT), in combination with clinical variables, have been found to predict SICH, albeit with modest accuracy. In this proof-of-concept study, we determine whether machine learning of CT images can predict which patients receiving tPA will develop SICH as opposed to showing clinical improvement with no haemorrhage. Clinical records and CT brains of 116 acute ischemic stroke patients treated with intravenous thrombolysis were collected retrospectively (including 16 who developed SICH). The sample was split into training (n = 106) and test sets (n = 10), repeatedly for 1760 different combinations. CT brain images acted as inputs into a support vector machine (SVM), along with clinical severity. Performance of the SVM was compared with established prognostication tools (SEDAN and HAT scores; original, or after adaptation to our cohort). Predictive performance, assessed as area under receiver-operating-characteristic curve (AUC), of the SVM (0.744) compared favourably with that of prognostic scores (original and adapted versions: 0.626-0.720; p < 0.01). The SVM also identified 9 out of 16 SICHs, as opposed to 1-5 using prognostic scores, assuming a 10% SICH frequency (p < 0.001). In summary, machine learning methods applied to acute stroke CT images offer automation, and potentially improved performance, for prediction of SICH following thrombolysis. Larger-scale cohorts, and incorporation of advanced imaging, should be tested with such methods.

Effect of genetic variants associated with plasma homocysteine levels on stroke risk.

BACKGROUND AND PURPOSE: Elevated total plasma homocysteine (tHcy) levels are known to be associated with increased risk of ischemic stroke (IS). Given that both tHcy and IS are heritable traits, we investigated a potential genetic relationship between homocysteine levels and stroke risk by assessing 18 polymorphisms previously associated with tHcy levels for their association with IS and its subtypes. METHODS: Previous meta-analysis results from an international stroke collaborative network, METASTROKE, were used to assess association of the 18 tHcy-associated single-nucleotide polymorphisms (SNPs) in 12 389 IS cases and 62 004 controls. We also investigated the associations in regions located within 50 kb from the 18 tHcy-related SNPs and the association of a genetic risk score, including the 18 SNPs. RESULTS: One SNP located in the RASIP1 gene and a cluster of 3 SNPs located at and near SLC17A3 were significantly associated with IS (P<0.0003) after correcting for multiple testing. For stroke subtypes, the sentinel SNP located upstream of MUT was significantly associated with small-vessel disease (P=0.0022), whereas 1 SNP located in MTHFR was significantly associated with large-vessel disease (P=0.00019). A genetic risk score, including the 18 SNPs, did not show significant association with IS or its subtypes. CONCLUSIONS: This study found several potential associations with IS and its subtypes: an association of an MUT variant with small-vessel disease, an MTHFR variant with large-vessel disease, and associations of RASIP1 and SLC17A3 variants with overall IS.

Genome-wide analysis of blood pressure variability and ischemic stroke.

BACKGROUND AND PURPOSE: Visit-to-visit variability in blood pressure (vBP) is associated with ischemic stroke. We sought to determine whether such variability has genetic causes and whether genetic variants associated with BP variability are also associated with ischemic stroke. METHODS: A Genome Wide Association Study (GWAS) for loci influencing BP variability was undertaken in 3802 individuals from the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) study, in which long-term visit-to-visit and within-visit BP measures were available. Because BP variability is strongly associated with ischemic stroke, we genotyped the sentinel single nucleotide polymorphism in an independent ischemic stroke population comprising 8624 cases and 12 722 controls and in 3900 additional (Scandinavian) participants from the ASCOT study to replicate our findings. RESULTS: The ASCOT discovery GWAS identified a cluster of 17 correlated single nucleotide polymorphisms within the NLGN1 gene (3q26.31) associated with BP variability. The strongest association was with rs976683 (P=1.4×10(-8)). Conditional analysis of rs976683 provided no evidence of additional independent associations at the locus. Analysis of rs976683 in patients with ischemic stroke found no association for overall stroke (odds ratio, 1.02; 95% CI, 0.97-1.07; P=0.52) or its subtypes: cardioembolic (odds ratio, 1.07; 95% CI, 0.97-1.16; P=0.17), large vessel disease (odds ratio, 0.98; 95% CI, 0.89-1.07; P=0.60), and small vessel disease (odds ratio, 1.07; 95% CI, 0.97-1.17; P=0.19). No evidence for association was found between rs976683 and BP variability in the additional (Scandinavian) ASCOT participants (P=0.18). CONCLUSIONS: We identified a cluster of single nucleotide polymorphisms at the NLGN1 locus showing significant association with BP variability. Follow-up analyses did not support an association with risk of ischemic stroke and its subtypes.

Triple dissociation of attention networks in stroke according to lesion location.

OBJECTIVE: To determine whether behavioral dissociations and interactions occur between the attentional functions-alerting, orienting, and conflict resolution-depending upon stroke location and to determine the approximate proportion of patients who can be classified into 1 of these 3 anatomical networks. METHODS: We recruited 110 anatomically unselected acute stroke patients and 62 age-matched controls. Subjects underwent the attention network test (ANT), which provides a measure of each attention type. Their performance was related to lesion anatomy on MRI using a voxel-lesion mapping approach. RESULTS: Patients as a whole performed poorer than controls, but there were no group differences in the size of attentional effects. Specific deficits in 1 of the 3 ANT-tested functions were found in the following lesion locations: alerting deficiency with bilateral anteromedial thalamus and upper brainstem (17% of patients); orienting impairment with right pulvinar and right temporoparietal cortex (15%); conflict resolution with bilateral prefrontal and premotor areas (23%). Lesions to right frontoparietal regions also modified interactions among the 3 types of attention. CONCLUSIONS: More than half of all stroke patients can be expected to have a lesion location classifiable into 1 of the 3 principal attention networks. Our results have potential implications for therapy personalization in focal brain diseases including stroke.