Exploring Motor Learning in Acute Stroke Through Robotics

The acute phase of stroke is characterized by an enhancement of neural plasticity which supports rapid motor recovery. It is unclear whether acute stroke patients can acquire new motor skills with their affected upper limb. The aims of this research program are: To test the capacity of acute stroke patients (< 21 days) to learn and retain a complex unimanual motor skill. To explore whether acute stroke to different brain regions (quantified with brain MRI) induces specific deficits in motor skill learning. To compare acute stroke patients with healthy individuals and with chronic stroke patients.

Over 3 consecutive days, the subjects will be evaluated and will train on the rehabilitation robot REAplan® (http://www.axinesis.com/). They will practice 2 serious games on the robot. In order to differentiate the effect of motor control recovery from that of MskL, the acute stroke patients will be randomised 4/1 to "MskL" (n=120) ,to "motor control recovery" (n=30) or to "conventional" group (n=15) with a minimisation software. The experimental design will be similar except that the "motor control recovery" group will practice the serious game EASY instead of CIRCUIT (see below) and the "conventional" group will practice conventional therapy instead of CIRCUIT. The performances on both EASY & CIRCUIT will be compared between groups (subjects in both groups will perform the EASY & CIRCUIT tasks).The total time of rehabilitation will be the same. The motor skill learning setup (CIRCUIT + EASY) that we developed and successfully used in healthy individuals and stroke patients has already been implemented in the REAplan environment and will be used as innovative serious games based on a speed/accuracy trade-off (SAT), allowing a detailed analysis of motor skill learning components (speed, accuracy, SAT, movement smoothness, dynamics...). For the serious game CIRCUIT, who based on motor skill learning, the subjects will have to practice a complex circuit and move as a cursor quickly and accurately as possible by controlling the handle of the robot with their affected hand/arm. For the other task EASY (a brick busters serious game), the aim will be to go back and forth between walls presented in different locations. The CONVENTIONAL therapy will consist in classical exercices focused in the upper limb administered by occupational therapist. The subacute stroke phase is a unique opportunity to investigate the role of brain structures in motor learning/control. Compared to chronic impairments (> 6 months post-stroke), the subacute phase provides a window into how a lesion perturbs sensorimotor functions prior to reorganisation driven by plasticity and neurorehabilitation. To clarify the role of different brain structures in MskL, Voxel-based Lesion Symptom Mapping (VLSM) based on high-resolution brain magnetic resonance imaging (MRI) scans, will be used to analyse the relationship between tissue damage and MskL scores on a voxel-by-voxel basis. In addition, several "classical" clinical scales and tests will be used to evaluate overall motor-sensory-cognitive functions. The subjects will practice serious games on the robot REAplan (R), requiring movements with the affected arm (unimanual tasks). And, we used a Dextrain® tool which allows quantification of key components of manual dexterity : forces, selectivity (independance of fingers movement) and coactivation of the fingers.Moreover, we added a Transcranial magnetic stimulation (TMS), as a tool for predicting recovery of motor function after stroke. In addition to the (sub)acute stroke patients, 4 others groups will be recruited for this study : a group of acute stroke patients who will receive "conventional rehabilitation" and be shortly tested on the robot (N=15), a group of chronic stroke patients (stroke > 6 months) who will not be hospitalized and will not undergo MRI (N=30), a group of healthy individuals who will not undergo MRI (N=50) and a group of patients with a transient global amnesia which is a sudden, temporary episode (<24hours) of memory loss (N=15). Subjects in these 4 groups will be randomized 1/1 in the two arms ("MSkL" versus "motor control recovery" arms), except the patients with a TGA who will be included in the "MSkL" arm only.

Intervention: training on the REAplan robot with a serious game based on motor skill learning (MSkL) serious game, the CIRCUIT.

Training on the REAplan robot with a serious game that requires similar type and amount of movements but does not rely on motor skill learning (EASY), a brick buster game.

Training sessions with classical exercices focused on the upper limb administered by occupation therapist.

change between Baseline Day1 and Day3 (acute) + between Baseline Day1 and 3/6 and 12 months post-stroke (subacute - chronic)

change between Baseline Day1 and Day3 (acute) + between Baseline Day1 and 3/6 and 12 months post-stroke (subacute - chronic)

change between Baseline Day1 and Day3 (acute) + between Baseline Day1 and 3/6 and 12 months post-stroke (subacute - chronic)

change between Baseline Day1 and Day3 (acute) + between Baseline Day1 and 3/6 and 12 months post-stroke (subacute - chronic)

Visual Analog Scale to evaluate fatigue between 0 and 10. The maximum value (10) indicate a high level of fatiguability.

change between Baseline Day1 and Day3 (acute) + between Baseline Day1 and 3/6 and 12 months post-stroke (subacute - chronic)

High-resolution 3D-MRI, diffusion MRI (DWI) & perfusion MRI (PWI with Arterial SPin Labelling technique) will be acquired. The stroke areas will be drawn with MRIcron as volumes of interest (VOI) in native space and compared.

change between Baseline Day1 and Day3 (acute) + between Baseline Day1 and 3/6 and 12 months post-stroke (subacute - chronic)

change between Baseline Day1 and Day3 (acute) + between Baseline Day1 and 3/6 and 12 months post-stroke (subacute - chronic)

change between Baseline Day1 and Day3 (acute) + between Baseline Day1 and 3/6 and 12 months post-stroke (subacute - chronic)

change between Baseline Day1 and Day3 (acute) + between Baseline Day1 and 3/6 and 12 months post-stroke (subacute - chronic)

correlation with the measure realized Day 1 with progression of the motor skill learning (change between Baseline Day1 and Day 3)

ACUTE STROKE PATIENTS: Inclusion Criteria: acute stroke (> 21 days) aged 18-90 years with a stroke lesion on brain imaging Exclusion Criteria: " classical " contre-indication to MRI (non-MR-compatible pacemaker, pregnancy, non-MR-compatible implanted devices, claustrophoby, etc ...) difficulty in understanding or executing commands drug/alcohol abuse severe aphasia / cognitive deficits interfering with study inability to voluntarily move the affected arm (i.e. complete paralysis of the arm) multiple strokes / dementia / psychiatric condition PATIENTS WITH TRANSIENT GLOBAL AMNESIA: Clinical diagnosis, criteria of Hodge & Warlow (1990): Anterograde amnesia observed by a witness No alteration of consciousness or loss of identity Cognitive dysfunction limited to amnesia Lack of focused neurological deficit or argument for a comitiality Absence of head trauma Symptom resolution within 24 hours Possible existence of vegetative symptoms Inclusion criteria: Transient global amnesia 8-90 years old Be able to perform 3 consecutive sessions on a rehabilitation robot Exclusion criteria: Severe aphasia / cognitive deficits interfering with study Psychiatric disorders Alcohol / drug addiction Exclusion criteria related to MRI HEALTHY INDIVIDUALS: Inclusion Criteria: • 18-90 years Exclusion Criteria: medical history with a previous stroke/neurological deficit drug/alcohol abuse psychiatric condition/ dementia CHRONIC STROKE PATIENTS: Inclusion Criteria: chronic stroke (>6 months) aged 18-90 years with a stroke lesion on brain imaging Exclusion Criteria: difficulty in understanding or executing commands drug/alcohol abuse severe aphasia / cognitive deficits interfering with study inability to voluntarily move the affected arm (i.e. complete paralysis of the arm) multiple strokes / dementia / psychiatric condition

the precise IPD plan has to be worked out if an easy and user-friendly solution is available, we intend to make the data available (after anonymisation of personal data).