Noninvasive brain stimulation to improve motor outcomes after stroke.

PURPOSE OF REVIEW: This review highlights recent developments in noninvasive brain stimulation (NIBS) techniques and applications for improving motor outcomes after stroke. Two promising areas of development relate to deep brain neuromodulation and the use of single-pulse transcranial magnetic stimulation (TMS) within a prediction tool for predicting upper limb outcome for individual patients. RECENT FINDINGS: Systematic reviews highlight the inconsistent effect sizes of interventional NIBS for motor outcome after stroke, as well as limited evidence supporting the interhemispheric competition model. To improve the therapeutic efficacy of NIBS, studies have leveraged metaplasticity and priming approaches. Transcranial temporal interference stimulation (tTIS) and low-intensity focused ultrasound stimulation (LIFUS) are emerging NIBS techniques with potential for modulating deeper brain structures, which may hold promise for stroke neurorehabilitation. Additionally, motor evoked potential (MEP) status obtained with single-pulse TMS is a prognostic biomarker that could be used to tailor NIBS for individual patients. SUMMARY: Trials of interventional NIBS to improve stroke outcomes may be improved by applying NIBS in a more targeted manner. This could be achieved by taking advantage of NIBS techniques that can be targeted to deeper brain structures, using biomarkers of structural and functional reserve to stratify patients, and recruiting patients in more homogeneous time windows.

Biomarkers of Motor Outcomes After Stroke.

Predicting motor outcomes after stroke based on clinical judgment alone is often inaccurate and can lead to inefficient and inequitable allocation of rehabilitation resources. Prediction tools are being developed so that clinicians can make evidence-based, accurate, and reproducible prognoses for individual patients. Biomarkers of corticospinal tract structure and function can improve prediction tool performance, particularly for patients with initially moderate to severe motor impairment. Being able to make accurate predictions for individual patients supports rehabilitation planning and communication with patients and families.

Accuracy and Reliability of Remote Categorization of Upper Limb Outcome After Stroke.

BACKGROUND: There is an increasing need for motor assessments after stroke that can be performed quickly and remotely. The Fast Outcome Categorization of the Upper Limb after Stroke-4 (FOCUS-4) assessment remotely classifies upper limb outcome into 1 of 4 categories after stroke and was developed via retrospective analysis of Action Research Arm Test (ARAT) scores. OBJECTIVE: The aim of this study was to prospectively evaluate the accuracy and reliability of FOCUS-4 assessments for categorizing upper limb outcome after stroke when administered remotely during a videocall compared to an in-person ARAT. METHODS: Data were collected from 26 participants at 3 months post-stroke (3M), 27 participants at 6 months post-stroke (6M), and 56 participants at the chronic stage of stroke (>6M). Participants performed an in-person ARAT and a remote FOCUS-4 assessment administered during a videocall, and accuracy was evaluated by comparing the upper limb outcome categories. Participants at the chronic stage of stroke also performed a second remote FOCUS-4 assessment to assess between-day reliability. RESULTS: Overall accuracy of the remote FOCUS-4 assessment was 88% at 3M and 96% at 6M. Overall accuracy of the first and second remote FOCUS-4 assessments at the chronic stage was 75% and 79%, respectively. Reliability of the FOCUS-4 assessment at the chronic stage was 82%. The remote FOCUS-4 assessment was most accurate and reliable for participants with mild or severe upper limb functional impairment. CONCLUSIONS: The remote FOCUS-4 assessment has potential to classify upper limb functional capacity or to screen possible participants for stroke trials, but external validation is required.

Modulation of ipsilateral motor evoked potentials during bimanual coordination tasks.

Introduction: Ipsilateral motor evoked potentials (iMEPs) are difficult to obtain in distal upper limb muscles of healthy participants but give a direct insight into the role of ipsilateral motor control. Methods: We tested a new high-intensity double pulse transcranial magnetic stimulation (TMS) protocol to elicit iMEPs in wrist extensor and flexor muscles during four different bimanual movements (cooperative-asymmetric, cooperative-symmetric, non-cooperative-asymmetric and non-cooperative-symmetric) in 16 participants. Results: Nine participants showed an iMEP in the wrist extensor in at least 20% of the trials in each of the conditions and were classified as iMEP+ participants. iMEP persistence was greater for cooperative (50.5 ± 28.8%) compared to non-cooperative (31.6 ± 22.1%) tasks but did not differ between asymmetric and symmetric tasks. Area and amplitude of iMEPs were also increased during cooperative (area = 5.41 ± 3.4 mV × ms; amplitude = 1.60 ± 1.09 mV) compared to non-cooperative (area = 3.89 ± 2.0 mV × ms; amplitude = 1.12 ± 0.56 mV) tasks and unaffected by task-symmetry. Discussion: The upregulation of iMEPs during common-goal cooperative tasks shows a functional relevance of ipsilateral motor control in bimanual movements. The paired-pulse TMS protocol is a reliable method to elicit iMEPs in healthy participants and can give new information about neural control of upper limb movements. With this work we contribute to the research field in two main aspects. First, we describe a reliable method to elicit ipsilateral motor evoked potentials in healthy participants which will be useful in further advancing research in the area of upper limb movements. Second, we add new insight into the motor control of bimanual movements. We were able to show an upregulation of bilateral control represented by increased ipsilateral motor evoked potentials in cooperative, object-oriented movements compared to separate bimanual tasks. This result might also have an impact on neurorehabilitation after stroke.

Fast Outcome Categorization of the Upper Limb After Stroke.

BACKGROUND AND PURPOSE: The ARAT (Action Research Arm Test) has been used to classify upper limb motor outcome after stroke in 1 of 3, 4, or 5 categories. The COVID-19 pandemic has encouraged the development of assessments that can be performed quickly and remotely. The aim of this study was to derive and internally validate decision trees for categorizing upper limb motor outcomes at the late subacute and chronic stages of stroke using a subset of ARAT tasks. METHODS: This study retrospectively analyzed ARAT scores obtained in-person at 3 months poststroke from 333 patients. In-person ARAT scores were used to categorize patients' 3-month upper limb outcome using classification systems with 3, 4, and 5 outcome categories. Individual task scores from in-person assessments were then used in classification and regression tree analyses to determine subsets of tasks that could accurately categorize upper limb outcome for each of the 3 classification systems. The decision trees developed using 3-month ARAT data were also applied to in-person ARAT data obtained from 157 patients at 6 months poststroke. RESULTS: The classification and regression tree analyses produced decision trees requiring 2 to 4 ARAT tasks. The overall accuracy of the cross-validated decision trees ranged from 87.7% (SE, 1.0%) to 96.7% (SE, 2.0%). Accuracy was highest when classifying patients into one of 3 outcome categories and lowest for 5 categories. The decision trees are referred to as FOCUS (Fast Outcome Categorization of the Upper Limb After Stroke) assessments and they remained accurate for 6-month poststroke ARAT scores (overall accuracy range 83.4%-91.7%). CONCLUSIONS: A subset of ARAT tasks can accurately categorize upper limb motor outcomes after stroke. Future studies could investigate the feasibility and accuracy of categorizing outcomes using the FOCUS assessments remotely via video call.

The modulation of short and long-latency interhemispheric inhibition during bimanually coordinated movements.

Bimanual coordination is essential for the performance of many everyday tasks. There are several types of bimanually coordinated movements, classified according to whether the arms are acting to achieve a single goal (cooperative) or separate goals (independent), and whether the arms are moving symmetrically or asymmetrically. Symmetric bimanual movements are thought to facilitate corticomotor excitability (CME), while asymmetric bimanual movements are thought to recruit interhemispheric inhibition to reduce functional coupling between the motor cortices. The influences of movement symmetry and goal conceptualisation on interhemispheric interactions have not been studied together, and not during bimanually active dynamic tasks. The present study used transcranial magnetic stimulation (TMS) to investigate the modulation of CME and short- and long-latency interhemispheric inhibition (SIHI and LIHI, respectively) during bimanually active dynamic tasks requiring different types of bimanual coordination. Twenty healthy right-handed adults performed four bimanual tasks in which they held a dumbbell in each hand (independent) or a custom device between both hands (cooperative) while rhythmically flexing and extending their wrists symmetrically or asymmetrically. Motor-evoked potentials were recorded from the right extensor carpi ulnaris. We found CME was greater during asymmetric tasks than symmetric tasks, and movement symmetry did not modulate SIHI or LIHI. There was no effect of goal conceptualisation nor any interaction with movement symmetry for CME, SIHI or LIHI. Based on these results, movement symmetry and goal conceptualisation may not modulate interhemispheric inhibition during dynamic bimanual tasks. These findings contradict prevailing thinking about the roles of CME and interhemispheric inhibition in bimanual coordination.

Effects of bilateral priming on motor cortex function in healthy adults.

Bilateral priming is a rehabilitation adjuvant that can improve upper limb motor recovery poststroke. It uses a table-top device to couple the upper limbs together such that active flexion and extension of one wrist leads to passive movement of the opposite wrist in a mirror symmetric pattern. Bilateral priming increases corticomotor excitability (CME) in the primary motor cortex (M1) of the passively driven wrist; however, the neurophysiological mechanisms underlying this increase remain unclear. This study explored these mechanisms by using transcranial magnetic stimulation over the right M1 and recording motor-evoked potentials from the passively driven left extensor carpi radialis of healthy adults. Intracortical measures were recorded before and 5 and 35 min after a single 15-min session of priming. One-millisecond short-interval intracortical inhibition, long-interval intracortical inhibition, late cortical disinhibition (LCD), and intracortical facilitation were recorded with a posterior-anterior (PA) intracortical current, whereas CME and short-interval intracortical facilitation (SICF) were recorded with both PA and anterior-posterior (AP) currents. CME with PA stimulation was also recorded ~1 h postpriming. PA CME was elevated 35 min postpriming and remained elevated ~1 h postpriming. LCD decreased, and AP SICF increased at both 5 and 35 min postpriming. However, these changes in LCD and AP SICF are unlikely to be the cause of the increased PA CME because of the differing timelines of their effects and AP and PA currents activating separate interneuron circuits. These results suggest that bilateral priming does not increase CME through alterations of the intracortical circuits investigated here. NEW & NOTEWORTHY This is the first study to measure how bilateral priming modulates corticomotor excitability with posterior-anterior and anterior-posterior intracortical currents, 1-ms short-interval intracortical inhibition, late cortical disinhibition, intracortical facilitation, and short-interval intracortical facilitation. We found corticomotor excitability with a posterior-anterior current increased by 35 min until ~1 h postpriming. Short-interval intracortical facilitation with an anterior-posterior current was greater for at least 35 min postpriming. This provides further insight into the neurophysiological mechanisms underlying bilateral priming.

Parallelizing a DNA simulation code for the Cray MTA-2.

The Cray MTA-2 (Multithreaded Architecture) is an unusual parallel supercomputer that promises ease of use and high performance. We describe our experience on the MTA-2 with a molecular dynamics code, SIMU-MD, that we are using to simulate the translocation of DNA through a nanopore in a silicon based ultrafast sequencer. Our sequencer is constructed using standard VLSI technology and consists of a nanopore surrounded by Field Effect Transistors (FETs). We propose to use the FETs to sense variations in charge as a DNA molecule translocates through the pore and thus differentiate between the four building block nucleotides of DNA. We were able to port SIMU-MD, a serial C code, to the MTA with only a modest effort and with good performance. Our porting process needed neither a parallelism support platform nor attention to the intimate details of parallel programming and interprocessor communication, as would have been the case with more conventional supercomputers.