Neural Stimulation for Motor Adaptation

Overseen By Brooke Dexheimer, PhD, OTD, OTR/L

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Commonwealth University

Disqualifiers: Epilepsy, Concussion, Migraines, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Single visit, approx 20 minutes

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Motor adaptation and generalization are believed to occur via the integration of various forms of sensory feedback for a congruent representation of the body's position in space along with estimation of inertial properties of the limb segments for accurate specification of movement. Thus, motor adaptation is often studied within curated environments incorporating a "mis-match" between different sensory systems (i.e. a visual field shift via prism googles or a visuomotor rotation via virtual reality environment) and observing how motor plans change based on this mis-match. However, these adaptations are environment-specific and show little generalization outside of their restricted experimental setup. There remains a need for motor adaptation research that demonstrates motor learning that generalizes to other environments and movement types. This work could then inform physical and occupational therapy neurorehabilitation interventions targeted at addressing motor deficits.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It might be best to discuss this with the trial coordinators.

What data supports the effectiveness of the treatment for motor adaptation reaching performance?

Research shows that electrical stimulation can enhance neural plasticity (the brain's ability to change and adapt) in motor networks, leading to improved motor function. This suggests that similar treatments, like neural stimulation, could help improve motor adaptation in patients. ^{1 2 3 4 5}

Is neural stimulation for motor adaptation safe for humans?

The DyNeuMo Mk-1 system, a type of neural stimulator, was designed with safety in mind using international risk management standards and has been validated for use in movement disorders under emergency authorization. Additionally, the translational framework for peripheral nerve stimulating electrodes highlights the importance of safety measures in the development and clinical deployment of neural interfaces. ^{6 7 8 9 10}

How does the treatment for motor adaptation differ from other treatments?

The treatment for motor adaptation using neural stimulation is unique because it involves transcranial magnetic stimulation (TMS) to directly influence the motor cortex, which helps in adapting motor skills by modulating corticospinal excitability. This approach is different from traditional methods as it targets the brain's plasticity to improve motor learning and adaptation. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for right-handed individuals aged between 18 and 40. It's designed to explore how the brain adapts motor control when faced with conflicting sensory information, which could help improve physical and occupational therapy methods.

Inclusion Criteria

Right-handed as determined by the short-form Edinburgh Handedness Inventory

Exclusion Criteria

Current implanted device(s) (i.e. cardiac pacemaker)

Self-reported history of fainting spells

Self-reported history of concussion with loss of consciousness

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo non-invasive neural stimulation to study motor adaptation and generalization

Single visit, approx 20 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Treatment Details

Interventions

• Comparing motor adaptation reaching performance

Trial Overview The study tests how well people can adapt their reaching movements when experiencing a mismatch in sensory feedback, like wearing prism goggles or using virtual reality that alters visual input.

Participant Groups

Group I: Posterior parietal cortex group Experimental Treatment 1 Intervention

Posterior parietal cortex group, which will receive the stimulation to their left posterior parietal cortex

Group II: Cerebellum group Experimental Treatment 1 Intervention

Cerebellum group, which will receive stimulation to their right cerebellum,

Group III: Sham group Placebo Group 1 Intervention

Sham group, which will have the electrode cap placed on their head but receive no stimulation

Comparing motor adaptation reaching performance is already approved in European Union, United States for the following indications:

Approved in European Union as Lynparza for:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Lynparza for:

• Ovarian, fallopian tube, and primary peritoneal cancer
• Breast cancer
• Prostate cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

Findings from Research

In a study involving 28 chronic stroke patients, an auditory-motor intervention using digital musical instruments significantly improved the control of paretic limb movements, as indicated by increased peak power in acceleration profiles over nine sessions.

The findings suggest that using accelerometry to measure paretic limb function can provide valuable insights into motor recovery, with improvements in movement control correlating with clinical assessments like the Fugl-Meyer - Upper Extremity test.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Music-based intervention drives paretic limb acceleration into intentional movement frequencies in chronic stroke rehabilitation. Loria, T., de Grosbois, J., Haire, C., et al.[2022]

Neuromuscular electrical stimulation (NMES) can aid in motor rehabilitation for individuals with brain injuries by stimulating muscle contractions, which helps compensate for disabilities like foot drop and assists in movements such as hand opening.

NMES may also promote long-term changes in central motor pathways, enhancing intrinsic functional capacity, especially when combined with techniques like mental imagery that engage the central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromuscular electrical stimulation-promoted plasticity of the human brain. Carson, RG., Buick, AR.[2021]

In a study involving nonhuman primates, adaptive decoding methods were used to enhance neuroprosthetic control, demonstrating that neuroplasticity can be effectively shaped to improve performance in changing neural environments.

The research showed that combining decoder adaptation with neuroplasticity led to better skill retention and reduced interference from natural motor functions, suggesting a promising approach for developing advanced neuroprosthetic systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Closed-loop decoder adaptation shapes neural plasticity for skillful neuroprosthetic control. Orsborn, AL., Moorman, HG., Overduin, SA., et al.[2022]

Recent advancements in neurostimulation technology enable precise, closed-loop systems that can enhance neural plasticity in motor networks, which is crucial for neural repair.

Clinical studies show that electrical stimulation can effectively promote recovery in damaged motor circuits, leading to significant improvements in motor function for users, suggesting potential for treating various motor system disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovations in electrical stimulation harness neural plasticity to restore motor function. Peng, X., Hickman, JL., Bowles, SG., et al.[2023]

In a study involving 9 chronic stroke survivors, a combination of repetitive task-specific practice (RTP) with electrical stimulation and behavioral supports led to significant improvements in upper extremity function and dexterity over an 8-week period.

Participants showed marked increases in their ability to use their affected arm for daily activities, indicating that this intervention not only improved physical capabilities but also enhanced their quality of life by enabling them to perform valued tasks they had previously been unable to do.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Reps" Aren't Enough: Augmenting Functional Electrical Stimulation With Behavioral Supports Significantly Reduces Impairment in Moderately Impaired Stroke. Page, SJ., Levine, PG., Basobas, BA.[2018]

The DyNeuMo Mk-1 is a new, fully-implantable adaptive research stimulator designed to personalize therapy by adjusting stimulation based on circadian rhythms and patient movement, which could enhance treatment outcomes for movement disorders.

Developed with a focus on patient safety using ISO standards, the DyNeuMo Mk-1 has received emergency-device authorization from the MHRA, paving the way for first-in-human trials to test its effectiveness in real-world applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DyNeuMo Mk-1: Design and pilot validation of an investigational motion-adaptive neurostimulator with integrated chronotherapy. Zamora, M., Toth, R., Morgante, F., et al.[2023]

Neural prosthetic systems, which use intracortical electrode arrays to translate brain signals into control signals for assistive devices, show promise in helping disabled patients, but face significant challenges in achieving consistent performance and sensory feedback.

Key challenges include the need for these systems to perform at able-bodied levels across various tasks and environments, maintain robustness over decades, and restore natural proprioception and somatosensation, which are crucial for effective use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges and opportunities for next-generation intracortically based neural prostheses. Gilja, V., Chestek, CA., Diester, I., et al.[2021]

The CLARA system is a groundbreaking closed-loop neuromodulation technology that uses markerless tracking to monitor and stimulate animal behavior in real-time, allowing for precise delivery of neural stimulation based on behavioral outcomes.

In experiments, vagus nerve stimulation (VNS) delivered through the CLARA system significantly improved skilled reaching performance and consistency in healthy animals, highlighting its potential for enhancing motor function through neurostimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Closed-loop automated reaching apparatus (CLARA) for interrogating complex motor behaviors. Bowles, S., Williamson, WR., Nettles, D., et al.[2023]

A new psychometric questionnaire was developed to effectively characterize somatosensory sensations evoked by electrical stimulation in humans, showing strong reliability in a study with 13 subjects.

This questionnaire captured a greater variety of sensory descriptors compared to previous methods, enhancing the understanding of how different electrical stimulation patterns affect sensory perception, which is crucial for improving neural prostheses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new psychometric questionnaire for reporting of somatosensory percepts. Kim, LH., McLeod, RS., Kiss, ZHT.[2019]

This review outlines a comprehensive framework for translating neural interfaces for electrical modulation of the peripheral nervous system (PNS) from design to clinical use, emphasizing the importance of following FDA guidelines for safety and efficacy.

Key steps in the translational process include quantitative human anatomy, neural modeling, acute testing, and chronic deployment, with case studies demonstrating successful applications of specific electrode designs like the spiral cuff and Flat Interface Nerve Electrode (FINE).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A translational framework for peripheral nerve stimulating electrodes: Reviewing the journey from concept to clinic. Charkhkar, H., Christie, BP., Pinault, GJ., et al.[2021]

In a study involving 16 human subjects, researchers used transcranial magnetic stimulation to explore how different adaptation processes in motor learning operate on varying timescales.

The findings revealed that motor-evoked potentials (MEPs) indicate a fast but short-lived adaptation process, while cortical silent periods (CSPs) are associated with a slower but more enduring adaptation, linking neural activity to motor learning theories.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticospinal correlates of fast and slow adaptive processes in motor learning. Sarwary, AME., Wischnewski, M., Schutter, DJLG., et al.[2019]

Participants demonstrated the ability to adapt their muscle responses to unexpected force fields during reaching tasks, indicating that the nervous system can quickly adjust to disturbances.

Feedback adaptation occurred approximately 250 milliseconds after the start of the movement, suggesting that this rapid response time is a key feature of motor learning and adaptation in the nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feedback Adaptation to Unpredictable Force Fields in 250 ms. Crevecoeur, F., Mathew, J., Bastin, M., et al.[2021]

Abrupt perturbations in motor tasks lead to significant changes in the excitability of the corticospinal network, as indicated by increased motor-evoked potentials (MEPs) before reaching, while gradual perturbations do not show this effect.

The study suggests that the repetition of motor commands during abrupt training is crucial for inducing plasticity in the primary motor cortex, and that the effects of adaptation persist even after a washout period, indicating a lasting change in the neural network involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in corticospinal excitability during reach adaptation in force fields. Orban de Xivry, JJ., Ahmadi-Pajouh, MA., Harran, MD., et al.[2021]

The study found that pretarget neural activity in the motor cortex of macaques reflects their internal model of visuomotor gain, which can predict the speed of their reaching movements, indicating that the brain prepares for movement even before a target is presented.

This internal model estimation could enhance brain-machine interfaces by compensating for errors in reach extent, suggesting potential applications for improving motor prostheses for individuals with paralysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial-by-Trial Motor Cortical Correlates of a Rapidly Adapting Visuomotor Internal Model. Stavisky, SD., Kao, JC., Ryu, SI., et al.[2018]

The study found that the primary motor cortex (M1) plays a significant role in behavioral adaptation during voluntary movement, particularly in adjusting motor responses after incongruent trials in a flanker task.

Using transcranial magnetic stimulation (TMS), researchers observed that increased corticospinal excitability for antagonist movements after incongruent trials correlates with improved reaction times, suggesting that M1 helps the motor system adapt to changing contexts by balancing readiness for different actions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bypassing use-dependent plasticity in the primary motor cortex to preserve adaptive behavior. Bosc, M., Bucchioni, G., Ribot, B., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Music-based intervention drives paretic limb acceleration into intentional movement frequencies in chronic stroke rehabilitation. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Neuromuscular electrical stimulation-promoted plasticity of the human brain. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Closed-loop decoder adaptation shapes neural plasticity for skillful neuroprosthetic control. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Innovations in electrical stimulation harness neural plasticity to restore motor function. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

"Reps" Aren't Enough: Augmenting Functional Electrical Stimulation With Behavioral Supports Significantly Reduces Impairment in Moderately Impaired Stroke. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

DyNeuMo Mk-1: Design and pilot validation of an investigational motion-adaptive neurostimulator with integrated chronotherapy. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Challenges and opportunities for next-generation intracortically based neural prostheses. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Closed-loop automated reaching apparatus (CLARA) for interrogating complex motor behaviors. [2023]

9. England pubmed.ncbi.nlm.nih.gov

A new psychometric questionnaire for reporting of somatosensory percepts. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

A translational framework for peripheral nerve stimulating electrodes: Reviewing the journey from concept to clinic. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Corticospinal correlates of fast and slow adaptive processes in motor learning. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Feedback Adaptation to Unpredictable Force Fields in 250 ms. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Changes in corticospinal excitability during reach adaptation in force fields. [2021]

14. United States pubmed.ncbi.nlm.nih.gov

Trial-by-Trial Motor Cortical Correlates of a Rapidly Adapting Visuomotor Internal Model. [2018]

15. England pubmed.ncbi.nlm.nih.gov

Bypassing use-dependent plasticity in the primary motor cortex to preserve adaptive behavior. [2021]