Posts Tagged motor cortex

[Abstract] Evidence for a Window of Enhanced Plasticity in the Human Motor Cortex Following Ischemic Stroke



In preclinical models, behavioral training early after stroke produces larger gains compared with delayed training. The effects are thought to be mediated by increased and widespread reorganization of synaptic connections in the brain. It is viewed as a period of spontaneous biological recovery during which synaptic plasticity is increased.


To look for evidence of a similar change in synaptic plasticity in the human brain in the weeks and months after ischemic stroke.


We used continuous theta burst stimulation (cTBS) to activate synapses repeatedly in the motor cortex. This initiates early stages of synaptic plasticity that temporarily reduces cortical excitability and motor-evoked potential amplitude. Thus, the greater the effect of cTBS on the motor-evoked potential, the greater the inferred level of synaptic plasticity. Data were collected from separate cohorts (Australia and UK). In each cohort, serial measurements were made in the weeks to months following stroke. Data were obtained for the ipsilesional motor cortex in 31 stroke survivors (Australia, 66.6 ± 17.8 years) over 12 months and the contralesional motor cortex in 29 stroke survivors (UK, 68.2 ± 9.8 years) over 6 months.


Depression of cortical excitability by cTBS was most prominent shortly after stroke in the contralesional hemisphere and diminished over subsequent sessions (P = .030). cTBS response did not differ across the 12-month follow-up period in the ipsilesional hemisphere (P = .903).


Our results provide the first neurophysiological evidence consistent with a period of enhanced synaptic plasticity in the human brain after stroke. Behavioral training given during this period may be especially effective in supporting poststroke recovery.


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[WEB PAGE] Small ‘window of opportunity’ for best recovery after stroke

by University of South Australia

Credit: Unsplash/CC0 Public Domain

An international study has shown, for the first time, that the capacity of the human brain to recover and rewire itself peaks around two weeks after a stroke and diminishes over time.

The finding, published today in the Neurorehabilitation and Neural Repair journal, is the result of a study in London and Adelaide that followed the recovery of 60 stroke patients up to one year after their stroke.

Lead author Dr. Brenton Hordacre, from the University of South Australia, says the multi-site study showed conclusive evidence that the brain only has a small window of opportunity to more easily repair itself after stroke.

“Earlier animal studies suggested this was the case, but this is the first time we have conclusively demonstrated this phenomenon exists in humans,” Dr. Hordacre says.

The researchers scanned the brains of stroke survivors as they recovered over 12 months. They found that in the initial days following an ischemic stroke (caused by a blocked artery to the brain), the brain has a greater capacity to modify its neural connections and its plasticity is increased.

“It is during this early period after stroke that any physiotherapy is going to be most effective because the brain is more responsive to treatment.

“Earlier experiments with rats showed that within five days of an ischemic stroke they were able to repair damaged limbs and neural connections more easily than if therapy was delayed until 30 days post stroke.”

The researchers used continuous transcranial magnetic stimulation (cTBS) to repetitively activate different hemispheres of the motor cortex to measure brain plasticity.

The Adelaide laboratory tested the stroke damaged motor cortex, which is the main area that controls movement. The London laboratory tested the non-stroke damaged hemisphere which is also important to help recovery.

“Our assessments showed that plasticity was strongest around two weeks after stroke in the non-damaged motor cortex. Contrary to what we expected, there was no change in the damaged hemisphere in response to cTBS.”

Dr. Hordacre says the findings confirm the importance of initiating therapy as soon as possible after a stroke.

Current evidence indicates that less than eight minutes of daily therapy is dedicated to upper limb recovery within the first four weeks of a stroke.

“Delivering more treatment within this brief window is needed to help people recover after stroke.

“The next step is to identify techniques which prolong or even re-open a period of increased brain plasticity, so we can maximise recovery,” Dr. Hordacre says.


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[Abstract] Primary motor cortex excitability as a marker of plasticity in a stimulation protocol combining action observation and kinesthetic illusion of movement


Action observation combined with proprioceptive stimulation able to induce a kinesthetic illusion of movement (AO‐KI) was shown to elicit a plastic increase in primary motor cortex (M1) excitability, with promising applications in rehabilitative interventions. Nevertheless, the known individual variability in response to combined stimulation protocols limits its application.

The aim of this study was to examine whether a relationship exists between changes in M1 excitability during AO‐KI and the long‐lasting changes in M1 induced by AO‐KI.

Fifteen volunteers received a conditioning protocol consisting in watching a video showing a thumb‐opposition movement and a simultaneous proprioceptive stimulation that evoked an illusory kinesthetic experience of their thumbs closing. M1 excitability was evaluated by means of single‐pulse transcranial magnetic stimulation before, DURING the conditioning protocol, and up to 60 minutes AFTER it was administered.

M1 excitability significantly increased during AO‐KI with respect to a rest condition. Furthermore, AO‐KI induced a long‐lasting increase in M1 excitability up to 60 minutes after administration. Finally, a significant positive correlation appeared between M1 excitability changes during and after AO‐KI; that is, participants who were more responsive during AO‐KI showed greater motor cortical activity changes after it.

These findings suggest that M1 response during AO‐KI can be considered a neurophysiological marker of individual responsiveness to the combined stimulation since it was predictive of its efficacy in inducing a long‐lasting M1 increase excitability. This information would allow knowing in advance whether an individual will be a responder to AO‐KI.


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[WEB SITE] Can a Bit of Electricity Improve Your Brain?

Neuromodulation expands beyond health care.


Source: PublicDomainPictures/Pixabay

Neuromodulation is the use of electrical, magnetic, or chemical stimulation to modulate nervous tissue function. Research studies with promising results from novel treatments using neuromodulations are emerging.

On October 4, 2019, a study published in the American Journal of Psychiatry, led by Professor Helen S. Mayberg, M.D. at the Icahn School of Medicine at Mount Sinai and Dr. Andrea Crowell at Emory University, showed that deep brain stimulation for treatment-resistant depression for a majority of the participants had a “robust and sustained antidepressant response” in an over eight-year period, and there were not any suicides.

Earlier this year, in April, Boston University scientists Robert M. G. Reinhart and John A. Nguyen published in Nature Neuroscience a neuromodulation study that demonstrated noninvasive electrical brain stimulation temporarily improved the working memory accuracy in older adults. The study used 84 people—half between the ages of 20-29, and the other half between 60-76 years old.

The scientists hypothesize that their technique improved behavior due to neuroplastic changes in functional connectivity for up to 50 minutes afterward. Additional studies with more test subjects are needed to test the hypothesis and determine the full course potential of the effects.

These are just a few examples of the numerous research studies in neuromodulation. Neuromodulation methods include optogenetics, cochlear implants, retinal implants, deep brain and spinal cord stimulators, pharmacotherapy, and electroceuticals. Potential applications for neuromodulation may include chronic pain managementAlzheimer’s disease, depression, complications due to stroke, traumatic brain injuries, Parkinson’s disease, epilepsy, migraines, spinal cord injuries, and other conditions. Currently, there are over 590 neuromodulation clinical studies worldwide, according to the U.S. National Institute of Health’s Library of Medicine database of privately and publicly funded clinical studies conducted around the world.

Within the growing neuromodulation market, one segment, transcranial direct current stimulation (tDCS), is moving beyond health care and is making inroads into the consumer segment. Transcranial direct current stimulation is a form of noninvasive brain stimulation using a constant weak electrical current. Typically the voltage is less than two milliamps.

One of the earliest records of transcranial direct current stimulation dates to the ancient Roman Empire. The physician to Roman Emperor Tiberius Claudius Nero Caesar, Scribonius Largus, put a live torpedo fish, an electric ray capable of delivering up to 220 volts, directly on a patient in an effort to use the animal’s electrical discharges for pain therapy.

Fast forward to present day, and transcranial direct current stimulation is being used for a variety of purposes as an emerging technology for neuroscientists, elite athletes, e-sports gamers, neurologists, musicians, and psychiatrists—sans the torpedo fish. Instead, electronic devices in various form-factors are used to deliver currents to the human brain noninvasively via the scalp. Consumer-based transcranial direct current stimulation devices operate on the principle of neuroplasticity—the brain’s ability to change neural connections and behavior.

“Neuroplasticity is the property of the brain that enables it to change its own structure and functioning in response to activity and mental experience,” wrote the New York Times bestselling author, psychiatrist, and psychoanalyst, Norman Doidge, FRCPC, in his 2015 book The Brain’s Way of Healing: Remarkable Discoveries and Recoveries from the Frontiers of Neuroplasticity.

An example of a consumer-based transcranial direct current stimulation device is the Halo Sport 2, a wireless headset introduced in January 2019 that stimulates the brain’s motor cortex through electrical currents to create a temporary state of neuroplasticity. Whether the activity is learning music, dance, or sports, the human brain learns movement via the motor cortex.

The device is made by venture-backed startup Halo Neuroscience, a company founded in 2013 by Daniel Chao, Brett Wingeier, Lee von Kraus, Ph.D., and Amol Sarva, with investments from Jazz Venture Partners, Lux Capital, TPG, Andreessen Horowitz, and others. To use the Halo Sport 2 is simple—neuroprime with the headset on for 20 minutes, then train for an hour afterward.

Halo Sport users include athletes, musicians, and the military—such as members of Major League Baseball’s San Francisco Giants, National Basketball Association’s Golden State Warriors, the U.S. Navy SEALs, USA Cycling, the United States Ski Team, Berklee College of Music, Invictus, as well as many others.

World champion triathlete Timothy O’Donnell is a Halo Sport user. O’Donnell has over 50 podium finishes, including 22 wins. He won two IRONMAN titles, six Armed Forces National Championships, nine Ironman 70.3 races, an ITU Long Distance World Champion race, and many other prestigious competitive triathlon medals. As a world-class elite athlete, O’Donnell is constantly seeking innovative ways to improve his performance. He reportedly reached out to Halo Neuroscience after reading about the technology and incorporates Halo Sport neuropriming in his training to give him an edge.

A number of investments in neuroscience companies have emerged in recent years, such as Bryan Johnson’s Kernel, Elon Musk’s Neuralink, and Tej Tadi’s MindMaze. Other neurotechnology startups include Synchron, founded by Nicholas Opie and Thomas Oxley, BIOS founded by Emil Hewage and Oliver Armitage, BrainCo founded by Bicheng Han, Nextmind founded by Gwendal Kerdavid and Sid Kouider, Thync founded by Isy Goldwasser and Jamie Tyler, EMOTIV founded by Tan Le and Dr. Geoff Mackellar, Paradromics founded by Matt Angle, Bitbrain founded by Javier Minguez Zafra and Maria Lopez Valdes, Flow Neuroscience founded by Daniel Månsson and Erik Rehn, Dreem founded by Hugo Mercier and Quentin Soulet de Brugière, Neuros Medical founded by Jon J. Snyder, Neurable founded by James Hamet, Michael Thompson and Ramses Alcaide, Cognixion founded by Andeas Forsland, Q30 Innovations founded by Bruce Angus and Thomas Hoey, Neuroscouting founded by Dr. Wesley Clapp and Dr. Brian Miller, and Meltin MMI founded by Masahiro Kasuya, and Neuropace founded by David R. Fischell.

The global neuromodulation device industry is expected to increase to 13.3 billion by 2022, according to Neurotech Reports figures published in September 2018. Within this growing space, consumer-based transcranial direct current stimulation is an emerging market to watch.


via Can a Bit of Electricity Improve Your Brain? | Psychology Today

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[ARTICLE] Large-scale changes in cortical dynamics triggered by repetitive somatosensory electrical stimulation – Full Text



Repetitive somatosensory electrical stimulation (SES) of forelimb peripheral nerves is a promising therapy; studies have shown that SES can improve motor function in stroke subjects with chronic deficits. However, little is known about how SES can directly modulate neural dynamics. Past studies using SES have primarily used noninvasive methods in human subjects. Here we used electrophysiological recordings from the rodent primary motor cortex (M1) to assess how SES affects neural dynamics at the level of single neurons as well as at the level of mesoscale dynamics.


We performed acute extracellular recordings in 7 intact adult Long Evans rats under ketamine-xylazine anesthesia while they received transcutaneous SES. We recorded single unit spiking and local field potentials (LFP) in the M1 contralateral to the stimulated arm. We then compared neural firing rate, spike-field coherence (SFC), and power spectral density (PSD) before and after stimulation.


Following SES, the firing rate of a majority of neurons changed significantly from their respective baseline values. There was, however, a diversity of responses; some neurons increased while others decreased their firing rates. Interestingly, SFC, a measure of how a neuron’s firing is coupled to mesoscale oscillatory dynamics, increased specifically in the δ-band, also known as the low frequency band (0.3- 4 Hz). This increase appeared to be driven by a change in the phase-locking of broad-spiking, putative pyramidal neurons. These changes in the low frequency range occurred without a significant change in the overall PSD.


Repetitive SES significantly and persistently altered the local cortical dynamics of M1 neurons, changing both firing rates as well as the SFC magnitude in the δ-band. Thus, SES altered the neural firing and coupling to ongoing mesoscale dynamics. Our study provides evidence that SES can directly modulate cortical dynamics.


Somatosensory input is essential for skilled movements [1,2,3]; this is particularly true for dexterous movements [14,5,6]. Interestingly, the somatosensory system has been shown to experience relatively rapid bidirectional changes in organization as a result of repetitive manipulations of peripheral inputs. Consistent with this notion are seminal studies in both animals and humans which demonstrated that reductions in sensory feedback, either by denervation or ischemic nerve block, induced changes in motor representations [78].

Studies have also shown that increases in afferent input by stimulating peripheral pathways (i.e. repetitive somatosensory electrical stimulation or SES) can alter sensorimotor representations of the stimulated body part [910]. One of the first studies examining this neuromodulation method found that sensory stimulation of oral structures resulted in prolonged changes in excitability as well as an increase in the area of representation determined using functional imaging [11]. Consistent with these results are studies demonstrating that altered patterns of physical contacts to the fingers can also persistently reorganize sensory maps [1213]. Importantly, repetitive SES has also proven to be a promising therapeutic tool for motor rehabilitation [1014,15,16].

In both humans and rodents, SES can increase excitability as measured by responses to transcranial magnetic stimulation (TMS) pulses [917]. Past studies have used non-invasive measures to examine cortical excitability such as motor evoked potentials (MEPs) with TMS [917] and cortical reorganization using blood oxygenation signals [11]. It remains unclear what are the precise mechanisms underlying these changes. For example, the observed change in the evoked MEPs following SES may occur without changes in brainstem electrical stimulation-evoked potentials or spinal reflexes [91819]. This suggests the possibility that the cortex may be an important site of plasticity. While our recent study showed that SES can also modify low-frequency dynamics as measured using electroencephalogram (EEG) [20], it remains unclear if these changes are local to cortex. Invasive electrophysiology offers one method to assess if SES can directly alter local motor cortical dynamics.

While the body of literature summarized above has provided important mechanistic insight, little is known about how SES interacts with ongoing cortical dynamics at the level of single neurons and groups of neurons, or neural ensembles. Single neurons are a fundamental unit of the nervous system. The coordinated firing of neural ensembles, e.g. co-firing of neurons in a temporally coupled manner, is now also recognized as an important module for information processing [21,22,23,24,25,26]. In addition, oscillations may provide a mechanism for dynamic coordination of ensembles across motor and sensory areas [21,22,23,24,2527]. Oscillations likely reflect synchronized rhythmic excitability linked to coordinated firing of neurons [28]. Our collective understanding of both single neuron and ensemble firing patterns has greatly improved our understanding of how neural activity patterns underlie complex sensory and motor behaviors. Similarly, it is likely that such activity may play an important role in driving neural plasticity after injury and during neuromodulation using methods such as SES.

The goal of this study was to develop a model of the cortical effects of SES using high-resolution, invasive recording of neurons. We were particularly interested in understanding the diversity of single neuron responses to SES. It is unlikely that all neurons respond identically to a given perturbation. This may be, in part, the result of the multiple cell-types in a given region and the diversity of network connectivity for single neurons [29]. We also wanted to compare changes in neural activity related to larger scale network oscillatory activity. More specifically, we examined the effects of SES on primary motor cortex (M1) at the level of single neuron firing rates as well as the neural coupling to ongoing spontaneous oscillations. We found that SES could independently change both the firing rate and the phase locking, i.e. the consistency of the neural firing relative to oscillatory dynamics. Together, our results provide evidence that SES can directly modulate neural dynamics in M1.


Animal and surgery preparation

All animal procedures were in accordance with protocols approved by the Institutional Animal Care and Use Committee at the San Francisco Veterans Affairs Medical Center. Adult male Long Evans rats (n = 8, 250-400 g, ~ 8 weeks old, Charles River Laboratories) were housed in a 12 h light:12 h dark cycle with lights out at 6:00 AM and were kept under controlled temperature. One animal was excluded from the study due to significant recording drift and electrical noise in the recording, thus n = 7 animals were used for the analysis shown. Animals were initially anesthetized using a ketamine/xylazine cocktail (85 mg/kg ketamine, and 10 mg/kg xylazine), with supplemental ketamine (at half of the induction dose) given every 40–60 min as needed to maintain a stable anesthetic level, and also to maintain anesthesia at stage III characterized by predominantly slow oscillations. Moreover, 0.05 mg/kg of atropine was given separately to counter respiratory and cardiac depression, and decrease secretion. Animals were sacrificed at the end of the recordings.

Somatosensory electrical stimulation and electrophysiology

After anesthesia induction, transcutaneous stimulation electrodes were clipped near forelimb peripheral nerves (medial, ulnar, and radial nerve), in the configuration noted in Fig. 1a. These copper metal clips were wrapped around the forelimb and then connected to a Multi-Channel Systems Stimulus Generator (MCS STG4000 series) to deliver transcutaneous stimulation. SES current parameters were set by determining the maximum amount of current where no evoked movement in the forelimb was seen (typically 300–750 μA currents).



Fig. 1 Schematic of the Experiment. a, Somatosensory electrical stimulation was applied directly to the distal forelimb while neural activity was recorded under anesthesia. b, Schematic of the stimulation paradigm. c, Averaged evoked potential in the local field potential during SES



Continue —>  Large-scale changes in cortical dynamics triggered by repetitive somatosensory electrical stimulation | Journal of NeuroEngineering and Rehabilitation | Full Text

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[Abstract] Differential Poststroke Motor Recovery in an Arm Versus Hand Muscle in the Absence of Motor Evoked Potentials

Background. After stroke, recovery of movement in proximal and distal upper extremity (UE) muscles appears to follow different time courses, suggesting differences in their neural substrates.

Objective. We sought to determine if presence or absence of motor evoked potentials (MEPs) differentially influences recovery of volitional contraction and strength in an arm muscle versus an intrinsic hand muscle. We also related MEP status to recovery of proximal and distal interjoint coordination and movement fractionation, as measured by the Fugl-Meyer Assessment (FMA).

Methods. In 45 subjects in the year following ischemic stroke, we tracked the relationship between corticospinal tract (CST) integrity and behavioral recovery in the biceps (BIC) and first dorsal interosseous (FDI) muscle. We used transcranial magnetic stimulation to probe CST integrity, indicated by MEPs, in BIC and FDI. We used electromyography, dynamometry, and UE FMA subscores to assess muscle-specific contraction, strength, and inter-joint coordination, respectively.

Results. Presence of MEPs resulted in higher likelihood of muscle contraction, greater strength, and higher FMA scores. Without MEPs, BICs could more often volitionally contract, were less weak, and had steeper strength recovery curves than FDIs; in contrast, FMA recovery curves plateaued below normal levels for both the arm and hand.

Conclusions. There are shared and separate substrates for paretic UE recovery. CST integrity is necessary for interjoint coordination in both segments and for overall recovery. In its absence, alternative pathways may assist recovery of volitional contraction and strength, particularly in BIC. These findings suggest that more targeted approaches might be needed to optimize UE recovery.


via Differential Poststroke Motor Recovery in an Arm Versus Hand Muscle in the Absence of Motor Evoked Potentials – Heidi M. Schambra, Jing Xu, Meret Branscheidt, Martin Lindquist, Jasim Uddin, Levke Steiner, Benjamin Hertler, Nathan Kim, Jessica Berard, Michelle D. Harran, Juan C. Cortes, Tomoko Kitago, Andreas Luft, John W. Krakauer, Pablo A. Celnik, 2019

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[WEB SITE] Transcranial Magnetic Stimulation for the Recovery of Gait and Balance in Stroke Patients – BrainPost

Post by Thomas Brown

What’s the science?

The permanent brain damage which occurs following ischemic stroke makes functional recovery difficult. While physiotherapy can result in improved voluntary motor recovery, the improvement of balance and gait can be harder. Issues with balance pose a safety risk for stroke patients, who may be more likely to fall. Ultimately, problems with balance can mean reduced independence for patients. The cerebellum, a structure located at the back of the brain, is known to regulate movement, gait and balance. Deficits to the cerebellum often result in ataxia and widened gaits, making this area a prime target for functional recovery analysis. This week in JAMA Neurology Koch and colleagues demonstrate in a phase IIa clinical trial, an increase in gait and balance in hemiparetic stroke patients, up to three weeks after physiotherapy supplemented with transcranial magnetic stimulation of the cerebellum.

How did they do it?

A group of 36 hemiparetic (one side affected) stroke patients were randomly assigned to one of two age-matched groups; control or experimental. The experimental group was treated with intermittent theta-burst magnetic stimulation (TBS) of the cerebellar region ipsilateral (same side) to their motor issues. Intermittent TBS is a process by which bursts of magnetic energy are applied to the scalp over an area of interest. TBS was administered in conjunction with physiotherapy to the experimental group for three weeks. The control group still received physiotherapy, but received sham (fake) TBS. Patients were assessed using a wide range of balance and gait analysis tests to determine the degree of recovery. The authors relied primarily on the Berg Balance Scale, which is a series of 14 tests that determine the ability of an individual to balance without aid. Gait analysis was also performed, in which patients were asked to walk while a machine measured their gait (the space between each foot while walking). Neural activity was measured with electroencephalography while transcranial magnetic stimulation was applied simultaneously (EEG-TMS). This technique was used to measure neural activity changes in motor regions of the brain following activation of the motor cortex using a different TMS paradigm than the one used for treatment.

What did they find?

The authors found that after three weeks of the last treatment with either sham or cerebellar TBS, there was an average increase in the Berg Balance Scale score in those treated with TBS compared to controls. They also showed a reduction in gait width; a wide gait is often associated with the body’s attempt to compensate for problems with balance. This finding was supported by correlational analysis which found that a reduction is step width was associated with an improvement in Berg Balance Scale score. Interestingly, three weeks after treatment there was also an increase in neural activity in the motor (M1) region of the brain in the hemispheres affected by the stoke, in treated patients compared to controls. This area of the cortex is associated with the movement execution. Altogether these findings suggest that there were significant balance, gait and motor cortex activity improvements following treatment with TBS. Critically, no adverse effects were observed following treatment with TBS during the clinical trial.


What’s the impact?

These findings suggest that theta-burst stimulation may be an effective way of supplementing physiotherapy in those suffering with balance and gait deficits following stroke. Theta-burst stimulation in conjunction with physiotherapy, was able to improve both balance and gait in stroke patients. Treatment with theta-burst stimulation could reduce the chance of falling and improve independence in stroke patients.


Koch et al. Effect of Cerebellar Stimulation on Gait and Balance Recovery
in Patients With Hemiparetic Stroke. JAMA Neurology (2018).Access the original scientific publication here


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[Abstract] Vagus nerve stimulation intensity influences motor cortex plasticity


Recovery after neurological injury is thought to be dependent on plasticity.

Moderate intensity VNS paired with motor training enhances motor cortex plasticity.

Low and high intensity VNS paired with motor training fail to enhance plasticity.

The intensity of stimulation is a critical factor in VNS-dependent plasticity.

Optimizing stimulation paradigms may enhance VNS efficacy in clinical populations.



Vagus nerve stimulation (VNS) paired with forelimb motor training enhances reorganization of movement representations in the motor cortex. Previous studies have shown an inverted-U relationship between VNS intensity and plasticity in other brain areas, such that moderate intensity VNS yields greater cortical plasticity than low or high intensity VNS. However, the relationship between VNS intensity and plasticity in the motor cortex is unknown.


In this study we sought to test the hypothesis that VNS intensity exhibits an inverted-U relationship with the degree of motor cortex plasticity in rats.


Rats were taught to perform a lever pressing task emphasizing use of the proximal forelimb musculature. Once proficient, rats underwent five additional days of behavioral training in which low intensity VNS (0.4 mA), moderate intensity VNS (0.8 mA), high intensity VNS (1.6 mA), or sham stimulation was paired with forelimb movement. 24 h after the completion of behavioral training, intracortical microstimulation (ICMS) was used to document movement representations in the motor cortex.


VNS delivered at 0.8 mA caused a significant increase in motor cortex proximal forelimb representation compared to training alone. VNS delivered at 0.4 mA and 1.6 mA failed to cause a significant expansion of proximal forelimb representation.


Moderate intensity 0.8 mA VNS optimally enhances motor cortex plasticity while low intensity 0.4 mA and high intensity 1.6 mA VNS fail to enhance plasticity. Plasticity in the motor cortex exhibits an inverted-U function of VNS intensity similar to previous findings in auditory cortex.

via Vagus nerve stimulation intensity influences motor cortex plasticity – Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation

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[ARTICLE] Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke – Full Text PDF

A Blinded Randomized Pilot Study

Background and Purpose

We assessed safety, feasibility, and potential effects of vagus nerve stimulation (VNS) paired with rehabilitation for improving arm function after chronic stroke.


We performed a randomized, multisite, double-blinded, sham-controlled pilot study. All participants were implanted with a VNS device and received 6-week in-clinic rehabilitation followed by a home exercise program. Randomization was to active VNS (n=8) or control VNS (n=9) paired with rehabilitation. Outcomes were assessed at days 1, 30, and 90 post-completion of in-clinic therapy.


All participants completed the course of therapy. There were 3 serious adverse events related to surgery. Average FMA-UE scores increased 7.6 with active VNS and 5.3 points with control at day 1 post–in-clinic therapy (difference, 2.3 points; CI, −1.8 to 6.4; P=0.20). At day 90, mean scores increased 9.5 points from baseline with active VNS, and the control scores improved by 3.8 (difference, 5.7 points; CI, −1.4 to 11.5; P=0.055). The clinically meaningful response rate of FMA-UE at day 90 was 88% with active VNS and 33% with control VNS (P<0.05).


VNS paired with rehabilitation was acceptably safe and feasible in participants with upper limb motor deficit after chronic ischemic stroke. A pivotal study of this therapy is justified.


Full Text PDF

via Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke | Stroke

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[ARTICLE] Effects of 8-week sensory electrical stimulation combined with motor training on EEG-EMG coherence and motor function in individuals with stroke – Full Text


The peripheral sensory system is critical to regulating motor plasticity and motor recovery. Peripheral electrical stimulation (ES) can generate constant and adequate sensory input to influence the excitability of the motor cortex. The aim of this proof of concept study was to assess whether ES prior to each hand function training session for eight weeks can better improve neuromuscular control and hand function in chronic stroke individuals and change electroencephalography-electromyography (EEG-EMG) coherence, as compared to the control (sham ES). We recruited twelve subjects and randomly assigned them into ES and control groups. Both groups received 20-minute hand function training twice a week, and the ES group received 40-minute ES on the median nerve of the affected side before each training session. The control group received sham ES. EEG, EMG and Fugl-Meyer Assessment (FMA) were collected at four different time points. The corticomuscular coherence (CMC) in the ES group at fourth weeks was significantly higher (p = 0.004) as compared to the control group. The notable increment of FMA at eight weeks and follow-up was found only in the ES group. The eight-week rehabilitation program that implemented peripheral ES sessions prior to function training has a potential to improve neuromuscular control and hand function in chronic stroke individuals.


Stroke is one of the leading contributing factors to the loss of functional abilities and independence in daily life in adults1. The most common and widely observed impairment following stroke is motor impairment, which can be regarded as a loss or limitation of function in muscle control or movement25. Most stroke survivors later regain the ability to walk independently, but only fewer than 50% of them will have fully recovered upper extremity functions6,7. From a review focusing on motor recovery after stroke, it has been indicated that the recovery of both arm and hand function among subacute and chronic stroke survivors is limited in current neural rehabilitation settings4; therefore, additional management with activating plasticity before or during performing motor training is necessary for better motor recovery.

The fundamental principle of stroke rehabilitation is inducing brain plasticity by sensory or proprioceptive input in order to facilitate motor functions8,9. It has been demonstrated that strong sensory input can induce plastic changes in the motor cortex via direct or indirect pathways1017. In this case, electrical stimulation (ES) that provides steady and adequate somatosensory input can be an ideal method of stimulating the motor cortex.

Recent studies using functional magnetic resonance imaging (fMRI) or transcranial magnetic stimulation (TMS) suggest that ES on peripheral nerves can increase motor-evoked potential (MEP)1820, increase the active voxel count in the corresponding motor cortex13, and increase blood-oxygen-level dependent (BOLD) signals in fMRI, suggesting peripheral ES induced higher excitability and activation level of cortical neurons21. Since the expansion of the motor cortical area or increase in the excitability of neural circuits is associated with learning new motor skills2226, clinicians should take advantage and assist patients with stroke on motor tasks training during this period of time. Celnik and colleagues27found that the hand function of chronic stroke subjects improved immediately after two-hour peripheral nerve stimulation combined with functional training, and the effect lasted for one day. Based on previous studies, the ES that increases corticomuscular excitability may turn out to be an ideal intervention added prior to traditional motor training to “activate” the neural circuit, so that patients may get the most out of the training. According to a recent study that applied single session peripheral ES on post-stroke individuals, the corticomuscular coherence (CMC), which is the synchronization level between EEG and EMG, increased significantly and was accompanied by improvement in the steadiness of force output28.

To our knowledge, however, there is no study investigating the long-term effect of ES combined with functional training on both motor performance and cortical excitability. We targeted the median nerve because its distribution covered the dorsal side of index, middle, and half of ring finger and the palmar side of the first three fingers and half of the ring finger. Besides, median nerve is in charge of the flexion of the first three fingers, which combined they accounts for most of the functional tasks of hand. Therefore, the purpose of this pilot study was to preliminarily evaluate the effect of eight-week ES-combined hand functional training among chronic stroke patients based on CMC and motor performance. We followed up for four weeks after the intervention ceased and examined the lasting effect. We hypothesized that those who received intervention with ES would have better hand function and higher CMC than those who received intervention with sham ES. We also hypothesized that the effect would last for at least four weeks during our follow-up.[…]


Continue —>  Effects of 8-week sensory electrical stimulation combined with motor training on EEG-EMG coherence and motor function in individuals with stroke

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