Posts Tagged TMS

[Abstract] YouTube as a Source of Information for Transcranial Magnetic Stimulation in Stroke: A Quality, Reliability and Accuracy Analysis


•TMS is used to treat various diseases such as stroke and depression.

•Patients may be at risk of exposure to false information about TMS on YouTube.

•It is necessary to access the accurate information on YouTube about TMS treatment.

•Academicians need to be encouraged to create videos with better educational quality.


Background and objectives

Studies using YouTube data for various diseases are rapidly increasing. This study aimed to investigate the educational quality, reliability and accuracy of the YouTube videos concerning repetitive transcranial magnetic stimulation (rTMS) applications in patients with stroke.


This is a descriptive study. A video based search on YouTube was performed on April 18th, 2020 by using keyword ‘stroke repetitive transcranial magnetic stimulation’. The videos were queried using the default settings on YouTube and the results were listed according to relevance. Video parameters and sources were recorded. Quality, reliability and accuracy of the videos were determined with Global Quality Score (GQS), Journal of American Medical Association (JAMA) Benchmark Criteria and Modified DISCERN Questionnaire, respectively.


A total of 21 videos were included in the study. The median number of views for videos was 884 (range: 89-28589) and the median duration was 135 seconds. None of the videos had a negative interaction index. The median value was found to be 3 for all three measurements (GQS, JAMA, and DISCERN). Most of the videos were of intermediate quality (47.6%) and had partial sufficient data (61.9%). In the high-quality group, the number of views, dislikes, the duration of the videos, JAMA and DISCERN scores were higher than the low-quality group (p < 0.05). At the same time, viewing rates of the high-quality group were better than the low and the intermediate-quality group (p < 0.05). There was a significant positive correlation between GQS and number of the views, video duration, number of likes, number of dislikes, viewing rate and modified DISCERN questionnaire scores (p < 0.05).


Our results showed that most of the rated videos were of intermediate quality and had partially sufficient data. It has also been found that high-quality videos have higher viewing rates, more dislikes, longer video durations as well as better reliability and accuracy scores. YouTube videos of higher quality and accuracy are needed to increase awareness of rTMS by stroke patients.


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[VIDEO] 2019 Research about Transcranial Magnetic Stimulation TMS | NYC Psychiatrist – YouTube

Psychiatrist Robert D. McMullen – NYC – Depression Specialist – TMS BrainCare

In this video, we introduce Robert D. McMullen, MD who is a psychiatrist in NYC who has been performing psychopharmacology for over 30 years, the last 10 of which includes transcranial magnetic stimulation(TMS). Today, he will discuss some recent developments in research regarding TMS.

There were recently two conferences held in Vancouver, Canada regarding TMS research. The first was a 2 day conference held by the Clinical Society of TMS, which is the U.S organization for TMS research that has been around for 10 years. The second was the three day International Brain Stimulation held every 2 years. During these conferences, new research on TMS was presented.

Usually TMS treatments have been left excitatory on the left dorsolateral prefrontal cortex. It was then observed that if you performed inhibitory treatment on the right side it worked as well. Afterwards, many started doing bilateral treatments. Recent studies suggest that all those forms of treatment work equally as well, although for some, bilateral treatment might work better.

Another breakthrough in TMS treatment in the last few years is theta burst stimulation. It shortens the length of treatment on both sides of the brain(40 seconds on the right and 3 minutes and 8 seconds on the left side).

Recent findings suggest that doing 2 TMS treatments per day increases the odds of patients responding to TMS treatments. One recent study shows that people who receive 2 treatments per day for 15 days did just as well as people who did 1 treatment per day for 30 days. Using theta bursts significantly lowers the length of the treatment allowing multiple treatments to be performed in one day. Ideally, each treatment should be performed 15 minutes apart for optimal effect.

These were just a few of the findings presented at the conferences. Although TMS research is still ongoing, the future is looking bright for this method of treatment.

To learn more:

Psychiatrist Robert D. McMullen – NYC – Depression Specialist – TMS BrainCare

Location 1: 171 W 79th St #2, New York, NY 10024

Location 2: 344 Main St, Mt Kisco, NY 10549 Phone: 212 362-9635

TMS BrainCare

Address: #2, 171 W 79th St, New York, NY 10024

Phone: (212) 362-9635

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[Abstract] Effects of transcranial magnetic stimulation on the performance of the activities of daily living and attention function after stroke: a randomized controlled trial

We aimed to interrogate the effects of transcranial magnetic stimulation (TMS) on the performance in activities of daily living (ADL) and attention function after stroke.

Randomized controlled trial.

Inpatient rehabilitation hospital.

We randomized 62 stroke patients with attention dysfunction who were randomly assigned into two groups, and two dropped out from each group. The TMS group (n = 29) and a sham group (n = 29), whose mean (SD) was 58.12 (6.72) years. A total of 33 (56.9%) patients had right hemisphere lesion while the rest 25 (43.1%) patients had left hemisphere lesion.

Patients in the TMS group received 10 Hz, 700 pulses of TMS, while those in the sham group received sham TMS for four weeks. All the participants underwent comprehensive cognitive training.

At baseline, and end of the four-week treatment, the performance in the activities of daily living was assessed by Functional Independence Measure (FIM). On the other side, attention dysfunction was screened by Mini-Mental State Examination (MMSE), while the attention function was assessed by the Trail Making Test-A (TMT-A), Digit Symbol Test (DST) and Digital Span Test (DS).

Our data showed a significant difference in the post-treatment gains in motor of Functional Independence Measure (13.00 SD 1.69 vs 4.21 SD 2.96), cognition of Functional Independence Measure (4.69 SD 1.56 vs 1.52 SD 1.02), total of Functional Independence Measure (17.69 SD 2.36 vs 5.72 SD 3.12), Mini-Mental State Examination (3.07 SD 1.36 vs 1.21 SD 0.62), time taken in Trail Making Test-A (96.67 SD 25.18 vs 44.28 SD 19.45), errors number in Trail Making Test-A (2.72 SD 1.03 vs 0.86 SD 1.03), Digit Symbol Test (3.76 SD 1.09 vs 0.76 SD 0.87) or Digital Span Test (1.69 SD 0.54 vs 0.90 SD 0.72) between the TMS group and the sham group (P < 0.05).

Taken together, we demonstrate that TMS improves the performance in the activities of daily living and attention function in patients with stroke.

via Effects of transcranial magnetic stimulation on the performance of the activities of daily living and attention function after stroke: a randomized controlled trial – Yuanwen Liu, Mingyu Yin, Jing Luo, Li Huang, Shuxian Zhang, Cuihuan Pan, Xiquan Hu, 2020

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[VIDEO] Harnessing the Power of Neuroplasticity: The Nuts and Bolts of Better Brains – YouTube

What if your brain at 77 were as plastic as it was at 7? What if you could learn Mandarin with the ease of a toddler or play Rachmaninoff without breaking a sweat? A growing understanding of neuroplasticity suggests these fantasies could one day become reality. Neuroplasticity may also be the key to solving diseases like Alzheimer’s, depression, and autism. In this program, leading neuroscientists discuss their most recent findings and both the tantalizing possibilities and pitfalls for our future cognitive selves.

PARTICIPANTS: Alvaro Pascual-Leone, Nim Tottenham, Carla Shatz



This program is part of the BIG IDEAS SERIES, made possible with support from the JOHN TEMPLETON FOUNDATION.

TOPICS: – Opening film 00:07 – What is neuroplasticity? 03:53 – Participant introductions 04:21 – Structure of the brain 05:21 – Is the brain fundamentally unwired at the start? 07:02 – Why does the process of human brain development seem inefficient? 08:30 – Balancing stability and plasticity 10:43 – Critical periods of brain development 13:01 – Extended human childhood development compared to other animals 14:54 – Stability and. plasticity in the visual system 17:37 – Reopening the visual system 25:13 – Pros and cons of brain plasticity vs. stability 27:28 – Plasticity in the autistic brain 29:55 – What is Transcranial magnetic stimulation (TMS) 31:25 – Phases of emotional development 33:10 – Schizophrenia and plasticity 37:40 – Recovery from brain injury 40:24 – Modern rehabilitation techniques 47:21 – Holy grail of Neuroscience 50:12 – Enhancing memory performance as we age 53:37 – Regulating emotions 57:19

PROGRAM CREDITS: – Produced by Nils Kongshaug – Associate Produced by Christine Driscoll – Opening film written / produced by Vin Liota – Music provided by APM – Additional images and footage provided by: Getty Images, Shutterstock, Videoblocks

This program was recorded live at the 2018 World Science Festival and has been edited and condensed for YouTube.

via Harnessing the Power of Neuroplasticity: The Nuts and Bolts of Better Brains – YouTube

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[BLOG POST] tES vs. TMS: pros and cons of the two techniques


At Neuroelectrics, we believe in the advantages and effectiveness of transcranial electric stimulation (tES) in treating numerous brain diseases. Yet, despite the increasing number of tES publications per year, the lion’s share in the market of non-invasive brain stimulation technologies is still played by transcranial magnetic stimulation (TMS), likely because TMS received US-FDA approval in 2008 whereas tES has not yet.

Does this mean TMS is more effective? Well, it’s not quite fair to say so, considering TMS studies started at least 10 years earlier than those of tES. Therefore, there are several more clinical trials proving TMS efficacy.

However, the two techniques are close relatives: you can think of TMS as the elderly, stiff and sturdy brother, and tES as the younger, more flexible and easy-going one.
In this blogpost, we’ll go over the roots of their differences and see when and why you might prefer one over the other.

[E-fields patterns and biophysical substrates]

At a fundamental level, the two techniques rely on different physics and induce distinct patterns of electric fields (E-field) on the cortex, acting on a different neural substrate.

TMS is based on electromagnetic induction: a large magnetic coil is placed just a few centimetres above the scalp to stimulate over a specific cortical area. When the operator launches the electric pulse, vast amounts of current flows suddenly through the coil and creates a magnetic field around it, which varies rapidly in time. This changing magnetic field induces a very short (order of 1ms), highly localized (figure 1), super-threshold (order of 100V/m) E-field in the cortex. The E-field maximum is reached on the gyrus right under the coil, and the orientation is mostly parallel to the cortical surface.
The most sensitive cells to an E-field with such characteristics are interneurons and collaterals of pyramidal cells aligned tangentially to the cortical surface, which are automatically triggered to fire.

Instead, tES operates in the (quasi-)static regime, as only a small amount of direct current (DC) or low frequency alternating current (AC) is applied through electrodes placed directly on the scalp. The temporal resolution of the technique is low because the neuromodulatory effects begins a few seconds after the start of stimulation. Moreover, the E-field generated is much weaker (order of 0.1V/m) and less focalized (although the focality can be improved by using multichannel montages, it remains much lower than TMS E-field). Depending on the electrodes’ geometry, the maxima can occur on the gyri at the edges of the electrodes or between them. The overall orientation of the E-field is normal to the cortical surface, which indicates that tES probably influences layer V pyramidal neurons, as they are mostly perpendicular to the cortex.

Given the low, subthreshold intensity, the tES E-field cannot cause neural firing, but it is able to modulate the firing rate, facilitating or inhibiting the activation of pyramidal cells.


Other important differences concerning system setup.

TMS technology is more complex and cumbersome. The cost of the whole equipment is between 50-100k USD or Euros. This includes a wall-powered and heavy stimulator about the size of a fridge, a coil connected to the stimulator by a high-voltage cable, a mechanical arm to hold it in place, and a neuro-navigation system to accurately place the coil over the target brain region. The coil hangs suspended over the head of the patient, and since the strength of the effects depends on the coil-cortex distance, it’s crucial to keep it at the specific distance. For this, during the treatment session, the patient must sit still in a specially designed chair, with positioning frames around the chin and forehead.

On the contrary, tES is much cheaper and effortless: the cost is between an average of 6-30k USD/Euros, and the whole setup fits a shoe box. The stimulator can be as small as a mobile phone, light/portable, and almost always battery powered. The electrodes are directly in contact with the scalp, held in place by a rubber band or a neoprene cap. This way, the patient can move and even walk during the stimulation session.


Despite the underlying differences, TMS and tES are both quite versatile tools for treatment and research, and they offer similar options.

In research settings, you can leverage on TMS’ high spatial and temporal resolution to study how brain networks dynamically operate. In this context, TMS is usually performed online (during task performance) by applying one pulse at the onset of a stimulus (single-pulse TMS), or two pulses over separate regions which are interconnected (paired-pulses TMS). But tES too allows one to study the causal link between cortical areas. For instance, with tACS, one can simultaneously apply oscillatory currents over distinct regions at the same frequency but with different phases to promote or hamper the synchronization of functional networks.

Clinical applications of brain stimulation techniques instead tend to focus more on long-term effects, promoting network neuroplasticity that can outlast the period of stimulation.
In this case, TMS is usually ran in the repetitive mode (rTMS), which consists in multiple pulses within just microseconds. Frequency lower than 1Hz has been linked to long term depression (LTD), whereas frequency above 5Hz to long term potentiation (LTP). Similar outcomes can be achieved with tCS using either tDCS anodal or cathodal stimulation, which has been shown promoting and inhibiting synaptic activation, respectively.

The side effects of both techniques are quite moderate – with one important exception. While tES can induce only mild and temporary itching, tingling, and skin reddening when done properly, TMS might cause mild headaches, facial twitching, seizures in extreme cases.

For both TMS and tES, medical treatment must be performed mostly in clinical settings, which means you will have to find a clinician who provides these services in their clinic. However, one of the strengths of tES is the possibility to perform stimulation telemedically (under the remote guidance of a clinicians) via home-treatment. This is important as it will boost therapeutic effects for pathologies such as motor rehabilitation, depression, Alzheimer’s disease, etc in the comfort of one’s home. And it has been shown that the number of sessions modulates the length of the long-term plastic effects.

Interested in home-application of tCS? Check our home-kit here.


Figure 1 Distribution of the E-field magnitude on the GM surface (left) and on a midsagittal slice (right) during TMS (A,C) and tDCS  with 35cm2 rectangular sponges (B, D). E-field magnitude is in V/m. Courtesy of Salvador et. al. 2015


Polanía R, Nitsche M.A., Ruff C., Studying and modifying brain function with non-invasive brain stimulation, Nat. neurosci., 21:174–187 (2018)

Dayan E., Censor N., Buch E.R., Sandrini M, Cohen L.G., Noninvasive brain stimulation: from physiology to network dynamics and back, Nat. Neurosci., 16:838–844 (2013)

Salvador R., Wenger C., Miranda P.C. Investigating the cortical regions involved in MEP modulation in tDCS, Front. Cell. Neurosci. 9:405 (2015)


via tES vs. TMS: pros and cons of the two techniques – Blog Neuroelectrics

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[ARTICLE] Methods for an Investigation of Neurophysiological and Kinematic Predictors of Response to Upper Extremity Repetitive Task Practice in Chronic Stroke – Full Text PDF



To demonstrate the feasibility of algorithmic prediction utilizing a model of baseline arm movement, genetic factors, demographic characteristics, and multi-modal assessment of the structure and function of motor pathways. To identify prognostic factors and the biological substrate for reductions in arm impairment in response to repetitive task practice.


This prospective single-group interventional study seeks to predict response to a repetitive task practice program using an intent-to-treat paradigm. Response is measured as a change of ≥5 points on the Upper Extremity Fugl-Meyer from baseline to final evaluation (at the end of training).


General community


Anticipated enrollment of 96 community-dwelling adults with chronic stroke (onset ≥6 months) and moderate to severe residual hemiparesis of the upper limb as defined by a score of 10-45 points on the Upper Extremity Fugl-Meyer.


The intervention is a form of repetitive task practice using a combination of robot-assisted therapy coupled with functional arm use in real-world tasks administered over 12 weeks.

Main outcome measures

Upper extremity Fugl-Meyer Assessment (primary outcome), Wolf Motor Function Test, Action Research Arm Test, Stroke Impact Scale, questionnaires on pain and expectancy, magnetic resonance imaging, transcranial magnetic stimulation, arm kinematics, accelerometry, and a saliva sample for genetic testing.


Methods for this trial are outlined and an illustration of inter-individual variability is provided by example of two participants who present similarly at baseline but achieve markedly different outcomes.


This article presents the design, methodology, and rationale of an ongoing study to develop a predictive model of response to a standardized therapy for stroke survivors with chronic hemiparesis. Applying concepts from precision medicine to neurorehabilitation is practicable and needed to establish realistic rehabilitation goals and to effectively allocate resources.

Download full text in PDF

via Methods for an Investigation of Neurophysiological and Kinematic Predictors of Response to Upper Extremity Repetitive Task Practice in Chronic Stroke – ScienceDirect

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[WEB SITE] What is neurohacking and can it actually rewire your brain?

Marc Bordons / Stocksy

What is neurohacking and can it actually rewire your brain?

Although at one point, “hack” referred to a creative solution to a tech problem, the term can apply to pretty much anything now. There are kitchen hacks, productivity hacks, personal finance hacks. Brain hacks, or neurohacks, are among the buzziest, though, thanks largely to the Silicon Valley techies who often swear by them as a way to boost their cognitive function, focus, and creativity. Mic asked a neuroscientist to explain neurohacking, which neurohacking methods are especially promising, which are mostly hype, and how to make neurohacking work for you.

First things first: Neurohacking, is a broad umbrella term that encompasses anything that involves “manipulating brain function or structure to improve one’s experience of the world,” says neuroscientist Don Vaughn of Santa Clara University and the University of California, Los Angeles. Like the other myriad forms of hacking, neurohacking uses an engineering approach, treating the brain as a piece of hardware that can be systematically modified and upgraded.

Neurohacking techniques can fall under a number of categories — here are a few of the most relevant ones, as well as the thinking behind them.

Brain stimulation

This involves applying an electric or magnetic field to certain regions of the brain in non-neurotypical people to make their activity more closely resemble that seen in a neurotypical brain. In 2008, the Food and Drug Administration approved transcranial magnetic stimulation (TMS) — a noninvasive form of brain stimulation which delivers magnetic pulses to the brain in a noninvasive manner — for major depression. Since then, the FDA has also approved TMS for pain associated with migraines with auras, as well as obsessive-compulsive disorder. Established brain stimulation techniques (such as TMS or electroconvulsive therapy) performed by an expert provider, such as a psychiatrist or neuroscientist, are generally safe, Vaughn says.


This one involves using a device that measures brain activity, such as an electroencephalogram (EEG) or a functional magnetic resonance imaging (fMRI) machine. People with neuropsychological disorders receive feedback on their own brain activity — often in the form of images or sound — and focus on trying to make it more closely resemble the brain activity in a healthy person, Vaughn says. This could happen through changing their thought patterns, Vaughn says. Another possibility is that the feedback itself, or the person’s thoughts about the feedback, may somehow lead to a change in their brain’s wiring.

Reducing cognitive load

This means minimizing how much apps, devices, and other tech compete for your attention. Doing so can sharpen and sustain your focus, or what Vaughn refers to as your attention quotient (AQ). To boost his AQ, Vaughn listens to brown noise, which he likens to “white noise, but deeper.” (Think the low rush of a waterfall versus pure static.) He also chews gum, which he says provides an outlet for his restless “monkey mind” while still allowing him to focus on the task at hand.

Reducing cognitive load can also deepen your connection with others. Vaughn uses Voicea, an app based on an AI assistant that takes and store notes of meetings, whether over the phone or in-person, allowing him to focus solely on the conversation, not on recording it. “If we can quell those disruptions that occur because of the way work is done these days, it will allow us to focus and be more empathic with each other,” he says.

Monitoring sleep

Tracking your sleep patterns and adjusting them accordingly. Every night, you go through around five or so stages of sleep, each one deeper than the last. “People are less groggy and make fewer errors when they wake up in a lighter stage of sleep,” Vaughn says. He uses Sleep Cycle, an app that tracks your sleep patterns based on your movements in bed to rouse you during your lightest sleep stage.

Andrey Popov / Shutterstock


Microdosing is the routinely consumption of teensy doses of psychedelics like LSD, ecstasy, or magic mushrooms. Many who practice microdosing follow the regimen recommended by James Fadiman, psychologist and author of The Psychedelic Explorer’s Guide: Safe, Therapeutic, and Sacred Journeys: a twentieth to a tenth of a regular dose, once every three days for about a month. While a regular dose may make you trip, a microdose has subtler effects, with some users reporting, for instance, enhanced energy and focus, per The Cut.


These are OTC supplements or drugs taken to enhance cognitive function. They range from everyday caffeine and vitamin B12 (B12 deficiency has been associated with cognitive decline) to prescription drugs like Ritalin and Adderall, used to treat ADHD and narcolepsy, as well as Provigil (modafinil), used to treat extreme drowsiness resulting from narcolepsy and other sleep disorder. (All three of these drugs promote wakefulness.) The science behind nootropic supplements in particular remains rather murky, though.

Does neurohacking work, though?

Vaughn finds microdosing, neurostimulation, and neurofeedback especially promising for neuropsychological disorders. Although studies suggest that larger doses of psychedelics could help with disorders such as PTSD and treatment-resistant major depression, there are few studies on microdosing psychedelics. “The little science that has been done…is mixed—perhaps slightly positive,” Vaughn says. “Microdosing is promising mainly because of anecdotal evidence.” Meanwhile, neurostimulation can be used noninvasively in some cases, and TMS has already received FDA approval for a handful of conditions. Neurofeedback is not only non-invasive, but offers immediate feedback, and studies suggest it could be effective for PTSD and addiction.

But it’s important to note that just because these methods could positively alter brain function in people with neuropsychological disorders, that “doesn’t mean it’s going to take a normal system and make it superhuman,” Vaughn says. “I think there are lots of small hacks to be done that could add up to something big,” rather than huge hacks that can vastly upgrade cognitive function, a la Limitless. Thanks to millions of years of evolution, the human brain is already pretty damn optimized. “I just don’t know how much more we can tweak it to make it better,” Vaughn says.

As far as enhancements for neurotypical brains, he says that “you’ll probably see a much greater improvement” from removing distractions in your environment to reduce cognitive load than say, increasing your B12 intake — which brings us to an important disclaimer about nootropic supplements in particular. As with all supplements, they aren’t FDA-regulated, meaning that companies that sell them don’t need to provide evidence that they’re safe or effective. Vaughn recommends trying nootropics that research has shown to be safe and effective, like B12 or caffeine.

How can I start neurohacking?

As tempting as it is, adopting every neurohack under the sun is “not the answer,” Vaughn says. Remember, everyone is different. While your best friend may gush about how much her mood has improved since she began microdosing shrooms, your brain might not respond to microdosing—or maybe taking psychedelics just doesn’t align with your ethics.

Start by exploring different neurohacks, and of course, be skeptical of any product that makes outrageous claims. Since neurofeedback isn’t a common medical treatment, talk to your doctor about enrolling in academic studies on neurofeedback, or companies that offer it if you’re interested, Vaughn says. You should also talk to your doctor if you want to try brain stimulation. A doctor can prescribe you Adderall, Ritalin, or Provigil but only for their indicated medical uses, not for cognitive enhancement.

Ultimately, neurohacks are tools, Vaughn says. “You have to find the one that works for you.” If anything, taking this DIY approach to improving your brain function will leave you feeling empowered, a benefit that probably rivals anything a supplement or sleep tracking app could offer.


via What is neurohacking and can it actually rewire your brain?

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[Abstract] Role of Interhemispheric Cortical Interactions in Poststroke Motor Function

Background/Objective. We investigated interhemispheric interactions in stroke survivors by measuring transcranial magnetic stimulation (TMS)–evoked cortical coherence. We tested the effect of TMS on interhemispheric coherence during rest and active muscle contraction and compared coherence in stroke and older adults. We evaluated the relationships between interhemispheric coherence, paretic motor function, and the ipsilateral cortical silent period (iSP).

Methods. Participants with (n = 19) and without (n = 14) chronic stroke either rested or maintained a contraction of the ipsilateral hand muscle during simultaneous recordings of evoked responses to TMS of the ipsilesional/nondominant (i/ndM1) and contralesional/dominant (c/dM1) primary motor cortex with EEG and in the hand muscle with EMG. We calculated pre- and post-TMS interhemispheric beta coherence (15-30 Hz) between motor areas in both conditions and the iSP duration during the active condition.

Results. During active i/ndM1 TMS, interhemispheric coherence increased immediately following TMS in controls but not in stroke. Coherence during active cM1 TMS was greater than iM1 TMS in the stroke group. Coherence during active iM1 TMS was less in stroke participants and was negatively associated with measures of paretic arm motor function. Paretic iSP was longer compared with controls and negatively associated with clinical measures of manual dexterity. There was no relationship between coherence and. iSP for either group. No within- or between-group differences in coherence were observed at rest.

Conclusions. TMS-evoked cortical coherence during hand muscle activation can index interhemispheric interactions associated with poststroke motor function and potentially offer new insights into neural mechanisms influencing functional recovery.


via Role of Interhemispheric Cortical Interactions in Poststroke Motor Function – Jacqueline A. Palmer, Lewis A. Wheaton, Whitney A. Gray, Mary Alice Saltão da Silva, Steven L. Wolf, Michael R. Borich, 2019

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[Abstract] Bilateral Contralaterally Controlled Functional Electrical Stimulation Reveals New Insights Into the Interhemispheric Competition Model in Chronic Stroke

Background. Upper-limb chronic stroke hemiplegia was once thought to persist because of disproportionate amounts of inhibition imposed from the contralesional on the ipsilesional hemisphere. Thus, one rehabilitation strategy involves discouraging engagement of the contralesional hemisphere by only engaging the impaired upper limb with intensive unilateral activities. However, this premise has recently been debated and has been shown to be task specific and/or apply only to a subset of the stroke population. Bilateral rehabilitation, conversely, engages both hemispheres and has been shown to benefit motor recovery. To determine what neurophysiological strategies bilateral therapies may engage, we compared the effects of a bilateral and unilateral based therapy using transcranial magnetic stimulation.

Methods. We adopted a peripheral electrical stimulation paradigm where participants received 1 session of bilateral contralaterally controlled functional electrical stimulation (CCFES) and 1 session of unilateral cyclic neuromuscular electrical stimulation (cNMES) in a repeated-measures design. In all, 15 chronic stroke participants with a wide range of motor impairments (upper extremity Fugl-Meyer score: 15 [severe] to 63 [mild]) underwent single 1-hour sessions of CCFES and cNMES. We measured whether CCFES and cNMES produced different effects on interhemispheric inhibition (IHI) to the ipsilesional hemisphere, ipsilesional corticospinal output, and ipsilateral corticospinal output originating from the contralesional hemisphere.

Results. CCFES reduced IHI and maintained ipsilesional output when compared with cNMES. We found no effect on ipsilateral output for either condition. Finally, the less-impaired participants demonstrated a greater increase in ipsilesional output following CCFES.

Conclusions. Our results suggest that bilateral therapies are capable of alleviating inhibition on the ipsilesional hemisphere and enhancing output to the paretic limb.


via Bilateral Contralaterally Controlled Functional Electrical Stimulation Reveals New Insights Into the Interhemispheric Competition Model in Chronic Stroke – David A. Cunningham, Jayme S. Knutson, Vishwanath Sankarasubramanian, Kelsey A. Potter-Baker, Andre G. Machado, Ela B. Plow, 2019

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[ARTICLE] Paired Associative Stimulation as a Tool to Assess Plasticity Enhancers in Chronic Stroke – Full Text

Background and Purpose: The potential for adaptive plasticity in the post-stroke brain is difficult to estimate, as is the demonstration of central nervous system (CNS) target engagement of drugs that show promise in facilitating stroke recovery. We set out to determine if paired associative stimulation (PAS) can be used (a) as an assay of CNS plasticity in patients with chronic stroke, and (b) to demonstrate CNS engagement by memantine, a drug which has potential plasticity-modulating effects for use in motor recovery following stroke.

Methods: We examined the effect of PAS in fourteen participants with chronic hemiparetic stroke at five time-points in a within-subjects repeated measures design study: baseline off-drug, and following a week of orally administered memantine at doses of 5, 10, 15, and 20 mg, comprising a total of seventy sessions. Each week, MEP amplitude pre and post-PAS was assessed in the contralesional hemisphere as a marker of enhanced or diminished plasticity. Strength and dexterity were recorded each week to monitor motor-specific clinical status across the study period.

Results: We found that MEP amplitude was significantly larger after PAS in baseline sessions off-drug, and responsiveness to PAS in these sessions was associated with increased clinical severity. There was no observed increase in MEP amplitude after PAS with memantine at any dose. Motor threshold (MT), strength, and dexterity remained unchanged during the study.

Conclusion: Paired associative stimulation successfully induced corticospinal excitability enhancement in chronic stroke subjects at the group level. However, this response did not occur in all participants, and was associated with increased clinical severity. This could be an important way to stratify patients for future PAS-drug studies. PAS was suppressed by memantine at all doses, regardless of responsiveness to PAS off-drug, indicating CNS engagement.


The capacity of the brain to make structural, physiological, and genetic adaptations following stroke, otherwise known as plasticity, is likely to be critical for improving sensorimotor impairments and functional activities. Promotion of adaptive plasticity in the central nervous system (CNS) leading to sustained functional improvement is of paramount importance, given the personal suffering and cost associated with post-stroke disability (Ma et al., 2014). In addition to rehabilitation therapies to retrain degraded motor skills, animal and human studies have tried to augment recovery with neuropharmacologic interventions. Unfortunately, few if any have had a notable effect in patients or have come into routine use (Martinsson et al., 2007Chollet et al., 2011Cramer, 2015Simpson et al., 2015). Methods to screen drugs based on their presumed mechanism of action on plasticity in human motor systems could speed translation to patients. However, there is currently no accepted method in stroke patients for evaluating the potential effectiveness or individual responsiveness to putative “plasticity enhancing” drugs in an efficient, low-cost, cross-sectional manner, in order to establish target engagement in humans and to avoid the extensive time and cost of protracted clinical trials.

Paired associative stimulation (PAS) is a safe, painless, and non-invasive technique known to result in short-term modulation of corticospinal excitability in the adult human motor system, lasting ∼90 min (Stefan et al., 2000Wolters et al., 2003). Post-PAS excitability enhancement has been considered an LTP-like response thought to relate to transient changes in synaptic efficacy in the glutamatergic system at the N-methyl-D-aspartate (NMDA) receptor, since both human NMDA receptor deficiency (Volz et al., 2016) and pharmacological manipulation with dextromethorphan (Stefan et al., 2002) can block the effect. While PAS has been explored as a potential therapeutic intervention in patients with residual motor deficits after stroke (Jayaram and Stinear, 2008Castel-Lacanal et al., 2009), it has not previously been investigated for its potential use as an assay of motor system plasticity in this context. Prior studies have suggested that motor practice and PAS share the same neuronal substrates, modulating LTP and LTD-like plasticity in the human motor system (Ziemann et al., 2004Jung and Ziemann, 2009); therefore, as an established non-invasive human neuromodulation method (Suppa et al., 2017), we reasoned that PAS would be a suitable assay in the present study to examine the effect of a drug on motor system plasticity.

Here, we examine the effect of memantine, a drug used for treatment of Alzheimer’s disease, on the PAS response in patients with chronic stroke. Memantine is described pharmacologically as a low affinity, voltage dependent, non-competitive, NMDA antagonist (Rogawski and Wenk, 2003). At high concentrations, like other NMDA-R antagonists, it can inhibit synaptic plasticity. At lower, clinically relevant concentrations, memantine can, under some circumstances, promote synaptic plasticity by selectively inhibiting extra-synaptic glutamate receptor activity while sparing normal synaptic transmission, and hence may have clinical utility for rehabilitation (Xia et al., 2010). Interest in specifically using the drug for its interaction with stroke pathophysiology stems from animal models of both prevention (Trotman et al., 2015), in which pre-conditioning reduced infarct size, as well as for functional recovery, in which chronic oral administration starting >2 h post-stroke resulted in improved function through a non-neuroprotective mechanism (López-Valdés et al., 2014). In humans, memantine taken over multiple days has been used to demonstrate that the NMDA receptor is implicated in specific transcranial magnetic paired-pulse measures (Schwenkreis et al., 1999), and short-term training-induced motor map reorganization (Schwenkreis et al., 2005). In studies of neuromodulation, memantine blocked the facilitatory effect of intermittent theta-burst stimulation (iTBS) (Huang et al., 2007). Similarly, LTP-like plasticity induced by associative pairing of painful laser stimuli and TMS over primary motor cortex (M1) can also be blocked by memantine (Suppa et al., 2013). The effects of memantine on the PAS response have not yet been demonstrated, including examination of potential dose-response effects, which would be important for the potential clinical application of memantine for stroke recovery.

In our study, we set out to determine whether PAS might be a useful tool to probe the potential for plasticity after stroke in persons with chronic hemiparesis and apply PAS as an assay to look at drug effects on motor system plasticity using memantine. We hypothesized that (a) PAS would enhance corticospinal excitability in the contralesional hemisphere of stroke patients, and that (b) since PAS-induced plasticity is thought to involve a short-term change in glutamatergic synaptic efficacy, memantine would have a dose-dependent effect on PAS response. We predicted that at low doses, memantine would enhance PAS-induced plasticity through selective blockade of extrasynaptic NMDA receptors, whereas higher doses would inhibit PAS-induced plasticity.[…]


Continue —> Frontiers | Paired Associative Stimulation as a Tool to Assess Plasticity Enhancers in Chronic Stroke | Neuroscience

Figure 1. Axial MR/CT images for individual patients illustrating the stroke lesion. Images are displayed in radiological convention. Images are labeled by participant number.


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