Posts Tagged neuromodulation

[ARTICLE] A Novel tDCS Sham Approach Based on Model-Driven Controlled Shunting – Full Text

Abstract

Background

Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique able to transiently modulate brain activity, is surging as one of the most promising therapeutic solutions in many neurological and psychiatric disorders. However, profound limitations exist in current placebo (sham) protocols that limit single- and double-blinding, especially in non-naïve subjects.

Objective

/hypothesis: To ensure better blinding and strengthen reliability of tDCS studies and trials, we tested a new optimization algorithm aimed at creating an “active” sham tDCS condition (ActiSham hereafter) capable of inducing the same scalp sensations perceived during real stimulation, while preventing currents from reaching the cortex and cause changes in brain excitability.

Methods

A novel model-based multielectrode technique —optimizing the location and currents of a set of small electrodes placed on the scalp— was used to control the relative amount of current delivered transcranially in real and placebo multichannel tDCS conditions. The presence, intensity and localization of scalp sensations during tDCS was evaluated by means of a specifically designed questionnaire administered to the participants. We compared blinding ratings by directly addressing subjects’ ability to discriminate across conditions for both traditional (Bifocal-tDCS and -Sham, using sponge electrodes) and our novel multifocal approach (both real Multifocal-tDCS and ActiSham). Changes in corticospinal excitability were monitored based on Motor Evoked Potentials (MEPs) recorded via concurrent Transcranial Magnetic Stimulation (TMS) and electromyography (EMG).

Results

Subjects perceived Multifocal-tDCS and ActiSham similarly in terms of both scalp sensations and their localization on the scalp, whereas traditional Bifocal stimulation was rated as more painful and annoying compared to its Sham counterpart. Additionally, differences in scalp localization were reported for active/sham Bifocal-tDCS. As for MEPs amplitude, a main effect of stimulation was found when comparing Bifocal-Sham and ActiSham (F(1,13)= 6.67, p=.023), with higher MEPs amplitudes after the application of Bifocal-Sham.

Conclusions

Compared to traditional Bifocal-tDCS, ActiSham offers better participants’ blinding by inducing very similar scalp sensations to those of real Multifocal tDCS both in terms of intensity and localization, while not affecting corticospinal excitability.

Introduction

Non-invasive Brain Stimulation (NIBS) techniques are used to modulate brain activity in a safe and well-tolerated way [1]. In particular, Transcranial direct current stimulation (tDCS), uses low-intensity electrical currents to modulate cortical excitability in a polarity-specific manner [1]. Classical tDCS montages consist of two rectangular sponge electrodes with a contact area of ∼25-35 cm2, where electrical current between 0.5mA and 4mA flows from a positively charged electrode (anode) to a negative one (cathode)[2] passing through various tissue compartments including skin, muscle, bone, cerebrospinal fluid and brain. Due to its safety and relatively low-cost, tDCS experiments have been widely carried out to investigate human neurophysiology and to test its application as a new potential therapeutic solution for neurological and psychiatric conditions. To ensure adequate understanding of the observed effects, however, researchers need to rely on valid and approved control placebo conditions, a fundamental requirement in randomized controlled trials. Traditional standard sham protocols consist on an initial ramp up of the current, followed by a short stimulation period (usually for 5-60 seconds) and a final ramp down [[3][4][5]], (i.e., Fade In of current, brief real Stimulation, Fade-Out; commonly known as “FISSFO” protocol), an approach thought to cause sensory stimulation similar to real tDCS without affecting cortico-spinal excitability [6]. However, both these assumptions (i.e., adequate blinding and absence of effects on the brain) are still under examination. FISSFO sham has been considered effective in providing a proper blinding when compared with real tDCS at 1mA for 20 minutes [6], becoming the standard for sham tDCS [7]. The rationale stems from participants’ reports in which the cutaneous perceptions that generally cue subjects on tDCS being effectively delivered (i.e., tingling or itching sensation), have been mostly reported during the first 30-60 seconds of stimulation to then gradually decrease, possibly due to habituation [4]. However, a recent investigation has revealed that even naïve subjects (N=192) are capable of distinguishing classic sham stimulation (FISSFO) from active tDCS when delivered at 1 mA for 20 minutes over the left dorsolateral prefrontal cortex (DLPFC) [8]. Prior experiments had already suggested blinding inefficacy when real tDCS is applied at 1.5-2 mA, even for only 10 minutes [9,10]. Accordingly, non-naïve subjects seem more capable of distinguishing real from sham tDCS [11] and extreme individual variability has been reported with regard to sensibility to stimulation intensity and duration, with subjects being able to perceive tDCS even at very low intensity (i.e., 400 μA) [11].

On the other hand, additional sham protocols have been developed with modified durations of ramp up/down, or even delivering constant low intensity currents (0.016 or 0.034 mA) [7,12,13]. However, these approaches have not been properly tested on large sample of patients/subjects, with no data on the effects of such alternative sham protocols on the brain, while inconsistent results on many neurophysiological parameters have been documented when adopting such modified approaches [13].

Beyond the single or double blinding efficacy of FISSFO and related approaches [14], an element of interest is the question of whether tDCS effects are due to cortical interaction of the generated electric fields or from peripheral nervous system (PNS) stimulation. Since the ramp-up/ramp-down method for blinding decreases both cortical and peripheral stimulation, they cannot help disentangling cortical and peripheral effects. In addition, cortical effects of the brief period of real stimulation during sham protocols may not completely be excluded [15].

An additional challenge is the fact that the induced tDCS electric field is conditioned by the heterogeneity of cortical and non-cortical tissues, as well as by the complexity of cortical geometry [16]. In recent years, this has been addressed by the use of multichannel tDCS systems in combination with realistic finite element modeling of current propagation in the head derived from subject neuroimaging data (e.g. MRI, fMRI) [17,18]. The rationale for multifocal stimulation resides on both the need for more targeted stimulation of the cortex, as well as the notion that brain regions operate in networks and communicate with each other’s through modulatory interactions [[19][20][21]]. Realistic physical models provide a crucial element for better experimental understanding and control of the electric fields generated by tDCS.

In the present study, we investigate a novel approach to sham stimulation based on controlled shunting of currents via a model-based quantification of transcutaneous and transcranial effects. Specifically, the novel sham tDCS solution benefits from the use of an optimization algorithm allowing tDCS montages to be tailored in such a way that zero or very low magnitude electric fields are delivered on the brain, while medium to high intensity currents are maintained in at least some scalp electrodes, thus eliciting scalp sensations necessary for blinding. Notably, this allows to maintain the stimulation ON for the entire duration of sham tDCS, therefore inducing scalp sensations similar to real tDCS, while avoiding known limitations of the FISSFO protocol. We hypothesize that such montage (Active Sham, ActiSham hereafter) (i) will generate scalp sensations similar to a Multifocal (real) tDCS montage based on the same electrodes’ location and identical stimulation intensity/duration; and that (ii) ActiSham will not induce changes in cortico-spinal excitability (CSE), as assessed through Motor Evoked Potentials (MEPs) induced by Transcranial Magnetic Stimulation (TMS) as an index of corticospinal excitability. If successful, this and similar other approaches for improved sham stimulation could contribute to more efficient design of future tDCS research studies and clinical trials.

Methods

Study design

Fourteen subjects participated in 4 randomized tDCS stimulation visits, spaced 7±3 days to ensure no carryover effects. The tDCS conditions were: real Bifocal-tDCS, Bifocal-Sham, real Multifocal-tDCS and ActiSham. Each session lasted approximately 90 minutes during which participants seated in a comfortable chair with their eyes open. To measure changes in corticospinal excitability, single pulse TMS was applied over the left primary motor cortex (M1) at the beginning and the end of each stimulation session. Somatosensory sensations elicited by tDCS were addressed by means of ad-hoc questionnaires. See dedicated sections below for further details about tools and procedures.

Participants

Fourteen healthy right-handed naïve subjects (25.4 years ± 2.1; 5 males) were recruited at the University Campus of Siena, School of Medicine (Siena, Italy). Possible contraindications to either TMS or tDCS were assessed by means of a screening questionnaire [22]. Exclusion criteria included: history of seizures, head injury, pacemakers or other implanted medical devices, metallic objects in the head, hearing impairments, medications altering cortical excitability or other significant medical concerns. All participants gave written informed consent prior to participating to the study. The research proposal and associated methodologies were approved by the local ethical committee in accordance with the principles of the Declaration of Helsinki.

tDCS

tDCS sessions lasted 15 minutes, with electrode types, scalp montages and stimulation intensities customized for each tDCS protocol (Figure 1). Transcranial stimulation was delivered using a “Starstim 8” brain stimulator controlled via Bluetooth using a laptop computer (Neuroelectrics, Barcelona, Spain). For canonical Bifocal-tDCS (active or sham), stimulation was delivered through traditional 5×7 cm rectangular sponge electrodes, with a contact area of 35 cm2 (SPONSTIM, Neuroelectrics, Barcelona, Spain). Before current delivery, electrodes were soaked with 15 ml of sterile sodium chloride solution (0.9%). For Multichannel stimulation conditions (real and ActiSham), current was instead delivered using circular Ø 20 mm PISTIM electrodes (Neuroelectrics, Barcelona, Spain) with an Ag/AgCl core and a gel/skin contact area of 3.14 cm2. Electrodes were filled with a conductive gel before the tDCS intervention. To further improve current conductivity, the scalp was gently rubbed with an alcohol solution at the beginning of each session. Electrodes were inserted in a neoprene cap with available positions following the 10/20 EEG system.

Figure 1

Figure 1Study design. (A) Active stimulation was delivered for 15 minutes, (30 seconds of ramp up and down). Corticospinal excitability was measured via TMS three times prior to stimulation (Pre-10, Pre-5 and Pre-0) and compared with post measurements collected up to 15 minutes after stimulation (Post-0, Post-5, Post-10, Post-15). Halfway through the protocol (i.e., at minute 7), subjects were asked to rate stimulation-related annoyance and pain levels. tDCS montages for Multifocal-tDCS (B), ActiSham (C), Bifocal-tDCS and Bifocal-Sham (D) are shown.

[…]

Continue —-> A Novel tDCS Sham Approach Based on Model-Driven Controlled Shunting – ScienceDirect

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

Neuromodulation expands beyond health care.

PublicDomainPictures/Pixabay

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] Searching for the optimal tDCS target for motor rehabilitation – Full Text

Abstract

Background

Transcranial direct current stimulation (tDCS) has been investigated over the years due to its short and also long-term effects on cortical excitability and neuroplasticity. Although its mechanisms to improve motor function are not fully understood, this technique has been suggested as an alternative therapeutic method for motor rehabilitation, especially those with motor function deficits. When applied to the primary motor cortex, tDCS has shown to improve motor function in healthy individuals, as well as in patients with neurological disorders. Based on its potential effects on motor recovery, identifying optimal targets for tDCS stimulation is essential to improve knowledge regarding neuromodulation as well as to advance the use of tDCS in clinical motor rehabilitation.

Methods and results

Therefore, this review discusses the existing evidence on the application of four different tDCS montages to promote and enhance motor rehabilitation: (1) anodal ipsilesional and cathodal contralesional primary motor cortex tDCS, (2) combination of central tDCS and peripheral electrical stimulation, (3) prefrontal tDCS montage and (4) cerebellar tDCS stimulation. Although there is a significant amount of data testing primary motor cortex tDCS for motor recovery, other targets and strategies have not been sufficiently tested. This review then presents the potential mechanisms and available evidence of these other tDCS strategies to promote motor recovery.

Conclusions

In spite of the large amount of data showing that tDCS is a promising adjuvant tool for motor rehabilitation, the diversity of parameters, associated with different characteristics of the clinical populations, has generated studies with heterogeneous methodologies and controversial results. The ideal montage for motor rehabilitation should be based on a patient-tailored approach that takes into account aspects related to the safety of the technique and the quality of the available evidence.

Introduction

Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique which delivers a constant electric current over the scalp to modulate cortical excitability [1,2,3]. Different montages of tDCS may induce diverse effects on brain networks, which are directly dependent on the electrodes positioning and polarity. While anodal tDCS is believed to enhance cortical excitability, cathodal tDCS diminishes the excitation of stimulated areas, and these electrodes montages define the polarity-specific effects of the stimulation [4,5,6]. Due to the effects of tDCS on modulating cortical excitability, especially when applied to the primary motor cortex [2], this method of brain stimulation has been intensively investigated for motor function improvement both in healthy subjects [78] and in various neurological pathologies [910]. Neurological conditions that may obtain benefits from the use of tDCS include Stroke [11,12,13,14], Parkinson’s disease [15], Multiple Sclerosis [1617], among others.

The mechanisms of action underlying the modulation of neuronal activity induced by tDCS are still not completely understood. However, studies have demonstrated that the electric current generated by tDCS interferes in the resting membrane potential of neuronal cells, which modulates spontaneous brain circuits activity [1,2,3]. Some studies have suggested that tDCS could have an effect on neuronal synapsis’ strength, altering the activity of NMDA and GABA receptors, thus triggering plasticity process, such as long-term potentiation (LTP) and long-term depression (LTD) [1819]. The long-term effects of tDCS are also thought to be associated to changes in protein synthesis and gene expression [2021]. Additionally, neuroimaging study showed blood flow changes following stimulation, which may be related to a direct effect of tDCS over blood flow, with an increase in oxygen supply on cortical areas and subsequent enhancement of neuronal excitability [22]. Given these mechanisms, tDCS seems to be a potential valuable tool to stimulate brain activity and plasticity following a brain damage.

The advantages of using tDCS include its low cost, ease of application, and safety. To date, there is no evidence of severe adverse events following tDCS in healthy individuals, as well as in patients with neurological conditions, such as stroke [2324]. Among the potential side effects presented after this type of stimulation, the most common ones consist of burn sensation, itching, transient skin irritation, tingling under the electrode, headache, and low intensity discomfort [25]. As serious and irreversible side effects have not been reported, tDCS is considered a relatively safe and tolerable strategy of non-invasive brain stimulation.

The modifications of physiological and clinical responses induced by tDCS are extremely variable, as this type of stimulation can induce both adaptive or maladaptive plastic changes, and a wide spectrum of tDCS parameters influence the effects of this technique. Electrodes combination, montage and shape can easily interfere in the enhancement or inhibition of cortical excitability [626]. Other parameters that may influence these outcomes include current intensity, current flow direction, skin preparation, and stimulation intervals [32728] . In addition, in clinical populations, the heterogeneity of the brain lesions can also influence the inconsistency in tDCS effects [29]. Despite the goal of tDCS of modulating cortical areas by using different parameters, some studies have showed that, by altering cortical excitability, the electrical field could reach subcortical structures, such as basal ganglia, due to brain connections between cortical and subcortical areas [30,31,32,33]. This potential effect on deeper brain structure has supported the broad investigation of tDCS in various disorders, even if the cortical region under stimulating electrode is not directly linked to the neurological condition being investigated. Indeed, the current variable and moderate effect sizes from clinical tDCS studies in stroke encourage researchers to test alternative targets to promote motor recovery in this condition.

In this review, we discuss evidence on the application of four different tDCS montages to promote and enhance motor rehabilitation: [1] anodal tDCS ipsilateral and cathodal tDCS bilateral, [2] combination of central and peripheral stimulation, [3] prefrontal montage and [4] cerebellar stimulation.[…]

 

Continue —> Searching for the optimal tDCS target for motor rehabilitation | Journal of NeuroEngineering and Rehabilitation | Full Text

figure1

Fig. 1 Motor cortex stimulation in a scenario where the left hemisphere was lesioned. Figure a Anodal stimulation of left primary motor cortex: anode over the left M1 and cathode over the right supraorbital region. Figure b Cathodal stimulation of right primary motor cortex: cathode over the right M1 and anode over the left supraorbital region. Figure c Bilateral stimulation: anode over the affected hemisphere (left) and cathode over the non-affected hemisphere (right)

 

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[WEB SITE] How to help patients recover after a stroke

stroke
Credit: CC0 Public Domain

The existing approach to brain stimulation for rehabilitation after a stroke does not take into account the diversity of lesions and the individual characteristics of patients’ brains. This was the conclusion made by researchers of the Higher School of Economics (HSE University) and the Max Planck Institute of Cognitive Sciences in their article, “Predicting the Response to Non-Invasive Brain Stimulation in Stroke.”

Among the most common causes of death worldwide,  ranks second only to myocardial infarction (heart attack). In addition, a stroke is also a chronic disease that leaves patients disabled for many years.

In , non-invasive neuromodulation methods such as electric and magnetic stimulation of various parts of the nervous system have been increasingly used to rehabilitate patients after a stroke. Stimulation selectively affects different parts of the , which allows you to functionally enhance activity in some areas while suppressing unwanted processes in others that impede the restoration of brain functions. This is a promising mean of rehabilitation after a stroke. However, its results in patients remain highly variable.

The study authors argue that the main reason for the lack of effectiveness in neuromodulation approaches after a stroke is an inadequate selection of patients for the application of a particular brain stimulation technique.

According to the authors, the existing approach does not take into account the diversity of lesions after a stroke and the variability of individual responses to brain stimulation as a whole. Researchers propose two criteria for selecting the optimal brain  strategy. The first is an analysis of the interactions between the hemispheres. Now, all patients, regardless of the severity of injury after a stroke, are offered a relatively standard treatment regimen. This approach relies on the idea of interhemispheric competition.

“For a long time, it was believed that when one hemisphere is bad, the second, instead of helping it, suppresses it even more,” explains Maria Nazarova, one of the authors of the article and a researcher at the HSE Institute of Cognitive Neurosciences. “In this regard, the suppression of the activity of the “unaffected” hemisphere should help restore the affected side of the brain. However, the fact is that this particular scheme does not work in many  after a stroke. Each time it is necessary to check what the impact of the unaffected hemisphere is—whether it is suppressive or activating.”

The second criterion, scientists call the neuronal phenotype. This is an individual characteristic of the activity of the brain, which is “as unique to each person as their fingerprints.” Such a phenotype is determined, firstly, by the ability of the brain to build effective structural and functional connections between different areas (connectivity). And, secondly, the individual characteristics of neuronal dynamics, including its ability to reach a . This is the state of the neuronal system in which it is the most plastic and capable of change.

Only by taking these criteria into account, the authors posit, can neuromodulation methods be brought to a new level and be effectively used in clinical practice. To do this, it is necessary to change the paradigm of the universal approach and select methods based on the individual characteristics of the brain of a particular person and the course of his or her disease.


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How electrical stimulation reorganizes the brain

 

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[WEB SITE] Neuromodulation helps rehabilitate patients after a stroke

How neuromodulation helps patients recover after a stroke.

The neuromodulation methods can be brought to a new level and be effectively used in clinical practice only by taking these criteria into account. (Photo: Representational/Pixabay)

 The neuromodulation methods can be brought to a new level and be effectively used in clinical practice only by taking these criteria into account. (Photo: Representational/Pixabay)

Washington: The current approach used for brain stimulation to rehabilitate patients after a stroke does not look into the diversity of lesions and the individual characteristics of the brains of patients, finds a recent study.

The study was published in the journal ‘Frontiers in Neurology’. In recent decades, non-invasive neuromodulation methods such as electric and magnetic stimulation of various parts of the nervous system have been increasingly used to rehabilitate patients after a stroke.

Stimulation selectively affects different parts of the brain, which allows you to functionally enhance activity in some areas while suppressing unwanted processes in others that impede the restoration of brain functions.

This is a promising mean of rehabilitation after a stroke. However, its results in patients remain highly variable. The study authors argued that the main reason for the lack of effectiveness in neuromodulation approaches after a stroke is an inadequate selection of patients for the application of a particular brain stimulation technique.

According to the authors, the existing approach does not take into account the diversity of lesions after a stroke and the variability of individual responses to brain stimulation as a whole. Researchers proposed two criteria for selecting the optimal brain stimulation strategy. The first is an analysis of the interactions between the hemispheres.

Now, all patients, regardless of the severity of injury after a stroke, are offered a relatively standard treatment regimen. This approach relied on the idea of inter-hemispheric competition.

“For a long time, it was believed that when one hemisphere is bad, the second, instead of helping it, suppress it even more,’ explained Maria Nazarova, one of the authors of the article.

“In this regard, the suppression of the activity of the ‘unaffected’ hemisphere should help restore the affected side of the brain. However, the fact is that this particular scheme does not work in many patients after a stroke. Each time it is necessary to check what the impact of the unaffected hemisphere is, whether it is suppressive or activating,” said Nazarova.

The second criterion is the neuronal phenotype. This is an individual characteristic of the activity of the brain, which is ‘unique to each person like their fingerprints’. Such a phenotype is determined, firstly, by the ability of the brain to build effective structural and functional connections between different areas (connectivity).

Secondly, the individual characteristics of neuronal dynamics. This is the state of the neuronal system in which it is the most plastic and capable of change. The neuromodulation methods can be brought to a new level and be effectively used in clinical practice only by taking these criteria into account.

 

via Neuromodulation helps rehabilitate patients after a stroke

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[NEWS] Researchers propose new approach for post-stroke rehabilitation

The existing approach for brain stimulation to rehabilitate patients after a stroke does not take into account the diversity of lesions and the individual characteristics of patients’ brains, a study has found.

In recent decades, non-invasive neuromodulation methods such as electric and magnetic stimulation of various parts of the nervous system have been increasingly used to rehabilitate patients after a stroke.

Stimulation selectively affects different parts of the brain, which allows you to functionally enhance activity in some areas while suppressing unwanted processes in others that impede the restoration of brain functions.

This is a promising mean of rehabilitation after a stroke. However, its results in patients remain highly variable.

Authors of the study, which was published in the journal ‘Frontiers in Neurology’, argued that the main reason for the lack of effectiveness in neuromodulation approaches after a stroke is an inadequate selection of patients for the application of a particular brain stimulation technique.

They said the existing approach does not take into account the diversity of lesions after a stroke and the variability of individual responses to brain stimulation as a whole.

The researchers have proposed two criteria for selecting the optimal brain stimulation strategy.

The first is an analysis of the interactions between the hemispheres. Now, all patients, regardless of the severity of injury after a stroke, are offered a relatively standard treatment regimen. This approach relies on the idea of interhemispheric competition.

“For a long time, it was believed that when one hemisphere is bad, the second, instead of helping it, suppresses it even more,” said

Maria Nazarova, researcher at the HSE Institute of Cognitive Neurosciences.

“In this regard, the suppression of the activity of the “unaffected” hemisphere should help restore the affected side of the brain. However, the fact is that this particular scheme does not work in many patients after a stroke. Each time it is necessary to check what the impact of the unaffected hemisphere is — whether it is suppressive or activating,” she said.

According to the researchers, the second criterion is the neuronal phenotype.

This is an individual characteristic of the activity of the brain, which is ‘unique to each person like their fingerprints’.

Such a phenotype is determined, firstly, by the ability of the brain to build effective structural and functional connections between different areas (connectivity).

Secondly, the individual characteristics of neuronal dynamics, including its ability to reach a critical state. This is the state of the neuronal system in which it is the most plastic and capable of change.

(This story has not been edited by Business Standard staff and is auto-generated from a syndicated feed.

First Published: Fri, June 28 2019. 15:20 IST

 

via Researchers propose new approach for post-stroke rehabilitation | Business Standard News

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[ARTICLE] Transcranial Focused Ultrasound (tFUS) and Transcranial Unfocused Ultrasound (tUS) Neuromodulation: From Theoretical Principles to Stimulation Practices

Transcranial focused ultrasound is an emerging technique for non-invasive neurostimulation. Compared to magnetic or electric non-invasive brain stimulation, this technique has a higher spatial resolution and can reach deep structures. In addition, both animal and human studies suggest that, potentially, different sites of the central and peripheral nervous system can be targeted by this technique. Depending on stimulation parameters, transcranial focused ultrasound is able to determine a wide spectrum of effects, ranging from suppression or facilitation of neural activity to tissue ablation. The aim is to review the state of the art of the human transcranial focused ultrasound neuromodulation literature, including the theoretical principles which underlie the explanation of the bioeffects on neural tissues, and showing the stimulation techniques and parameters used and their outcomes in terms of clinical, neurophysiological or neuroimaging results and safety.

Introduction

Preliminary animal studies suggest that, potentially, different sites in the peripheral nervous system, from nerves (1) to spinal roots (2), and in the central nervous system, from superficial regions like primary motor cortex (3) or frontal eye field (4), to more deep areas like hippocampus (3), amygdala (5), or thalamus (6) can be targeted by focused ultrasound stimulation technique. In addition, animal studies showed that this technique has a high spatial resolution, useful also for mapping small brain areas, as shown by Fry (7) for the mapping of lateral geniculate nucleus, or by Ballantine et al. (2) for the stimulation of Edinger-Westphal nucleus.

Furthermore, a recent fMRI resting-state functional connectivity animal study (8), showed that the effect of tFUS neuromodulation can last for up to 2 h after stimulation, opening a new way to explore not only the online effect but also the long lasting effect of neuromodulation. The first human transcranial application of ultrasounds for neuromodulation was described by Hameroff et al. (9), with an unfocused transcranial ultrasound (tUS) continuous stimulation of posterior frontal cortex, applied on 31 patients affected by chronic pain. The first human application of focused transcranial ultrasound (tFUS) technique was described by Legon et al. (10). They targeted the primary somatosensory cortex of healthy volunteers, in a within-subjects, sham-controlled study. One of the most interesting results of tFUS applications was a case report of emergence from minimally conscious state, after low intensity non-invasive ultrasonic thalamic stimulation in a patient after acute brain injury (11). Following this first single evidence, a clinical trial is ongoing to explore the effect of thalamic low intensity focused ultrasound in acute brain injury patients (12).

Regarding peripheral nervous system neuromodulation, Bailey et al. (13) explored the ability of continuous US at 1.5 MHz in modulating the ulnar nerve stimulation response to magnetic stimulation (MS). This study showed no significant change in electromyographic response during magnetic plus US ulnar nerve stimulation. However, further studies are needed in order to explore different parameter of stimulation.

In recent years, the scientific community showed a progressive increasing interest on FUS neuromodulation, and some reviews have been published in order to summarize the state of the art on this topic (1418).

Mechanisms of Actions of US Neuromodulation

Focused ultrasound is a non-invasive, non-ionizing technique. In order to target a brain region, the first challenge is to let ultrasounds single waves to reach the target at the same time, without different acoustic reflection, refraction, and distortion due to the inhomogeneity of skull bone. This problem can be solved by time shifting each single ultrasound wave, according to the related skull bone acoustical properties, in order to let all the waves to reach the target at the same time (1922).

The mechanical interaction between US and neuronal membranes can modify the membrane gating kinetics through the action on mechanosensitive voltage-gated ion channels or neurotransmitter receptors (2325). The study of Tyler et al. (25) supports this hypothesis. Their study showed, on ex vivo mouse brains and hippocampal slice cultures, that low-intensity, low-frequency ultrasound (LILFU) is able to activate voltage-gated sodium and calcium channels. However, this can’t be the only mechanism of action, explaining the action potential induction, since in simulations, considering the role of membrane tension on activation of mechanically sensitive voltage gated channels, the resulting effect was too low to induce an excitation (2627).

In addition, the mechanical action of US is able to induce cavitation into the cellular membrane, by means of membrane pore formation, which changes the membrane permeability.

The bilayer sonophore model (28) was introduced to better explain the bioeffects of US, taking into consideration the biomechanical proprieties of US and of cell membranes. According to this model (28), the mechanical energy of US leads to periodic expansions and contractions of the membrane. In this model, the US bioeffect is dependent on the tension applied to the membrane. With a progressive increase in membrane stretch intensity, the bioeffect is mediated by different mechanisms. First by the activation of mechanosensitive proteins. Then, with an increase of intensity, there is a pore formation and with the maximum stretch that can be achieved with the technique a membrane rupture and irreversible lesion is obtained (28) (Figure 1).

Figure 1. Ultrasound gradually increases tension in the membrane. From the reference stage (S0), the stretch first activates mechanosensitive proteins (S1); growing tension might damage membrane proteins (S2) and then might induce pore formation (S3a, S3b) or cause membrane rupture [modified, with permission, from Krasovitski et al. (28)].

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[Abstract] Vagus Nerve Stimulation for the Treatment of Epilepsy

First page of article

Vagus nerve stimulation (VNS) was the first neuromodulation device approved for treatment of epilepsy. In more than 20 years of study, VNS has consistently demonstrated efficacy in treating epilepsy. After 2 years, approximately 50% of patients experience at least 50% reduced seizure frequency. Adverse events with VNS treatment are rare and include surgical adverse events (including infection, vocal cord paresis, and so forth) and stimulation side effects (hoarseness, voice change, and cough). Future developments in VNS, including closed-loop and noninvasive stimulation, may reduce side effects or increase efficacy of VNS.

via Vagus Nerve Stimulation for the Treatment of Epilepsy – Neurosurgery Clinics

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[ARTICLE] Home-based transcranial direct current stimulation plus tracking training therapy in people with stroke: an open-label feasibility study – Full Text

Abstract

Background

Transcranial direct current stimulation (tDCS) is an effective neuromodulation adjunct to repetitive motor training in promoting motor recovery post-stroke. Finger tracking training is motor training whereby people with stroke use the impaired index finger to trace waveform-shaped lines on a monitor. Our aims were to assess the feasibility and safety of a telerehabilitation program consisting of tDCS and finger tracking training through questionnaires on ease of use, adverse symptoms, and quantitative assessments of motor function and cognition. We believe this telerehabilitation program will be safe and feasible, and may reduce patient and clinic costs.

Methods

Six participants with hemiplegia post-stroke [mean (SD) age was 61 (10) years; 3 women; mean (SD) time post-stroke was 5.5 (6.5) years] received five 20-min tDCS sessions and finger tracking training provided through telecommunication. Safety measurements included the Digit Span Forward Test for memory, a survey of symptoms, and the Box and Block test for motor function. We assessed feasibility by adherence to treatment and by a questionnaire on ease of equipment use. We reported descriptive statistics on all outcome measures.

Results

Participants completed all treatment sessions with no adverse events. Also, 83.33% of participants found the set-up easy, and all were comfortable with the devices. There was 100% adherence to the sessions and all recommended telerehabilitation.

Conclusions

tDCS with finger tracking training delivered through telerehabilitation was safe, feasible, and has the potential to be a cost-effective home-based therapy for post-stroke motor rehabilitation.

Background

Post-stroke motor function deficits stem not only from neurons killed by the stroke, but also from down-regulated excitability in surviving neurons remote from the infarct [1]. This down-regulation results from deafferentation [2], exaggerated interhemispheric inhibition [3], and learned non-use [4]. Current evidence suggests that post-stroke motor rehabilitation therapies should encourage upregulating neurons and should target neuroplasticity through intensive repetitive motor practice [56]. Previously, our group has examined the feasibility and efficacy of a custom finger tracking training program as a way of providing people with stroke with an engaging repetitive motor practice [789]. In this program, the impaired index finger is attached to an electro-goniometer, and participants repeatedly move the finger up and down to follow a target line that is drawn on the display screen. In successive runs, the shape, frequency and amplitude of target line is varied, which forces the participant to focus on the tracking task. In one study, we demonstrated a 23% improvement in hand function (as measured by the Box and Block test; minimal detectable change is 18% [10]) after participants with stroke completed the tracking training program [9]. While our study did not evaluate changes in activity in daily life (ADL) or quality of life (because efficacy of the treatment was not the study objective), the Box and Block test is moderately correlated (r = 0.52) to activities in daily life and quality of life (r = 0.59) [11]. In addition, using fMRI, we showed that training resulted in an activation transition from ipsilateral to contralateral cortical activation in the supplementary motor area, primary motor and sensory areas, and the premotor cortex [9].

Recently, others have shown that anodal transcranial direct current stimulation (tDCS) can boost the beneficial effects of motor rehabilitation, with the boost lasting for at least 3 months post-training [12]. Also, bihemispheric tDCS stimulation (anodal stimulation to excite the ipsilateral side and cathodal stimulation to downregulate the contralateral side) in combination with physical or occupational therapy has been shown to provide a significant improvement in motor function (as measured by Fugl-Meyer and Wolf Motor Function) compared to a sham group [13]. Further, a recent meta-analysis of randomized-controlled trials comparing different forms of tDCS shows that cathodal tDCS is a promising treatment option to improve ADL capacity in people with stroke [14]. Compared to transcutaneous magnetic stimulation (TMS), tDCS devices are inexpensive and easier to operate. Improvement in upper limb motor function can appear after only five tDCS sessions [15], and there are no reports of serious adverse events when tDCS has been used in human trials for periods of less than 40 min at amplitudes of less than 4 mA [16].

Moreover, tDCS stimulation task also seems beneficial for other impairments commonly seen in people post-stroke. Stimulation with tDCS applied for 20 sessions of 30 min over a 4-week period has been shown to decrease depression and improve quality of life in people after a stroke [1718]. Four tDCS sessions for 10 min applied over the primary and sensory cortex in eight patients with sensory impairments more than 10 months post-stroke enhanced tactile discriminative performance [19]. Breathing exercises with tDCS stimulation seems to be more effective than without stimulation in patient with chronic stroke [20], and tDCS has shown promise in treating central post-stroke pain [21]. Finally, preliminary research on the effect of tDCS combined with training on resting-state functional connectivity shows promise to better understand the mechanisms behind inter-subject variability regarding tDCS stimulation [22].

Motor functional outcomes in stroke have declined at discharge from inpatient rehabilitation facilities [2324], likely a result of the pressures to reduce the length of stay at inpatient rehabilitation facilities as part of a changing and increasingly complex health care climate [2526]. Researchers, clinicians, and administrators continue to search for solutions to facilitate and post-stroke rehabilitation after discharge. Specifically, there has been considerable interest in low-cost stroke therapies than can be administered in the home with only a modest level of supervision by clinical professionals.

Home telerehabilitation is a strategy in which rehabilitation in the patient’s home is guided remotely by the therapist using telecommunication technology. If patients can safely apply tDCS to themselves at home, combining telerehabilitation with tDCS would be an easy way to boost therapy without costly therapeutic face-to-face supervision. For people with multiple sclerosis, the study of Charvet et al. (2017) provided tDCS combined with cognitive training, delivered through home telerehabilitation, and demonstrated greater improvement on cognitive measures compared to those who received just the cognitive training [27]. The authors demonstrated the feasibility of remotely supervised, at-home tDCS and established a protocol for safe and reliable delivery of tDCS for clinical studies [28]. Some evidence shows that telerehabilitation approaches are comparable to conventional rehabilitation in improving activities of daily living and motor function for stroke survivors [2930], and that telemedicine for stroke is cost-effective [3132]. A study in 99 people with stroke receiving training using telerehabilitation (either with home exercise program or robot assisted therapy with home program) demonstrated significant improvements in quality of life and depression [33].

A recent search of the literature suggests that to date, no studies combine tDCS with repetitive tracking training in a home telerehabilitation setting to determine whether the combination leads to improved motor rehabilitation in people with stroke. Therefore, the aim of this pilot project was to explore the safety, usability and feasibility of the combined system. For the tDCS treatment, we used a bihemispheric montage with cathodal tDCS stimulation to suppress the unaffected hemisphere in order to promote stroke recovery [34353637]. For the repetitive tracking training therapy, we used a finger tracking task that targets dexterity because 70% of people post-stroke are unable to use their hand with full effectiveness after stroke [38]. Safety was assessed by noting any decline of 2 points or more in the cognitive testing that persists over more than 3 days. We expect day to day variations of 1 digit. Motor decline is defined by a decline of 6 blocks on the Box and Block test due to muscle weakness. This is based on the minimal detectable change (5.5 blocks/min) [10]. The standard error of measurement is at least 2 blocks for the paretic and stronger side. We expect possible variations in muscle tone that could influence the scoring of the test. Usability was assessed through a questionnaire and by observing whether the participant, under remote supervision, could don the apparatus and complete the therapy sessions. Our intent was to set the stage for a future clinical trial to determine the efficacy of this approach.

Methods

Participants

Participants were recruited from a database of people with chronic stroke who had volunteered for previous post-stroke motor therapy research studies at the University of Minnesota. Inclusion criteria were: at least 6 months post-stroke; at least 10 degrees of active flexion and extension motion at the index finger; awareness of tactile sensation on the scalp; and a score of greater than or equal to 24 (normal cognition) on the Mini-Mental State Examination (MMSE) to be cognitively able to understand instructions to don and use the devices [39]. We excluded those who had a seizure within past 2 years, carried implanted medical devices incompatible with tDCS, were pregnant, had non-dental metal in the head or were not able to understand instructions on how to don and use the devices. The study was approved by the University of Minnesota IRB and all enrolled participants consented to be in the study.

Apparatus

tDCS was applied using the StarStim Home Research Kit (NeuroElectrics, Barcelona, Spain). The StarStim system consists of a Neoprene head cap with marked positions for electrode placement, a wireless cap-mounted stimulator and a laptop control computer. Saline-soaked, 5 cm diameter sponge electrodes were used. For electrode placement, we followed a bihemispheric montage [14] involving cathodal stimulation on the unaffected hemisphere with the anode positioned at C3 and the cathode at C4 for participants with left hemisphere stroke, and vice versa for participants with right hemisphere stroke. Stimulation protocols were set by the investigator on a web-based application that communicated with the tDCS control computer. A remote access application (TeamViewer) was also installed on the control computer, as was a video conferencing application (Skype).

The repetitive finger tracking training system was a copy of what we used in our previous stroke studies [789]. The apparatus included an angle sensor mounted to a lightweight brace and aligned with the metacarpophalangeal (MCP) joint of the index finger, a sensor signal conditioning circuit, and a target tracking application loaded on a table computer. Figure 1 shows a participant using the apparatus during a treatment session.

Fig. 1

Fig. 1 Participant with right hemiparesis receiving transcranial direct current magnetic stimulation (tDCS) in their home simultaneous while performing the finger movement tracking task on the tracking computer (left). The tDCS computer (right) shows the supervising investigator, located off-site, who communicated with the participant through the video conferencing application, controlled the tDCS stimulator through web-based software, and controlled the tracking protocols. (Permission was obtained from the participant for the publication of this picture)

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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.

Methods

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.

Results

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).

Conclusions

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.

 

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