- •This study uses a systematic, bibliometric approach to assess the TMS literature base.
- •Annual TMS research output has increased dramatically over the period 1988–2017.
- •The top disease entities studied to date have been stroke and depression.
The functional outcome after stroke is improved by more intensive or sustained therapy. When the affected hand has no functional movement, therapy is mainly passive movements. A novel device for repeating controlled passive movements of paralysed fingers has been developed, which will allow therapists to concentrate on more complicated tasks. A powered cam shaft moves the four fingers in a physiological range of movement.
After refining the training protocol in 2 chronic patients, 8 sub-acute stroke patients were randomised to receive additional therapy with the Finger Trainer for 20 min every work day for four weeks, or the same duration of bimanual group therapy, in addition to their usual rehabilitation.
In the chronic patients, there was a sustained reduction in finger and wrist spasticity, but there was no improvement in active movements. In the subacute patients, mean distal Fugl-Meyer score (0–30) increased in the control group from 1.25 to 2.75 (ns) and 0.75 to 6.75 in the treatment group (p < .05). Median Modified Ashworth score increased 0/5 to 2/5 in the control group, but not in the treatment group, 0 to 0. Only one patient, in the treatment group, regained function of the affected hand. No side effects occurred.
Treatment with the Finger Trainer was well tolerated in sub-acute & chronic stroke patients, whose abnormal muscle tone improved. In sub-acute stroke patients, the Finger Trainer group showed small improvements in active movement and avoided the increase in tone seen in the control group. This series was too small to demonstrate any effect on functional outcome however.
The annual stroke incidence is approximately 180 patients per 100,000 inhabitants in the industrialized world. About 30% of the surviving patients suffer from a severe upper limb paresis with a non functional hand. The prognosis for regaining meaningful hand activity six months after stroke onset is poor : this may partly be because current rehabilitation practice puts more emphasis on the compensatory use of the non-affected upper extremity .
Powered machines which can allow prolonged repetition of a controlled movement are a promising way of increasing the intensity of rehabilitation after stroke. Several devices, to treat wrist, elbow & shoulder movements, have been developed since the pioneering MIT-Manus in the early 1990s . Randomized controlled trials show a convincing beneficial effect of robot-assisted upper limb treatment on the impairment of severely affected stroke patients [4–9].
There are fewer clinical reports of machine-assisted movement of paralysed fingers. The Rutgers Hand Masters I and II use pistons mounted inside the palm to move the fingers, with virtual reality to improve motivation. Chronic stroke patients improved range of motion, motor control and speed of the paretic fingers over several weeks of training, and the benefits were retained at follow-up [10, 11].
With the Howard Hand Robot, pistons assist with patient initiated grasping and releasing movements around virtual or real objects. In moderately affected chronic stroke subjects, upper limb motor functions improved, and functional MRI revealed increased sensorimotor cortex activation during the grasping task which was not seen during a non-practiced task, supination/pronation .
Fischer et al assisted the finger extension of mildly affected stroke patients with the help of a powered orthosis. Following six weeks of training in reach-to-grasp of virtual and actual objects, patients’ active motor performance had shown a moderate improvement .
The treatment of the plegic fingers after stroke is pertinent given their large cortical representation, the presumed competition between proximal and distal limb segments for plastic brain territory , and recent results from the MIT-group promoting earlier active treatment of distal limb . Further, paresis-related immobilization seems to contribute to the development of long-term disabling finger flexor spasticity .
We have designed an electromechanical Finger Trainer to move individual fingers in a physiological range of movement. This article describes the device and reports its use in a small number of chronic and acute stroke patients with completely paralysed hands.
The Finger Trainer, Reha-Digit, (figure 1) consists of four, mutually independent plastic rolls, each fixed eccentrically to the powered axle of the device, forming a cam-shaft. Each finger-roll can be repositioned & secured by turning a knob on the main axle, on the other end from the motor, to fit the size & range of movement of each individual finger.
The surface of each finger roll is concave, forming a gutter to maximise the contact area between finger & roll. Two smaller locking rollers, also concave, hold each finger against the larger finger roll. Each pair of locking rollers moves orthogonally to the axis of the finger roll, and an elastic spring pulls each pair of locking rollers towards the finger roller. These can be lifted out of the way when first positioning the hand & fingers in the device.
A spacing bar, parallel to the drive axle, holds the hand in the optimal position: a thumb stop may be used to provide additional stability. This can be moved to either side, to accommodate either the left or right hand. There are emergency-stop switches at each end of the spacing bar. The forearm can be stabilised at the correct angle & height on a gutter support.
A 24 V DC motor rotates the drive axle up to 30 times a minute through a clutch mechanism, which allows the axle to stop rotating if the hand goes into a powerful spasm. A vibration engine, situated under the base plate, provides small amplitude (2 mm) stimulation at a frequency which can be set between 0 to 30 Hz, by turning a knob. The device’s weight is 7 kg, and its dimensions are 35 cm × 24 cm × 22 cm.[…]
Continue —-> A new electromechanical trainer for sensorimotor rehabilitation of paralysed fingers: A case series in chronic and acute stroke patients | Journal of NeuroEngineering and Rehabilitation | Full Text
Background. Severe poststroke arm impairment is associated with greater activation of the nonlesioned hemisphere during movement of the affected arm. The circumstances under which this activation may be adaptive or maladaptive remain unclear.
Objective. To identify the functional relevance of key lesioned and nonlesioned hemisphere motor areas to reaching performance in patients with mild versus severe arm impairment.
Methods. A total of 20 participants with chronic stroke performed a reaching response time task with their affected arm. During the reaction time period, a transient magnetic stimulus was applied over the primary (M1) or dorsal premotor cortex (PMd) of either hemisphere, and the effect of the perturbation on movement time (MT) was calculated.
Results. For perturbation of the nonlesioned hemisphere, there was a significant interaction effect of Site of perturbation (PMd vs M1) by Group (mild vs severe; P < .001). Perturbation of PMd had a greater effect on MT in the severe versus the mild group. This effect was not observed with perturbation of M1. For perturbation of the lesioned hemisphere, there was a main effect of site of perturbation (P < .05), with perturbation of M1 having a greater effect on MT than PMd.
Conclusions. These results demonstrate that, in the context of reaching movements, the role of the nonlesioned hemisphere depends on both impairment severity and the specific site that is targeted. A deeper understanding of these individual-, task-, and site-specific factors is essential for advancing the potential usefulness of neuromodulation to enhance poststroke motor recovery.
via Roles of Lesioned and Nonlesioned Hemispheres in Reaching Performance Poststroke – Rachael M. Harrington, Evan Chan, Amanda K. Rounds, Clinton J. Wutzke, Alexander W. Dromerick, Peter E. Turkeltaub, Michelle L. Harris-Love,
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
MODERATOR: Guy McKhann
MORE INFO ABOUT THE PROGRAM AND PARTICIPANTS: https://www.worldsciencefestival.com/…
This program is part of the BIG IDEAS SERIES, made possible with support from the JOHN TEMPLETON FOUNDATION.
FOLLOW us on Twitter: https://twitter.com/WorldSciFest
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.
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.
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.
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)
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
Background. After stroke, recovery of movement in proximal and distal upper extremity (UE) muscles appears to follow different time courses, suggesting differences in their neural substrates.
Objective. We sought to determine if presence or absence of motor evoked potentials (MEPs) differentially influences recovery of volitional contraction and strength in an arm muscle versus an intrinsic hand muscle. We also related MEP status to recovery of proximal and distal interjoint coordination and movement fractionation, as measured by the Fugl-Meyer Assessment (FMA).
Methods. In 45 subjects in the year following ischemic stroke, we tracked the relationship between corticospinal tract (CST) integrity and behavioral recovery in the biceps (BIC) and first dorsal interosseous (FDI) muscle. We used transcranial magnetic stimulation to probe CST integrity, indicated by MEPs, in BIC and FDI. We used electromyography, dynamometry, and UE FMA subscores to assess muscle-specific contraction, strength, and inter-joint coordination, respectively.
Results. Presence of MEPs resulted in higher likelihood of muscle contraction, greater strength, and higher FMA scores. Without MEPs, BICs could more often volitionally contract, were less weak, and had steeper strength recovery curves than FDIs; in contrast, FMA recovery curves plateaued below normal levels for both the arm and hand.
Conclusions. There are shared and separate substrates for paretic UE recovery. CST integrity is necessary for interjoint coordination in both segments and for overall recovery. In its absence, alternative pathways may assist recovery of volitional contraction and strength, particularly in BIC. These findings suggest that more targeted approaches might be needed to optimize UE recovery.
via Differential Poststroke Motor Recovery in an Arm Versus Hand Muscle in the Absence of Motor Evoked Potentials – Heidi M. Schambra, Jing Xu, Meret Branscheidt, Martin Lindquist, Jasim Uddin, Levke Steiner, Benjamin Hertler, Nathan Kim, Jessica Berard, Michelle D. Harran, Juan C. Cortes, Tomoko Kitago, Andreas Luft, John W. Krakauer, Pablo A. Celnik, 2019
Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulatory technique that has broad diagnostic and therapeutic potential across a range of neurological and psychiatric diseases.
This study utilises a bibliometric approach to systematically and comprehensively evaluate the literature on TMS from the last three decades.
The Scopus citation database was used to identify all peer-reviewed journal articles concerning TMS over the period 1988–2017. Frequency-distribution, cross-tabulation and keyword analyses were performed to determine the most prolific researchers, institutions, nations, journals and the foremost studied disease entities within the TMS field. Given recent heightened awareness of gender bias across many fields of biomedicine, female representation among the most prolific authors was determined. Open-access publication rates and types of study design utilised were also quantified.
17,492 TMS-related articles were published during the study period 1988–2017. The annual TMS research output has increased dramatically over this time, despite a recent levelling-off of publications per year. The most prolific institutions were based in the United Kingdom, the United States and Canada. The top disease entities studied were stroke, depression and Parkinson’s disease. Only 4/52 of the most productive researchers during the study period were female. A minority (4.81%) of publications were published as gold open-access.
This study implemented a systematic, bibliometric approach to quantitively assess the breadth of the TMS literature base and identify temporal publication and authorship trends. Drawing on these insights may aid understanding of historical progress in TMS over the last 30 years and help identify into unmet needs and opportunities to improve scientific and publishing practices to contribute to the future health of the field. These findings are likely to be relevant to researchers, clinicians, funders, industry collaborators and other stakeholders.
Post by Thomas Brown
The permanent brain damage which occurs following ischemic stroke makes functional recovery difficult. While physiotherapy can result in improved voluntary motor recovery, the improvement of balance and gait can be harder. Issues with balance pose a safety risk for stroke patients, who may be more likely to fall. Ultimately, problems with balance can mean reduced independence for patients. The cerebellum, a structure located at the back of the brain, is known to regulate movement, gait and balance. Deficits to the cerebellum often result in ataxia and widened gaits, making this area a prime target for functional recovery analysis. This week in JAMA Neurology Koch and colleagues demonstrate in a phase IIa clinical trial, an increase in gait and balance in hemiparetic stroke patients, up to three weeks after physiotherapy supplemented with transcranial magnetic stimulation of the cerebellum.
A group of 36 hemiparetic (one side affected) stroke patients were randomly assigned to one of two age-matched groups; control or experimental. The experimental group was treated with intermittent theta-burst magnetic stimulation (TBS) of the cerebellar region ipsilateral (same side) to their motor issues. Intermittent TBS is a process by which bursts of magnetic energy are applied to the scalp over an area of interest. TBS was administered in conjunction with physiotherapy to the experimental group for three weeks. The control group still received physiotherapy, but received sham (fake) TBS. Patients were assessed using a wide range of balance and gait analysis tests to determine the degree of recovery. The authors relied primarily on the Berg Balance Scale, which is a series of 14 tests that determine the ability of an individual to balance without aid. Gait analysis was also performed, in which patients were asked to walk while a machine measured their gait (the space between each foot while walking). Neural activity was measured with electroencephalography while transcranial magnetic stimulation was applied simultaneously (EEG-TMS). This technique was used to measure neural activity changes in motor regions of the brain following activation of the motor cortex using a different TMS paradigm than the one used for treatment.
The authors found that after three weeks of the last treatment with either sham or cerebellar TBS, there was an average increase in the Berg Balance Scale score in those treated with TBS compared to controls. They also showed a reduction in gait width; a wide gait is often associated with the body’s attempt to compensate for problems with balance. This finding was supported by correlational analysis which found that a reduction is step width was associated with an improvement in Berg Balance Scale score. Interestingly, three weeks after treatment there was also an increase in neural activity in the motor (M1) region of the brain in the hemispheres affected by the stoke, in treated patients compared to controls. This area of the cortex is associated with the movement execution. Altogether these findings suggest that there were significant balance, gait and motor cortex activity improvements following treatment with TBS. Critically, no adverse effects were observed following treatment with TBS during the clinical trial.
These findings suggest that theta-burst stimulation may be an effective way of supplementing physiotherapy in those suffering with balance and gait deficits following stroke. Theta-burst stimulation in conjunction with physiotherapy, was able to improve both balance and gait in stroke patients. Treatment with theta-burst stimulation could reduce the chance of falling and improve independence in stroke patients.
Koch et al. Effect of Cerebellar Stimulation on Gait and Balance Recovery
in Patients With Hemiparetic Stroke. JAMA Neurology (2018).Access the original scientific publication here