Effects On Tapping Performance And Spectral Power Of Tremor Movements
Tapping performance was assessed as another lateralized endpoint. A mixed model analysis was used to identify tapping parameters that optimally predicted the MDS-UPDRS-III akinesia score of the corresponding arm.
The MDS-UPDRS-III hand akinesia scores were well-predicted by the model . Out of 8 parameters we determined mean tapping force , mean interval between taps , standardized tapping force , and standardized tapping interval as significant for MDS-UPDRS-III prediction. The effect of ADS-rTMS intervention on this set of informative parameters was then evaluated, for the treated hand only, using repeated measures ANOVA. For the mean tapping force, there was a trend for CONDITION , but no interaction CONDITION * TIME . The effect of CONDITION was driven by a slightly higher tapping force throughout the day of the VERUM intervention. For the remaining parameters, we found neither a significant main effect of CONDITION nor an interaction CONDITION * TIME .
In summary, there were neither meaningful beneficial nor detrimental effects of the intervention on either tapping performance or tremor.
We conducted additional experiments involving stimulation of M1 and either SMA or M1+50 as a premotor site as detailed in the Supplementary Material. These interventions did not yield any beneficial effect either .
What Is Tms Therapy
Transcranial magnetic stimulation is a type of brain stimulation therapy.
Its a noninvasive treatment that uses electromagnetic pulses to stimulate nerve cells, which may improve symptoms of neurological or mental health disorders.
TMS is mainly used to treat depression. Its had success helping people who dont respond to antidepressant medication and psychotherapy. In fact, in 2008 the Food and Drug Administration approved TMS for this purpose.
Theres also some evidence that TMS may help other disorders, like anxiety and Parkinsons disease.
Since TMS uses repetitive electrical impulses, its sometimes called repetitive transcranial magnetic stimulation . The terms are often used interchangeably.If youre curious about the benefits and side effects of TMS, read on.
The therapy is done by a TMS technician or TMS physician. Its an outpatient procedure, so it may be done in a medical clinic. If its done in a hospital, you wont need to stay overnight.
Before the procedure, youll need to remove items that are sensitive to magnets, like jewelry.
Heres what you can expect during TMS:
What Can It Treat
Currently, TMS is only FDA-approved to treat Major Depression Disorder. However, other disorders are suspected to be respondent to TMS as well. These include bipolar disorder, attention-deficit/hyperactivity disorder, panic disorder, obsessive compulsive disorder, schizophrenia, ALS, and Parkinsonâs.
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Approaches: Rtms As A Therapy
The effects of rTMS usually last about 30-60 minutes in humans, depending on protocols and usage patterns, such as pulse number, rate and intensity12. Of course, if this were the only effect, rTMS would not make real sense. Permanent changes are crucial for using it as a therapy.
Repeated induction of plasticity seems to fill that gap by creating temporary changes for a long time . This seems to depend on the number of sessions, so protocols of 10 or more days of use are often applied. So far, depression may warrant therapies of up to six weeks, at least 20-30 sessions for best effects13. The idea is to create structural and functional changes gradually, to âregularizeâ the neuronal interconnections.
In order to apply rTMS, the patient must be seated or in a ârelaxedâ position, in a comfortable environment. Some even consider using rTMS prior to physical or psychological therapy, which seems to cause dramatic changes and increases its effectiveness dramatically14. We will discuss the pathologies where rTMS has proven to be effective, going deeper into their theoretical bases and the various studies that corroborate these data.
Quality Assessment Of The Studies
Table shows the quality assessments of the included studies. Randomized allocation of the patients was applied in most studies. Most of these studies were doubleblind or singleblind. There was insufficient information to categorize the blind procedure in two studies . Nine studies described the dropout number.
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Neuroplastic Effects Of Tms
The neural effects of TMS depend on the frequency of stimulation. When the frequency of TMS stimulation is 1 Hz or greater, the stimulation is called repetitive TMS . If rTMS is pulsed at a low frequency , cortical excitability generally decreases, while higher-frequency rTMS can increase cortical excitability, though there are exceptions to this general rule. The modulation of cortical excitability with rTMS lasts beyond the stimulating train typically, the effects of a series of rTMS trains applied over a 10- to 30-minute period lasts between approximately 10 and 60 minutes., This up- or downregulation of cortical excitability extended beyond the period of stimulation demonstrates the ability of TMS to affect cortical plasticity. The ratedependent nature of this modulation is reminiscent of long-term potentiation and long-term depression , which represent the leading models for the physiological basis of plasticity and memory, developed by studying the effects of electrical stimulation of hippocampal slices of animals. High-frequency stimulation trains that increased the excitability of granule cells from the dentate gyrus for periods from 30 minutes to 10 hours provided the first evidence of LTP. LTP- and LTD-like plasticity effects have been found noninvasively in humans with TMS through examination of motor evoked potentials generated from stimulation of the primary motor neurons.,,
Negative And Positive Effect In Rtms Trials
Although this meta-analysis shows a favourable effect of TMS on motor function in PD, a positive effect was not observed in every trial. One of the reasons may be the small sample size of these negative studies. In this scenario, the meta-analysis technique is a valuable method to combine the data from small studies in order to provide a conclusion based on an analysis with better power. However, two studies with relatively large sample sizes showed negative results. One explanation for this contradiction might be the interaction of antiparkinson drugs with TMS, as these studies assessed the motor UPDRS after the use of levodopa . This medication might mask the effects of TMS due to a ceiling effect. Therefore, assessment of patients in the off state may provide a more sensitive measure of the benefit of TMS. An alternative explanation is that the variability of the results stems from the wide range of TMS parameters and patient selection criteria used in these studies, that is, the optimal TMS parameters might vary depending on disease duration and severity. Although the meta-regression results failed to show that TMS parameters could significantly account for the variability across studies in motor improvement, the interaction term was not analysed because of lack of power for this type of test.
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Tms For Parkinsons Disease
DBS can be a life-changing procedure for many, but its invasive. Patients have electrodes implanted in their brains and a battery like a pacemaker installed in the abdomen.
Is there a non-surgical treatment for PD? The answer is yes.
Repetitive TMS is non-invasive. And its FDA-approved to treat mental health disorders like depression and OCD. It is nothing like electroconvulsive therapy.
When you come in for a TMS session, youll sit comfortably as a magnetic coil placed gently on your head stimulates the dorsolateral prefrontal cortex of your brain.
This creates a chain reaction that helps regrow neuronal connections and wake up parts of the brain that have become underactive.
Clinical studies are happening to see if TMS can become an effective brain stimulation treatment for Parkinsons along the lines of DBS but without a surgical procedure.
One such study was conducted by Dr. Biagioni at the Marlene and Paolo Fresco Institute for Parkinsons and Movement Disorders at NYU Langone Health. In this controlled study, a group of Parkinsons disease patients completed an aerobic exercise, and some in that group were given TMS.
Aerobic exercise and TMS both produce brain-derived neurotrophic factor signaling in the brain. Researchers wanted to see what would happen if both treatments were used together. BDNF is a protein in the brain that promotes neuron growth and prevents neurons from dying. Exercise and antidepressants work in part by increasing BDNF.
Repetitive Transcranial Magnetic Stimulation For Treatment Of Parkinsons Disease
By Douglas Labar, MD, PhD
Professor of Neurology, Weill Cornell Medical College
Dr. Labar reports no financial relationships relevant to this field of study.
Synopsis: In several randomized, sham-controlled trials, repetitive transcranial magnetic stimulation was shown to be effective in reducing the motor manifestations of Parkinsons disease, with minimal side effects.
Chou Y, et al. Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinsons disease. A systematic review and meta-analysis. JAMA Neurol 2015 72:432-440.
Parkinsons disease prevalence is increasing with our aging population. Medical therapy typically is beneficial, but side effects, such as dyskinesias, may develop, and medication efficacy may be lost. Deep brain stimulation may help, but there are associated brain surgery risks. Increasingly, recent attention has been directed toward non-invasive brain stimulation as an alternative treatment. This includes repetitive transcranial magnetic stimulation .
The mean improvement on the UPDRS-III was -6.42 there was a medium effect size favoring active over sham treatments. Motor outcomes from high-frequency stimulation applied over primary motor cortex , and low-frequency stimulation applied over other frontal areas, were superior to sham. In contrast, low-frequency stimulation applied over M1, and high-frequency stimulation applied over other frontal areas, did not change motor function significantly.
References
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Treatments For The General Public
Neurosurgery planning
Nexstim obtained United States Federal Food, Drug, and Cosmetic Act§Section 510 clearance for the assessment of the primary motor cortex for pre-procedural planning in December 2009 and for neurosurgical planning in June 2011.
Depression
In 2008, the US Food and Drug Administration authorized the use of rTMS as a treatment for depression that has not improved with other measures. A number of deep TMS have received FDA 510k clearance to market for use in adults with treatment resistant major depressive disorders. The Royal Australian and New Zealand College of Psychiatrists has endorsed rTMS for treatment resistant major depressive disorder .
Migraine
The use of single-pulse TMS was approved by the FDA for treatment of migraines in December 2013. It is approved as a Class II medical device under the “de novo pathway”.
Other neurological areas
In the European Economic Area, various versions of Deep TMS H-coils have CE marking for Alzheimer’s disease,autism,bipolar disorder,epilepsy, chronic pain,major depressive disorder,Parkinson’s disease,posttraumatic stress disorder ,schizophrenia and to aid smoking cessation. One review found tentative benefit for cognitive enhancement in healthy people.
In August 2018, the US Food and Drug Administration authorized the use of TMS in the treatment of obsessive-compulsive disorder .
What Is Transcranial Magnetic Stimulation
In short, it is a non-invasive neurophysiological technique that can stimulate the human brain through the intact skull, without producing significant discomfort. In another era, we would call it a miracle. However, the lack of knowledge about its exact mechanisms takes us a bit further away from this eponymous.
It was discovered and developed by Barker and colleagues in 19853 and has been used in healthy and psychiatrically disturbed patients to explore their cortical functions. Some studies have tried to demonstrate an early therapeutic effect. Most of these studies focused on the primary motor cortex, although much attention was also diverted to depression, where it appears to be quite effective.4
Simply put, TMS uses magnetic stimulators that consist of small capacitors that discharge currents of extremely short duration through an induction coil placed on the scalp5. The idea is to create a magnetic field from the current that passes through the brain perpendicularly and reaches values up to 3 Tesla. In this process, part of the current is displaced and creates a second side in the brain, which also has some effect.
Due to the short duration of the original current, the intensity of the magnetic field decreases rapidly and does not allow it to reach long distances. Therefore, the effect is thought to be limited to the cortex and part of the subcortical white matter.6
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Tms In Geriatric Disorders
While the mechanisms of longer-lasting effects of TMS are still under investigation, there is a large body of evidence in the neuropsychiatric arena that TMS does indeed result in neuroplastic changes that can improve therapeutic outcomes . Much of the clinical research with TMS has been conducted in adult cohorts, but it has also been extended to elderly adults. For instance, investigations have examined the effects of TMS in geriatric patients with stroke, Alzheimer’s disease, and MDD.
Neuronal Plasticity The Secret Of Long
Research that has demonstrated the effects of rTMS on synaptic plasticity has focused on the primary motor cortex, although there are many studies related to depression and other psychiatric disorders such as anxiety and OCD.
According to these studies, depending on the intensity and direction of the current, it is possible to activate an entire pathway of neurons directly or trans-synaptically. We know from previous studies, especially animal-based studies, that repeated impulses through neurons can increase or decrease synaptic conduction in the long term, which is known as long-term âdepressionâ or âpotentiationâ .9
This is the basis for the short-term effect of rTMS. By increasing the intensity of rTMS, we can generate changes in neurons, creating new synaptic interconnections that stimulate various receptors. The more intense and repeated the impulses, the longer the changes will last. However, in order to obtain definitive results, changes at the protein level are necessary.
This conclusion was supported by studies on rodent brains where it was revealed that there are changes at the molecular level which may be the basis of synaptic plasticity and the crucial effect of rTMS in humans9. According to the available data, there are not only changes in synaptic structure , but also dynamic changes in calcium receptors, which modulate the expression of glutamate receptors10. Some data even show early gene changes that regulate the expression of previous genes.
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Sample Size Estimation And Interim Analyses
Initial study design called for enrollment of 160 participants on the basis of predicted motor effects of 0.9 in the M1 + DLPFC group and 0.6 in the other 2 rTMS groups compared to double sham . Effect sizes for mood were predicted to be larger., Controlling for 2 primary outcome measures across 3 rTMS groups , this sample size provided 81.7% power to claim that at least one of the active groups was significantly different from the double sham in the mean change of UPDRS-III.
An interim analysis was planned a priori at the study midpoint to potentially eliminate 1 of the 4 subgroups, thus increasing power in the remaining groups. This interim analysis was conducted early because of slower-than-expected recruitment.
Patients And Tms Protocol
PD patients were recruited through the outpatient clinic of the Department of Neurology, University Hospital of Leipzig. Inclusion criteria were: age of 1875 years, Hoehn and Yahr stage 13 and a baseline MDS-UPDRS-III of 8 points. Exclusion criteria were relevant cognitive impairment , manifest depression , atypical Parkinsonian disorder, other severe illness interfering with safe participation, participations in other studies at the moment of inclusion and known contraindications to TMS .
Patients received two interventionsVERUM and SHAM in a cross-over design following overnight withdrawal of their PD medication. They were randomized to receive either VERUM or SHAM as the first intervention, then they received the complementary procedure at least 1 week later . Subjects were blinded to the condition and told that one of two different interventions would be used. At the day of the intervention, subjects were assessed before , immediately after and 1 h after the intervention , comparable to a standardized Levodopa test. Administered tests are detailed below.
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How Does It Work
During a session of TMS, a coil is fitted against the patientâs head to conduct magnetic pulses emitted by a TMS machine and regulated by a trained technician. These magnetic pulses are similar to those used during MRIs.
The electromagnetic pulses administered during a TMS treatment are thought to stimulate activity in parts of the brain that are behaving abnormally or displaying signs of under-activity.
In patients with depression, TMS is used to reactivate stagnant areas of the brain by targeting mood centers in the brain.
TMS is relatively painless, although some patients might experience a slight headache or pain in the scalp following the treatment.
Inclusion Criteria And Exclusion Criteria
The studies were included if they met the following criteria: studies that evaluated the effectiveness of rTMS in adult patients with PD the design of studies was randomized controlled or crossover design studies that measured outcomes of motor dysfunction symptoms the outcomes were reported or could be calculated from the original data of the study and the studies were published in English. Studies were excluded if the outcome assessments were not or could not be expressed as a mean value ± standard deviation .
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Transcranial Direct Current Stimulation For The Treatment Of Parkinsons Disease
Objective/Rationale:Current treatments for Parkinsons disease are either associated with side effects, expensive, or their efficacy diminishes over time. Thus, the development of practical, inexpensive and effective long-term, adjunct treatments is needed in PD research. Transcranial direct current stimulation may represent one such intervention with a realistic potential to be translated into clinical practice. The goal of this project is to identify the optimal stimulation parameters for the application of tDCS to improve motor and cortical function in PD.
Project Description:The project comprises two studies designed to examine the efficacy of different tDCS protocols of improving motor function in PD. The first study will determine the optimal timing of tDCS relative to practice of a motor task to improve motor performance, whereas the second study will examine the optimal intensity of tDCS to improve motor performance. The studies will also determine if motor performance improvements attained in a task practiced in association with tDCS can be generalized to non-trained tasks such as a common clinical measure of motor function and various functional manual dexterity tests. Additionally, transcranial magnetic stimulation will be performed before and after the tDCS interventions to assess selected cortical pathways that are commonly impaired in PD and determine the extent to which tDCS impacts these pathways.