TMS for Parkinson's

TMS for Parkinson's

Published: November 10, 2022

With millions of people worldwide living with Parkinson's disease, non-invasive treatment with little to no side effects could be of great help. You may be wondering what TMS is, and just how it can affect the incurable disease.

Parkinson's disease TMS could help alleviate a variety of symptoms.

What Is Transcranial Magnetic Stimulation?

Transcranial Magnetic Stimulation (TMS) is a treatment tool that uses non-invasive brain stimulation. It uses electromagnetic induction to stimulate underactive neurons or brain cells, which greatly improves neurological symptoms in mental health disorders.

By reactivating dormant brain areas and targeting mood centers, transcranial magnetic stimulation is most commonly used for the treatment of major depression. It is especially effective for those who have treatment-resistant depression, meaning patients who do not respond to conventional treatment methods such as anti-depressant medications.

However, it can also be used to treat other mood disorders, and recent studies have shown its efficiency in treating Parkinson's disease.

There are various types of transcranial magnetic stimulation, each using different parameters for treating different cases.

Repetitive Transcranial Magnetic Stimulation (rTMS)

Repetitive TMS, known as rTMS treatment,uses a neural modulation technique to treat various psychiatric disorders. It refers to the application of repeated magnetic pulses delivered to the scalp. A time-varying current is passed through an insulated coil, which is placed parallel to the scalp surface. This generates a magnetic field that induces a small current within the underlying cerebral cortex.

Repetitive transcranial magnetic stimulation may be done with a coil that is shaped in the form of an 8, targeting stimulation with a specific functional or spatial resolution. It could also be done with a coil that is shaped like a circle, inducing a nonfocal band of stimulation in the brain.

By producing changes in the excitability of cortical circuits in the brain that continue after the stimulation has taken place, repetitive transcranial magnetic stimulation opens the possibility of directly intervening with the cortical plasticity mechanisms of the human cortex. Repetitive transcranial magnetic stimulation also serves as a tool for investigation. As the effects of rTMS are not limited to the area it stimulated, but instead also give rise to functional changes in cortical areas that are interconnected, it can help investigate plasticity within a functional network.

Deep Transcranial Magnetic Stimulation

Deep transcranial magnetic stimulation stimulates cells in broader and deeper areas of the brain. It stimulates deeper cortical regions and extensive neuronal pathways directly. The direct stimulation reaches specific brain regions without a significant increase in the strength of the magnetic field and therefore does not come with any extra adverse effects.

While traditional TMS reaches a depth of 0.7 cm, deep TMS manages to reach 3.2 cm. It does so by the use of a coil that is shaped in the form of an H, which is held inside a padded helmet.

By working with a bigger range in pulse, it targets both the right and left dorsolateral prefrontal cortex, overcoming a narrower range of conventional TMS.

The improper function of neurons and nerve cells in the limbic system strongly correlates to symptoms of depression. By reaching the limbic systemtreatments like deep TMS, which promote healthy neuron function, can therefore serve to alleviate depression symptoms.

Deep TMS has undergone more than sixty double-blind clinical trials and is an FDA-approved treatment for Major Depression and treatment-resistant depression.

A Look at Parkinson's Disease

A Look at Parkinson's Disease

Parkinson's disease was first described as 'shaking palsy' by Dr. James Parkinson in 1817. Today, the American Parkinson Disease Association estimates that 1 million Americans live with Parkinson's disease, while around 10 million people are affected globally.

The chronic and progressive disease with a neurodegenerative nature involves motor and non-motor functions. The degenerative disorder of the nervous system progresses slowly, and the disease duration is usually around ten years, although it could vary from person to person.

What Causes Parkinson's Disease?

Structures deep within the brain that control our automatic elements of movement, those without conscious control, are called the basal ganglia. This part of the brain is at the top of the spinal cord, and functions by turning thoughts into movement. Basal ganglia neurons usually release dopamine, the neurotransmitter that is crucial for control and planning, and that transmits signals to the area of the brain related to movement and coordination.

In Parkinson's disease patients,the death of a very specific group of cells found in an area that is part of the basal ganglia, called the substantia nigra, causes abnormal functioning of the basal ganglia. It is believed to cause a depletion of the neurotransmitter dopamine.

The exact causes of the disease are unclear, but a number of factors have been proposed to be relevant. Poisoning with metals such as manganese has been implicated in Parkinson's disease, while the impairment of a liver's ability to detoxify and exposure to sulfur-containing compounds has also placed people at risk for harm from neurotoxins. Prolonged exposure to neurotoxins could in that case manifest as a clinical disease. Other risk factors that have been proposed include genetic factors, age, and family history of the disease.

Symptoms of Parkinson's Disease

Signs and symptoms develop slowly in Parkinson's disease. As the abnormal function of the basal ganglia affects automatic aspects of movement, Parkinson's disease patients suffer from motor symptoms. These functions may affect only one side of the body initially but can become bilateral as the disease progresses.

Despite being defined as a movement disorder, Parkinson's disease also involves a range of behavioral and neuropsychiatric symptoms that can greatly impact a person's quality of life. These non-motor symptoms play an equally important part in the disease.

In PD patients, the expression of motor and non-motor symptoms varies greatly from individual to individual.

Motor Functions

Motor function refers to activity that occurs as a result of stimulating motor neurons. This includes glandular activity, voluntary and involuntary muscle contractions, as well as reflexes. Our motor neurons allow us to talk, eat, swallow, breathe and move, and without these, we may have difficulty in many basic life functions.

The compromise of dopamine release and dopamine receptors in Parkinson's disease patients causes the cardinal motor symptoms of poverty of movement, involuntary movements, slowness of movement, and rigidity. Parkinson's disease can also cause impaired grip force or handwriting, and speech deficits.

A general summary of motor symptoms includes:

  • Postural instability (inability to balance)
  • Slowness in movement (bradykinesia)
  • Involuntary resting tremors (rhythmic shaking)
  • Impaired grip force and impaired handwriting
  • Stiffness of the arms and legs
  • Decreased facial expressions
  • Loss of voluntary muscle movement(akinesia)
  • Gait disturbances, meaning a deviation from normal walking
  • Muscle cramps and dystonia
  • Falls
  • Speech deficits

Non-motor Functions

Non-motor functions are those that do not affect movement but instead include other issues such as tiredness, physical pain, mental health, and memory problems.

In the early stages of Parkinson's disease, non-motor symptoms contribute more to the reduction of health-related quality of life than motor symptoms.

The broad spectrum of non-motor symptoms in Parkinson's involves apathy, depression, cognitive dysfunction, and complex behavioral disorders. Among individuals with young onset Parkinson's, there can be subtle changes in their personality. While some non-motor signs may occur in later stages of the disease, such as the development of dementia, many precede the first appearance of motor signs, such as sensory impairment (usually hyposmia), depression, fatigue, and sleep behavior disorder.

The series of non-motor symptoms in Parkinson's disease patients usually include:

  • Depression and anxiety
  • Cognitive impairment, including memory loss
  • Cardiovascular problems
  • Hallucinations and delusions
  • Rapid Eye movement and Sleep disorder
  • Urinary issues
  • Gastrointestinal symptoms
  • Low blood pressure when standing after sitting or lying down (postural hypotension)
  • Decreased sense of smell, or a decreased ability to detect odors through your nose

How Is Parkinson's Disease Usually Treated?

How Is Parkinson's Disease Usually Treated?

In order to assess executive functions, memory, attention and concentration, calculation and orientation, language, and visuoconstructional skills, a screening instrument is used. The Montreal Cognitive Assessment (MoCA) is usually involved in clinical practice, screening for cognitive impairment.

Medicines Used in Parkinson's Disease

As dopamine production is inhibited by Parkinson's disease, dopaminergic medications are often prescribed to help PD patients produce more dopamine. The most common drug used in the management of Parkinson's disease is Levodopa, belonging to a class of medicines known as central nervous system agents.

It works by undergoing a conversion into dopamine in the brain. But the long-term use of Levodopa causes PD patients to change from no moving muscle ability to a hyperkinetic state. This is called Levodopa-Induced Dyskinesia (LID).

The drug side effect manifests as clinical features, which include involuntary, unpredictable, and irregular muscle movements, abnormal postures, and slow, repetitive movements, with limited therapeutic solutions. The medication-induced involuntary movements developed in many PD patients limit the ability of medications to remain effective. There is also the 'on-off' symptom or wearing-off (WO) phenomenon, which is a frequent complicationinvolving the reoccurrence of motor and non-motor symptoms during levodopa-free intervals.

There are some modifications to dopaminergic therapy that help in the management of LID; doctors may prescribe other medicines such as monoamine oxidase inhibitors, or dopamine agonists. Amantadine, currently regarded as the most effective medicine in treating LID, stimulates the release of dopamine from neurons. However, it can cause confusion, hallucinations, and a worsening of dyskinesia when discontinued.

Drugs such as Bromocriptine replaces dopamine. It releases a substance that mimics dopamine activity, while other drugs, such as Azilect and Selegiline, can slow down the progression of the disease, especially if taken during the early stages.

While dopamine replacement medications are an effective way of current medical management of motor symptoms in Parkinson's disease, there are dopamine-resistant symptoms too. Cognitive defects, freezing of gait, depression, dementia, and hallucinations are increasingly recognized as contributing to morbidity in PD.

Using medication for treating Parkinson's comes with the great challenge of finding the right balance. PD patients who do not take enough medicine may have difficulty moving, while an overdose can lead to unwanted movements. The fact that the body reacts to the drugs variably makes determining the dosage very difficult.

Unfortunately, as the disease progresses, drugs also become less effective, and long-term treatment with dopaminergic medications could result in problematic fluctuations of motor function. With the progression of Parkinson's disease, deep brain stimulation becomes the second line of treatment.

Deep Brain Stimulation (DBS)

Another option when it comes to treating Parkinson's is surgery. The most common procedure involves implanting a deep brain stimulator. This device uses electrical pulses to stimulate a deep area of the brain related to movement, called the subthalamic nucleus.

Although it does not cure the disease, it does improve motor symptoms. Some of these, for example, gait deficits, and impaired speech and handwriting, respond similarly to dopaminergic medication and deep brain stimulation since they have similar clinical profiles and neural substrates. It can also treat medication-induced motor fluctuations in some cases.

But DBS comes with some risks. It can negatively impact cognition or memory, and there is increasing recognition of the mood side effects caused by it. It also comes with the additional risks of invasive surgery and may not be suitable for all PD patients. Unfortunately, DBS is not effective in treating non-motor features either.

Electroconvulsive Therapy

Those who do not have optimal responses to medicines or experience side effects of Levodopa-induced dyskinesia may experience efficacy in electroconvulsive therapy. In select patients, it can be an effective option for acute treatment and maintenance treatment of Parkinson’s disease.

Studies point out that ECT has beneficial effects on both the core motor symptoms of PD, as well as the commonly occurring psychiatric co-morbidities. ECT has significantly improved motor-related symptoms in patients with PD, as well as depression and psychosis; and ECT significantly relieves the wearing-off phenomenon.

Perhaps due to the inability to predict how long the beneficial effects of ECT therapy will last, it has not gained acceptance as a clinical treatment option, despite its beneficial effects. ECT also requires general anesthesia and often necessitates a hospital stay, while patients may feel confused for several hours after the treatment. Feeling ill or nauseous, and experiencing headaches, jaw, and muscle aches also come with ECT. Electric shocks place quite a bit of stress on the cardiovascular system, which may cause changes in blood pressure. This means that people with any type of diagnosed heart disease may not consider it the best treatment.

ECT can also cause short-term memory loss, whereby a person could forget events that occurred for months leading to the treatment.

Can TMS Help with Parkinson's Disease?

Can TMS Help with Parkinson's Disease?

As a safe, noninvasive therapy, TMS delivers magnetic pulses through a device placed over the head. Without the delivery of electric shock or invasive surgery, TMS can take place within half an hour sessions over several weeks. Magnetic pulses reach and stimulate parts of the brain that have become inactive due to Parkinson's. It activates synapses and cells that enable one cell to 'tell' another cell what to do.

The changes in cortical excitability caused by TMS can persist beyond the treatment session itself and have thereby helped in the study of movement disorders, and neurological and mood disorders.

TMS is involved in multiple mechanisms that contribute to its clinical effects in movement disorders, including the normalization of cortical excitability, the induction of dopamine release, and a rebalancing of distributed neural activity. TMS can also help to unveil subtle modifications in the pathophysiology of the M1 receptor - which plays a vital role in learning and memory processes- making it more helpful than clinical observation alone in detecting a neurodegenerative disorder, even in early phases.

Treatment parameters include stimulation parameters - meaning stimulation frequency, stimulation intensity- and the number of treatment sessions. It also varies according to the diagnosis of the patient.

TMS can be applied at high and low frequencies, each with different effects. Generally, low frequency is associated with inhibiting neuronal activity, whereas high frequency is related to facilitation. In addition, different frequencies of stimulation may contribute to distinct effects on cortical metabolism and cerebral blood flow.

As discussed before, Parkinson's disease (PD) has both motor and nonmotor features. While motor symptoms can sometimes respond to therapies like deep brain stimulation, non-motor symptoms usually don't respond to it. That is why rTMS is ideal to treat Parkinson's disease, as it has shown significant differences in both motor outcomes, as well as in non-motor outcomes.

TMS Addressing Motor Functions

Both high and low-frequency repetitive transcranial magnetic stimulation (rTMS), effectively reduces motor-related symptoms in Parkinson’s disease patients, but the effects of high-frequency rTMS last longer than low-frequency rTMS, a clinical trial shows. A further systematic review of controlled clinical trialshas shown the benefit of high-frequency rTMS on motor signs in PD.

rTMS has been beneficial in treating freezing of gait, which is a brief, episodic absence of forward progression of the feet despite having the intention to walk, and one of the most debilitating symptoms in patients with Parkinson's disease. rTMS can improve cognitive dysfunction and freezing of gait scores in the short- and long-term.

Addressing Dyskinesia

TMS is widely studied as the most non-invasive technology for treating levodopa-induced dyskinesia.

TMS's success in treating levodopa-induced dyskinesia in Parkinson's disease is related to changes in neurotransmitters, neuroplasticity, brain connectivity, and neuro restoration. Blood flow modulation could also play a crucial role.

The prefrontal cortex is considered a target for modulating dyskinesia in PD patients by using repetitive transcranial magnetic stimulation. Studies have shown that high-frequency rTMS of the dorsolateral prefrontal cortex can lead to dopamine release. The management of LID is improved by modifying dopamine stimulation, and in the case of TMS, it is done without any of the drug side effects.

TMS and Sleep

TMS can also help non-motor symptoms, such as sleep disorders in Parkinson's disease.

PD patients may sleep shorter durations, sleep more fragmented, have lower sleep efficiency, and have longer awakenings at night than those without PD. Studies show that rTMS over the parietal cortex has been shown to improve sleep fragmentation and efficiency and reduce the average duration of nocturnal awakenings. It also did so without affecting motor or mood symptoms.

Another sleep disorder common in Parkinson's disease is excessive daytime sleepiness (EDS), which can seriously affect a person's quality of life. Low-frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) could improve symptoms of EDS.

TMS and Dopamine

As discussed before, Parkinson's disease inhibits the production of dopamine - a chemical involved in the regulation of movement attention, learning, and reward - leading to a series of negative consequences.

Studies have shown that high-frequency rTMS of the human motor cortex can lead todopamine release, bringing a range of benefits to those struggling with Parkinson's.

TMS and Exercise

There is great importance in exercise for improving the health and well-being of individuals with PD.

Longevity in Parkinson's disease is related to an increase in physical activity, and cardiovascular fitness has been related to better motor and cognitive scores in those who have PD. Bodies of evidence suggest that vigorous exercise should be accorded a central place in the treatment of PD, as beyond its benefits on physical health, exercise also gives patients a more active role in the management of their Parkinson's disease.

Studies have shown that exercise can improve gait speed, fitness, and muscle strength for patients with Parkinson's disease. In a randomized, single-blinded clinical trial of 3 different types of exercise (high-intensity treadmill, low-intensity treadmill, or stretching and resistance training) among PD patients, the primary outcome measures of gait speed in all training types increased the distance they could walk in six minutes. Both treadmill groups demonstrated improvement in the secondary outcome measures of cardiovascular fitness.

TMS studies have shown findings that repetitive transcranial magnetic stimulation in combination with treadmill training enhances the effect of improvement in walking performance in those with Parkinson's disease, as well as modulation of motor inhibition.

How TMS Targets the Human Brain

How TMS Targets the Human Brain

In contrast to deep brain stimulation which stimulates small subcortical regions of the brain - where multiple loops converge - repetitive transcranial magnetic stimulation can be applied over specifically selected cortical regions. Thereby it can modulate particular networks that are linked with a given set of symptoms. This avoids the risk of unintended effects across multiple domains that DBS carries.

The Prefrontal Cortex

A key cortical target for a circuit in the brain involved with attention, mood regulation, and working memory, lies in the dorsolateral prefrontal cortex (DLPFC). A TMS session involves a patient sitting comfortably while a magnetic coil stimulates the dorsolateral prefrontal cortex of the brain. This creates a chain reaction, helping to 'wake up' underactive parts of the brain, and helping to regrow neuronal connections.

High-frequency rTMS treatment over the DLPFC has a significant effect on the executive function of PD patients.

Many PD patients suffer from comorbid depression, and usually, depression in Parkinson's disease is resistant to medication. Repetitive transcranial magnetic stimulation of the left prefrontal cortex is shown effective in treating this non-motor symptom. TMS is especially helpful, as it has a high success rate for treatment-resistant depression.

In a controlled study of depressed PD patients, a 10-day course of rTMS over the left DLPFC showed equivalent efficacy on depression rating scales as the antidepressant medication fluoxetine. But in contrast to anti-depressants, TMS does not come with side effects.

The Human Motor Cortex and Motor Function

Transcranial magnetic stimulation can activate circuits of the human motor cortex non-invasively. Because neural circuits in the cerebral cortex are not static, repetitive transcranial magnetic stimulation produces changes that outlast the stimulation in a session.

In the cerebral cortex, cortical excitability can be modulated and this can be beneficial in treating different elements of Parkinson's disease; high frequencies can alter neuronal activity and increase the excitability of the cerebral cortex, while low-frequency stimulation can reduce excitability and inhibit neuronal activity.

Studies show that high-frequency rTMS decreased bradykinesia and rigidity in the upper limb opposing stimulation, while low frequencies reduced upper limb rigidity bilaterally and also improved walking. Additionally, high frequencies increased cortical excitability and low frequencies showed intracortical inhibition.

TMS has also provided new pathophysiological insights, pointing out the primary motor cortex's central role in the movement disorder commonly occurring in Parkinson's. When repetitive transcranial magnetic stimulation over the primary motor cortex is continued in repeated sessions, it has shown significant improvement in the motor performance of Parkinson's disease patients.

One study examined high-frequency rTMS applied to the primary motor cortex frequently, tracking changes in functional MRI activity. This demonstrated that reductions in bradykinesia occurred after twelve weeks of rTMS treatment. As the amount of improvement was linked to increased activity in the caudate nucleus of the basal ganglia, it showed that prolonged TMS stimulation could induce plastic changes to subcortical structures of the brain.

The Supplementary Motor Area

The supplementary motor area seems to play an important role in the preparation and execution of learned motor sequences, as well as in linking cognition to action. Neuroimaging has demonstrated that patients with dyskinetic Parkinson's disease have an overactivation of the supplementary motor area.

One study has provided Class I evidence that supplementary motor area stimulation with repetitive TMS is effective in treating motor symptoms in Parkinson's disease. Another proved how low-frequency rTMS over the supplementary motor area was able to reduce drug-induced dyskinesia in Parkinson's.

High frequency over the SMA has also been proved to improve the brain connectivity pattern specifically associated with freezing of gait. It was also associated with the pattern of Parkinson's disease overall. Results from these studies indicate that the normalization of abnormal brain connectivity patterns by rTMS can alleviate the freezing of gait.

TMS on Brain-Derived Neurotrophic Factor

Studies at the Institute for Parkinson's and Movement Disorders analyzed the signal between Brain-Derived Neurotrophic Factor (BDNF), a vital molecule involved in changes that are related to learning and memory, and TrkB, a receptor that regulates the growth and survival of cells. They noticed that signals were lower in those with Parkinson's than in healthy controls.

Various forms of TMS therapy stimulates BDNF release in neurons. The forms include prolonged depolarization, high-frequency stimulation (HFS), or theta-burst stimulation (TBS). Regular TMS treatment increases the activity of Brain-Derived Neurotrophic Factor. It also increases the signaling of the receptor TrkB. This combination helps the neuroplasticity of the brain and can potentially slow down the progression of Parkinson's disease. 

The novel finding that multiple rTMS treatments elevate the BDNF levels in the plasma of both rats and humans and that it improves signaling between BDNF and TrKB supports the application of rTMS in the treatment of depression and anxiety. The study also showed that the effects of rTMS extend beyond the nervous system, and could increase signal interaction in the lymphocytes.

Other Benefits of TMS for Parkinson's

While the effect of transcranial magnetic stimulation on various brain regions comes with many advantages, there are some other basic pros to the treatment.

Eliminated Side Effects

Transcranial magnetic stimulation avoids any side effects of systemic medications as it does not involve the use of drugs or sedatives.

Some estimates say that almost half of Parkinson's disease patients suffer from comorbid depression or depressive symptoms. Repetitive transcranial magnetic stimulation (rTMS) has the same antidepressant efficiency as some antidepressant medications while having the additional advantage of earlier cognitive improvement and some motor improvement.

TMS is an excellent alternative to antidepressant medications as it avoids weight gain, fatigue, insomnia, sexual dysfunction, and many more systemic side effects associated with these medicines. Transcranial magnetic stimulation comes with mild discomfort as its most common side effect. These discomforts are reported as a tapping sensation in the scalp, tingling of facial muscles, mild headaches, or redness at the site of stimulation, that pass as the treatment progresses.

TMS does not come with the negative cognitive effects commonly associated with deep brain stimulation either, nor with those of electroconvulsive therapy. TMS does not affect memory and has few reported adverse events.

An Outpatient Procedure

Transcranial magnetic stimulation can change the activity of nerve cells in the brain without requiring anesthesia or hospitalization. Compared to electroconvulsive therapy - which requires the aforementioned - TMS does not require any sedation and is done on an outpatient basis.

Non-invasive and Safe

TMS is an effective brain stimulation treatment but without a surgical procedure. Because repetitive transcranial magnetic stimulation is applied non-invasively, the technique avoids any complications that could occur with surgery.

Transcranial magnetic stimulation has not been related to any cognitive decline or brain damage. No negative long-term effects, including memory loss or decreased concentration, have been found in clinical studies or systematic reviews and evaluations. This makes TMS different from other brain stimulation therapies - like electroconvulsive therapy - that are related to memory loss.

The magnetic fields used in TMS are also very safe. It is similar to the magnetic fields used in MRI scans, but a complete TMS therapy uses only a small fraction of the magnetism used in one MRI scan.

What Would TMS Therapy Be Like?

Undergoing TMS therapy means attending weekly sessions that last between four to six weeks. It does not require a person to reside at a treatment center.

TMS therapy involves a treatment provider placing an electromagnetic coil on a person's scalp, near the forehead. Short pulses of the magnetic field painlessly produce an electric current in the brain that stimulates underactive neurons.

Steps of the TMS Procedure

TMS treatment follows simple steps and allows someone to resume normal activity after treatment, including driving themselves home.

Measurements are made to ensure that the TMS coil is in the right position over a person's head and the electromagnetic coil is then suspended over the scalp. The motor threshold is different from person to person, so a TMS physician will measure it by releasing brief impulses and monitoring a twitching of the thumb

Once the threshold is established, magnetic stimulation begins, which may feel like a knocking sensation. Depending on the diagnosis, a person waits thirty minutes to one hour for the session to finish, and can then continue about their daily life.

Where Can I Find TMS for Parkinson's Disease?

If you or a loved one are struggling with Parkinson's disease, GIA Chicago can help. As a health clinic specializing in TMS therapy, our treatment center provides the most cutting-edge evidence-based therapy techniques. These are also custom designed to meet your specific needs.

A full psychiatric evaluation of your emotional, psychological and behavioral health and a consideration of medical, personal, and family histories help our expert psychiatrists to formulate an assessment and evaluate your needs. GIA Chicago's experts with extensive clinical experience then formulate the most effective, individualized treatment program for you.

As mental health plays a vital part in Parkinson's disease, we offer a combination of TMS therapy and talking therapies and a caring expert team who can work with you throughout your treatment journey. GIA Chicago can help you experience significant improvement, starting today.

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