What is neuromodulation and how can it be used to treat Parkinson’s disease?
Medication remains the primary method of treating Parkinson’s disease (PD). However, neuromodulation, or therapies that involve the manipulation of brain circuitry, can also be very effective in controlling PD symptoms in particular clinical situations.
Two current neuromodulatory techniques for PD are deep brain stimulation (DBS) and high intensity focused ultrasound (HIFU). DBS requires the implantation of a wire deep into the brain which stimulates the abnormal circuitry with electricity. HIFU requires the directing of focused ultrasound waves on a small area of the brain to create a lesion.
But what if manipulation of the circuitry can be done less invasively, providing the same relief without disturbing brain tissue?
Non-invasive neuromodulation options to treat Parkinson’s disease
Currently, there are several different methods of non-invasive neuromodulation being tested for Parkinson’s treatment.
In this blog, we will explore three options:
- Transcranial Magnetic Stimulation (TMS)
- Transcranial Direct Current Stimulation (tDCS)
- Low Intensity Focused Ultrasound (LIFU)
Transcranial Magnetic Stimulation (TMS): Targeting Brain Activity in Parkinson’s Disease with Magnetic Currents
TMS uses magnetic fields to stimulate nerve cells in specific regions of the brain. This is done by placing a magnetic coil against the scalp with careful precision and sending painless magnetic pulses that penetrate the skull and activate neurons within the brain.
TMS is an approved treatment for depression, obsessive-compulsive disorder, and smoking cessation, with the therapy directed to different locations of the brain for each of these disorders. It is also being studied for a myriad of other conditions, including Parkinson’s disease. The goal of TMS is to restore physiological conditions in the motor circuits of the brain that are disrupted by PD. There have been a number of research studies that have shown TMS to be a promising candidate for improving motor symptoms such as tremor and rigidity as well as non-motor symptoms like depression and fatigue. A meta-analysis (analyzing results from different studies) of randomized controlled clinical trials published in The Lancet in 2022 found that repetitive TMS at high-frequencies significantly improved motor function while inducing an anti-depressive effect as compared to the control.
Clinical trials are still trying to delineate the optimal settings and target brain areas for TMS in Parkinson’s patients. An ongoing clinical trial to keep an eye on is NCT06350617 which aims to investigate a personalized approach to repetitive TMS, while studying the safety and efficacy profile of this kind of treatment.
Keep in mind, TMS has not entered the realm of standard care for PD, but continued research and clinical trials investigating its validity will help it gain traction as an effective option for those patients seeking alternatives.
Transcranial Direct Current Stimulation (tDCS): Gentle Electrical Stimulation Under Investigation for Parkinson’s
In contrast to TMS which uses magnetic fields, tDCS uses a constant and weak electrical current to manipulate brain circuitry. This current, thought to promote neuronal activity, is delivered by two small electrodes placed on the head with constant electricity flowing between them. tDCS is not FDA-approved for any medical condition, but it is being actively researched in various clinical settings, including PD.
One major advantage of tDCS over TMS is that tDCS is a simpler and more portable technology. It is even being explored as an at-home option under clinical supervision and guidance. To date, the results have been mixed for this technology in the realm of PD. Despite this, there are several trials for both motor and non-motor symptoms that have shown positive results.
For example, a 2022 publication in Frontiers in Aging Neuroscience presented the results of a double-blinded (neither the patient nor the doctor knows which treatment is being administered) randomized controlled clinical trial. tDCS improved gait in PD patients when the applied current stimulated a particular region of the brain called the dorsal lateral prefrontal cortex as compared to controls and as compared to stimulation of other regions of the brain.
In addition, the results of a triple-blinded (neither the patient, doctor, nor the person analyzing the data knows who received what treatment) randomized controlled clinical trial published in 2024 in Clinical Neurophysiology found that tDCS treatment to the primary motor cortex of the brain significantly improved PD-related pain.
This treatment is not currently available, and more research will determine if this is a useful treatment for PD.
Low Intensity Focused Ultrasound Neuromodulation (LIFU): Sound Waves for Brain Health
High intensity focused ultrasound is an established procedure used for PD symptoms in which beams of ultrasound waves are focused on a designated target in the body, thereby concentrating enough energy to create a small lesion.
Other capabilities of ultrasound as a therapeutic agent are being explored in which lower amounts of energy are applied, and a lesion is not created. One method is called low intensity focused ultrasound (LIFU) in which ultrasound waves are used to increase brain activity in highly specific target area. A proof-of-concept study has recently been completed (NCT04593875).
Another use for LIFU within PD is being investigated as a method of disrupting the blood brain barrier for small intervals to allow medications used for treating the disease to cross into targeted regions of the brain for effective results.
In this study, for example, focused ultrasound is being used to disrupt the blood brain barrier in order for a large molecule, the enzyme glucocerebrocidase (GBA), to be able to pass into the brain. This trial is designed specifically for those who have a mutation in GBA, with the goal of introducing normal GBA back into the brain.
We will keep you updated as we learn more about the potential of these therapies.
We extend our thanks to Clark Jones, PhD, for his significant contributions to this blog.
Tips & Takeaways
- Neuromodulation therapies refer to therapies that alter brain circuitry. Deep brain stimulation and focused ultrasound are two therapies that are approved for use in PD, but are invasive, in that they disturb brain tissue as they are performed
- Non-invasive neuromodulation refers to therapies that alter brain circuitry, but do so without disturbing brain tissue
- Transcranial magnetic stimulation, transcranial direct current stimulation, and low intensity focused ultrasound are three examples of non-invasive neuromodulation techniques that are being studied as therapeutic procedures for PD