towards modulation of deep brain stimulation?

towards modulation of deep brain stimulation?
towards modulation of deep brain stimulation?

Paris, France – Used in the treatment of Parkinson’s disease, continuous deep brain stimulation is associated with long-term worsening of symptoms. Research is currently being carried out to develop so-called intelligent stimulation, which can be modulated depending in particular on the patient’s activity. This approach was the subject of a presentation during the French-language neurology days (JNLF 2024)[1].

In order to determine the right moment to stimulate the subthalamic nuclei of the brain of Parkinson’s patients, “we need to better understand and characterize the electrical signals [produits par les neurones] in conditions close to the patient’s daily life”, commented the Professor Dominique Guehl (Bordeaux University Hospital), during his presentation. “The stimulation could be interrupted or vary in intensity.”

Deep brain stimulation is indicated in patients under 70 years of age suffering from Parkinson’s disease for at least five years and presenting a response to dopaminergics which is associated with complications (variable effectiveness, abnormal movements induced by medications, etc.). . Between 15 to 20% of Parkinson’s patients are affected.

Continuous stimulation day and night

The surgical operation consists of implanting two electrodes in the subthalamic nuclei. These are connected to a battery placed under the skin at the level of the collarbones, which continuously sends electrical pulses with an intensity of 2 to 3 volts and with a frequency of 130 pulses per second. The stimulation settings are adapted to the patient.

In application of the brain stimulation mode currently used in Parkinson’s disease, once the settings have been defined, “patients are continuously stimulated with the same parameters, day and night, regardless of the dopaminergic treatment and their clinical state”, he said. clarified Professor Guehl.

By activating nerve cells in the subthalamic nuclei, stimulation corrects the effects of dopamine deficiency characteristic of Parkinson’s disease. The main motor symptoms (tremors, rigidity and slowing) are then improved and drug treatment can be reduced.

This method of continuous stimulation is, however, contested due to a potential risk of long-term complications. “The evolution of certain patients leads us to wonder if this permanent stimulation might not be the cause of dyskinesia, walking disorders and dysarthria. [incapacité à articuler correctement, ndr] observed after a few years of use,” underlined the neurologist.

The question then arose of using stimulation that could vary according to various parameters, such as the patient’s activity or the treatment administered. For this, it appeared necessary to have a better knowledge of brain activity at the level of the subthalamic nuclei to know when to administer the impulses.

Modulation according to brain waves

Analysis of data from the use of deep stimulation electrodes has shown that, in Parkinson’s patients, populations of neurons in the subthalamic nuclei synchronize their activity by essentially emitting beta-type brain waves (12 to 30 Hz ), which are linked to muscular activity.

“There is a correlation between beta oscillations and the severity of Parkinson’s disease symptoms. These oscillations are more linked to the appearance of bradykinesia [lenteur des mouvements volontaires, ndr] and muscular rigidity, as well as tremors,” explained Professor Guehl. Tremors are more often associated with slower oscillations (alpha and theta waves) [2,3].

Since stimulation has the capacity to modify brain waves, tests have recently been carried out to determine the effect of stimulation modulated and adapted according to the oscillations recorded at the level of the subthalamic nuclei. The new parameters are then defined by an algorithm placed in the stimulator.

A recent English study was able to compare continuous stimulation with adapted stimulation in around ten patients with Parkinson’s disease not treated with dopaminergics. [4]. In the adapted stimulation, the impulses were triggered depending in particular on the quantity of beta waves detected.

It will be necessary to develop electrodes and boxes capable of overcoming these artifacts in order to be able to analyze clean signals.

Gamma waves more preserved

The results showed similar effectiveness between the two techniques with an improvement in symptoms such as bradykinesia and muscle rigidity. Adapted stimulation, however, appears less effective on tremors. Positive point: it has less impact on gamma waves, “oscillations that must be preserved because they are associated with voluntary motor skills”.

Further research is still necessary to, among other things, know how to adjust the modulation according to dopaminergic treatment, which also has repercussions on brain waves. It is also necessary to be able to take into account artifacts that disrupt the recordings, linked for example to cardiac activity or the patient’s movements, said the neurologist.

“It will be necessary to develop electrodes and boxes capable of getting rid of these artifacts in order to be able to analyze clean signals. Other teams are working on separating the recording site from the stimulation site to avoid stimulation artifacts. We would also need to be able to detect and interpret several frequencies simultaneously.”

Modulation, which involves software based on artificial intelligence, “must also take into account the patient’s motor state, their activity and their treatment”. “It’s much more complex than expected,” continues Professor Guehl. “It’s not just a question of stimulating or not from a certain oscillation threshold.”

Further data is needed to refine the device. Researchers are counting in particular on the PREDI-STIM study currently being conducted in France to evaluate the predictive factors of the response to subthalamic stimulation. If adaptive stimulation seems on track to be offered to patients, “there is still much to do,” concluded the neurologist.

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