ReTune at the 16th World Congress of the INS 2024

May 29, 2024

ReTune at the 16th World Congress of the International Neuromodulation Society 2024 in Vancouver: an interview with Dr Jennifer Kim Behnke

This year’s World Congress of Neuromodulation (INS) 2024 took place in Vancouver from May 11 to 16. Members of the Transregional Collaborative Research Centre (TRR 295) ReTune were actively involved in this event. In our interview, Dr Jennifer Kim Behnke, a resident at the Department of Neurology with Experimental Neurology, Charité – Universitätsmedizin Berlin, provides insights into her work and reports on the latest study results from Vancouver.

Dr Behnke, you work in the Movement Disorders Section at the Charité. What are the main research areas in your field and how is this project connected to ReTune?

Thank you very much for this interview and your interest in our research. The overarching goal of ReTune is to better understand symptom-specific neuronal networks, to optimize the treatment of neurological diseases using neuromodulation. In this context, Prof Andrea Kühn’s research group is focusing, among other things, on better understanding the neuronal brain activity of patients with Parkinson’s disease who are being treated with an invasive neuromodulation technique known as deep brain stimulation (DBS). My research focus in the Kühn group and within ReTune include the longitudinal characterization of an electrophysiological biomarker for motor symptoms of Parkinson’s disease, as well as its use to optimize the stimulation setting.

DBS is an invasive therapy used to effectively treat motor symptoms of Parkinson’s disease, such as tremor, bradykinesia and rigidity. In this procedure, a neurosurgeon implants electrodes into the brain to apply electrical current to a specific deep brain structure. The target area is the subthalamic nucleus (STN), a structure of the basal ganglia. The local brain activity can also be measured and examined as a so-called local field potential from these implanted electrodes. Local field potentials contain valuable dynamic information about the symptomatic state of the patient, from which corresponding symptom-specific biomarkers can be identified. One biomarker that has already been identified is the so-called beta activity in the frequency range 13-35 Hz, which I investigate in more detail in my project. Beta activity is already well characterized in many different patient conditions. Its strength correlates with the bradykinetic-rigid symptom load of patients and is modulated accordingly by efficient therapeutic measures. So far, only little is known about the longitudinal dynamics of this biomarker. One of my projects focuses on analyzing the longitudinal stability of this biomarker, which is of great relevance for its clinical use, for example as a feedback signal for adaptive stimulation techniques or for optimizing the stimulation setting.

Can you give us a summary of your highlights from the World Congress on Neuromodulation? Which study data was particularly relevant for you?

The breakout session ‘Neuromodulation for Movement Disorders’ was particularly relevant to our research activities in the Kühn group and ReTune . Results on two relevant electrophysiological phenomena were presented that are currently also being investigated in the Kühn group and could contribute to the future optimization of Parkinson’s disease therapy using DBS:

One of these two phenomena are oscillations in the gamma frequency range, which have been identified in connection with drug-induced hyperkinesia (dyskinesia). Gamma oscillations can occur spontaneously under dopaminergic medication and moreover DBS can entrain finely tuned gamma half of the stimulation frequency. The significance of these oscillations and their connection with dyskinetic symptoms is being intensively studied also in Prof Kühn’s research group. At the INS conference, Prof Philip Starr’s research group (UCSF, San Francisco, USA) presented the latest data from simultaneous subcortical and cortical recordings from Parkinson’s patients with chronically implanted DBS and electrocorticography electrodes. The results of the Starr group indicated that stimulation-entrained gamma oscillations were also detected at the cortical level with the application of subcortical stimulation. Furthermore, these gamma oscillations occurred independently of spontaneous gamma oscillations under dopaminergic medication and did not correlate with corresponding dyskinesia scores. The relevance of these oscillations as a new therapeutic electrophysiological biomarker will be further investigated in the future.

Another electrophysiological biomarker that has been increasingly investigated in recent years, also within ReTune, is stimulation-evoked resonant neuronal activity (ERNA). This is a high-frequency (200-500 Hz), decaying oscillatory response to DBS that has been identified in two subcortical brain structures (STN and globus pallidus internus, GPi). Previous studies in Parkinson’s patients have suggested that ERNA could be localized in the therapeutic target area and could also correlate with effective stimulation parameters. Kara Johnson, PhD, from the University of Florida presented her results on the directionality of this biomarker in both subcortical brain structures, with more distinct directionality in the STN. This directionality varied depending on the individual location of the implanted electrodes and their relation to the ERNA hotspot. Future research will generate directional ERNA heatmaps and investigate their clinical significance for the adjustment of stimulation parameters.

Which current research results in the field of neuromodulation will be of particular relevance to the public?

The increasing progress in the field of neuromodulation and the diversity of neuromodulation techniques, which offer numerous possibilities for the treatment of neurological and psychiatric diseases, are of great relevance to the public. This diversity of treatment options is clearly illustrated, for example, by the neuromodulation technique using ultrasound. Prof Andres Lozano from the University of Toronto, Canada, gave an overview of the progress and latest findings in this neuromodulation technique:

The main advantage of focused ultrasound stimulation is that it can generate a targeted, small stimulation focus without the need for invasive implantation of electrodes. Neural tissue can either be irreversibly damaged by high-intensity focused ultrasound (HIFU) stimulation or reversibly modulated (inhibition and activation) without destroying brain tissue using low-intensity focused ultrasound (LIFU). HIFU therapy leads to a focal ablation of brain tissue and thus to an irreversible lesion in the target area. This is used, for example, to create a therapeutic thalamic lesion for treating patients with essential tremor. In contrast, LIFU therapy enables reversible neuromodulation reaching both superficial and deep brain structures. These properties make LIFU therapy an attractive form of neuromodulation that is currently being tested and investigated for the treatment of various neurological and psychiatric disorders, including Parkinson’s disease, Alzheimer’s disease, depression, addiction and epilepsy.

Two promising new findings in LIFU stimulation technology were presented that could be of great benefit:

First, cortical plasticity can be induced with LIFU using a specific stimulation pattern, known as theta burst stimulation. This means that this stimulation has led to long-lasting stimulation effects at the cortical level, which could be useful in the treatment of many diseases. This goal of inducing plasticity is also currently being pursued with invasive stimulation techniques such as DBS in deeper brain structures and is also a research topic in Prof Kühn’s group and another focus of my research work.

Second, LIFU stimulation offers the unique possibility of opening the blood-brain barrier in a targeted and reversible manner at the stimulation focus. This could provide easier access to targeted brain areas via the bloodstream. The topographical specificityof this method is promising for future advances in the targeted administration of chemotherapeutic agents to the central nervous system, in the non-invasive diagnosis of brain tumours, and in the removal of pathological proteins from the central nervous system, e.g. to inhibit the progression of Alzheimer’s disease. The safety and reversibility of this method have already been described in initial studies.

This wide range of treatment options and new findings in ultrasound stimulation is just one example and reflects the growing interest and progress in the field of neuromodulation. These findings form the basis for the further development of future treatment strategies for neurological and psychiatric diseases.

Thank you very much for the interview.

The transregional collaborative research centre (TRR 295) ‘ReTune’, which is funded by the German Research Foundation (DFG) with 10 million euros, aims to better understand information processing in dynamic brain networks and to improve and expand treatment options for people with motor network disorders. We are also happy to announce that after a successful first funding period, a second funding period has been approved recently, which allows us to further pursue this goal in the upcoming years.