TUS to disrupt pathological oscillations
Research type
Research Study
Full title
Transcranial ultrasound to disrupt pathological oscillations in the brain of people with Parkinson’s Disease and other neurological disorders
IRAS ID
322261
Contact name
Alex Green
Contact email
Sponsor organisation
University of Oxford
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
Scientists and clinicians are interested in measuring and perturbing the signals in the brain – both to better understand normal operation and explore new therapy options for disease. One example of a signal is a “brainwave,” also called a neural oscillation, which is a periodic oscillation of the electrical signals in the brain and which are linked to both normal and abnormal brain function.
When circuits in the brain are not working properly, we can see changes in the characteristics of these oscillations. Many neurological conditions produce changes in brainwaves. For example, in patients with Parkinson’s disease, oscillations in the “beta band” (approximately 15Hz) are observed to be more prominent. In another example, we see similar large oscillations in the presence of a seizure in people with epilepsy. Disrupting these abnormal oscillations can treat some of the symptoms of disease. One example of this is found in Parkinson’s disease, where surgeons can implant electrodes deep in the brain and electrically stimulate cells by a process called deep brain stimulation (DBS). With DBS, it is possible to suppress these beta oscillations and improve symptoms. However, DBS is a highly invasive procedure that includes the need for a burr hole in the skull, placement of the electrode in the brain, and insertion of a “pacemaker” in the chest with wires tunnelled through the neck. We propose to use ultrasound to modify pathological brainwaves non-invasively.
Recent results support this goal by showing that transcranial ultrasound stimulation (TUS), which focuses low intensity ultrasound to a target location in the brain, can modulate brain function. To date, studies of TUS to date in humans have relied on behavioural tasks or externally measured electric fields (EEG), and the local impact of ultrasound on brain circuits is unknown. Our proposal will provide a direct read-out of local brainwave activity caused by the TUS. We will use a specific cohort of patients with Parkinson’s disease (PD) that already have state-of-the-art DBS sensing devices implanted either in the globus pallidus interna (GPi) or subthalamic nucleus (STN), which are associated with beta oscillations in Parkinson’s disease and are common locations for applying DBS. The sensing system will allow direct monitoring of brain oscillations during ultrasound stimulation. We propose to use TUS to modify brainwaves in PD patients by using pulsing strategies already successfully employed in DBS, while simultaneously monitoring beta oscillations that are linked with lack of motion (akinesia/bradykinesia) and gamma oscillations (approximately 65 Hz) that are linked to undesired movement (dyskinesia). The TUS induced impact on beta and gamma oscillations will be measured in real-time, and ultrasound pulsing strategies will be optimized to improve the balance of brainwaves correlated with clinical improvements. To control for ultrasound having a general effect on the brain, we will also apply ultrasound to the hippocampus (HPC) and the anterior cingulate cortex (ACC). The HPC is a region in the brain that has limited connectivity to GPI or STN, and so we predict that will not affect the beta or gamma oscillations, or clinical state. The ACC is thought to connect to the basal ganglia and is involved in decision making so is considered a non-motor target, allowing differentiation between movement and non-movement effects of TUS.
While the proof-of-concept is in Parkinson’s disease, the potential impact is much broader – if successful, we will provide a non-invasive paradigm for probing the brain and exploring novel treatments for neurological conditions, such as pain and cognitive disorders.
REC name
East Midlands - Nottingham 2 Research Ethics Committee
REC reference
23/EM/0165
Date of REC Opinion
18 Sep 2023
REC opinion
Further Information Favourable Opinion