Non-invasive Electrical Deep Brain Stimulation Technology
Lead Research Organisation:
Imperial College London
Department Name: Brain Sciences
Abstract
The ageing of the world population has had a devastating impact on the prevalence of people with brain disorders. The most common brain disorder with age is dementia - a neurodegenerative disease that leads to cognitive impairment that progressively affects activities of daily living erodes independence and impairs quality of life. The leading cause of dementia is Alzheimer's disease, accounting for 60-70% of all dementia cases1. There are approximately 50 million people with dementia worldwide, and this number is projected to increase to 152 million by 20502. In the UK there are approximately 850,000 people with dementia, and this number is projected to increase to 1.6 million by 2040 (translating to 1 new dementia case every 3 minutes). The global costs of dementia are estimated to be US$1 trillion annually2. The estimated cost of dementia care in the UK is £35 billion, which is projected to rise sharply to £95 billion by 2040. At every given time, about one out of four beds in the NHS hospitals is occupied by a patient with dementia3, thus impeding care for other medical conditions. During the last decades, large-scale efforts to delay or stop the progression of dementia due to Alzheimer's disease via pharmacological interventions have failed to produce viable treatment.
This project will develop a technology that aims to slow or reverse the progression of Alzheimer's disease by boosting the resilience to the pathology in the most vulnerable regions at the early stages of the disease. Our approach is based on non-invasive electrical stimulation of the activity in those vulnerable structures to build up their intrinsic metabolic and energetic functionalities, in a way that is conceptionally similar to how exercise builds up the metabolic and energetic functionalities in the muscles. To non-invasively stimulate the activity at the target brain structures which are often at deep locations, we will use a novel method, called temporal interference (TI) stimulation, that we recently discovered. We have already shown that TI stimulation can be used to change the activity in the hippocampus, a deep brain structure that is critical for memory and cognitive function and strongly affected in the early stages of Alzheimer's disease, in an animal model and in healthy humans.
In this project, we will address the most critical engineering challenges to develop our concept to a reliable and precise non-invasive deep brain stimulation technology that can be deployed in large-scale clinical testing. In addition, we will test and iteratively improve the effect of the temporal interference stimulation on the pathology of the hippocampus in animal models of Alzheimer's disease. Finally, we will start developing the pathway to translate the technology to a viable healthcare treatment with affordable and wearable hardware that can also be deployed at the patients' home.
The temporal interference brain stimulation technology with its capability to target arbitrary deep brain structures will provide a platform for developing therapies for multiple brain disorders underpinned by aberrant activity in those structures. The development of such a disruptive technology will place the UK at the frontiers of the neurotechnology industry that is poised for the fastest growth in the medical industry.
1. Livingston, G. et al. The Lancet (2017)
2. Patterson, C. World Alzheimer Report 2018, London, UK (2018).
3. Alzheimer's Society (2009).
This project will develop a technology that aims to slow or reverse the progression of Alzheimer's disease by boosting the resilience to the pathology in the most vulnerable regions at the early stages of the disease. Our approach is based on non-invasive electrical stimulation of the activity in those vulnerable structures to build up their intrinsic metabolic and energetic functionalities, in a way that is conceptionally similar to how exercise builds up the metabolic and energetic functionalities in the muscles. To non-invasively stimulate the activity at the target brain structures which are often at deep locations, we will use a novel method, called temporal interference (TI) stimulation, that we recently discovered. We have already shown that TI stimulation can be used to change the activity in the hippocampus, a deep brain structure that is critical for memory and cognitive function and strongly affected in the early stages of Alzheimer's disease, in an animal model and in healthy humans.
In this project, we will address the most critical engineering challenges to develop our concept to a reliable and precise non-invasive deep brain stimulation technology that can be deployed in large-scale clinical testing. In addition, we will test and iteratively improve the effect of the temporal interference stimulation on the pathology of the hippocampus in animal models of Alzheimer's disease. Finally, we will start developing the pathway to translate the technology to a viable healthcare treatment with affordable and wearable hardware that can also be deployed at the patients' home.
The temporal interference brain stimulation technology with its capability to target arbitrary deep brain structures will provide a platform for developing therapies for multiple brain disorders underpinned by aberrant activity in those structures. The development of such a disruptive technology will place the UK at the frontiers of the neurotechnology industry that is poised for the fastest growth in the medical industry.
1. Livingston, G. et al. The Lancet (2017)
2. Patterson, C. World Alzheimer Report 2018, London, UK (2018).
3. Alzheimer's Society (2009).
Publications
Luff C
(2023)
The neuron mixer and its impact on human brain dynamics
Luff CE
(2024)
The neuron mixer and its impact on human brain dynamics.
in Cell reports
Luff CE
(2024)
Pulse-width modulated temporal interference (PWM-TI) brain stimulation.
in Brain stimulation
Rintoul J
(2023)
Remote focused encoding and decoding of electric fields through acoustoelectric heterodyning
in Communications Physics
Schreglmann SR
(2021)
Non-invasive suppression of essential tremor via phase-locked disruption of its temporal coherence.
in Nature communications
Sunshine MD
(2021)
Restoration of breathing after opioid overdose and spinal cord injury using temporal interference stimulation.
in Communications biology
Vinao-Carl M
(2024)
Just a phase? Causal probing reveals spurious phasic dependence of sustained attention.
in NeuroImage
Violante IR
(2023)
Non-invasive temporal interference electrical stimulation of the human hippocampus.
in Nature neuroscience
Wessel M
(2023)
Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning
in Nature Neuroscience
Description | 1. Develop an ultra-high bandwidth and voltage current source. 2. Experimental feasibility validation in a mouse model of a noninvasive deep brain stimulation therapy for Alzheimer's disease. 3. Developing a strategy for simultaneous electrophysiological recording |
Exploitation Route | The non-invasive deep brain stimulation tool we have developed can be used by the neuroscientific community for brain research. The animal results can set the foundation for a new therapy for Alzheimer's disease. |
Sectors | Electronics Healthcare |
URL | https://helixcentre.com/project-brain |
Description | Creating a cohort of potential end-users and initial engagement. We created a group of AD end-users (7 patients, 13 carers, and 8 health professionals who care for people with dementia in the UK) (Aim 3a). Through a series of thematic workshops (3 online, 2 in-person), we have explored the key considerations/concerns related to a prospective TI brain stimulation therapy for AD and summarised the findings in a written report (Aim 3b). During this process, we discovered that the current requirement for daily clinical visits is a major barrier to clinical studies and future healthcare adoption of the technology. A summary of the engagement has been shared with the public on the following website. A written summary of the outcomes can be downloaded from here. We also created a userbase consisting of labs around the world (~75 labs from ~20 countries) interested in using the TI stimulation for various clinical applications. |
First Year Of Impact | 2022 |
Sector | Healthcare |
Impact Types | Societal |
Description | Non-invasive brain stimulation intervention to ameliorate pathogenic sleep-arousal impairment in dementia |
Amount | £99,639 (GBP) |
Organisation | UK Dementia Research Institute |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2022 |
End | 03/2023 |
Title | Phase-locked brain stimulation |
Description | Aberrant synchronous oscillations have been associated with numerous brain disorders. I discovered a strategy to phase-lock stimulation to endogenous neural oscillatory activity. By mitigating the Gibbs phenomenon distortion from the ends of the Hilbert transformation, we could accurately compute the instantaneous phase of oscillatory signal in real-time and deliver stimulation at fix phase-lags. Then, together with John Rothwell at UCL, I used the ecHT to show that the aberrant synchronous oscillation that hallmarks essential tremor (ET) syndrome, the most common adult movement disorder, can be transiently suppressed via transcranial electrical stimulation of the cerebellum phase-locked to the tremor. We also showed that the tremor suppression was mechanistically attributed to a disruption of the temporal coherence of the aberrant oscillations in the olivocerebellar loop, thus establishing its causal role. |
Type Of Material | Technology assay or reagent |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | The suppression of aberrant neural oscillation via phase-locked driven disruption of temporal coherence represents a novel powerful neuromodulatory strategy to treat brain disorders. |
Description | Imperial- Surrey sleep & vigilance |
Organisation | University of Surrey |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I collaborate with Prof Derk-Jan Dijk (Surrey) and Dr Ines Violante (Surrey) in the development of intervention for vigilance decline and sleep disturbance with age. In this collaboration, I lead the development of the work that is carried out jointly by the 3 labs. |
Collaborator Contribution | Prof Dijk provides state-of-the-art sleep experimentation facilities, Dr Violante leads subset of the experiments and conducts them with her lab members. Both Prof Dijk and Dr Violante help steering the direction of the experiments. |
Impact | The collaboration brings together expertise in biophysics and non-invasive brain stimulation (Grossman), sleep (Dijik) and cognition (Violante). |
Start Year | 2018 |
Description | Imperial-MIT-Harvard |
Organisation | Harvard University |
Country | United States |
Sector | Academic/University |
PI Contribution | I collaborate with Prof Ed Boyden (MIT) and Prof Alvaro Pascual-Leone (Harvard) in the development of new brain stimulation technology. In this collaboration, I lead the development of the work that is carried out jointly by the 3 labs. I sent a PhD student to Prof Ed Boyden (MIT) and co-fund a postdoc at Boyden's lab who carry key experiments in animals for us. |
Collaborator Contribution | Prof Ed Boyden (MIT) raised funding, via donation, to support the joint development work of the technology and the dissemination of the technology to labs around the world. Prof Boyden hosts a PhD from my lab (for 2 terms) and recruited a postdoc scientists to carry key experiments for us. Prof Alvaro Pascual-Leone (Harvard) dedicates a part-time post-doc to conduct proof-of-concept testing in humans. |
Impact | Publication (https://www.ncbi.nlm.nih.gov/pubmed/28575667); Funding (donation to MIT, NIH grant under review); IP; Dr Nir Grossman, biophysics; Prof Ed Boyden (MIT), preclinical electrophys and neurotech; Prof Alvaro Pascual-Leone (Harvard), clinical neuroscience |
Start Year | 2012 |
Description | Imperial-MIT-Harvard |
Organisation | Massachusetts Institute of Technology |
Country | United States |
Sector | Academic/University |
PI Contribution | I collaborate with Prof Ed Boyden (MIT) and Prof Alvaro Pascual-Leone (Harvard) in the development of new brain stimulation technology. In this collaboration, I lead the development of the work that is carried out jointly by the 3 labs. I sent a PhD student to Prof Ed Boyden (MIT) and co-fund a postdoc at Boyden's lab who carry key experiments in animals for us. |
Collaborator Contribution | Prof Ed Boyden (MIT) raised funding, via donation, to support the joint development work of the technology and the dissemination of the technology to labs around the world. Prof Boyden hosts a PhD from my lab (for 2 terms) and recruited a postdoc scientists to carry key experiments for us. Prof Alvaro Pascual-Leone (Harvard) dedicates a part-time post-doc to conduct proof-of-concept testing in humans. |
Impact | Publication (https://www.ncbi.nlm.nih.gov/pubmed/28575667); Funding (donation to MIT, NIH grant under review); IP; Dr Nir Grossman, biophysics; Prof Ed Boyden (MIT), preclinical electrophys and neurotech; Prof Alvaro Pascual-Leone (Harvard), clinical neuroscience |
Start Year | 2012 |
Title | Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields |
Description | A device to stimulate deep brain activity non-invasively. |
Type Of Technology | New/Improved Technique/Technology |
Year Produced | 2017 |
Impact | We have received >35 requests from leading labs around the world to use the brain stimulation device that we developed. Using donation fund, we are currently building more devices to loan, free of charge, to these labs. |