"We are devoted to transforming the lives of people living with neurodegenerative diseases by pioneering non-invasive neuromodulatory interventions that correct the abnormal brain activity that underpins the pathology and its symptomatic manifestation." Nir Grossman
UK DRI Group Leader
Combining his skills in physics and neuroscience, Dr Nir Grossman, Lecturer in Dementia Research at Imperial College London, is at the forefront of cutting-edge techniques modulating aberrant neural activity in brain disorders. Obtaining his PhD in 2009, he was awarded fellowships from BBSRC and the Wellcome Trust, completing further training at Imperial, the Massachusetts Institute of Technology and Harvard. In 2018, Nir was awarded the Science & PINS Prize for Neuromodulation, for his pioneering work on noninvasive brain stimulation method. He joins the UK DRI at Imperial to apply this work to neurodegenerative diseases.
1. At a glance
Using brain stimulation to help treat dementia
The neural cells in our brains use electrical signalling to receive and send information. But people affected with brain conditions, such as dementia, often have imbalance patterns of electrical activity that affects their cognitive function and brain health. Correcting these patterns of electrical activity in the brain, may be a viable treatment approach.
Deep brain stimulation (DBS) is a procedure already being used to treat Parkinson’s disease, and its success provides hope that this therapeutic method could be utilised for other dementias, such as Alzheimer’s Disease (AD). However, this is an invasive technique involving brain surgery, which brings risks for individuals involved.
Dr Nir Grossman aspires to uncover the mechanisms by which imbalance brain activity impacts brain conditions, such as dementia, and pioneer non-invasive treatment strategies. His team is developing new tools to correct imbalanced activity in deep areas of the brain affected in dementia, and use these tools to investigate the therapeutic effects on the development of dementia and its symptoms.
2. Scientific goals
Aberrant brain activity plays a critical role in the progression of neurodegenerative diseases, such as Alzheimer’s disease (AD), since it disrupts the critical framework of cognitive processing and motor control, and dysregulates cellular processes in both neural and glia cells that are key for their health.
Physical means of brain stimulation, known as ‘neuromodulation’, are tenable, non-pharmacological means to correct aberrant brain activity. Indeed, patients severe movement disorders, such as Parkinson’s disease, can be treated with deep brain stimulation (DBS), which is also being investigated as a treatment for Alzheimer’s disease (AD), with early reports showing an increase in the metabolism of brain regions affected. However, the risk from implanting electrodes in the brain limits the potential therapeutic impact and makes exploration of new brain targets difficult.
Dr Nir Grossman and his team have recently discovered a strategy for non-invasive DBS by temporal interference (TI) of kHz electrical fields. They showed that TI stimulation can drive action potential activity in the live mouse brain, recruit deep brain structures without the overlying cortex, and functionally map a brain region without physically moving the electrodes. The TI stimulation uses familiar and well-tested electric fields and hence it is deployable as well into human studies.
Main objectives and research goals:
The overarching aim of this UK DRI programme is to develop non-invasive neuromodulatory intervention for dementia via direct control of the aberrant brain activity that underpins the pathology and its symptoms.
The rationale underlying the research of Dr Nir Grossman is to drive innovation through a rigorous scientific exploration of the biophysical rules underpinning the neural processing of electromagnetic stimulation. The specific aims are:
1. To develop tools to non-invasively control brain activity via exploration of fundamental biophysical principles.
2. To discover neuromodulatory principles to mitigate the disease pathophysiology and symptomatic cognitive decline via exploration of the causal role of network-level brain activity.
3. To develop the translation of the tools and principles developed in Aim 1 & 2 to treat patients with neurodegenerative disorders.
3. Team members
Dr Eddy Rhodes (Postdoctoral Researcher)
Dr Robert Peach (Postdoctoral Researcher)
Dr Maria Garcia Garrido (Postdoctoral Researcher)
Dr Kate Godfrey (Research Associate)
Dr Danielle Kurtin (Research Associate)
Dr Simon Williamson (PhD Student)
Kety Alania (PhD Student)
Matteo Vinao-Carl (PhD Student)
Junheng Li (PhD Student)
Jean Rintoul (PhD Student)
Assaf Touboul (PhD Student)
Thomas Deegan (PhD Student)
Caroline Rew (PhD Student)
Sofia Peressotti (PhD Student)
Julia Borella (PhD Student)
Tianyu Wei (PhD Student)
Kaarin Sabad (Research Assistant)
4. Collaborations
Within UK DRI:
- Prof Paul Matthews, UK DRI at Imperial
- Giles Hardingham, UK DRI at Edinburgh
- Prof David Sharp, UK DRI at Care Research & Technology at Imperial
- Prof Derk-Jan Dijk, UK DRI at Care Research & Technology at Imperial
- Dr Sam Barnes, UK DRI at Imperial
Beyond UK DRI:
- Prof Ed Boyden, MIT
- Prof Alvaro Pascual-Leone, Harvard University
- Prof Niels Kuster, ETH Zurich
- Prof John Rothwell, University College London
- Prof Mauricio Barahona, Imperial College London
- Dr Adam Hampshire, Imperial College London
- Dr Ines Violante, University of Surrey
5. Topics
non-invasive brain stimulation, deep brain stimulation, transcranial current stimulation, transcranial alternating current stimulation, neuromodulation, temporal interference, phase-locked brain stimulation, closed-loop brain stimulation, corrective plasticity, aberrant network activity, systems neuroscience, neural network, neurodegeneration, Alzheimer’s disease, dementia, Parkinson’s disease, vigilance, sleep, sustained attention, memory consolidation, cognition, cognitive control, tremor, essential tremor
6. Techniques
Techniques to modulate brain activity:
non-invasive brain stimulation, deep brain stimulation, transcranial current stimulation, transcranial alternating current stimulation, TACS, neuromodulation, temporal interference stimulation, TI stimulation, phase-locked brain stimulation, closed-loop brain stimulation.
Techniques to record brain activity:
electrophysiology, patch clamp recording, in-vivo patch clamp recording, electroencephalography, EEG, magnetic resonance imaging, MRI, functional magnetic resonance imaging, fMRI, MRI, behaviour assay
Computational techniques:
Finite element method, FEM, neurophysiological modelling, Hodgkin–Huxley model, circuit modelling
7. Key publications
Schreglmann, Sebastian R., et al. Non-invasive suppression of essential tremor via phase-locked disruption of its temporal coherence. Nature communications, 2021; 12.1: 1-15.
Grossman N, Okun MS, Boyden ES. Translating Temporal Interference Brain Stimulation to Treat Neurological and Psychiatric Conditions. JAMA Neurology, 2018; 75(11):1307-1308
Grossman N. Modulation without surgical intervention. Science 2018; 361(6401): 461-462
Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A. Noninvasive deep brain stimulation via temporally interfering electric fields. Cell. 2017 Jun 1;169(6):1029-41.
Grossman N, Nikolic K, Toumazou C, Degenaar P. Modeling study of the light stimulation of a neuron cell with channelrhodopsin-2 mutants. IEEE Transactions on Biomedical Engineering. 2011 Jun;58(6):1742-51.
Grossman N, Poher V, Grubb MS, Kennedy GT, Nikolic K, McGovern B, Palmini RB, Gong Z, Drakakis EM, Neil MA, Dawson MD. Multi-site optical excitation using ChR2 and micro-LED array. Journal of neural engineering. 2010 Jan 14;7(1):016004.
