Imperial College London

DrNirGrossman

Faculty of MedicineDepartment of Brain Sciences

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 6805nirg Website

 
 
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Location

 

E503Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

35 results found

Vinao-Carl M, Gal-Shohet Y, Rhodes E, Li J, Hampshire A, Sharp D, Grossman Net al., 2024, Just a phase? Causal probing reveals spurious phasic dependence of sustained attention, NeuroImage, Vol: 285, ISSN: 1053-8119

For over a decade, electrophysiological studies have reported correlations between attention / perception and the phase of spontaneous brain oscillations. To date, these findings have been interpreted as evidence that the brain uses neural oscillations to sample and predict upcoming stimuli. Yet, evidence from simulations have shown that analysis artefacts could also lead to spurious pre-stimulus oscillations that appear to predict future brain responses. To address this discrepancy, we conducted an experiment in which visual stimuli were presented in time to specific phases of spontaneous alpha and theta oscillations. This allowed us to causally probe the role of ongoing neural activity in visual processing independent of the stimulus-evoked dynamics. Our findings did not support a causal link between spontaneous alpha / theta rhythms and behaviour. However, spurious correlations between theta phase and behaviour emerged offline using gold-standard time-frequency analyses. These findings are a reminder that care should be taken when inferring causal relationships between neural activity and behaviour using acausal analysis methods.

Journal article

Luff CE, Dzialecka P, Acerbo E, Williamson A, Grossman Net al., 2024, Pulse-width modulated temporal interference (PWM-TI) brain stimulation, Brain Stimulation, Vol: 17, Pages: 92-103, ISSN: 1876-4754

BACKGROUND: Electrical stimulation involving temporal interference of two different kHz frequency sinusoidal electric fields (temporal interference (TI)) enables non-invasive deep brain stimulation by creating an electric field that is amplitude modulated at the slow difference frequency within the neural range at the target brain region. OBJECTIVE: Here, we investigate temporal interference neural stimulation using square, rather sinusoidal, electric fields that create an electric field that is pulse-width, but not amplitude, modulated at the difference frequency (pulse-width modulated temporal interference, (PWM-TI)). METHODS/RESULTS: We show, using ex-vivo single-cell recordings and in-vivo calcium imaging, that PWM-TI effectively stimulates neural activity at the difference frequency at a similar efficiency to traditional TI. We then demonstrate, using computational modelling, that the PWM stimulation waveform induces amplitude-modulated membrane potential depolarization due to the membrane's intrinsic low-pass filtering property. CONCLUSIONS: PWM-TI can effectively drive neural activity at the difference frequency. The PWM-TI mechanism involves converting an amplitude-fixed PWM field to an amplitude-modulated membrane potential via the low-pass filtering of the passive neural membrane. Unveiling the biophysics underpinning the neural response to complex electric fields may facilitate the development of new brain stimulation strategies with improved precision and efficiency.

Journal article

Violante IR, Alania K, CassarĂ  AM, Neufeld E, Acerbo E, Carron R, Williamson A, Kurtin DL, Rhodes E, Hampshire A, Kuster N, Boyden ES, Pascual-Leone A, Grossman Net al., 2023, Publisher Correction: Non-invasive temporal interference electrical stimulation of the human hippocampus., Nat Neurosci, Vol: 26

Journal article

Wessel MJ, Beanato E, Popa T, Windel F, Vassiliadis P, Menoud P, Beliaeva V, Violante IR, Abderrahmane H, Dzialecka P, Park C-H, Maceira-Elvira P, Morishita T, Cassara AM, Steiner M, Grossman N, Neufeld E, Hummel FCet al., 2023, Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning, Nature Neuroscience, Vol: 26, Pages: 2005-2016, ISSN: 1097-6256

The stimulation of deep brain structures has thus far only been possible with invasive methods. Transcranial electrical temporal interference stimulation (tTIS) is a novel, noninvasive technology that might overcome this limitation. The initial proof-of-concept was obtained through modeling, physics experiments and rodent models. Here we show successful noninvasive neuromodulation of the striatum via tTIS in humans using computational modeling, functional magnetic resonance imaging studies and behavioral evaluations. Theta-burst patterned striatal tTIS increased activity in the striatum and associated motor network. Furthermore, striatal tTIS enhanced motor performance, especially in healthy older participants as they have lower natural learning skills than younger subjects. These findings place tTIS as an exciting new method to target deep brain structures in humans noninvasively, thus enhancing our understanding of their functional role. Moreover, our results lay the groundwork for innovative, noninvasive treatment strategies for brain disorders in which deep striatal structures play key pathophysiological roles.

Journal article

Violante IR, Alania K, CassarĂ  AM, Neufeld E, Acerbo E, Carron R, Williamson A, Kurtin DL, Rhodes E, Hampshire A, Kuster N, Boyden ES, Pascual-Leone A, Grossman Net al., 2023, Non-invasive temporal interference electrical stimulation of the human hippocampus., Nat Neurosci, Vol: 26, Pages: 1994-2004

Deep brain stimulation (DBS) via implanted electrodes is used worldwide to treat patients with severe neurological and psychiatric disorders. However, its invasiveness precludes widespread clinical use and deployment in research. Temporal interference (TI) is a strategy for non-invasive steerable DBS using multiple kHz-range electric fields with a difference frequency within the range of neural activity. Here we report the validation of the non-invasive DBS concept in humans. We used electric field modeling and measurements in a human cadaver to verify that the locus of the transcranial TI stimulation can be steerably focused in the hippocampus with minimal exposure to the overlying cortex. We then used functional magnetic resonance imaging and behavioral experiments to show that TI stimulation can focally modulate hippocampal activity and enhance the accuracy of episodic memories in healthy humans. Our results demonstrate targeted, non-invasive electrical stimulation of deep structures in the human brain.

Journal article

Rintoul JL, Neufeld E, Butler C, Cleveland RO, Grossman Net al., 2023, Remote focused encoding and decoding of electric fields through acoustoelectric heterodyning, Communications Physics, Vol: 6, ISSN: 2399-3650

Heterodyning of signals through physical multiplication is the building block of numerous modern technologies. Yet, it has been mostly limited to the interaction between electromagnetic fields. Here, we report that heterodyning occurs also between acoustic and electric fields in liquid electrolytes. We predict acoustoelectric heterodyning via computational field modelling, which accounts for the vector nature of the electrolytic acoustoelectric interaction. We then experimentally validate the spatiotemporal characteristics of the field emerging from the acoustoelectric heterodyning effect. The electric field distribution generated by the applied fields can be controlled by the propagating acoustic field and the orientation of the applied electric field, enabling the focusing of the resulting electric field at remote locations. Finally, we demonstrate detection of multi-frequency ionic currents at a distant focal location via signal demodulation using pressure waves in electrolytic liquids. As such, acoustoelectric heterodyning could open possibilities in non-invasive biomedical and bioelectronics applications.

Journal article

Hebron H, Lugli B, Dimitrova R, Jaramillo V, Rhodes E, Grossman N, Dijk D-J, Violante IRet al., 2022, Alpha closed-loop auditory stimulation modulates waking alpha oscillations and sleep onset dynamics in a phase-dependent manner in humans

<jats:title>Abstract</jats:title><jats:p>Alpha oscillations play a vital role in managing the brain’s resources, inhibiting neural activity as a function of their phase and amplitude, and are changed in many brain disorders. Developing minimally invasive tools to modulate alpha activity and identifying the parameters that determine its response to exogenous modulators, is essential for the implementation of focussed interventions. We introduce Alpha Closed-Loop Auditory Stimulation (<jats:italic>αCLAS</jats:italic>) as an EEG-based method to augment and investigate these brain rhythms in humans with specificity and selectivity, using targeted auditory stimulation. Across three independent studies, we demonstrate that<jats:italic>αCLAS</jats:italic>alters alpha power, frequency, and connectivity in a phase, amplitude and topography-dependent manner. Using a single-pulse-<jats:italic>αCLAS</jats:italic>evoked potentials approach we show that the effects of auditory stimuli on alpha oscillations and resulting evoked potentials can be explained within the theoretical framework of oscillator theory and a phase-reset mechanism. Finally, we demonstrate the functional relevance of our approach by showing that<jats:italic>αCLAS</jats:italic>modulates sleep onset dynamics in an alpha phase-dependent manner.</jats:p>

Journal article

Hebron H, Lugli B, Dimitrova R, Rhodes E, Grossman N, Violante I, Dijk D-Jet al., 2022, EEG alpha phase-locked auditory stimulation to selectively modulate the sleep onset process, 26th Conference of the European-Sleep-Research-Society (ESRS), Publisher: WILEY, ISSN: 0962-1105

Conference paper

Sunshine MD, Cassara AM, Neufeld E, Grossman N, Mareci TH, Otto KJ, Boyden ES, Fuller DDet al., 2021, Restoration of breathing after opioid overdose and spinal cord injury using temporal interference stimulation, COMMUNICATIONS BIOLOGY, Vol: 4

Journal article

Beppi C, Violante IR, Hampshire A, Grossman N, Sandrone Set al., 2020, Patterns of Focal- and Large-Scale Synchronization in Cognitive Control and Inhibition: A Review, FRONTIERS IN HUMAN NEUROSCIENCE, Vol: 14, ISSN: 1662-5161

Journal article

Schreglmann S, Wang D, Peach R, Li J, Zhang X, Latorre A, Rhodes E, Panella E, Boyden E, Barahona M, Santaniello S, Bhatia K, Rothwell J, Grossman Net al., 2020, Non-invasive amelioration of essential tremor via phase-locked disruption of its temporal coherence, Nature Communications, Vol: 12, ISSN: 2041-1723

Abstract Aberrant neural oscillations hallmark numerous brain disorders. Here, we first report a method to track the phase of neural oscillations in real-time via endpoint-corrected Hilbert transform (ecHT) that mitigates the characteristic Gibbs distortion. We then used ecHT to show that the aberrant neural oscillation that hallmarks essential tremor (ET) syndrome, the most common adult movement disorder, can be noninvasively suppressed via electrical stimulation of the cerebellum phase-locked to the tremor. The tremor suppression is sustained after the end of the stimulation and can be phenomenologically predicted. Finally, using feature-based statistical-learning and neurophysiological-modelling we show that the suppression of ET is mechanistically attributed to a disruption of the temporal coherence of the oscillation via perturbation of the tremor generating a cascade of synchronous activity in the olivocerebellar loop. The suppression of aberrant neural oscillation via phase-locked driven disruption of temporal coherence may represent a powerful neuromodulatory strategy to treat brain disorders.

Journal article

Grossman N, Okun MS, Boyden ES, 2018, Translating Temporal Interference Brain Stimulation to Treat Neurological and Psychiatric Conditions, JAMA NEUROLOGY, Vol: 75, Pages: 1307-1308, ISSN: 2168-6149

Journal article

Schreglmann S, Wang D, Boyden E, Bhatia K, Rothwell J, Grossman Net al., 2018, Phase-locked transcranial alternating current stimulation of the cerebellum for essential tremor, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S537-S537, ISSN: 0885-3185

Conference paper

Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk H-J, Cassara AM, Neufeld E, Kuster N, Tsai L-H, Pascual-Leone A, Boyden ESet al., 2017, Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields, CELL, Vol: 169, Pages: 1029-1041.e16, ISSN: 0092-8674

We report a noninvasive strategy for electrically stimulating neurons at depth. By delivering to the brain multiple electric fields at frequencies too high to recruit neural firing, but which differ by a frequency within the dynamic range of neural firing, we can electrically stimulate neurons throughout a region where interference between the multiple fields results in a prominent electric field envelope modulated at the difference frequency. We validated this temporal interference (TI) concept via modeling and physics experiments, and verified that neurons in the living mouse brain could follow the electric field envelope. We demonstrate the utility of TI stimulation by stimulating neurons in the hippocampus of living mice without recruiting neurons of the overlying cortex. Finally, we show that by altering the currents delivered to a set of immobile electrodes, we can steerably evoke different motor patterns in living mice.

Journal article

Bouchard M, Fortin-Langelier E, Frenette S, Cyr G, Latreille C, Lina J, Grossman N, Carrier Jet al., 2017, IS TRANSCRANIAL ALTERNATING CURRENT STIMULATION (TACS) AN EFFECTIVE TOOL TO ENTRAIN SPINDLES DURING SLEEP IN OLDER INDIVIDUALS?, 31st Annual Meeting of the Associated-Professional-Sleep-Societies (APSS), Publisher: OXFORD UNIV PRESS INC, Pages: A105-A105

Conference paper

Nikolic K, Jarvis S, Schultz S, Grossman Net al., 2013, Controlling the neuronal balancing act: optical coactivation of excitation and inhibition in neuronal subdomains, Publisher: BioMed Central, ISSN: 1471-2202

Conference paper

Grossman N, Simiaki V, Martinet C, Toumazou C, Schultz SR, Nikolic Ket al., 2013, The spatial pattern of light determines the kinetics and modulates backpropagation of optogenetic action potentials, JOURNAL OF COMPUTATIONAL NEUROSCIENCE, Vol: 34, Pages: 477-488, ISSN: 0929-5313

Journal article

Nikolic K, Jarvis S, Grossman N, Schultz Set al., 2013, Computational Models of Optogenetic Tools for Controlling Neural Circuits with Light, 35th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC), Publisher: IEEE, Pages: 5934-5937, ISSN: 1557-170X

Conference paper

Manoli Z, Grossman N, Samaras T, 2012, Theoretical Investigation of Transcranial Alternating Current Stimulation using Realistic Head Model, 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS), Publisher: IEEE, Pages: 4156-4159, ISSN: 1557-170X

Conference paper

Lopes S, Davies N, Toumazou C, Grossman Net al., 2012, Theoretical Investigation of Transcranial Alternating Current Stimulation using Laminar Model, 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS), Publisher: IEEE, Pages: 4152-4155, ISSN: 1557-170X

Conference paper

Grossman N, Nikolic K, Toumazou C, Degenaar Pet al., 2011, Modeling Study of the Light Stimulation of a Neuron Cell With Channelrhodopsin-2 Mutants, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, Vol: 58, Pages: 1742-1751, ISSN: 0018-9294

Journal article

Le TT, Wilde CP, Grossman N, Cass AEGet al., 2011, A simple method for controlled immobilization of proteins on modified SAMs, PHYSICAL CHEMISTRY CHEMICAL PHYSICS, Vol: 13, Pages: 5271-5278, ISSN: 1463-9076

Journal article

McGovern B, Berlinguer-Palmini R, Grossman N, Drakakis E, Pohrer V, neil MAA, Degenaar Pet al., 2010, A new individually addressable micro-LED array for photogenetic neural stimulation, IEEE Trans. Biomedical Circuits and Systems, Vol: In press

Journal article

McGovern BP, Palmini RB, Grossman N, Neil M, Drakakis E, Degenaar PAet al., 2010, Towards an Optogenetic Retinal Prosthesis, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Grossman N, Poher V, Grubb MS, Kennedy GT, Nikolic K, McGovern B, Palmini RB, Gong Z, Drakakis EM, Neil MAA, Dawson MD, Burrone J, Degenaar Pet al., 2010, Multisite optical excitation using ChR2 and micro-LED array, Journal of Neural Engineering, Vol: 7, ISSN: 1741-2560

Journal article

Degenaar P, Grossman N, Berlinguer-Palmini R, McGovern B, Pohrer V, Dawson M, Toumazou C, Burrone J, Nikolic K, Neil Met al., 2010, Optoelectronic microarrays for retinal prosthesis, IEEE Biomedical Circuits and Systems Conference, BioCAS 2009, Pages: 183-186

Conference paper

McGovern B, Drakakis EM, Neil M, O'Brian P, Corbett B, Degenaar Pet al., 2010, Individually Addressable Optoelectronic Arrays for Optogenetic Neural Stimulation, IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE, Pages: 170-173

Conference paper

Degenaar P, Grossman N, Memon MA, Burrone J, Dawson M, Drakakis EM, Neil M, Nikolic Ket al., 2009, Optobionic vision-a new genetically enhanced light on retinal prosthesis, Journal of Neural Engineering, Vol: 6, ISSN: 1741-2560

Journal article

Nikolic K, Grossman N, Grubb M, Burrone J, Toumazou C, Degenaar Pet al., 2009, Photocycles of Channelrhodopsin-2, Photochemistry and Photobiology, Vol: 85, Pages: 400-411

Journal article

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