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.
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•Noninvasive TI stimulation electrically stimulates neurons at depth selectively•Neurons are stimulated by interference between multiple electric fields•Neurons in mouse hippocampus can be stimulated without affecting the overlying cortex
A noninvasive method for deep-brain stimulation may be a new approach for the treatment of neuropsychiatric diseases.
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 transiently suppressed via transcranial electrical stimulation of the cerebellum phase-locked to the tremor. The tremor suppression is sustained shortly after the end of the stimulation and can be phenomenologically predicted. Finally, we use feature-based statistical-learning and neurophysiological-modelling to show that the suppression of ET is mechanistically attributed to a disruption of the temporal coherence of the aberrant oscillations in the olivocerebellar loop, thus establishing its causal role. The suppression of aberrant neural oscillation via phase-locked driven disruption of temporal coherence may in the future represent a powerful neuromodulatory strategy to treat brain disorders.
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 (αCLAS) as an EEG-based method to modulate and investigate these brain rhythms in humans with specificity and selectivity, using targeted auditory stimulation. Across a series of independent experiments, we demonstrate that αCLAS alters alpha power, frequency, and connectivity in a phase, amplitude, and topography-dependent manner. Using single-pulse-αCLAS, we show that the effects of auditory stimuli on alpha oscillations 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 αCLAS can interfere with sleep onset dynamics in a phase-dependent manner.
Noninvasive deep brain stimulation can be achieved via temporally interfering electric fields
A multitude of brain disorders have debilitating impacts on the quality of life of a large patient ...populace, accounting for ∼30% of the global burden of disease (
1
). Most patients with brain disorders are unamenable to any form of treatment when first- and second-line interventions are ineffective (
2
,
3
). Neuromodulation technologies can help millions of patients who suffer from such brain disorders.
A signal mixer facilitates rich computation, which has been the building block of modern telecommunication. This frequency mixing produces new signals at the sum and difference frequencies of input ...signals, enabling powerful operations such as heterodyning and multiplexing. Here, we report that a neuron is a signal mixer. We found through ex vivo and in vivo whole-cell measurements that neurons mix exogenous (controlled) and endogenous (spontaneous) subthreshold membrane potential oscillations, producing new oscillation frequencies, and that neural mixing originates in voltage-gated ion channels. Furthermore, we demonstrate that mixing is evident in human brain activity and is associated with cognitive functions. We found that the human electroencephalogram displays distinct clusters of local and inter-region mixing and that conversion of the salient posterior alpha-beta oscillations into gamma-band oscillations regulates visual attention. Signal mixing may enable individual neurons to sculpt the spectrum of neural circuit oscillations and utilize them for computational operations.
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•A single neuron mixes exogenous and endogenous oscillations to produce new frequencies•Neural frequency mixing originates in the nonlinearity of voltage-gated ion channels•The human brain EEG displays local and inter-region frequency mixing interactions•Mixing of human posterior alpha and beta oscillations correlates with visual attention
Luff, Peach, et al. demonstrate that the single neuron can act as a signal mixer to create new oscillatory frequencies from exogenous or endogenous subthreshold membrane potential oscillations. They demonstrate that this frequency mixing originates in voltage-gated ion channels and show evidence of functional mixing in the human brain activity.
Neural synchronisation patterns are involved in several complex cognitive functions and constitute a growing trend in neuroscience research. While synchrony patterns in working memory have been ...extensively discussed, a complete understanding of their role in cognitive control and inhibition is still elusive. Here we provide an up-to-date review on synchronisation patterns underlying behavioural inhibition, extrapolating common grounds and dissociating features with other inhibitory functions. Moreover, we suggest a schematic conceptual framework and highlight existing gaps in the literature, current methodological challenges and compelling research questions for future studies.
Photocycles of Channelrhodopsin-2 Nikolic, Konstantin; Grossman, Nir; Grubb, Matthew S. ...
Photochemistry and photobiology,
01/2009, Letnik:
85, Številka:
1
Journal Article
Recenzirano
Recent developments have used light‐activated channels or transporters to modulate neuronal activity. One such genetically‐encoded modulator of activity, channelrhodopsin‐2 (ChR2), depolarizes ...neurons in response to blue light. In this work, we first conducted electrophysiological studies of the photokinetics of hippocampal cells expressing ChR2, for various light stimulations. These and other experimental results were then used for systematic investigation of the previously proposed three‐state and four‐state models of the ChR2 photocycle. We show the limitations of the previously suggested three‐state models and identify a four‐state model that accurately follows the ChR2 photocurrents. We find that ChR2 currents decay biexponentially, a fact that can be explained by the four‐state model. The model is composed of two closed (C1 and C2) and two open (O1 and O2) states, and our simulation results suggest that they might represent the dark‐adapted (C1‐O1) and light‐adapted (C2‐O2) branches. The crucial insight provided by the analysis of the new model is that it reveals an adaptation mechanism of the ChR2 molecule. Hence very simple organisms expressing ChR2 can use this form of light adaptation.
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