Neurophysiological mechanisms of deep brain stimulation across spatiotemporal resolutions

Brain, Journal Year: 2023, Volume and Issue: 146(11), P. 4456 - 4468

Published: July 13, 2023

Deep brain stimulation is a neuromodulatory treatment for managing the symptoms of Parkinson's disease and other neurological psychiatric disorders. Electrodes are chronically implanted in disease-relevant regions pulsatile electrical delivery intended to restore neurocircuit function. However, widespread interest application expansion this clinical therapy has preceded an overarching understanding alterations invoked by deep stimulation. Over years, various forms neurophysiological evidence have emerged which demonstrate changes activity across spatiotemporal resolutions; from single neuron, local field potential, brain-wide cortical network effects. Though fruitful, such studies often led debate about singular putative mechanism. In Update we aim produce integrative account complementary instead mutually exclusive effects derive generalizable concept mechanisms particular, offer critical review most common historical competing theories, updated discussion on recent literature animal human studies, synthesis synaptic scales observation, including micro-, meso- macroscale circuit alterations.

Language: Английский

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Chronic adaptive deep brain stimulation versus conventional stimulation in Parkinson’s disease: a blinded randomized feasibility trial

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(11), P. 3345 - 3356

Published: Aug. 19, 2024

Language: Английский

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Motor network gamma oscillations in chronic home recordings predict dyskinesia in Parkinson’s disease

Brain, Journal Year: 2024, Volume and Issue: 147(6), P. 2038 - 2052

Published: Jan. 9, 2024

Abstract In Parkinson’s disease, imbalances between ‘antikinetic’ and ‘prokinetic’ patterns of neuronal oscillatory activity are related to motor dysfunction. Invasive brain recordings from the network have suggested that medical or surgical therapy can promote a prokinetic state by inducing narrowband gamma rhythms (65–90 Hz). Excessive in cortex promotes dyskinesia rodent models, but relationship humans has not been well established. To assess this relationship, we used sensing-enabled deep stimulator system, attached both basal ganglia (subthalamic pallidal) leads, paired with wearable devices continuously tracked signs contralateral upper limbs. We recorded 984 h multisite field potentials 30 hemispheres 16 subjects disease (2/16 female, mean age 57 ± 12 years) while at home on usual antiparkinsonian medications. Recordings were done 2–4 weeks after implantation, prior starting therapeutic stimulation. Narrowband was detected precentral gyrus, subthalamic nucleus structures least one side 92% clinical history dyskinesia. globus pallidus. spectral power co-fluctuated similarly scores (mean correlation coefficient ρ = 0.48 range 0.12–0.82 for cortex, 0.53 0.5–0.77 nucleus). Stratification analysis showed correlations driven outlier values, could distinguish ‘on’ periods without Time lag comparisons confirmed oscillations herald onset time either structure when using 2-min epochs. A linear model incorporating three bands (beta, theta/alpha gamma) increased predictive several subject hemispheres. further identified spectrally distinct low (40–60 Hz) subjects, variable. Our findings support hypothesis excessive 65–90 Hz tracks across structures, detectable lag. This rhythm may serve as promising control signal closed-loop stimulation cortical detection.

Language: Английский

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Electrophysiological approaches to informing therapeutic interventions with deep brain stimulation

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 20, 2025

Abstract Neuromodulation therapy comprises a range of non-destructive and adjustable methods for modulating neural activity using electrical stimulations, chemical agents, or mechanical interventions. Here, we discuss how electrophysiological brain recording imaging at multiple scales, from cells to large-scale networks, contribute defining the target location stimulation parameters neuromodulation, with an emphasis on deep (DBS).

Language: Английский

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Finely Tuned γ Tracks Medication Cycles in Parkinson's Disease: An Ambulatory Brain‐Sense Study

Movement Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract Background Novel commercial brain‐sense neurostimulators enable us to contextualize brain activity with symptom and medication states in real‐life ambulatory settings Parkinson's disease (PD). Although various candidate biomarkers have been proposed for adaptive deep stimulation (DBS), a comprehensive comparison of their profiles is lacking. Objectives To systematically compare the neurophysiological dynamics clinical properties three biomarkers—low‐frequency, beta (β), finely tuned γ (FTG) activity. Methods We investigated 14 PD patients implanted Medtronic Percept PC, who underwent up two 4‐week multimodal recording periods on regular stimulation. Subthalamic nucleus local field potentials (LFPs) low‐frequency, β, FTG were recorded. Additionally, objective motor states, physical heart rate using wearables, as well medication‐intake times, sleep‐awake subjective diaries co‐registered. LFP also compared high‐resolution in‐hospital recordings under off / dopaminergic conditions. Results reliably indexed setting at group individual levels, these spectral could be anticipated by recordings. Both low‐frequency correlated wearable‐based dyskinesia scores, whereas diary‐based events only linked FTG. Importantly, indicated ‐medication regardless presence despite potential motion artifacts. The 24‐hour profile revealed large circadian power shifts that may overdrive dynamics. Conclusion Despite limitations low‐temporal resolution recordings, this work provides valuable insights into biomarkers. Specifically, it highlights utility primary reliable indicator DBS. © 2025 Author(s). Movement Disorders published Wiley Periodicals LLC behalf International Parkinson Disorder Society.

Language: Английский

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Long-Term Analysis of Subthalamic Local Field Potentials (Lfp) in Parkinson's Disease: Insights into Circadian Rhythms, Medication, and Personalized Treatment Effects

Published: Jan. 1, 2025

Language: Английский

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Deep brain stimulation-entrained gamma oscillations in chronic home recordings in Parkinson’s disease

Brain stimulation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Highlights•Cortical gamma oscillations often entrain with pallidal and subthalamic stimulation•Entraining levodopa-induced diminishes their prodyskinetic effect•Levodopa-induced oscillation peak frequency variance reduces when entrainedAbstractBackgroundIn Parkinson's disease, invasive brain recordings show that dopaminergic medication can induce narrowband rhythms in the motor cortex nucleus, which co-fluctuate dyskinesia scores. Deep stimulation these to a subharmonic frequency. However, incidence of entrainment during chronic therapeutic stimulation, its relationship basal ganglia site, effect on remain unknown.ObjectiveDetermine whether behavioral effects statistical properties are altered entrained deep stimulation.MethodsWe used sensing-enabled stimulator system, attached both (n=15) or (n=5) leads, record 993 hours multisite field potentials, 656 recorded prior initiating stimulation. 13 subjects (20 hemispheres) disease (1/13 female, mean age 59±9 years) streamed data while at home usual antiparkinsonian medication. Recordings occurred least five months after stimulation.ResultsCortical were detected 4/5 hemispheres undergoing 12/15 Entraining either site reduced effects. Cortical had frequency, increased spectral power, higher power than oscillations.ConclusionStimulation-entrained functionally physiologically distinct from occur absence Understanding discrepancies between types may improve programming protocols.

Language: Английский

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Gamma entrainment induced by deep brain stimulation as a biomarker for motor improvement with neuromodulation

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 26, 2025

Abstract Finely tuned gamma (FTG) oscillations from the subthalamic nucleus (STN) and cortex in Parkinson’s disease (PD) patients undergoing deep brain stimulation (DBS) are often associated with dyskinesia. Recently it was shown that DBS entrains activity at 1:2 of frequency; however, functional role this signal is not yet fully understood. We recorded local field potentials STN 19 chronically implanted PD on dopaminergic medication during DBS, rest, repetitive movements. Here we show high-frequency induced entrainment 15/19 patients. Spontaneous FTG present 8 patients; five these dyskinesia occurred or were enhanced entrained stimulation. Further, there a significant increase power movement comparison to while had faster movements compared those without. These findings argue for relevance stimulation-induced as prokinetic that, necessarily promoting DBS-induced can be promising neurophysiological biomarker identifying optimal amplitude closed-loop DBS.

Language: Английский

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1:2 entrainment is not a device-induced artefact, except when it is

Brain stimulation, Journal Year: 2024, Volume and Issue: 17(2), P. 149 - 151

Published: Feb. 6, 2024

Dear Editor, Deep Brain Stimulation (DBS) is a well-established invasive therapeutic approach for Parkinson's disease (PD). However, the mechanisms of DBS remain unclear. A transition from established open-loop paradigm to closed-loop holds promise enhancing outcomes and optimising device efficiency [1Simon Little, Alex Pogosyan, Spencer Neal, Baltazar Zavala, Ludvic Zrinzo, Marwan Hariz, Thomas Foltynie, Patricia Limousin, Keyoumars Ashkan, James FitzGerald, Alexander L. Green, Tipu Z. Aziz, Peter Brown. Adaptive deep brain stimulation in advanced parkinson disease. Annals neurology, 74, 2013.Google Scholar, 2Carina R Oehrn, Stephanie Cernera, Lauren H Hammer, Maria Shcherbakova, Jiaang Yao, Amelia Hahn, Sarah Wang, Jill L Ostrem, Simon Philip Starr. Personalized chronic adaptive outperforms conventional parkinson's medRxiv, 2023.Google Scholar]. This requires identifying reliable biomarkers algorithm. Recent studies suggest that associated with harmonics frequency may offer viable options (aDBS) provide mechanistic insights [2Carina 3James J. Sermon, Olaru, Juan Anso, Rafal Bogacz, A. Starr, Timothy Denison, Benoit Duchet. Sub-harmonic entrainment cortical gamma oscillations disease: Model based predictions validation three human subjects. Stimulation, Previously subharmonic have been avoided, often dismissed as artefactual. partly due there being no clear physiological/non-physiological differentiating factor when considering steady signals during short time periods. To advance sense-stimulation therapies aDBS, it imperative identify artefact-free bands effective biomarker monitoring. Here, we present framework discerning artefacts at half harmonic frequency. Do We Expect Entrainment? Yes! It should be noted theoretically expect see periodic perturbations certain nonlinear systems [[4]Namiko Mitarai, Uri Alon, Mogens H. Jensen. Entrainment noise-induced limit cycle oscillators under weak noise. Chaos, 23:023125, 6 Cortical 1:2 finely tuned (FTG) through has demonstrated occur predictable manner PD [[3]James Scholar] (Fig. 1A). key requirement believed neuronal ensembles natural close (discussed Scholar]). can seen Fig. 1C where only observed cortex which displays FTG activity approximately 75 Hz off-stimulation, unlike pallidum around stimulation. Theory account neurophysiological phenomenon but further checks are required rule out presence artefacts. Physiological Confirmation Steps Initially, important treat cautiously an artefact. evidence demonstrates physiological origin must open exploit potential clinical implications. demonstrate by how evolves independent physiology or 1) Medication dependent: modulated medication on-medication states 5Nicole C. Swann, Coralie De Hemptinne, Svjetlana Miocinovic, Salman Qasim, S. Nathan Ziman, Marta San Luciano, Nicholas B. Galifianakis, Gamma hyperkinetic state detected recordings Journal Neuroscience, 36:6445–6458, 2016.Google 1B). 2) Sleep-wake Neural selectively entrain subharmonics according sleep [[6]Clay Smyth, Md Fahim Anjum, Shravanan Ravi, Little. stage targeting 16(5):1292–1296, In system signal processing unchanged, appear disappear solely reflects change underlying neural circuitry. 3) Clinical observations: power entrained shown predict prokinetic patients, was identified optimal control aDBS reducing residual motor fluctuation [[2]Carina 4) Location Specific: specific structures (Fig 1C, RCS10 reported The observation response pallidal limited contacts. These contacts not stimulating electrode. indicates volume conduction artefact electrode source activity. 5) Nonlinear stimulation: also parameters 1D). lost higher amplitudes, demonstrating simply observing aliased signal; amplifier saturation might some effect, monitored. Additionally, results line up closely computational model Electrical Signal Chain Checklist When there's evidence, proceed eliminate most commonly hypothesised sources benchtop testing simulations. begin our checklist difficult sources, easiest modulate. Tissue-electrode-interfaces (TEIs): TEIs cause [[7]Yue Chen, Bozhi Ma, Hongwei Hao, Luming Li. Cause local field potentials recorded sensing-enabled neurostimulator. Proceedings Annual International Conference IEEE Engineering Medicine Biology Society, EMBS, 2021.Google Scholar], eliminated simulate output 130 monophasic square wave pulses applied resistor network TEI 1F, Scholar]) used capacitor parallel 1E). did induced either TEI. surprising these models made linear time-invariant components. element produce anything other than scaled phase-shifted output. Stimulator Circuits: findings characterisation Picostim DyNeuMo-2 saline tank 1H), shows range frequencies used. agreement both Medtronic Percept PC [[8]Yohann Thenaisie, Chiara Palmisano, Andrea Canessa, Bart Keulen, Philipp Capetian, Mayte Castro Jiménez, Julien F. Bally, Elena Manferlotti, Laura Beccaria, Rodi Zutt, Grégoire Courtine, Jocelyne Bloch, Niels Van Der Gaag, Carel Hoffmann, Eduardo Martin Moraud, Ioannis U. Isaias, M. Fiorella Contarino. Towards technical notes on novel commercial sensing, Summit RC+S [[9]Scott Stanslaski, Jeffrey Herron, Tom Chouinard, Duane Bourget, Ben Isaacson, Vaclav Kremen, Enrico Opri, William Drew, Benjamin Brinkmann, Aysegul Gunduz, Adamski, Gregory Worrell, Denison. chronically implantable coprocessor investigating treatment neurological disorders. Transactions Biomedical Circuits Systems, 12, 2018.Google 1G). Subharmonic arise stimulators, PINS structured noise More researchers characterise their chain (as they observe suspected instead ruling responses without investigation. Analogue-to-digital converters (ADCs): ADC primary suspect external easily simulated. downsampled 1K) well delta-sigma 1L, more common devices) variable sampling rates. possible prominent 1I). precise predicted (Github Artefact Calculator). stimulators use today already constrained factors [[10]Juan Ansó, Moaad Benjaber, Brandon Parks, Samuel Parker, Carina Renate Matthew Petrucci, Ro'Ee Gilron, Robert Wilt, Helen Bronte-Stewart, David Borton, Concurrent sensing bi-directional interfaces: multi-site translational experience. Engineering, 19, 2022.Google this included another constraint. Looking future, manufacturers design electrical avoid masking biomarkers. summary, simulations combination modulation state, location stimulation, effectively Detailed study still few research groups, replication will increase confidence does By better understanding stimulating, able obtain into therapy robust algorithms. PS receives support Inc (providing investigational devices free charge). TD founder, director, shareholder Amber Therapeutics, Ltd, controlling interest Bioinduction Ltd Finetech Medical respective designers DyNeuMo system. advisor Synchron Cortec Neuro. Sermon: Data curation, Methodology, Software, Validation, Writing – review & editing, Conceptualization, Formal analysis, Investigation, Visualization, original draft. Benjaber: Resources, editing. Duchet: Funding acquisition, Supervision, Anso: Olaru: Starr: Denison: JS supported DARPA HR0011- 20-2-0028 Manipulating Optimising Rhythms Enhancement Sleep (Morpheus) UK Research Council grant MC UU 00003/3. MO NIH/NINDS award R01NS090913. JA Swiss National Science Foundation (Early Postdoc Mobility P2BEP3 188140). BD jointly Royal Academy Rosetrees Fellowship programme, 00003/1. Content represents views authors funders.

Language: Английский

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Prospects of cognitive-motor entrainment: an interdisciplinary review

Frontiers in Cognition, Journal Year: 2024, Volume and Issue: 3

Published: Feb. 21, 2024

Entrainment theory, a multidisciplinary concept referring to the automatic synchronization of oscillatory patterns, can be used explain interactions across motor production, cognition, and environmental processing. This review summarizes findings from three primary categories naturally occurring neural entrainment: body-brain entrainment involuntary self-produced rhythms, bottom-up between stimuli brain, top-down processes. Studies evaluating entrainment's impact on cognition suggest that synchronized activation may alleviate cognitive constraints. has also been therapeutically implemented decrease production variation enhance movement quality. When considering evidence for ability attentional load task increase or quality, promising technique applied dual-tasking. An emerging body literature suggests cognitive-motor dual-task cost and, in some cases, lead higher quality psychological physiological performance than when same tasks are performed isolation. We propose pathways future research emphasize therapeutic relevance further experimentation topic provide. By understanding how maximize benefits, scientists practitioners able harness its benefits learning rehabilitative practices.

Language: Английский

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