Concurrent decoding of distinct neurophysiological fingerprints of tremor and bradykinesia in Parkinson's disease
- Brown University, United States
- Brigham and Women's Hospital, United States
Abstract
Parkinson's Disease (PD) is characterized by distinct motor phenomena that are expressed asynchronously. Understanding the neurophysiological correlates of these motor states could facilitate monitoring of disease progression and allow improved assessments of therapeutic efficacy, as well as enable optimal closed-loop neuromodulation. We examined neural activity in the basal ganglia and cortex of 31 subjects with PD during a quantitative motor task to decode tremor and bradykinesia - two cardinal motor signs of PD - and relatively asymptomatic periods of behavior. Support-vector regression analysis of microelectrode and electrocorticography recordings revealed that tremor and bradykinesia had nearly opposite neural signatures, while effective motor control displayed unique, differentiating features. The neurophysiological signatures of these motor states depended on the signal type and location. Cortical decoding generally outperformed subcortical decoding. Within the subthalamic nucleus (STN), tremor and bradykinesia were better decoded from distinct subregions. These results demonstrate how to leverage neurophysiology to more precisely treat PD.
Data availability
The raw datasets supporting the current study contain patient information and are unique datasets under continued investigation for additional projects, including those of junior trainees.Deidentified neural/behavioral estimates and related code to reproduce all analyses in the manuscript will be made available in a public repository (Dryad; https://doi.org/10.5061/dryad.h9w0vt4n4).To request raw datasets, please contact the corresponding authors (me@peterlauro.me, wael_asaad@brown.edu) with a project proposal. Based upon the granularity of the data requested and potential for patient information exposure, data sharing would granted in consultation with the Lifespan IRB. There are no commercial restrictions for these data currently.
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Data from: Concurrent decoding of distinct neurophysiological fingerprints of tremor and bradykinesia in Parkinson's diseaseDryad Digital Repository, doi:10.5061/dryad.h9w0vt4n4.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (T32MH020068)
- Peter M Lauro
Doris Duke Charitable Foundation (Clinical Scientist Development Award#2014101)
- Wael F Asaad
National Institute of General Medical Sciences (P20 GM103645)
- Wael F Asaad
Neurosurgery Research and Education Foundation
- Wael F Asaad
Lifespan Norman Prince Neurosciences Institute
- Shane Lee
- Umer Akbar
- Wael F Asaad
Brown University Robert J. and Nancy D. Carney Institute for Brain Science
- Peter M Lauro
- Shane Lee
- Daniel E Amaya
- Umer Akbar
- Wael F Asaad
NIH Office of the Director (S10OD025181)
- Wael F Asaad
Medtronic
- Wael F Asaad
WFA has received proprietary equipment and technical support for unrelated research through the Medtronic external research program.The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Patients and control subjects agreeing to participate in this study signed informed consent, and experimental procedures were undertaken in accordance with an approved Rhode Island Hospital human research protocol (Lifespan IRB protocol #263157) and the Declaration of Helsinki.
Copyright
© 2023, Lauro et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Concurrent decoding of distinct neurophysiological fingerprints of tremor and bradykinesia in Parkinson's disease
eLife 12:e84135.
https://doi.org/10.7554/eLife.84135
Further reading
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- Neuroscience
Sleep cycles are defined as episodes of non-rapid eye movement (non-REM) sleep followed by an episode of REM sleep. Fractal or aperiodic neural activity is a well-established marker of arousal and sleep stages measured using electroencephalography. We introduce a new concept of ‘fractal cycles’ of sleep, defined as a time interval during which time series of fractal activity descend to their local minimum and ascend to the next local maximum. We assess correlations between fractal and classical (i.e. non-REM – REM) sleep cycle durations and study cycles with skipped REM sleep. The sample comprised 205 healthy adults, 21 children and adolescents and 111 patients with depression. We found that fractal and classical cycle durations (89±34 vs 90±25 min) correlated positively (r=0.5, p<0.001). Children and adolescents had shorter fractal cycles than young adults (76±34 vs 94±32 min). The fractal cycle algorithm detected cycles with skipped REM sleep in 91–98% of cases. Medicated patients with depression showed longer fractal cycles compared to their unmedicated state (107±51 vs 92±38 min) and age-matched controls (104±49 vs 88±31 min). In conclusion, fractal cycles are an objective, quantifiable, continuous and biologically plausible way to display sleep neural activity and its cycles.
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- Medicine
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Background:
Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients, like those with SAH, have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this approach is safe in this fragile population. Therefore, this study assessed the impact of both acute and repetitive taVNS on cardiovascular function.
Methods:
In this randomized clinical trial, 24 SAH patients were assigned to either a taVNS treatment or a sham treatment group. During their stay in the intensive care unit, we monitored patient electrocardiogram readings and vital signs. We compared long-term changes in heart rate, heart rate variability (HRV), QT interval, and blood pressure between the two groups. Additionally, we assessed the effects of acute taVNS by comparing cardiovascular metrics before, during, and after the intervention. We also explored acute cardiovascular biomarkers in patients exhibiting clinical improvement.
Results:
We found that repetitive taVNS did not significantly alter heart rate, QT interval, blood pressure, or intracranial pressure (ICP). However, repetitive taVNS increased overall HRV and parasympathetic activity compared to the sham treatment. The increase in parasympathetic activity was most pronounced from 2 to 4 days after initial treatment (Cohen’s d = 0.50). Acutely, taVNS increased heart rate, blood pressure, and peripheral perfusion index without affecting the corrected QT interval, ICP, or HRV. The acute post-treatment elevation in heart rate was more pronounced in patients who experienced a decrease of more than one point in their modified Rankin Score at the time of discharge.
Conclusions:
Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a safe immunomodulatory treatment approach for SAH patients. The observed acute increase in heart rate after taVNS treatment may serve as a biomarker for SAH patients who could derive greater benefit from this treatment.
Funding:
The American Association of Neurological Surgeons (ALH), The Aneurysm and AVM Foundation (ALH), The National Institutes of Health R01-EB026439, P41-EB018783, U24-NS109103, R21-NS128307 (ECL, PB), McDonnell Center for Systems Neuroscience (ECL, PB), and Fondazione Neurone (PB).
Clinical trial number:
