Dopamine-dependent scaling of subthalamic gamma bursts with movement velocity in patients with Parkinson's disease
- Charité - Universitätsmedizin Berlin, Germany
- Medizinische Hochschule Hannover, Germany
Abstract
Gamma synchronization increases during movement and scales with kinematic parameters. Here, disease-specific characteristics of this synchronization and the dopamine-dependence of its scaling in Parkinson's disease are investigated. In 16 patients undergoing deep brain stimulation surgery, movements of different velocities revealed that subthalamic gamma power peaked in the sensorimotor part of the subthalamic nucleus, correlated positively with maximal velocity and negatively with symptom severity. These effects relied on movement-related bursts of transient synchrony in the gamma band. The gamma burst rate highly correlated with averaged power, increased gradually with larger movements and correlated with symptom severity. In the dopamine-depleted state, gamma power and burst rate significantly decreased, particularly when peak velocity was slower than ON medication. Burst amplitude and duration were unaffected by the medication state. We propose that insufficient recruitment of fast gamma bursts during movement may underlie bradykinesia as one of the cardinal symptoms in Parkinson's disease.
Article and author information
Author details
Wolf-Julian Neumann
Funding
Deutsche Forschungsgemeinschaft (DFG KFO247)
- Andrea A Kühn
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: All participants provided written informed conset which was approved by the local review boeards of the Charité - Universitätsmedizin Berlin and Hannover Medical School and in accordance with the standards set by the Declaration of Helsinki (EA2/071/08).
Copyright
© 2018, Lofredi 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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Dopamine-dependent scaling of subthalamic gamma bursts with movement velocity in patients with Parkinson's disease
eLife 7:e31895.
https://doi.org/10.7554/eLife.31895
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Background:
Under which conditions antibiotic combination therapy decelerates rather than accelerates resistance evolution is not well understood. We examined the effect of combining antibiotics on within-patient resistance development across various bacterial pathogens and antibiotics.
Methods:
We searched CENTRAL, EMBASE, and PubMed for (quasi)-randomised controlled trials (RCTs) published from database inception to 24 November 2022. Trials comparing antibiotic treatments with different numbers of antibiotics were included. Patients were considered to have acquired resistance if, at the follow-up culture, a resistant bacterium (as defined by the study authors) was detected that had not been present in the baseline culture. We combined results using a random effects model and performed meta-regression and stratified analyses. The trials’ risk of bias was assessed with the Cochrane tool.
Results:
42 trials were eligible and 29, including 5054 patients, qualified for statistical analysis. In most trials, resistance development was not the primary outcome and studies lacked power. The combined odds ratio for the acquisition of resistance comparing the group with the higher number of antibiotics with the comparison group was 1.23 (95% CI 0.68–2.25), with substantial between-study heterogeneity (I2=77%). We identified tentative evidence for potential beneficial or detrimental effects of antibiotic combination therapy for specific pathogens or medical conditions.
Conclusions:
The evidence for combining a higher number of antibiotics compared to fewer from RCTs is scarce and overall compatible with both benefit or harm. Trials powered to detect differences in resistance development or well-designed observational studies are required to clarify the impact of combination therapy on resistance.
Funding:
Support from the Swiss National Science Foundation (grant 310030B_176401 (SB, BS, CW), grant 32FP30-174281 (ME), grant 324730_207957 (RDK)) and from the National Institute of Allergy and Infectious Diseases (NIAID, cooperative agreement AI069924 (ME)) is gratefully acknowledged.
