Dominant neuroanatomical models hold that humans regulate their movements via loop-like cortico-subcortical networks, which include the subthalamic nucleus (STN), motor thalamus, and sensorimotor cortex (SMC). Inhibitory commands across these networks are purportedly sent via transient, burst-like signals in the β frequency (15-29Hz). However, since human depth-recording studies are typically limited to one recording site, direct evidence for this proposition is hitherto lacking. Here, we present simultaneous multi-site recordings from SMC and either STN or motor thalamus in humans performing the stop-signal task. In line with their purported function as inhibitory signals, subcortical β-bursts were increased on successful stop-trials. STN bursts in particular were followed within 50ms by increased β-bursting over SMC. Moreover, between-site comparisons (including in a patient with simultaneous recordings from SMC, thalamus, and STN) confirmed that β-bursts in STN temporally precede thalamic β-bursts. This highly unique set of recordings provides empirical evidence for the role of β-bursts in conveying inhibitory commands along long-proposed cortico-subcortical networks underlying movement regulation in humans.
All data analyzed during this study and scripts used for analyses are available on Dryad.
Cortico-subcortical β burst dynamics underlying movement cancellation in humansDryad Digital Repository, doi:10.5061/dryad.gf1vhhmq0.
- Darcy A Diesburg
- Jan R Wessel
- Jan R Wessel
- Jeremy DW Greenlee
- Jan R Wessel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: Research participants signed a written informed consent document during a clinic visit prior to surgery. Experimental protocols were approved by the University of Iowa's Institutional Review Board (#201402720).
- Nicole C Swann, University of Oregon, United States
© 2021, Diesburg 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.
Mathys et al. conducted the first single-nucleus RNA-seq (snRNA-seq) study of Alzheimer’s disease (AD) (Mathys et al., 2019). With bulk RNA-seq, changes in gene expression across cell types can be lost, potentially masking the differentially expressed genes (DEGs) across different cell types. Through the use of single-cell techniques, the authors benefitted from increased resolution with the potential to uncover cell type-specific DEGs in AD for the first time. However, there were limitations in both their data processing and quality control and their differential expression analysis. Here, we correct these issues and use best-practice approaches to snRNA-seq differential expression, resulting in 549 times fewer DEGs at a false discovery rate of 0.05. Thus, this study highlights the impact of quality control and differential analysis methods on the discovery of disease-associated genes and aims to refocus the AD research field away from spuriously identified genes.
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