Journal article
A causal role for the human subthalamic nucleus in non-selective cortico-motor inhibition
Current biology, Vol.32(17), pp.3785-3791.e3
07/15/2022
DOI: 10.1016/j.cub.2022.06.067
PMCID: PMC9511894
PMID: 35841891
Abstract
Common cortico-basal ganglia models of motor control suggest a key role for the subthalamic nucleus (STN) in motor inhibition.1, 2, 3 In particular, when already-initiated actions have to be suddenly stopped, the STN is purportedly recruited via a hyperdirect pathway to net inhibit the cortico-motor system in a broad, non-selective fashion.4 Indeed, the suppression of cortico-spinal excitability (CSE) during rapid action stopping extends beyond the stopped muscle and affects even task-irrelevant motor representations.5,6 Although such non-selective CSE suppression has long been attributed to the broad inhibitory influence of STN on the motor system, causal evidence for this association is hitherto lacking. Here, 20 Parkinson’s disease patients treated with STN deep-brain stimulation (DBS) and 20 matched healthy controls performed a verbal stop-signal task while CSE was measured from a task-unrelated hand muscle. DBS allowed a causal manipulation of STN, while CSE was measured using transcranial magnetic stimulation (TMS) over primary motor cortex and concurrent electromyography. In patients OFF-DBS and controls, the CSE of the hand was non-selectively suppressed when the verbal response was successfully stopped. Crucially, this effect disappeared when STN was disrupted via DBS in the patient group. Using this unique combination of DBS and TMS during human behavior, the current study provides first causal evidence that STN is likely involved in non-selectively suppressing the physiological excitability of the cortico-motor system during action stopping. This confirms a core prediction of long-held cortico-basal ganglia circuit models of movement. The absence of cortico-motor inhibition during STN-DBS may also provide potential insights into the common side effects of STN-DBS, such as increased impulsivity.7, 8, 9, 10, 11
Details
- Title: Subtitle
- A causal role for the human subthalamic nucleus in non-selective cortico-motor inhibition
- Creators
- Jan R Wessel - University of Iowa, Iowa Neuroscience InstituteDarcy A DiesburgNathan H Chalkley - University of Iowa, NeurologyJeremy D W Greenlee - University of Iowa, Neurosurgery
- Resource Type
- Journal article
- Publication Details
- Current biology, Vol.32(17), pp.3785-3791.e3
- DOI
- 10.1016/j.cub.2022.06.067
- PMID
- 35841891
- PMCID
- PMC9511894
- NLM abbreviation
- Curr Biol
- ISSN
- 0960-9822
- eISSN
- 1879-0445
- Publisher
- Elsevier
- Grant note
- This research was funded by grants from the National Institutes of Health (R01 NS102201) and National Science Foundation (NSF CAREER 1752355) to J.R.W. and training grant funding from the National Institutes of Health (T32 GM108540) to D.A.D.
- Comment
- All original code has been deposited at the OSF and is publicly available as of the date of publication. De-identified data have been deposited at the OSF and are publicly available as of the date of publication. DOIs are listed in the key resources table.
- Language
- English
- Electronic publication date
- 07/15/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Stead Family Department of Pediatrics; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neurosurgery; Otolaryngology
- Record Identifier
- 9984275848402771
Metrics
25 Record Views