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To effectively interact with their environment, humans must often select actions from multiple incompatible options. Existing theories propose that during motoric response-conflict, inappropriate motor activity is actively (and perhaps non-selectively) suppressed by an inhibitory fronto-basal ganglia mechanism. We here tested this theory across three experiments. First, using scalp-EEG, we found that both outright action-stopping and response-conflict during action-selection invoke low-frequency activity of a common fronto-central source, whose activity relates to trial-by-trial behavioral indices of inhibition in both tasks. Second, using simultaneous intracranial recordings from the basal ganglia and motor cortex, we found that response-conflict increases the influence of the subthalamic nucleus on M1-representations of incorrect response-tendencies. Finally, using transcranial magnetic stimulation, we found that during the same time period when conflict-related STN-to-M1 communication is increased, cortico-spinal excitability is broadly suppressed. Together, these findings demonstrate that fronto-basal ganglia networks buttress action-selection under response-conflict by rapidly and non-selectively net-inhibiting inappropriate motor tendencies.
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In Search of a Feedback Signal for Closed-Loop Deep Brain Stimulation: Stimulation of the Subthalamic Nucleus Reveals Altered Glutamate Dynamics in the Globus Pallidus in Anesthetized, 6-Hydroxydopamine-Treated Rats
Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is a surgical procedure for alleviating motor symptoms of Parkinson’s Disease (PD). The pattern of DBS (e.g., the electrode pairs used and the intensity of stimulation) is usually optimized by trial and error based on a subjective evaluation of motor function. We tested the hypotheses that DBS releases glutamate in selected basal ganglia nuclei and that the creation of 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions alters glutamate release during DBS in those basal ganglia nuclei. We studied the relationship between a pseudo-random binary sequence of DBS and glutamate levels in the STN itself or in the globus pallidus (GP) in anesthetized, control, and 6-OHDA-treated rats. We characterized the stimulus–response relationships between DBS and glutamate levels using a transfer function estimated using System Identification. Stimulation of the STN elevated glutamate levels in the GP and in the STN. Although the 6-OHDA treatment did not affect glutamate dynamics in the STN during DBS in the STN, the transfer function between DBS in the STN and glutamate levels in the GP was significantly altered by the presence or absence of 6-OHDA-induced lesions. Thus, glutamate responses in the GP in the 6-OHDA-treated animals (but not in the STN) depended on dopaminergic inputs. For this reason, measuring glutamate levels in the GP may provide a useful feedback target in a closed-loop DBS device in patients with PD since the dynamics of glutamate release in the GP during DBS seem to reflect the loss of dopaminergic neurons in the SNc.
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- Award ID(s):
- 2042543
- PAR ID:
- 10413811
- Date Published:
- Journal Name:
- Biosensors
- Volume:
- 13
- Issue:
- 4
- ISSN:
- 2079-6374
- Page Range / eLocation ID:
- 480
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/bios13040480
