In:
Journal of Neurochemistry, Wiley, Vol. 146, No. 3 ( 2018-08), p. 333-347
Abstract:
Clonidine is an anti‐hypertensive medication which acts as an alpha‐adrenergic receptor agonist. As the noradrenergic system is likely to support cognitive functions including attention and executive control, other clinical uses of clonidine have recently gained popularity for the treatment of neuropsychiatric disorders like attention‐deficit hyperactivity disorder or Tourette syndrome, but the mechanism of action is still unclear. Here, we test the hypothesis that the noradrenergic system regulates the activity of subthalamo‐motor cortical loops, and that this influence can be modulated by clonidine. We used pharmacological manipulation of clonidine in a placebo‐controlled study in combination with subthalamic nucleus‐deep brain stimulation ( STN ‐ DBS ) in 16 Parkinson's disease patients performing a reaction time task requiring to refrain from reacting (proactive inhibition). We recorded electroencephalographical activity of the whole cortex, and applied spectral analyses directly at the source level after advanced blind source separation. We found only one cortical source localized to the supplementary motor area ( SMA ) that supported an interaction of pharmacological and subthalamic stimulation. Under placebo, STN ‐ DBS reduced proactive alpha power in the SMA , a marker of local inhibitory activity. This effect was associated with the speeding‐up of movement initiation. Clonidine substantially increased proactive alpha power from the SMA source, and canceled out the benefits of STN ‐ DBS on movement initiation. These results provide the first direct neural evidence in humans that the tonic inhibitory activity of the subthalamocortical loops underlying the control of movement initiation is coupled to the noradrenergic system, and that this activity can be targeted by pharmacological agents acting on alpha‐adrenergic receptors. image
Type of Medium:
Online Resource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1111/jnc.2018.146.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
80158-6
detail.hit.zdb_id:
2020528-4
SSG:
12
