Noradrenaline and Movement Initiation Disorders in Parkinson's Disease: A Pharmacological Functional MRI Study with Clonidine

TY - JOUR

T1 - Noradrenaline and Movement Initiation Disorders in Parkinson's Disease: A Pharmacological Functional MRI Study with Clonidine

AU - Criaud, Marion

AU - Laurencin, Chloé

AU - Poisson, Alice

AU - Metereau, Elise

AU - Redouté, Jérôme

AU - Thobois, Stéphane

AU - Boulinguez, Philippe

AU - Ballanger, Bénédicte

PY - 2022/8/25

Y1 - 2022/8/25

N2 - Slowness of movement initiation is a cardinal motor feature of Parkinson's disease (PD) and is not fully reverted by current dopaminergic treatments. This trouble could be due to the dysfunction of executive processes and, in particular, of inhibitory control of response initiation, a function possibly associated with the noradrenergic (NA) system. The implication of NA in the network supporting proactive inhibition remains to be elucidated using pharmacological protocols. For that purpose, we administered 150 μg of clonidine to 15 healthy subjects and 12 parkinsonian patients in a double-blind, randomized, placebo-controlled design. Proactive inhibition was assessed by means of a Go/noGo task, while pre-stimulus brain activity was measured by event-related functional MRI. Acute reduction in noradrenergic transmission induced by clonidine enhanced difficulties initiating movements reflected by an increase in omission errors and modulated the activity of the anterior node of the proactive inhibitory network (dorsomedial prefrontal and anterior cingulate cortices) in PD patients. We conclude that NA contributes to movement initiation by acting on proactive inhibitory control via the α2-adrenoceptor. We suggest that targeting noradrenergic dysfunction may represent a new treatment approach in some of the movement initiation disorders seen in Parkinson's disease.

AB - Slowness of movement initiation is a cardinal motor feature of Parkinson's disease (PD) and is not fully reverted by current dopaminergic treatments. This trouble could be due to the dysfunction of executive processes and, in particular, of inhibitory control of response initiation, a function possibly associated with the noradrenergic (NA) system. The implication of NA in the network supporting proactive inhibition remains to be elucidated using pharmacological protocols. For that purpose, we administered 150 μg of clonidine to 15 healthy subjects and 12 parkinsonian patients in a double-blind, randomized, placebo-controlled design. Proactive inhibition was assessed by means of a Go/noGo task, while pre-stimulus brain activity was measured by event-related functional MRI. Acute reduction in noradrenergic transmission induced by clonidine enhanced difficulties initiating movements reflected by an increase in omission errors and modulated the activity of the anterior node of the proactive inhibitory network (dorsomedial prefrontal and anterior cingulate cortices) in PD patients. We conclude that NA contributes to movement initiation by acting on proactive inhibitory control via the α2-adrenoceptor. We suggest that targeting noradrenergic dysfunction may represent a new treatment approach in some of the movement initiation disorders seen in Parkinson's disease.

KW - Noradrenaline

KW - Functional MRI

KW - Clonidine

KW - Parkinson’s Disease

KW - Inhibitory Control

KW - Akinesia

KW - Α2-adrenoceptor

KW - Movement Initiation

KW - Humans

KW - Parkinson Disease

KW - Norepinephrine

KW - Magnetic Resonance Imaging

KW - Movement

U2 - 10.3390/cells11172640

DO - 10.3390/cells11172640

M3 - Article

SN - 2073-4409

VL - 11

SP - 2640

JO - Cells

JF - Cells

IS - 17

ER -