Muscarinic antagonist effects on executive control of attention.
Acetylcholine plays a major role in mediating attention processes. We investigated the muscarinic antagonist effect of scopolamine on functional neuro-anatomy of attention and cognition. We assessed 12 healthy volunteers while performing the Attention Network Task on 0.4 mg scopolamine and placebo in a single-blind randomized trial in a 1.5 T magnetic resonance scanner. Neurocognitive measures included verbal learning, verbal memory, verbal fluency, trail making, digit span, a continuous performance task and a planning task (Tower of London). When compared to placebo, scopolamine increased reaction times for conflicting stimulus processing, together with decreasing brain activation in the anterior cingulate cortex (a brain region involved in conflict processing) suggestive of a muscarinic antagonist effect on executive control of attention. Contrary to the notion of a predominantly right-hemispheric lateralization of cognitive processes associated with orienting attention, scopolamine reduced brain activity in left superior and left middle frontal brain areas. Our neuropsychological test data revealed a selective effect of scopolamine on verbal learning and memory while other cognitive domains, such as planning and working memory, were unaffected. These findings are consistent with muscarinic modulation of dopaminergic neurotransmission in frontal attention networks when processing conflicting information.
Centre for Rural and Remote Mental Health, University of Newcastle, Australia. renate.thienel@newcastle.edu.au
Renate
R
Thienel
Thilo
T
Kellermann
Ulrich
U
Schall
Bianca
B
Voss
Martina
M
Reske
Sarah
S
Halfter
Abigail J
AJ
Sheldrick
Katrin
K
Radenbach
Ute
U
Habel
Nadim Jon
NJ
Shah
Tilo
T
Kircher
D000328:Adult; D001288:Attention / Q000187:drug effects* / Q000502:physiology*; D018592:Cross-Over Studies; D056344:Executive Function / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology; D016037:Single-Blind Method; D055815:Young Adult
D018727:Muscarinic Antagonists; D012601:Scopolamine