Central cholinergic pathway involvement in the regulation of pupil diameter, blink rate and cognitive function

Neuroscience. 2016 Oct 15:334:180-190. doi: 10.1016/j.neuroscience.2016.08.009. Epub 2016 Aug 13.


Anticholinergic medications can exert their effects by acting on muscarinic receptors, which mediates the function of acetylcholine in the central nervous system. Acetylcholine plays a number of roles, particularly in regard to the control of muscle activity and normal cognitive functioning. Eighteen subjects were recruited into the human, double-blind, placebo-controlled, four-way crossover study. Pupil diameter and blink rate were assessed at rest while eye tracking technology recorded eye characteristics. Thereafter a cognitive task was performed, where pupil size and blink rate were once again measured. Assessments were performed pre-ingestion, 0.5h and 2h following the ingestion of a strong centrally acting anticholinergic (promethazine hydrochloride), a moderate centrally acting anticholinergic (hyoscine hydrobromide), an anticholinergic devoid of central effects (hyoscine butylbromide) and placebo. At rest, hyoscine hydrobromide was the only medication to increase pupil diameter and no drug intervention influenced blink rate. During performance of the cognitive task, hyoscine hydrobromide increased pupil diameter and promethazine increased blink rate. Promethazine was the only medication to influence the modified attention network test (ANT) by increasing the conflict effect and grand mean reaction time (RT). Pupil diameter and blink rate were both influenced by the central anticholinergics during performance of the cognitive test, thus highlighting the importance of central cholinergic pathways in the control of pupil diameter and blink rate. The collective effects of central anticholinergics on the modified ANT and on pupil diameter and blink rate during its performance, conveys the importance of central cholinergic pathways in cognitive function.

Keywords: anticholinergic; attention; blink rate; eye tracker; motor control; pupil diameter.

MeSH terms

  • Attention / drug effects
  • Attention / physiology
  • Blinking / drug effects*
  • Blinking / physiology
  • Butylscopolammonium Bromide / pharmacology
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism
  • Cholinergic Antagonists / pharmacology*
  • Cognition / drug effects*
  • Cognition / physiology
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Linear Models
  • Male
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neuropsychological Tests
  • Organ Size
  • Promethazine / pharmacology
  • Pupil / drug effects*
  • Pupil / physiology
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Rest
  • Scopolamine / pharmacology
  • Time Factors
  • Young Adult


  • Cholinergic Antagonists
  • Butylscopolammonium Bromide
  • Scopolamine
  • Promethazine