Muscarinic M1, but not M4, receptor antagonism impairs divided attention in male rats.

Divided attention may be more important than ever to comprehend, given ubiquitous distractors in modern living. In humans, concern has been expressed about the negative impact of distraction in education, the home, and the workplace. While acetylcholine supports divided attention, in part via muscarinic receptors, little is known about the specific muscarinic subtypes that may contribute. We designed a novel, high-response rate test of auditory sustained attention, in which rats complete variable-ratio runs on one of two levers, rather than emitting a single response. By doing this, we can present a secondary visual distractor task during some trials, for which a correct nosepoke response is reinforced with a more palatable food pellet. The nonspecific muscarinic antagonist scopolamine impaired performance, and slowed and reduced lever press activity. We then explored antagonists that preferentially block the M1 and M4 subtypes, because these receptors are potential therapeutic targets for cognitive enhancers. Telenzepine, an M1-preferring antagonist, impaired divided attention performance, but not performance of the attention task without distraction. Telenzepine also had fewer nonspecific effects than scopolamine. In contrast, the M4-preferring antagonist tropicamide had no effects. Analysis of overall behavior also indicated that accuracy in the main attention task decreased as a function of engagement with the distractor task. These results implicate the M1 receptor in divided attention.

The influence of dopaminergic medication on balance automaticity in Parkinson's disease.

BACKGROUND: Studies have shown that dual-task standing balance in Parkinson's disease (PD) is significantly diminished. Additionally, it is well accepted that dopaminergic medication improves dynamic balance (Berg Balance Scale, mini-BESTest), but standing balance (force platform posturography) may suffer. What remains unknown is how dopaminergic medication influences standing balance automaticity in PD. RESEARCH QUESTION: Does dopaminergic medication improve standing balance automaticity during a phoneme monitoring dual-task in PD? METHODS: This was a cross-sectional study. Sixteen subjects with PD completed single- and dual-task standing with eyes open and eyes closed for 3 min each in off and on medication states. 95% confidence ellipse area, anterior-posterior sway velocity, medial-lateral sway velocity, and integrated time to boundary were calculated. Data were analyzed with a repeated measures ANOVA. RESULTS: Dopaminergic medication significantly increased ellipse area (p = 0.002) and decreased the performance on the secondary task (p = 0.004). Different eyes conditions (open vs. closed) significantly increased both sway velocities (anterior-posterior = p < 0.001, medial-lateral = p < 0.001), and increased integrated time to boundary (p < 0.001). There were also task by eyes condition interaction effects for anterior-posterior velocity and integrated time to boundary (p = 0.015 and p = 0.009, respectively). Increases in sway velocity and integrated time to boundary seen in the eyes condition and interaction effects are traditionally interpreted as poorer balance performance. However, in the context of stability/maneuverability tradeoff, the changes may indicate an increase in freedom of movement instead of a decrease in stability. SIGNIFICANCE: The data did not support a medication-induced improvement in automaticity, as measured by significant medication by task interactions. An alternate interpretation for medication-induced balance changes in PD includes an increase in maneuverability without sacrificing stability after taking dopaminergic medication.