PT  - JOURNAL ARTICLE
AU  - William M. Howe
AU  - Anne S. Berry
AU  - Jennifer Francois
AU  - Gary Gilmour
AU  - Joshua M. Carp
AU  - Mark Tricklebank
AU  - Cindy Lustig
AU  - Martin Sarter
TI  - Prefrontal Cholinergic Mechanisms Instigating Shifts from Monitoring for Cues to Cue-Guided Performance: Converging Electrochemical and fMRI Evidence from Rats and Humans
AID  - 10.1523/JNEUROSCI.5809-12.2013
DP  - 2013 May 15
TA  - The Journal of Neuroscience
PG  - 8742--8752
VI  - 33
IP  - 20
4099  - http://www.jneurosci.org/content/33/20/8742.short
4100  - http://www.jneurosci.org/content/33/20/8742.full
SO  - J. Neurosci.2013 May 15; 33
AB  - We previously reported involvement of right prefrontal cholinergic activity in veridical signal detection. Here, we first recorded real-time acetylcholine release in prefrontal cortex (PFC) during specific trial sequences in rats performing a task requiring signal detection as well as rejection of nonsignal events. Cholinergic release events recorded with subsecond resolution (“transients”) were observed only during signal-hit trials, not during signal-miss trials or nonsignal events. Moreover, cholinergic transients were not observed for consecutive hits; instead they were limited to signal-hit trials that were preceded by factual or perceived nonsignal events (“incongruent hits”). This finding suggests that these transients mediate shifts from a state of perceptual attention, or monitoring for cues, to cue-evoked activation of response rules and the generation of a cue-directed response. Next, to determine the translational significance of the cognitive operations supporting incongruent hits we used a version of the task previously validated for use in research in humans and blood oxygenation level-dependent (BOLD)-functional magnetic resonance imaging. Incongruent hits activated a region in the right rostral PFC (Brodmann area 10). Furthermore, greater prefrontal activation was correlated with faster response times for incongruent hits. Finally, we measured tissue oxygen in rats, as a proxy for BOLD, and found prefrontal increases in oxygen levels solely during incongruent hits. These cross-species studies link a cholinergic response to a prefrontal BOLD activation and indicate that these interrelated mechanisms mediate the integration of external cues with internal representations to initiate and guide behavior.