487 Cholinergic Blockade Alters Hippocampal-posterior Cingulate Cortex Synchrony During Episodic Memory Encoding

Abstract

INTRODUCTION: The posterior cingulate cortex (PC) is an important region for episodic memory. Its synchrony with the hippocampus in the theta frequency, in particular, has been shown to underlie successful memory encoding. Cholinergic signaling is another important component of episodic memory, and manipulation of cholinergic signaling is often employed to better understand memory. However, the specific relationship between cholinergic signaling and hippocampal-PC synchrony has not been explored. METHODS: Eight patients with intracranial electrodes underwent two sessions of a free recall task, one in which they were given scopolamine and the other, saline. EEG recordings from these sessions during early and late encoding were then analyzed. The phases of high (5-9 Hz) and low (2-5 Hz) theta frequencies were calculated with hilbert transform, and synchrony was measured with phase-locking value (PLV), calculated for each electrode pair. Permutation tests were used to compare PLV between saline and scopolamine conditions for each electrode pair, producing a distribution of z-scores for each region-region connection. Electrodes were grouped into the regions anterior hippocampus (AH), posterior hippocampus(PH), and PC. The z-score distributions were compared against a distribution centered at zero with a t-test. RESULTS: The z-score distributions from permutation were significantly different from a null distribution for AH-PC connections in the left and right hemispheres during late encoding in high theta frequencies; AH-PH and PH-PC connections in the right hemisphere during early encoding in low theta frequencies; and PH-PC connections in the right hemisphere during late encoding in low theta frequencies. CONCLUSIONS: Changes in synchrony between PC, AH, and PH due to cholinergic blockade differ between low and high theta as well as early and late encoding.