Anesthetic Effects on Neuronally-based Resting-state Functional Connectivity (S43.008)

To investigate the impact of tribromoethanol, isoflurane, and ketamine/xylazine on neuronally- and hemodynamically-based functional connectivity. Resting-state functional connectivity (RSFC) captures correlated signals among brain regions while at rest. In humans, RSFC is imaged using fMRI by tracking spontaneous blood-oxygen-level-dependent (BOLD) fluctuations. Although distinct anesthetics have been shown to modulate RSFC in mice via a BOLD-like hemodynamic signal, the exploration of their effects on the neuronally based signals is less well known. We used Thy1-GCaMP6f mice with a genetically encoded calcium indicator in excitatory pyramidal neurons, to detect neuronal calcium activity. We implanted a chronic imaging window, followed by GCaMP fluorescence and optical intrinsic signal imaging. Each mouse sequentially received each of the anesthetics-tribromoethanol, isoflurane, or ketamine/xylazine-in random order. We calculated several connectivity metrics including a bihemispheric connectivity index (BCI) to determine the overall connectivity between homotopic regions on each hemisphere. Correlation coefficients were z-transformed to enable comparisons between groups. Tribromoethanol consistently exhibited the highest BCI values. Tribromoethanol's z-transformed BCI for neuronal GCaMP and hemodynamic connectivity was significantly higher than the metrics for ketamine/xylazine and isoflurane (tribromoethanol 1.06, ketamine/xylazine 0.67, isoflurane 0.80, p < 0.01 for tribromoethanol vs. others). Ketamine/xylazine displayed reduced variability when compared to tribromoethanol and isoflurane. All anesthetics had high correlations between the GCaMP signal and the oxy-hemoglobin signal, with ketamine/xylazine displaying the highest z-transformed correlation of the group (ketamine/xylazine 1.33, tribromoethanol 1.09, isoflurane 1.01), p < 0.01 for KX vs. others). While all three anesthetics demonstrate varied effects, tribromoethanol notably optimized BCI compared to ketamine/xylazine and iso. Isoflurane displayed marked variability. This study underscores the importance of anesthetic selection for studies involving functional connectivity. Disclosure: Mr. Lai has nothing to disclose. Tao Qin has received personal compensation for serving as an employee of Helix Nanotechnologies. Prof. Boas has received personal compensation for serving as an employee of Boston University. An immediate family member of Prof. Boas has received personal compensation for serving as an employee of Massachusetts General Hospital. The institution of Prof. Boas has received research support from NIH. The institution of Dr. Sakadzic has received research support from National Institute of Health. Dr. Ayata has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quris. Dr. Ayata has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurelis. The institution of Dr. Ayata has received research support from NIH. The institution of Dr. Ayata has received research support from Takeda. The institution of Dr. Ayata has received research support from Neurelis. Dr. Chung has received research support from NIH/NINDS. Dr. Chung has received research support from The Aneurysm and AVM Foundation.