Frontal cortical functional connectivity is impacted by anaesthesia in macaques

Abstract

A critical aspect of neuroscience is to establish whether and how brain networks evolved across primates. To date, most comparative studies have used resting-state functional Magnetic Resonance Imaging (rs-fMRI) in anaesthetized non-human primates and in awake humans. However, anaesthesia strongly affects rs-fMRI signals. The present study investigated the impact of the awareness state (anaesthesia vs. awake) within the same group of macaque monkeys on the rs-fMRI functional connectivity (FC) organization of a well characterized network in the human brain, the cingulo-frontal lateral network. Results in awake macaques revealed a similar FC pattern to that previously uncovered in the human brain. Rostral seeds in the cingulate sulcus exhibited stronger correlation strength with rostral compared to caudal lateral frontal cortical areas while caudal seeds in the cingulate sulcus displayed stronger correlation strength with caudal compared to anterior lateral frontal cortical areas. Critically, this inverse rostro-caudal functional gradient was abolished under anaesthesia. This study demonstrates that the FC pattern of cingulo-frontal cortical networks is preserved from macaque to human but some of its properties can only be observed in the awake state, warranting significant caution when comparing FC patterns across species under different states.

Resting-state fMRI-based screening of deschloroclozapine in rhesus macaques predicts dosage-dependent behavioral effects

“…Seven subjects underwent anesthetized functional MRI scanning using isoflurane levels below those shown to adversely impact functional connectivity in frontal cortex [22] ( Figure 1 ). To assess the changes in brain-wide functional connectivity following DCZ administration, we calculated functional connectivity using predetermined regions of interest (ROIs) based on the cortical hierarchical atlas (CHARM) [16] and subcortical hierarchical atlas (SARM) [17] for rhesus macaques ( Figure 2A and C ).…”

“…Consequently, we conducted an rs-fMRI experiment with seven rhesus monkeys and assessed the effect of different dose levels of DCZ. Animals were only lightly anesthetized throughout the scan sessions so that the resting-state brain activity was preserved as closes to that of the awake state as possible [11,22]. We hypothesized that low-dose DCZ, which is functionally effective in chemogenetic experiments in non-human primates [5,28], would not affect resting-state functional connectivity in non-transfected animals.…”