Effects of isoflurane anesthesia on resting‐state fMRI signals and functional connectivity within primary somatosensory cortex of monkeys

Abstract

IntroductionCorrelated low‐frequency fluctuations of resting‐state functional magnetic resonance imaging (rsfMRI) signals have been widely used for inferring intrinsic brain functional connectivity (FC). In animal studies, accurate estimate of anesthetic effects on rsfMRI signals is demanded for reliable interpretations of FC changes. We have previously shown that inter‐regional FC can reliably delineate local millimeter‐scale circuits within digit representations of primary somatosensory cortex (S1) subregions (areas 3a, 3b, and 1) in monkeys under isoflurane anesthesia. The goals of this study are to determine (1) the general effects of isoflurane on rsfMRI signals in the S1 circuit and (2) whether the effects are functional‐ and regional‐ dependent, by quantifying the relationships between isoflurane levels, power and inter‐regional correlation coefficients in digit and face regions of distinct S1 subregions.MethodsFunctional MRI data were collected from male adult squirrel monkeys at three different isoflurane levels (1.25%, 0.875%, and 0.5%). All scans were acquired on a 9.4T magnet with a 3‐cm‐diameter surface transmit‐receive coil centered over the S1 cortex. Power and seed‐based inter‐regional functional connectivity analyses were subsequently performed.ResultsAs anesthesia level increased, we observed (1) diminishing amplitudes of signal fluctuations, (2) reduced power of fluctuations in the low‐frequency band used for connectivity measurements, (3) decreased inter‐voxel connectivity around seed regions, and (4) weakened inter‐regional FC across all pairs of regions of interest (digit‐to‐digit). The low‐frequency power measures derived from rsfMRI signals from control muscle regions, however, did not exhibit any isoflurane level‐related changes. Within the isoflurane dosage range we tested, the inter‐regional functional connectivity differences were still detectable, and the effects of isoflurane did not differ across region‐of‐interest (ROI) pairs.ConclusionOur data demonstrate that isoflurane induced similar dose‐dependent suppressive effects on the power of rsfMRI signals and local fine‐scale FC across functionally related but distinct S1 subregions.

Effects of anesthesia on resting state BOLD signals in white matter of non-human primates

“…For example, it has been shown that with increased anesthesia levels, functional connectivity decreases between cortices in macaque monkeys [17]. Similarly, we have also reported diminishing contributions of low frequency fluctuations and correlation strengths between regions in the primary somatosensory cortex of squirrel monkeys as anesthesia levels were increased [18]. A recent observational study in rhesus monkeys on dose-dependent effects of anesthesia on regional activity also demonstrated a similar phenomenon [19].…”

Delineating the Macroscale Areal Organization of the Macaque Cortex In Vivo

“…However, unlike prior studies, which largely relied on variations of depth of anesthesia, our comparison of awake states and anesthesia also suggested that the visual networks and their connectivity with default and frontoparietal networks actually showed anesthesia-related increases in connectivity. Overall, these findings echo recent studies of the impact of anesthetics on brain differences in humans, which suggested a loss of complexity in the functional architecture of the brain (Chang et al, 2016; Hutchison et al., 2014; Peltier et al, 2005; Smith et al, 2017; Wu et al, 2016). Further work will be required to rule out other possibilities, such as differences in respiration associated with differing states (awake or anesthesia).…”

“…Unlike traditionally defined neocortical areas, which are grounded in architectonics, they are not necessarily expected to be stable across all conditions, as FC patterns are known to vary as a function of state. Previous studies have demonstrated that FC patterns are sculpted more by structural connectivity under deep anesthesia than the awake state (Barttfeld and Uhrig, 2015; Wu et al, 2016). In anesthesia states, when isoflurane levels were varied, the signal fluctuations and connectivity also exhibited distinct profiles at each level within the same animal (Smith et al, 2017; Gao et al, 2017; Peltier et al, 2005; Hutchison et al., 2014).…”

Brain Connectivity in Ateles geoffroyi: Resting-State Functional Magnetic Resonance Imaging of Working Memory and Executive Control

“…Although the methods of identification and the nomenclature for naming them have been different, similar anatomical patterns have been detected through temporal correlations. The correlated areas suggest that many elements of the resting state may be conserved across primate species and even other mammals [Damoiseaux et al, 2006;Vincent et al, 2007;Kannurpatti et al, 2008;Pawela et al, 2008;Hutchison et al, 2011;Hutchinson and Everling, 2012;Barks et al, 2015;Wu et al, 2016]. Interestingly, recent works have argued that resting-state activity may underlie rudimentary brain functioning, showing that several brain regions can be tonically active at rest, maximizing the efficiency of information transfer while preserving a low physical connection cost [Bullmore and Sporns, 2009;Hutchinson and Everling, 2012].…”

“…Low-frequency fluctuations (less than 0.1 Hz) in the blood oxygen leveldependent (BOLD) signals are detected [Fox and Greicius, 2010] and can be observed regardless of the type of anesthetic used [Horwitz, 2003;Vincent et al, 2007;Kannurpatti et al, 2008;Zhao et al, 2008;Hutchison et al, 2010;Wu et al, 2016]. Functional connectivity is defined as the temporal correlations between brain structures [Beckmann et al, 2005;Bonnefond et al, 2017].…”