Effects of anesthesia on BOLD signal and neuronal activity in the somatosensory cortex

Abstract

Most functional magnetic resonance imaging (fMRI) animal studies rely on anesthesia, which can induce a variety of drug-dependent physiological changes, including depression of neuronal activity and cerebral metabolism as well as direct effects on the vasculature. The goal of this study was to characterize the effects of anesthesia on the BOLD signal and neuronal activity. Simultaneous fMRI and electrophysiology were used to measure changes in single units (SU), multi-unit activity (MUA), local field potentials (LFP), and the blood oxygenation level-dependent (BOLD) response in the somatosensory cortex during whisker stimulation of rabbits before, during and after anesthesia with fentanyl or isoflurane. Our results indicate that anesthesia modulates the BOLD signal as well as both baseline and stimulus-evoked neuronal activity, and, most significantly, that the relationship between the BOLD and electrophysiological signals depends on the type of anesthetic. Specifically, the behavior of LFP observed under isoflurane did not parallel the behavior of BOLD, SU, or MUA. These findings suggest that the relationship between these signals may not be straightforward. BOLD may scale more closely with the best measure of the excitatory subcomponents of the underlying neuronal activity, which may vary according to experimental conditions that alter the excitatory/inhibitory balance in the cortex.

Figure 1

Effect of anesthesia on blood oxygenation level-dependent activation. Functional images of the stimulation of two whiskers (A2 and A3) are shown from a single subject before (A), during (B), and after (C) fentanyl+isoflurane anesthesia. Before anesthesia, a cluster of activation in the whisker barrel cortex contralateral to the stimulated whiskers can be seen extending through all layers of cortex. The activated area in the cortex contracts primarily to layer IV during anesthesia, and subsequently expands during recovery. The color bar represents the magnitude of the correlation coefficient. The blood oxygenation level-dependent time course averaged across the subjects (D) showed a decrease in magnitude during anesthesia (E), followed by recovery of the signal (F). Error bars represent the s.e.m. The horizontal gray bar indicates the timing of the stimulus presentation.

Figure 2

Effect of anesthesia on local field potential, single unit, and multi-unit activity responses. Peri-stimulus histograms of local field potential (A–C), single unit (D–F), and multi-unit activity (G–I) activity in the whisker barrel cortex averaged across subjects are shown before, during, and after fentanyl+isoflurane anesthesia. Responses are shown using both 100 ms (gray) and 1 second (black) bins. Local field potential and multi-unit activity was normalized to the baseline level before stimulus presentation and drug administration. All three measures of neural activity show a biphasic response characterized by initial peak (transient) followed by a plateau (sustained). Although fentanyl+isoflurane anesthesia produced little change in local field potentials peak, both baseline and plateau response decreased and subsequently recovered. Single unit and multi-unit activity baseline, peak, and plateau decreased with anesthesia and later recovered. The gray bar indicates the stimulus presentation.

Figure 3

Effect of anesthesia on evoked responses. The mean local field potential, single unit, multi-unit activity, and blood oxygenation level-dependent responses during anesthesia are shown for each drug condition. Values are normalized to the level before anesthesia (100%) for each case. The significant differences in single unit, multi-unit activity, and blood oxygenation level-dependent responses between fentanyl (FEN) and isoflurane (ISO) are indicated with brackets. Note that mean multi-unit activity, single unit, and blood oxygenation level-dependent response show significant differences across drug conditions, whereas local field potential remains relatively unchanged.

Figure 4

Effect of anesthesia on transient and sustained components of neuronal response. The local field potential (A) and single unit (B) peak and plateau responses to whisker stimulus during anesthesia are shown for each drug condition. Values are normalized to the level before anesthesia (100%) for each case. Peak response magnitude decreased for local field potential during fentanyl anesthesia, but increased in the presence of isoflurane, with the greatest change occurring under isoflurane alone. Local field potential plateau showed a consistent decrease for each drug condition. Single unit peak and plateau magnitude decreased for all anesthesia conditions, with the greatest change occurring under isoflurane+fentanyl. Error bars represent the s.e.m. Significant changes are indicated by brackets.