Brainstem Stimulation Increases Functional Connectivity of Basal Forebrain-Paralimbic Network in Isoflurane-Anesthetized Rats

Abstract

Brain states and cognitive-behavioral functions are precisely controlled by subcortical neuromodulatory networks. Manipulating key components of the ascending arousal system (AAS), via deep-brain stimulation, may help facilitate global arousal in anesthetized animals. Here we test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO) under light isoflurane anesthesia, associated with loss of consciousness, leads to cortical desynchronization and specific changes in blood-oxygenation-level-dependent (BOLD) functional connectivity (FC) of the brain. BOLD signals were acquired simultaneously with frontal epidural electroencephalogram before and after PnO stimulation. Whole-brain FC was mapped using correlation analysis with seeds in major centers of the AAS. PnO stimulation produced cortical desynchronization, a decrease in d-and h-band power, and an increase in approximate entropy. Significant increases in FC after PnO stimulation occurred between the left nucleus Basalis of Meynert (NBM) as seed and numerous regions of the paralimbic network. Smaller increases in FC were present between the central medial thalamic nucleus and retrosplenium seeds and the left caudate putamen and NBM. The results suggest that, during light anesthesia, PnO stimulation preferentially modulates basal forebrain-paralimbic networks. We speculate that this may be a reflection of disconnected awareness.

Neural effects of propofol-induced unconsciousness and its reversal using thalamic stimulation

“…The stimulation increased cortical spike rates, diminished slow-frequency power, and re-instated higher-frequency power. Our studies are consistent with rodent studies that have shown recovery of consciousness and awake-like cortical dynamics after stimulation in a variety of brain regions (Pillay et al, 2014;Solt et al, 2014).…”

Restoring Conscious Arousal During Focal Limbic Seizures with Deep Brain Stimulation

“…Multiple drug infusion studies have solidified its role as a sleep regulatory region (Lopez-Rodriguez et al 1994;Bourgin et al 1995;Marks and Birabil 1998;Ahnaou et al 1999). More recently, stimulation of the PnO has been shown to induce cortical desynchronization in lightly anesthetized rats as well as increase functional connectivity to basal forebrain-paralimbic structures such as the nucleus basalis of Meynert (Pillay et al 2014).…”

“…While therapeutic electrodes have been implanted in infratentorial targets very near PnO in humans, such as the pedunculopontine nucleus (Mazzone et al 2005;Plaha and Gill 2005), a supratentorial target may offer a decreased surgical risk profile. Of note, the nucleus basalis is supratentorial, is in the ascending projection pathway of PnO, and has widespread cholinergic and noncholinergic arousal connections with the neocortex Pillay et al 2014;Motelow et al 2015) making it a promising potential future target for stimulation.…”

Propofol anesthesia reduces Lempel-Ziv complexity of spontaneous brain activity in rats

“…Briefly, 6 adult, male, Sprague-Dawley rats were scanned during light and deep sedation with propofol at 20 or 40 mg/kg/h equivalent to conscious sedation and unconsciousness [10,12]; the order of doses was reversed in consecutive experiments. The animals’ lungs were artificially ventilated; arterial blood pressure, heart rate, arterial oxygen saturation, core temperature, respiratory rate, inspired and expired oxygen and carbon-dioxide concentrations were continuously monitored.…”

“…From all sliding windows, a common subset of voxels with ReHo values exceeding the threshold of mean + 2 standard deviations (SD) was defined as the region of interest. This threshold was previously found optimal to delineate functionally connected regions of the brain with all voxels present at both anesthetic concentrations [10,12]. …”