Changes in nonhuman primate brain function following chronic alcohol consumption in previously naïve animals

Abstract

Introduction Chronic alcohol abuse is associated with neurophysiological changes in brain activity; however, these changes are not well localized in humans. Non-human primate models of alcohol abuse enable control over many potential confounding variables associated with human studies. The present study utilized high-resolution magnetoencephalography (MEG) to quantify the effects of chronic EtOH self-administration on resting state (RS) brain function in vervet monkeys. Methods Adolescent male vervet monkeys were trained to self-administer ethanol (n=7) or an isocaloric malto-dextrin solution (n=3). Following training, animals received 12 months of free access to ethanol. Animals then underwent RS magnetoencephalography (MEG) and subsequent power spectral analysis of brain activity at 32 bilateral regions of interest associated with the chronic effects of alcohol use. Results Results demonstrate localized changes in brain activity in chronic heavy drinkers, including reduced power in the anterior cingulate cortex, hippocampus, and amygdala as well as increased power in the right medial orbital and parietal areas. Discussion The current study is the first demonstration of whole-head MEG acquisition in vervet monkeys. Changes in brain activity were consistent with human electroencephalographic studies; however, MEG was able to extend these findings by localizing the observed changes in power to specific brain regions. These regions are consistent with those previously found to exhibit volume loss following chronic heavy alcohol use. The ability to use MEG to evaluate changes in brain activity following chronic ethanol exposure provides a potentially powerful tool to better understand both the acute and chronic effects of alcohol on brain function.

Functional Brain Networks and Alcohol Consumption: From the Naïve State to Chronic Heavy Drinking

“…Animals were placed in a supine position and artificially ventilated. These preparations are consistent with our previous reports 22,23 .…”

“…MEG recordings were acquired under EtOH naïve conditions (Baseline), after completion of the induction phase (Post Induction) and after 180 open access drinking days (Free Access). Control animals were not utilized in the current study due to the previously wellestablished effects of EtOH in this model contrasting EtOH-exposed and control animals [14][15][16][17][18][19][20][21]23 .…”

“…A limitation of studies involving humans is the significant individual variation in history regarding substance use, comorbid exposure to substances, and living environments. NHP models 13 have demonstrated that daily drinking for 15 months causes functional and genomic changes across the brain when contrasted against the alcohol naïve brain [14][15][16][17][18][19][20][21] , as well as reorganization of brain networks measured by fMRI 22 and significantly altered signal power of multiple bandwidths across the brain using magnetoencephalography (MEG) 23 .…”

Magnetoencephalography: Clinical and Research Practices

“…MEG data are acquired with a sampling rate of 600–2400 Hz, and data are preprocessed offline with synthetic 3rd order gradiometry, DC-offsetting, and powerline filtering [ 11 , 117 , 118 , 119 ]. The SAM(g2) method is comprised of a sequence of steps in which the sensor data are filtered from 20–70 Hz and then beamformed in single-state mode.…”

“…These studies are performed both humans and nonhuman primates. The cognitive and precognitive tasks developed can be used to probe network behavior in each of these conditions, and are deployed as translational assays of function in populations as diverse as children, Veterans with posttraumatic stress disorder (PTSD) and/or traumatic brain injury (TBI) [ 117 , 118 ], normal adults, and nonhuman primates [ 119 , 121 ]. The goal in coupling MEG with probes of brain function is to develop a set of metrics that typify a particular disorder, and may eventually lead to better diagnosis and clinical interventions.…”