Biological Psychiatry: An Electroencephalogram Signature of Melanin-Concentrating Hormone Neuron Activities Predicts Cocaine Seeking

Identifying biomarkers that can predict future drug use may open new avenues for individualized medicine in preventing and treating substance use disorders. Melanin-concentrating hormone (MCH) neuron activity is an integral component of rapid eye movement sleep, and rapid eye movement sleep powerfully regulates the formation and modification of emotional memories. Following cocaine self-administration and withdrawal, MCH neurons in rats exhibit reduced membrane excitability and decreased glutamate receptor, whereas enhancing MCH neuron activities in sleep decreases relapse-like behaviors, accompanied by reversal of cocaine-induced cellular changes in the reward circuit. However, MCH neuron activities can be monitored only through invasive and low-throughput in vivo recordings combined with genetic labeling of these neurons.

Surface electroencephalogram depicts the temporal dynamics of whole-brain electrical activities, though it is not known whether activities in deep structures such as the lateral hypothalamus—where MCH neurons mediate interactions between sleep and substance use—may be deduced from surface electroencephalogram signals. To evaluate whether electroencephalogram may serve as a noninvasive measure for assessing melanin-concentrating hormone neuron activities in vivo, investigators including Yao Wang, PhD (University of Pittsburgh Department of Anesthesiology and Perioperative Medicine), and Yanhua Huang, PhD (Pittsburgh Foundation Endowed Professor in Brain and Behavior Research and Associate Professor of Psychiatry), used electroencephalogram to deduce hypothalamic activities in a cell type–specific manner by recording surface electroencephalogram signals and real-time calcium (Ca2+) activities of lateral hypothalamus melanin-concentrating hormone neurons (Ca2+melanin-concentrating hormone) in adult rats.

In a paper published in Biological Psychiatry, the investigators reported that an electroencephalogram (EEG) waveform derivative—a modified theta-delta-theta peak ratio (EEGTDT ratio)—accurately tracked real-time Ca2+melanin-concentrating hormone in rats. The prediction was robust during rapid eye movement sleep (rapid eye movement sleep) and persisted through vigilance states, sleep manipulations, and circadian phases. Moreover, cocaine self-administration and long-term withdrawal altered EEGTDT ratio, suggesting shortening and circadian redistribution of synchronous melanin-concentrating hormone neuron activities. In addition, features of EEGTDT ratio indicative of prolonged synchronous melanin-concentrating hormone neuron activities predicted lower subsequent cocaine seeking. EEGTDT ratio also exhibited advantages over conventional rapid eye movement sleep measures for the predictions.

“We hope this provides a new tool for sleep researchers to analyze sleep waves – to assess sleep quality as well as to identify potential biomarkers for psychiatric diseases. This is only the beginning and we look forward to testing its translational potential,” said Dr. Huang, the study’s senior and corresponding author.

An Electroencephalogram Signature of Melanin-Concentrating Hormone Neuron Activities Predicts Cocaine Seeking
Wang Y, Li D, Widjaja J, Guo R, Cai L, Yan R, Ozsoy S, Allocca G, Fang J, Dong Y, Tseng GC, Huang C, Huang YH
Biological Psychiatry, 2024, ISSN 0006-3223, https://doi.org/10.1016/j.biopsych.2024.04.009.