Human Cocaine and Heroin Addiction May be Tied to Impairments in a Specific Brain Region

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Human Cocaine and Heroin Addiction May be Tied to Impairments in a Specific Brain Region  

Jim Windell

          What does the prefrontal cortex and the connectivity of the tract between the prefrontal cortex have to do with drug addiction?

          The prefrontal cortex is the part of the brain that is critical for regulating higher-order executive functions. But, a lesser known region of the brain is the habenula. The habenula is a paired structure in the epithalamus, which serves to connect more recently evolved structures involved in executive function in the neocortex and limbic forebrain with ancient areas that process sleep, pain, and reward in the midbrain and hindbrain.

           More importantly, the habenula is the area that plays a critical role in reward and reward-associated learning, and it has emerged as a key driver of drug-seeking behaviors in animal models of addiction. Specifically, signaling from the prefrontal cortex to the habenula is disrupted in rodent cocaine addiction models, implicating this prefrontal cortex to habenula circuit in withdrawal and cue-induced relapse behaviors. However, until now, the prefrontal cortex-habenula path has remained poorly understood in the human brain. Furthermore, its involvement in the neuropathological effects of drugs other than cocaine has not been previously explored.

           A new study recently published October 6 in Neuron and conducted by researchers from the Icahn School of Medicine at Mount Sinai and Baylor College of Medicinehas taken a look at the connectivity of the tract between the prefrontal cortex and the habenula. Using diffusion magnetic resonance imaging (MRI) tractography, a team led by Rita Z. Goldstein, Ph.D., and Junqian Xu, Ph.D., investigated the microstructural features of the prefrontal cortex- habenula circuit in people with cocaine or heroin addiction compared to healthy control participants. Diffusion MRI tractography uses noninvasive brain imaging to model fiber bundles in the living human brain. This study was a first of a kind in studying the human brain in this manner.

           The results suggest that white matter in the brain that was previously implicated in animal studies has now been shown to be specifically impaired in the brains of people with addiction to  cocaine or heroin.

           According to Sarah King, a Ph.D. student in Neuroscience in the Graduate School of Biomedical Sciences at Icahn Mount Sinai, “In addition to identifying microstructural differences, specifically reduced coherence in the orientation of the white matter fibers in the cocaine-addicted group that comprised both current cocaine users and those with short-term abstinence, we extended results beyond cocaine (a stimulant) to heroin (an opioid), suggesting that abnormalities in this path may be generalized in addiction.”

           King, who led the analyses and is first author of the paper, went on to say that, “Importantly, we found that across all addicted individuals, greater impairment was correlated with earlier age of first drug use, which points to a potential role for this circuit in developmental or premorbid risk factors.”

           The authors point out that the results of this advance ongoing research in the field by targeting a previously unexplored circuit in the pathophysiology of addiction in humans, where deficits may predispose an individual to both the development of drug addiction and to relapse and which may be potentially amenable for individually tailored treatment or prevention efforts.

             To read the original report, find it with this reference:

King, S., Gaudreault, P. O., Malaker, P., Kim, J. W., Alia-Klein, N., Xu, J., & Goldstein, R. Z. Prefrontal-Habenular Microstructural Impairments in Human Cocaine and Heroin Addiction. (2022).  Neuron (2022). DOI: 10.1016/j.neuron.2022.09.011.; Also available at SSRN 4072042.

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