A new study analyzed medical data of patients who were addicted to smoking cigarettes at the time they suffered injuries to specific regions of the brain and reported that certain brain injuries resulted in the addiction disappearing. The researchers report that these injuries were to different parts of the brain, but were all characterized by a specific pattern of brain connectivity that was associated with reductions in other types of addictions. The study was published in Nature Medicine.
Substance use disorders are a leading cause of death in young people and are considered a public health crisis in the US. They affect 8-10% of the adult population and the existing treatments are inadequate and insufficiently successful. This drives the need for new therapies. One of the alternatives considered is modulating brain regions that have to do with addiction.
“I started investigating addiction disorders already more than a decade ago when I was doing my PhD,” said study author Juho Joutsa, an associate professor, at the University of Turku. “It has bothered me for a long time that although we know so much about the neurobiological mechanisms of addiction, we haven’t been able to figure out how to treat these disorders or even which brain areas to target with treatment. With the new approach here, we were finally able to address this issue.”
New therapeutic approaches that have been tried included various types of brain stimulation and surgical interventions to targeted brain regions. However, for surgical intervention of this type, a target brain region responsible for the addiction behavior needs to be known precisely and that is not the case at the moment.
A possible path to solving this problem lies in studying patients with already existing brain injuries and identifying those with whom addictions they had disappeared after the brain injury. To that point, recent advances in medical technology made it possible to link injuries to different brain regions to changes in brain connectivity using a map of human brain connectivity called “the human connectome”.
This technology was applied by Joutsa and his colleagues in a study attempting to identify brain injuries that result in the disappearance of addiction to cigarette smoking. They examined neuroimaging and other medical data from two groups of patients, one from the University of Iowa and another from the University of Rochester, to identify those that were active daily cigarette smokers at the time of the brain injury, but who stopped smoking less than a day after their brain injury. Of these, they included in the study only the patients whose brain injury location was clear (as opposed to being unclear or diffuse).
Researchers manually traced the locations of injuries and transferred information on those locations to an atlas of the human brain they were using, the so-called MNI space (Montreal Neurological Institute and hospital coordinate system space). They then used a method called lesion network mapping (LNM) to investigate functional connectivity between the location of each injury and all other points in the brain. To verify the validity of their findings they used two separate brain connectivity maps – one derived from 126 current smokers and another one from 1,000 healthy volunteers.
Researchers created a mathematical model to relate brain connectivity at the point of injury to the outcome – quitting smoking or not quitting smoking. They reconstructed the expected damage to brain white matter tracts based on locations of the injury and estimated the associations between functional and structural brain connectivity at the site of the injury.
“Our study identified the brain network mediating addiction remission, providing directly testable targets for future treatment trials,” Joutsa told PsyPost. “We hope that this line will lead to new targeted therapies for addiction.”
The results showed that brain injuries that disrupted the smoking addiction occurred in many different parts of the brain, but they were all characterized by a specific pattern of connectivity. “This pattern involved positive connectivity to the dorsal cingulate, lateral prefrontal cortex, and insula and negative connectivity to the medial prefrontal and temporal cortex,” the researchers wrote. This circuit of neural connection was also associated with reduced alcohol addiction risk and other specific addiction measures.
“Hubs that best matched the connectivity profile for addiction remission were the paracingulate gyrus, left frontal operculum, and medial fronto-polar cortex. We conclude that brain lesions disrupting addiction map to a specific human brain circuit and that hubs in this circuit provide testable targets for therapeutic neuromodulation,” the study authors said.
“During this study, other researchers had (independently from us) tested the noninvasive brain stimulation to facilitate smoking cessation and treat alcohol use disorder with positive results,” Joutsa noted. “Although they did not target the network we identified, their peak stimulation electric fields aligned with the main cortical hub of our network, adding confidence that our findings may have therapeutic relevance.”
The study gives an important contribution for developing new ways to treat addictions. However, it should be noted that the study focused on nicotine/smoking addiction and results for other types of addictions might not be the same. Additionally, the study did not take into account whether patients were exposed to cigarettes after discharge from the hospital, nor their ability for daily functioning after the injury.
“Now that we have identified the network, we still need to figure out what is the best way to modify this network and the efficacy of a treatment targeting the network needs to be properly tested in a randomized controlled study,” Joutsa said.
“This paper was a product of a team effort and could not have been done without such an incredible team of researchers working together,” the researcher added.
The study, “Brain lesions disrupting addiction map to a common human brain circuit”, was authored by Juho Joutsa, Khaled Moussawi , Shan H. Siddiqi, Amir Abdolahi, William Drew, Alexander L. Cohen , Thomas J. Ross, Harshawardhan U. Deshpande, Henry Z. Wang, Joel Bruss, Elliot A. Stein, Nora D. Volkow, Jordan H. Grafman, Edwin van Wijngaarden, Aaron D. Boes , and Michael D. Fox.
