Drug and alcohol abuse is one of the top causes of death among teenagers in the US. Deep brain stimulation is one treatment that has shown potential in helping people overcome addiction, but there are still numerous issues about brain areas that should be addressed.
Researchers are learning new things from people who used to be addicted to nicotine but no longer are because they had a brain lesion like a stroke.
Researchers at Brigham and Women’s Hospital used a new approach called lesion network mapping to map addiction remission to entire brain circuits rather than single brain regions, suggesting new therapeutic options.
Their findings were reported in the journal Nature Medicine.
“By looking beyond individual brain regions and, instead, at the brain circuit, we have found targets for addiction remission and are eager to rigorously test them through clinical trials,” remarked Michael Fox, MD, PhD, of the Brigham and Women’s Hospital’s Department of Neurology. “Ultimately, our goal is to take larger steps towards improving existing therapies for addiction and open the door for remission.”
Deep brain stimulation, transcranial magnetic stimulation, and MRI-guided focused ultrasound are examples of neuromodulation therapies that allow clinicians at the Brigham’s Center for Brain Circuit Therapeutics to directly target brain circuits and improve symptoms in ways that medication alone may not be able to achieve.
However, understanding where to aim is crucial. In a recent study, researchers examined individuals with resolving essential tremors using lesion network mapping, confirming the therapy objectives for deep brain stimulation. The authors of the study wanted to take the same strategy for addiction remission.
“Although we know a great deal about the neurobiological mechanisms in addiction, treatment options are still very limited. Our findings with essential tremor made us realize the potential of this approach to localize key brain circuits mediating symptom improvement,” explained Juho Joutsa, MD, PhD, of the Turku Brain and Mind Center and Clinical Neurosciences at the University of Turku.
Fox and colleagues analyzed data from two separate cohorts of nicotine addicts who afterwards developed a brain lesion, generally due to a stroke. Fox’s team compared lesions in patients who couldn’t quit smoking to lesions that resulted in smoking addiction remission.
They then mapped each lesion to the wider brain circuit using a database known as the human connectome. They discovered that the two smoking lesions datasets that resulted in smoking addiction remission corresponded to a single brain circuit.
Surprisingly, they also showed that a reduced risk of alcoholism matched to a similar brain circuit in a third alcoholic lesion dataset, implying a potential therapeutic, targetable neural pathway for addiction in general, rather than addiction to a specific substance.
“Although neuromodulation treatments using electricity or even brain lesions have shown promise in relieving substance addiction, the therapeutic target has been unclear,” Fox added. “Now that our study has identified a target — a specific human brain circuit — we hope to test whether targeted neuromodulation to this brain circuit provides sustainable symptom relief to our patients.”
The authors admit that there are two significant limitations to the study. The findings are based primarily on a retrospective examination of existing records, and the datasets under consideration only included specific substances of misuse. To see if their findings can be applied widely, the researchers call for prospective validation of their findings by clinical trial testing and an examination of additional addictive chemicals.
“We were excited to discover that our mapped lesions associated with addiction remission led back to a common brain circuit. While our findings point towards therapeutic targets for addiction, we need to test these targets in randomized clinical trials,” Fox said.
“We study brain lesions in the context of the brain circuit because it provides a powerful way to understand the causal links between addiction and our neuroanatomy. We have hope that we can make significant strides towards helping patients with substance use disorders.”
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