Hitting the Target
Although the human brain is only about 3 pounds, it is packed with 86 billion neurons and billions of other cells, including those that make up blood vessels – all encased in a protective bone structure. Finding the precise spot to target with a stimulating contact and electrode is tricky.
This deep brain stimulation procedure takes about 6 hours, during which Rezai threads a tiny 1 mm-diameter brain lead with four electrode contacts through a nickel-sized hole in the skull and down to brain structures that are part of the reward circuit. The brain wire is connected to a pacemaker in the chest that can both stimulate and record electrical activity. Only the research team can tune up or down electrical stimulation of brain within study participants.
Magnetic resonance imaging guides neurosurgeons like Rezai to be able to see the reward structures in a participant’s brain, and a computer modeling program uses those images to create a 3D map of the brain circuit. Because those patterns are highly unique among brain regions, they can be used to distinguish circuits right next to each other that perform completely different functions. Thus, the implant can be placed precisely where it needs to go.
Perhaps the most important help, though, comes from the person on the operating table, who is awake and can respond to cues (like being shown a picture of drug injection). The research team measures reactions to these cues that cause changes in brain activity both to guide placement of the implant and to calibrate the device for each patient. Because the brain and skull are not able to sense pain, and the scalp has been numbed in advance, the procedure does not hurt.
Throughout the study, Rezai and his research team offer 24/7 support to all participants and can tweak stimulation as needed. For example, one individual called over a weekend and was struggling with severe anxiety. When the researchers took another look at their brain imaging maps and the location of the implant, they knew why: too much stimulation to a nearby brain region linked to fear and emotions.
“So we moved the stimulation higher up,” Rezai explains, to get closer to the prefrontal cortex, “and his symptoms dramatically improved.”
In the search for lasting treatments for opioid addiction, a person-centric focus is necessary to accommodate individuals on their personal road to recovery. Most people need a range of strategies, including medications, counseling, and other support services. All of these are continued after an implant is placed within an individual’s brain to deliver stimulation treatment.
Another important goal of this research is to better understand how reward and behavior pathways change with craving, relapse, and recovery. Rezai and his team are looking for electrical signatures of brain changes that affect behavior: “We’re working on ways to continuously monitor addiction pathways in the brain wirelessly.”
As a first step to finding such signatures, the scientists use the implanted electrodes to measure electrical activity in the brains of people participating in the study. In time, as these paths become clearer, deep brain technology could be able to automatically sense and deliver therapy to optimize electrical signals and restore healthy rhythms.
Although the main goal of this research study is to determine safety, the team is cautiously optimistic from early results and thrilled for the improved health of the small group of participants who have undergone the procedure.
“Our first patient celebrated sobriety and complete abstinence for 3 years. He used to relapse every other week,” Rezai says, adding that another has been entirely abstinent for more than a year and is now working as a peer recovery coach.
“They go from severe, end-stage addiction to becoming therapists themselves … that’s really amazing.”
Read About This Project on NIH RePORTER
Learn more about "Feasibility of Deep Brain Stimulation as a Novel Treatment for Refractory Opioid Use Disorder."
Read More About This Program
Read about the research program, Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose.