New Technology Helps Pinpoint the Brain Functions Involved in Addiction

Leading-edge technologies help researchers pinpoint how brain pathway activity differs between addicts and nonaddicts.

Published in Connection magazine, Winter 2017

Dr. Susan FergusonDr. Susan Ferguson and her team are using leading-edge technologies to study the pathways in the brain involved in reward, motivation, decision-making and impulsivity. “We’re in a neuroscience revolution,” says Ferguson. “The kinds of technologies we now have in our basic science research are completely changing the way we do science.”

If you love dessert, the smell of warm apple pie will make you stop and look for the source. Your mouth might water in anticipation of that first sweet bite. You might find yourself distracted until you take it.

But what if you had that same reaction to seeing a syringe full of heroin? The impulses we experience when we smell fresh apple pie are the same that someone who uses heroin experiences when they see and anticipate the drug.

So why can some people resist the urge to take a slice of pie, or a drug or a drink … yet others can’t?

Dr. Susan Ferguson thinks the answer rests in the way information moves along the pathways connecting the brain structures that regulate motivation, reward, decision-making and impulsivity. Her team is mapping these movements at a cellular level in rodents to better understand the brain functions that lead to mental health disorders like addiction.

One of their research studies looks at two pathways in the brain: the Go pathway that acts like an accelerator to go ahead and do something; and the Stop pathway that holds back an action. By mapping these two pathways, they hope to pinpoint how the brain activity of rodents that exhibit addict-like behavior in response to drugs differs from those that don’t.

“Healthy behavior results from an optimal balance of the Go and Stop pathways,” says Ferguson. “We think that exposure to drugs leads to – or intensifies – an imbalance in these two pathways and that this imbalance makes it hard to resist drugs. If we can pinpoint where the imbalance is taking place and then find ways to re-establish a balance – perhaps by tamping down the Go or bumping up the Stop – we might be able to solve this problem.”

Unprecedented precision

Dr. Lindsay Yager and RA Tess DonkelsDr. Lindsay Yager (right) is a post-doctoral fellow studying how imbalances in the brain pathways change motivation for rewards. Research associate Tess Donkels assists others in the lab with their projects and studies the differences in brain circuits activated by different drugs.

Ferguson and her team are using innovative new technologies that provide unprecedented precision to monitor and control regions of the brain in rodents. One technology (called optogenetics) is rooted in light and the other (called chemogenetics) in drugs. By modifying the neurons along the pathways to be light or drug sensitive, the team can observe and modify the brain’s activity in ways not previously possible.

Once areas of imbalance are identified, these advanced technologies may also hold the key to delivering treatments directly to the impacted areas of the brain. This could side-step the biggest current challenge in treating addiction and other psychiatric diseases like depression and ADHD: unwanted side effects.

“Because many structures in the brain have cells with the same types of receptors, our best current treatments often affect too many parts of the brain and balance isn’t restored. Many people find today’s treatments difficult to tolerate,” she explains.

Not equally compelled

Of those who drink or use drugs regularly, about 10% to 20% develop addictions. Once addicted, staying away from the substance is an ongoing challenge: 90% of recovering addicts will relapse at least once in their lifetime and many relapse repeatedly.

10% to 20% of people who use drugs regularly become addicts.

“It isn’t the intoxicating effect of a drug that causes addictive behavior, it’s how the brain responds to triggers associated with the drug experience,” says Ferguson. “Adolescents are particularly vulnerable to addiction because their brains are growing and developing, thus making it more likely that exposure to drugs will change the balance of their brain pathways.”

Promising new findings

Grad student Kanichi NakataGraduate student Kanichi Nakata is tracing the role of connections from the cortex to downstream structures of the brain in behaviors related to addiction. Though the Ferguson Lab focuses on the neuroscience of addiction, their work has implications for psychiatric conditions like obsessive-compulsive disorder and ADHD.

The team is preparing to publish a study (led by graduate student Amanda Wunsch) that looks at the role of the thalamus in regulating relapse. While most studies on relapse focus on the role of the prefrontal cortex, Ferguson’s team found that, in response to the presence of a drug or a cue, the thalamus sends an excitatory neurotransmitter to the striatum (a brain structure involved in decision-making). By selectively decreasing the activity of the thalamus, they could dampen the striatum’s response, which then decreased the desire for the drug.

“We’re super excited because this has great potential for a targeted therapy,” notes Ferguson. “If we can spur development of tailored therapies that only affect the brain structures involved, it will be more likely that patients stick with them. If we can help even one young person avoid becoming an addict, we change the trajectory of their life.”