Mapping the circuitry of the human brain could yield important clues about how to help patients. Researchers from the Brigham’s Center for Brain Circuit Therapeutics are working to map brain circuits — sets of connected brain cells that, together, help people perform daily functions such as speaking or walking and may underlie a variety of conditions and behaviors. These circuits can be damaged by brain disease or stroke, leading to changes in behavior or symptoms. Many neuroscientists have begun to focus on imaging the brain rather than mapping its circuits, but investigators at the center are interested in how a return to brain mapping in combination with modern brain imaging techniques can be used to gain new insights. Shan Siddiqi, MD, MBBS, of the Center for Brain Circuit Therapeutics and colleagues recently published a review paper on brain mapping in Nature Reviews Neuroscience. He told us more about his area of research:

Q: What is brain mapping?

Shan Siddiqi

SS: Brain mapping is the study of how different parts of the brain interact with each other and how these interactions make us who we are. Different brain regions with different functions can interact with each other to produce human behavior. For example, we are naturally motivated to seek rewarding experiences, but some people are more motivated by rewards than others; this depends on how the “reward” region communicates with the “motivation” region. Some of these interactions are direct, while others are indirect.

I like to think of this as the organization of different functions in a country — if we want to think about the production of fuel-efficient cars, it might relate to indirect interactions between oil refineries in Texas and auto manufacturers in Michigan. If you want to modify that industry, it might help if you can navigate to Texas or Michigan (or at least contact people there). Similarly, if we want to modify a certain behavior (such as a mental illness), it helps if we can map the locations of that behavior in the brain. An important challenge is disentangling cause from effect in the brain. California is the state with the most cars and the greatest fuel consumption, but that’s not because California is the source of cars or oil. If you want to modify the auto industry, California might not be the best place to start. We have similar problems when observing the brain — it can be tricky to tell which regions are causing a behavior, which regions are affected by a behavior, and which regions are just bystanders. That is the premise of our recent work which outlines a new model for causal mapping of human brain function.

Q: What are some examples of conditions or behaviors that can be mapped to specific circuits in the brain?

SS: Depression is the condition that we have studied most thoroughly. However, this approach has also been used for addiction, movement disorders (such as Parkinson’s disease), hallucinations, and many other disorders. It has also been used to map more abstract behaviors such as moral decision-making, religiosity, and free will.

Q: What are the pros and cons of human brain mapping?

SS: The biggest pro is that it gives us treatment targets. Once we map a circuit that is causally implicated in a symptom, then we can target that circuit with focal electromagnetic brain stimulation to improve that symptom. This has led to treatments like transcranial magnetic stimulation for depression and deep brain stimulation for movement disorders, both of which can be life-changing for patients.

One important con is the potential ethical question of when to use this type of technology. When we are treating diseases, it’s straightforward — we want to make our patients better. However, when we also have circuit maps for things like morality and free will, it raises concerns about what would happen if those behaviors were targeted inappropriately.

Q: How is what we are learning about brain circuits leading to changes in treatment?

SS: We have already started using brain maps to identify treatment targets for brain stimulation. Early clinical trials have been quite promising; therefore, the circuit-targeted neuropsychiatric treatment appears to be very close to becoming a reality. It seems to work for depression, so now we’re trying to expand it to other disorders.

Q: What do you hope to see change or improve in the future regarding not only mapping in the brain but treating specific conditions?

SS: One big challenge is finding the right target for the right patient. Since each person’s brain is unique, we need to refine the mapping technology used. In the future, it would be beneficial to customize treatment based on a patient’s specific symptoms and medical history using brain mapping. A patient with severe anxiety and a history of post-traumatic stress disorder might not require the same target as a patient with profound suicidal thoughts and a history of bipolar disorder.

Read the full Nature Reviews Neuroscience paper here.