Mapping the Human Brain: Advancing Treatment with Technology and AI

A researcher at Massachusetts General Hospital is leading a five-year, $24 million grant from the National Institutes of Health (NIH) to map the brain's connections in unprecedented detail. Mapping this "connectome" is critical for knowing which connections to target with neuromodulation techniques, including deep brain stimulation (DBS), which is used to treat motor disorders, such as Parkinson's disease, Tourette syndrome, and dystonia, as well as psychiatric disorders such as obsessive-compulsive disorder (OCD) and depression.

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"We know that deep brain stimulation works, but we are not exactly sure how it works," says Anastasia Yendiki, PhD, associate investigator at Massachusetts General Hospital and director of circuit analysis at the Athinoula A. Martinos Center for Biomedical Imaging. "We are going to map these connections in human brains at a microscopic scale for the first time to give clinicians a clear picture of how brain regions are interconnected—and hopefully improve how these diseases are targeted."

Mapping the Neural Pathways of the Brain Connectome

Different parts of the brain must communicate with each other for us to think, move, speak, and behave. These communications occur via signals that travel along a complex network of neural pathways—the brain connectome. Scientists and clinicians know surprisingly little about this network or the relationship between the brain's structure and function, Dr. Yendiki says. "But we do know that some of these connections and communications are not normal in certain types of disorders, including psychiatric disorders and motor disorders."

Mass General's grant is part of the Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, which aims to advance the technology necessary to map brain structure and function in both animal and human brains comprehensively. Thus far, most of the information researchers have about neural pathways comes from non-human research, which allows for more invasive investigative procedures. Some of that information can be translated to humans. However, a more detailed map of the human brain connectome is critical for better understanding and treating human brain disorders.

Dr. Yendiki's team will leverage a one-of-a-kind, state-of-the-art scanner: the Connectome 2.0, located at the Martinos Center. The machine was designed to image the human connectome in vivo in human subjects with very high fidelity, taking diffusion MRI technology beyond what was previously possible.

The scanner can capture images with unprecedented resolution because it can nearly double the previous maximum gradient strength and triple the previous maximum slew rate. The machine has a one-of-a-kind head gradient coil that minimizes peripheral nerve stimulation, and it contains technology to minimize distortions and artifacts.

The research team will use the Connectome 2.0 to conduct extensive scans of cadaver human brains, which will then be imaged with cutting-edge light and X-ray microscopy techniques. These data will be combined to build an unprecedented map of the brain connectome at different scales. The ultimate goal is to develop machine learning models that can map the connectome accurately from MRI scans that can be collected from living human subjects.

Improving the Efficacy of Deep Brain Stimulation

DBS is an invasive, elective procedure to implant electrodes in the brain and deliver electrical impulses to control or reset abnormal brain activity. It is used to treat several psychiatric and motor conditions when other treatments are not effective.

Neurosurgeons place DBS electrodes so that they stimulate brain circuits associated with a specific disorder, but without affecting circuits that control other important brain functions. Although DBS is generally safe and effective in appropriately selected patients, it sometimes has side effects. For example, depression may be a side effect of DBS for the treatment of Parkinson's disease. A more precise understanding of the intricate pathways in the human brain will help neurosurgeons more accurately place electrodes for better symptom relief and less risk.

Parkinson's disease is an example of a disorder where clinicians have two good target areas for DBS that seem to be effective in a large number of patients. But for other disorders, particularly those in the psychiatric realm, there is more debate around the best locations to target. Dr. Yendiki and colleagues recently published the results of a study mapping the connections of the zona incerta, which suggest that this brain area may be an effective target for DBS for OCD.

The imaging technologies that will be developed by the new grant will greatly enhance the accuracy of such brain mapping studies in the future, she says. "We're going to be able to map the connections directly in human brains at microscopic scale for the first time to give clinicians a clear picture of the brain circuits that are implicated in different disorders."

Connecting Healthcare, Technology, and Artificial Intelligence (AI)

Dr. Yendiki will work closely with investigators at seven other sites, including co-principal investigators Suzanne Haber, PhD, of the University of Rochester, and Elizabeth Hillman, PhD, of Columbia University. She is excited about the opportunity to work with this unique team on a truly interdisciplinary project.

"At Mass General, we are at a place that is an intersection of excellent healthcare and healthcare research, as well as all the research happening in academic institutions within the Boston area," Dr. Yendiki says. "We are situated to use all the latest developments in machine learning and AI, as well as the unique instrumentation available here at Mass General for imaging. We can benefit from new ideas in many fields, from engineering to healthcare and clinical practice to neuroscience."

Learn more about the Martinos Center for Biomedical Imaging

Learn more about Mass General Neuroscience