Cerebrum Winter 2021

ENTAL AND NEURODEGENERATIVE DISORDERS ARE AMONG the most costly and common causes of disability in society today. Because the brain is the most complex organ in the human body, diagnosing and treating problems when things go wrong poses enormous challenges. Even before the 1990s was designated the Decade of the Brain, the potential of neuroimaging—the technology that makes it possible to see inside the working brain—was a major focus in psychiatry. Since that time, expectations have been high that neuroimaging would move the needle forward in unraveling the mystery of mental illness.

Living in a time of such national programs as the BRAIN Initiative and Human Connectome Project, we’ve become accustomed to hearing terms such as artificial intelligence, virtual reality, and brain-machine interface. In light of the exponential increase in computational and algorithmic power, one can only assume that we have made great progress via psychiatric neuroimaging. But just how far have we actually come in the last half-century? How close are we to having neuroimaging-based tools that can be used in the clinic? Have we learned anything about diagnosis or mental illness from the vast trove of neuroimaging data that has been collected over the years? I wish I could point to specific examples where the widening use of neuroimaging is beginning to help the mentally ill, but we are just not there yet. As an undergraduate electrical engineering student at the University of Kansas in 1991, I became enthralled with magnetic resonance imaging (MRI), which makes it possible to see inside the body, noninvasively and safely, using magnetic fields and radio waves. This was the beginning of a career in brain imaging that led me to spend 12 years in a psychiatry department at Johns Hopkins where, I like to joke, I was an engineer “studying the psychiatrists.” In reality, it was a fascinating experience, as I learned the complexity of the problems under study, saw the potential for applying engineering and signal processing principles, and gravitated to the emerging specialty of psychiatric neuroimaging. It didn’t take me long to realize that the study of psychiatric disorders is extremely difficult, in part, since the assessment of the individual is mainly based on their medical history and symptoms they are experiencing at that moment. And while these assessments can be reliable up to a point, they largely lack biological validity. If someone is feeling depressed, for example, they may be diagnosed with depression. If, however, a few months later they are experiencing hallucinations or

their thoughts are confused, the diagnosis is likely to be schizophrenia or bipolar disorder. There are no objective tests to confirm or rule out any of these disorders. Nor are there cures, although existing treatments may mitigate symptoms. But even determining appropriate treatment can be a formidable challenge, often requiring sequential effort to determine, and the wrong treatment can muddle diagnosis and, in some cases, the wrong medication can make a condition worse. The Promise of Magnetic Imaging MRI has been used to visualize the size (i.e., volume) of various brain structures for over 40 years now. And for almost 30 years we have been able to see fluctuations in brain activity using a technique called functional MRI (fMRI), which tracks magnetic signals that reflect changes in blood flow and oxygenation level associated with neuronal activity. The discovery of fMRI raised hopes for a clinical breakthrough in assessment and treatment. Beyond the challenges that lay before them, the psychiatric research community saw the potential that neuroimaging held for helping patients whose lives were disrupted by a malfunctioning brain. We believed we were on the verge of better understanding how the brain worked, and developing tools and treatments to address what are now understood to be brain disorders, including depression, schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. Using neuroimaging to identify disrupted brain regions could provide information useful to develop and evaluate new treatments, enable prediction of individual response to such treatments, and help subtype individuals (e.g., schizophrenia and schizoaffective disorder). The obstacles, however, turned out to be more formidable, and progress slower than we would have liked. Our challenges and successes might be best understood through the evolution of five different eras.

20 DANA FOUNDATION CEREBRUM | Winter 2021

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