Neuroimaging in Psychiatry: A Quarter Century of Progress

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In many respects, advances in neuroimaging have transformed the field of psychiatry over the past quarter century. The field has yet to deliver, however, on the promise of translating these advances to substantially improved care or better outcomes.
The ability to visualize and quantify brain structure and function—in vivo, noninvasively—is particularly important for psychiatric illnesses. These conditions produce disruptions of perception, cognition, emotion, and behavior that affect distinctly human mental life and behavior. Such phenomena have long been difficult to associate with biological substrates, resulting in residual dualism and stigma. The absence of macroscopic neuropathology has also separated psychiatric from neurologic disorders: the identification of a stroke or tumor with neuroimaging confirms disease localization and guides clinical decision making, and post-mortem findings help to define disorders more clearly by their demonstrable pathology in the brain. While contemporary psychiatric neuroimaging techniques have yet to deliver clinical utility, they have permitted an increasingly sophisticated understanding of brain circuit abnormalities in psychiatric disease. This increased understanding, in combination with advances in basic neuroscience, has laid a foundation for medical progress.
The late 1980s set the stage for the functional-imaging revolution, building upon earlier efforts that established structural tomographic imaging via CT. A few major academic medical centers had developed interdisciplinary positron emission tomography groups and facilities (PET, which required cyclotrons, was more precise than SPECT, single-photon emission computed tomography, which could be performed in nuclear medicine departments). 18-fluorodeoxyglucose (FDG) PET, measuring glucose metabolism associated with neuronal activity, provided a robust baseline map of resting activity, and allowed a number of important comparisons among patient and control groups. Shortly thereafter, H2(15)O PET, with multiple measures of regional cerebral blood flow (also localized to neuronal activity), allowed the isolation of differentially active brain states associated with particular mental states; what enabled this advance was the development of neuropsychological (aka cognitive-affective neuroscience) activation paradigms with control conditions, performed in the scanner.1
Neural circuit dysfunction associated with psychiatric symptoms or syndromes could now be localized. A number of fundamental findings were produced with these methods, including demonstrations of dorsolateral prefrontal hypoactivity in schizophrenia,2 subgenual prefrontal cortex hyperactivity in major depression,3 neural correlates of psychotic hallucinations,4 cortico-striatal dysfunction in OCD and related disorders,5 and amygdalar hyperreactivity in anxiety disorders and PTSD.6 Such studies established typical profiles of increased limbic emotional processing in the presence of decreased prefrontal executive processing, along with aberrant subcortical automatic processing, in psychiatric disorders.
The 1990s saw the advent of functional magnetic resonance imaging (fMRI), which provided increased spatial and temporal resolution, and more within-session repeated measurements, without the use of injections or ionizing radioactivity. The Martinos Center at Massachusetts General Hospital was a pioneer in the development of this technology. Its image-acquisition and processing methods, as well as those of a few other major centers, were combined with automated, whole-brain image-analysis methods (such as Statistical Parametric Mapping, developed in London), allowing the rapid spread of cognitive neuroscience and disease-application studies to scores of major university medical centers. Work in these settings has been highly interdisciplinary, involving teams that bridge the medical, (neuro)biological, psychological, and physical sciences.
In the 2000s, the resulting investigations have created a large literature in which psychological functions, systems-level brain processes, and their disruption in psychiatric disorders are enumerated with ever increasing precision. These phenomena include elements and interactions of sensory processing, salience detection, reward processing, stress reactivity, emotional evaluation, memory, attention, decision making, goal-directed behavior, and executive control.7,8 Specific abnormalities in each (or a combination) of these have been localized and associated with subtypes of mental illness.

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