David A. Silbersweig, MD
Functional neuroimaging is a set of techniques that allow one to look at the brain in action, noninvasively, in living breathing people to be able to track changes when you think, when you feel, when you’re perceiving, when you’re behaving, in brain activity to be able to identify the circuits that are active or less active under different mind/brain conditions.
What functional brain imaging is doing is allowing us to be able to identify the areas in the brain and the circuits where there is abnormal activity, when people experience depression, anxiety, psychosis, and thereby to be able to start to pinpoint where new treatments can be developed and to allow us to start to develop a biologically based diagnostic system in the future.
We’re looking at the whole brain, but we pay particular attention to areas in the frontal lobe that are involved in controlling and being aware of our thoughts and emotions, areas in the limbic system that are involved in emotional reactivity and processing, and areas in the motivational systems of the brain deep in what we call the ventral striatum and basal forebrain. We’re also looking at how the brain coordinates its activity among these regions and how that communication or coordination may break down in disease states.
As we understand more and more about the specific brain regions and processes and circuits that are abnormally active or deficient in activity in association with specific mental states and psychiatric disorders and symptoms, then we are able to develop evidence-based, scientifically-based treatments that can, in individual patients, ultimately engage those brain regions or modulate them and decrease suffering.
In schizophrenia, with colleagues, we were able to identify brain regions associated with hallucinations, hearing voices or seeing visions of things that are not there in the world. Those results have informed work in transcranial magnetic stimulation that has experimentally to date shown that it can modulate or decrease the amount of hallucinations in patients with schizophrenia by targeting the brain regions that we have found in those studies.
In depression we have probed circuits that are involved in motivation and shown that these regions are hypoactive in patients with depression and, in particular, patients who have anhedonia, which is a lack of interest or pleasure in engaging in usual activities. Also in depression we have performed what are called multivariate analyses to identify patterns of brain activity throughout the brain that can start to separate out the depressed brain from the healthy brain and can start to form a foundation, hopefully, for future diagnostic tests, although this is still very early days.
We’re examining patients before and after cognitive behavioral therapy for post-traumatic stress disorder and are able to identify the changes in the profile of activity that accompany successful treatment, and that is associated with an increase in the executive functions of the frontal lobe that engage and modulate activity in the more primitive areas of the brain.
In borderline personality disorder, characterized by impulsivity and emotional lability, we are finding that a key area of the brain that is involved in controlling your behavior in the context of negative emotional states is deficient in its activity and in its modulation.
PMDD is pre-menstrual dysphoric disorder, and more than typical PMS and in a way that really demonstrates biologically that a subset of women, in this case five to eight percent of women, have profound changes in their mood and behavior across the menstrual cycle. We have been able to show that the brain does indeed have changes in activity in relevant emotional and behavioral control areas across the menstrual cycle and that pre-menstrually there is a profile that correlates with the symptom expression.
The aim ultimately is just like for cancer or heart disease to be able to look at profiles or tests in individual patients and to predict who is going to be able to respond to treatment A versus treatment B or some combination of treatments across modalities in a way that engages the mechanisms that are abnormal in them. We and others are now combining brain imaging, structural and functional brain imaging with genetics and epigenetic studies that look at the way in which our genetic makeup influences the disorders that we may develop or the symptoms that we may have, and the way in which the genetic changes may influence brain activity and vice-versa, although it’s early days still.
I think what is relatively unique about the Functional Neuroimaging Laboratory at Brigham and Women’s Hospital is the confluence of methods development pushing the envelope on advancing these techniques and the study of patients across the whole range of neuropsychiatric disorders in order to put together the circuit models of these conditions.
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