Thursday, May 13, 2004

Functional Neuroimaging:
Introduction and First Article

The April 2004 issue of CNS Spectrums is titled Neuroimaging of Emotions in Psychiatry.  The forward was written by the guest editor,  Israel Liberzon.  Dr. Liberzon is associate professor of psychiatry and co-director of the Trauma, Stress, and Anxiety Research Center in the Department of Psychiatry at the University of Michigan Medical School.  Much of his work was done here.

This post includes a discussion of the Introduction to the CNS Spectrums issue and a review of the first article.  The article itself describes some of the corellations found between activation of specific parts of the brain, and general vs. specific emotional tasks.  I include some comments about the potential practical significance of this kind of work.  Please refer to my previous posts (1  2) for an introduction to the topic.  For a quick review of neuroanatomy and neuroimaging, go here

Some of you may have heard an interview with Dr. Liberzon.  He was interviewed on the Todd Mundt  show on Sept. 18, 2001.  Understandably, Posttraumatic Stress Disorder was an item of interest to the media at the time.  Unfortunately, the streaming audio is not available any longer, although you can order a tape if you want.  In any case, Dr. Liberzon is a bit of a character, and a very good scientist who is interested in the neurobiology of PTSD.  A quick (not necessarily exhaustive) Medline search turns up 26 articles that he has published in his career.  An example is Brain-Imaging Studies of Posttraumatic Stress Disorder.

In his introduction (which in not online), he points out that functional neuroimaging has "revolutionized the field of cognitive neuroscience," adding that "Investigators are now able to identify the neurocircuitry associated with specific cognitive functions."  What he means is that it is possible to present a person with a cognitive task and see what specific parts of the brain become more (or less) active when the task is performed.  Equally important, it is possible to do the same thing with emotional stimuli.  That is, you can present the person with a stimulus to provoke a particular emotional state, and see what parts of the brain get triggered.  He states, "This work carries a great promise to facilitate our our efforts to advance understanding of abnormal emotional functioning in psychiatric illness." 

From time to time, one hears that psychiatry is "not really a science," or "it's all intuitive."  those who may hold such beliefs may be interested to read what Dr. Liberzon points out: "This [neuroimaging] approach also allows us to examine empirically prevailing but difficult to test beliefs or hypotheses, such as the predominance of right hemisphere in processing emotions."  Regarding one of the papers, he comments: "They demonstrate how major hypotheses, such as the involvement of serotonergic systems in affective disorders, can be critically examined in vivo, and how a new hypothesis regarding the involvement of opioidergic systems, can be derived from neuroimaging findings. 

Science, of course, is all about generating and testing hypotheses. 

The editor of CNS Spectrums is Dr. Jack Gorman.  In the forward to the issue, he begins, "In most medical specialties, detailed knowledge of the normal anatomy, physiology, and histology of the organs of interest were known before the specifics of disease states were revealed."  He adds, "In psychiatry, and to some extent neurology, we have tried to do things in the opposite direction."  There is some precedent fro this.  The field of speech pathology was in a state of prolonged infancy until World War II.  Then, studies on soldiers with head and neck injuries led to remarkable advances in the field. 

In some ways, the strategy of studying disease states to understand normal function Is like the modern developments in some technical fields.  For example, the space program led to the development of all kinds of technology that nowadays is used in everyday living.  The principle here is that you study the exceptions, or extreme cases, in order to further your understanding of ordinary things. 

The first paper in the issue is Functional Neuroimaging Studies of Human Emotions, By K. Luan Phan, MD, Tor D. Wager, PhD, Stephan F. Taylor, MD, and Israel Liberzon, MD.  In addition to Dr. Liberzon, the only one I know is Dr. Taylor.  Dr. Taylor is one of those quietly brilliant people that inspires awe in ordinary intelligent people.  Dr. Phan trained at the  University of Michigan, but  I don't recall meeting him.  He started his training about the time I finished.  The paper they wrote is a survey of 55 PET and fMRI studies that were done to assess various aspects of brain function in response to emotional stimuli.  They set out to basically develop an atlas of corellations between different emotional responses and different parts of the brain.  This is something that is inherently difficult to do.  As you might expect, different brains can have widely different responses to the same stimuli.  In order to try to make sense of this, it is necessary to study several different people and average the results.  One of the strongest corellations they found was the relationship between fear and increased metabolic activity in the amygdala.  (If you are curious to know where all the different brain parts are, see this guide in Wikipedia.  You can see pictures of brain dissection here, and a neuroimaging atlas of the human brain here.) 

From the Harvard Whole Brain AtlasAnother strong correlation they found was that the medial prefrontal cortex often is activated in response to generic emotional stimuli.  By this I mean that the activation occurred without regard to the type of emotion involved.  As they put it: "The findings suggest that the MPFC may have a 'general' role in emotional processing."  Although they found that "no single brain region is commonly activated by all emotional tasks," the MPFC was the one that was turned on most often.  Its location in the prefrontal cortex suggests that it may be a linkage point between emotional processing and cognitive processing: one of the bridges between thinking and feeling.  They point out that "several studies have been recently published demonstrating that when subjects turn their attention inward toward themselves, as often required during general emotional processing, activity within the MPFC is increased.  Studies requiring subjects to determine if personality trait adjectives are descriptive of themselves (versus someone else) or to reflect on their own abilities/traits/attitudes have observed engagement of the MPFC."

Thus, all those internet quizzes that we see from time to time actually exercise your MPFC. 

Another area of interest in emotional neuroscience is the anterior cingulate cortex.  It has been know for a long time that injury to the ACC can lead to wither apathy or lability (instability).  Therefore, it is tempting to speculate that the ACC is involved in the regulation or modulation of emotional responses.  Their review of neuroimaging studies of the ACC shows that it is involved in detecting emotional cues.  For example, when watching a movie, your brain is flooded with all kinds of stimuli, but only some of them have any emotional significance.  The ACC seems to be involved in distinguishing the emotional figure  from the background noise.  The authors speculate about some possible functions: "As a detector of salient information in general, the ACC could serve to allocate brain resources, heighten sensitivity and direct attention to environmental cues produced by the evocative stimulus."  They found also that the ACC is activated when people are asked to recall events that are linked to a particular emotional state. 

Another finding with regard to the ACC is that it often is activated when people feel sad.  In fact, activity there is increased during the depressive phase of some types of major depressive disorder.  This kind of finding is interesting because it indicates that neuroimaging studies may someday be useful in the task of making diagnoses that are more specific than those made using current descriptive methods.  This, in turn, could lead to better selection of treatments. 

The third and final brain region described in the article is the insula.  The insula, like the ACC, is activated during emotional recall tasks.  Unlike the ACC, the insula is not activated by viewing external cues, such as movies, with emotional content.   This finding has been duplicated in studies of non-human primates.  It appears that the insula is activated most strongly in response to aversive or threat-related emotions.  Some, but no all, studies showed a specific activation of the insula in response to disgust.  It is activated when the brain receives visceral (primarily gastrointestinal) aversive sensations.  the authors speculate that the insula may be the center that is responsible for literal "gut feelings." 

The authors conclude that there is emerging evidence that some brain structures are involved in specific emotional states, whereas others serve a more general function of emotional processing.  They are hopeful that these and future studies will permit the understanding of the functional neuroanatomy of emotion. 

I already have commented that this kind of work shows that psychiatry does have a foundation in hard science, and that the generation and testing of hypotheses is possible using neuroimaging studies.  The paper by Phan et. al. shows that we are beginning to find ways of possibly increasing the specificity of psychiatric diagnoses.  This may enable us to select treatments ahead of time that are more likely to work, as opposed to the current process of trying one thing after another, without much specific indication of what treatment is most likely to do the job.

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