Functional Brain Imaging in PTSD

A National Center for PTSD Fact Sheet

By Matthew Friedman, M.D, Ph.D.

Functional brain imaging research has confirmed what clinicians have suspected for many years, that people with PTSD exhibit altered brain processes. Furthermore, the nature of these alterations is consistent with expectations that have been based on basic human and animal research regarding how the brain handles powerful emotional input and how the brain reacts to extremely stressful situations.

Methodological issues

There have been a number of studies of functional brain imaging in PTSD. Comparison between studies is not always easy because of the different techniques utilized, such as: Positron Emission Tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI). Comparison between studies is difficult also because different studies use different measurements (e.g., cerebral blood flow vs. specific ligand binding). In addition, the conditions under which measurements have been obtained differ from one study to the next. For example, participants in one study may have been evaluated during provocative exposure to traumatic visual images while those in another study may have been evaluated while listening to an audiotape of a personal traumatic event.

Findings

Despite the methodological issues reviewed above, a number of consistent findings have emerged. From a basic science perspective, the most exciting observation is that animal models concerning fear conditioning and acute stress paradigms appear to predict the human brain imaging results quite well. Three major brain structures are implicated in the animal models:

· the amygdala, which is activated by fear and stress

· the prefrontal cortex (PFC), which has major inhibitory control over the amygdala, and

· the hippocampus, which is important for context conditioning but which is taken offline by excessive arousal states.

Thus, the major prediction for PTSD patients exposed to fearful or trauma-related stimuli is that the amygdala (and related structures) will be activated, PFC activity will be reduced, and hippocampal activity will be reduced.

Summarizing a complicated and growing literature in this field, the major findings are:

· increased amygdala activity

· decreased activity in the PFC

· decreased benzodiazepine binding in the PFC, indicating reduced capacity to inhibit amygdala activity

· decreased blood flow to the hippocampus, thalamus, orbital frontal cortex, and anterior cingulate gyrus

· excessive sensitivity to norepinephrine (indicated by reduced cerebral blood flow following administration of yohimbine).

Practical applications

Practical application of these findings is a work in progress. The most direct translation of these scientific findings into clinical practice is twofold:

· develop pharmacological and/or psychosocial interventions that will reduce activation of the amygdala and all downstream mechanisms under its control;

· develop pharmacological and/or psychosocial interventions that enhance PFC activity, since PFC activity is the brain's major mechanism for reining in the amygdala and associated structures.

Conclusions

In short, PTSD is associated with significant alterations in brain function that are consistent with what have been predicted from animal research, basic investigations on fear conditioning, and studies of acute stress. Effective current treatments can be understood within this context. Selective serotonin reuptake inhibitors (SSRIs), such as Prozac, inhibit amygdala function, and cognitive behavioral therapy (CBT) is thought to bolster cortical function, especially that of the PFC. Initiatives are now underway to develop even more effective therapeutic interventions that will normalize the abnormalities in brain function associated with PTSD.

For a good recent review of this literature, see: Hull, A. (2002). Neuroimaging findings in post-traumatic stress disorder. British Journal of Psychiatry, 181, 102-110.

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