Activation of Certain Brain Regions Correlated with Subsequent Response to CBT for PTSD

CBT for treatment-resistant depression
CBT for treatment-resistant depression
While trauma-focused cognitive-behavioral therapy is an important component of evidence-based treatment for posttraumatic stress disorder, the efficacy of treatment can vary between individuals. It is thought that some of this variability is derived from interindividual differences in the brain’s intrinsic response to trauma-related stimuli and in activity of executive functional regions. The authors of this study sought to characterize these differences using a functional MRI in patients about to undergo CBT for PTSD.

Study data published in the Journal of Neuropsychiatry and Clinical Neurosciences outline the neural underpinnings of response to cognitive behavioral therapy (CBT) for posttraumatic stress disorder (PTSD). In an imaging study that characterized the brain’s response to trauma-related stimuli, patients with greater benefit from CBT displayed higher activation of the rostral dorsomedial prefrontal cortex (rdmPFC). Patients who had responded less to CBT had lower activation in response to the same stimuli, suggesting that the neural processes associated with self-reflection may potentiate response to CBT.

Trauma-focused CBT is an important component of PTSD therapy, though its efficacy varies from individual to individual. Prior studies have hypothesized that patient-level differences in neural activation may partially drive this variability in CBT effectiveness. To characterize these differences, the investigators conducted a study of patients who were scheduled to receive trauma-focused CBT at hospitals in New York.

Eligible participants had PTSD related to sexual and/or physical trauma with no psychiatric or medical comorbidities. Following a baseline functional magnetic resonance imaging (fMRI) scan, patients underwent a 16-session course of trauma-focused CBT.

Scans were obtained while participants completed an emotional word task, which comprised of reading 48 negative or anxiety-provoking words, 48 neutral words, and 48 positive words. Blood-oxygenation-level-dependent signal was measured during exposure to each word.

CBT response was measured using the Clinician Administered PTSD Scale (CAPS) with greater change from baseline score indicating a treatment response. Multiple regression was used to assess the relationship between CBT efficacy and differential response to trauma-related and neutral stimuli.

Complete data were available for 12 patients, all of whom were women. Mean age was 35.4 years (range, 23–48 years); mean baseline CAPS score was 63.2 (range, 46–84). Following completion of CBT, mean total CAPS score was 36.9 (range, 9-54); average score reduction was 26.3 (1-57). When asked to recall words from the stimuli task, participants exhibited significantly better recall for PTSD-related words compared to neutral (P =.002) or positive words (P <.001).

In fMRI scans, PTSD-related words were found to more strongly active the rdmPFC compared to panic disorder-related, neutral, and positive words. PTSD-related words were also associated with stronger activation in a “network” of thalamic, basal ganglia, and midbrain regions.

Activation of the rdmPFC in relation to PTSD-related words was positively associated with greater CBT response. Specifically, patients who experienced greater reductions in CAPS score displayed greater activation of the rdmPFC following exposure to trauma-related words compared to neutral or positive words.

Improved treatment response was also positively associated with activation of the dorsal anterior cingulate cortex (dACC) and negatively associated with activation of the ventromedial prefrontal cortex in response to PTSD-related words. However, neither of these associations were statistically significant.

Limitations to this study include the small sample size and the fixed-effects analysis, which may limit the generalizability of the findings beyond the particular group studied. Also, as this study included only female participants with PTSD symptoms related to sexual or physical assault, it is unclear whether these findings will generalize to men or to PTSD related to other types of trauma.

In this study of patients about to undergo CBT for PTSD, the rdmPFC was activated in response to trauma-related words, though not neutral words. Activation of this region was more pronounced in CBT responders compared to patients with less symptom improvement. Investigators hypothesized that rdmPFC activation in response to trauma-related stimuli may reflect a greater inclination for self-reflection, and thus a greater capacity to benefit from CBT. However, given the small study cohort, data may not be generalizable to the larger population with PTSD. Further analysis of a larger group with various forms of trauma is necessary to better parse out the relationship between rdmPFC activation and CBT response. 


Weisholtz D, Silbersweig D, Pan H, Cloitre M, LeDoux J, Stern E. Correlation between rostral dorsomedial prefrontal cortex activation by trauma-related words and subsequent response to CBT for PTSD. J Neuropsychiatry Clin Neurosci. doi: 10.1176/appi.neuropsych.20030058