July 28, 2017
2 min read

NIMH study identifies neural markers of treatment success in PTSD

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Recent findings from two studies suggested the frontopolar cortex plays a significant role in successful prolonged exposure therapy for PTSD.

“Although psychotherapy is widely utilized and highly effective, it requires a considerable investment of time and effort, with roughly one-quarter of patients not completing treatment and one-third to one-half of those who complete treatment remaining symptomatic and impaired,” Gregory A. Fonzo, PhD, of Stanford University School of Medicine, and colleagues wrote. “It is therefore critical to identify who will benefit from this treatment and why — information that remains largely unknown.”

To identify traits of individuals most likely to benefit from PTSD psychotherapy, researchers conducted functional MRI while individuals with PTSD completed three tasks assessing emotional reactivity and regulation. Study participants were randomly assigned to receive immediate prolonged exposure treatment (n = 36) or a waiting list condition (n = 30). To determine if predictive activation patterns indicated causal influence within circuits, a random subset of participants who received prolonged exposure (n = 17) underwent single-pulse transcranial magnetic stimulation (TMS) concurrent with functional MRI.

At baseline, participants with greater treatment-related symptom reductions exhibited higher dorsal prefrontal activation and lower left amygdala activation during emotion reactivity.

Further, participants with greater treatment-related symptom reductions at baseline exhibited better inhibition of the left amygdala induced by single TMS pulses to the right dorsolateral prefrontal cortex and greater ventromedial prefrontal/ventral striatal activation during emotional conflict regulation.

Reappraisal-related activation did not significantly moderate treatment effect.

Brain biomarkers

To assess changes in brain function after prolonged exposure therapy, researchers conducted a second MRI approximately 4 weeks after the last treatment session.

Researchers observed treatment-specific changes only during cognitive reappraisal of negative images.


Psychotherapy increased lateral frontopolar cortex activity and connectivity with ventromedial prefrontal cortex/ventral striatum.

Improvement in hyperarousal symptoms and psychological well-being was associated with greater increases in frontopolar activation.

After treatment, the frontopolar cortex exhibited a greater variety of temporal resting-state signal pattern changes.

Concurrent TMS and functional MRI in healthy participants indicated the lateral frontopolar cortex had downstream influence on the ventromedial prefrontal cortex/ventral striatum.

“Our findings have import for understanding the mechanism of exposure therapy by demonstrating that the most prominent functional brain change during the processing and regulation of non-traumatic emotional stimuli occurs in an anatomically distinct, higher-order frontal structure. This region may also be responsible for the instantiation of a conceptually distinct process — a gating mechanism dictating the balance of awareness of the internal and external world,” the researchers wrote. “Although additional studies are needed to further elaborate on the functional significance of the frontopolar cortex in PTSD and its change after exposure therapy, the present findings identify an underexplored anatomical brain target and pathway of influence to the ventromedial prefrontal cortex with promise for stimulation-based therapeutics and augmentation of psychotherapy effects.” – by Amanda Oldt

Disclosure: Fonzo reports no relevant financial disclosures. Please see the study for a full list of relevant financial disclosures.