Posted July 30, 2019

John Hart, Jr., MD, University of Texas at Dallas

Post-traumatic stress disorder (PTSD) is a debilitating condition that can result from serving in combat, which affects many military Service members and Veterans. Traditionally, PTSD is treated with cognitive behavioral therapy (CBT), or specific subtypes of CBT, such as cognitive processing therapy (CPT), which is focused more on managing PTSD symptoms. More recently, other therapies have become available as alternative or adjunctive methods to CPT for managing PTSD symptoms. Repetitive transcranial magnetic stimulation (rTMS) is one such therapy that involves placing a magnetic coil against the scalp and delivering low-level electrical pulses to the brain. The pulses can stimulate or inhibit the neural activity located underneath the coil. This technique of neuromodulation can lead to short- and long-term changes in brain activity.

With support from a Fiscal Year 2010 Applied Research and Advanced Technology Development Award, Dr. Hart and his team of clinicians and researchers have been studying the therapeutic effects of rTMS combined with CPT in Veterans with PTSD. To date, their work has shown success for rTMS in reducing PTSD symptoms. In a recent study, 103 Veterans were assigned to PTSD treatment groups: rTMS given at 1 Hertz once a week for 12 weeks + CPT, or sham (control) rTMS + CPT. Symptoms of PTSD were assessed and functional magnetic resonance imaging (fMRI), and electroencephalogram (EEG) measures were collected before treatment, and at 1, 3, and 6 months following treatment. Although both groups showed an attenuation of PTSD symptom severity over the course of the study and follow-up testing sessions, the group receiving active rTMS + CPT showed greater reductions in severity over the group receiving sham rTMS + CPT as early as the fifth therapy session, and the greater reduction was present at 1, 3, and 6 months after treatment.

Additionally, results from the fMRI scans revealed that brain regions such as the pre-supplementary motor area, dorsal anterior cingulate cortex, and the right inferior frontal gyrus had reduced blood oxygen level-dependent signals in response to threatening combat-related stimuli in patients after receiving treatment compared to before treatment. These findings provide evidence that potential target neural mechanisms may be undergoing change with treatments.

Lastly, Dr. Hart and his group measured evoked response potential (ERP) amplitudes from auditory stimuli. Once again, both threatening and non-threatening stimuli were administered at baseline, and at 1 and 6 months post-treatment. ERP responses to the task-relevant target stimuli were improved with treatment. ERP responses to the task-irrelevant threatening stimuli at baseline indicated that these stimuli were overly salient and distracting, but at baseline this pattern was significantly diminished. In addition, this reduction in response to threatening stimuli was correlated with reduction in PTSD cluster symptoms.

In this multi-site study, up to 330 Veterans with combat-related PTSD will be divided into three treatment conditions: The rTMS alone condition with 1 Hz rTMS given at the right dorsolateral prefrontal cortex for 30 minutes, rTMS + CPT, or sham rTMS + CPT, with each treatment being administered one session per week for 12 weeks . As with the previous study, evaluations in PTSD symptoms, EEG, and fMRI measures will be gathered before and at 1, 6, and 12 months after treatment.

With the same treatment protocol in place at each site, Dr. Hart and his team hope to show the efficacy of this method when employed at various treatment facilities and to diverse Veteran populations. Empirically demonstrating the beneficial effects of rTMS alone or combined with CPT would be a step forward in bringing neuromodulation therapies into common practice and hence providing more treatment options to Veterans with PTSD.

Publications:

https://neuro.psychiatryonline.org/doi/full/10.1176/appi.neuropsych.15070183?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed

Kozel FA, Didehbani N, DeLaRosa B, Bass C, Schraufnagel CD, Morgan CR, Jones P, Spence JS, and Hart J, Jr. (2016). Factors impacting functional status in veterans of recent conflicts with PTSD. The Journal of Neuropsychiatry and Clinical Neurosciences 28:112-117. https://doi.org/10.1176/appi.neuropsych.15070183

Kozel FA, Motes MA, Didehbani N, DeLaRosa B, Bass C, Schraufnagel CD, Jones P, Morgan CR, Spence JS, Kraut MA, and Hart J, Jr. (2018). Repetitive TMS to augment cognitive processing therapy in combat veterans of recent conflicts with PTSD: A randomized clinical trial. Journal of Affective Disorders 18:506-514. https://doi.org/10.1016/j.jad.2017.12.046

Links:

Public and Technical Abstracts: Novel Treatment of Emotional Dysfunction in PTSD

Technical Abstract: Multi-Site Confirmatory Efficacy Treatment Trial of Combat-Related PTSD

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