Identifying Targets for Neuromodulation of PTSD
Post by Kelly Kadlec
The takeaway
In this study, the authors investigated the functional connectivity between brain regions of veterans with and without brain lesions to identify a neural circuit for Post-traumatic stress disorder (PTSD). They demonstrated the potential therapeutic benefits of targeting brain regions within this circuit using noninvasive neuromodulation.
What's the science?
Post-traumatic stress disorder can result from the experience of a traumatic event or series of events and symptoms can include anxiety and depression. Despite its prevalence, traditional medication and psychotherapy treatments are often not effective, leading researchers to explore neuromodulation techniques such as transcranial magnetic stimulation (TMS). Unfortunately, one of the most commonly implicated regions in PTSD, the amygdala, is not accessible by TMS. Therefore, there is a need to identify alternative modulation targets. Recently in Nature Neuroscience, Siddiqi and colleagues investigated circuits involved in PTSD in veterans and identified and demonstrated the medial prefrontal cortex (mPFC) as a potential target for TMS treatment of PTSD.
How did they do it?
First, the authors compared rates of PTSD in veterans with and without penetrating traumatic brain injury (TBI), and examined which lesioned brain areas were most associated with reduced rates of PTSD. Additionally, they used functional MRI (fMRI) to determine the functional connectivity (FC) of brain areas where lesions seemed to protect against PTSD. This connectivity was established by lesion network mapping, which relies on the connectome database of resting-state fMRI for 1,000 individuals. Then, they compared the patterns of FC found in veterans with TBI to those without TBI including a large cohort of veterans with PTSD.
The authors then assessed whether neuromodulation of implicated brain regions resulted in changes in PTSD symptoms. First, they evaluated how TMS in regions identified by the connectivity results compared with TMS in other regions in terms of the ability to relieve PTSD symptoms. In addition, they evaluated how different types of modulation (i.e. inhibitory, excitatory) impacted PSTD symptoms.
What did they find?
First, the authors report that veterans with penetrative brain injuries had reduced rates of PTSD. In particular, individuals with damage to the amygdala were the most protected against developing PTSD.
Next, the authors found that reduced functional connectivity between the mPFC, amygdala, and hippocampus, was associated with reduced PTSD symptoms. This ‘lesion-derived PTSD circuit’ was also validated in veterans without TBI by comparing FC in individuals with and without PTSD. They were able to further examine this circuit in individuals who had received TMS for PTSD in a previous study and found that, as hypothesized, a reduction in these patient’s symptoms was associated with a reduction in FC between the areas in this circuit.
Finally, the authors validated the neural circuit they identified as a target for TMS-based treatment of PTSD by showing that TMS in regions within the circuit was more effective than TMS in other areas in reducing symptom severity. In addition, as predicted by the FC results, applying inhibitory modulation to these regions resulted in a decrease in PTSD symptom severity while applying excitatory modulation had the opposite effect.
What's the impact?
PTSD can have a negative impact on the quality of life of individuals afflicted and current treatments are unfortunately limited in their efficacy. The findings in this study demonstrate the mPFC as a promising target for non-invasive neuromodulation and reduction of PTSD symptoms. Further, the results of this study present causal evidence for a critical neural circuit in PTSD.