Targeting brain lesions with TMS holds promise for treating PTSD in veterans

Researchers pinpoint brain lesions that reduce PTSD symptoms in veterans, and targeting PTSD circuitry with TMS could lead to breakthroughs in non-invasive treatments for trauma survivors It was shown that

study: Potential targets for non-invasive neuromodulation of PTSD symptoms derived from focal brain lesions in military veterans.. Image credit: Andrew Angelov / Shutterstock.com

recent natural neuroscience Research explores optimal neuroanatomical targets for treating post-traumatic stress disorder (PTSD) in veterans.

Neuromodulation and PTSD

Approximately 30% of veterans and trauma survivors develop PTSD, which is characterized by depression, suicidality, and substance use. Existing treatments for PTSD include pharmacotherapy and psychotherapyboth have moderate effects. Therefore, there is an urgent need to develop more effective treatments for PTSD.

Neuromodulation is a powerful technique to activate or inhibit brain circuits associated with specific symptoms or disorders. Preliminary evaluations show that focusing the amygdala with deep brain stimulation (DBS), reactive nerve stimulation, and laser ablation are effective in managing PTSD.

Non-invasive techniques such as transcranial magnetic stimulation (TMS) cannot directly access deep targets within the brain, particularly the amygdala. Nevertheless, this approach can target the dorsolateral prefrontal cortex (DLPFC), which has been shown to reduce major depression.

Importantly, two multicenter clinical trials have shown that effective antidepressant targeting can negatively impact PTSD, thus highlighting the importance of developing targeted treatments specific to PTSD. This means that sexuality is emphasized.

About research

Building on previous causal lesion-derived circuit models of PTSD, the current study identified TMS targets associated with PTSD symptoms independent of depression. All relevant data were obtained from the Vietnam Head Injury Study (VHIS).

Participants who sustained severe trauma during the Vietnam War were recruited to the study, 197 of whom had a history of penetrating head injury that caused focal brain lesions. Fifty-five study participants had non-neurological injuries of comparable severity and were considered controls.

The boundaries of each lesion were identified by head computed tomography (CT) scan. Study participants with incomplete data were excluded from the analysis.

The Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Non-Patient Version (SCID) was considered the primary endpoint. To determine whether specific brain lesions influenced PTSD symptoms, we performed an unpaired t-test to compare PTSD scores between brain lesions and control groups. Voxel lesion symptom mapping (VLSM) was used to determine specific voxels associated with PTSD.

Resting state functional connectivity (rsFC) between each lesion location and all other brain voxels was estimated using a standard human connectome database. This approach created a “connectivity map” of each participant's entire brain.

To assess whether brain connectivity influences PTSD, a total of 193 veterans with penetrating traumatic brain injury (TBI) were studied. Additionally, 20 military veterans were selected to determine whether TMS-induced changes in this circuitry ameliorate PTSD severity.

Research results

Although patients with amygdala lesions had lower PTSD scores than those with other lesions, most patients without PTSD symptoms developed lesions outside the amygdala.

Brain lesions associated with reduced PTSD incidence include the medial prefrontal cortex (mPFC), medial temporal lobe, and anterolateral temporal lobe, collectively referred to as the “PTSD circuitry.” . Within the PTSD circuit, the tapetum of the corpus callosum, which connects both medial temporal lobes, was identified as a peak region. PTSD circuitry was not associated with comorbidities such as anxiety, alcohol dependence, or cognitive impairment.

Whole-brain analysis using VLSM maps did not identify individual locations associated with PTSD.

To clarify the generalizability of the circuit, we compared the lesion-derived PTSD circuit to published maps of PTSD-related neuroimaging findings. To this end, previously published neuroimaging correlates of PTSD were consistent with the lesion-based PTSD circuitry identified in the current study.

The researchers also conducted a connectome-wide association study (CWAS) and showed that PTSD-related voxels likely reside within PTSD circuits. The default mode network (DMN), which refers to the brain regions active during self-directed thinking, contains a significant proportion of PTSD-related voxels, although to a lesser extent than the voxel density present in lesion-based PTSD. I did. circuit.

Targeting PTSD circuitry with TMS

Previous research on targeted TMS has shown that this treatment induced increased fear changes when targeting PTSD circuitry. Additional studies were also considered, showing that inhibitory TMS reduces fear conditioning and thereby increases the impact of traumatic events in affected individuals, whereas excitatory TMS on PTSD circuitry may improve fear. The results confirmed the researchers' hypothesis that there is.

In the current study, researchers treated a 62-year-old man with treatment-resistant PTSD due to childhood physical abuse with TMS, which targets PTSD circuitry. The patient received a total of 50 sessions of accelerated intermittent theta burst stimulation (iTBS) over 7 days, after which the patient reported sustained improvement in PTSD symptom severity for 4 weeks.

The medial prefrontal cortex, the peak superficial node of the PTSD circuit, may serve as a promising TMS target for PTSD. ”