Left Dorsolateral Prefrontal Cortex rTMS in Alleviating MTBI Related Headaches and Depressive Symptoms

Neuromodulation. 2018 Jun;21(4):390-401. doi: 10.1111/ner.12615. Epub 2017 May 30.


Objective: Persistent mild traumatic brain injury related headache (MTBI-HA) represents a neuropathic pain state. This study tested the hypothesis that repetitive transcranial magnetic stimulation (rTMS) at the left prefrontal cortex can alleviate MTBI-HA and associated neuropsychological dysfunctions.

Methods and materials: Veterans with MTBI-HA were randomized to receive four sessions of either real (REAL group) or sham (SHAM group) high frequency rTMS delivered at 10 Hz, 80% of resting motor threshold and 2000 pulses per session at >24 and <72 hours apart. Pre-treatment, post-treatment 1-week and 4-week headache and neuropsychological assessments were conducted.

Results: Twenty nine out of forty-four consented subjects completed the study. A two-factor (visit × treatment) repeated measures ANOVA showed a significant (p = 0.002, F = 11.63, df = 1) interaction for the average daily persistent headache intensity with the REAL group exhibiting a significant (p < 0.0001) average reduction (±SD) of 25.3 ± 16.8% and 23.0 ± 17.7% reduction in their numerical rating scale at the one-week and four-week post-treatment assessments in comparison to <1 ± 11.7% and 2.3 ± 14.5% reduction found in the SHAM group. In addition, a significant (p < 0.01) 50% and 57% reduction was found in the prevalence of persistent headache in the REAL group at the one-week and four-week assessments in comparison to 7% and 20% reduction found in the SHAM group. Furthermore, the REAL group demonstrated a significant (p = 0.033) improvement (from 22.3 ± 6.4 at pre-treatment to 19.0 ± 5.0 at post-treatment one-week) in the Hamilton Rating Scale for Depression score, while the SHAM group's score remained largely unchanged (from 25.33 ± 8.43 to 24.64 ± 5.03) in the same time frame. This trend of improvement, although not statistically significant, continues to the post-treatment four-week assessment.

Conclusion: A short-course rTMS at the left DLPFC can alleviate MTBI-HA symptoms and provide a transient mood enhancing benefit. Further studies are required to establish a clinical protocol balancing both treatment efficacy and patient compliance.

Keywords: Chronic posttraumatic headaches; MTBI; MTBI-HA; neuropathic pain; rTMS; transcranial magnetic stimulation; traumatic brain injury.

MeSH terms

  • Adult
  • Analysis of Variance
  • Brain Concussion / complications*
  • Brain Concussion / epidemiology
  • Depression / etiology*
  • Depression / rehabilitation*
  • Female
  • Functional Laterality / physiology*
  • Glasgow Outcome Scale
  • Headache / epidemiology
  • Headache / etiology*
  • Headache / rehabilitation*
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Prefrontal Cortex / physiology*
  • Random Allocation
  • Transcranial Magnetic Stimulation / methods
  • Veterans