Effect of Bilateral Prefrontal rTMS on Left Prefrontal NAA and Glx Levels in Schizophrenia Patients with Predominant Negative Symptoms: An Exploratory Study

Brain Stimul. 2017 Jan-Feb;10(1):59-64. doi: 10.1016/j.brs.2016.08.002. Epub 2016 Aug 5.

Abstract

Background: Prefrontal repetitive Transcranial Magnetic Stimulation (rTMS) may improve negative symptoms in patients with schizophrenia, but few studies have investigated the underlying neural mechanism.

Objective: This study aims to investigate changes in the levels of glutamate and glutamine (Glx, neurotransmitter and precursor) and N-Acetyl Aspartate (NAA) in the left dorsolateral prefrontal cortex of patients with schizophrenia treated with active bilateral prefrontal rTMS as compared to sham-rTMS, as measured with 1H-Magnetic Resonance Spectroscopy (1H-MRS).

Methods: Patients were randomized to a 3-week course of active or sham high-frequency rTMS. Pre-treatment and post-treatment 1H-MRS data were available for 24 patients with schizophrenia with moderate to severe negative symptoms (Positive and Negative Syndrome Scale (PANSS) negative subscale ≥ 15). Absolute metabolite concentrations were calculated using LCModel with the water peak as reference. To explore the association between treatment condition and changes in concentration of Glx and NAA, we applied a linear regression model.

Results: We observed an increase of Glx concentration in the active treatment group and a decrease of Glx concentration in the group receiving sham treatment. The association between changes in Glx concentration and treatment condition was significant. No significant associations between changes in NAA and treatment condition were found.

Conclusions: Noninvasive neurostimulation with high-frequency bilateral prefrontal rTMS may influence Glx concentration in the prefrontal cortex of patients with schizophrenia. Larger studies are needed to confirm these findings and further elucidate the underlying neural working mechanism of rTMS.

Keywords: (1)H-Magnetic resonance spectroscopy; Dorsolateral prefrontal cortex; Glutamate; N-Acetyl aspartate; Negative symptoms; Randomized controlled trial; Schizophrenia; Transcranial magnetic stimulation.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Double-Blind Method
  • Female
  • Glutamic Acid / metabolism*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Pessimism*
  • Prefrontal Cortex / metabolism*
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / metabolism*
  • Schizophrenia / therapy
  • Transcranial Magnetic Stimulation / methods*
  • Treatment Outcome
  • Young Adult

Substances

  • Aspartic Acid
  • Glutamic Acid
  • N-acetylaspartate