Abstract
Background: Dorsolateral prefrontal cortex (DLPFC) low frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise as a treatment and investigative tool in the medical and research communities. Researchers have made significant progress elucidating DLPFC LF-rTMS effects—primarily in individuals with psychiatric disorders. However, more efforts investigating underlying molecular changes and establishing links to functional and behavioral outcomes in healthy humans are needed.Objective: We aimed to quantify neuromolecular changes and relate these to functional changes following a single session of DLPFC LF-rTMS in healthy participants.Methods: Eleven participants received sham-controlled neuronavigated 1 Hz rTMS to the region most activated by a 7-letter Sternberg working memory task (SWMT) within the left DLPFC. We quantified SWMT performance, functional magnetic resonance activation and proton Magnetic resonance spectroscopy (MRS) neurometabolite measure changes before and after stimulation.Results: A single LF-rTMS session was not sufficient to change DLPFC neurometabolite levels and these changes did not correlate with DLPFC activation changes. Real rTMS, however, significantly altered neurometabolite correlations (compared to sham rTMS), both with baseline levels and between the metabolites themselves. Additionally, real rTMS was associated with diminished reaction time (RT) performance improvements and increased activation within the motor, somatosensory and lateral occipital cortices.Conclusion: These results show that a single session of LF-rTMS is sufficient to influence metabolite relationships and causes widespread activation in healthy humans. Investigating correlational relationships may provide insight into mechanisms underlying LF-rTMS.
Highlights
Within the past decade, low frequency repetitive transcranial magnetic stimulation (LF-rTMS, typically delivered at 1 Hz) applied to the dorsolateral prefrontal cortex (DLPFC; Dayan et al, 2013) has shown potential in treating a broad spectrum of clinical diseases/disorders
We did not find significant differences between real and sham conditions for all baseline behavioral and Magnetic resonance spectroscopy (MRS) dependent variables (DVs) measures (p > 0.347). This result suggests as whole that biases in working memory performance and neuromolecular levels did not exist in subject populations prior to stimulation, which could potentially influence LF-rTMS after-effects
RT showed a statistically significant decrease from pre to post L-DLPFC LF-rTMS for the sham group only (t = −4.12, P = 0.002). This pre-post stimulation change was statistically greater for the sham group compared to the real group (t = 3.30, P = 0.008; see Figure 2A). These results indicate a RT learning effect with task practice and that left DLPFC LF-rTMS abolished this learning effect
Summary
Low frequency repetitive transcranial magnetic stimulation (LF-rTMS, typically delivered at 1 Hz) applied to the dorsolateral prefrontal cortex (DLPFC; Dayan et al, 2013) has shown potential in treating a broad spectrum of clinical diseases/disorders. DLPFC LF-TMS has resulted in decreased oxygenated hemoglobin levels at the stimulation site (Kozel et al, 2009) as well as altered fMRI activation (van der Werf et al, 2010) and cortical potentials (De Ridder et al, 2013) in remote brain regions. These results generally suggest that DLPFC rTMS causes decreased activation at the stimulation site, but that these changes can influence functionally connected remote brain regions. More efforts investigating underlying molecular changes and establishing links to functional and behavioral outcomes in healthy humans are needed
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