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Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method commonly used in the disciplines of neuroscience, neurology, and neuropsychiatry to examine or modulate brain function. Low frequency rTMS (e.g., 1 Hz) is associated with a net suppression of cortical excitability, whereas higher frequencies (e.g., 5 Hz) purportedly increase excitability. Magnetic resonance spectroscopy (MRS) and resting-state functional MRI (rsfMRI) allow investigation of neurochemistry and functional connectivity, respectively, and can assess the influence of rTMS in these domains. This pilot study investigated the effects of rTMS on the primary motor cortex using pre and post MRS and rsfMRI assessments at 7 T. Seven right-handed males (age 27 ± 7 y.o.) underwent single-voxel MRS and rsfMRI before and about 30-min after rTMS was administered outside the scanner for 20-min over the primary motor cortex of the left (dominant) hemisphere. All participants received 1-Hz rTMS; one participant additionally received 5-Hz rTMS in a separate session. Concentrations of 17 neurochemicals were quantified in left and right motor cortices. Connectivity metrics included fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) of both motor cortices, strength of related brain networks, and inter-hemispheric connectivity. The group-analysis revealed few trends (i.e., uncorrected for multiple comparisons), including a mean increase in the concentration of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) after the inhibitory rTMS protocol as compared to baseline in the stimulated (left) motor cortex (+8%, p = 0.043), along with a slight increase of total creatine (+2%, p = 0.018), and decrease of aspartate (−18%, p = 0.016). Additionally, GABA tended to decrease in the contralateral hemisphere (−6%, p = 0.033). No other changes of metabolite concentrations were found. Whereas functional connectivity outcomes did not exhibit trends of significant changes induced by rTMS, the percent changes of few connectivity metrics in both hemispheres were negatively correlated with GABA changes in the contralateral hemisphere. While studies in larger cohorts are needed to confirm these preliminary findings, our results indicate the safety and feasibility of detecting changes in key metabolites associated with neurotransmission after a single 1-Hz rTMS session, establishing the construct for future exploration of the neurochemical, and connectivity mechanisms of cortical responses to neuromodulation.
Highlights
Repetitive transcranial magnetic stimulation is a noninvasive brain stimulation method commonly used in the disciplines of neuroscience, neurology, and neuropsychiatry to examine or modulate brain function
At baseline, several metabolite concentrations had higher concentration in right vs. left motor cortex, including glutamate and γ-aminobutyric acid (GABA) (24%, p = 0.002), glutamate (8%, p = 0.003), glutamine (16%, p = 0.001), Cho (6%, p = 0.019), Ins (7%, p = 0.003), GSH (18%, p = 0.041), and NAA (6%, p = 0.011)
After the 1-Hz Repetitive transcranial magnetic stimulation (rTMS) intervention (Figure 4), GABA concentration in the ipsilateral motor cortex increased on average by 8% as compared to pre-rTMS (p = 0.043), while in the contralateral motor cortex, decreased by 6% (p = 0.033)
Summary
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation method commonly used in the disciplines of neuroscience, neurology, and neuropsychiatry to examine or modulate brain function. Studies in animals and humans have provided evidence that rTMS protocols can influence the excitability and function of neurons (neuromodulation), both near to, and distant from, the site of stimulation (Dayan et al, 2013; Liew et al, 2014; Huang et al, 2017). While it is still unclear how local and distant changes in function induced by specific rTMS protocols are mediated, changes in the levels of excitatory and inhibitory neurotransmitters, glutamate and γ-aminobutyric acid (GABA), respectively, most likely play a critical role in neuromodulation effects
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