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. 2022 Sep 30:16:997259.
doi: 10.3389/fnins.2022.997259. eCollection 2022.

Low frequency repetitive transcranial magnetic stimulation to the right dorsolateral prefrontal cortex engages thalamus, striatum, and the default mode network

Elisabeth de Castro Caparelli  1 , Osama A Abulseoud  1   2 , Hong Gu  1 , Tianye Zhai  1 , Brooke Schleyer  1   3 , Yihong Yang  1
Affiliations

Low frequency repetitive transcranial magnetic stimulation to the right dorsolateral prefrontal cortex engages thalamus, striatum, and the default mode network

Elisabeth de Castro Caparelli et al. Front Neurosci. .

Abstract

The positive treatment outcomes of low frequency (LF) repetitive transcranial magnetic stimulation (rTMS) when applied over the right dorsolateral prefrontal cortex (DLPFC) in treatment-refractory depression has been verified. However, the mechanism of action behind these results have not been well-explored. In this work we used simultaneous functional magnetic resonance imaging (fMRI) during TMS to explore the effect of LF rTMS on brain activity when applied to the right [RDLPFC1 (MNI: 50, 30, 36)] and left DLPFC sites [LDLPFC1 (MNI: -50, 30, 36), LDLPFC2 (MNI: -41, 16, 54)]. Seventeen healthy adult volunteers participated in this study. To identify brain areas affected by rTMS, an independent component analysis and a general linear model were used. Our results showed an important laterality effect when contrasting rTMS over the left and right sites. Specifically, LF rTMS increased brain activity at the striatum, thalamus, and areas of the default mode network when applied to the right, but not to the contralateral left DLPFC. In contrast, no site differences were observed when evaluating the effect of LF rTMS over the two left sites. These findings demonstrate that LF rTMS to the right DLPFC was able to stimulate the cortico-striato-thalamo-cortical pathway, which is dysregulated in patients with major depressive disorder; therefore, possibly providing some neurobiological justification for the successful outcomes found thus far for LF rTMS in the treatment of depression.

Keywords: DLPFC; TMS; fMRI; low frequency; multimodality.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The TMS-fMRI session is composed of two fMRI scans. Each scan starts with a baseline followed by three stimulation blocks alternated by three resting blocks. During the stimulation block, each TMS pulse is applied 100 ms before the next EPI acquisition (400 ms after the previous EPI acquisition). TMS, transcranial magnetic stimulation; LF, low frequency; EPI, echo-planar imaging.
FIGURE 2
FIGURE 2
Display of the 15 meaningful ICs from group independent component analysis (ICA). Radiological convention.
FIGURE 3
FIGURE 3
Laterality test. Plots for the mean correlation values (z-values) for ICs with significant laterality effects. *Two-sample t-test significant after Bonferroni correction as shown on Table 4 (*pcorr < 0.05). Error bars: standard deviation. LF, low frequency; LDLPFC1, left dorsolateral prefrontal cortex #1; RDLPFC1, right dorsolateral prefrontal cortex #1.
FIGURE 4
FIGURE 4
Results of general linear model (GLM) based analysis, one sample T-test for each stimulation site. Significance: uncorrected p-value (p = 0.001), corrected p-value (pcorr < 0.05). Radiological convention. LDLPFC1, left dorsolateral prefrontal cortex #1; RDLPFC1, right dorsolateral prefrontal cortex #1; LDLPFC2, left dorsolateral prefrontal cortex #2; LF, Low frequency; R, right; L, left.
See this image and copyright information in PMC

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