High-Frequency Transcranial Magnetic Stimulation Combined With Functional Magnetic Resonance Imaging Reveals Distinct Activation Patterns Associated With Different Dorsolateral Prefrontal Cortex Stimulation Sites

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

“…Seventeen healthy adult volunteers (nine males, eight females, age: 37.1 ± 11.2 years old) participated in the study, among which fifteen were completers (participants who completed all four study visits) and two non-completers [one lost contact, and the other withdrew from the study (Caparelli et al, 2022)]. Participants with any neuropsychiatric disorder and/or any contraindication to fMRI scanning or rTMS administration were excluded (Caparelli et al, 2022). The study was approved by the Institutional Review Board panel of the National Institute on Drug Abuse and written informed consent was obtained from each participant.…”

“…As previously described (Caparelli et al, 2022), this study was composed of four study visits (days). On the first day the three stimulation sites, LDLPFC1 (MNI: -50, 30, 36), LDLPFC2 16,54) and RDLPFC1 (MNI: 50,30,36) were localized and the resting motor threshold (rMT) was determined outside the MRI scanner.…”

“…On the following three study days the simultaneous TMS-fMRI sessions (one stimulation site per day) were carried out using a TMS intensity of 100% of the rMT. The LF (0.4 Hz) rTMS sessions were carried out in the morning, and the HF (10 Hz) rTMS sessions (Caparelli et al, 2022) were acquired in the afternoon, with a minimum of 1.5 h between sessions.…”

“…In general, depression treatment protocols employ high frequency (HF-10 to 20 Hz) rTMS to the left DLPFC (Polley et al, 2011;McClintock et al, 2018). While the efficacy of this approach has been verified (George et al, 1995(George et al, , 1997 and its mechanism explored (Strafella et al, 2001;Cho and Strafella, 2009;Caparelli et al, 2022), more recently it has been demonstrated that low frequency (LF) rTMS, which refers to a stimulation rate of ≤1 Hz (Wassermann, 1998), to the right DLPFC is as effective as HF rTMS to the left DLPFC in attenuating the severity of TRD (Chen et al, 2013;Garnaat et al, 2018). However, whether LF TMS activates the CSTC network, or other key limbic structures remains largely unknown.…”

“…In this study we aimed to investigate the differences in the mechanism of action for LF rTMS when applied to the right DLPFC and to the left DLPFC, since, clinically, the left DLPFC is the most commonly used stimulation target followed by the right DLPFC. Following the approach of our previous work (Caparelli et al, 2022), where the effect of HF rTMS was evaluated on three different DLPFC sites, we evaluated LF rTMS for the same three sites, two sites on the left: (1) Montreal Neurological Institute (MNI) coordinates = -50, 30, 36 [chosen because it has previously shown to have promising treatment results for cocaine addiction, such as, reduction of craving and cocaine use, as well as improvement of their depressive symptoms (Terraneo et al, 2016)], (2) MNI coordinates = -41, 16, 54 [chosen as a standardized metric, the "5 cm rule" (Fox et al, 2012)], and one on the right: MNI coordinates = 50, 30, 36 (the contralateral side of site #1), since the functional asymmetric aspect of the DLPFC has been previously reported (Chen et al, 2018). Here we aspire to verify the top-down mechanism of LF (0.4 Hz) rTMS on these three different DLPFC sites and to understand the site and laterality differences of LF rTMS.…”