Improving the efficacy and reliability of rTMS language mapping by increasing the stimulation frequency

Abstract

Repetitive TMS (rTMS) with a frequency of 5–10 Hz is widely used for language mapping. However, it may be accompanied by discomfort and is limited in the number and reliability of evoked language errors. We, here, systematically tested the influence of different stimulation frequencies (i.e., 10, 30, and 50 Hz) on tolerability, number, reliability, and cortical distribution of language errors aiming at improved language mapping. 15 right‐handed, healthy subjects (m = 8, median age: 29 yrs) were investigated in two sessions, separated by 2–5 days. In each session, 10, 30, and 50 Hz rTMS were applied over the left hemisphere in a randomized order during a picture naming task. Overall, 30 Hz rTMS evoked significantly more errors (20 ± 12%) compared to 50 Hz (12 ± 8%; p <.01), whereas error rates were comparable between 30/50 and 10 Hz (18 ± 11%). Across all conditions, a significantly higher error rate was found in Session 1 (19 ± 13%) compared to Session 2 (13 ± 7%, p <.05). The error rate was poorly reliable between sessions for 10 (intraclass correlation coefficient, ICC = .315) and 30 Hz (ICC = .427), whereas 50 Hz showed a moderate reliability (ICC = .597). Spatial reliability of language errors was low to moderate with a tendency toward increased reliability for higher frequencies, for example, within frontal regions. Compared to 10 Hz, both, 30 and 50 Hz were rated as less painful. Taken together, our data favor the use of rTMS‐protocols employing higher frequencies for evoking language errors reliably and with reduced discomfort, depending on the region of interest.

Neuromodulatory effects of transcranial magnetic stimulation on language performance in healthy participants: Systematic review and meta-analysis

“…The current results confirmed that both high and low TMS frequencies could affect healthy participants’ language performance, with high frequencies exerting more stable effects. This accords with a series of studies focusing on the influence of specific stimulation parameters (including frequency) on TMS effects ( Sparing et al, 2001 ; Sollmann et al, 2015 , 2018 ; Nettekoven et al, 2021 ), which support the idea that higher frequencies may induce more reliable disruption of language functions. There are two possible explanations for this finding.…”

“…The distraction caused by physical discomfort (e.g., twitching and contractions of face muscles) or more severe side effects (e.g., dysarthria resulting from stimulation-induced contraction of cranial muscles, Sollmann et al, 2018 ) are non-specific TMS effects and are very likely to confound the interpretation of the results. Therefore, it has been proposed that higher frequencies correlated with lower pain levels and were therefore more optimal for obtaining reliable TMS effects ( Nettekoven et al, 2021 ). Secondly, it is likely that using TMS frequencies matching with the natural frequency band of endogenous brain oscillations increases the probability of TMS pulses to interfere with cortical processing at the appropriate timing ( Thut and Miniussi, 2009 ; Miniussi et al, 2013 ; Nettekoven et al, 2021 ).…”

“…Therefore, it has been proposed that higher frequencies correlated with lower pain levels and were therefore more optimal for obtaining reliable TMS effects ( Nettekoven et al, 2021 ). Secondly, it is likely that using TMS frequencies matching with the natural frequency band of endogenous brain oscillations increases the probability of TMS pulses to interfere with cortical processing at the appropriate timing ( Thut and Miniussi, 2009 ; Miniussi et al, 2013 ; Nettekoven et al, 2021 ). Indeed, evidence from MEG studies has associated language-related processing with brain oscillations in higher frequency bands, such as the beta (17–25 Hz) and the low gamma band (26–50 Hz) ( Hirata et al, 2010 ; Hinkley et al, 2020 ; Youssofzadeh et al, 2020 ).…”

“…Initially introduced for the stimulation of human motor cortex [Barker et al, 1985, as cited in Hartwigsen (2015) ], TMS has been widely applied in clinical studies on language performance in recent years, including the identification of language lateralization as well as the localization of language-related brain regions before surgical resection in tumor patients ( Han et al, 2021 ; Nettekoven et al, 2021 ), and the rehabilitation or treatment of language impairments such as post-stroke aphasia ( Murdoch and Barwood, 2013 ). To guide such clinical applications and provide insight into the functional relevance of the language network, TMS studies in the healthy population are essential.…”

Visual Short-Term Memory for Coherent and Sequential Motion: A rTMS Investigation

“…This procedure was designed to induce a stimulation-related interference either during the encoding phase (early TMS) or on the retention phase (late rTMS) of the memory items, respectively. A rapid sequence of pulses at 30 Hz has been shown to improve the efficacy and reliability of the interference effects of TMS compared to lower stimulation frequencies [ 60 ]. rTMS trials were interleaved by trials with no stimulation (i.e., No-TMS trials).…”