Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS‐EEG and working memory performance

Abstract

Intermittent theta burst stimulation (iTBS) is a noninvasive brain stimulation technique capable of increasing cortical excitability beyond the stimulation period. Due to the rapid induction of modulatory effects, prefrontal application of iTBS is gaining popularity as a therapeutic tool for psychiatric disorders such as depression. In an attempt to increase efficacy, higher than conventional intensities are currently being applied. The assumption that this increases neuromodulatory may be mechanistically false for iTBS. This study examined the influence of intensity on the neurophysiological and behavioural effects of iTBS in the prefrontal cortex. Sixteen healthy participants received iTBS over prefrontal cortex at either 50, 75 or 100% resting motor threshold in separate sessions. Single-pulse TMS and concurrent electroencephalography (EEG) was used to assess changes in cortical reactivity measured as TMS-evoked potentials and oscillations. The n-back task was used to assess changes in working memory performance. The data can be summarised as an inverse U-shape relationship between intensity and iTBS plastic effects, where 75% iTBS yielded the largest neurophysiological changes. Improvement in reaction time in the 3-back task was supported by the change in alpha power, however, comparison between conditions revealed no significant differences. The assumption that higher intensity results in greater neuromodulatory effects may be false, at least in healthy individuals, and should be carefully considered for clinical populations. Neurophysiological changes associated with working memory following iTBS suggest functional relevance. However, the effects of different intensities on behavioural performance remain elusive in the present healthy sample.

The effects of individualised intermittent theta burst stimulation in the prefrontal cortex: A TMS‐EEG study

“…The amplitude of N100 increased following SAI both in motor and prefrontal cortex (Noda et al, 2016;Noda, Zomorrodi, Backhouse, et al, 2017c), but decreased following cerebellar iTBS (Casula, Pellicciari, Ponzo, et al, 2016b), which are in line with the change observed in N100 following Ind iTBS. However, our previous studies showed increased N100 following prefrontal iTBS (50 Hz at 5 Hz) (Chung et al, 2017;Chung, Rogasch, Hoy, & Fitzgerald, 2018a;Chung, Rogasch, Hoy, Sullivan, et al, 2018b), and the discrepancy of the outcome…”

“…However, several studies with large sample sizes (n > 50) have found no group-level change in MEPs following 50 Hz iTBS (Hamada et al, 2013;Lopez-Alonso et al, 2014;Player, Taylor, Alonzo, & Loo, 2012). Similarly, prefrontal iTBS has shown an improvement in working memory in some studies Lowe et al, 2018), however, not in other studies (Chung, Rogasch, Hoy, Sullivan, et al, 2018b;Grossheinrich et al, 2009;Viejo-Sobera et al, 2017). Similarly, prefrontal iTBS has shown an improvement in working memory in some studies Lowe et al, 2018), however, not in other studies (Chung, Rogasch, Hoy, Sullivan, et al, 2018b;Grossheinrich et al, 2009;Viejo-Sobera et al, 2017).…”

“…The edge of the coil was marked on the cap for consistent re-positioning of the coil. This intensity was selected as our previous study demonstrated more robust cortical effects following iTBS compared with 50% or 100% rMT (Chung, Rogasch, Hoy, Sullivan, et al, 2018b). (a) Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG), 3-back task and mood rating were completed at baseline (BL).…”

“…The balance between excitation and inhibition may be more critical to neural function and behaviour than either neural excitability or inhibition alone (Bonansco & Fuenzalida, 2016;Cash, Udupa, et al, 2017d;Meunier, Chameau, & Fossier, 2017;Turrigiano, 2011), and evidence suggests TBS may have an influence in this regulatory property in animal (Moreau, Amar, Callebert, & Fossier, 2013) and humans (Chung, Rogasch, Hoy, Sullivan, et al, 2018b;Hoy et al, 2016;Legon et al, 2016). Therefore, exploratory analyses were performed regarding the relationship between iTBS-induced change in P60 and N100 amplitudes in order to examine whether significant differences in any of the iTBS conditions could reflect altered inhibitory/excitatory balances (Noda, Zomorrodi, Cash, et al, 2017d).…”

“…Due to the implications of P60 and N100 in cortical plasticity mentioned above and the frequent observation of the change in the amplitude of these peaks following neuromodulatory paradigms over the left prefrontal cortex (Chung, Rogasch, Hoy, Sullivan, et al, 2018b;Hill et al, 2017;Noda, Zomorrodi, Backhouse, et al, 2017c), we hypothesised that individualised iTBS would produce the strongest change in these components. We also measured mood on a visual analogue scale (VAS) and working memory performance via 3-back task following iTBS to investigate relationship between the neurobiological effects of iTBS and the change in behaviour.…”