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

Abstract

IntroductionIntermittent theta burst stimulation (iTBS) is a non-invasive brain stimulation technique capable of increasing cortical excitability beyond the stimulation period. Due to the rapid induction of modulatory effects compared to conventional repetitive transcranial magnetic stimulation (rTMS) paradigms, 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 effect is well established for the standard rTMS paradigms but 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.Methods16 healthy participants received iTBS over prefrontal cortex (F1 electrode) at either 50, 75 or 100% resting motor threshold (rMT) in separate sessions. Single-pulse TMS and concurrent electroencephalography (EEG) was used to assess changes in cortical reactivity measured as TMS-evoked potentials (TEPs) and TMS-evoked oscillations. The n-back task (2-back and 3-back) were used to assess changes in working memory (accuracy and reaction time).ResultsThe data can be summarised as an inverse U-shape relationship between intensity and iTBS plastic effects, where 75% iTBS resulted in the largest neurophysiological changes both in TMS-EEG and working memory. Even though 75% iTBS showed significantly decreased reaction time in the 3-back task, between condition comparisons revealed no significant differences.ConclusionsThe assumption that higher intensity results in greater neuromodulatory effects is 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.HighlightsEffects of prefrontal iTBS at 50, 75 and 100% rMT were investigatedInverse U-shape relationship between intensity and neurophysiological effectsEffects on the behavioural performance remain elusive in healthy individualsDisclosures and conflict of interestsSWC was supported by a Monash Graduate Scholarship. NCR is supported by a NHMRC Early Career Fellowship (1072057). KEH is supported by a NHMRC Career Development Fellowship (1082894). PBF is supported by a NHMRC Practitioner Fellowship (1078567). PBF has received equipment for research from MagVenture A/S, Medtronic Ltd, Cervel Neurotech and Brainsway Ltd and funding for research from Neuronetics and Cervel Neurotech. He is on the scientific advisory board for Bionomics Ltd. There are no other conflicts.

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

“…Measuring TMS-evoked responses before and after neuromodulatory paradigms provides a metric of neural plasticity at the cortical level. For instance, a positive peak at a latency of 60 ms (P60) may provide a marker of excitability in motor and prefrontal regions Hill et al, 2017), whereas a negative peak at a latency of 100 ms (N100) may be associated with GABA B -mediated inhibitory mechanisms [in motor regions (Bonnard, Spieser, Meziane, de Graaf, & Pailhous, 2009;Premoli, Rivolta, et al, 2014b;Rogasch, Daskalakis, & Fitzgerald, 2013a); in prefrontal regions (Chung et al, 2017;Rogasch, Daskalakis, & Fitzgerald, 2015)], and these two peaks have been the most consistent neuromodulatory-mediated effects observed in recent literature using prefrontal TMS-EEG (Casula, Pellicciari, Picazio, Caltagirone, & Koch, 2016a;Chung, Rogasch, Hoy, Sullivan, et al, 2018b;Hill et al, 2017).…”

“…The EEG cap was applied first, and then the resting motor threshold (rMT) was determined (i.e., by applying TMS over the cap) as the minimum stimulus intensity required to elicit at least three out of six motor evoked potentials (MEPs) >0.05 mV in amplitude (Conforto, Z'Graggen, Kohl, Rosler, & Kaelin-Lang, 2004) in the relaxed first dorsal interosseous muscles. Prefrontal TMS was administered over F1 electrode as previously described (Chung, Rogasch, Hoy, & Fitzgerald, 2018a;Chung, Rogasch, Hoy, Sullivan, et al, 2018b). This electrode sits over the superior frontal gyrus (BA 6, 8 and 9) (Koessler et al, 2009) which is part of left dorsolateral prefrontal cortex (DLPFC).…”

“…The intensity of stimulation was adjusted to 75% of individuals' rMT. 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).…”

“…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. 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 anticipated 30 Hz iTBS to be superior to 50 Hz stimulation given the robustness seen in the motor cortex study (Chung et al, 2016;Goldsworthy et al, 2012).…”

The Current and Future Potential of Transcranial Magnetic Stimulation With Electroencephalography in Psychiatry

“…In the DLPFC, this plasticity is thought to underlie various cognitive processes, such as attention, emotion regulation, and executive functions. 13 To assess such plasticity in the DLPFC, a TMS-EEG technique termed paired-associative stimulation (PAS) is used. PAS involves a sensory input, typically an electrical stimulation of the median nerve, paired with magnetic stimulation of the DLPFC at a specific time interval to recruit LTP-like mechanisms, leading to potentiation of cortical activity.…”