Theta Burst Stimulation of the Cerebellum Modifies the TMS-Evoked N100 Potential, a Marker of GABA Inhibition

Abstract

Theta burst stimulation (TBS) of the cerebellum, a potential therapy for neurological disease, can modulate corticospinal excitability via the dentato-thalamo-cortical pathway, but it is uncertain whether its effects are mediated via inhibitory or facilitatory networks. The aim of this study was to investigate the effects of 30Hz cerebellar TBS on the N100 waveform of the TMS-evoked potential (TEP), a marker of intracortical GABAB-mediated inhibition. 16 healthy participants (aged 18–30 years; 13 right handed and 3 left handed) received 30Hz intermittent TBS (iTBS), continuous TBS (cTBS) or sham stimulation over the right cerebellum, in three separate sessions. The first 8 participants received TBS at a stimulus intensity of 80% of active motor threshold (AMT), while the remainder received 90% of AMT. Motor evoked potentials (MEP) and TEP were recorded before and after each treatment, by stimulating the first dorsal interosseus area of the left motor cortex. Analysis of the 13 right handed participants showed that iTBS at 90% of AMT increased the N100 amplitude compared to sham and cTBS, without significantly altering MEP amplitude. cTBS at 80% of active motor threshold decreased the N100 amplitude and cTBS overall reduced resting MEP amplitude. The study demonstrates effects of 30Hz cerebellar TBS on inhibitory cortical networks that may be useful for treatment of neurological conditions associated with dysfunctional intracortical inhibition.

Cerebellar theta burst stimulation modulates the neural activity of interconnected parietal and motor areas

“…Thus, conclusion in the spatial domain should be taken with caution. A recent study by Harrington and Hammond-Tooke27 found that 30Hz-iTBS at 90% of AMT increased N100 amplitude whereas 30 Hz-cTBS at 80% of AMT (but not at 90%) produced the opposite effect. These results are in contrast with what we observed in the present work and with previous studies using cerebellar TBS7.…”

Effects of cerebellar theta-burst stimulation on arm and neck movement kinematics in patients with focal dystonia

“…Studies using 1 Hz rTMS applied over the cerebellum led to an increase of MEP amplitude (Oliveri et al, 2005; Fierro et al, 2007; Popa et al, 2010), thus suggesting a decrease of the Purkinje output to dentate nucleus and as a consequence disinhibition of the dentate-cortical drive. Harrington and Hammond (2015), however, have recently demonstrated that cTBS (delivered at low intensity, i.e., 80% of AMT) decreased the N100 waveform of the TMS-evoked potential, an indirect measure of cortical inhibition, and the resting MEP amplitude in the contralateral M1. These authors thus concluded that the effects of cTBS are likely exerted by inhibition of the superficial layer of the cerebellum (which has an inhibitory role on Purkinje cell activity).…”

Non-invasive brain stimulation as a tool to study cerebellar-M1 interactions in humans

“…FDIM1 and CRB: figure-of-eight (90 mm)Pre/Post 5, 25 minHC and PD: ↓ MEP↓ symptomsBologna et al (2015) [38]11 HC16 ETRight CRBSham (neck muscles)cTBS600 pulses80 % AMT2 randomizedRight FDIM1 and CRB: figure-of-eightPre/Post 5, 45 minHC: ↓ MEP RC ET: ↔ MEP RC ↔ symptomsBologna et al (2015) [37]10 HC13 RTIpsi. CRB to tremor handSham (neck muscles)cTBS600 pulses80 % AMT2 randomizedFDI (tremor hand)M1 and CRB: figure-of-eightPre/Post 5, 45 minHC and RT: ↓ MEP RC ↔ symptomsHarrington et al (2015) [39]13 HCRight CRBcTBSiTBSSham TBS600 pulses80 % AMT (6 subjects)90 % AMT (7 subjects)3randomizedcrossoverRight FDIM1 and CRB: figure-of-eightPre/PostcTBS: ↓ MEP AD Alzheimer’s disease, AMT active motor threshold, APB abductor pollicis brevis, CBI cerebellar brain inhibition, CBI RC cerebellar brain inhibition recruitment curve, CRB cerebellum, Contra contralateral, CSP cortical silent period, ET essential tremor, FDI first dorsal interosseous, HC healthy controls, ICF intracortical facilitation, Isps ipsilateral, LICI long interval intracortical inhibition, M1 primary motor cortex, MEP motor evoked potential, MEP RC motor evoked potential recruitment curve, MSO maximal stimulator output, PAS paired-associative stimulation, PCS posterior circulation stroke, PD Parkinson’s disease, PSP progressive supranuclear palsy, SAI short latency afferent inhibition, SAI RC short latency afferent inhibition recruitment curve, SICI short interval intracortical inhibition, SICF short interval intracortical facilitation, WD writing dystonia …”

“…Intracortical inhibitionSICIAnodal TDCSGalea et al (2009) [41]ISI: 2 msCS: 80 % RMTTS: 1 mV (adjusted post)↔Cathodal TDCSGalea et al (2009) [41]ISI: 2 msCS: 80 % RMTTS: 1 mV (adjusted post)↔1 Hz rTMSOliveri et al (2005) [30]ISI: 1 and 3 msCS: 70 % RMTTS: 1 mV (adjusted post)↔Fierro et al (2007) [31]ISI: 2 and 4 msCS: 80 % RMTTS: 120 % RMT (adjusted post)↔Langguth et al (2008) [47]ISI: 2, 3, 4 and 5 msCS: 90 % AMT, TS: 1 mV↑ (averaged ISIs)10 Hz rTMSLangguth et al (2008) [47]ISI: 2, 3, 4 and 5 msCS: 90 % AMT, TS: 1 mV↔cTBSKoch et al (2008) [34]ISI: 1, 2, 3, 4 and 5 msCS: 80 % AMT, TS: 1 mV↓ (3 ms, contralateral only)Carrillo et al (2013) [36]ISI: 1, 2, 3, 4 and 5 msCS: 80 % AMTTS: 1 mV↓ (2 and 3 ms, 0–20 min)Di Lorenzo et al (2013) [40]ISI: 1, 2, 3, 4 and 5 msCS: 80 % AMTTS: 1 mV↔Hubsch et al (2013) [49]SI: 2.5 msCS: 70 % RMTTS: 130 % RMT (adjusted post)↔iTBSKoch et al (2008) [34]ISI: 1, 2, 3, 4 and 5 msCS: 80 % AMTTS: 1 mV↔CB-M1 PASLu et al (2012) [19]ISI: 2 msCS: 70 to 90 % AMT (50 % inh. )↓ (all PAS ISIs)LICITACSNaro et al (2016) [45]ISI: 50 msCS: 120 % RMTTS: 120 % RMT↔cTBSKoch et al (2008) [34]ISI: 100 and 150 msCS: 120 % RMTTS: 1 mV↑ (100 ms)Hubsch et al (2013) [49]SI: 100 msCS: 120 % RMTTS: 130 % RMT (adjusted post)↔iTBSKoch et al (2008) [34]ISI: 100 and 150 msCS: 120 % RMTTS: 1 mV↓ (100 ms)CSP1 Hz rTMSOliveri et al (2005) [30]30 % maximal forceTS: 1 mV↔cTBSHarrington et al (2015) [39]20 Newton forceTS:110 % RMT...…”

“…Cerebellar cTBS (cTBS CB ), which like 1 Hz rTMS is usually claimed to have an inhibitory effect on M1 excitability, appears to have an opposite effect on cerebellum: cTBS CB reduced MEP amplitudes in 7 studies (and in 2 of them it also reduced the slope of the MEP recruitment curve) [33–39], but had no effect in two others [32, 40]. Cerebellar iTBS (iTBS CB ) was reported to increase MEPs in one study [34] but there was no effect in two studies [32, 39]. …”