No abstract

While previous research using transcranial magnetic stimulation (TMS) suggest that cerebellum (CB) influences the neuroplastic response of primary motor cortex (M1), the role of different indirect (I) wave inputs in M1 mediating this interaction remains unclear. The aim of this study was therefore to assess how CB influences neuroplasticity of early and late I-wave circuits. 22 young adults (22 ± 2.7 years) participated in 3 sessions in which I-wave periodicity repetitive transcranial magnetic stimulation (iTMS) was applied over M1 during concurrent application of cathodal transcranial direct current stimulation over CB (tDCSCB). In each session, iTMS either targeted early I-waves (1.5 ms interval; iTMS1.5), late I-waves (4.5 ms interval; iTMS4.5), or had no effect (variable interval; iTMSSham). Changes due to the intervention were examined with motor evoked potential (MEP) amplitude using TMS protocols measuring corticospinal excitability (MEP1mV) and the strength of CB-M1 connections (CBI). In addition, we indexed I-wave activity using short-interval intracortical facilitation (SICF) and low-intensity single-pulse TMS applied with posterior-anterior (MEPPA) and anterior-posterior (MEPAP) current directions. Following both active iTMS sessions, there was no change in MEP1mV, CBI or SICF (all P > 0.05), suggesting that tDCSCB broadly disrupted the excitatory response that is normally seen following iTMS. However, although MEPAP also failed to facilitate after the intervention (P > 0.05), MEPPA potentiated following both active iTMS sessions (both P < 0.05). This differential response between current directions could indicate a selective effect of CB on AP-sensitive circuits.

Previous research using transcranial magnetic stimulation (TMS) has demonstrated weakened connectivity between dorsal premotor cortex (PMd) and motor cortex (M1) with age. While this alteration is probably mediated by changes in the communication between the two regions, the effect of age on the influence of PMd on specific indirect (I) wave circuits within M1 remains unclear. The present study therefore investigated the influence of PMd on early and late I‐wave excitability in M1 of young and older adults. Twenty‐two young (mean ± SD, 22.9 ± 2.9 years) and 20 older (66.6 ± 4.2 years) adults participated in two experimental sessions involving either intermittent theta burst stimulation (iTBS) or sham stimulation over PMd. Changes within M1 following the intervention were assessed with motor‐evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle. We applied posterior–anterior (PA) and anterior–posterior (AP) current single‐pulse TMS to assess corticospinal excitability (PA1mV; AP1mV; PA0.5mV, early; AP0.5mV, late), and paired‐pulse TMS short intracortical facilitation for I‐wave excitability (PA SICF, early; AP SICF, late). Although PMd iTBS potentiated PA1mV and AP1mV MEPs in both age groups (both P < 0.05), the time course of this effect was delayed for AP1mV in older adults (P = 0.001). Furthermore, while AP0.5mV, PA SICF and AP SICF were potentiated in both groups (all P < 0.05), potentiation of PA0.5mV was only apparent in young adults (P < 0.0001). While PMd influences early and late I‐wave excitability in young adults, direct PMd modulation of the early circuits is specifically reduced in older adults. Key points Interneuronal circuits responsible for late I‐waves within primary motor cortex (M1) mediate projections from dorsal premotor cortex (PMd), but this communication probably changes with advancing age. We investigated the effects of intermittent theta burst stimulation (iTBS) to PMd on transcranial magnetic stimulation (TMS) measures of M1 excitability in young and older adults. We found that PMd iTBS facilitated M1 excitability assessed with posterior–anterior (PA, early I‐waves) and anterior–posterior (AP, late I‐waves) current TMS in young adults, with a stronger effect for AP TMS. M1 excitability assessed with AP TMS also increased in older adults following PMd iTBS, but there was no facilitation for PA TMS responses. We conclude that changes in M1 excitability following PMd iTBS are specifically reduced for the early I‐waves in older adults, which could be a potential target for interventions that enhance cortical excitability in older adults.

Cerebellar-brain inhibition (CBI) is a transcranial magnetic stimulation (TMS) paradigm indexing excitability of cerebellar projections to motor cortex (M1). Stimulation involved with CBI is often considered to be uncomfortable, and alternative ways to index connectivity between cerebellum and the cortex would be valuable. We therefore sought to assess the utility of electroencephalography in conjunction with TMS (combined TMS-EEG) to record the response to CBI. A total of 33 volunteers (25.7 ± 4.9 years, 20 females) participated across three experiments. These investigated EEG responses to CBI induced with a figure-of-eight (F8; experiment 1) or double cone (DC; experiment 2) conditioning coil over cerebellum, in addition to multisensory sham stimulation (experiment 3). Both F8 and DC coils suppressed early TMS-evoked EEG potentials (TEPs) produced by TMS to M1 (P < 0.05). Furthermore, the TEP produced by CBI stimulation was related to the motor inhibitory response to CBI recorded in a hand muscle (P < 0.05), but only when using the DC coil. Multisensory sham stimulation failed to modify the M1 TEP. Cerebellar conditioning produced changes in the M1 TEP that were not apparent following sham stimulation, and that were related to the motor inhibitory effects of CBI. Our findings therefore suggest that it is possible to index the response to CBI using TMS-EEG. In addition, while both F8 and DC coils appear to recruit cerebellar projections, the nature of these may be different.

Previous research using transcranial magnetic stimulation (TMS) demonstrates that dorsal premotor cortex (PMd) influences neuroplasticity within primary motor cortex (M1). This communication is likely mediated by indirect (I) wave inputs within M1, the activity of which are altered by ageing. However, it remains unclear if age-related changes in the I-wave circuits modify the influence of PMd on M1 plasticity. The present study therefore investigated the influence of PMd on the plasticity of early and late I-wave circuits within M1 of young and older adults. 15 young (mean ± SD; 24.7 ± 5.0 years) and 15 older adults (67.2 ± 5.4 years) participated in two experimental sessions that examined the effects of intermittent theta burst stimulation (iTBS) to M1 when preceded by iTBS (PMd iTBS-M1 iTBS) or sham stimulation (PMd sham-M1 iTBS) to PMd. Changes in M1 excitability post-intervention were assessed with motor evoked potentials (MEP) recorded from right first dorsal interosseous muscle, with posterior-to-anterior (PA) and anterior-to-posterior (AP) current single-pulse TMS assessing corticospinal excitability (PA1mV; AP1mV; PA0.5mV, early I-wave; AP0.5mV, late I-wave). Although PA1mVdid not change post-intervention (P= 0.628), PMd iTBS-M1 iTBS disrupted the expected facilitation of AP1mV(to M1 iTBS in isolation) in young and older adults (P= 0.002). Similarly, PMd iTBS-M1 iTBS disrupted PA0.5mVfacilitation in young and older adults (P= 0.030), whereas AP0.5mVfacilitation was not affected in either group (P= 0.218). This suggests that while PMd specifically influences the plasticity of early I-wave circuits, this communication is preserved in older adults.Key pointsThe influence of dorsal premotor cortex (PMd) on M1 plasticity is likely mediated by late I-wave interneuronal circuits within M1, but this communication may change with advancing age.We investigated the effects of intermittent theta burst stimulation (iTBS) to M1 when preceded by iTBS to PMd on transcranial magnetic stimulation (TMS) measures of M1 excitability in young and older adults.We found that PMd iTBS disrupts the plasticity induction of M1 iTBS in both young and older adults when measured with posterior-anterior (PA, early I-waves) current TMS, but not with anterior-posterior (AP, late I-waves) TMS measures of M1 excitability.The plasticity of early I-waves within M1 are specifically influenced by PMd iTBS in both young and older adults, suggesting that this communication is preserved with ageing.