State-Dependent and Timing-Dependent Bidirectional Associative Plasticity in the Human SMA-M1 Network

Abstract

The supplementary motor area (SMA-proper) plays a key role in the preparation and execution of voluntary movements. Anatomically, SMA-proper is densely reciprocally connected to primary motor cortex (M1), but neuronal coordination within the SMA-M1 network and its modification by external perturbation are not well understood. Here we modulated the SMA-M1 network using MR-navigated multicoil associative transcranial magnetic stimulation in healthy subjects. Changes in corticospinal excitability were assessed by recording motor evoked potential (MEP) amplitude bilaterally in a hand muscle. We found timing-dependent bidirectional Hebbian-like MEP changes during and for at least 30 min after paired associative SMA-M1 stimulation. MEP amplitude increased if SMA stimulation preceded M1 stimulation by 6 ms, but decreased if SMA stimulation lagged M1 stimulation by 15 ms. This associative plasticity in the SMA-M1 network was highly topographically specific because paired associative stimulation of pre-SMA and M1 did not result in any significant MEP change. Furthermore, associative plasticity in the SMA-M1 network was strongly state-dependent because it required priming by near-simultaneous M1 stimulation to occur. We conclude that timing-dependent bidirectional associative plasticity is demonstrated for the first time at the systems level of a human corticocortical neuronal network. The properties of this form of plasticity are fully compatible with spike-timing-dependent plasticity as defined at the cellular level. The necessity of priming may reflect the strong interhemispheric connectivity of the SMA-M1 network. Findings are relevant for better understanding reorganization and potentially therapeutic modification of neuronal coordination in the SMA-M1 network after cerebral lesions such as stroke.

Paired Associative Stimulation Enforces the Communication between Interconnected Areas

“…When looking at TEPs at baseline, TMS pulse elicited several responses with latency and scalp distributions matching those already described (Komssi et al, 2002;Bonato et al, 2006;Litvak et al, 2007). However, the activity evoked by PPC stimulation was smaller in amplitude than TEPs evoked by M1 stimulation.…”

“…As expected, TMS evoked an EEG activity lasting up to 300 ms regardless of the stimulated cortex, resulting in a sequence of deflections of alternating positive and negative polarity starting a few milliseconds after stimulation (Komssi et al, 2002;Bonato et al, 2006;. Figure 2 illustrates the distribution of the TEPs components at all recording sites evoked by M1 ( A) and PPC ( B) stimulation.…”

“…LTP-and LTDlike effects can be induced in the primary motor cortex (M1) following the repeated application of paired pulses over interconnected areas such as contralateral M1 (Rizzo et al, 2009), ventral premotor cortex (Buch et al, 2011, or supplementary motor area (Arai et al, 2011). Recently, by targeting the posterior parietal cortex (PPC) and M1, we provided evidence suggesting the existence of both hebbian and anti-hebbian phenomena in humans (Koch et al, 2013).…”

Applications of TMS to Study Brain Connectivity

“…Some studies have defined SMA-M1 connectivity as being inhibitory (Civardi et al 2001;Oliveri et al 2003), whereas others using similar ISIs have described a more robust facilitatory interaction (Arai et al 2011). These inconsistencies might be because of differences in the localization of SMA and/or because the spatial resolution of TMS does not allow for clear discrimination between ipsilateral and contralateral SMA.…”

Non-invasive induction of plasticity in the human cortex: Uses and limitations

“…The induced changes in excitability are critically dependent on the interval between the peripheral and central (TMS) stimuli; increases in cortical excitability can be induced when the interval between the peripheral and cortical stimuli is ~25 ms (PAS 25 ; arrival of the afferent volley in the cortex at approximately the same time that the TMS is applied) and decreases in excitability can be induced when the interval is ~10 ms (PAS 10 ; afferent volley arriving before the cortical stimulus is applied) (Stefan, Kunesch, Benecke, Cohen, & Classen, 2002;Stefan et al, 2000;Wolters et al, 2003). More recently, PAS-like protocols have been used to modulate connectivity within corticocortical pathways (Arai et al, 2011;Buch, Johnen, Nelissen, O'Shea, & Rushworth, 2011;Groppa et al, 2012). While only a few studies to date have used 'cortical PAS', they suggest that cortical PAS can induce changes in synaptic strength in the stimulated pathways.…”