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. 2013 Apr 1;591(7):1889-906.
doi: 10.1113/jphysiol.2012.245746. Epub 2013 Jan 7.

Intracortical circuits, sensorimotor integration and plasticity in human motor cortical projections to muscles of the lower face

G Pilurzi  1 , A Hasan, T A Saifee, E Tolu, J C Rothwell, F Deriu
Affiliations

Intracortical circuits, sensorimotor integration and plasticity in human motor cortical projections to muscles of the lower face

G Pilurzi et al. J Physiol. .

Abstract

Previous studies of the cortical control of human facial muscles documented the distribution of corticobulbar projections and the presence of intracortical inhibitory and facilitatory mechanisms. Yet surprisingly, given the importance and precision in control of facial expression, there have been no studies of the afferent modulation of corticobulbar excitability or of the plasticity of synaptic connections in the facial primary motor cortex (face M1). In 25 healthy volunteers, we used standard single- and paired-pulse transcranial magnetic stimulation (TMS) methods to probe motor-evoked potentials (MEPs), short-intracortical inhibition, intracortical facilitation, short-afferent and long-afferent inhibition and paired associative stimulation in relaxed and active depressor anguli oris muscles. Single-pulse TMS evoked bilateral MEPs at rest and during activity that were larger in contralateral muscles, confirming that corticobulbar projection to lower facial muscles is bilateral and asymmetric, with contralateral predominance. Both short-intracortical inhibition and intracortical facilitation were present bilaterally in resting and active conditions. Electrical stimulation of the facial nerve paired with a TMS pulse 5-200 ms later showed no short-afferent inhibition, but long-afferent inhibition was present. Paired associative stimulation tested with an electrical stimulation-TMS interval of 20 ms significantly facilitated MEPs for up to 30 min. The long-term potentiation, evoked for the first time in face M1, demonstrates that excitability of the facial motor cortex is prone to plastic changes after paired associative stimulation. Evaluation of intracortical circuits in both relaxed and active lower facial muscles as well as of plasticity in the facial motor cortex may provide further physiological insight into pathologies affecting the facial motor system.

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Figures

Figure 1
Figure 1. Motor responses with short (S), medium (M) and long (L) latency recorded from resting and active depressor anguli oris (DAO) muscles following single-pulse transcranial magnetic stimulation (TMS) of the left facial motor cortex, in a representative subject
In both resting and active muscle states, the S-wave is present only ipsilaterally to the stimulation side, with no volume conduction to the contralateral muscle. By contrast, M- and L-waves are detected bilaterally. Each trace reports 5 superimposed trials. The TMS intensities were 120% of resting motor threshold (RMT) in the resting conditions and 120% of active motor threshold (AMT) in the active conditions (10% of maximal voluntary contraction).
Figure 2
Figure 2. Motor-evoked potentials (MEPs) recorded from resting and active DAOs of a representative subject, following single-pulse TMS of the left facial motor cortex
The ipsilateral MEP is smaller and delayed when compared with the contralateral MEP, in both resting and active conditions (10% of maximal voluntary contraction). Each trace is the average of 10 single trials. The TMS intensities were 120% of RMT in the resting conditions and 120% of AMT in the active conditions. Arrows indicate the time of stimulus delivery. M, medium-latency wave.
Figure 3
Figure 3. Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) assessed in the cortical representation of the DAO, in the resting and active conditions
A, mean data obtained from 14 subjects at rest are reported. Paired TMS of the left facial motor cortex [control stimulus (CS) 0.7RMT] induced significant inhibition [interstimulus intervals (ISIs) of 2–3 ms] and facilitation (ISIs of 10–15 ms) of ipsi- and contralateral MEPs. At SICI ISIs, a significantly (‡P < 0.01) stronger effect was observed on the contralateral (cDAO) than on the ipsilateral projection (iDAO). In contrast, at ICF ISIs, MEP facilitation did not differ significantly between sides. B, mean data from 16 subjects in the active conditions are reported. The MEP amplitudes at the two CS intensities (0.7AMT and 0.8AMT) and on the two sides were averaged. A significant inhibition at 2–3 ms and a significant facilitation at 10–15 ms were observed. Ordinates indicate MEP amplitude expressed as a percentage of unconditioned MEP induced by the test stimulus (TS alone), taken as 100% (horizontal dashed line). *P < 0.05. Error bars represent means ± SEM.
Figure 4
Figure 4. Comparison of SICI and ICF in the lower facial motor cortex in resting and active conditions
Data from contralateral and ipsilateral DAO muscles as well as SICI and ICF intervals were analysed separately (n = 14 subjects). The extent of SICI and ICF was significantly different in the resting and active muscle states (0.7RMT versus 0.8AMT) at different ISIs depending on the ipsi- and contralateral projection. Ordinates indicate MEP amplitude expressed as a percentage of unconditioned MEP induced by the TS alone, which was taken as 100% (horizontal dashed line). ‡P < 0.05. Error bars represent means + SEM.
Figure 5
Figure 5. Effects of stimulation of the right facial nerve on motor potentials induced in the DAO by TMS of the left facial motor cortex
A, the graph shows mean data obtained from the relaxed cDAO of 15 subjects. Facial nerve electrical stimulation preceded single-pulse TMS of the left facial motor cortex by time intervals of 5, 10, 15, 20, 25 and 30 ms. No evidence of significant short-afferent inhibition of the conditioned MEP was observed at any ISI tested. B, the graph shows mean data obtained from the relaxed cDAO of 7 subjects. Long-afferent inhibition was tested by pairing facial nerve stimulation with a TMS pulse at ISIs of 150 and 200 ms. A significant inhibition at 200 ms ISI was observed. Ordinates indicate MEP amplitude expressed as a percentage of the unconditioned MEP induced by the TS alone, taken as 100% (horizontal dashed line). *P < 0.05. Error bars represent means ± SEM.
Figure 6
Figure 6. Effects of PAS20 intervention on the facial motor cortex
A, the left panel reports the averaged motor-evoked potential recorded from the relaxed right depressor anguli oris muscle following single-pulse TMS of the left facial motor cortex, before PAS20 intervention (baseline MEP). The right panel shows MEP changes observed 20 min after PAS20 intervention. The PAS20 protocol consisted of pairing 200 stimuli (electrical stimulation of the right facial nerve and TMS of the left facial motor cortex) with an ISI of 20 ms. The intensity of electrical stimulation was 3 times subject perceptual threshold; TMS intensity was 1.1RMT. Each trace is the average of 20 single trials. B, the graph reports data from 15 subjects showing the time course of mean MEP changes, compared with the baseline (MEP pre), observed after 0, 10, 20 and 30 min from the PAS20 intervention. *P < 0.05. Error bars represent means ± SEM.
Figure 7
Figure 7. Effects of PAS10 and PAS20 interventions on the magnitude of MEPs recorded from the DAO, at rest
A, the graph shows, for each subject, average MEPs recorded from the relaxed DAO following PAS20 (filled diamonds, n = 15 subjects) and PAS10 interventions (open diamonds, n = 14 subjects). Post-PAS, the MEP amplitude was calculated as the mean of MEPs collected at T0–T30. Ordinates indicate MEP amplitude expressed as a percentage of baseline MEP, which was taken as 100% (horizontal dashed line). Note that, compared with baseline, MEP size was enhanced in 86.6% of subjects after PAS20 and in 42.8% of subjects after PAS10 intervention. B, the histogram shows the time course of effects of PAS20 (filled columns) and PAS10 (open columns) in 14 subjects. Amplitudes of baseline MEP (MEP pre) and of MEP collected after 0, 10, 20 and 30 min are reported for PAS20 and PAS10 protocols. Compared with baseline, a significant facilitatory effect was observed only after PAS20 at all time points tested, whereas no significant effects were detected after PAS10. Comparing MEP amplitudes in the two experimental conditions, a significant difference was detected only 20 min after PAS intervention. *P < 0.05. Error bars represent means + SEM.
Figure 8
Figure 8. Simultaneous EMG recording from the relaxed orbicularis oculi (O oculi), nasalis (Nas) and DAO muscles during ipsilateral stimulation of supraorbital and facial nerves, in a representative subject
A, electrical stimulation of the supraorbital nerve (pulse duration 0.2 ms, intensity 9 mA) induced clear R1 and R2 responses of the blink reflex in the orbicularis oculi and small conducted R1 and R2 responses in the Nas; by contrast, neither R1 nor R2 responses were seen in the DAO. B, electrical stimulation of the facial nerve (pulse duration 0.2 ms, intensity 3 mA) showed an electrical stimulation-induced motor potential, which was clearly visible in the DAO but not in the Nas and orbicularis oculi. Each trace reports 10 superimposed trials. Each trial was DC corrected, and traces in A were also rectified.
Figure 9
Figure 9. Effects of PAS20 intervention on the blink reflex and on MEPs evoked by TMS of the left facial motor cortex in the contralateral DAO
The histogram reports data from 6 subjects in whom long-lasting effects induced by PAS20on the area of the first (R1) and second (R2) areas of the blink reflex as well as on the amplitude of DAO MEPs were measured after 0 min (T0) and 20 min (T20) from PAS20 delivery. Post-PAS effects on R1 and R2 areas and on MEP amplitude were expressed at T0 and T20 as a percentage of the pre-PAS (baseline) value. A significant post-PAS facilitatory effect was observed only for DAO MEP amplitude at all time points tested (*P < 0.05), whereas no significant effects were detected in R1 and R2 areas. Comparing PAS long-lasting effects on MEP and blink reflex, a significant difference was found between DAO and R2 at the T20 time point (‡P < 0.05). Error bars represent means + SEM.
Figure 10
Figure 10. Effects of PAS20 intervention on the blink reflex recovery cycle, R2 recovery index and MEPs evoked by TMS of the left facial motor cortex in the contralateral DAO
Graphs show mean data obtained from 6 subjects. A, the blink reflex recovery cycle was tested by pairing electrical stimuli given to the supraorbital nerve at ISIs of 250, 500 and 1000 ms. The ratio of the R2 conditioned area/unconditioned area was calculated for each ISI. The R2 recovery cycle was measured before PAS20 (baseline, filled diamonds) and after 0 min (T0, open squares) and 20 min (T20, open circles) from PAS delivery. Compared with baseline, no significant change of R2 recovery cycle was observed at any time point tested, for all ISIs. B, effects of the PAS20 protocol on the amplitude of DAO MEPs and on the R2 recovery index (calculated as the average of the R2 ratio at 250 and 500 ms) are reported in the graph. The DAO MEP and R2 recovery index ratios at T0 and T20 are expressed as a percentage of baseline values. A significant facilitatory effect of the PAS protocol was observed on DAO MEPs at both T0 and T20, whereas no significant changes were observed in the R2 recovery index at any time point tested. *P < 0.05. Error bars represent means + SEM.
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