Short-and long-latency afferent inhibition of the human leg motor cortex by H-reflex subthreshold electrical stimulation at the popliteal fossa

Abstract

In humans, peripheral sensory stimulation inhibits subsequent motor evoked potentials (MEPs) induced by transcranial magnetic stimulation; this process is referred to as short- or long-latency afferent inhibition (SAI or LAI, respectively), depending on the inter-stimulus interval (ISI) length. Although upper limb SAI and LAI have been well studied, lower limb SAI and LAI remain under-investigated. Here, we examined the time course of the soleus (SOL) muscle MEP following electrical tibial nerve (TN) stimulation at the popliteal fossa at ISIs of 20-220 ms. When the conditioning stimulus intensity was three-fold the perceptual threshold, MEP amplitudes were inhibited at an ISI of 220 ms, but not at shorter ISIs. TN stimulation just below the Hoffman (H)-reflex threshold intensity inhibited MEP amplitudes at ISIs of 30, 35, 100, 180 and 200 ms. However, the relationship between MEP inhibition and the P30 latency of somatosensory evoked potentials (SEPs) did not show corresponding ISIs at the SEP P30 latency that maximizes MEP inhibition. To clarify whether the site of afferent-induced MEP inhibition occurs at the cortical or spinal level, we examined the time course of SOL H-reflex following TN stimulation. H-reflex amplitudes were not significantly inhibited at ISIs where MEP inhibition occurred but at an ISI of 120 ms. Our findings indicate that stronger peripheral sensory stimulation is required for lower limb than for upper limb SAI and LAI and that lower limb SAI and LAI are of cortical origin. Moreover, the direct pathway from the periphery to the primary motor cortex may contribute to lower limb SAI.

Keywords: Hoffman reflex; Long-latency afferent inhibition; Sensorimotor integration; Short-latency afferent inhibition; Transcranial magnetic stimulation.

Fig. 1

Experimental setup and somatosensory evoked potential waveform. A Electrodes for conditioning and test tibial nerve (TN) stimulation (CS and TS_TN, the black and white are the anode and cathode, respectively) and for electromyography (EMG) recording. B The H-reflex and M-wave recruitment curves (a black line and circles: H-reflex, a gray line and squares: M-wave). PT perceptual threshold, HT H-reflex threshold, MT motor threshold C an averaged waveform of somatosensory evoked potentials following TN stimulation in a representative participant. P30 appeared first. Following N70, negative and positive peaks appeared at approximately 100 and 200 ms after stimulation, respectively

Fig. 2

Time course of soleus muscle motor evoked potentials following conditioning tibial nerve stimulation with three-fold the perceptual threshold intensity at inter-stimulus intervals of 20–220 ms. The baseline is the mean motor evoked potential (MEP) amplitude with test transcranial magnetic stimulation (TS_TMS) alone (Pre-TS alone) and is shown as a black dotted line. Conditioned MEP amplitudes and MEP amplitude with TS_TMS alone after paired stimulation (Post-TS alone) are normalized by the baseline. The boxplot shows group data, and the gray dots show individual participant data. ** P < 0.01 compared to baseline. ISI inter-stimulus interval

Fig. 3

Soleus motor evoked potentials following conditioning tibial nerve stimulation with the H-reflex threshold minus 1 mA intensity. A Examples of mean soleus (SOL) muscle motor evoked potentials (MEPs) following conditioning tibial nerve (TN) stimulation (CS) in a representative participant with test transcranial magnetic stimulation (TS_TSM) at inter-stimulus intervals (ISIs) of 30, 45, and 100 ms. B Time course of SOL MEPs following CS with the H-reflex threshold minus 1 mA intensity at ISIs of 20–220 ms. The baseline is the mean MEP amplitude with TS_TMS alone (Pre-TS alone) and is shown as a black dotted line. Conditioned MEP amplitudes and MEP amplitude with TS_TMS alone after paired stimulation (Post-TS alone) are normalized by the baseline. The boxplot shows group data, and the gray dots show individual participant data. C A second-order polynomial trend between ISIs relative to the somatosensory evoked potential P30 latency and MEP modulation is shown as a dark gray dotted curve with a minimum at P30–1.7 ms. The ISI and MEP distributions are shown as a density plot with the maximum value being one. SOL MEPs following TN stimulation were the least inhibited at an ISI of approximately 5 ms after P30 latency. * P < 0.05, ** P < 0.01, *** P < 0.001 compared to baseline

Fig. 4

Time course of the soleus muscle H-reflex following conditioning tibial nerve stimulation with the H-reflex threshold minus 1 mA intensity at inter-stimulus intervals of 20–220 ms. A Examples of mean soleus (SOL) muscle H-reflex following conditioning tibial nerve (TN) stimulation (CS) in a representative participant with test TN stimulation (TS_TN) at inter-stimulus intervals (ISIs) of 30, 45, and 100 ms. B Time course of SOL H-reflex following CS with the H-reflex threshold minus 1 mA intensity at ISIs of 20–220 ms. The baseline is the mean H-reflex amplitude with test tibial nerve stimulation (TS_TN) alone (Pre-TS alone) and is shown as a black dotted line. Conditioned H-reflex amplitudes and H-reflex amplitude with TS_TN alone after paired stimulation (Post-TS alone) are normalized by the baseline. The boxplot shows group data, and the gray dots show individual participant data. * P < 0.05 compared to baseline. ISI inter-stimulus interval

Fig. 5

Modulation of soleus muscle motor evoked potentials and H-reflexes following conditioning tibial nerve stimulation at long inter-stimulus intervals. A and B Time course of soleus muscle motor evoked potentials (MEPs) and H-reflex, respectively, following conditioning tibial nerve (TN) stimulation with the H-reflex threshold minus 1 mA intensity at inter-stimulus intervals (ISIs) of 60–200 ms. The baseline is the mean MEP with test transcranial magnetic stimulation (TS_TMS) alone (A) or the mean H-reflex amplitude with test tibial nerve stimulation (TS_TN) alone (B) (Pre-TS alone) and is shown as a black dotted line. Conditioned amplitudes and the amplitude with TS alone after paired stimulation (Post-TS alone) are normalized by the baseline. The boxplot shows group data, and the gray dots show individual participant data. * P < 0.05 compared to baseline