Modulation of long-latency afferent inhibition by the amplitude of sensory afferent volley

Long-latency afferent inhibition (LAI) is the inhibition of the transcranial magnetic stimulation (TMS) motor-evoked potentials (MEP) by the sensory afferent volley following electrical stimulation of a peripheral nerve. It is unknown how the activation of sensory afferent fibers relates to the magnitude of LAI. This study investigated the relationship between LAI and the sensory nerve action potentials (SNAP) from the median nerve (MN) and the digital nerves (DN) of the second digit. LAI was obtained by delivering nerve stimulation 200 ms before a TMS pulse delivered over the motor cortex. Experiment 1 assessed the magnitude of LAI following stimulation of the contralateral MN or DN using nerve stimulus intensities relative to the maximum SNAP (SNAPmax) of that nerve and two TMS intensities (0.5- and 1-mV MEP). Results indicate that MN LAI is maximal at ~50% SNAPmax, when presumably all sensory afferents are recruited for TMS of 0.5-mV MEP. For DN, LAI appears at ~50% SNAPmax and does not increase with further recruitment of sensory afferents. Experiment 2 investigated the magnitude of LAI following ipsilateral nerve stimulation at intensities relative to SNAPmax. Results show minimal LAI evoked by ipsilateral MN and no LAI following ipsilateral DN stimulation. Implications for future studies investigating LAI include adjusting nerve stimulation to 50% SNAPmax to obtain maximal LAI. Additionally, MN LAI can be used as a marker for neurological disease or injury by using a nerve stimulation intensity that can evoke a depth of LAI capable of increasing or decreasing. NEW & NOTEWORTHY This is the first investigation of the relationship between long-latency afferent inhibition (LAI) and the sensory afferent volley. Differences exist between median and digital nerve LAI. For the median nerve, LAI increases until all sensory fibers are presumably recruited. In contrast, digital nerve LAI does not increase with the recruitment of additional sensory fibers but rather is present when a given volume of sensory afferent fibers is recruited (~50% of maximum sensory nerve action potential). This novel data provide practical guidelines and contribute to our understanding of the mechanisms underlying LAI.

Short-latency afferent inhibition determined by the sensory afferent volley

Short-latency afferent inhibition (SAI) is characterized by the suppression of the transcranial magnetic stimulation motor evoked potential (MEP) by the cortical arrival of a somatosensory afferent volley. It remains unknown whether the magnitude of SAI reflects changes in the sensory afferent volley, similar to that observed for somatosensory evoked potentials (SEPs). The present study investigated stimulus-response relationships between sensory nerve action potentials (SNAPs), SAI, and SEPs and their interrelatedness. Experiment 1 ( n = 23, age 23 ± 1.5 yr) investigated the stimulus-response profile for SEPs and SAI in the flexor carpi radialis muscle after stimulation of the mixed median nerve at the wrist using ∼25%, 50%, 75%, and 100% of the maximum SNAP and at 1.2× and 2.4× motor threshold (the latter equated to 100% of the maximum SNAP). Experiment 2 ( n = 20, age 23.1 ± 2 yr) probed SEPs and SAI stimulus-response relationships after stimulation of the cutaneous digital nerve at ∼25%, 50%, 75%, and 100% of the maximum SNAP recorded at the elbow. Results indicate that, for both nerve types, SAI magnitude is dependent on the volume of the sensory afferent volley and ceases to increase once all afferent fibers within the nerve are recruited. Furthermore, for both nerve types, the magnitudes of SAI and SEPs are related such that an increase in excitation within somatosensory cortex is associated with an increase in the magnitude of afferent-induced MEP inhibition.

The pulse duration of electrical stimulation influences H-reflexes but not corticospinal excitability for tibialis anterior

The afferent volley generated by neuromuscular electrical stimulation (NMES) influences corticospinal (CS) excitability and frequent NMES sessions can strengthen CS pathways, resulting in long-term improvements in function. This afferent volley can be altered by manipulating NMES parameters. Presently, we manipulated one such parameter, pulse duration, during NMES over the common peroneal nerve and assessed the influence on H-reflexes and CS excitability. We hypothesized that compared with shorter pulse durations, longer pulses would (i) shift the H-reflex recruitment curve to the left, relative to the M-wave curve; and (ii) increase CS excitability more. Using 3 pulse durations (50, 200, 1000 μs), M-wave and H-reflex recruitment curves were collected and, in separate experiments, CS excitability was assessed by comparing motor evoked potentials elicited before and after 30 min of NMES. Despite finding a leftward shift in the H-reflex recruitment curve when using the 1000 μs pulse duration, consistent with a larger afferent volley for a given efferent volley, the increases in CS excitability were not influenced by pulse duration. Hence, although manipulating pulse duration can alter the relative recruitment of afferents and efferents in the common peroneal nerve, under the present experimental conditions it is ineffective for maximizing CS excitability for rehabilitation.

Cortical Representation of Venous Nociception in Humans

Painful sensations can be evoked by application of thermal, mechanical, and chemical stimuli to the blood vessels. The cortical substrates of these sensations are unknown. We therefore used whole-head magnetoencephalography to record cortical responses to painful laser stimuli applied cutaneously and intravenously to the dorsum of the hand in healthy human subjects. Similar to the cutaneous stimuli, venous stimulation nearly simultaneously activated the contralateral primary and the bilateral secondary somatosensory cortices. In the venous stimulation condition, all activation peaks were about 50 ms earlier than in the cutaneous stimulation condition. Locations of responses to both stimuli did not differ. These results show that the afferent volley from the veins reaches the cerebral cortex significantly earlier than that from the skin. This might be due to differences in peripheral conduction velocity. Apart from this, these findings demonstrate that venous nociception shares the cortical representation of cutaneous nociception in human somatosensory cortices. Thus the cortical representation of nociceptive processing from tissues of mesodermal and ectodermal origin appears to be similar.

A cortical evoked potential study of afferents mediating human esophageal sensation

The aim of this study was to compare the characteristics of esophageal cortical evoked potentials (CEP) following electrical and mechanical stimulation in healthy subjects to evaluate the afferents involved in mediating esophageal sensation. Similarities in morphology and interpeak latencies of the CEP to electrical and mechanical stimulation suggest that they are mediated via similar pathways. Conduction velocity of CEP to either electrical or mechanical stimulation was 7.9–8.6 m/s, suggesting mediation via thinly myelinated Aδ-fibers. Amplitudes of CEP components to mechanical stimulation were significantly smaller than to electrical stimulation at the same levels of perception, implying that electrical stimulation activates a larger number of afferents. The latency delay of ∼50 ms for each mechanical CEP component compared with the corresponding electrical CEP component is consistent with the time delay for the mechanical stimulus to distend the esophageal wall sufficiently to trigger the afferent volley. In conclusion, because the mechanical and electrical stimulation intensities needed to obtain esophageal CEP are similar and clearly perceived, it is likely that both spinal and vagal pathways mediate esophageal CEP. Esophageal CEP to both modalities of stimulation are mediated by myelinated Aδ-fibers and produce equally robust CEP responses. Both techniques may have important roles in the assessment of esophageal sensory processing in health and disease.

Hypoxia on Hippocampal Slices from Mice Deficient in Dystrophin (mdx) and Isoforms (mdx3cv)

Slices from control C57, mdx, and mdx3cv mice were made hypoxic until both field excitatory postsynaptic potential (fEPSP) and presynaptic afferent volley (AV) disappeared (H1). After reoxygenation and recovery of fEPSP, a second and longer hypoxic test (H2) lasted 3 minutes beyond the time required to block AV. When slices were kept in 10 mmol/L glucose, H1 abolished AV 37 and 19% earlier in slices from mdx and mdx3cv mutants than in control slices (where H1 = 12 ± 4.6 minutes, mean ± SD). During H2 or when slices were kept in 4 mmol/L glucose, AV vanished even more quickly, but the times to block did not differ significantly between slices from controls and mutants. After reoxygenation, AV fully recovered in most slices. Rates of blockade of fEPSPs were comparable in all slices, and most fEPSPs recovered fully after H1. But even in the presence of 10 mmol/L glucose, the second hypoxia suppressed fEPSPs irreversibly in some slices: 2 of 10 from control, 3 of 7 from mdx, and 1 of 6 from mdx3cv mice. Most slices in 4 mmol/L glucose showed no recovery at all: six of seven from control, three of five from mdx, and four of five from mdx3cv mice. Thus, slices from mdx mice were more susceptible than other slices to irreversible hypoxic failure when slices were kept in 10 mmol/L glucose, but they were less susceptible than other slices when kept in 4 mmol/L glucose. In conclusion, the lack of full-length dystrophin (427 kDa) predisposes to quicker loss of nerve conduction in slices from mdx and mdx3cv mutants and improved posthypoxic recovery of fEPSPs in 4 mmol/L glucose in slices from mdx but not mdx3cv mutants, perhaps because the 70-kDa and other C-terminal isoforms are still present in mdx mice.

Altered patterns of reflex excitability subsequent to contusion injury of the rat spinal cord

1. The present study investigated regulation of reflex excitability after experimental contusion injury of the spinal cord. 2. Four measures of H-reflex excitability were evaluated in normal rats and at 6, 28, and 60 days after contusion injury at the T8 level: 1) reflex thresholds, 2) slope of the reflex recruitment curves, 3) maximal plantar H-reflex/maximal plantar M-response (Hmax/Mmax) ratios, and 4) rate-sensitive depression (i.e., the decrease in reflex magnitude relative to repetition rate). 3. Tested as a function of the afferent volley magnitude, the thresholds for reflex initiation fell progressively subsequent to contusion injury. No change was observed at 6 days postinjury, and the decrease at 28 days was not significant. However, by 60 days postinjury, the threshold had decreased by 23% of the maximal afferent volley, and this decrease was significant, [analysis of variance (ANOVA, P < or = 0.01)]. 4. Hmax/Mmax ratios elicited in postcontusion animals at 0.3 Hz were not significantly different from those recorded in normal animals. 5. The slopes of the recruitment curves were markedly reduced subsequent to contusion injury. The decrease was greatest at 6 days postinjury. Although some recovery toward normal occurred at 28 and 60 days postinjury, the slopes of recruitment curves in postcontusion animals remained significantly decreased. 6. H-reflexes elicited at 1-5 Hz were less sensitive to rate depression in postcontusion animals than in normal animals at the same respective frequencies. The decrease was progressive in onset, becoming significant by 28 days postinjury, and of an enduring nature, i.e., still significantly different from normal in the reflexes tested 60 days postinjury. 7. Rate sensitivity of the tibial nerve monosynaptic reflex (MSR) was also compared in normal and postcontusion animals. Rate sensitivity of the tibial MSRs was significantly reduced at 28 and 60 days post-contusion, compared with normal animals. 8. These data indicate that significant changes in lumbar reflex excitability result from midthoracic contusion injury of the spinal cord. These changes include reflex threshold, slope of recruitment, and rate-sensitive depression. Although recruitment slope was most altered in the shortest postinjury interval tested, followed by some recovery, the other changes were progressive in onset and enduring in duration.

Spinal Neuronal activity During the Pectoral Fin Reflex of the Dogfish: Pathways For Reflex Generation and Cerebellar Control

ingle units were recorded from the spinal cord of decerebrate dogfish (Scyliorhinus canicula) during pectoral fin reflexes (PFR) evoked by electrical pulse trains to the fin. The units were classified as primary afferent neurones, motoneurones or interneurones. Motoneurones discharged for limited (and various) periods during the reflex at latencies of 20 ms or more. There was no evidence for monosynaptic activation by primary afferents. Short-latency (S) units received monosynaptic input from fast-conducting afferents at latencies (&lt;20 ms) appropriate for pre-motor interneurones. However, excitation of individual S-units by intracellular current injection never evoked motoneurone discharges, suggesting that convergence is necessary for motoneurone activation. Intracellular recordings from S-units which discharged for periods longer than the duration of the afferent volley generated by the fin stimulus showed that they receive other inputs in addition to those from primary afferent fibres. Intermediate-latency (I) units had similar properties to S-units except for a longer latency (&gt;30ms), which ruled out monosynaptic excitation by fast-conducting afferents. Antidromic activation of S- and I-units by high spinal stimulation was rarely seen and orthodromic driving was also uncommon. A significant number of interneurones with latencies greater than 60 ms (L-units) were antidromically activated by high spinal stimulation. Their discharges were often long-lasting (&gt;1 s) and we suggest that they may provide input to the cerebellum during the PFR.