Negative difference potential isolates scalp potentials generated by activity in supraspinal nociceptive pathways

A negative difference potential (75–240 ms poststimulus) was computed by subtracting the sural nerve-evoked somatosensory evoked potential (SEP) elicited at the pain threshold level from SEPs elicited at noxious levels. The effects of stimulus intensity and interstimulus interval on the negative difference potential amplitude plus conduction velocity measurements and a dipole source localization analysis all suggest that the negative difference potential reflects the response of neurons in the primary somatosensory cortex to inputs that arise from the nociceptive A delta peripheral afferents. Furthermore, a comparison of these results with our earlier sural nerve-evoked SEP studies suggests that these pain-related inputs to the primary somatosensory cortex are largely inhibitory.     

Effects of interstimulus interval on scalp topographies evoked by noxious sural nerve stimulation

The amplitude of the late pain-related negative-positive peak complex, which we have labeled SP3 (134–150 ms) and SP6 (277–331 ms), respectively, increased with increasing interstimulus interval (ISI). This contrasts with the nociceptive spinal withdrawal reflex and subjective pain rating data, which implied that nociceptive somatosensory processes were unaffected by ISI at stimulus levels that were well within the pain range. A scalp topographic analysis strongly suggested that none of the brain areas responsible for SP3 or SP6 are involved exclusively in nociception. We also observed a pain-related positive potential apporximately 161–177 ms following sural nerve stimulation that has not been reported by others. A dipole source localization analysis and the effects of ISI and stimulus intensity on this potential suggest that it is generated by the response of primary somatosensory cortex neurons to inputs arising from the innocuous peripheral afferents and that this response is inhibited by noxious inputs.     

Activation of respiratory afferents by resistive loaded breathing modifies somatosensory evoked potentials to median nerve stimulation in humans

The cortical projections of respiratory afferents (vagus and respiratory muscle nerves) are well documented in humans. It is also shown that their activation during loaded breathing modifies the perception of tactile sensation as well as the motor drive to skeletal muscles. The effects of expiratory or inspiratory loaded breathing on somatosensory evoked potentials (SEPs) elicited by median nerve stimulation were studied in eight healthy subjects. No significant changes occurred in latencies of N20, N30 and P40 throughout the expiratory loading period, except for a significant lengthening in P1 latency compared with unloaded breathing. However, inspiratory loading induced a significant increase in peak latency of N20, N30 and P40 components. We suggest that projections of inspiratory afferents from the diaphragm and the intercostal muscles, activated by inspiratory loading, could be responsible for the lengthened latency of median nerve SEP components. Thus, respiratory afferents very likely interact with pathways of the somatosensory system.     

Interstimulus Interval Has No Effect on a Mid-Latency Scalp Potential Generated by Innocuous-Related Activity in the Primary Somatosensory Cortex

The sural nerve-evoked somatosensory evoked potential (SEP) scalp topography was separated into stable periods, where a stable period refers to consecutive time points with the same topographic pattern. The stimulus intensity-amplitude function, conduction velocity measurements, and a dipole source localization analysis of one of these stable periods, SP1 (60-90 ms post-stimulus), strongly suggests that it is generated by the response of neurons in the primary somatosensory cortex (SI) to inputs arising from the innocuous A peripheral afferents. Interstimulus intervals (ISI) ranging between 2.5 s and 10.0 s had no effect on SP1 amplitude. This contrasts with an earlier report from this laboratory demonstrating that subjective magnitude ratings and the amplitude of another stable period that appears at about 160-180 ms post-stimulus and that is also generated in SI, increase with decreasing ISI. Thus, ISI appears to affect perception and the late but not the mid-latency responses in SI.     

A comparison of awake and sleeping cortical states by analysis of the somatosensory-evoked response of postcentral area 1 in rhesus monkey

Summary The response of primary somatosensory cortex (SI) to cutaneous stimulation of the hand was studied in one unanesthetized monkey to examine more closely the previously reported dependence of a behaviorally relevant late component of the evoked potential, N1, upon two behavioral states of arousal, slow-wave sleep (SWS) and inactive wakefulness. Simultaneous recordings of the somatosensory-evoked potentials (SEP), multiple unit activities (MUA) and current source-densities (CSD) at 12 depths through area 1 were collected during both states and analyzed to identify the cortical events that generate the SEP. As previously reported, the N1 component of the SEP was diminished during sleep. Although the earlier components of the SEP were evoked during both states, the excitatory events that characterize the awake N1 were replaced during SWS by an interval of strong inhibition which was terminated by a burst of cortical MUA. CSD analysis of the SWS inhibitory interval revealed large current sources through layer III above the depth of maximal MUA inhibition indicating that an outward conductance became activated on the apical trunks of pyramidal neurons during SWS. These data support the proposed involvement of events underlying N1 in the coding of touch experience.     

Timing and characteristics of perceptual attenuation by transcranial stimulation: a study using magnetic cortical stimulation and somatosensory-evoked potentials.

Transcranial cortical magnetic stimulation (CMS) is a noninvasive, non-noxious procedure to induce perceptual attenuation when applied concomitant to sensory stimuli. To investigate the perceptual timing of simple stimulus features in the somatosensory modality, we applied right hemisphere CMS at different intervals following a stimulus delivered to the left hand. Different intervals between peripheral stimuli and CMS were defined according to the components of the somatosensory-evoked potentials (SEP), previously obtained in response to the same stimulus. Perceptual attenuation was maximal when CMS coincided with the primary cortical response (parietal N20 potential); conversely, perception of stimulus intensity was not modified when CMS was concomitant with the N200 and P300 potentials. Using small CMS intensities, a "perceptual dip" was observed when CMS arrived in coincidence with the N120 potential, a SEP response thought to be originated in part in the second somatic area. Our results support the view that both N200 and P300 are post-perceptual responses. The results also suggest that the cortical processes active during the N20 and N120 potentials may be essential for the conscious perception of somatosensory stimuli delivered to the hand.     

Sensitisation of articular afferents in normal and inflamed knee joints by substance P in the rat

To examine whether substance P (SP) influences the response properties of fine articular afferents in normal and acutely inflamed joints, single units were recorded from the rat knee during normal and noxious joint rotations. Only three of 39 units were activated by a single bolus injection of 0.1 mM SP. However, 35% (7/20) of the nerve fibres from the normal joint and 21% (4/19) of the units from the inflamed joint significantly increased their responses to movements after the SP injection. This was most prominent during noxious movements in normal joints, whereas in inflamed joints increase of responses occurred mainly during normal movements. These data indicate that SP may also be involved in the process of sensitisation of primary afferents during an inflammation.     

Gating of somatosensory evoked potentials during voluntary movement of the lower limb in man

Somatosensory evoked potentials (SEPs) evoked by stimulation of the tibial nerve (TN) in the popliteal fossa, the sural nerve (Sur) at the lateral malleole, and an Achilles tendon (Achilles) tap were recorded before and during voluntary plantarflexion, dorsiflexion, and cocontraction of the ipsi- and contralateral foot in normal subjects. Suppression (gating) of the TN-SEP began around 60 ms before the onset of electromyographic activity (EMG), and became maximal 50–100 ms after the onset of EMG. Similar gating was observed for the SEP evoked by activation of muscle afferents (Achilles) and cutaneous afferents (Sur). The TN-SEP was similarly depressed at the onset of a plantarflexion as at the onset of dorsiflexion. A depression, although much smaller, was also observed at the onset of movement of the contralateral limb. The depression of the TN-SEP after the onset of EMG decreased when fast-conducting afferents were blocked by ischemia below the knee joint. The TN-SEP was equally depressed during tonic dorsiflexion, plantarflexion, and cocontraction of dorsi- and plantarflexors. The TN-SEP was depressed for up to 300 ms when preceded by stimulation of Sur or a biceps femoris tendon tap. Gating of lower limb SEPs thus appears to have both central and peripheral components of which neither seems to be specific for the muscle being contracted or the sensory afferents being stimulated. We encourage that caution is taken when drawing functional conclusions regarding movement-specific modulation of afferent inflow to the somatosensory cortex based on observations of gating of lower limb SEP. Received: 25 March 1997 / Accepted: 20 October 1997     

Attentional set effects on spinal and supraspinal responses to pain

The effects of attentional set on subjective magnitude ratings, spinal reflexes, and somatosensory evoked potentials (SEP) elicited by innocuous and painful sural nerve stimulation were investigated in 24 subjects. Cuing stimuli informed subjects as to whether a visual identification or a somatosensory rating task would follow. Twenty percent of the trials were invalidly cued, where the subjects were expecting a visual stimulus but were given a sural nerve stimulus and vice versa. Subjective magnitude ratings were lower in the invalidly cued condition than the validly cued condition. Attentional set had no effect on innocuous-related spinal or early cortical responses, nor on the spinal nociceptive withdrawal reflex. The pain-related negative difference potential (NDP) and P2 component of the SEP were largest in the invalidly cued condition. These results provide further support for our hypothesis that the NDP is generated in part by the anterior cingulate, and suggest that the anterior cingulate response to pain reflects non-pain-specific cognitive processes (e.g., orienting attention towards important stimuli in the environment and/or response competition) and not some aspect of the pain experience. The effects of attentional set on the pain-related P2 suggests that it might correspond to the P3a event-related potential. If this is the case, the pain-related P2 could serve as a useful index of neural processes involved in the cognitive-evaluative aspect of pain.     

Structure of visual evoked magnetic field during sleep in humans

Electrical median nerve stimulation during rest results in two cortical responses: the somatosensory evoked potential (SEP); and the induced beta oscillations (beta event-related synchronization (ERS)). Both types of responses were recorded with electroencephalography and studied during rest and motor behavior in eight normal subjects. During manipulation of a cube with the fingers of the right hand, the beta ERS around 20 Hz, induced by right hand median nerve stimulation, is significantly suppressed, whereas the long-latency SEP components are significantly enhanced. The results suggest that both phenomena can be interpreted as responses of different neuronal structures in sensorimotor areas.     

Dipole-tracing of 'awareness' attenuating the cortical components of somatosensory evoked potentials

Using the dipole-tracing method, the source generators of N18, P22 and P40 of the somatosensory evoked potential (SEP) were estimated as the equivalent dipole. After voluntary action of the thumb flexion, no changes were observed in N18 or P40, but the amplitude of P22 was suppressed. The after-effects of intention accompanied by a voluntary action or the subject's awareness that electrical stimulation will be given after the voluntary action were treated as 'awareness'. By subtracting the pure SEP from SEP during 'awareness', it was found that the equivalent dipole of 'awareness' of P22 was located at the same region of pure P22, but the vector was of opposite orientation. 'Awareness' attenuated the perceptive potential of SEP like P22 generated in the cortex.     

Task-dependent modulation of inhibitory actions within the primary motor cortex

 In 11 healthy subjects motor-evoked potentials (MEPs) and silent periods (SPs) were measured in the right first dorsal interosseus (FDI) and abductor pollicis brevis muscles (APB): (1) when transcranial magnetic cortex stimulation (TMS) was applied at tonic isometric contraction of 20% of maximum force, (2) when TMS was applied during tactile exploration of a small object in the hand, (3) when TMS was applied during visually guided goal-directed isometric ramp and hold finger flexion movements, and (4) when at tonic isometric contraction peripheral electrical stimulation (PES) of the median nerve was delivered at various intervals between PES and TMS. Of the natural motor tasks, duration of SPs of small hand muscles was longest during tactile exploration (APB 205±42 ms; FDI 213±47 ms). SP duration at tonic isometric contraction amounted to 172±35 ms in APB and 178±31 ms in FDI, respectively. SP duration in FDI was shortest when elicited during visually guided isometric finger movements (159±15 ms). At tonic isometric contraction, SP was shortened when PES was applied at latencies –30 to +70 ms in conjunction with TMS. The latter effect was most pronounced when PES was applied 20 ms before TMS. PES-induced effects increased with increasing stimulation strength up to a saturation level which appeared at the transition to painful stimulation strengths. Both isolated stimulation of muscle afferents and of low-threshold cutaneous afferents shortened SP duration. However, PES of the contralateral median nerve had no effect on SPs. Amplitudes of MEPs did not change significantly in any condition. Inhibitory control of motor output circuitries seems to be distinctly modulated by peripheral somatosensory and visual afferent information. We conclude that somatosensory information has privileged access to inhibitory interneuronal circuits within the primary motor cortex. Received: 24 November 1997 / Accepted: 11 August 1998     

Reconsiderations about the abnormalities of somatosensory evoked potentials in motor neuron disease

The frequency of involvement of sensory pathways in motor neuron disease (MND) remains the matter of controversy. For this reason the purpose of the present work was to test how often sensory system involvement might be detected by somatosensory evoked potentials (SEP) studies and then to verify the presence of alteration of the sensory conduction and to detect the frequency of abnormalities of somatosensory peripheral, spinal, subcortical and cortical potentials in MND. SEP were tested after median nerve stimulation at the wrist, recorded from Erb's point, Ce2, Ce7 and scalp. Pearson's correlation coefficients test and Wilcoxon rank-sum test were used for statistical analysis. 74 patients (22 women and 52 men) were examined. Mean age of patients was 54.07 +/- 11.24 years; mean duration of the disease -19.25 +/- 15.87 months. SEP were abnormal in 39 of 74 patients (about 53%) whereas the sensory NCV in median nerve was abnormal in 14 of 74 patients (19%). The most frequent pattern of abnormalities consisted of the absence or delay of cortical responses. The mean values of SEP latencies (N9, N11, N13, N20 and P25) were significantly increased in MND patients (p < 0.05) as compared with controls. The N9 and N11 latencies correlated with the duration of the disease. The results of our study (concerning a large group of MND patients) suggest that the involvement of sensory pathways is not rare in MND.     

Electrophysiological indices of orienting attention toward pain

This study examined the effects of orienting on two pain-related components of the sural nerve-evoked somatosensory evoked potential: the NDP (80-230 ms), which is generated in part by the anterior cingulate cortex (ACCc), and SP6 (280-340 ms). NDP and SP6 amplitudes were larger when subjects oriented their attention away from an invalidly cued location and toward the sural nerve pain than when their attention remained focused on the pain. These results and our earlier studies suggest that the ACCc activity generating the NDP is involved in detecting transient painful stimuli. This activity is enhanced when the pain occurs outside the focus of attention, and it may signal other brain areas that attention should be oriented away from its current focus and toward the pain. SP6 appears to be a pain-evoked P3a event-related potential, with an anterior component involved in orienting attention away from some other task and toward the pain, and an posterior component involved in evaluating the pain.     

经皮电极下神经电刺激场的理论研究

体感诱发电位是检测脊神经和周围神经活动的重要方法，而经皮电刺激是体感诱发电位检测中的常用手段，通过对经皮刺激电极下电势场和电流密度场的分布的研究，可以提高检测的效率与质量。本采用镜像法，对经皮刺激电极下人体组织中电位场和电流密度场的分布进行了理论的推导，得到了场分布的解析解，以此解析解为基础，就可以得到电极放置位置下场分布的数值解，为临床神经刺激提供理论指导。     

Tetrodotoxin block of A-fibre afferents from skin and muscle - a tool to study pure C-fibre effects in the spinal cord

The properties of tetrodotoxin (TTX)-resistant C-fibre afferents of the dorsal roots were tested in Sprague-Dawley rats. Dorsal roots (L4-L6) were blocked with TTX (0.5-1 micro M) and the amplitude of the first response of the dorsal horn superficial interneurones (cord dorsum potential, CDP) to electrical stimulation of peripheral C-fibres in combination with natural noxious stimulation was taken as measure for intact conductivity of different kinds of noxious input by means of the C-fibre refractory period. After blockade of dorsal roots with TTX, formerly masked CDPs from muscle C-fibre afferents were uncovered. Noxious pressure to the gastrocnemius soleus muscle belly and noxious pinch to the calcanean tendon proved to be TTX resistant and therefore was propagated centrally. For cutaneous heat nociceptors it could also be shown that conductivity was intact after blockade of the dorsal roots with TTX. However, we could not exclude the TTX resistance of non-nociceptive receptors of muscle or skin. Nevertheless, blockade of afferents with TTX together with suitable stimulation techniques proves to be a reliable method to investigate central effects from C-fibre afferents without contaminating effects from A-fibres in the rat.     

Shift of attention to the body location of distracters is mediated by perceptual load in sustained somatosensory attention

We investigated the impact of task difficulty on neuronal facilitation of to-be-attended somatosensory vibrotactile stimuli and transient tactile distracters during sustained attention. In Experiment 1, we employed an easy detection task and in Experiment 2 a challenging discrimination task. Sustained attention was manipulated by presenting vibrotactile stimuli simultaneously to the index fingers of both hands for a period of 3 s. These stimuli elicited the steady-state somatosensory evoked potential (SSSEP). Subjects attended to one body side and had to detect target-stimuli that were embedded in the ongoing vibratory streams. When subjects discriminated target-stimuli we found increased SSSEP amplitudes of the to-be-attended vibrotactile stream and greater N140 amplitudes of the somatosensory evoked potential (SEP). During stimulus detection no such facilitation of the SSSEP was found. Greater N140 amplitudes elicited by to-be-ignored distracters indicated that they pull attention to that body location under conditions of low load.     

Physiological characteristics of the solitario-parabrachial relay neurons with tongue afferent inputs in rats

Summary Among 180 units in the solitary tract nucleus (NTS) of rats, 34 solitario-parabrachial relay neurons (SP neurons), were identified by antidromic activation from the parabrachial nucleus. The SP neurons were classified into two groups, fast and slow, according to their antidromic latencies. The responsiveness of the SP in comparison with non-SP neurons was studied by electrical stimulation of three tongue nerves: the lingual (L), chorda tympani (CT) and glossopharyngeal (G) nerves. About half the SP neurons produced a single spike with an orthodromic latency of 2–5 ms, while about one third of them discharged more than two spikes. A few neurons gave rise to a long-lasting discharge consisting of five or six spikes. Some SP neurons were excited by stimulation of the tongue afferents with a low stimulus intensity, but other SP neurons produced spikes at only very high voltages. Fast SP cells were not differentiated from slow SP cells, except that latency of orthodromic responses to CT stimulation was significantly shorter in the former than in the latter (P<0.05, Mann-Whitney U-test). Locations of the SP and non-SP neurons, reconstructed histologically, indicate that they do not distribute evenly throughout the mediolateral extent at the rostral pole of the NTS, but clustered in its medial half.     

Eye movements and vestibular-nerve responses produced in the squirrel monkey by rotations about an earth-horizontal axis

Summary The eye movements produced by constant-speed rotations about an earth-horizontal axis (EHA) are similar in the alert squirrel monkey to those observed in other species. During EHA rotations, there are persistent eye movements, including a nonreversing nystagmus at lower rotation speeds and either a direction-reversing nystagmus or sinusoidal eye movements at higher rotation speeds. Horizontal eye movements are produced by barbecuespit (yaw) rotations, vertical eye movements by head-over-heels (pitch) rotations. The responses can be viewed as composed of a bias component, reflected in the nonreversing nature of the nystagmus, and a cyclic component, reflected in the periodic modulation of slow-phase eye velocity as head position varies. Vestibular-nerve recordings in the barbiturate-anesthetized monkey indicate that neither semicircular-canal nor otolith afferents give rise to a directionally specific dc signal which can account for the bias component. Apparently the appropriate dc signal has to be constructed centrally from a sinusoidal or ac peripheral input. The otolith organs are a likely source of this peripheral input, although contributions from the semicircular canals and from somatosensory receptors must also be considered. Our results suggest that the directional information required to distinguish rotation direction, rather than being contained in the discharge of individual otolith afferents, is encoded across a population of afferents. Possible sources of such information are the phase differences in the sinusoidal responses of otolith afferents differing in their functional polarization vectors.Supported by Grants NS 01330 from the National Institutes of Health and NGR-14-001-225 from the National Aeronautics and Space Administration     

Sensitisation of group III articular afferents to mechanical stimuli by substance P

OBJECTIVE: To examine the excitatory and sensitising effects of substance P (SP) on articular afferents in normal and acutely inflamed cat knee joints. MATERIALS AND METHODS: In anesthetised cats recordings were made from 15 group III (conduction velocity 2.5-20 m/s) and 25 group IV afferent units (conduction velocity < 2.5 m/s) of the medial articular nerve of normal and acutely inflamed knee joints. SP (10 and 100 microg) was administered close-arterially. RESULTS: SP at doses of 10 microg and 100 microg activated less than 50% of both group III and group IV units. The proportion of SP-positive units was significantly higher in inflamed (10 of 21) than in normal joints (2 of 18). SP induced activity in initially silent units or increased ongoing activity after latencies varying from 2 s to 5 min. The SP-evoked activity had an irregular pattern, a variable duration, and was not related to the dose injected. Bolus injections of SP (100 microg) sensitised group III articular afferents but not group IV units to noxious movements of the joint, regardless whether the units were from normal or acutely inflamed joints. The responses to innocuous movements were not influenced by SP. Group III units, initially not activated by any movement, displayed vigorous discharges to noxious movements after close-arterial SP. In 3 group III units tested, the SP-induced augmentation of responses to noxious movements was not mimicked by close-arterial injection of histamine (3.3 microg). CONCLUSIONS: It is concluded that SP contributes to the sensitisation of a subpopulation of high-threshold articular afferents. Thus this neuronal mediator released peripherally in response to an injury or acute inflammation causes considerable changes in the mechanosensitivity of this subpopulation of nociceptive joint afferents.