Topography of middle-latency somatosensory evoked potentials following painful laser stimuli and non-painful electrical stimuli

The aim of this study was to compare cerebral evoked potentials following selective activation of Aβ and Aδ fibers. In 15 healthy subjects, Aβ fibers were activated by electrical stimulation of the left radial nerve at the wrist. Aδ fibers were activated by short painful radian heat pulses, applied to the dorsum of the left hand by a CO₂ laser. Evoked potentials were recorded with 15–27 scalp electrodes, evenly distributed over both hemispheres (bandpass 0.5–200 Hz). The laser-evoked potentials exhibited a component with a mean peak latency of 176 msec (N170). Its scalp topography showed a parieto-temporal maximum contralateral to the stimulus side. In contrast, the subsequent vertex negativity (N240), which appeared about 60 msec later, had a symmetrical scalp distribution. Electrically evoked potentials showed a component at 110 msec (N110), that had a topography similar to the laser-evoked N170. The topographies of the N170 and N110 suggest that they may both be generated in the secondary somatosensory cortex. There was no component in the electrically evoked potential that had a comparable interpeak latency to the following vertex potential: for N60 it was longer, for N110 it was shorter. On the other hand, in the laser-evoked potentials no component could be identified the topography of which corresponded to the primary cortical component N20 following electrical stimulation.     

Pain-related and cognitive components of somatosensory evoked potentials following CO2 laser stimulation in man

We recorded cortical potentials evoked by painful CO₂ laser stimulation (pain SEP), employing an oddball paradigm in an effort to demonstrate event-related potentials (ERP) associated with pain. In 12 healthy subjects, frequent (standard) pain stimuli (probability 0.8) were delivered to one side of the dorsum of the left hand while rare (target) pain stimuli (probability 0.2) were delivered to the other side of the same hand. Subjects were instructed to perform either a mental count or button press in response to the target stimuli. Two early components (N2 and P2) of the pain SEP demonstrated a Cz maximal distribution, and showed no difference in latency, amplitude or scalp topography between the oddball conditions or between response tasks. In addition, another positive component (P3) following the P2 was recorded maximally at Pz only in response to the target stimuli with a peak latency of 593 msec for the count task and 560 msec for the button press task. Its scalp topography was the same as that for electric and auditory P3. The longer latency of pain P3 can be explained not only by its slower impulse conduction but also by the effects of task difficulty in the oddball paradigm employing the pain stimulus compared with electric and auditory stimulus paradigms. It is concluded that the P3 for the pain modality is mainly related to a cognitive process and corresponds to the P3 of electric and auditory evoked responses, whereas both N2 and P2 are mainly pain-related components.     

Pain-related somatosensory evoked potentials following CO2 laser stimulation in man

0ain-related somatosensory evoked potentials (SEPs) following CO₂ laser stimulation were analyzed in normal volunteers. Low power and long wavelength CO₂ laser stimuli to the hand induced a sharp pain which was associated with a large positive component, P320, recorded over the scalp. Amplitude decreased and latency increased with reduction in stimulus intensity and subjective pain feeling. P320 was maximal at the vertex but was distributed widely over the scalp. There were no topographic differences between left- and right-hand stimulation, or between hand and chest stimulation. Lidocaine injection to produce anesthetic nerve block resulted in loss of P320, but the potential was relatively preserved during ischemic nerve block. No potential corresponding to P320 could be recorded following electrical or mechanical tactile stimulation.We consider P320 to be generated by impulses arising from pain stimuli and ascending through Aδ fibers. We propose the thalamus as a generator source from considering its scalp topography, but pain-specific cognition or perception may also be involved in generating this potential.     

Estimation of conduction velocity of the spino-thalamic tract in man

This is the first report of estimating conduction velocity (CV) of the slowly conducting somatosensory spinal tracts or the spino-thalamic tract (STT) in man. The CV of the STT was measured by recording somatosensory evoked potentials (SEPs) following CO₂ laser stimulation of the hand and foot, which was previously shown to cause pain or heat sensation by activating cutaneous nociceptors and by its ascending signals through Aδ fibers and probably STT. When the CV of Aδ fibers was assumed to be 10–15 m/sec, the CV of STT was found to be approximately 8–10 m/sec in normal young subjects. It was slightly slower in subjects over 60 years of age. In contrast, the CV of the posterior column, which was calculated based on SEPs following electrical stimulation of the median and posterior tibial nerves, was approximately 50–60 m/sec.     

Scalp-recorded short and middle latency peroneal somatosensory evoked potentials in normals: comparison with peroneal and median nerve SEPs in patients with unilateral hemispheric lesions

Peroneal somatosensory evoked potentials (SEPs) were performed on 23 normal subjects and 9 selected patients with unilateral hemispheric lesions involving somatosensory pathways.Recording obtained from right and left peroneal nerve (PN) stimulations were compared in all subjects, using open and restricted frequency bandpass filters. Restricted filter (100–3000 Hz) and linked ear reference (A1–A2) enhanced the detection of short latency potentials (P1, P2, N1 with mean peak latency of 17.72, 21.07, 24.09) recorded from scalp electrodes over primary sensory cortex regions. Patients with lesions in the parietal cortex and adjacent subcortical areas demonstrated low amplitude and poorly formed short latency peroneal potentials, and absence of components beyond P3 peak with mean latency of 28.06 msec. In these patients, recordings to right and left median nerve (MN) stimulation showed absence or distorted components subsequent to N1 (N18) potential.These observations suggest that components subsequent to P3 potential in response to PN stimulation, and subsequent to N18 potential in response to MN stimulation, are generated in the parietal cortical regions.     

Neurophysiological evaluation of central-peripheral sensory and motor pudendal fibres

Extensive neurophysiological investigations were carried out in 18 healthy volunteer subjects, and 6 patients with neurological disease. The tests consisted of spinal and scalp somatosensory evoked potentials (SEPs) to stimulation of the dorsal nerve of penis/clitoris, motor evoked potentials (MEPs) from the bulbocavernosus muscle (BC) and anal sphincter (AS) in response to scalp and sacral root stimulation, and measurement of sacral reflex latency (SRL) from BC and AS.In the control subjects, the mean sensory total conduction time (sensory TCT), as measured at the peak of the scalp P40 wave was 40.9 msec (range: 37.8–44.2). The mean sensory central conduction time (sensory CCT = spine-to-scalp conduction time) was 27.0 msec (range: 23.5–30.4).Transcranial brain stimulation was performed by using a magnetic stimulator both at rest and during voluntary contraction of the examined muscle. Sacral root stimulation was performed at rest. Motor total conduction times (motor TCT) to BC and AS muscles were respectively 28.8 and 30.0 msec at rest, and 22.5 and 22.8 msec during contraction. Motor central conduction times (motor CCT) to sacral cord segments controlling BC and AS muscles were respectively 22.4 and 21.2 msec at rest, and 15.1 and 12.4 msec during contraction.The mean latencies of SRL were respectively 31.4 msec in the bulbocavernosus muscle and 35.9 msec in the anal sphincter. Combined or isolated abnormalities of SEPs, MEPs and SRL were found in a small group of patients with neurological disorders primarily or secondarily affecting the genito-urinary tract.     

Electric and CO2 laser SEPs in a patient with asymptomatic syringomyelia

We recorded electrically stimulated somatosensory evoked potentials (electric SEPs) and pain-related SEPs following CO₂ laser stimulation (CO₂ laser SEPs) from a 17-year-old patient affected by myotonic dystrophy whose MRI disclosed a large syrinx extending from spinal level C2 to S3. Careful clinical and electromyographic examinations revealed no motor or sensory disturbances, apart from myotonia. The only abnormality noted in median and ulnar nerve short-latency electric SEPs (recorded with a non-cephalic reference electrode) was the absence of cervical component N13, the other SEP responses (N9, N10, N11, P14, N20) being normal. The cutaneous pain threshold and CO₂ laser SEPs (both obtained by a CO₂ laser beam applied to the back of the hand) were normal. Thus cervical component N13 appears to be highly sensitive to the effects of central cord lesions, even when these are asymptomatic.     

Scalp topography and dipolar source modelling of potentials evoked by CO2 laser stimulation of the hand

CO₂ laser evoked potentials to hand stimulation recorded using a scalp 19-channel montage in 11 normal subjects consistently showed early N1/P1 dipolar field distribution peaking at a mean latency of 159 ms. The N1 negativity was distributed in the temporoparietal region contralateral to stimulation and the P1 positivity in the frontal region. The N1/P1 response was followed by 3 distinct components: (1) N2a reaching its maximal amplitude at the vertex and ipsilaterally to the stimulated hand, (2) N2b mostly distributed in the frontal region, and (3) P2 with a mid-central topography. Brain electrical source analysis showed that this sequence was explained, with a residual variance below 5%, by a model including two dipoles in the upper bank of the Sylvian fissure of each hemisphere, a frontal dipole close to the midline, and two anterior medial temporal dipoles, thus suggesting a sequential activation of the two second somatosensory areas, anterior cingulate gyrus and the amygdalar nuclei or the hippocampal formations, respectively. This model fitted well with the scalp field topography of grand average responses to stimulation of left and right hand obtained across all subjects as well as when applied to individual data. Our findings suggest that the second somatosensory area contralateral to the stimulation is the first involved in the building of pain-related responses, followed by ipsilateral second somatosensory area and limbic areas receiving noxious inputs from the periphery.     

Middle-latency somatosensory evoked potentials following median and posterior tibial nerve stimulation in Down's syndrome

Middle-latency somatosensory evoked potentials (SEPs) following median and posterior tibial nerve stimulation were studied in 40 patients with Down's syndrome and in age- and gender-matched healthy controls as well as in middle-aged and aged healthy subjects. In median nerve SEPs, latencies of the initial cortical potentials, N18 and P18, showed no significant difference, but the following potentials N22, P25, N32, P41 and P46 were relatively or significantly shorter in latency in Down's patients than in the controls. Amplitudes of all components in Down's patients were significantly larger than those of age- and gender-matched controls as well as of those of middle-aged healthy subjects, but there was only a small difference in their amplitudes from aged healthy subjects. Results of posterior tibial nerve SEPs were generally consistent with those of median nerve SEPs. Therefore, ‘short latency with large amplitude’ is the main characteristic of middle-latency SEPs in Down's syndrome, possibly related to accelerated physiological aging of the central nervous system.     

The relations between long-latency reflexes in hand muscles,somatosensory evoked potentials and transcranial stimulation of motor tracts

In 15 normal subjects the latency of electrically elicited long-latency reflexes (LLRs) of thenar muscles was compared with somatosensory evoked potentials (SEPs) after median nerve stimulation and with the latencies of thenar muscle potentials after transcranial stimulation (TCS) of the motor cortex. Assuming a transcortical reflex pathway the intracortical relay time for the LLR was calculated to be 10.4±1.9 msec (mean±S.D.) or 8.1 ± 1.6 msec depending on the experimental conditions. The duration of the cortical relay time is not correlated with the peripheral or central conduction times, with body size or arm length. If the LLRs of hand muscles are conducted transcortically the long duration of the cortical relay time suggests a polysynaptic pathway.     

Effect of manipulation and fractionated finger movements on subcortical sensory activity in man

Previous studies have shown that the somatosensory evoked potentials (SEPs) recorded from the scalp are modified or gated during motor activity in man. Animal studies show corticospinal tract terminals in afferent relays, viz. dorsal horn of spinal cord, dorsal column nuclei and thalamus. Is the attenuation of the SEP during movement the result of gating in subcortical nuclei? This study has investigated the effect of manipulation and fractionated finger movements of the hand on the subcortically generated short latency SEPs in 9 healthy subjects. Left median nerve SEPs were recorded with electrodes optimally placed to record subcortical activity with the least degree of contamination. There was no statistically significant change in amplitude or latency of the P9, N11, N13, P14, N18 and N20 potentials during rest or voluntary movement of the fingers of the left hand or manipulation of objects placed in the hand. The shape of the N13 wave form was not modified during these 3 conditions. It is concluded that in man attenuation of cortical waves during manipulation is not due to an effect of gating in the subcortical sensory relay nuclei.     

Laser-evoked potentials: exogenous and endogenous components

The aim of this study was to distinguish the exogenous component (related to the physical properties of the stimulus) and the endogenous component (reflecting event-related cognitive processing) of the laser-evoked potential (LEP). Short painful radiant heat pulses generated by a CO₂-laser were applied to the dorsum of the right and left foot. LEPs were recorded with 5 scalp electrodes in the midline versus linked earlobes in 26 healthy subjects. In order to identify the exogenous component, the LEP was recorded during a standardised distraction task (reading a short story). To identify the endogenous component P3 for the LEP, a 2-stimulus oddball paradigm was used (20% probability of targets). When the task of the oddball paradigm consisted of pressing a button, a movement-related long-latency negativity (N1200) was recorded in frontal leads that was absent in a counting task. The LEP of targets, frequent non-targets and during distraction was dominated by a single large positivity. The amplitude of this positivity was task-dependent and increased the more attention the subject payed to the laser stimuli (distraction < neutral < non-target < target). The laser-evoked positivity during distraction had a peak latency of about 400 msec (P400) and a maximum amplitude at the vertex, which was independent of inter-stimulus interval. The P3 following laser stimulation had a significantly later peak at about 570 msec (P570) and a different scalp topography with a parietal maximum. Its amplitude decreased when the interstimulus interval was reduced from 10 to 6 sec. Under neutral instructions, the LEP positivity consisted of a superposition of both the exogenous P400 and the endogenous P570.     

Unmasking of cortical SEP components by changes in stimulus rate: a topographic study

We performed topographic mapping of somatosensory responses to median nerve stimulation delivered at 2, 5 and 10 Hz. Parietal N20 was significantly attenuated in 10 Hz somatosensory evoked potentials (SEPs), while central P22 diminished between 2 and 5 Hz, remaining stable thereafter. The single component most affected by increasing stimulus rate was N30, which abated by more than 50% in 10 Hz SEPs, as compared with basal responses. N30 attenuation disclosed the existence of an earlier negative component, N24, which appeared as a notch on the N30 ascending slope in 2 Hz SEPs, but became a well-defined peak at higher stimulus rates. The N24 negativity was not significantly modified by stimulus rate; it had a parietal counterpart (P24) with the same peak latency and identical behavior during the experimental procedure. Both P24 and N24 could be differentiated from central P22 on the basis of topographical distribution and response to stimulus frequency. P22 topography could be the result of a radially oriented generator, while P24/N24 appeared as the two poles of a neural source tangential to the scalp. P27 was seen in 40% of the subjects only; it is suggested that P27 is itself a composite potential to which the generator of N30 could contribute in part. We conclude that there is no single “optimal” stimulation rate for SEP recording. On the contrary, combination of different frequencies of stimulation should enhance the diagnostic utility of this technique by allowing a more selective assessment of overlapping activities.     

Neural generators of the somatosensory evoked potentials: Recording from the cuneate nucleus in man and monkeys

The neural generators of the somatosensory evoked potentials (SEPs) elicited by electrical stimulation of the median nerve were studied in man and in rhesus monkeys. Recordings from the cuneate nucleus were compared to the far-field potentials recorded from electrodes placed on the scalp. It was found that the shape of the response from the surface of the human cuneate nucleus to stimulation of the median nerve is similar to that of the response recorded more caudally in the dorsal column, i.e., an initially small positivity followed by a negative wave that is in turn followed by a slow positive wave. The beginning of the negative wave coincides in time with the N14 peak in the SEP recorded from the scalp, and its latency is 13 msec. The response from the cuneate nucleus in the rhesus monkey has a similar shape and its negative peak appears with the same latency as the positive peak in the vertex response that has a latency of 4.5 msec; the peak negativity has a latency of about 6 msec and thus coincides with P6.2 in the vertex recording. Depth recordings from the cuneate nucleus and antidromic stimulation of the dorsal column fibers in the monkey provide evidence that the early components of the response from the surface of the cuneate nucleus are generated by the dorsal column fibers that terminate in the nucleus.The results support the hypothesis that the P14 peak in the human SEP is generated by the termination of the dorsal column fibers and that the cuneate nucleus itself contributes little to the far-field potentials.     

Somatotopy of human hand somatosensory cortex revealed by dipole source analysis of early somatosensory evoked potentials and 3D-NMR tomography

Somatosensory evoked potentials (SEPs) to median nerve and finger stimulation were analyzed by means of spatio-temporal dipole modelling combined with 3D-NMR tomography in 8 normal subjects. The early SEPs were modelled by 3 equivalent dipoles located in the region of the brain-stem (B) and in the region of the contralateral somatosensory cortex (T and R). Dipole B explained peaks P14 and N18 at the scalp. Dipole T was tangentially oriented and explained the N20-P20, dipole R was radially oriented and modelled the P22. The tangential dipole sources T were located within a distance of 6 mm on the average and all were less than 9 mm from the posterior bank of the central sulcus. In 6 subjects the tangential sources related to finger stimulation arranged along the central sulcus according to the known somatotopy. The radial sources did not show a consistent somatotopic alignment across subjects. We conclude that the combination of dipole source analysis and 3D-NMR tomography is a useful tool for functional localization within the human hand somatosensory cortex.     

Direct recording of somatosensory evoked potentials in the vicinity of the dorsal column nuclei in man: their generator mechanisms and contribution to the scalp far-field potentials

Somatosensory evoked potentials (SEPs) in the vicinity of the dorsal column nuclei in response to electrical stimulation of the median nerve (MN) and posterior tibial nerve (PTN) were studied by analyzing the wave forms, topographical distribution, effects of higher rates of stimulation and correlation with components of the scalp-recorded SEPs. Recordings were done on 4 patients with spasmodic torticollis during neurosurgical operations for microvascular decompression of the eleventh nerve. The dorsal column SEPs to MN stimulation (MN-SEPs) were characterized by a major negative wave (N1; 13 msec in mean latency), preceded by a small positivity (P1) and followed by a large positive wave (P2). Similar wave forms (P1′-N1′-P2′) were obtained with stimulation of PTN (PTN-SEPs), with a mean latency of N1′ being 28 msec. Maximal potentials of MN-SEPs and PTN-SEPs were located in the vicinity of the ipsilateral cuneate and gracile nuclei, respectively, at a level slightly caudal to the nuclei. The latencies of P1 and N1 increased progressively at more rostral cervical cord segments and medulla, but that of P2 did not. A higher rate of stimulation (16 Hz) caused no effects on P1 and N1, while it markedly attenuated the P2 component. These findings suggest that P1 and N1 of MN-SEPs, as well as P1′ and N1′ of PTN-SEPs, are generated by the dorsal column fibers, and P2 and P2′ are possibly of postsynaptic origin in the respective dorsal column nuclei.The peak latency of N1 recorded on the cuneate nucleus was identical with the scalp-recorded far-field potential of P13–14 in all patients, while no scalp components were found which corresponded to P2. These findings support the previous assumption that the scalp-recorded P13–14 is generated by the presynaptic activities of the dorsal column fibers at their terminals in the cuneate nucleus.     

Unit responses of the first and second somatosensory areas to stimulation of the ventroposterior thalamic nucleus

Single unit responses of the first (SI) and second (SII) somatosensory areas to stimulation of the ventroposterior thalamic nucleus (VP) were investigated in cats immobilized with D-tubocurarine. In response to VP stimulation 12.0% of reacting SI neurons and 9.5% of SII neurons generated an antidromic spike. In most antidromic responses of both SI and SII neurons the latent period did not exceed 1.0 msec. The minimal latent period of spike potentials during orthodromic excitation was 1.5 msec in SI and 1.7 msec in SII. Neurons with an orthodromic spike latency of not more than 3.0 msec were more numerous in SI than those with a latency of 3.1–4.5 msec. The ratio between the numbers of neurons of these two groups in SII was the opposite. In SII there were many more neurons with a latency of 5.6–8.0 msec than in SI. EPSPs appeared after a latent period of 1.1–9.0 msec in SI and of 1.4–6.6 msec in SII. The latent period of IPSPs was 1.5–6.8 msec in SI and 2.2–9.4 msec in SII. The relative importance of different pathways for excitatory and inhibitory influences of VP on SI and SII neurons is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 8, No. 2, pp. 115–121, March–April, 1976.     

Rapid-Rate Paired Associative Stimulation over the Primary Somatosensory Cortex

Rapid-rate paired associative stimulation (rPAS) involves repeat pairing of peripheral nerve stimulation and Transcranial magnetic stimulation (TMS) pulses at a 5 Hz frequency. RPAS over primary motor cortex (M1) operates with spike-timing dependent plasticity such that increases in corticospinal excitability occur when the nerve and TMS pulse temporally coincide in cortex. The present study investigates the effects of rPAS over primary somatosensory cortex (SI) which has not been performed to date. In a series of experiments, rPAS was delivered over SI and M1 at varying timing intervals between the nerve and TMS pulse based on the latency of the N20 somatosensory evoked potential (SEP) component within each participant (intervals for SI-rPAS: N20, N20-2.5 ms, N20 + 2.5 ms, intervals for M1-rPAS: N20, N20+5 ms). Changes in SI physiology were measured via SEPs (N20, P25, N20-P25) and SEP paired-pulse inhibition, and changes in M1 physiology were measured with motor evoked potentials and short-latency afferent inhibition. Measures were obtained before rPAS and at 5, 25 and 45 minutes following stimulation. Results indicate that paired-pulse inhibition and short-latency afferent inhibition were reduced only when the SI-rPAS nerve-TMS timing interval was set to N20-2.5 ms. SI-rPAS over SI also led to remote effects on motor physiology over a wider range of nerve-TMS intervals (N20-2.5 ms – N20+2.5 ms) during which motor evoked potentials were increased. M1-rPAS increased motor evoked potentials and reduced short-latency afferent inhibition as previously reported. These data provide evidence that, similar to M1, rPAS over SI is spike-timing dependent and is capable of exerting changes in SI and M1 physiology.     

Dissociation induced by voluntary movement between two different components of the centro-parietal P40 SEP to tibial nerve stimulation

Whether the two earliest cortical somatosensory evoked potentials (SEPs) to tibial nerve stimulation (N37 and P40) are generated by the same dipolar source or, instead, originate from different neuronal populations is still a debated problem. We recorded the early scalp SEPs to tibial nerve stimulation in 10 healthy subjects at rest and during voluntary movement of the stimulated foot. We found that the P40, which reached its highest amplitude on the vertex at rest, changed its topography during movement, since its amplitude was reduced much more in the central than in the parietal traces. These findings suggest that two different components contribute to the centro-parietal positivity at rest: (1) the P37 response, which is parietally distributed and is not modified by movement, and (2) the `real' P40 SEP, which is focused on the vertex and is reduced in amplitude during voluntary movement. Since, also, the N37 response did not vary its amplitude under interference condition, it is possible that the N37 and P37 potentials are generated by the same dipolar source. Other later components, namely P50 and N50, were significantly reduced in amplitude during foot movement. Lastly, the subcortical P30 far-field remained unchanged and this suggests that the phenomenon of amplitude reduction during movement (i.e. gating) occurs above the cervico-medullary junction.     

Short latency somatosensory evoked potentials following mechanical taps to the face. Scalp recordings with a non-cephalic reference

Trigeminal somatosensory evoked potentials were recorded over the scalp using non-cephalic reference sites following mechanical taps to the face. A negative wave form, Nf17, was recorded bilaterally with its highest amplitude over the frontal scalp contralateral to the side of stimulation. A localized negative form, Np25, was recorded over the centro-parietal scalp contralateral to the side of stimulation. Np25 had an onset latency of 16.46 msec. The location and restricted spatial distribution of Np25 suggest that it represents the initial activation of the face area of the primary sensory cortex. The widespread bilateral nature of Nf17 and its latency of onset preceding that of Np25 suggest that Nf17 may be a ‘far-field’ potential reflecting activity in subcortical sensory pathways subserving the face.