Recovery functions of early cortical median nerve SSEP components: normative data

The recovery functions of parietal P14-N20, N20-P27 and frontal P22-N30 amplitudes were assessed in 17 healthy controls aged 20–50 years by means of the paired stimulus technique. One unpaired and 4 paired stimuli with interstimulus intervals (ISIs) of 25, 50, 75 and 100 msec were cyclically presented in a single run. Responses to the unpaired stimulus were subtracted off-line from paired stimulus responses. The highest suppression was reached at shorter ISIs for components with shorter latencies. The mean suppression of P22-N30 was influenced by the subject's age, being greater in younger subjects. Normative data are reported.     

Right or left ear reference changes the voltage of frontal and parietal somatosensory evoked potentials

Short-latency cortical somatosensory evoked potentials (SEPs) to left median nerve stimulation were recorded with either the left or right earlobe as reference. With a right earlobe reference the voltage of the parietal N20 and P27 was reduced while the voltage of the frontal P20 and N30 was enhanced. The effects were consistent, but their size varied with the SEP component considered and also among the subjects. Analysis of SEPs at different scalp sites and at either earlobe suggested that the ear contralateral to the side stimulated picked up transient potential differences, depending a.o. on side asymmetry and geometry of the neural generators as disclosed in topographic mapping. For example, the right ear potential can be shifted negatively by the right N20 field evoked by left median nerve stimulation. The changes involve the absolute potential values, but not the time features of the gradients of potential fields. Scalp current density (SCD) maps are not affected. The results are pertinent for current discussions about which reference to use and document the practical recommendation of recording short-latency cortical SEPs with a reference at the ear ipsilateral (not contralateral) to the side of stimulation.     

The effect of stimulus frequency on post- and pre-central short-latency somatosensory evoked potentials (SEPs)

We assessed the influence of the stimulus frequency on short-latency SEPs recorded over the parietal and frontal scalp of 26 subjects to median nerve stimulation and 16 subjects to digital nerve stimulation. When the stimulus frequency is increased from 1.6 Hz to 5.7 Hz, the amplitude of the N13 potential decreases whereas the P14 remains stable. The amplitude of the N20 is not changed significantly whereas the P22, the P27 and the N30 decrease significantly. In 50% of the subjects 2 components can be seen within the frontal negativity that follows the P22: an early ‘N24’ component, which is not affected by the stimulus rate, and the later N30, which is highly sensitive to the stimulus frequency. The distinct amplitude changes of the N20 and P22 with increasing stimulus frequency is one among other arguments to show that these potentials arise from separate generators.     

Median nerve somatosensory evoked potentials. Apomorphine-induced transient potentiation of frontal components Clin. Parkinson's disease and in parkinsonism

Somatosensory evoked potentials (SEPs) to median nerve stimulation have been recorded from parietal and frontal districts Clin. 43 parkinsonians, 17 patients with parkinsonism and 35 healthy controls matched for age and sex. Latency/ amplitude characteristics of the parietal P14-N20-P25 and of the frontal P20-N30-P40 wave complexes before and after (10, 20, 30 and 60 min) subcutaneous administration of apomorphine chloride were evaluated Clin. all the 60 patients and Clin. 3 controls. The frontal waves N30 and P40 were either absent or significantly smaller than normal Clin. 31 patients with Parkinson's disease (PD) (72.1%) and Clin. 9 with parkinsonism Clin. baseline records (56.3%). Following apomorphine, the parietal deflections did not significantly vary Clin. amplitude. On the contrary, the frontal complex showed a significant amplitude increase Clin. 27 PD and 8 parkinsonisms (respectively 62.8 and 47.1%): 79.1% of PD and 35.3% of parkinsonisms were improved clinically. Amplitude increase was evident at 10 min after apomorphine, Clin. parallel with clinical improvement, and vanished nearly Clin. coincidence with the end of the clinical effect.     

Giant central N20-P22 with normal area 3b N20-P20: an argument in favour of an area 3a generator of early median nerve cortical SEPs?

Generators of early cortical somatosensory evoked potentials (SEPs) still remain to be precisely localised. This gap in knowledge has often resulted in unclear and contrasting SEPs localisation in patients with focal hemispheric lesions. We recorded SEPs to median nerve stimulation in a patient with right frontal astrocytoma, using a 19-channel recording technique. After stimulation of the left median nerve, N20 amplitude was normal when recorded by the parietal electrode contralateral to the stimulation, while it was abnormally enhanced in traces obtained by the contralateral central electrode. The amplitude of the frontal P20 response was within normal limits. This finding suggests that two dipolar sources, tangential and radial to the scalp surface, respectively, contribute concomitantly to N20 generation. The possible location of the N20 radial source in area 3a is discussed. The P22 potential was also recorded with increased amplitude by the central electrode contralateral to the stimulation, while N30 amplitude was normal in frontal and central traces. We propose that the radial dipolar source of P22 response is independent from both N20 and N30 generators and can be located either in 3a or in area 4. This report illustrates the usefulness of multichannel recordings in diagnosing dysfunction of the sensorimotor cortex in focal cortical lesions.     

Somatosensory evoked potentials at rest and during movement in Parkinson's disease: evidence for a specific apomorphine effect on the frontal N30 wave

Studies attempting to relate the abnormalities of the frontal N30 components of the somatosensory evoked potentials (SEPs) to motor symptoms in Parkinson's disease (PD) have shown contradictory results. We recorded the frontal and parietal SEPs to median nerve stimulation in 2 groups of PD patients: a group of 17 patients presenting the wearing-off phenomenon, and a group of 10 untreated PD patients. The results were compared with a group of 13 healthy volunteers of the same age and with a group of 10 non-parkinsonian patients. All parkinsonian and non-parkinsonian patients were studied before (“off” condition) and after a subcutaneous injection of apomorphine (“on” condition). The gating effects of a voluntary movement (clenching of the hand) on the SEPs were also studied for the wearing-off group of PD patients (in states off and on) in comparison with the healthy subjects. At rest and in the off condition the amplitude of the frontal N30 was significantly reduced in the 2 groups of PD patients. We demonstrate that the movement gating ability of the PD patient is preserved in spite of the reduced amplitude of the frontal N30. This result suggests that the specific change in the frontal N30 in PD is not the consequence of a continuous gating of the sensory inflow by a motor corollary discharge. Clinical motor improvement induced by apomorphine was associated with a significant enhancement of the frontal N30 wave. In contrast, the subcortical P14 and N18 waves and the cortical N20, P22, P27 and N45 were not statistically modified by the drug. Apomorphine infusion did not change the absolute reduced voltage of the N30 reached during the movement gating. While the frontal N30 component of the non-parkinsonian patients was significantly lower in comparison to healthy subjects, this wave did not change after the apomorphine administration. In the wearing-off PD patient group the frontal N30 increment was positively correlated with the number of off hours per day. This specific apomorphine sensitivity of the frontal N30 was interpreted as a physiological index of the dopaminergic modulatory control exerted on the neuronal structures implicated in the generation of the frontal N30.     

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.     

Effects of interstimulus interval on somatosensory evoked magnetic fields (SEFs): a hypothesis concerning SEF generation at the primary sensorimotor cortex

Cerebral responses evoked by peripheral stimuli are known to depend critically on the interstimulus interval (ISI). Here we report on the effects of ISI on somatosensory evoked magnetic fields (SEFs) to right median nerve stimulation, obtained in 9 healthy adults with ISIs of 0.15, 0.3, 1, 3 and 5 s. At the contralateral (left) primary sensorimotor cortex (SMI), the first cortical response, N20m, was stable between the ISIs 0.3 and 5 s, but slightly attenuated at the shortest ISI of 0.15 s. In contrast, the P35m and P60m deflections were very sensitive to changes of the ISI, declining steadily with shortening of the ISI throughout the entire range. These deflections were frequently undetectable at the shortest ISI of 0.15 s. Concomitant with the reductions of P35m and P60m, an N45m deflection was enhanced toward the short ISIs. Responses from second somatosensory cortex (SII) and posterior parietal cortex (PPC) were seen only with ISIs of 1 s or greater, being strongest at the 5 s ISI. Based on known effects of the ISI on intracellular evoked potentials, we present the following tentative model for the generation mechanism of the SMI response: N20m represents early excitatory postsynaptic potentials (EPSPs), P35m early inhibitory postsynaptic potentials (IPSPs), N45m secondary EPSPs and P60m late IPSPs in pyramidal neurones of area 3b. For practical purposes, SEFs from SMI can be obtained with short ISIs, while responses from SII and PPC require an ISI of at least 1 s.     

Peri-rolandic and fronto-parietal components of scalp-recorded giant SEPs in cortical myoclonus

Scalp topography of giant SEPs to median nerve stimulation was studied in 4 patients with cortical myoclonus of various etiology. The positive peak (P30) at the contralateral parietal area was simultaneously accompanied by a negative peak at the frontal area (N30), and at least one of these two peaks was enhanced in 2 patients. Another positive peak (P25) and a negative peak (N35) were also identified at the peri-rolandic area with different latency from P30 and N30, respectively, in all patients. N35 was enhanced in 3 patients, and P25 in 2 patients. It is concluded that, as seen in normal subjects, tangential (P30-N30) and radial (P25 and N35) components of SEPs are most likely distinguishable in giant SEPs, and that either one or both of those components is enhanced in different ways depending on the patients.     

Interstimulus interval and auditory event-related potentials in children: evidence for multiple generators

In the present study, the component structure of auditory event-related potentials (ERP) was studied in children of 7–9 years old by presenting stimuli with different interstimulus intervals (ISI). A short-term auditory sensory memory, as reflected by ISI effects on ERPs, was also studied. Auditory ERPs were recorded to brief unattended 1000 Hz frequent, `standard' and 1100 Hz rare, `deviant' (probability 0.1) tone stimuli with ISIs of 350, 700 and 1400 ms (in separate blocks). With the 350 ms-ISI, the ERP waveform to the standard stimulus consisted of P100-N250 peaks. With the two longer ISIs, in addition, the frontocentral N160 and N460 peaks were observed. Results suggested that N160, found with the longer ISIs, is a correlate of the adult auditory N1. In difference waves, obtained by subtracting ERP to standard stimuli from ERP to deviant stimuli, two negativities were revealed. The first was the mismatch negativity (MMN), which is elicited by any discriminable change in repetitive auditory input. The MMN data suggested that neural traces of auditory sensory memory lasted for at least 1400 ms, probably considerably longer, as no MMN attenuation was found across the ISIs used. The second, later negativity was similar to MMN in all aspects, except for the scalp distribution, which was posterior to that of the MMN.     

Scalp topography of mechanically and electrically evoked somatosensory potentials in man

Scalp topography of somatosensory evoked potentials following mechanical (SEPs(M)) and electrical (SEPs(E)) stimulation of the left middle finger was investigated with linked ear reference in 21 normal young adults. A small plastic ball (touch) or needle (pain) was used for the mechanical stimulation. With mechanical stimulation, at least 3 positive and 3 negative potentials (P19(M), N24(M), P29(M), N36(M), P49(M) and N61(M)) were found in the post-rolandic area contralateral to the stimulation. The wave form in SEPs(M) was similar to those in SEPs(E), but the peak latency of each component in SEPs(M) was 1–4 msec longer than that in SEPs(E). Earlier components such as P19(M), N24(M) and P29(M) were not as clearly recognized as corresponding components in SEPs(E). However, the wave form recorded on the hemisphere ipsilateral to the stimulation or in the frontal area contralateral to the stimulation showed a greater difference from subject to subject. P19(M), N24(M) and P29(M) correlated positively both with arm length and height of the subject. There was no significant difference of the wave form between the linked ear reference and the bipolar (C4-Fz) derivation. Wave form of SEPs(M) by needle stimulation did not significantly differ from that by plastic ball stimulation.     

Bit-mapped somatosensory evoked potentials and muscular reflex responses in man: comparative analysis in different experimental protocols

Bit-colour maps of somatosensory evoked potentials (SEPs) and muscular responses from forearm and hand muscles were simultaneously recorded after median nerve stimulation. Subjects were asked either to relax totally (A), or to contract the examined muscle continuously and isometrically at 10–20% (B) and 80–100% (C) of the maximal strength. Isotonic contractions ipsilateral (D) and contralateral to the stimulus (E) were also examined. Both SEPs and EMG responses were elicited by individual near-motor threshold pulses delivered at 0.2/sec to the median nerve at the elbow. SEPs were maximal in amplitude during complete relaxation, whilst all the components following the parietal N20 were depressed by muscle contraction. Such decrements affected predominantly the parietal and frontal peaks of positive polarity during condition B, whilst the frontal negative component (wave N30) dropped remarkably in conditions C and D. Early EMG responses (V1 = spinal circuitry) were usually absent in condition A; they were present together with later components (= V2 possibly long-loop, transcortical circuitry) in C and D, whilst they were alone recordable in B and E. The amplitudes of the frontal wave N30 in SEPs and of V2 in LLRs were inversely correlated. This observation is consistent with the hypothesis that a change in the reactivity of the sensorimotor brain areas to afferent impulses is coupled to LLR elicitation in forearm and hand muscles.     

Abnormalities of parietal and prerolandic somatosensory evoked potentials in Huntington's disease

Cervical, parietal and prerolandic somatosensory evoked potentials (SEPs) to median nerve stimulation at the wrist were recorded with an earlobe reference in 24 patients with Huntington's disease (HD) and in 24 age-matched normal controls. Cortical responses of abnormal wave form and reduced amplitude were constantly observed in HD patients. SEP changes affected more severely the prerolandic (P22/N30) pattern, which could not be recognized in two-thirds of patients, than the parietal (N20/P27) pattern, which could be identified in all cases. The N20 latency and the central conduction time (N13–N20 interval) were significantly increased. The occurrence of abnormalities of central conduction and of a predominant involvement of the prerolandic SEP pattern suggests an impairment of impulse transmission along the somatosensory lemniscal pathway at subcortical, possibly thalamic, level in HD.     

SEPs in two patients with localized lesions of the postcentral gyrus

Scalp distributions of median nerve SEPs were studied in normal controls and 2 patients with localized lesions of the postcentral gyrus. In controls, parieto-occipital electrodes registered N20-P27 while frontal electrodes registered P20-N27. Other small components, parieto-occipital P22 and frontal N22, were recognized in about half of the control records. The wave forms at a frontal and a parieto-occipital electrode, both distant from the central region, formed exact mirror images of each other concerning N20-(P22)-P27 and P20-(N22)-N27. Electrodes near the central region contralateral to the stimulation registered cP22-cN30 (central P22 and central N30). When the postcentral gyrus was damaged, N20/P20-P27/N27 and cP22-cN30 were eliminated and the only remaining components were a frontal negative wave (frN) and a contralateral parieto-occipital positive wave (poP). Digital nerve stimulation also evoked poP and frN in both cases. In case 2, poP coincided with P22 of the non-affected side. The following generators were proposed; N20/P20-P27/N27: area 3b, cP22-cN30: areas 1 and 2, poP/early frN (= P22/N22): area 4 at the anterior wall of the central sulcus (due to direct thalamic inputs to motor cortex), late frN: uncertain (SMA?, SII?).     

Activation of a distributed somatosensory cortical network in the human brain: a dipole modelling study of magnetic fields evoked by median nerve stimulation. Part II: effects of stimulus rate,attention and stimulus detection

In this study we used a repeated measures design and univariate analysis of variance to study the respective effects of ISI, spatial attention and stimulus detection on the strengths of the sources previously identified by modelling SEFs during the 200 ms following mentally counted left median nerve stimuli delivered at long and random ISIs (Part I). We compared the SEF source strengths in response to frequent and rare stimuli, both in detection and ignoring conditions. This permitted us to establish a hierarchy in the effects of ISI, attention and stimulus detection on the activation of the cortical network of SEF sources distributed in SI and posterior parietal cortex contralateral to stimulation, and in the parietal operculum (SII) and premotor frontal cortex of both hemispheres. In all experimental conditions the SI and parietal opercular sources were the most active. All sources were more active in response to stimuli delivered at long and random ISIs and the frontal sources were activated only in this condition of stimulation. Driving the subject's attention toward the side stimulated had no detectable effect on the activity of SEF sources at short ISI. At long ISIs mental counting of the stimuli increased the responses of all sources except SI. These results suggest that activation of frontal sources during mental counting could reflect a working memory process, and that of posterior parietal sources a spatial attention effect detectable only at long ISIs.     

Recovery functions of somatosensory vertex potentials in man: interaction of evoked responses from right and left fingers

Somatosensory vertex potentials (SVPs) were examined in 12 healthy subjects in response to painful electrical stimulation of the finger. SVPs consisted of N1, P1, and N2. The average latencies of the 3 peaks were 150, 225, and 350 msec, respectively. The latency and amplitude of each potential were reproducible for each subject. Recovery functions of the SVPs were analyzed in 10 subjects. A pair of stimuli were delivered to the right or left finger with interstimulus intervals (ISIs) of 50, 100, 150, 200, 350, 500 and 650 msec. SVPs partially recovered with the shortest ISI (50 msec). Full recovery could not be obtained even with the longest ISI (650 msec). Differences in recoveries within 650 msec of ISI were not observed between right and left stimulations. To examine the interaction between SVPs evoked by right and left finger stimulation, recovery functions from prior contralateral finger stimulation were analyzed with the same ISIs. SVP recoveries for right after left or left after right patterns of stimulus delivery were nearly the same as those for ipsilateral ones. It is suggested that SVPs are generated at nearly the same site in the sensory pathway regardless of the side stimulated.     

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.     

SEPs to finger joint input lack the N20-P20 response that is evoked by tactile inputs: contrast between cortical generators in areas 3b and 2 in humans

A method using a DC servo motor is described to produce brisk angular movements at finger interphalangeal joints in humans. Small passive flexions of 2° elicited sizable somatosensory evoked potentials (SEPs) starting with a contralateral positive P34 parietal response thought to reflect activation of a radial equivalent dipole generator in area 2 which receives joint inputs. By contrast, electric stimulation of tactile (non-joint) inputs from the distal phalanx evoked the usual contralateral negative N20 reflecting a tangential equivalent dipole generator in area 3b. Finger joint inputs also evoked a precentral positivity equivalent to the P22 of motor area 4, and a large frontal negativity equivalent to N30. It is suggested that natural stimulation allows human SEP components to the differentiated in conjunction with distinct cortical somatotopic projections.     

The recovery functions of auditory event-related potentials during split-second discriminations

We examined the recovery cycles of auditory event-related potentials (ERPs) in a high-speed auditory discrimination task and in passive conditions. Each trial contained 3 tones cued by a warning flash. In passive conditions, auditory ERPs consisted mainly of N1 (108 msec) and P2 (213 msec) components superimposed on a small CNV. The N1 and P2 were comparable in amplitude and both had prolonged refractory periods. In discriminative reaction time (DRT) conditions the same tones cued or inhibited press responses and elicited additional endogenous components (principally the Nd and P3). ERPs in DRT conditions were superimposed upon a prominent CNV that began after the warning cue and lasted throughout the signal delivery period.The N1 was larger in active than passive conditions and showed less marked refractory effects, while the P2 was smaller and showed more marked refractoriness. Differences between active and passive conditions could be explained by the presence of an endogenous negative potential (the Nd) with a short refractory period that was superimposed upon the N1 and P2.The P3 was recorded only in active conditions. At short ISIs (0.5 sec), P3 amplitudes were reduced and P3 latencies lengthened in parallel with prolongations in reaction time due to so-called psychological refractory period (PRP) effects. Both P3 recovery and the PRP reflected central mechanisms since they were observed at short ISIs when stimuli cueing different responses succeeded one another.N1 and P3 amplitudes diminished over the course of the experiment in both active and passive conditions. The decrease (amounting to about 30% of initial amplitudes) did not appear due to reductions in vigilance, since it was not accompanied by changes in reaction time or response accuracy, or by changes in other endogenous components (CNV or Nd). Short-term N1 habituation was unaffected by long-term amplitude reductions suggesting that independent mechanisms were responsible for the two phenomena.     

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.