Jean Edouard Desmedt

Central somatosensory conduction in man: Neural generators and interpeak latencies of the far-field components recorded from neck and right or left scalp and earlobes

Early somatosensory evoked potential (SEP) components to median nerve or finger stimulation were recorded with non-cephalic references in normal young adults. Detailed topographic data over scalp and neck were related to anatomical observations on the actual conduction distances in dorsal column, medial lemniscus and thalamo-cortical parts of the somatosensory pathway. The extrapolation of afferent conduction velocity (CV) measured from sensory nerve potentials along the peripheral nerve to the C6-C7 spinal segments identified the spinal entry time with the onset of the neck N11 or scalp P11 (far field 2 or FF2). The first far field (FF1) is generated in the nerve proximal to axilla. The definite latency shift of the spinal negativity along the neck indicates a CV of 58 m/sec. Data about the maximal diameter of lemniscal axons in man were used to calculate a CV of 40.5 m/sec. Consideration of transit times from spinal entry to cortex and of synaptic delays clarified the arrival times of the afferent volley at various relay nuclei, and also suggested a thalamo-cortical CV of about 33 m/sec. Interpeak and onset-to-peak measures on scalp far fields suggest that FF3-FF4 are generated in medial lemniscus rather than above the thalamus. Consistent differences in amplitude, but not in wave form, were recorded at right and left earlobes for FF2 (larger ipsilaterally) and FF3-FF4 (larger contralaterally). The scalp topography of far fields was analysed in detail.

Non-cephalic reference recording of early somatosensory potentials to finger stimulation in adult or aging normal: differentiation of widespread N18 and contralateral N20 from the prerolandic p22 and N30 components

Prerolandic and parietal SEPs to electrical stimulation of fingers or median nerve were studied with non-cephalic reference in 40 normal young adults and in 35 healthy octogenarians. Limb temperatures were 36-37 degrees C. Intersubject variations of SEP components were analysed. A new widespread component N18 was identified and shown to be generated below the cortex. This N18 is about the only early component recorded at the parietal ipsilateral region after the positive far-field potentials P9, P11 and P13-P14. Transit times along the central somatosensory pathway were replicated and discussed as well as other evidence about the sequential activation of the various neural structures involved. The N20 potential representing the earliest cortical response is recorded from the contralateral parietal region, but is absent ipsilaterally. The prerolandic potential is related to distinct generators and is elicited by a separate thalamocortical pathway rather than by corticocortical connections from areas 2 and 5 in parietal cortex. The changes associated with normal aging have been confirmed and extended.

Color imaging of parietal and frontal somatosensory potential fields evoked by stimulation of median or posterior tibial nerve in man

Somatosensory evoked potentials (SEPs) to median or fingers or posterior tibial nerve stimulation were recorded with earlobe reference in normal young adults. A system of 16 electrodes on the scalp served to create bit-mapped images of the potential fields at 1 msec intervals. The P14 (median SEP) or P30 (tibial SEP) far fields thought to reflect the afferent volley in the medial lemniscus produced widespread positivity over the scalp. Subsequent components had a characteristic focal distribution suggesting that they reflected one or more generators in cortical areas. For the median SEP, the parietal N20 and the prerolandic P22 showed differences in onset and offset times as well as distribution that precluded their being related to the same generator. While N20 was contralateral, P22 extended ipsilaterally. P22 may be generated in the motor area 4 and the supplementary motor area. P22 was also distinct from the P27 field restricted to the contralateral parietal region. The frontal N30 had a bilateral distribution and the P45 presented variable features. For the tibial SEP, no phase reversal was confirmed between the parietal P38 (midline-ipsilateral focus) and N33 (contralateral focus). N37 over the contralateral prerolandic region might reflect a generator in the motor region. P58 was more symmetrically distributed than P38, possibly because it reflected generators more posteriorly on the parietal convexity. N75 had a widespread field with focus on the ipsilateral side of midline.

Prevertebral (oesophageal) recording of subcortical somatosensory evoked potentials in man: The spinal P13 component and the dual nature of the spinal generators

Abstract Short-latency somatosensory evoked potential (SEP) components to median nerve or finger stimulation were recorded in 12 normal young adults with 14 channels, using a non-cephalic reference. Several electrodes were placed along the posterior neck, earlobes and scalp while oesophageal probes provided 2–6 recording sites at known levels in front of vertebrae C2 to Th3 (Fig. 1). The oesophageal electrodes provided a new non-invasive point of entry that secured important data about the generator sources of the spinal SEP components. All cephalic electrodes recorded a P 9 far field which is greater over the scalp, earlobes and rostral cervical spine than over the caudal cervical spine. P 9 is the volume-conducted peripheral nerve volley coursing between axilla and spinal cord. The direct recording of arrival times of the peripheral volley along the median nerve and brachial plexus (Erbs point) served to estimate the spinal entry time which coincided with the onset of the posterior neck N 11 (at levels C6-C7) and of the scalp P 11 far field (Fig.3). The latency shift of the onset of N 11 from lower to upper neck has been replicated (Fig. 8C, D) and N 11 is interpreted as a presynaptic volley ascending the dorsal column (central branch of the primary neurone) at a velocity of 58 m/sec (Desmedt and Cheron 1980a). At oesophageal electrodes in front of the C7-Th3 vertebrae, the first negative component starts before the spinal entry time and it corresponds to action potentials in the spinal roots (Figs. 2 and 3). The most remarkable feature of oesophageal recordings in front of the C3 to Th2 vertebrae is the positive P 13 component which represented a phase reversal of the second negativity N 13 recorded from posterior neck (Fig. 5). The P 13 -N 13 phenomenon was recorded in all subjects and presented a stable latency throughout the cervical cord (Fig. 6C). It was clearly differentiated from the scalp far-field P 14 which is related to the ascending volley in the median lemniscus (Figs. 5 and 8; Tables I and II). The spinal P 13 did not extend above C2 and it was obviously generated below the foramen magnum. P 13 is interpreted as a dorsal horn postsynaptic potential which is elicited by collateral branches of the (bifurcated) primary afferent fibre. The use of 14 simultaneous recordings including a series of pre- and post-vertebral electrodes clearly identified two distinct generators for the spinal SEP components to median nerve stimulation: a presynaptic generator which ascends the dorsal column (N 11 ) and a postsynaptic fixed generator in the dorsal horn of the cervical spinal cord (N 13 -P 13 ).

Bit-mapped color imaging of human evoked potentials with reference to the N20, P22, P27 and N30 somatosensory responses ☆

Bit-mapped color imaging of scalp potential fields evoked by sensory stimulation in humans disclosed significant features not identified by mere inspection of multichannel traces. Methodological problems are considered in detail for early cortical SEPs which include several components with sharp rise times occurring at spatially distinct scalp locations. A manageable yet efficient imaging system requires recording electrodes in adequate number and scalp locations, bandpass fidelity to resolve slow and fast components, consistency of bioelectric input data, optimal interpolation and mapping algorithms, and consistent color scaling. Critical steps in these procedures were investigated in conjunction with new evidence on the scalp topography and neural generators of the N20, P20, P22, P27 and N30 SEP components. It is concluded that N20-P20 reflect a tangential equivalent dipole in parietal area 3b while P22 reflects a radial equivalent dipole in motor area 4.

Wave form and neural mechanism of the decision P350 elicited without pre-stimulus CNV or readiness potential in random sequences of near-threshold auditory clicks and finger stimuli

Abstract In 17 successful experiments on normal human adults random sequences of equiprobable acoustic clicks or electrical stimuli to the index finger were delivered at intervals varying at random from 1 to 15 sec. The stimuli were of low intensity and provided a feasible, but exacting task. No motor activity was involved. In alternate runs either the clicks or the finger stimuli were designated as targets to be identified and mentally counted by the subject. The accuracy of the counts was checked after each run. Scalp recorded brain potentials were stored on FM tape, edited for removal of sections with artifacts and averaged. Large P350 components were elicited by the targets, but not by identical stimuli when they were non-targets. The reciprocal experimental design provided consistent controls. No pre-stimulus negative shift of the CNV type was observed in spite of the use of long time constants (8 sec). The background EEG did not affect the results. The P350 to targets was maximal in the centro-parietal region and of equal amplitude on the left and right hemispheres. Because there was little overlap from other ERP components, the wave form of P350 could be analyzed, namely the latency to onset, the time from onset to peak and the total duration. The primary components of ERPs to finger stimuli were not modified by the cognitive task, which excludes centrifugal gating of corticipetal input as a mechanism. The ERPs to targets presented an increased N120. The latter was symmetrically distributed over the central region for target clicks, but was larger in the contralateral parietal region for target finger stimuli. The neural basis of CNV, P350 and N120 is discussed in detail. It is suggested that the mesencephalic reticular formation (MRF) exerts a diffuse bilateral facilitatory neuromodulation of cortical circuits which can be transiently adjusted (to produce CNV) by MRF control from prefrontal granular cortex. P350 is a post-decision event with bilateral distribution and results from a phasic inhibition of MRF at the closure of a cognitive processing epoch. P350 and CNV are dissociable: they are distinct events that involve roughly coextensive brain generators, but result from the operation of different prefrontal cortex controls on the MRF output to the telencephalon, in cognitive behavior. N120 indexes modality-specific focal processors engaged for stimulus identification before a decision is reached. N120 may involve the more specific thalamic reticular system that is also controlled by prefrontal cortex.

Somatosensory evoked potentials to finger stimulation in healthy octogenarians and in young adults: Wave forms, scalp topography and transit times of pariental and frontal components☆

Abstract Frontal and parietal SEPs to electrical stimulation of fingers were studied in conjunction with the spinal SEP and sensory nerve action potentials in 25 young adults and 19 healthy octogenarians. Limb temperatures were 36–37°C. Intersubject variations of SEP wave forms and detailed scalp topography helped delineate several genuine SEP components, namely the P25, N32 and N40, at precentral scalp sites. The parietal ‘W’ pattern (P30-N35-P45) was recorded in only 48% of the young, but 90% of the old subjects. All parietal components were significantly increased in size in the old, which contrasts with the reduced spinal SEP and sensory nerve potentials (Table II). The precentral SEP components were either maintained (P25) or reduced (N32). The primary afferent neurones appeared to age at a faster rate (CV reduced about 0.16 m/sec/year) than the second or third afferent neurones (no significant change in transit time from spinal entry to postcentral cortex or in mean central CV) (Table I). The scalp recorded SEPs were quite different in front of or behind the central fissure. Contrary to the ‘deep dipole’ hypothesis the SEPs recorded pre- or postcentrally were not mirror images and exhibited separate non-congruent intersubject variabilities (Figs. 1–5). The ‘travelling wave’ hypothesis was also rejected since the SEP components presented peak latencies that were stable within their scalp territory. It is suggested that the sequential activation of cortical modules in parietal and frontal areas, in part through demonstrated cortico-cortical axonal connections and possibly also through thalamo-cortical projections, could generate successive SEP components. The cortical generators of SEP components appeared to be similar in the octogenarians although their relative strengths changed and transit times between different components significantly increased (Table III).

Neural generators of N18 and P14 far-field somatosensory evoked potentials studied in patients with lesion of thalamus or thalamo-cortical radiations ☆

Somatosensory evoked potentials (SEPs) to electrical stimulation of the right or left median nerve were studied in 4 patients with hemianesthesia and a severe thalamic or suprathalamic vascular lesion on one side. The SEPs were recorded with a non-cephalic reference. The normal side of each patient served as his or her own control. The lesion consistently abolished the parietal N20-P27-P45 and the prerolandic P22-N30 SEP components. It did not significantly affect the P9-P11-P14 positive far fields, nor the widespread bilateral N18 SEP component. This allowed N18 features to be studied without interference from cortical components. It is proposed that N18 reflects several deeply located generators in brain stem and/or thalamus whereas N20 represents the earliest cortical response of the contralateral post-central receiving areas.

Spinal and far-field components of human somatosensory evoked potentials to posterior tibial nerve stimulation analysed with oesophageal derivations and non-cephalic reference recording.

Somatosensory evoked potentials (SEPs) were elicited by stimulation of the right posterior tibial nerve at the ankle in 20 experiments on 18 normal adults. A non-cephalic reference on the left knee was used throughout (with triggering of averaging cycles from the ECG), except for recording the peripheral nerve potentials. The responses were recorded along the spine, from oesophageal probes and from the scalp. The peripheral nerve volley propagated at a mean maximum conduction velocity (CV) of 59.2 m/sec served to identify the spinal entry time (mean 19.7 msec) at spinal segments S1-S3, under the D12 spine. This entry time coincided with the onset of the N21 component which was interpreted as the dorsal column volley and considered equivalent to the neck N11 of the median nerve SEP. The large voltage of the spinal response at the D12 spine probably results from summation of N21 with a fixed latency N24 potential that phase reverses at oesophageal recording sites into a P24. The N24-P24 reflects a horizontal dipole in the dorsal horn and is equivalent to the N13-P13 of the neck SEP to median nerve stimulation. Spinal conduction between D12-C7 spines was spuriously overestimated because the true length of the dorsal spinal cord is shorter by about 13% than the distance measured on the skin over the dorsal convexity. This correction should be applied routinely and it leads to a mean maximum spinal CV of 57 m/sec. Several positive far fields with widespread scalp distribution and stationary latencies have been identified. The P17 (over spine and head) reflects the peripheral nerve volley at the upper buttock. The P21 is synchronous with the N21 at the D12 spine and reflects the initial volley in the dorsal column. No far-field equivalent has been found for the N24-P24, due to the horizontal axis of the corresponding dipole. The P26 far field reflects the ascending volley at spinal levels D10-D4. The P31 reflects the initial volley in the medial lemniscus. The P40 at Cz represents the cortical response of the foot projection. Average central CVs were calculated and discussed.

Inhibition of the intracellular release of calcium by Dantrolene in barnacle giant muscle fibres.

1. Ca movements in resting and in activated single giant muscle fibres of the barnacle were analysed before and after exposure to Dantrolene Na, a synthetic hydantoin derivative. 2. In fibres micro‐injected with the photoprotein aequorin, the resting rate of light emission (resting glow) reversibly decreased upon exposure to Dantrolene. Similar results were obtained if the fibre had first been equilibrated in a O Ca‐1 mM‐EGTA medium. 3. The influx of 45Ca into resting muscle fibres was not modified by 35 micronM Dantrolene which also failed to significantly reduce the influx of 45Ca into muscle fibres which had been depolarized by exposure to external solutions in which K+ had been increased to 60 or 200 mM. 4. In fibres micro‐injected with 45Ca, the calcium efflux was reversibly decreased by Dantrolene. This effect was still observed in O Ca medium and in O Ca‐ONa medium. A possible effect of Dantrolene on the Na‐Ca exchange process at the outer membrane was excluded by showing that when the direction of the Ca2+ movement was inverted in aequorin‐loaded fibres by the sudden removal of Na+ from the external medium, a marked increase in the resting glow was recorded which was not affected by exposure to Dantrolene. 5. It is argued that the reduction of Ca2+ efflux by Dantrolene does not result from any direct inhibitory effect on the metabolically driven Ca pump at the outer membrane, but that it is rather related to the reduction of the concentration of myoplasmic Ca2+ which is indeed demonstrated by the reduced resting glow. This in turn is thought to result from a shift in the balance between Ca2+ movements into and out of the intracellular storage sites, and namely the sarcoplasmic reticulum (SR). 6. The Ca2+ transient in aequorin‐loaded fibres and the force of the isometric contraction elicited by imposed membrane depolarizations were markedly reduced by Dantrolene. The electrochemical threshold for eliciting intracellular Ca2+ release was not significantly modified. The linear relation between membrane depolarization and Ca2+ transient became less steep. The process of sequestration of myoplasmic Ca2+ back into SR was not significantly affected by Dantrolene which appeared to inhibit rather selectively the Ca2+ release from SR into the cytosol.