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.     

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?).     

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.     

Three-dimensional human somatosensory evoked potentials

Median nerve somatosensory evoked potentials were recorded from 30 normal adults using conventional scalp derivations and an orthogonal bipolar surface electrode montage. This allowed the determination of the spatial orientation of the hypothetical centrally located equivalent dipole derived from the evoked response recorded in 3-dimensional voltage space. The 3-dimensional voltage trajectory describing changes in equivalent dipole orientation and magnitude revealed 4 major apices between 5 and 25 msec, 3 of which corresponded to the traditional P14, N20 and P25 peaks. A fourth apex at 17 msec was not as evident in the conventional recordings and signaled a transition from a vertical P14–N18 generator process to a horizontal N20 generator process. The normal within- and between-subject variability of trajectory apices, segments and planes are described, along with the theoretical and practical implications of this recording technique.     

Topographic analyses of somatosensory evoked potentials following stimulation of tibial,sural and lateral femoral cutaneous nerves

Using topographic maps, we studied the scalp field distribution of somatosensory evoked potentials (SEPs) in response to the stimulation of the tibial (TN), sural (SN) and lateral femoral cutaneous (LFCN) nerves in 24 normal volunteers. Cortical peaks, i.e., N35, P40, N50 and P60 were generally dominant in the contralateral hemisphere for the LFCN-SEP, whereas all peaks except N35 had dominance in the ipsilateral hemisphere for TN- and SN-SEPs. The findings imply that ipsilateral or contralateral peak dominance for the lower extremity SEP is determined by where the cortical leg representation occurs. As a result, mesial hemisphere representation results in peak dominance projected to the hemisphere ipsilateral to stimulation. Representations at the superior lip of the interhemispheric fissure or lateral convexity lead to midline or contralateral peak dominance. These findings also suggest that the paradoxically lateralized P40 is not the result of a positive field dipole shadow generated by the primary negative wave in the mesial hemisphere, but is the primary positive wave, analogous to P26 of the median nerve SEP. Accordingly, contralaterally dominant N35 is likely equivalent to the first cortical potential of N20 in the median nerve SEP. The difference in vector directions of potential fields between N35 and P40 may account for the opposite hemispheric dominance for these peaks in TN- and SN-SEPs.     

Topography of somatosensory evoked potentials to median nerve stimulation in patients with cerebral lesions

Scalp distributions and topographies of early cortical somatosensory evoked potentials (SEPs) to median nerve stimulation were studied in 22 patients with 5 different types of cerebral lesion due to cerebrovascular disease or tumor (thalamic, postcentral subcortical, precentral subcortical, diffuse subcortical and parieto-occipital lesions) in order to investigate the origins of frontal (P20, N24) and central-parietal SEPs (N20, P22, P23).In 2 patients with thalamic syndrome, N16 was delayed in latency and N20/P20 were not recorded. No early SEP except for N16 was recorded in 2 patients with pure hemisensory loss due to postcentral subcortical lesion. In all 11 patients with pure hemiparesis or hemiplegia due to precentral subcortical lesion N20/P20 and P22, P23/N24 components were of normal peak latencies. The amplitude of N24 was significantly decreased in all 3 patients with complete hemiplegia. These findings support the hypothesis that N20/P20 are generated as a horizontal dipole in the central sulcus (3b), whereas P23/N24 are a reflection of multiple generators in pre- and post-rolandic fissures. P22 was very localized in the central area contralateral to the stimulation.Topographical studies of early cortical SEPs are useful for detecting each component in abnormal SEPs     

Median and tibial nerve somatosensory evoked potentials: middle-latency components from the vicinity of the secondary somatosensory cortex in humans

The topography of the middle-latency N110 after radial nerve stimulation suggested a generator in SII. To support this hypothesis, we have tried to identify a homologous component in the tibial nerve SEP (somatosensory evoked potential). Evoked potentials following tibial nerve stimulation (motor+sensory threshold) were recorded with 29 electrodes (bandpass 0.5–500 Hz, sampling rate 1000 Hz). For comparison, the median nerve was stimulated at the wrist. Components were identified as peaks in the global field power (GFP). Map series were generated around GFP peaks and amplitudes were measured from electrodes near map maxima. With median nerve stimulation, we recorded a negativity with a maximum in temporal electrode positions and 106±12 ms peak latency (mean±SD), comparable to the N110 following radial nerve stimulation. After tibial nerve stimulation the latency of a component with the same topography was 131±11 ms (N130). Both N110 and N130 were present ipsi- as well as contralaterally. Amplitudes were significantly higher on the contralateral than the ipsilateral scalp for both median (3.1±2.4 μV vs. 1.7±1.6 μV) and tibial nerve (1.9±1.2 μV vs. 0.6+1 μV). The topography of the N130 can be explained by a generator in the vicinity of SII. The latency difference between median and tibial nerve stimulation is related to the longer conduction distance (cf. N20 and P40). The smaller ipsilateral N130 is consistent with the bilateral body representation in SII.     

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 magnetic fields following stimulation of the lip in humans

The topography of somatosensory evoked magnetic fields (SEFs) following stimulation of the upper and lower lips was investigated in 6 normal subjects. When the lateral side of the upper lip was stimulated. P20m and its counterpart, N20m, were identified in the hemisphere contralateral to the stimulated side. The equivalent current dipoles (ECDs) of N20m-P20m were considered to be located in the lip area of the primary sensory cortex (SI). Middle latency deflections (N40m-P40m, N60m-P60m, and N80m-P80m) were identified in bilateral hemispheres. Their ECDs were located in the SI in both hemispheres. Long latency deflections (P110m-N110m) were recognized in both hemispheres, and their ECDs were located inferior to the SI, in an area considered to be the secondary sensory cortex (SII). When the midline of the lip was stimulated, similar short and middle latency deflections were also identified, but SII deflections (P110m-N110m) were decreased in amplitude. When the lower lip was stimulated, the ECDs of short and middle latency deflections were located at a site in the SI inferior to or near those elicited by upper lip stimulation. The ECDs of P110m-N110m were located in an area of the SII similar to that upon stimulation of the upper lip, but their orientations were different.     

Separate generators with distinct orientations for N20 and P22 somatosensory evoked potentials to finger stimulation?

Sequential spatial maps of scalp potentials, obtained with a 16-channel montage, were used in 12 healthy subjects in order to assess the temporal and spatial distribution of early cortical SEPs to single finger stimulation. It was found that when the contralateral parietal N20 negativity peaks there is a synchronous frontal P20 positivity, supporting the view of a tangentially orientated dipolar generator for this couple of scalp SEPs components. It was not possible to show a distribution of N20 peak on the scalp that would parallel the somatotopic finger representations in area S1; however, the orientation of the putative dipolar source of the N20/P20 complex was found to change according to the finger stimulated. A central P22 component was also constantly obtained without any synchronous negativity on the scalp surface corresponding to the electrode array; a clear somatotopic organisation was found for P22. These features favour the hypothesis that this latter component has a radially orientated generator situated in the prerolandic motor cortex, close to the scalp surface. Because of overlapping between the P20 and P22 components, the determination of P22 onset latency was hazardous in some cases, and spatial mapping was then essential to identify this component. The conclusion that the contralateral parietal N20 and central P22 could be generated by separate dipolar generators with distinct orientations is supported by recent data from combined electrical and magnetic field recording.     

Theta Burst Stimulation Applied over Primary Motor and Somatosensory Cortices Produces Analgesia Unrelated to the Changes in Nociceptive Event-Related Potentials

Continuous theta burst stimulation (cTBS) applied over the primary motor cortex (M1) can alleviate pain although the neural basis of this effect remains largely unknown. Besides, the primary somatosensory cortex (S1) is thought to play a pivotal role in the sensori-discriminative aspects of pain perception but the analgesic effect of cTBS applied over S1 remains controversial. To investigate cTBS-induced analgesia we characterized, in two separate experiments, the effect of cTBS applied either over M1 or S1 on the event-related brain potentials (ERPs) and perception elicited by nociceptive (CO₂ laser stimulation) and non-nociceptive (transcutaneous electrical stimulation) somatosensory stimuli. All stimuli were delivered to the ipsilateral and contralateral hand. We found that both cTBS applied over M1 and cTBS applied over S1 significantly reduced the percept elicited by nociceptive stimuli delivered to the contralateral hand as compared to similar stimulation of the ipsilateral hand. In contrast, cTBS did not modulate the perception of non-nociceptive stimuli. Surprisingly, this side-dependent analgesic effect of cTBS was not reflected in the amplitude modulation of nociceptive ERPs. Indeed, both nociceptive (N160, N240 and P360 waves) and late-latency non-nociceptive (N140 and P200 waves) ERPs elicited by stimulation of the contralateral and ipsilateral hands were similarly reduced after cTBS, suggesting an unspecific effect, possibly due to habituation or reduced alertness. In conclusion, cTBS applied over M1 and S1 reduces similarly the perception of nociceptive inputs originating from the contralateral hand, but this analgesic effect is not reflected in the magnitude of nociceptive ERPs.     

Pretecto-tectal influences

(1)From the dorsal surface of the toad (Bufo b. spinosus, B. marinus) optic tectum (OT), field potentials (FP) were recorded at 9 reference sites in response to electrical stimulation of the optic nerve (ON). The FP showed 4 main components, besides an initial deflection attributed to axonal potentials: two negative waves N1, N2 (attributed to postsynaptic excitatory processes) and two positive waves P2, P3 (attributed to postsynaptic inhibitory processes). The responses across the reference sites were rather similar in different individuals. (2) Electrical stimulation of an area in the ipsilateral pretectal lateral posterodorsal and posterior (Lpd/P) thalamic region evoked tectal FPs showing mainly a negative and a positive wave. Regarding wave amplitudes, the FPs displayed disproportionalities across the reference sites. (3) Electrical stimulation of the contralateral Lpd/P evoked mainly a positive wave in the tectal FP whose disproportionality corresponded roughly to the one obtained to ipsilateral Lpd/P stimulation. (4) The inital negative wave of the tectal FP in response to ON stimulation was nearly abolished, if Lpd/P stimulation preceded ON stimulation at a delay of 17–25 ms. (5) Since FPs showed adaptation to repetitive stimulation, various experiments were carried out to distinguish adaptation phenomena from effects of neuronal interactions between Lpd/P and OT. (6) The results provide evidence that ON- and Lpd/P-mediated inputs interact in superficial tectal layers, whereby pretectotectal input suppresses retinotectal excitatory information transfer. Input of Lpd/P to the contralateral superficial OT suggests postsynaptic inhibition. This study provides no information about pretectal inputs to deeper tectal layers, which anatomically are known to exist.Abbreviations A-I recording sites from the dorsal tectal surface - D _t delay between Lpd/P and ON stimulation - EPSP IPSP excitatory and inhibitory postsynaptic potentials, respectively - FP field potential - L latency of FP waves - ON optic nerve - OT optic tectum - Lpd/P lateral posterodorsal and posterior pretectal thalamic region - Lpv lateral posteroventral pretectal thalamic nucleus - N, P negative and positive waves of FPs, respectively - PRE presynaptic axonal input - TH pretectal thalamic neurons     

Pattern visual evoked potentials recorded from human occipital cortex with chronic subdural electrodes

Pattern evoked potentials to full- and partial-field stimulation were recorded simultaneously from scalp electrodes and from subdural electrodes located over the temporal and occipital cortex, including electrodes placed over or close to the lower lip of the calcarine fissure. High-amplitude pattern evoked potentials were recorded exclusively from electrodes localized in the vicinity of the calcarine fissure and showed a positive-negative deflection in phase with surface recordings, followed by a second negative peak phase reversed with respect to the major surface positive peak (“P100”). The findings suggest that the initial component is an expression of the afferent volley and that the second component (equivalent of the surface “P100”) is most probably generated as a dipole strictly localized to the visual cortex in close proximity of the calcarine fissure (area 17 and/or area 18).     

Origin of frontal N15 component of somatosensory evoked potential in man

Origin of the frontal somatosensory evoked potential (SEP) by median nerve stimulation was investigated in normal volunteers and in patients with localized cerebrovascular diseases, and the following results were obtained.

• 1.(1) In normal subjects, SEPs recorded at F3 (or F4) contralateral to the stimulating median nerve were composed of P12, N15, P18.5 and N26. Similar components were recognized in SEP recorded at Fz.
• 2.(2) In patients in whom putaminal or thalamic hemorrhages had destroyed the posterior limbs of the internal capsules, frontal N15 and parietal N18 (N20) disappeared. These components were also absent in patients with cortical (parietal) infarctions. Among these patients, the thalamus was not affected in cases with putaminal hemorrhages and cortical infarctions.

These facts indicate that the generator of the frontal N15 does not exist in the thalamus but that it originates from the neural structure central to the internal capsule, which suggests a similarity to the generator of the parietal N18.Because N15 was recorded in the midline of the frontal region with shorter latency than parietal N18, the frontal N15 might represent a response to the sensory input of the frontal lobe via the non-specific sensory system.     

Frontal distribution of early cortical somatosensory evoked potentials to median nerve stimulation

The topography of early frontal SEPs (P20 and N26) to left median nerve stimulation was studied in 30 normal subjects and 3 patients with the left frontal bone defect. The amplitudes of P20 and N26 were maximum at the frontal electrode (F4) contralateral to the stimulation and markedly decreased at frontal electrodes ipsilateral to the site of stimulation. There was, however, no latency difference of P20 and N26 between ipsilateral and contralateral frontal electrodes. These results suggest that the origin of the ipsilateral and contralateral P20 and N26 is the same. The wide distribution of P20 and N26 over both frontal areas could be explained by assuming a smearing effect from generators actually located in the rolandic fissure and motor cortex.     

Dissociation of temporal and frontal components in the human auditory N1 wave: a scalp current density and dipole model analysis

This study reports a combined scalp current density (SCD) and dipole model analysis of the N1 wave of the auditory event-related potentials evoked by 1 kHz tone bursts delivered every second. The SCD distributions revealed: (i) a sink and a source of current reversing in polarity at the inferotemporal level of each hemiscalp, compatible with neural generators in and around the supratemporal plane of the auditory cortex, as previously reported; and (ii) bilateral current sinks over frontal areas. Consistently, dynamic dipole model analysis showed that generators in and outside the auditory cortex are necessary to account for the observed current fields between 65 and 140 msec post stimulus. The frontal currents could originate from the motor cortex, the supplementary motor area and/or the cingulate gyrus. The dissociation of an exogenous, obligatory frontal component from the sensory-specific response in the auditory N1 suggests that parallel processes served by distinct neural systems are activated during acoustic stimulation. Implications for recent models of auditory processing are discussed.     

Early postnatal maturation in vestibulospinal pathways involved in neck and forelimb motor control

To assess the organization and functional development of vestibulospinal inputs to cervical motoneurons (MNs), we have used electrophysiology (ventral root and electromyographic [EMG] recording), calcium imaging, trans‐synaptic rabies virus (RV) and conventional retrograde tracing and immunohistochemistry in the neonatal mouse. By stimulating the VIIIth nerve electrically while recording synaptically mediated calcium responses in MNs, we characterized the inputs from the three vestibulospinal tracts, the separate ipsilateral and contralateral medial vestibulospinal tracts (iMVST/cMVST) and the lateral vestibulospinal tract (LVST), to MNs in the medial and lateral motor columns (MMC and LMC) of cervical segments. We found that ipsilateral inputs from the iMVST and LVST were differentially distributed to the MMC and LMC in the different segments, and that all contralateral inputs to MMC and LMC MNs in each segment derive from the cMVST. Using trans‐synaptic RV retrograde tracing as well as pharmacological manipulation of VIIIth nerve‐elicited synaptic responses, we found that a substantial proportion of inputs to both neck and forelimb extensor MNs was mediated monosynaptically, but that polysynaptic inputs were also significant. By recording EMG responses evoked by natural stimulation of the vestibular apparatus, we found that vestibular‐mediated motor output to the neck and forelimb musculature became more robust during the first 10 postnatal days, concurrently with a decrease in the latency of MN discharge evoked by VIIIth nerve electrical stimulation. Together, these results provide insight into the complexity of vestibulospinal connectivity in the cervical spinal cord and a cogent demonstration of the functional maturation that vestibulospinal connections undergo postnatally. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1061–1077, 2016     

The effects of stimulus rates upon median,ulnar and radial nerve somatosensory evoked potentials

We examined the effect of stimulus rates on the somatosensory evoked potential (SEP) amplitude following stimulation of the median nerve (MN) and the ulnar nerve (UN) at the elbow or wrist, and the radial nerve (RN) at the wrist in 12 normal subjects. We measured the amplitude of frontal (P14-N18-P22-N30) and parietal peaks (P14-N20-P26-N34) at a stimulus rate of 1.1, 3.5 and 5.7 Hz. The amplitude attenuation was found at frontal P22 and N30 and to a lesser degree at parietal N20 and P26 peaks with an increasing stimulus rate from 1.1 to 5.7 Hz. The amplitude attenuation was greatest at the elbow when compared to the wrist stimulation for both MN and UN. The attenuation was least for wrist stimulation for the RN. The UN block by local anesthesia just distal to the stimulus electrode at the elbow abolished the amplitude attenuation caused by the fast stimulus rate. The observed amplitude attenuation with the faster stimulus rate is probably due, in part, to interference from the “secondary” afferent inputs. The secondary afferent inputs arise from peripheral receptor stimulation (muscle, joint and/or cutaneous) as a subsequent effect of efferent volleys initiated from the point of stimulation. The greater number of peripheral receptors being activated as more proximal sites of stimulation in a mixed nerve would result in greater attenuation of the SEP recorded from scalp electrodes. We postulate that the attenuation of frontal peaks by the fast stimulus rate is due to the frontal projection of interfering “secondary” afferent inputs.     

The reactions of the cat motor cortex neurons to electrical stimulation of the base of the forebrain as a conditioned signal for the reflex of placing the forelimb on a support]

Electrical stimulation of the globus pallidus (500 ms, 300 Hz) in the area restricted by the stereotaxic coordinates AP 14-AP 16, L5-L8 at the level of the anterior commissura (HO) evoked food reactions in the form of mouth opening, chewing, and licking in the absence of food. There were no visible motor effects in the case of electrical stimulation of the subcommissural area (H-2-H-4) corresponding to the ventral pallidum and substantia innominata. The conditioned forepaw placing reaction was elaborated with the basal forebrain stimulation used as a conditioned stimulus. After conditioning, the short (3-5 pulses) conditioned basal forebrain stimulation evoked a prolonged (up to 500-1000 ms) activation of neurons in the motor cortex. This activation did not change in the absence of the movement, i.e., after acute extinction of the contralateral forepaw placing or transfer of placing reaction to the ipsilateral forepaw.     

Influence of acute cerebellar lesions on somatosensory evoked potentials (SEPs) in cats.

We studied the effect of acute unilateral cerebellar lesions on the cerebello-thalamo-cortical projection in cats. The lesions were classified into two groups according to their extent. In group I the lesion only covered the cerebellar cortex, while in group II both the cerebellar cortex and deep cerebellar nuclei were removed. Early (short-latency) and late (long-latency) waves, evoked by an electrical stimulation of a forelimb, were collected contralateral to the stimulated leg hemisphere. Pre- and postsurgery recordings from primary and non-primary (motor and parietal) cortices were compared. Cerebellar impairment had a strong influence on discharges of all the considered cortical areas. Early non-primary and primary responses increased in group I and remained unchanged in group II. Late somatosensory evoked potentials components were suppressed in both groups. An inhibitory influence of the cerebellar cortex on the thalamo-cortical projection was confirmed. Changes within the primary sensory cortex may suggest an engagement of that area in the compensation process of cerebellar dysfunction shortly after cerebellar lesion. An alteration in the unaffected hemisphere activation indicate that the spino-cerebellar and cerebello-cortical inputs, responsible for somatosensory evoked potentials generation, are regulated through contralateral and ipsilateral pathways. These pathways are unmasked by cerebellar lesion.