Mapping somatosensory evoked potentials to finger stimulation at intervals of 450 to 4000 msec and the issue of habituation when assessing early cognitive components

Somatosensory evoked potentials (SEPs) to mild electric stimulation of two fingers of the left hand were studied at regular interstimulus intervals (ISIs) of 450, 800, 1400, 2500 and 4000 msec. Habituation was evaluated while the subject was reading a novel so as to virtually ignore the finger stimuli while maintaining steady vigilance levels. Brain SEPs recorded from 25 scalp electrodes were assessed by scatter displays, electronic subtraction, bit-mapped potentials fields, and by calculating theZ estimator and dilation factor. Similar results were obtained with randomly varying ISIs. The P14 farfield and cortical N20 did not change with ISIs. The parietal P27–P45 decreased at ISIs of 800 and 450 msec, but showed no significant habituation at ISIs of 1400, 2500 or 4000 msec. This validated the control conditions used for assessing the early cognitive P30 and P40 to attended target stimuli. The frontal N30 also decremented at the shorter ISIs but still habituated up to ISIs of 2500 msec. The clear dissociation between frontal N30 and parietal P27 at the larger ISIs suggests that they involve at least in part distinct neural generators.     

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.     

Somatosensory evoked potential recovery (SEP-R) in various neurological disorders

Recovery functions of somatosensory evoked potentials were studied by the paired stimulation technique in 61 patients with various neurological disorders. A less suppressive or hyperexcitable phase at short intervals, which had been shown in myoclonic patients, was seen in 22 patients. This abnormality was observed even in patients without myoclonus or involuntary movements, which suggests that this phenomenon is not mainly due to some dysfunction causing myoclonus or movement disorders. Less suppression at short intervals was observed for both N20-P25 and P25-N33 components in most of them. Less suppressive recovery of the N20-P25 component with normal recovery of the P25-N33 component was shown only in 3 patients with subcortical lesions with relative sparing of the cortical elements (Binswanger's subcortical encephalopathy). We conclude that less suppressive recovery of only the N20-P25 component suggests the presence of subcortical lesions.     

Post-activation depression of primary afferents reevaluated in humans

Amplitude variation of Hoffmann Reflex (H-reflex) was used as a tool to investigate many neuronal networks. However, H-reflex itself is a subject to intrinsic changes including post-activation depression (P-AD). We aimed to investigate P-AD and its implication on motor control in humans. Upon tibial nerve stimulation in 23 healthy participants, peak-to-peak amplitude change of H-reflex was investigated using surface electromyography (SEMG) of soleus muscle. Variety of stimulus intensities, interstimulus intervals (ISIs), voluntary contraction levels/types and force recording were used to investigate the nature of P-AD. We have shown that P-AD was significantly stronger in the shorter ISIs. The only exception was the ISI of 200 msecs which had a weaker P-AD than some of the longer ISIs. Sudden muscle relaxation, on the other hand, further increased the effectiveness of the ongoing P-AD. Moreover, P-AD displayed its full effect with the first stimulus when there was no muscle contraction and was efficient to reduce the muscle force output by about 30%. These findings provide insight about the variations and mechanism of P-AD and could lead to improvements in diagnostic tools in neurological diseases.     

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.     

Classical Conditioning-Induced Changes in Low-Molecular-Weight GTP-Binding Proteins in Rabbit Hippocampus

Classical conditioning of Hermissenda, involving paired light-rotation events, results in a 30-35% decrease in the levels of a 20-kDa G protein (cp20). To test whether a similar protein exists in vertebrates, rabbits were trained to associate a tone with periorbital electrical stimulation and G proteins were analyzed by photoaffinity labeling with [alpha-32P]GTP-azidoanilide. A 20-kDa G protein similar to cp20 decreased by 36% in the hippocampus of rabbits subjected to paired tone and electrical stimulation, but not in unpaired controls. Learning-specific decreases were also found in the amount of ras protein.     

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?).     

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.     

Augmented P22-N31 SEP component in a patient with a unilateral space occupying lesion

A patient presented with a right rolandic space occupying lesion resulting in a decrease of position sense, touch and stereognosis in the left upper limb.SEPs revealed an augmentation of the right hemisphere P22 component co-existing with relative attenuation of all other right hemisphere components. The augmented P22-N31 complex represented a ‘giant’ potential in relation to a control group (> 2.5 S.D.).The data provide further evidence that the P22-N31 complex has separate generators from those responsible for the N20-P27-N33 components parietally and P20-N30 components frontally. The focal nature of the lesion and symptomatology are of interest.     

Enhanced amplitude reduction of somatosensory evoked potentials by voluntary movement in the elderly

We studied the effects of aging on modification of the median nerve somatosensory evoked potentials (SEPs) by voluntary movement in 17 aged (66.5±8.9 years, mean±SD) and 12 young normal humans (27.5±5.0 years). The amplitudes of cortical SEP components were generally larger in the aged group than in the young group. Following isometric contraction of the thenar muscle, the aged group showed significant attenuation of the prerolandic P22-N28-P45 and the postrolandic P24-N30-P45, while the young group only demonstrated significant reduction of the prerolandic P22-N28 amplitude. In the prerolandic N28-P45 and the postrolandic P24-N30 and N30-P45, amplitudes reduced by voluntary movement (gated amplitude) significantly correlated with amplitudes at rest (resting amplitude) and with the age of subjects. The effects of stimulus intensity and frequency on gating supported the correlative changes between gated and resting amplitudes. These results suggest that the magnitude of gating depends on SEP amplitudes at rest, and that augmented gating in the aged group is a result of enlarged SEPs. Since the cervical and Erb's potentials were not changed by movement, and passive movement did not significantly affect the SEPs, a centrifugal mechanism is probably responsible for gating in this study.     

Effect of US identity on elimination and recovery of autoshaped responding with explicitly unpaired and degraded contingency extinction procedures

The depressive effects of noncontingent and explicitly unpaired food unconditioned stimuli (USs) and the recovery from those effects on autoshaped responding were examined in a series of experiments with pigeons. In Experiments 1 and 2, responding to a keylight conditioned stimulus (CS) previously paired with food was depressed equally by explicitly unpaired presentations of either that same food or a different food. Furthermore, responding recovered equally following removal of the explicitly unpaired foods. In contrast, Experiments 3 and 4 showed that noncontingent presentations of a food US depressed responding more to a keylight CS paired with that same food than to a keylight CS paired with a different food. Moreover, removal of the noncontingent foods led to complete recovery but more rapid extinction of responding to the same keylight relative to the different keylight. The implications of these results for understanding the mechanisms underlying depression and recovery of responding following degraded contingency and explicitly unpaired extinction procedures are discussed.     

Adaptive significance of winter pair bond in male pintail, Anas acuta

To test the female-advantage hypothesis that has been proposed to explain the adaptive significance of winter pair bonds in ducks, we examined the feeding and social behaviors of the northern pintail, Anas acuta. The female-advantage hypothesis assumes that male attendance offers paired females the benefits of increased social status and access to food, as well as less harassment from conspecifics, allowing them to spend more time feeding. Paired females dominated unpaired females, but neither time budgets of feeding nor frequency of feeding was significantly different between unpaired and paired females. The female-advantage hypothesis predicts that paired males spend less time feeding because they must closely guard their partners from harassment by male conspecifics. Paired males defended their mates by chasing and pecking the unpaired males. However, both time budgets of feeding and frequency of feeding were significantly higher in paired males than in unpaired males. Unpaired males frequently approached females while swimming. They performed courtship displays, mostly toward unpaired females. Paired males spent more time feeding by saving time and energy in courtship. We consider that the advantage of winter pairing for males comes from having a mate plus having an increase in feeding frequency. Received: February 20, 2000 / Accepted: May 22, 2000     

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.     

Pavlovian conditioning with proximal stimuli

This experiment was conducted with the objective of demonstrating that the effective stimuli in Pavlovian Conditioning are not environmental stimuli but internal physiological processes elicited by environmental input (proximal stimuli). In order to achieve the objective, afterimages in color vision were used: looking at a diffuse lightened circle after seeing a red circle yields an image of a green circle. A differential conditioning paradigm with two sequential compounds was run. In one group (G+B-: n1 = 10), a red circle followed by a green circle was paired with shock, whereas a red circle followed by a blue circle remained unpaired. A second group (G-B+: n2 = 10) received red-blue paired trials and unpaired red-green trials. Immediately after that training, subjects were tested with a new, never trained sequential compound: a red circle followed by a diffuse lightened circle. Furthermore, they were tested with the already trained compounds. Taking the environmental point of view, the never trained stimulus should elicit an orienting response lying in between the excitatory reaction to the paired stimulus and the inhibitory reaction to the unpaired stimulus. From the proximal point of view, the diffuse light should elicit an excitatory reaction in group G+B- and an inhibitory reaction in group G-B+. Electrodermal conditioned anticipatory and omission responses were measured. The results supported the proximal hypothesis. Hence, defining input in environmental terms may be the wrong way. Instead, in conceptualizing the stimulus in conditioning, the following should be considered: the processing organism itself is creating the effective stimuli.     

Startle stimuli exert opposite effects on human cortical and spinal motor system excitability in leg muscles

Increased excitability of the spinal motor system has been observed after loud and unexpected acoustic stimuli (AS) preceding H-reflexes. The paradigm has been proposed as an electrophysiological marker of reticulospinal tract activity in humans. The brainstem reticular formation also maintains dense anatomical interconnections with the cortical motor system. When a startling AS is delivered, prior to transcranial magnetic stimulation (TMS), the AS produces a suppression of motor evoked potential (MEP) amplitude in hand and arm muscles of healthy subjects. Here we analyzed the conditioning effect of a startling AS on MEP amplitude evoked by TMS to the primary motor leg area. Ten healthy volunteers participated in two experiments that used a conditioning-test paradigm. In the first experiment, a startling AS preceded a suprathreshold transcranial test stimulus. The interstimulus interval (ISI) varied between 20 to 160 ms. When given alone, the test stimulus evoked a MEP amplitude of approximately 0.5 mV in the slightly preinervated soleus muscle (SOL). In the second experiment, the startling AS was used to condition the size of the H-reflex in SOL muscle. Mean MEP amplitude was calculated for each ISI. The conditioning AS suppressed MEP amplitude at ISIs of 30-80 ms. By contrast, H-reflex amplitude was augmented at ISIs of 100-200 ms. In conclusions, acoustic stimulation exerts opposite and ISI-specific effects on the amplitude of MEPs and H-reflex in the SOL muscle, indicating different mechanism of auditory-to-motor interactions at cortical and spinal level of motor system.     

Hippocampal place cells acquire location-specific responses to the conditioned stimulus during auditory fear conditioning

We recorded neurons from the hippocampus of freely behaving rats during an auditory fear conditioning task. Rats received either paired or unpaired presentations of an auditory conditioned stimulus (CS) and an electric shock unconditioned stimulus (US). Hippocampal neurons (place and theta cells) acquired responses to the auditory CS in the paired but not in the unpaired group. After CS-US pairing, rhythmic firing of theta cells became synchronized to the onset of the CS. Conditioned responses of place cells were gated by their location-specific firing, so that after CS-US pairing, place cells responded to the CS only when the rat was within the cell's place field. These findings may help to elucidate how the hippocampus contributes to context-specific memory formation during associative learning.     

Schistosoma mansoni: influence of the female parasite on glutathione biosynthesis in the male

The glutathione (GSH) content of male Schistosoma mansoni increases in the absence of the female. This phenomenon, originally observed in vitro, also occurs within the host. At the time of recovery from mice, the GSH content of males from single-sex infections was 1.7-fold higher than that of paired males from mixed sex infections (P less than 0.01). The effect of mating status on male GSH biosynthetic and turnover rates was examined to determine the basis for increased GSH content in unpaired males. GSH turnover rates, measured when GSH biosynthesis was inhibited by greater than 95% with 5.0 mM DL-buthionine-SR-sulfoximine, were indistinguishable between unpaired and paired males with a first-order rate constant of 0.018 hr-1. In contrast, incorporation of L-[35S]cysteine into GSH revealed that GSH biosynthesis was 5-fold higher in unpaired than in paired males. Transport of L-cystine into male schistosomes, the presumed rate-limiting step in GSH biosynthesis, was unaffected by mating status. The GSH content increased when males were incubated in medium that had previously contained females or when separated from females by a microporous membrane. Males paired to 50% ethanol-fixed females had unchanged GSH content in vitro. It appears that male GSH biosynthesis may be regulated by a response stimulated by the female's physical presence in the gynechophoral canal and not by a soluble factor released from the female.     

Rapid Plasticity in the Prefrontal Cortex during Affective Associative Learning

MultiCS conditioning is an affective associative learning paradigm, in which affective categories consist of many similar and complex stimuli. Comparing visual processing before and after learning, recent MultiCS conditioning studies using time-sensitive magnetoencephalography (MEG) revealed enhanced activation of prefrontal cortex (PFC) regions towards emotionally paired versus neutral stimuli already during short-latency processing stages (i.e., 50 to 80 ms after stimulus onset). The present study aimed at showing that this rapid differential activation develops as a function of the acquisition and not the extinction of the emotional meaning associated with affectively paired stimuli. MEG data of a MultiCS conditioning study were analyzed with respect to rapid changes in PFC activation towards aversively (electric shock) paired and unpaired faces that occurred during the learning of stimulus-reinforcer contingencies. Analyses revealed an increased PFC activation towards paired stimuli during 50 to 80 ms already during the acquisition of contingencies, which emerged after a single pairing with the electric shock. Corresponding changes in stimulus valence could be observed in ratings of hedonic valence, although participants did not seem to be aware of contingencies. These results suggest rapid formation and access of emotional stimulus meaning in the PFC as well as a great capacity for adaptive and highly resolving learning in the brain under challenging circumstances.     

Recovery function of somatosensory evoked potentials in juvenile myoclonic epilepsy*

Abstract

Objective: We analysed the recovery function of somatosensory evoked potentials (SEPs) in juvenile myoclonic epilepsy (JME) patients. We hypothesized that there may be disinhibition in the recovery of SEPs at 20–100?ms intervals in JME patients.

Methods: We recorded SEPs and SEP recovery in 19 consecutive patients with JME admitted for a routine follow-up examination, and in a control group composed of 13 healthy subjects who were similar to the patient group regarding age and sex. The recovery function of SEPs was examined using paired stimuli at 30, 40, 60, and 100?ms intervals.

Results: The amplitudes of N20-P25 and P25-N33 components were higher in patients with JME. Ten patients had high-amplitude SEPs. By paired stimulation, there was inhibition of SEPs in both groups. The mean recovery percentages of N20-P25 and P25-N33 components at 30, 40, 60, and 100?ms were not different between healthy subjects and patients with JME.

Conclusions: The recovery function of SEP is normal in JME even in the presence of high-amplitude SEPs.     

Olfactory event-related potentials: older males demonstrate the greatest deficits

Olfactory event-related potentials (OERPs) were recorded monopolarly at the Fz, Cz, and Pz electrode sites in 16 young adults (8M/8F) and 16 older adults (8M/8F) with inter-stimulus intervals (ISI) of 45, 60 and 90 s using amyl acetate as the odorant stimulus. N1, P2, and N2 peak amplitudes and latencies were measured. Young participants demonstrated significantly shorter peak latencies than older participants. Older males demonstrated significantly smaller peak amplitudes than the other participant groups. Peak amplitudes also increased with longer ISIs for older males. The OERP is compared to traditional olfactory psychophysical testing.