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

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

The genesis of movement-related human brain potentials in different forms of motor pathology]

To study the role of subcortical structures and cerebellum nuclei in the genesis of the human brain potentials connected with motion patients were examined with parkinsonism and hyperkinetic form of children cerebral paralysis. In one group of patients the motor responses were recorded by means of long-term electrodes implanted with the medical purpose into the ventro-oral group of thalamus nuclei, subcortical nuclei and dentate cerebellum nuclei. In patients of the second group potentials, connected with motion were led from the scalp before and after one-moment destruction in the zone of the same structures. In ventro-oral and reticular thalamus nuclei lateral and medial segments of the pale globe and in the cerebellum dentate nucleus post-motor components were recorded which were considered as electrographic expression of motion realization and completion processes (P2 and N3) and also as slow negative oscillation (component N1), that pointed to participation of the studied structures not only in regulation of voluntary movement but also in the process of movement preparation. Absence of N2 component at recording motor responses from deep electrodes and its sufficient stability at scalp leads gave the reason to suggest that its genesis was connected with the cortex activity.     

Decreased response to novel stimuli after prefrontal lesions in man

Experiments were conducted to study the contribution of prefrontal cortex to the generation and modulation of two varieties of P300 activity. Control subjects generated typical parietal maximal P300 responses to detected target stimuli. Unexpected, novel auditory stimuli presented to controls generated an earlier latency, fronto-centrally distributed P300 response. A similar earlier latency, fronto-central P300 is generated to unexpected, novel visual stimuli. The occurrence of this phenomenon in both the auditory and visual modalities suggests that it may reflect neural activity of a common CNS system involved in the orienting response.Subjects with unilateral prefrontal damage generated P300 complexes to target stimuli that did not differ from the control responses. Prefrontal damage, however, resulted in a specific defect in the P300 response to the unexpected novel stimulus. Prefrontal patients showed neither N200 enhancement nor the fronto-central P300 response to the novel stimulus that was found in control subjects. These findings indicate that prefrontal regions are critical for the organism's response to unexpected novel stimuli. Abnormalities in prefrontal control of sensory-limbic integration may be a critical element in the decreased P300 to novel stimuli found in these unilateral prefrontal lesioned patients. It is suggested that major features of the human frontal lobe syndrome may be explained by a physiological inability to control attention and orientation systems after prefrontal damage.     

Sensory and cognitive evoked potentials in a case of congenital hydrocephalus

We studied auditory and visual evoked potentials in D.W., a patient with congenital stenosis of the cerebral aqueduct. Head CT scans revealed marked hydrocephalus with expanded ventricles filling more than 80% of the cranium and compressing brain tissue to less than 1 cm in thickness. Despite the striking neuroanatomical abnormalities, however, the patient functioned well in daily life and was attending a local community college at the time of testing.Evoked potentials provided evidence of preserved sensory processing at cortical levels. Pattern reversal visual evoked potentials had normal latencies and amplitudes. Brain-stem auditory evoked potentials (BAEPs) showed normal wave V latencies. Na and Pa components of middle-latency AEP had normal amplitudes and latencies at the vertex, although amplitudes at lateral electrodes were larger than at the midline.In contrast to the normal sensory responses, long-latency auditory evoked potentials to standard and target tones showed abnormal P3 components. Standard tones (probability 85%), evoked NN1 components with normal amplitudes (−3.7 μV) and latencies (103 msec), but also elicited large P3 components (17 μV, latency 305 msec) that were never observed following frequent stimuli in control subjects. Target stimuli (probability 15%) elicited P3s in D.W. and controls, but P3 amplitudes were enhanced in D.W. (to more than 40 μV) and the P3 showed an unusual, frontal distribution. The results are consistent with a subcortical sources of the P300. Moreover, they suggest that the substitution of controlled for automatic processes may help high-functioning hydrocephalics compensate for abnormalities in cerebral structure.     

Event-related potentials recorded from the scalp and nasopharynx. I. N1 and P2

Event-related potentials were recorded from the scalp and nasopharynx during a signal-detection task. These responses were evaluated with respect to the effects of interstimulus interval, intensity, frequency, attention and modality. Our results indicate the existence of at least 4 distinct processes occurring in the 75–150 msec latency range following auditory stimuli. The first process is indexed in the vertex-N1b/temporal-N1a component. This component does not reverse in polarity below the sylvian fissure and is not seen in nasopharyngeal recordings. The location of its generator is not known. Probably there are two or more sources active at this latency. The second process finds reflection in the N1c/PgP120 component. This component is recorded with maximum amplitude on the side contralateral to the ear of delivery. A source in the lateral surface of the temporal lobe is a likely generator. The third process corresponds to Wolpaw and Penry's (1975) Ta positivity. How much of this represents the underside of a vertically oriented dipole and how much a surface positivity is unknown. Finally, during attention, a lateralized processing negativity seems to overlap these components at the scalp, but not at the nasopharynx. The auditory vertex N1 peak is quite distinct from the visual N1 which is more posteriorly recorded on the scalp and which is associated with a definite nasopharyngeal positive wave. The P2 peak is quite similar across auditory and visual modalities. In both modalities it is maximally recorded from the vertex and has no nasopharyngeal concomitant.     

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

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

Clinical application of the P3 component of event-related potentials. I. Normal aging

Normal adult volunteer subjects ranging in age from 18 to 90 years participated in a study in which analogous auditory and visual paradigms, with infrequently occurring target and non-target events, were used to elicit event-related potentials (ERPs) with a prominent P3 component. Of the 135 subjects participating, 66 completed both auditory and visual paradigms. The amplitude and latency of P3 were analyzed using average ERPs, single trials (adaptive filter) and principal components analysis (PCA). Age regressions were calculated using measures derived from average ERPs and single trials. Single trial measures were better than average ERP measures in demonstrating age-related changes in P3 latency. There was a significant increase in P3 latency with age of 1–1.5 msec/year. The range of normal P3 latency for a given age (1 S.E. of the regression = 40 msec for the visual target stimuli) was much larger than obtained by other investigators.The visual paradigm produced higher P3 latency/age correlations than the auditory paradigm (visual target r = 0.52, non-target r = 0.42; auditory target r = 0.32, non-target r = 0.33). Within individuals, the amplitude and latency of P3 generated by auditory and visual stimuli were highly correlated, though the visual paradigm produced larger and later P3s than the auditory paradigm.There is an apparent change in the scalp topography of P3 with age. In young adults, P3s to target stimuli have a markedly parietal distribution. The distribution of P3 becomes more uniformly distributed from Pz to Fz with age. This may be due to changes in overlapping components such as the slow wave (SW) rather than to changes in the amplitude of P3 per se.     

An overview of age-related changes in the scalp distribution of P3b

In this overview of 7 studies, the scalp distribution of the P3b component (i.e. the P3 or P300) of the event-related potential elicited by target events in young and older adults was assessed. The target P3b data were recorded in either auditory oddball paradigms or in visual study tasks in which orienting activity was manipulated (as a within-subjects variable) in investigations of indirect memory. Some of the studies required choice reaction time responses, whereas others required responses only to the target stimuli. Motor response requirements had a profound effect on the P3b scalp distribution of older but not of younger subjects. The presence of a frontally oriented scalp focus in the topographies of the older adults in most of the tasks described here is consistent with older adults continuing to use prefrontal processes for stimuli that should have already been well encoded and/or categorized. However, although older subjects generally had different P3b scalp distributions than younger subjects, their scalp distributions were modulated similarly by task requirements. These data suggest that similar mechanisms modulate the scalp distribution of P3b in older compared to younger adults. However, in the older adult, these scalp distribution changes in response to task demands are superimposed on a frontally oriented scalp focus due to a putative frontal lobe contribution to target P3b topography.     

Mismatch negativity of ERP in cross-modal attention

Event-related potentials were measured in 12 healthy youth subjects aged 19-22 using the paradigm "cross-modal and delayed response" which is able to improve unattended purity and to avoid the effect of task target on the deviant components of ERP. The experiment included two conditions: (i) Attend visual modality, ignore auditory modality; (ii) attend auditory modality, ignore visual modality. The stimuli under the two conditions were the same. The difference wave was obtained by subtracting ERPs of the standard stimuli from that of the deviant stim-uli. The present results showed that mismatch negativity (MMN), N2b and P3 components can be produced in the auditory and visual modalities under attention condition. However, only MMN was observed in the two modalities un-der inattention condition. Auditory and visual MMN have some features in common: their largest MMN wave peaks were distributed respectively over their primary sensory projection areas of the scalp under attention condition, but over front     

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

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

Task difficulty,probability, and inter-stimulus interval as determinants of P300 from auditory stimuli

The P300 event-related potential was elicited with auditory stimuli in 4 experiments which manipulated combinations of stimulus target probability (10% vs. 30%), task difficulty (easy vs. hard), and inter-stimulus interval (5 sec vs. 2 sec). P300 amplitude was smaller and peak latency longer for the more difficult relative to the easier tasks across experiments. Increases in stimulus target probability generally diminished P300 amplitude and shortened peak latency more for the easy relative to difficult task conditions. Increasing the number of non-target stimulus tones decreased P300 amplitude reliably, but increased latency only slightly. Task difficulty did not interact with variations in inter-stimulus interval which produced generally weak effects for both amplitude and latency. These findings suggests that P300 amplitude and latency obtained from auditory discrimination paradigms reflect processing difficulty independently of stimulus target probability unless differences in task requirements affect stimulus encoding.     

Potentials evoked in human and monkey medial temporal lobe during auditory and visual oddball paradigms

Event-related potentials (ERPs) were recorded from epileptic patients with electrodes chronically implanted in the medial temporal lobe (MTL) and other intracranial locations, and from monkeys with epidural, transcortical, and MTL electrodes. For both humans and monkeys, the eliciting events consisted of trains of auditory or visual stimuli in which a random 10–20% deviated in pitch or pattern from the remaining stimuli. The distribution of ERPs elicited by the rare (oddball) stimuli in both species was similar, consisting of a P3 recorded from the scalp or cortical surface and a slightly later, but temporally overlapping, focal negativity in the hippocampus and nearby MTL structures. The similarity between the patterns of ERPs in humans and monkeys establishes the feasibility of studying the electrogenesis of P3-like activity with detailed intracranial recordings in an animal model. The data also establish that the MTL ERPs in human patients represent a normal neurophysiological process unrelated to epilepsy.     

Somatosensory evoked potentials from the thalamic sensory relay nucleus (VPL) in humans: correlations with short latency somatosensory evoked potentials recorded at the scalp

Somatosensory evoked potentials (SEPs) were recorded in humans from an electrode array which was implanted so that at least two electrodes were placed within the nucleus ventralis posterolateralis (VPL) of the thalamus and/or the medial lemniscus (ML) of the midbrain for therapeutic purposes. Several brief positive deflections (e.g., P11, P13, P14, P15, P16) followed by a slow negative component were recorded from the VPL. The sources of these components were differentiated on the basis of their latency, spatial gradient, and correlation with the sensory experience induced by the stimulation of each recording site. The results indicated that SEPs recorded from the VPL included activity volume-conducted from below the ML (P11), activity in ML fibers running through and terminating within the VPL (P13 and P14), activity in thalamocortical radiations originating in and running througn the VPL (P15, P16 and following positive components) and postsynaptic local activity (the negative component). The sources of the scalp-recorded SEPs were also analyzed on the basis of the timing and spatial gradients of these components. The results suggested that the scalp P11 was a potential volume-conducted from below the ML, the scalp P13 and P14 were potentials reflecting the activity of ML fibers, the small notches on the ascending slope on N16 may potentially reflect the activity of thalamocortical radiations, and N16 may reflect the sum of local postsynaptic activity occurring in broad areas of the brain-stem and thalamus.     

Contributions from the auditory nerve to the brain-stem auditory evoked potentials (BAEPs): results of intracranial recording in man

Intraoperative recordings obtained from electrodes placed on the scalp (vertex and earlobe or ear canal) in response to click stimulation were compared with recordings made directly from the auditory nerve in patients undergoing microvascular decompression (MVD) operations to relieve hemifacial spasm (HFS) and disabling positional vertigo (DPV). The results support earlier findings that show that the auditory nerve is the generator of both peak I and peak II in man, and that it is the intracranial portion of the auditory nerve that generates peak II. The results indicate that the second negative peak in the potentials recorded from the earlobe is generated by the auditory nerve where it passes through the porus acusticus into the skull cavity, and that the proximal portion of the intracranial portion of the auditory nerve generates a positive peak in the potentials that are recorded from the vertex. This peak appears with a latency that is slightly longer than that of the second negative peak in the potentials recorded from the earlobe (or ear canal). The second negative peak in the recording from the ear canal and the positive peak in the vertex recording contribute to peak II in the differentially recorded BAEP. Since our results indicate that the difference in the latency of the second negative peak in the recording from the earlobe and that of the positive peak in the vertex recording represents the neural travel time in the intracranial portion of the auditory nerve, this measure may be valuable in the differential diagnosis of eighth nerve disorders such as vascular compression syndrome.     

Scalp potentials following sudden coherence and discoherence of binaural noise and change in the inter-aural time difference: a specific binaural evoked potential or a “mismatch” response?

When uncorrelated random noise signals presented to the two ears suddenly become identical (coherent), a centrally located sound image is abruptly perceived and long latency scalp potentials are evoked. When the same signals are presented monaurally there is no perceived change and no potentials are evoked: hence the response must be purely a function of the binaural interaction.P70, N130 and P220 components were consistently recorded to both coherence and discoherence. N130 was usually largest at Fz and P220 at Cz. No potentials of shorter latency were identified, even after averaging 5000 or more sweeps. When the noise became coherent with an inter-aural time difference (δT) of ±0.5 msec (giving rise to an off-centre sound image), the responses were of slightly longer latency and showed no significant asymmetries between C3 and C4. In binaurally coherent noise, δT changes of ±0.5 or ±1.0 msec evoked similar responses which showed no significant asymmetries on the scalp. N130 was of longer latency when δT was changed from ±0.5 msec to zero, as compared with the converse change.In view of the similarity of all these responses it is considered unlikely that they were due to specific populations of binaurally responsive cortical neurones. The N130 and P220 components are thought to be non-specific potentials which are elicited by amy perceptible change in steady auditory stimulus conditions, due to a “mismatch” between the stimulus and the contents of a short-term auditory memory.     

Origin of scalp far-field N18 of SSEPs in response to median nerve stimulation

To identify the origin of scalp-recorded far-field negativity of short-latency somatosensory evoked potentials to median nerve stimulation (designated N18), direct records were made from the thalamus and ventricular system during 4 stereotaxic and 3 posterior fossa operations.In the thalamus a negative potential with almost the same latency as the scalp N18 was restricted to the Vim nucleus, but there was a large positive potential in the VC nucleus and medial lemniscus. Vim negativity increased in amplitude when high frequency stimulation was given to the median nerve, indicative of a facilitation effect. In contrast, the amplitude of scalp N18 decreased at high frequency stimulus.Direct recordings made through the medulla oblongata to the mid-brain showed a negative potential with gradually increasing latency. Above the upper pons, there was stationary negativity with no latency shift. The similarity between this negative potential and N18 is shown by their having the same latency and same response to the amplitude reduction and latency prolongation produced by high frequency stimulus.Our data suggest that scalp N18 comes from brain-stem activity between the upper pons and the mid-brain rather than from the thalamus.     

Visual event-related potentials to moving stimuli: normative data

Visual cognitive responses (P300) to moving stimuli were tested in 36 subjects with the aim to find the normal range of P300 parameters. Concomitantly, the circadian intra-individual variability of the P300 was studied in a subgroup of 6 subjects. Visual stimuli consisted of either coherent (frequent stimulus) or non-coherent motion (random stimulus). The oddball paradigm was applied for recording cognitive responses. P300 to rare stimuli had an average latency of 447.3 +/- 46.6 ms and amplitude of 12.9 +/- 6.0 microV. The average reaction time was in the range from 322 to 611 ms and there was no correlation between the reaction time and P300 latency. We did not find any significant circadian changes of the P300 parameters in the 6 subjects tested four times during the same day. Cognitive (event-related) responses (P300) displayed distinctly greater inter-individual variability (S.D. of 50 ms) when compared with pattern-reversal and motion-onset VEPs (S.D. of 6.0 ms and 14 ms, respectively). For this reason, the clinical use of P300 elicited by this kind of visual stimuli seems to be rather restricted and the evaluation of its intra-individual changes is preferable.     

P300 from a single-stimulus paradigm: passive versus active tasks and stimulus modality

The P300 component of the event-related brain potential (ERP) was elicited with auditory and visual stimuli in separate experiments. Each study compared an oddball paradigm that presented both target and standard stimuli with a single-stimulus paradigm that presented a target but no standard stimuli. Subjects were instructed in different conditions either to ignore the stimuli, press a response key to the target, or maintain a mental count of the targets. For the passive ignore conditions, P300 amplitude from the single-stimulus paradigm was larger than that from the oddball paradigm. For the active tasks, P300 amplitude from the oddball paradigm was larger than that from the single-stimulus paradigm. For the press and count conditions, P300 amplitude and latency were highly similar for the oddball and single-stimulus procedures. The findings suggest that the single-stimulus paradigm can provide reliable cognitive measures in clinical/applied testing for both passive and active response conditions.     

Cerebral-evoked responses elicited by direct stimulation of the lateral spinothalamic tract in the human

The authors recorded cerebral-evoked responses elicited by direct stimulation of the human lateral spinothalamic tract (LST) during percutaneous cordotomy to investigate central conduction of noxious stimuli. These responses consisted of four negative potentials, peak latency being 3.8 (N1), 8.4 (N2), 12.2 (N3) and 21.9 (N4) ms respectively. N1 showed wide distribution over the scalp and was considered to be of subcortical origin. N2-N4 were distributed in both the temporal and central area. The different distribution pattern of N2-N4 from conventional somatosensory-evoked potential suggested a different projection of LST from the medial lemniscus system.     

On the problem of cooperation of the reactions of hands: III. Cooperation of hand reactions to auditory and visual stimuli in patients with focal lesions of the brainstem and diencephalon

The response time (simple mental reaction time) cooperation was estimated in 53 patients with focal lesions of the brainstem and diencephalon (thalamus). The cooperation between the left-and right-hand simple mental reactions to auditory and visual stimuli presented after a warning stimulus was analyzed to determine the morphological structures responsible for the cooperation of responses. The cooperation of the simple mental reaction remained normal in some of the subjects and was disturbed in others. In the latter case, the correlation coefficient between the left-and right-hand simple mental reactions to an auditory or visual stimulus or both stimuli simultaneously was changed. The disturbances were detected in patients with lesions of the tectum at the boundary between the medulla and the pons and in those with affected lateral regions of the thalamus.