P300-like potentials in the normal monkey using classical conditioning and an auditory ‘oddball’ paradigm

Endogenous components of evoked potentials resembling P300 in humans were sequentially studied in 3 cynomolgus monkeys (Macaca fascicularis) using an auditory ‘oddball’ paradigm. The two different auditory stimuli were 500 Hz and 4000 Hz tones, designated as the ‘frequent’ and ‘rare’ stimuli, respectively. The probability of ‘rare’ tone presentation was initially 0.2. We further used probabilities of 0.1, 0.3 and 0.5. The ‘rare’ stimulus was reinforced by electrical stimulation, which followed the onset of the high tone by 700 msec. After 3–5 training sessions, a late positive wave was observed following the ‘rare’ tone. The latency of this P300-like signal was 314±16.2 msec, and teh amplitude 23.6±3.14 μV. The amplitude of this potential was modified by changes in stimulus presentation probability and by withholding reinforcement.     

Event-related potentials in the dorsal hippocampus of rats during an auditory discrimination paradigm

The relation of the hippocampal neuronal activity to the rat event-related potential (ERP) generation was examined during an auditory discrimination oddball paradigm. ERPs were recorded using a linearly-arranged series of electrodes chronically implanted at the skull, in the frontoparietal cortex, in the CA1 and CA3 regions of the dorsal hippocampus and in the thalamus. The target tone elicited N40, P100, N200, and P450 at the skull electrode. The non-target tone, on the other hand, prominently evoked only the P100 component. At the intracranial electrodes, the ERP amplitude at the latency of the skull P450 was significantly greater in the CA3 region than that at other recording sites, although a phase reversal was not observed. The results indicate that the P450 of the rat may correspond to the human P3, and that the neuronal activity in the hippocampus is involved in its generation.     

Comparison of the electrophysiological effect of amiodarone, lidocaine and quinidine on rat ventricular cells.

The effects of 20 microM each of amiodarone, lidocaine and quinidine on action potential and membrane currents were studied in rat ventricular cells. At a stimulation frequency of 0.1 Hz, quinidine prolonged the action potential duration (APD50) from 120 +/- 26 to 660 +/- 8 msec and increased the time to peak (Tp) amplitude from 7 +/- 1 msec to 32 +/- 6 msec. Lidocaine shortened APD50 from 123 +/- 15 to 83 +/- 6 msec without altering Tp. Amiodarone changed neither APD50 nor Tp. Voltage clamp study revealed that quinidine inhibited sodium inward current (INa) even when this current was elicited by depolarizing pulses at 0.1 Hz from a holding potential of -90 mV. For amiodarone and lidocaine, the inhibition was observed when INa was elicited from a holding potential of -70 mV. A frequency-dependent inhibition of INa by amiodarone and lidocaine was observed at frequencies higher than 1 Hz. Quinidine showed this inhibition even at 1 Hz. In correlation with the stronger frequency dependent inhibition of INa, a greater delay of the recovery and increase of the non-recovery fraction of INa was induced by quinidine. For lidocaine and amiodarone, only the recovery time constant was delayed. In cells treated with sea anemone toxin (ATX, 0.2 microM), APD50 was prolonged to 4-5 sec in 5 min. Quinidine, but not amiodarone, completely reversed the effect of ATX. Quinidine showed use-dependent inhibition of INa in these ATX-treated cells. Amiodarone, however, did not show this inhibition. It is likely that amiodarone suppresses INa by delaying the recovery of INa instead of blocking the open-state Na(+)-channels.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Laser-evoked potentials: exogenous and endogenous components

The aim of this study was to distinguish the exogenous component (related to the physical properties of the stimulus) and the endogenous component (reflecting event-related cognitive processing) of the laser-evoked potential (LEP). Short painful radiant heat pulses generated by a CO₂-laser were applied to the dorsum of the right and left foot. LEPs were recorded with 5 scalp electrodes in the midline versus linked earlobes in 26 healthy subjects. In order to identify the exogenous component, the LEP was recorded during a standardised distraction task (reading a short story). To identify the endogenous component P3 for the LEP, a 2-stimulus oddball paradigm was used (20% probability of targets). When the task of the oddball paradigm consisted of pressing a button, a movement-related long-latency negativity (N1200) was recorded in frontal leads that was absent in a counting task. The LEP of targets, frequent non-targets and during distraction was dominated by a single large positivity. The amplitude of this positivity was task-dependent and increased the more attention the subject payed to the laser stimuli (distraction < neutral < non-target < target). The laser-evoked positivity during distraction had a peak latency of about 400 msec (P400) and a maximum amplitude at the vertex, which was independent of inter-stimulus interval. The P3 following laser stimulation had a significantly later peak at about 570 msec (P570) and a different scalp topography with a parietal maximum. Its amplitude decreased when the interstimulus interval was reduced from 10 to 6 sec. Under neutral instructions, the LEP positivity consisted of a superposition of both the exogenous P400 and the endogenous P570.     

P300 from a single auditory stimulus

The P3(00) event-related brain potential (ERP) was elicited with auditory stimuli to compare 2 different discrimination tasks. The oddball paradigm presented both target and standard tones; the single-stimulus paradigm presented at target but no standard tone stimulus. Experiment 1 manipulated target stimulus probability (0.20, 0.50, 0.80) and produced highly similar P3 amplitude and latency results across probability levels for each paradigm. Experiment 2 factorially varied inter-stimulus interval (2 sec, 6 sec) and target stimulus probability (0.20, 0.80). P3 amplitude and latency were highly similar for both the oddball and single-stimulus procedures across all conditions.     

Neural generators of the somatosensory evoked potentials: Recording from the cuneate nucleus in man and monkeys

The neural generators of the somatosensory evoked potentials (SEPs) elicited by electrical stimulation of the median nerve were studied in man and in rhesus monkeys. Recordings from the cuneate nucleus were compared to the far-field potentials recorded from electrodes placed on the scalp. It was found that the shape of the response from the surface of the human cuneate nucleus to stimulation of the median nerve is similar to that of the response recorded more caudally in the dorsal column, i.e., an initially small positivity followed by a negative wave that is in turn followed by a slow positive wave. The beginning of the negative wave coincides in time with the N14 peak in the SEP recorded from the scalp, and its latency is 13 msec. The response from the cuneate nucleus in the rhesus monkey has a similar shape and its negative peak appears with the same latency as the positive peak in the vertex response that has a latency of 4.5 msec; the peak negativity has a latency of about 6 msec and thus coincides with P6.2 in the vertex recording. Depth recordings from the cuneate nucleus and antidromic stimulation of the dorsal column fibers in the monkey provide evidence that the early components of the response from the surface of the cuneate nucleus are generated by the dorsal column fibers that terminate in the nucleus.The results support the hypothesis that the P14 peak in the human SEP is generated by the termination of the dorsal column fibers and that the cuneate nucleus itself contributes little to the far-field potentials.     

Is the somatosensory N250 related to deviance discrimination or conscious target detection?

Effects of attention to, and probability of sudden changes in, repetitive stimuli on somatosensory evoked potentials (SEP) were studied. Low- (30 Hz) and high-frequency (140 Hz) vibratory stimuli were delivered in random order to the middle finger of the left hand with different presentation probabilities in different blocks. Also ignore conditions were administered.In the ignore conditions, the probability had no effect on SEPs. However, when the standard stimuli were omitted, the “deviants” elicited small N140 and P300 deflections not observed in response to deviants when standards were also present. In the attention conditions, deviant stimuli (targets) elicited large N250 and P300 deflections which increased in amplitude with a decreased target probability. However, when subjects counted infrequently presented “deviants” alone (standards omitted) the enhanced N140 and the P300 with shortened latency were elicited, but no N250 wave could be found. At the ipsilateral side, a distinct N200 deflection was seen which could be the N250 with a shorter latency because of an easier task (detection instead of discrimination). The results might be interpreted as suggesting that the somatosensory N250 is related to conscious detection of target stimuli.     

用园窗法记录的豚鼠听觉早潜伏期40Hz相关电位

采用适宜的参数,从豚鼠园窗记录出一种新的听觉４０Ｈｚ相关电位,它不同于Ｇａｌａｍｂｏｓ提出的听觉中潜伏期４０Ｈｚ相关电位。通过不同部位引导的对比观察,对该电位的基本特征、影响因素及其可能发生机理进行了初步探讨,结果显示４０ＨｚＡＥＲＰ－ＥＬＲ波形稳定,振幅高,频率响应好,反应阈值低。在０．５ｋＨｚ短纯音的反应阈值为１３．７５ｄＢｎＨＬ,较颅顶的听觉中潜伏期４０Ｈｚ相关电位低３５ｄＢｎＨＬ。     

P300, probability,and the three-tone paradigm

The effects of stimulus probability on P300 from a 3-tone paradigm were examined in two experiments. Experiment 1 manipulated the probability of the non-target tone as 0.10, 0.45, or 0.80, while the target tone probability was always 0.10. Experiment 2 manipulated the probability of 3 tones as 0.10, 0.30, or 0.60, with one of the infrequent tones assigned as the target in each condition. Subjects were required to press a button in response to the target stimulus in both experiments. The results indicated that the P300 to the target and the non-target were both affected by the probability of the eliciting stimulus, such that component amplitude was inversely related to probability; no reliable P300 latency effects were found. Target tones elicited larger P300 amplitude than the non-target tones at the same probability. The findings suggest that probability effects on P300 amplitude are independent of responding to a specific target stimulus and are discussed with reference to the clinical utility of the 3-tone paradigm.     

P300 assessment of early Alzheimer's disease

The P300 (P3) event-related brain potential (ERP) was elicited in 16 demented patients presumed to be in the early stages of Alzheimer's disease and 16 normal control subjects well matched for age, sex, education and occupational level. All subjects performed a simple auditory discrimination task in which a target tone was presented randomly on 20% of the trials. P3 amplitude was smaller and peak latency longer for the Alzheimer patients compared to control subjects. A second ERP task also was administered in which the target tone occurred 50% of the time. Analysis of the target/standard tone presentation sequences indicated that the Alzheimer patient group demonstrated less amplitude difference between the target and standard sequences and longer overall latencies compared to the control group. The results that the P3 ERP component from auditory stimuli can provide useful information about Alzheimer's disease during its early stages.     

Long latency auditory evoked potentials: intensity, inter-stimulus interval, and habituation

Experiment 1 elicited the P1, N1, P2, and N2 components of the long latency auditory evoked potential (AEP) using a 1000 Hz tone presented at 30, 50, or 70 dB SPL and 1-, 3-, or 5-second inter-stimulus intervals to assess the relative effects of the combination of these variables on component amplitude and latency. Four blocks of 16 tone presentations each were recorded from each subject to determine if changes in the AEP would occur because of short-term habituation. Both stimulus factors interacted significantly in a systematic fashion for the amplitude measures, with increases in latency also associated with increases in intensity and inter-stimulus interval. Only minor changes across the four trial blocks for either the amplitude or latency measures were observed over the various stimulus presentation conditions. Experiment 2 employed the same tone stimulus presented at 50 dB SPL and a 3-second inter-stimulus interval. Eight blocks of 64 trials were recorded from each subject on each day for four days to investigate long-term habituation effects. No substantial changes in any of the component amplitudes or latencies were obtained across the 32 trial blocks. It was concluded that intensity and inter-stimulus interval interact to determine AEP amplitude as well as latency values and that the constituent components do not change appreciably with repeated stimulus presentations, even after several days.     

Auditory event-related potentials to deviant stimuli during drowsiness and stage 2 sleep

Twelve subjects were tested using a 3-tone auditory oddball paradigm consisting of a standard 1000 Hz tone (P = 80%) and two deviants, namely, a 1200 Hz tone and a 2000 Hz tone (both P = 10%). Testing took place in 3 conditions: (1) attend, in which the subject had to count one of the deviant tones; (2) ignore, in which the subject read a book; and (3) sleep, in which the subject was encouraged to go to sleep during presentation of the tones.In the awake conditions stimulus deviance elicited mismatch negativity (MMN) and P3. During drowsiness, no separate mismatch negativity (MMN) could be detected, but the 2000 Hz tone evoked a broad fronto-central early negative deflection, suggesting an overlap of N₁ and MMN. In the same condition, P210, N330 and P430 appeared, all being sensitive to magnitude of deviance. During stage 2, the P210, N330 and P430 amplitudes increased, most notably to the large deviant.These data indicate that differential processing of auditory inputs is maintained during drowsiness and stage 2 sleep, but do not support the notion that MMN or P3 activity comparable to the waking state occurs to oddball stimuli during this stage. It is hypothesised that during light sleep, scanning of the environment is performed by a different system than in the awake state and that during drowsiness a gradual switch between these two systems takes place.     

Early deflections of cerebral magnetic responses to median nerve stimulation

We have recorded early components of somatosensory evoked magnetic fields with a sensitive 7-channel first-order gradiometer using a wide recording passband (0.05–2000 Hz) and high sampling frequency (8000 Hz). The left median nerve was stimulated at the wrist and responses were recorded over the right hemisphere. The responses typically consisted of a N20m peaking at 18–20 msec, a small P22m peaking at 21–23 msec and a P27m peaking at 29–31 msec. The topography of N20m could be explained by a tangential current dipole in the posterior wall of the central sulcus (probably in area 3b). The equivalent dipoles of P27m were located on average 10 mm antero-medially to the sources of N20m. This suggests that P27m may get a contribution from the anterior wall of the central sulcus. An increase of stimulus repetition rate from 2 to 5 Hz decreased the amplitude of P27m more than that of N20m, which implies that these two deflactions are generated by different neural netwoks.     

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.     

Pitch change of a continuous tone activates two distinct processes in human auditory cortex: a study with whole-head magnetometer

Previous studies have shown that a frequency change in a continuous tone elicits an NI type of ERP (event-related potential) component. It remained unclear, however, whether this response is a “genuine” N1 (onset detector response) or the mismatch negativity (MMN), a change-detector type of ERP response, elicited in previous studies by an infrequent change in a sequence of homogeneous stimuli. A further possibility is a nearly perfect overlap of the two types of ERP components. The advent of modern, high-resolution magnetometers has opened a new, powerful way to tackle such component-overlap problems.Subjects were presented with a continuous tone of 988 Hz which was occasionally increased to 1108 Hz for a period of 100 msec. The magnetic responses to this change consisted of two partially overlapping components with peaks separated by 30 msec. The earlier component was probably generated by neuronal populations of the auditory cortex corresponding to the supratemporal N1, whereas the later one, generated anteriorly and inferiorly to the first, probably reflects a mismatch process causing the magnetic equivalent of the electrical MMN.     

Short and middle latency vestibular evoked responses to acceleration in man

We have succeeded in recording short and middle latency vestibular evoked responses in human subjects. The head was held rigidly in a special, patented head holder, constructed individually for each subject, which gripped the teeth of the upper jaw. The stimulus consisted of 2/sec steps of angular acceleration impulses produced by a special motor with intensities of about 10,000°/sec² and with a rise time of 1–2 msec. The electrical activity was recorded as the potential difference between special forehead and mastoid electrodes having a large, secure contact area with the skin. The activity was digitally filtered and averaged in 2 separate channels by means of a Microshev 2000 evoked response system. The short latency responses, with peaks at about 3.5 msec (forehead positive), 6.0 msec (forehead negative) and 8.4 msec (forehead positive; bandpass: 200–2000 Hz; average of 1024 trials), had amplitudes of about 0.5 μV. The middle latency responses had peaks at about 8.8 msec (forehead positive), 18.8 msec (forehead negative) and 26.8 msec (forehead positive; 30–300 Hz; N = 128 trials), with larger amplitudes (about 15 μV). These responses were consistently recorded in the same subject at different times and were similar in different normal subjects. Strenuous control experiments were conducted in order to ensure that these responses are not artefacts due to the movement of conducting media (head, electrodes and leads) in the electromagnetic field of the motor and are elicited by activation of normal labyrinths. Among other controls, they were not present in a cadaver, in patients with bilateral absence of nystagmus to caloric stimuli and in conducting volumes the size of the human head. They were also not masked by white noise.     

Questions regarding the sequential neural generator theory of the somatosensory evoked potential raised by digital filtering

Digital bandpass filtering (300–2500 Hz) designed for zero phase shift was applied to somatosensory evoked potentials recorded with cephalic bipolar montages. Four consistent negative and corresponding positive peaks with latencies of about 16, 18, 19, and 20 msec were elicited with median nerve stimulation. Peroneal nerve stimulation also elicited 4 reproducible negative-positive peaks having latencies of about 24, 26, 28, and 30 msec. Interpeak latencies measured 1.3 ± 0.2 msec and 1.8 ± 0.25 msec for median and peroneal elicited SEPs respectively. Becaise cephalic bipolar recordings cancel most far-field potentials, multiple generators cannot account for all the additional components seen. It is hypothesized that some of the high frequency components recorded are due to activity in recurrent intrathalamic neuronal networks.     

Sensory and cognitive components of the CO2 laser evoked cerebral potential

We recorded CO₂ laser evoked cerebral potentials in 6 healthy subjects using both a standard technique and an oddball paradigm. In the standard technique stimuli were aimed at the dorsum of the left hand with the subject passive; in the oddball paradigm, target infrequent stimuli (P = 0.15) were directed to one side of the dorsum of the left hand and the subject was instructed to count their occurrence, the frequent stimulus being delivered to the other side of the hand. In both standard and oddball frequent recordings, CO₂ laser evoked potentials were a well-formed negative-positive complex with a peak latency and amplitude around 305 msec (to positivity) and 32 μV respectively. However, in the oddball target task a later potential was also recorded, with a mean latency and amplitude of 621 msec and 24 μV respectively which we believe to be a laser oddball potential. These results demonstrate that the CO₂ potential is not altered by manipulations of attention to any significant extent and suggests that it is therefore closely related to the primary sensory input. They also provide further evidence of the non-specificity of the oddball potential across sensory modalities.     

Effects of isolated and combined exposures to whole-body vibration and noise on auditory-event related brain potentials and psychophysical assessment

Auditory event-related brain potentials (ERP) in response to two different tone stimuli (1.1 kHz or 1 kHz, 80 dB, 50 ms; given by headphones at a regular interstimulus interval of 5 s with a probability distribution of 70:30) were recorded from 12 healthy male subjects (Ss) during four different conditions with two repetitions: A-60 dBA white noise (wN), no whole-body vibration (WBV); B-60 dBA wN plus sinusoidal WBV in the az-direction with a frequency of 2.01 Hz and acceleration of 2 m.s-2 root mean square; C-80 dBA wN, no WBV; D-80 dBA wN plus WBV. Each condition consisted of two runs of about 11 min interrupted by a break of 4 min. During the break with continuing exposure, but without auditory stimuli, Ss judged the difficulty of the tone-detection task and intensity of noise by means of cross-modality matching (CMM). Vibration-synchronous activity in the electrocardiogram was eliminated by a subtraction-technique. Noise caused an attenuation of the N1 and P2 amplitudes and prolongation of P3 latencies. The WBV did not cause systematic ERP effects. Condition B was associated with higher N1 and smaller P3 amplitudes. The factor "condition" had a significant effect on the peak latencies of P3 to target stimuli and the task difficulty judged by CMM. Both effects exhibited significant linear increases in the sequence of conditions A, B, C, D. For the evaluation of exposure conditions at work, it can be suggested that noise has a strong systematic effect which can be enhanced by WBV.(ABSTRACT TRUNCATED AT 250 WORDS)