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.     

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.     

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.     

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.     

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.     

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.     

Identification of pain,intensity and P300 components in the pain evoked potential

This study examined the relationships among 3 components of the somatosensory evoked potential (SEP) to painful stimuli. Painful stimuli were produced using intracutaneous electrical stimulation of a fingertip and two levels of non-painful stimuli were produced by superficial electrical stimulation of a neighboring fingertip. SEPs were recorded from Cz-A1 and Pz-A1, and difference waves were computed for 3 components: (1) a pain component (the difference between SEPs to painful vs. strong but non-painful stimuli); (2) an intensity component that is not related to pain (the difference between SEPs to strong non-painful vs. mild non-painful stimuli); and (3) a P300 component (the difference between SEPs to the same stimuli under Target instructions vs. Standard instructions).The positive peaks in the 3 types of difference waves differed in both latency and topography, although with latency and topography overlap. The intensity component had an earlier positive peak than the pain component, and the pain component had an earlier positive peak than the P300 component. The pain and intensity components were larger at Cz than Pz, whereas the P300 component was larger at Pz than Cz. Under certain conditions, the pain evoked SEP consists of a weighted combination of the 3 components, complicating interpretation of the positive peaks in the recorded wave forms.     

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.     

Mapping P300 waves onto inhibition: Go/NoGo discrimination

Subjects viewed letters presented at 2 sec intervals and prepared a fast button press whenever an “O” appeared. If the next letter was an “X” the button press was executed (Go signal), but if the letter was a non-X character (T, H, Z) suppression of the response was required (NoGo cue). NoGo signals elicited a P300-like wave that was larger at central and frontal scalp sites contralateral to the prepared movement, compared to P300s elicited by Go cues which were symmetric about the sagittal midline and dominant at parietal sites. Subtraction of preparatory CNVs from the NoGo P300 did not remove differences in scalp topography, or reduce the amplitude of the NoGo P300 to that seen following control letters that required perceptual identification but did not call for suppression of prepared motor responses. Principal components analysis identified a middle positive wave following X-alone control stimuli whose topography resembled the NoGo P300. These findings suggest that the source of augmented NoGo P300s is a generator involved with sensorimotor inhibition. We discuss the mechanism of P300 waves and evidence linking these waves with inhibition in other task arrangements.     

Fast detection of unexpected sound intensity decrements as revealed by human evoked potentials

The detection of deviant sounds is a crucial function of the auditory system and is reflected by the automatically elicited mismatch negativity (MMN), an auditory evoked potential at 100 to 250 ms from stimulus onset. It has recently been shown that rarely occurring frequency and location deviants in an oddball paradigm trigger a more negative response than standard sounds at very early latencies in the middle latency response of the human auditory evoked potential. This fast and early ability of the auditory system is corroborated by the finding of neurons in the animal auditory cortex and subcortical structures, which restore their adapted responsiveness to standard sounds, when a rare change in a sound feature occurs. In this study, we investigated whether the detection of intensity deviants is also reflected at shorter latencies than those of the MMN. Auditory evoked potentials in response to click sounds were analyzed regarding the auditory brain stem response, the middle latency response (MLR) and the MMN. Rare stimuli with a lower intensity level than standard stimuli elicited (in addition to an MMN) a more negative potential in the MLR at the transition from the Na to the Pa component at circa 24 ms from stimulus onset. This finding, together with the studies about frequency and location changes, suggests that the early automatic detection of deviant sounds in an oddball paradigm is a general property of the auditory system.     

Latency of the P3 event-related potential: Normative aspects and within-subject variability

A growing body of research has focused on the P3 (P300) event-related potential as an electrophysiological correlate of selective attention. The present investigation examines the intrasubject test-retest reliability of the auditory evoked P3 latency measure for neurologically and audiologically normal young adults aged 22–34 years across test sessions separated by 2–4 weeks (N = 9) and across trials within one test session (N = 20). In a target-selection (‘oddball’) paradigm, subjects mentally counted infrequent 2 kHz tone bursts (targets) randomly interspersed within a sequence of 1 kHz tone bursts (non-targets). A strong positive correlation was demonstrated between latencies of test sessions I and II. An analysis of variance did not demonstrate statistically significant latency differences as a function of either tests of trials for the test-retest group (N = 9). Although analysis of variance demonstrated a statistically significant difference between trials within one test session for 20 subjects, the small mean latency difference between trials (4.7 msec) is interpreted as being clinically unimportant. The stability of P3 latency found in this study over a period of 2–4 weeks supports its application to the study of normal and disordered cognitive processes.     

A subcortical correlate of P300 in man

Event-related potentials in visual and auditory target detection tasks were recorded simultaneously from the scalp, somatosensory thalamus and periaqueductal gray in a chronic pain patient with electrodes implanted subcortically for therapeutic purposes. Short latency tactile responses confirmed the location of the thalamic electrodes.Rare auditory stimuli which were detected by the subject were accompanied by a prominent P300 component at the scalp, and by negative activity at the subcortical sites with the same latency as the scalp positivity. This activity was not seen in responses to frequent non-target stimuli and was not dependent on an overt motor response.Similarly, rare visual stimuli generated a scalp P300 and negative activity subcortically; both scalp and subcortical waves had a longer latency than in the auditory experiment. The reaction time was similarly longer to visual targets.These data are inconsistent with a hippocampal generator for P300, but are consistent with a generator in the thalamus or more dorsally located structures.     

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.     

Event-related Potential Study of Novelty Processing Abnormalities in Autism

To better understand visual processing abnormalities in autism we studied the attention orienting related frontal event potentials (ERP) and the sustained attention related centro-parietal ERPs in a three stimulus oddball experiment. The three stimulus oddball paradigm was aimed to test the hypothesis that individuals with autism abnormally orient their attention to novel distracters as compared to controls. A dense-array 128 channel EGI electroencephalographic (EEG) system was used on 11 high-functioning children and young adults with autism spectrum disorder (ASD) and 11 age-matched, typically developing control subjects. Patients with ASD showed slower reaction times but did not differ in response accuracy. At the anterior (frontal) topography the ASD group showed significantly higher amplitudes and longer latencies of early ERP components (e.g., P100, N100) to novel distracter stimuli in both hemispheres. The ASD group also showed prolonged latencies of late ERP components (e.g., P2a, N200, P3a) to novel distracter stimuli in both hemispheres. However, differences were more profound in the right hemisphere for both early and late ERP components. Our results indicate augmented and prolonged early frontal potentials and a delayed P3a component to novel stimuli, which suggest low selectivity in pre-processing and later-stage under-activation of integrative regions in the prefrontal cortices. Also, at the posterior (centro-parietal) topography the ASD group showed significantly prolonged N100 latencies and reduced amplitudes of the N2b component to target stimuli. In addition, the latency of the P3b component was prolonged to novel distracters in the ASD group. In general, the autistic group showed prolonged latencies to novel stimuli especially in the right hemisphere. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. We propose the potential application of ERP evaluations in a novelty task as outcome measurements in the biobehavioral treatment (e.g., EEG biofeedback, TMS) of autism.     

Visual cognitive dysfunction in depression: an event-related potential study

The P3(00) event-related potentials (ERPs) elicited by visual stimuli in two visual tasks were assessed in depressed patients (12 patients with major depression and 11 patients with bipolar disorder) and compared with those of 20 age-matched normal controls. At remission, the ERPs from 18 of the depressed patients were again recorded. The visual oddball (VO) paradigm presented both target and standard visual stimuli and the simple visual (SV) paradigm presented a target but no standard visual stimulus. Subjects performed the VO task significantly less accurately than the SV task, as reflected by the behavioral measures (reaction-time and task accuracy). Depressed patients of the bipolar group showed longer P3 peak latency for the VO task and no change in P3 amplitude. No significant differences were found in any other ERP component between the groups. During remission, slowing RTs and reduced P3 peak latencies were observed for both major depression and bipolar disorder groups. Thus, the P3 ERP may be an index of the contribution of the slowed central processing to psychomotor retardation in clinically homogenous samples of depressive patients performing an appropriately demanding task.     

Electrophysiological and Behavioral Outcomes of Berard Auditory Integration Training (AIT) in Children with Autism Spectrum Disorder

Autism is a pervasive developmental disorder of childhood characterized by deficits in social interaction, language, and stereotyped behaviors along with a restricted range of interests. It is further marked by an inability to perceive and respond to social and emotional signals in a typical manner. This might due to the functional disconnectivity of networks important for specific aspects of social cognition and behavioral control resulting in deficits of sensory information integration. According to several recent theories sensory processing and integration abnormalities may play an important role in impairments of perception, cognition, and behavior in individuals with autism. Among these sensory abnormalities, auditory perception distortion may contribute to many typical symptoms of autism. The present study used Berard’s technique of auditory integration training (AIT) to improve sound integration in children with autism. It also aimed to understand the abnormal neural and functional mechanisms underlying sound processing distortion in autism by incorporating behavioral, psychophysiological and neurophysiological outcomes. It was proposed that exposure to twenty 30-min AIT sessions (total 10 h of training) would result in improved behavioral evaluation scores, improve profile of cardiorespiratory activity, and positively affect both early [N1, mismatch negativity (MMN)] and late (P3) components of evoked potentials in auditory oddball task. Eighteen children with autism spectrum disorder (ASD) participated in the study. A group of 16 typically developing children served as a contrast group in the auditory oddball task. Autonomic outcomes of the study reflected a linear increase of heart rate variability measures and respiration rate. Comparison of evoked potential characteristics of children with ASD versus typically developing children revealed several group difference findings, more specifically, a delayed latency of N1 to rare and frequent stimuli, larger MMN; higher P3a to frequent stimuli, and at the same time delayed latency of P3b to rare stimuli in the autism group. Post-AIT changes in evoked potentials could be summarized as a decreased magnitude of N1 to rare stimuli, marginally lower negativity of MMN, and decrease of the P3a to frequent stimuli along with delayed latency and higher amplitude of the P3b to the rare stimuli. These evoked potential changes following completion of Berard AIT course are in a positive direction, making them less distinct from those recorded in age-matched group of typical children, thus could be considered as changes towards normalization. Parental questionnaires clearly demonstrated improvements in behavioral symptoms such as irritability, hyperactivity, repetitive behaviors and other important behavioral domains. The results of the study propose that more controlled research is necessary to document behavioral and psychophysiological changes resulting from Berard AIT and to provide explanation of the neural mechanisms of how auditory integration training may affect behavior and psychophysiological responses of children with ASD.     

Readiness to respond in a target detection task: pre- and post-stimulus event-related potentials in normal subjects

Brain potentials were recorded from 12 normal subjects engaged in an auditory target detection task (target stimulus probability of 0.2, stimulus rate of 1 every 2 sec) when instructions were (1) to press a response button with the thumb of the dominant hand to each target or (2) to keep a mental count of each target. A pre-stimulus slow negative potential was identified before every stimulus except non-targets immediately after targets. The amplitude of the pre-stimulus negativity was significantly affected by task instructions and was up to 4 times larger during the button press than the mental count condition. In contrast, the amplitudes and latencies of the event-related components (N100, P200, N200 and P300), when slow potentials were removed by filtering, were not different as a function of press or count instructions. The immediately preceding stimulus sequence affected both the amplitude and onset latency of the pre-stimulus negativity; both measures increased as the number of preceding non-targets increased. The amplitude of the pre-stimulus negative shift to targets also increased significantly as RT speed decreased. The major portion of the pre-stimulus negative potential is considered a readiness potential (RP) reflecting preparations to make a motor response. The amplitude of the RP during the target detection task did not significantly lateralize in contrast to the RP accompanying self-paced movements.     

P300 from a passive auditory paradigm

The P300 (P3) event-related brain potential (ERP) was elicited with a passive tone sequence paradigm and evaluated in 2 studies. Experiment 1 compared ERPs from the passive procedure with those from an active discrimination (oddball) task. The passive sequence paradigm yielded P3 wave forms remarkably similar to those obtained from the active task since both demonstrated central-parietal maximum scalp distributions and virtually identical peak latencies. No differences between tasks were found when ERPs were elicited with subject's eyes open or closed. Experiment 2 compared ERPs from the passive sequence paradigm obtained when subjects were attempting to solve a word puzzle with those from a simple ignore condition. The puzzle-solving secondary task produced a decrease in P3 amplitude relative to the ignore condition, although P3 peak latency was unaffected. These results suggest that the passive sequence paradigm may be a useful and reliable means of eliciting the P3 ERP in subject populations or experimental situations in which an active discrimination task cannot be performed.     

A topographical ERP study of healthy premature 5 year old children in the auditory and visual modalities

The aim of this research is to study the impact of extreme prematurity on the cognitive development of the child as assessed at age 5 years 9 months. Our samples include 15 healthy prematures born between 25 and 28 weeks of gestational age carefully matched with 15 full-term controls. In the first experiment, two different auditory stimuli were presented to the subjects who listened passively without instruction. The second experiment consisted of a standard visual oddball task in which the subjects were instructed to `catch' two different animals, by pushing a left or right button for a moose (n=120) or a raccoon (n=40), respectively. In the auditory task, 3 ERP peaks were analyzed (frontal N100 and P3a, temporal P2). All premature children demonstrated normal early frontal N100 and temporal P2 responses. The group differences were apparent in the late positivity (P3a) where controls showed a larger amplitude to the rare tones applied evenly to both ears. In contrast, the prematures did not show sensitivity to rare tones but showed a larger P3a upon left ear stimulation, when compared to the right. Also, the ERPs to the visual oddball task showed normal early positivities (P250–300) in the premature group. Once again, deviations from the normal were evident in late waves. The ERPs recorded from prematures showed a more diffuse topography especially between 500 and 600 ms post-stimulus and around the posterior area (P550). The succeeding negativity (SW) was not altered in the premature group. The ERP data suggest that premature children, even without clinically apparent problems, convey specific ERP singularity when engaged in a task that involves complex processing.     

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