518502 research-article2015

EEGXXX10.1177/1550059413518502Clinical EEG and NeuroscienceHernández et al


The Relationship between Parameters of LongLatency Evoked Potentials in a Multisensory Design

Clinical EEG and Neuroscience 1­–6 © EEG and Clinical Neuroscience Society (ECNS) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1550059413518502 eeg.sagepub.com

Oscar H. Hernández1,2, Rolando García-Martínez1, and Victor Monteón1

Abstract In previous papers, we have shown that parameters of the omitted stimulus potential (OSP), which occurs at the end of a train of sensory stimuli, strongly depend on the modality. A train of stimuli also produces long-latency evoked potentials (LLEP) at the beginning of the train. This study is an extension of the OSP research, and it tested the relationship between parameters (ie, rate of rise, amplitude, and peak latency) of the P2 waves when trains of auditory, visual, or somatosensory stimuli were applied. The dynamics of the first 3 potentials in the train, related to habituation, were also studied. Twenty healthy young college volunteers participated in the study. As in the OSP, the P2 was faster and higher for auditory than for visual or somatosensory stimuli. The first P2 was swifter and higher than the second and the third potentials. The strength of habituation depends on the sensory modality and the parameter used. All these findings support the view that many long-latency brain potentials could share neural mechanisms related to wave generation. Keywords evoked potentials, missing stimulus, multisensory, P2, habituation Received October 24, 2013; revised November 22, 2013; accepted December 2, 2013.

Introduction The application of trains of stimuli in the omitted stimulus task permits the recording of the OSP, a special form of eventrelated potential that occurs at the end of the train,1 and another kind of brain wave that occurs at the beginning of the train— the long-latency evoked potentials (LLEPs). There is a large amount of information about the late components of the evoked potentials.2-8 Besides cognition, the late components have helped in other important processes like the diagnosis of cerebral or neurologic dysfunction and hyperactivity.9 Previous studies have shown that the P2 component is a robust wave that appears in the averaged recordings of stimulus trains.2-8,10-13 There is evidence that the P2 wave is endogenous, that it represents the process of stimulus identification, and that the frontal associative cortex is involved in its generation.8,14 A train of stimuli also allows studying habituation, often described as the simplest form of nonassociative learning that can be observed throughout the animal kingdom.15 Although considerable progress has been made in determining the underlying mechanisms of habituation, we emphasize the need to understand the dynamics of the LLEPs in a multisensory design, before attempting to determine its underlying cellular machinery. Habituation is central to understanding the process of selective attention, which allows persons (or animals) to ignore common, irrelevant stimuli so that they can attend to stimuli important for survival.15 Habituation effects in the

amplitude of the LLEP are not uncommon, usually occurring in the first few stimuli.2,5 However, 3 parameters (rate of rise, amplitude, and peak latency) of the P2 component of the LLEP have never been analyzed together in a multimodal paradigm and related to habituation. Previous studies have shown that some cognitive components of reaction time and OSP wave are correlated.10 When this correlation was tested using a multisensory design, the auditory stimuli produced shorter responses.11 The present work is an extension of these studies testing the LLEP obtained by trains of auditory, visual, or somatosensory stimuli. We measured the rise rate, amplitude and peak latency and ascertained if they maintain a relationship to each other. Furthermore, averaging across modalities, an evaluation of every response


Centro de Investigaciones Biomédicas, Cuerpo Académico Biomedicina, Universidad Autónoma de Campeche, Campeche, México 2 Jefatura de Investigación, Hospital General de Especialidades “Dr. Javier Buenfil Osorio”, Secretaría de Salud, Campeche, México Corresponding Author: Oscar H. Hernández, Laboratorio de Neurobiología, Centro de Investigaciones Biomédicas, Universidad Autónoma de Campeche, Av. Agustín Melgar s/n entre Juan de la Barrera y calle 20, Col. Buenavista, Campeche, c.p., 24039, México. Email: [email protected] Full-color figures are available online at http://eeg.sagepub.com

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Clinical EEG and Neuroscience 

within the train in relation to their ordinal position is obtained to measure the strength of adaptation. Because the responses of some long-latency brain potentials are similar on multisensory paradigms, it seems possible that some common mechanisms may be involved in the generation of these waves. We hypothesized that LLEPs are also sensitive to sensory modality favoring the auditory system. Averaged recordings from the first, second, and the third stimuli on a train offer a great opportunity to study the effects of sensory modality on the habituation process of the P2 parameters. A better understanding of the mechanisms of sensory processing and habituation will improve our knowledge of the way the brain analyzes the dynamic changes in a train of different sensory stimuli.

Materials and Methods Participants Twenty right-handed Hispanic college student volunteers with a mean (SD) age of 23.7 years (2.3) participated in the study. Half were women with self-stated regular menstrual cycles and were tested during menstruation to avoid hormonal effects. All the experimental procedures were explained before subjects provided informed consent. The procedures were in accordance with current ethical standards and were reviewed and approved by the University of Campeche Ethics Committee.

Apparatus and Materials The Task Stimuli. The task stimuli and electrophysiological recording procedure are fully explained elsewhere,11-13 and are briefly described here. The task consists of trials that present repeated sensory stimuli (auditory, somatosensory, or visual) at a fixed frequency of 0.5 Hz and cease unpredictably after a random number of 3 to 8 stimuli. Auditory clicks of 10 ms were generated through an electrical stimulator (Grass S48, Natus Neurology, Inc, Middleton, WI) and delivered to both ears through headphones. The auditory threshold was determined, and then the voltage was set at 20 times the threshold for the experiment (equivalent to 50 ± 1.8 dB). A pattern generator (Grass model 10VPG) presented the visual stimuli as a black and white checkerboard on a monitor. The electrical stimulator released a pulse every 2 seconds that reversed the black and white squares. The visual angle of arc was 10.3° with a luminance of 17 candelas per square meter (cd/m2) and contrast of 90%. The apparatus also released somatosensory stimuli through an isolated unit (Grass SIU5) to activate 2 disc electrodes placed on the anterior surface of the left wrist. The 5-ms electrical stimulus was painless, and was set at 1.2 times the participant’s detection threshold. Recordings.  The trials of each sensory stimulus were presented consecutively, and in separate blocks counterbalanced across subjects. Each stimulus generated clear changes in voltage that

were collected online using a computer fitted with an AD/DA converter (MP100 System.) and analyzed using the AcqKnowledge software (BIOPAC Systems, Goleta, CA). The electroencephalography (EEG) data were obtained with surface disc electrodes. The active electrode was placed according to the International 10/20 System at the Cz location (impedance .118) and the entire sample of N = 20 was used for further analyses. A 3 (stimulus modality) × 3 (stimulus position) repeatedmeasures ANOVA was conducted for each variable. Figure 1 illustrates significant effects on rise rate for both modality, F(2, 38 = 9.69, P < .0001, and position, F(2, 38) = 18.40, P < .0001.

The interaction showed values close to statistical significance (P > .058). Paired comparisons with a Bonferroni test for each stimulus modality verified that auditory stimuli were faster than somatosensory (P < .043) and visual (P < .001) stimuli. No significant difference was observed between somatosensory and visual stimuli (P > .7). The first LLEP was also faster than the second (P < .0001) and third (P < .0001), but no differences were found between the last 2 waves (P > .9). Table 1 shows the mean LLEP rate of rise of the 3 waves in response to different sensory stimuli. The first LLEP was swifter in all sensory modalities, and stronger effects were obtained in somatosensory and visual tasks, where the first LLEP rises faster than the second and the third. No differences were observed between the second and third responses.

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Clinical EEG and Neuroscience  19) = 53.26, P < .001, slope B = 0.109, SE = 0.015, modalities. No significant effects were observed for peak latency and rise rate within any sensory modality (Ps > .522). The association of amplitude and latency was not significant for auditory and visual stimuli (Ps > .886), but a weak association was found with the somatosensory modality, F(1, 19) = 4.80, P < .042, slope B = 0.021; SE = 0.010.


Figure 2.  The peak latency of the long-latency evoked potential (LLEP) was shorter with auditory than with somatosensory and visual stimuli. Vertical bars show standard errors of the mean. *P < .001; **P < .0001.

ANOVA also showed main effects in peak latency for stimulus modality, F(2, 38) = 13.49, P < .0001, but not for position or interaction (Ps > .123). Figure 2 shows that waves evoked with auditory stimuli reached the peak sooner than those evoked by somatosensory (P < .001) or visual (P < .0001) stimuli. Somatosensory and visual modalities showed no differences (P > .9). The amplitude of the LLEP was different for modality, F(2, 38) = 8.36, P < .001; position, F(2, 38) = 23.5, P < .0001; and their interaction, F(4, 76) = 3.02, P < .023. The auditory (P < .002) and the somatosensory (P < .03) modalities produced higher waves than visual stimuli (Figure 3). No main effects were observed between auditory and somatosensory (P > .46) stimuli. The size of the first LLEP was higher than the second (P < .0001) and the third (P < .0001), but no differences were seen between the second and third waves (P > .9; Figure 3). The source of the interaction in the amplitude was investigated by a 3-way (position) ANOVA separately for each modality. Table 1 summarizes that the first LLEP was the highest in all sensory modalities, but strong effects were only attained in the somatosensory task, where the first LLEP was higher than the second (P < .001) and the third (P < .0001), and in the visual task, where the first and third visual LLEPs differed (P < .04).

Association Between the Evoked Potential Parameters The possibility that the rate of rise in the LLEP correlated with its amplitude and peak latency was tested by separate regressions for each of the 2 parameters. Figure 4 illustrates these relationships. A faster rise rate was associated with a higher LLEP wave amplitude for auditory, F(1, 19) = 278.50, P < .001, slope B = 0.131, SE = 0.008; somatosensory, F(1, 19) = 28.27, P < .001, slope B = 0.117, SE = 0.022; and visual, F(1,

This experiment demonstrated that auditory stimuli evoked faster and larger P2 waves than the somatosensory or visual stimuli. The rate of rise showed a main positive relationship with amplitude in the 3 sensory systems. Then, it is clear that the parameters of the P2 depend on the sensory modality of the stimulus. This study also showed that P2 parameters are larger and faster than OSP. The auditory P2 were about 8 µV, similar to Vartanyan et al.7 Instead, OSPs are 5 to 6 µV. The P2 showed positive peaks with a latency of 200 to 250 ms while it is common that OSP peaks above 250 ms.1,16 Although the “late” components of the evoked potential can occur in the 50- to 300-ms poststimulus period,8 it is commonly accepted that the P2 wave fluctuates between 150 and 220 ms.5 Because of the longlatency nature of these waves, these results are not explained simply by a shorter conduction distance from auditory receptors to cortical areas. Instead, afferent sensory volleys, perhaps at the level of the reticular formation, could be modulated by higher brain functions by means of complex feedback mechanisms.2 Habituation is also known as short-term adaptation or rate effects.2,5 It allows filtering out irrelevant stimuli and thereby focusing on important stimuli, a prerequisite for many cognitive tasks.18 Only the first 3 potentials were analyzed in this work because all trials had at least 3 stimuli. This is the first time that habituation is reported on the rise rate of a LLEP for auditory, visual, and somatosensory stimuli in the same subject. The P2 rate of rise and amplitude, but not the latency, were sensitive to their ordinal position within the train. The first averaged potential was faster and higher than the second and third. Johnson and Yonovitz8 mention that habituation is large for late evoked potentials because they are involved in higher order functioning related to structures such as the frontal cortex. According to these authors, the most significant changes in P2 occurred between the first and the second responses, whereas these values remain stable between the second and the third waves. Although reductions were observed in all sensory modalities, the present study clearly showed that the strength of habituations is modality dependent. While somatosensory stimuli produced a great adaptation in the second and third waves, the auditory modality was more resistant, whereas the visual system was intermediate. These results are not the product of a modality sequence, because special care was taken in presenting trials of each sensory stimulus in separate blocks counterbalanced across subjects. The results also showed that, although correlated with each other, the amplitude and rate of rise

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Hernández et al

Figure 3.  Amplitude of the long-latency evoked potential (LLEP) according to sensory modality and their ordinal position. The amplitude of auditory and somatosensory stimuli, and of the first LLEP in a series, was bigger than visual stimuli or the second and third LLEPs in a series. Vertical bars show standard errors of the mean. *P < .03; **P < .002; ***P < .0001.

Figure 4.  Scatterplots of data from tests with auditory, somatosensory, and visual stimuli show the positive relationship between longlatency evoked potential (LLEP) rise rate and amplitude. In all cases, the association was significant (P < .001). The solid lines indicate the least squares regression line.

parameters have subtle differences in the habituation process. The rate of rise showed to be more sensitive than the amplitude in reducing of the second waves under auditory and visual stimuli. This indicates that the strength of the habituation also depends on the parameter used. These differences in the strength of habituation could allow animals to adapt to rapidly changing environmental events. Understanding the factors that affect habituation is also important from the clinical point of view. Some mental and neurological disorders are associated with disruption of habituation, for example, schizophrenia, autism, obsessive–compulsive disorder, migraine, and headaches.19-22 Moreover, the inability to filter out irrelevant information is associated with disruption in higher cognitive functions, such as in different types of memory and attention. In conclusion, this study showed that some parameters of the LLEP in a train strongly depend on the sensory modality. The P2 waves are faster and larger than the OSP, and both are faster and larger in response to auditory stimuli compared with visual or somatosensory. P2 is sensitive to short-term adaptation from the second response in a train, and their strength

depends on the sensory modality and of the parameter used to measure it. This new evidence supports the proposal that the LLEPs are modulated by central mechanisms, according to their sensory modality, and could share some neural mechanisms with the OSP. The rise rate is a useful parameter that should be included in research of the brain potentials. Declaration of Conflicting Interests The author(s) declared no conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

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2. Prosser S, Arslan E, Michelini S. Habituation and rate effect in the auditory cortical potentials evoked by trains of stimuli. Arch Otorhinolaryngol. 1981;233:179-187. 3. Polich J. P300 development from auditory stimuli. Psychophysiology. 1986;23:590-597. 4. Woods DL, Clayworth CC, Knight RT, Simpson GV, Naeser M. Generators of middle- and long-latency auditory evoked potentials: Implications from studies of patients with bitemporal lesions. EEG Clin Neurophysiol. 1987;68:132-148. 5. Polich J, Aung M, Dalessio DJ. Long latency auditory evoked potentials: intensity, inter-stimulus interval, and habituation. Pavlov J Biol Sci. 1988;23:35-40. 6. Polich J, Alexander JE, Bauer LO, et al. P300 topography of amplitude/latency correlations. Brain Topogr. 1997;9:275-282. 7. Vartanyan IA, Andreeva IG, Markovich AM. Human longlatency auditory evoked potentials during radial motion of the sound source. Hum Physiol. 2001;27:9-16. 8. Johnson A, Yonovitz A. Habituation of auditory evoked potentials: the dynamics of waveform morphology. Aust N Z J Audiol. 2007;29:77-88. 9. Zambelli AJ, Stamm JS, Matinsky S, Loiselle DL. Auditory evoked potentials and selective attention in formerly hyperactive adolescents. Am J Psychiatry. 1977;134:742-747. 10. Hernández OH, Vogel-Sprott M. The omitted stimulus potential is related to the cognitive component of reaction time. Int J Neurosci. 2008;118:173-183. 11. Hernández OH, Vogel-Sprott M. Reaction time and brain waves in omitted stimulus tasks: a multisensory study. J Psychophysiol. 2010;24:1-6. 12. Hernández OH, Vogel-Sprott M. Alcohol slows the brain potential associated with cognitive reaction time to an omitted stimulus. J Stud Alcohol Drugs. 2010;71:268-277.

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The Relationship between Parameters of Long-Latency Evoked Potentials in a Multisensory Design.

In previous papers, we have shown that parameters of the omitted stimulus potential (OSP), which occurs at the end of a train of sensory stimuli, stro...
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