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P300, stimulus intensity, and modality
ELSEVIER
Electroencephalographyand clinical Neurophysiology 100 (1996) 579-584 Short communication
P300, stimulus intensity, and modality J a m e s W . C o v i n g t o n a, J o h n P o l i c h b'* aDepartment of Psychology, University of Cali]ornia, San Diego, La Jolla, CA 92093, USA bDepartment of Neuropharmacology, TPC-IO, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037. USA
Accepted for publication: 15 July 1996
Abstract
Auditory and visual stimulus intensity levels were manipulated systematically in separate conditions to assess the influence of these variables on the P300 event-related brain potential (ERP). Increases in stimulus intensity produced increases in P300 amplitude and decreases in peak latency for both modalities, although the latency effects were stronger for visual stimulation. Similar, somewhat weaker stimulus intensity effects also were observed for the N100, P200, and N200 components. The findings suggest that stimulus intensity contributes to both P300 amplitude and latency measures in important ways and are discussed in relation to the use of ERPs in applied contexts. Keywords: P300; ERP; Stimulus intensity; Auditory; Visual
1. Introduction
Many basic and applied studies of event-related brain potentials (ERPs) employ simple auditory or visual stimuli to elicit the P300 component (e.g. Johnson, 1989a; Johnson, 1989b; Polich et al., 1990; Goodin et al., 1992). When an 'oddball' paradigm is used in this context, subjects are required to discriminate between two stimuli that vary on some dimension by counting or responding to a designated target stimulus. This procedure will produce robust P300 components with relative ease and reliability in a wide variety of normal and patient populations (Picton, 1992; Polich, 1993). Despite the extensive application of this methodology in both theoretical and empirical contexts (e.g. Squires et al., 1977; Johnson, 1986; Knight et al., 1989; Polich, 1989a), the influence of stimulus variables on these results has been little addressed, since the P300 ERP component is assumed to be relatively immune to the effects of stimulus factors because of its putative endogenous rather than exogenous origin (Donchin et al., 1978; Hillyard and Picton, 1986). Although this viewpoint is predominant in the literature, several studies have investigated the role of stimulus effects on the P300 in the context of the auditory startle * Corresponding author. Tel.: +1 619 7848176; fax: +1 619 7849293; e-mail: [email protected]
response (Ford et al., 1976; Roth et al., 1982; Roth et al., 1984; Putnam and Roth, 1990) and when ERPs are elicited passively (Polich, 1986a; Polich, 1989c; Surwillo and Iyer, 1989; O'Donnell et al., 1990). However, only a few reports have directly assessed the role of stimulus factors in an active discrimination paradigm, with virtually all of these employing auditory stimuli. In general, variation in stimulus frequency, intensity, and the presence of white noise produces appreciable effects (10-30+ ms) on P300 peak latency (Papanicolaou et al., 1985; Polich et al., 1985; Polich, 1989b). Sugg and Polich (1996) also have reported that P300 amplitude increased and peak latency decreased as auditory stimulus intensity increased, with tone frequency also affecting these outcomes. Thus, the specific nature of auditory stimulus factors appear to contribute to P300 measures directly and robustly. Although of interest from a theoretical standpoint (cf. Johnson, 1986; Johnson, 1988), the import of these findings is particularly necessary to consider when P300 is employed in applied ERP studies, especially if elderly and/or clinical patient populations are evaluated. For example, P300 components elicited by auditory stimuli are affected by age-related sensitivity to low and high tone frequencies stemming from neural-sensory hearing loss (Pollock and Schneider, 1989). More important, auditory stimulus intensity and subject age interact with respect to both P300 amplitude and latency, such that the
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specific age-related effects appear to depend upon the stimulus frequencies and intensities employed (Squires et al., 1980; Pollock and Schneider, 1992; Vesco et al., 1993). Hence, the percentage of demented patients classified as having 'abnormal' P300 measures is at least in part determined by the auditory stimulus characteristics employed to elicit the P300 component (Polich, 1991). Indeed, a recent meta-analysis of P300 normative aging studies has revealed the systematic effects of stimulus variables on the definition of 'normal' P300 measures across modalities (Polich, 1996). Taken together, these results suggest that appreciable P300 amplitude and latency variability is caused by variation in stimulus factors that interacts with subject population characteristics, an outcome that has contributed significantly to the debate surrounding the applied utility of the P300 component as a measure of cognitive function (cf. Goodin, 1990; Pfefferbaum et al., 1990). The reasons stimulus variables influence P300 measures are not clear. However, stimulus parameters readily affect the amplitude and latency of exogenous (N100, P200, N200) auditory long-latency components (Polich and Starr, 1983; Polich and Starr, 1984; Hillyard and Picton, 1987; Polich et al., 1988), and it is not unreasonable to assume that because such variables can alter the 'sensory' components they also might contribute to the subsequent 'cognitive' portions of the ERP. However, even though both auditory and visual paradigms have been employed to evaluate various clinical populations (Pfefferbaum et al., 1984; Picton et al., 1984; Johnson, 1989a; Johnson, 1989b; Polich et al., 1994), assessment of how comparable changes in stimulus intensity for both modalities affect P300 measures has not been reported, particularly for visual stimuli, which have not been assessed comprehensively. The present study was designed as an initial step to identify these relationships by systematically manipulating stimulus intensity for both the auditory and visual modalities. 2. Methods 2.1. Subjects
A total of 32 (16 male, 16 female) undergraduate students (mean age 21.6 years, SD 4.4 years) from the University of California, San Diego participated in return for course credit. All subjects reported normal hearing and vision, no neurological or psychological problems, and all were naive to electrophysiological studies.
comfortable and would produce accurate task performance. Auditory stimuli were presented binaurally over headphones with a duration of 50 ms and 10 ms rise/fall times. The target was a 2000 Hz tone and the standard was a 1000 Hz tone, with stimulus intensity presented at either 40 (low), 60 (medium) or 80 (high) dB SPL (a range of values that covers the majority of P300 auditory studies). The visual target stimuli consisted of a black and white checkerboard (square = 2.5 cm 2) and the standard stimuli were horizontal black and white lines (2.5 cm wide) presented on a 21 inch monitor viewed from a distance of 1 m, with stimulus intensities at 0.60 (low), 35.0 (medium), or 150.0 (high) cd/m 2 (a range that includes relatively dim to very bright stimuli presented on a monochrome monitor). The presentation order of the experimental blocks was counterbalanced across subjects and within sex for each modality, with half the subjects receiving the auditory condition first and half receiving the visual condition first. A short practice block was presented initially to familiarize each subject with the task situation, which consisted of about 10 trials using the same conditions as the first experimental block. The inter-stimulus interval was 3.0 s. The target stimuli occurred randomly with a 0.20 probability. A total of 25 target stimulus artifact-free trials were acquired for each condition. Subjects were instructed to indicate the occurrence of a target stimulus by gently lifting the index finger of their preferred hand, and response accuracy was recorded. 2.3. Recording conditions
EEG activity was recorded at the Fz, Cz, and Pz electrode sites of the 10-20 system using gold-plated electrodes, affixed with electrode paste and tape, with impedances of 10 kf] or less. Linked earlobes were used as the reference with a forehead ground. Electro-ocular (EOG) activity was recorded bipolarly with electrodes placed at the outer canthus and supraorbitally to the left eye. The filter bandpass was 0.016-30 Hz (3 dB, 12 dB octave/rolloff), and EEG was digitized at 3 ms/point for 750 ms with a 75 ms prestimulus baseline. Waveforms were averaged on-line by a commercial signal averager, which also controlled the stimulus presentation and artifact rejection. Trials on which either the EEG or EOG exceeded a preset threshold of +90/zV were rejected automatically. 3. Results 3.1. Task performance
2.2. Stimuli and procedure
Low, medium, and high levels of stimulus intensities for auditory and visual stimuli were presented to each subject in separate conditions. The intensity levels were determined by pilot testing, such that the range of values was
Geisser-Greenhouse corrections were used in all analyses of variance, and only significant results by these criteria are reported. A two-factor (intensity x modality) analysis of variance was performed on the response error data. Low error rates for target detection were obtained
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.I.W. Covington, J. Polich / Electroencephalography and clinical Neurophysiology tO0 (1996) 579-584
(0.46% overall), with somewhat (but non-significantly, P > 0.45) fewer errors made with auditory (0.37%) compared to visual (0.56%) stimuli.
LOW INTENSITY - - t - MED INTENSITY " - I I - HIGH INTENSITY - -4~ -
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3.2. Component measurement
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The P300 component was designated as the largest positive peak that occurred after the N100-P200-N200 complex between 250 and 400 ms for the auditory and 3 0 0 500 for the visual stimuli. Amplitude was measured relative to the prestimulus baseline, and latency was defined as the time of maximum positive amplitude. The amplitudes and latencies of the N100, P200, N200 components also were measured at all electrode sites within ranges of 6 0 150, 120-220, and 180-300 ms for the auditory and 8 0 160, 140-240, and 240--350 ms for the visual stimuli, respectively. The grand average ERPs from the target stimuli for the various conditions are presented in Fig. 1. The mean P300 amplitudes and latencies from the target data LOW _" _- - - -
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Fig. 2. Mean P300 amplitude (top) and latency (bottom) from the target stimuli for each stimulus intensity and modality, as a function of electrode site. for each intensity level, modality, and electrode site are displayed in Fig. 2. A three-factor (intensity x modality x electrode) analysis of variance was applied to each dependent variable. The results of these analyses (and those performed on the other components) are summarized in Table 1.
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3.3. P300 component
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Fig. I. Grand average ERPs from the target stimuli for each of the intensity, modality, and electrode site conditions (N = 16).
For the target stimuli, P300 amplitude increased overall as stimulus intensity increased. The usual increase in P300 amplitude from the frontal to parietal electrode sites was obtained, with auditory stimuli demonstrating somewhat less steep increases compared to visual stimuli over the scalp. It should be noted explicitly that the intensity and modality variables did not interact with each other. Also, the modality x electrode interaction was confirmed (P < 0.002) when the data were scaled using a vector transformation (McCarthy and Wood, 1985), suggesting that different neural generators were operating for each modality across intensity levels (cf. Johnson, 1993). An additional modality x electrode analysis of variance also was conducted on the P300 amplitude data from each modality separately. For auditory stimuli, only the electrode effect was reliable (F(2,62) = 16.5, P < 0.001); for visual stimuli, amplitude increased significantly as intensity increased (F(2,62) = 6.3, P < 0.01), and as electrode position changed from frontal to parietal (F(2,62) = 52.9, P < 0.001). The same analysis was performed on the P300 latency
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J.W. Covington, J. Polich / Electroencephalography and clinical Neurophysiology 100 (1996) 579-584
Table 1 F-Ratios from analyses of variance (intensity (I) x modality (M) × electrode (E)) on the N100, P200, N200, and P300 amplitude and latency data from the target stimuli Factor (df)
Intensity ( 2 , 6 2 ) Modality ( 1 , 3 1 ) Electrode (2,62) I × M (2,62) I x E (4,124) M × E (2,62) I × M x E (4,124)
Amplitude
Latency
N 100
P200
17.3"**
-
. . 47.1"** . . 9.5* -
. 26.7*** . 4.6** 4.9* 4.4**
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.
P300
N 100
P200
N200
4.8*
4.3**
-
-
-
13.6"** -
22.7*** 17.5"**
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. .
#P < 0.10; *P < 0.05; **P < 0.01; ***P < 0.001. data. P300 latency decreased significantly as stimulus intensity increased, and auditory stimuli evinced shorter latencies than visual stimuli. The significant interaction between the intensity and modality factors stemmed from a relatively small latency decrease for the auditory stimuli compared to a larger decrease in peak latency for the visual stimuli as stimulus intensity was increased. No other reliable effects or interactions were obtained for any of the experimental variables. An additional modality x electrode analysis of variance also was conducted on the P300 latency data from each modality separately. For auditory stimuli, as intensity increased, latency decreased (F(2,62) = 5.4, P < 0.01); for visual stimuli, as intensity increased, latency decreased (F(2,62)= 13.1, P < 0.001). 3.4. N100, P200, N200 componen~
The mean N100, P200, and N200 amplitudes and latencies for each stimulus condition are illustrated by the grand average waveforms in Fig. 1. The amplitudes and latencies for the N100, P200, and N200 components were assessed separately with three-factor (intensity x modality x electrode) analyses of variance. The results of these analyses are summarized in Table 1. In general, only the N100 was affected directly by intensity increases such that amplitude increased and latency decreased. The significant interactions observed stemmed primarily from the effects of electrode site and were generally uninformative. Because intensity, modality, and electrode effects for these components have been well documented (Picton et al., 1974; Polich and Starr, 1983), analyses of the corresponding potentials from the standard stimuli are not presented. 4.
Discussion
4.1. P300 stimulus effects
The findings of the present study indicate that stimulus intensity affect P300 measures: increases in stimulus
intensity increased P300 amplitude and decreased peak latency, although significant amplitude changes were only observed for the visual modality. The results confirm and extend previous studies that manipulated auditory stimulus intensity and found increases in P300 latency (Papanicolaou et al., 1985; Polich et al., 1985; Polich, 1989b) and support findings that suggest stimulus factors can differentially influence P300 amplitude and latency measures across subject populations (Pollock and Schneider, 1989; Vesco et al., 1993). In this context, it should be noted expressly that P300 amplitude can increase with increases in stimulus intensity in young adult subjects, but that the range of intensity needs to be larger than those employed here (cf. Vesco et al., 1993; Sugg and Polich, 1996). In sum, assessment of ERP studies in applied contexts must consider the role of stimulus factors in general and especially when different subject groups are compared. 4.2. Exogenous versus endogenous contributions
Although the genesis of auditory and visual stimulus influences on the P300 component is uncertain, the effects of stimulus intensity on the 'exogenous' components are similar to those observed for the 'endogenous' P300 and provide a clue. Inspection of Fig. 1 suggests that across stimulus intensity levels P300 amplitude and latency evinced comparable profiles for the auditory and visual stimulus condition as did the N100 component (and to a lesser degree the P200 and N200 potentials): as intensity increased, component amplitudes increased and peak latencies decreased. Given that correlational associations between auditory N100 and P300 measures have been observed previously when relatively large numbers of data points were assessed (Polich, 1986b; Michalewski et al., 1988), it is speculative but not unreasonable to expect that stimulus variables affecting the N100 also might affect the P300. The similarity between the N100 and P300 stimulus effects may originate because both components have demonstrated appreciable sensitivity to the role of attention: increased amplitude reflects increased attentional processing for both components Because sti-
J.W. Covington. J. Polich / Electroencephalography and clinical Neurophysiology 100 (1996) 579-584 m u l u s parameters are important determinants o f E R P attention effects (Roth et al., 1982; H i l l y a r d and Picton, 1987), it is possible that such stimulus effects also m a y contribute to N 1 0 0 and P300 o u t c o m e s (Polich, 1986a; Picton, 1992; Polich, 1993). If this is the case, the relationship b e t w e e n e x o g e n o u s and e n d o g e n o u s influences on E R P c o m p o n e n t s must be evaluated w h e n auditory and visual stimulus factors are varied.
4.3. Stimulus factors in applied contexts As noted above, the percentage o f d e m e n t e d patients found to h a v e ' a b n o r m a l ' P300 latencies in a variety o f clinical studies was apparently related to the intensity o f the auditory stimuli (Polich, 1991). Other reports h a v e found that P300 m e a s u r e s o f aging are affected by the auditory stimulus f r e q u e n c y and intensity such that subject age interacts with these wtriables for E R P values (Squires et al., 1980; P o l l o c k and Schneider, 1992; V e s c o et al., 1993). Additional variation also can arise from the occurrence of m u l t i p l e peaks (P3a, P3b, etc.) that are s o m e t i m e s found in the P300 latency range (Squires et al., 1975; J o h n s o n and D o n c h i n , 1985; Polich, 1988) and are influenced by stimulus intensity (Ford et al., 1976; Roth et al., 1982; Roth et al., 1984). The effects of visual stimulus factors on the P300 E R P h a v e not been e v a l u a t e d as extensively as those for auditory stimuli, although the present results imply that this is an important issue as well for the visual modality. Further, the findings suggest that individual variation in auditory sensory thresholds (Pollock and Schneider, 1992; V e s c o et al., 1993) as well as visual acuity (Polich, 1996) must be e v a l u a t e d w h e n E R P s are used in applied settings. Thus, stimulus variables can contribute to the P300 o u t c o m e s by differentially affecting patient or control groups in u n k n o w n w a y s and need to be c o n s i d e r e d when such populations are assessed.
Acknowledgements This w o r k was supported by N I A grant A 6 1 0 6 0 4 - 0 5 and N I D A D A 0 8 3 8 3 - 0 1 to the second author. This paper is publication N P 9 8 1 2 from the Scripps R e s e a r c h Institute.
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Electroencephalographyand clinical Neurophysiology 100 (1996) 579-584 Short communication
P300, stimulus intensity, and modality J a m e s W . C o v i n g t o n a, J o h n P o l i c h b'* aDepartment of Psychology, University of Cali]ornia, San Diego, La Jolla, CA 92093, USA bDepartment of Neuropharmacology, TPC-IO, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037. USA
Accepted for publication: 15 July 1996
Abstract
Auditory and visual stimulus intensity levels were manipulated systematically in separate conditions to assess the influence of these variables on the P300 event-related brain potential (ERP). Increases in stimulus intensity produced increases in P300 amplitude and decreases in peak latency for both modalities, although the latency effects were stronger for visual stimulation. Similar, somewhat weaker stimulus intensity effects also were observed for the N100, P200, and N200 components. The findings suggest that stimulus intensity contributes to both P300 amplitude and latency measures in important ways and are discussed in relation to the use of ERPs in applied contexts. Keywords: P300; ERP; Stimulus intensity; Auditory; Visual
1. Introduction
Many basic and applied studies of event-related brain potentials (ERPs) employ simple auditory or visual stimuli to elicit the P300 component (e.g. Johnson, 1989a; Johnson, 1989b; Polich et al., 1990; Goodin et al., 1992). When an 'oddball' paradigm is used in this context, subjects are required to discriminate between two stimuli that vary on some dimension by counting or responding to a designated target stimulus. This procedure will produce robust P300 components with relative ease and reliability in a wide variety of normal and patient populations (Picton, 1992; Polich, 1993). Despite the extensive application of this methodology in both theoretical and empirical contexts (e.g. Squires et al., 1977; Johnson, 1986; Knight et al., 1989; Polich, 1989a), the influence of stimulus variables on these results has been little addressed, since the P300 ERP component is assumed to be relatively immune to the effects of stimulus factors because of its putative endogenous rather than exogenous origin (Donchin et al., 1978; Hillyard and Picton, 1986). Although this viewpoint is predominant in the literature, several studies have investigated the role of stimulus effects on the P300 in the context of the auditory startle * Corresponding author. Tel.: +1 619 7848176; fax: +1 619 7849293; e-mail: [email protected]
response (Ford et al., 1976; Roth et al., 1982; Roth et al., 1984; Putnam and Roth, 1990) and when ERPs are elicited passively (Polich, 1986a; Polich, 1989c; Surwillo and Iyer, 1989; O'Donnell et al., 1990). However, only a few reports have directly assessed the role of stimulus factors in an active discrimination paradigm, with virtually all of these employing auditory stimuli. In general, variation in stimulus frequency, intensity, and the presence of white noise produces appreciable effects (10-30+ ms) on P300 peak latency (Papanicolaou et al., 1985; Polich et al., 1985; Polich, 1989b). Sugg and Polich (1996) also have reported that P300 amplitude increased and peak latency decreased as auditory stimulus intensity increased, with tone frequency also affecting these outcomes. Thus, the specific nature of auditory stimulus factors appear to contribute to P300 measures directly and robustly. Although of interest from a theoretical standpoint (cf. Johnson, 1986; Johnson, 1988), the import of these findings is particularly necessary to consider when P300 is employed in applied ERP studies, especially if elderly and/or clinical patient populations are evaluated. For example, P300 components elicited by auditory stimuli are affected by age-related sensitivity to low and high tone frequencies stemming from neural-sensory hearing loss (Pollock and Schneider, 1989). More important, auditory stimulus intensity and subject age interact with respect to both P300 amplitude and latency, such that the
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specific age-related effects appear to depend upon the stimulus frequencies and intensities employed (Squires et al., 1980; Pollock and Schneider, 1992; Vesco et al., 1993). Hence, the percentage of demented patients classified as having 'abnormal' P300 measures is at least in part determined by the auditory stimulus characteristics employed to elicit the P300 component (Polich, 1991). Indeed, a recent meta-analysis of P300 normative aging studies has revealed the systematic effects of stimulus variables on the definition of 'normal' P300 measures across modalities (Polich, 1996). Taken together, these results suggest that appreciable P300 amplitude and latency variability is caused by variation in stimulus factors that interacts with subject population characteristics, an outcome that has contributed significantly to the debate surrounding the applied utility of the P300 component as a measure of cognitive function (cf. Goodin, 1990; Pfefferbaum et al., 1990). The reasons stimulus variables influence P300 measures are not clear. However, stimulus parameters readily affect the amplitude and latency of exogenous (N100, P200, N200) auditory long-latency components (Polich and Starr, 1983; Polich and Starr, 1984; Hillyard and Picton, 1987; Polich et al., 1988), and it is not unreasonable to assume that because such variables can alter the 'sensory' components they also might contribute to the subsequent 'cognitive' portions of the ERP. However, even though both auditory and visual paradigms have been employed to evaluate various clinical populations (Pfefferbaum et al., 1984; Picton et al., 1984; Johnson, 1989a; Johnson, 1989b; Polich et al., 1994), assessment of how comparable changes in stimulus intensity for both modalities affect P300 measures has not been reported, particularly for visual stimuli, which have not been assessed comprehensively. The present study was designed as an initial step to identify these relationships by systematically manipulating stimulus intensity for both the auditory and visual modalities. 2. Methods 2.1. Subjects
A total of 32 (16 male, 16 female) undergraduate students (mean age 21.6 years, SD 4.4 years) from the University of California, San Diego participated in return for course credit. All subjects reported normal hearing and vision, no neurological or psychological problems, and all were naive to electrophysiological studies.
comfortable and would produce accurate task performance. Auditory stimuli were presented binaurally over headphones with a duration of 50 ms and 10 ms rise/fall times. The target was a 2000 Hz tone and the standard was a 1000 Hz tone, with stimulus intensity presented at either 40 (low), 60 (medium) or 80 (high) dB SPL (a range of values that covers the majority of P300 auditory studies). The visual target stimuli consisted of a black and white checkerboard (square = 2.5 cm 2) and the standard stimuli were horizontal black and white lines (2.5 cm wide) presented on a 21 inch monitor viewed from a distance of 1 m, with stimulus intensities at 0.60 (low), 35.0 (medium), or 150.0 (high) cd/m 2 (a range that includes relatively dim to very bright stimuli presented on a monochrome monitor). The presentation order of the experimental blocks was counterbalanced across subjects and within sex for each modality, with half the subjects receiving the auditory condition first and half receiving the visual condition first. A short practice block was presented initially to familiarize each subject with the task situation, which consisted of about 10 trials using the same conditions as the first experimental block. The inter-stimulus interval was 3.0 s. The target stimuli occurred randomly with a 0.20 probability. A total of 25 target stimulus artifact-free trials were acquired for each condition. Subjects were instructed to indicate the occurrence of a target stimulus by gently lifting the index finger of their preferred hand, and response accuracy was recorded. 2.3. Recording conditions
EEG activity was recorded at the Fz, Cz, and Pz electrode sites of the 10-20 system using gold-plated electrodes, affixed with electrode paste and tape, with impedances of 10 kf] or less. Linked earlobes were used as the reference with a forehead ground. Electro-ocular (EOG) activity was recorded bipolarly with electrodes placed at the outer canthus and supraorbitally to the left eye. The filter bandpass was 0.016-30 Hz (3 dB, 12 dB octave/rolloff), and EEG was digitized at 3 ms/point for 750 ms with a 75 ms prestimulus baseline. Waveforms were averaged on-line by a commercial signal averager, which also controlled the stimulus presentation and artifact rejection. Trials on which either the EEG or EOG exceeded a preset threshold of +90/zV were rejected automatically. 3. Results 3.1. Task performance
2.2. Stimuli and procedure
Low, medium, and high levels of stimulus intensities for auditory and visual stimuli were presented to each subject in separate conditions. The intensity levels were determined by pilot testing, such that the range of values was
Geisser-Greenhouse corrections were used in all analyses of variance, and only significant results by these criteria are reported. A two-factor (intensity x modality) analysis of variance was performed on the response error data. Low error rates for target detection were obtained
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.I.W. Covington, J. Polich / Electroencephalography and clinical Neurophysiology tO0 (1996) 579-584
(0.46% overall), with somewhat (but non-significantly, P > 0.45) fewer errors made with auditory (0.37%) compared to visual (0.56%) stimuli.
LOW INTENSITY - - t - MED INTENSITY " - I I - HIGH INTENSITY - -4~ -
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3.2. Component measurement
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The P300 component was designated as the largest positive peak that occurred after the N100-P200-N200 complex between 250 and 400 ms for the auditory and 3 0 0 500 for the visual stimuli. Amplitude was measured relative to the prestimulus baseline, and latency was defined as the time of maximum positive amplitude. The amplitudes and latencies of the N100, P200, N200 components also were measured at all electrode sites within ranges of 6 0 150, 120-220, and 180-300 ms for the auditory and 8 0 160, 140-240, and 240--350 ms for the visual stimuli, respectively. The grand average ERPs from the target stimuli for the various conditions are presented in Fig. 1. The mean P300 amplitudes and latencies from the target data LOW _" _- - - -
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Fig. 2. Mean P300 amplitude (top) and latency (bottom) from the target stimuli for each stimulus intensity and modality, as a function of electrode site. for each intensity level, modality, and electrode site are displayed in Fig. 2. A three-factor (intensity x modality x electrode) analysis of variance was applied to each dependent variable. The results of these analyses (and those performed on the other components) are summarized in Table 1.
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3.3. P300 component
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Fig. I. Grand average ERPs from the target stimuli for each of the intensity, modality, and electrode site conditions (N = 16).
For the target stimuli, P300 amplitude increased overall as stimulus intensity increased. The usual increase in P300 amplitude from the frontal to parietal electrode sites was obtained, with auditory stimuli demonstrating somewhat less steep increases compared to visual stimuli over the scalp. It should be noted explicitly that the intensity and modality variables did not interact with each other. Also, the modality x electrode interaction was confirmed (P < 0.002) when the data were scaled using a vector transformation (McCarthy and Wood, 1985), suggesting that different neural generators were operating for each modality across intensity levels (cf. Johnson, 1993). An additional modality x electrode analysis of variance also was conducted on the P300 amplitude data from each modality separately. For auditory stimuli, only the electrode effect was reliable (F(2,62) = 16.5, P < 0.001); for visual stimuli, amplitude increased significantly as intensity increased (F(2,62) = 6.3, P < 0.01), and as electrode position changed from frontal to parietal (F(2,62) = 52.9, P < 0.001). The same analysis was performed on the P300 latency
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Table 1 F-Ratios from analyses of variance (intensity (I) x modality (M) × electrode (E)) on the N100, P200, N200, and P300 amplitude and latency data from the target stimuli Factor (df)
Intensity ( 2 , 6 2 ) Modality ( 1 , 3 1 ) Electrode (2,62) I × M (2,62) I x E (4,124) M × E (2,62) I × M x E (4,124)
Amplitude
Latency
N 100
P200
17.3"**
-
. . 47.1"** . . 9.5* -
. 26.7*** . 4.6** 4.9* 4.4**
N200 -
.
P300
N 100
P200
N200
4.8*
4.3**
-
-
-
13.6"** -
22.7*** 17.5"**
. 6.6** . 3.0* 11.8"** 2.9
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.
.
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. .
#P < 0.10; *P < 0.05; **P < 0.01; ***P < 0.001. data. P300 latency decreased significantly as stimulus intensity increased, and auditory stimuli evinced shorter latencies than visual stimuli. The significant interaction between the intensity and modality factors stemmed from a relatively small latency decrease for the auditory stimuli compared to a larger decrease in peak latency for the visual stimuli as stimulus intensity was increased. No other reliable effects or interactions were obtained for any of the experimental variables. An additional modality x electrode analysis of variance also was conducted on the P300 latency data from each modality separately. For auditory stimuli, as intensity increased, latency decreased (F(2,62) = 5.4, P < 0.01); for visual stimuli, as intensity increased, latency decreased (F(2,62)= 13.1, P < 0.001). 3.4. N100, P200, N200 componen~
The mean N100, P200, and N200 amplitudes and latencies for each stimulus condition are illustrated by the grand average waveforms in Fig. 1. The amplitudes and latencies for the N100, P200, and N200 components were assessed separately with three-factor (intensity x modality x electrode) analyses of variance. The results of these analyses are summarized in Table 1. In general, only the N100 was affected directly by intensity increases such that amplitude increased and latency decreased. The significant interactions observed stemmed primarily from the effects of electrode site and were generally uninformative. Because intensity, modality, and electrode effects for these components have been well documented (Picton et al., 1974; Polich and Starr, 1983), analyses of the corresponding potentials from the standard stimuli are not presented. 4.
Discussion
4.1. P300 stimulus effects
The findings of the present study indicate that stimulus intensity affect P300 measures: increases in stimulus
intensity increased P300 amplitude and decreased peak latency, although significant amplitude changes were only observed for the visual modality. The results confirm and extend previous studies that manipulated auditory stimulus intensity and found increases in P300 latency (Papanicolaou et al., 1985; Polich et al., 1985; Polich, 1989b) and support findings that suggest stimulus factors can differentially influence P300 amplitude and latency measures across subject populations (Pollock and Schneider, 1989; Vesco et al., 1993). In this context, it should be noted expressly that P300 amplitude can increase with increases in stimulus intensity in young adult subjects, but that the range of intensity needs to be larger than those employed here (cf. Vesco et al., 1993; Sugg and Polich, 1996). In sum, assessment of ERP studies in applied contexts must consider the role of stimulus factors in general and especially when different subject groups are compared. 4.2. Exogenous versus endogenous contributions
Although the genesis of auditory and visual stimulus influences on the P300 component is uncertain, the effects of stimulus intensity on the 'exogenous' components are similar to those observed for the 'endogenous' P300 and provide a clue. Inspection of Fig. 1 suggests that across stimulus intensity levels P300 amplitude and latency evinced comparable profiles for the auditory and visual stimulus condition as did the N100 component (and to a lesser degree the P200 and N200 potentials): as intensity increased, component amplitudes increased and peak latencies decreased. Given that correlational associations between auditory N100 and P300 measures have been observed previously when relatively large numbers of data points were assessed (Polich, 1986b; Michalewski et al., 1988), it is speculative but not unreasonable to expect that stimulus variables affecting the N100 also might affect the P300. The similarity between the N100 and P300 stimulus effects may originate because both components have demonstrated appreciable sensitivity to the role of attention: increased amplitude reflects increased attentional processing for both components Because sti-
J.W. Covington. J. Polich / Electroencephalography and clinical Neurophysiology 100 (1996) 579-584 m u l u s parameters are important determinants o f E R P attention effects (Roth et al., 1982; H i l l y a r d and Picton, 1987), it is possible that such stimulus effects also m a y contribute to N 1 0 0 and P300 o u t c o m e s (Polich, 1986a; Picton, 1992; Polich, 1993). If this is the case, the relationship b e t w e e n e x o g e n o u s and e n d o g e n o u s influences on E R P c o m p o n e n t s must be evaluated w h e n auditory and visual stimulus factors are varied.
4.3. Stimulus factors in applied contexts As noted above, the percentage o f d e m e n t e d patients found to h a v e ' a b n o r m a l ' P300 latencies in a variety o f clinical studies was apparently related to the intensity o f the auditory stimuli (Polich, 1991). Other reports h a v e found that P300 m e a s u r e s o f aging are affected by the auditory stimulus f r e q u e n c y and intensity such that subject age interacts with these wtriables for E R P values (Squires et al., 1980; P o l l o c k and Schneider, 1992; V e s c o et al., 1993). Additional variation also can arise from the occurrence of m u l t i p l e peaks (P3a, P3b, etc.) that are s o m e t i m e s found in the P300 latency range (Squires et al., 1975; J o h n s o n and D o n c h i n , 1985; Polich, 1988) and are influenced by stimulus intensity (Ford et al., 1976; Roth et al., 1982; Roth et al., 1984). The effects of visual stimulus factors on the P300 E R P h a v e not been e v a l u a t e d as extensively as those for auditory stimuli, although the present results imply that this is an important issue as well for the visual modality. Further, the findings suggest that individual variation in auditory sensory thresholds (Pollock and Schneider, 1992; V e s c o et al., 1993) as well as visual acuity (Polich, 1996) must be e v a l u a t e d w h e n E R P s are used in applied settings. Thus, stimulus variables can contribute to the P300 o u t c o m e s by differentially affecting patient or control groups in u n k n o w n w a y s and need to be c o n s i d e r e d when such populations are assessed.
Acknowledgements This w o r k was supported by N I A grant A 6 1 0 6 0 4 - 0 5 and N I D A D A 0 8 3 8 3 - 0 1 to the second author. This paper is publication N P 9 8 1 2 from the Scripps R e s e a r c h Institute.
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