Developmental changes in P300 wave elicited during two different experimental conditions

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Developmental Changes in P300 Wave Elicited During Two Different Experimental Conditions T a t s u o F u c h i g a m i , M D , O s a m i O k u b o , M D , K a z u o Ejiri, M D , Y u k i h i k o Fujita, M D , R y u t a r o K o h i r a , M D , Y u k i o N o g u c h i , M D , Sachiko F u c h i g a m i , M D , K a z u o Hiyoshi, M D , Atsushi N i s h i m u r a , M D , and K e n s u k e H a r a d a , M D

Age-related correlations on auditory event-related potentials were studied using a task-relevant oddball paradigm in 175 normal subjects aged 4-21 years and agerelated correlations in the "ignore" condition were studied in 108 normal subjects aged 1-21 years. In the ignore condition, subjects more than 4 years of age were instructed to read a book to divert attention from the auditory stimulus. From 4 to about 17 years of age, the latencies of task-relevant P300 in event-related potentials (ERPs) gradually shortened. In the ignore condition experiment, the P300 latency shortened progressively, but stabilized at about 12 years of age. Whereas P300 in the ignore condition likely corresponds to P3a described previously (passive attention), the conventional P300 wave corresponds to P3b (active attention). The findings indicate a developmental difference between the P3a and P3b potential. Fuchigami T, Okubo O, Ejiri K, Fujita Y, Kohira R, Noguchi Y, Fuchigami S, Hiyoshi K, Nishimura A, Harada K. Developmental changes in P300 wave elicited during two different experimental conditions. Pediatr Neurol 1995;13:25-28.

Introduction Event-related potentials (ERPs) reflect various cognitive functions and include a late positive wave that has been called P3 or P300 [1]. The P300 wave is generally interpreted as a neural correlate of decision making or of signal detection by an actively attentive subject [2-5]. In many studies of P300 or P3, a simple, auditory, 2-tone task is used. The test subject indicates when a "target" stimulus, distinct from a "standard" tone, is perceived.

From the Department of Pediatrics; Nihon University School of Medicine; Tokyo, Japan.

© 1995 by Elsevier Science Inc. • 0887-8994/95/$9.50 SSDI 0887-8994(95)00086-U

Without actively attending to the stimulus, if the subject perceives that the stimulus has an explicit quality P300like potential can be elicited. Polich reported P300 in association with a passive auditory paradigm [6]. The studies of ERPs in children, based on a taskrelevant oddball paradigm, reveal a decrease in the latency of P300 with increasing age [5,7-12]. This developmental change could be related to maturational phenomena in cognitive processes. Developmental changes in P300 in the "ignore" conditions have not been reported previously in children. The purpose of this study was to determine whether developmental changes in P300 in the ignore condition are the same as those in the attending condition (conventional P300) in a large number of normal children.

Methods Patients who presented at our outpatient pediatric clinics after various acute illnesses excluding those with neuroiogic or psychiatric features were studied. The tests were conducted after full recovery from the acute illnesses, so that subjects were essentially healthy. Informed consent was obtained from the patients or their parents. "Attending" Conditions. A total of 175 subjects (86 male, 89 female) between 4 and 21 years of age were tested. The subject lay on a bed and was instructed to relax, with eyes closed, in a semi-darkened, soundattenuated, electrically shielded chamber. The ERPs were elicited by binaural 1,000- and 2,000-Hz tone pips, with 10-ms rise and fall and 100-ms plateau time, presented through headphones at an intensity of 60-dB peak sound pressure (SPL). Of the 160 tones presented at 2-s intervals, 32 were 1,000-Hz (rare tones) and 128 were 2,000-Hz (frequent tones). The delivery sequence of frequent and rare tones was randomized, and the subject pressed a switch upon detection of rare tones randomly occurring within a steady series of frequent tones. This "oddball" method has been commonly used to record P300 potentials. Reaction time between rare tone and switch activation was measured. Electroencephalograms (EEGs) were recorded from Fz, Cz, and Pz scalp locations (International 10/20 System), referenced to linked earlobes. Electrode impedance was less than 5 k~. The ground electrode

Communications should be addressed to: Dr. Fuchigami; Department of Pediatrics; Nihon University School of Medicine; 30-10yaguchi, ltabashi-ku; Tokyo, 173, Japan.

Fuchigami et al: P300 From Two Conditions

25

was at Fpz. Electro-oculograms (EOGs) were recorded from electrodes above and below the right eye to detect artifacts produced by eye movement or blinking. The filter bandpass was set at 0.3 to 500 Hz. Evoked potentials were recorded off-line after the EEG information was stored in a magnetic tape by an analog data recorder. The digitized intersample interval was 1 ms, and the analysis time was 1,024 ms, beginning 100 ms before stimulation. A Signal Processor 7T17 (NEC Sanei, Tokyo, Japan) was used. The evoked potential waveforms for rare tones (32 responses) and frequent tones (128 responses) were averaged separately. "Ignore" Condition. For this experiment, 108 subjects (58 male, 50 female) between 1 and 21 years of age were tested. Subjects more than 4 years of age were instructed to read a book to divert attention from the stimulus. The EEG was recorded at the Fz, Cz, and Pz electrode sites of the International 10/20 System, referenced to linked earlobes with a forehead ground. Impedance was less than 5 kfl, and the filter bandpass was 0.3-60 Hz. Bipolar EOGs were made with electrodes placed above and below the right eye. The EEG was digitized at 1 ms per point for 750 ms with a 75-ms prestimulus baseline. Waveforms were averaged on-line by the Signal Processor 7T18 (NEC Sanei), which controlled the stimulus presentation and artifact rejection. Trials in which the EEG or EOG exceeded 100 IxV were automatically rejected. An auditory oddball paradigm was used in which a continuous series of 750-Hz frequent tones was presented with 1,000-Hz rare tones occurring randomly in 10% of the trials. The tones (100-ms duration, 10-ms rise/fall, 100-dB SPL) were presented at l-s intervals through headphones binaurally placed 30 cm behind the subject's head. The evoked potential waveforms for rare tones (100 responses) and frequent tones (900 responses) were averaged separately. Regression analyses of P300 latencies on age were performed, including tests for linear and nonlinear models. Significant comparisons were evaluated at P < .05 unless otherwise indicated.

Results The mean latencies of P300 at Pz in the 2 conditions are listed by age in Table 1. Figure 1 displays the ERPs and reaction times of a 4-year-old male and a 13-year-old female subject in the

Table 1. Latency (mean ± SD) of P300 at Pz in attending and ignore conditions, by age Age (yrs) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16-17 18-19 20-21

26

Attending (ms)

(n (n (n (n (n (n (n (n (n (n (n (n (n (n (n

= = = = = = = = = = = = = = =

9) 10) 12) 17) 19) 10) 10) 12) 10) 17) 18) 10) 7) 7) 7)

Ignore (ms)

447.5 - 4 8 . 8 411.6 +-- 52.7 428.9 --- 50.6 415.6-+ 49.6 399.7 -+ 50.3 388.8 -- 28.1 371.3 ± 29.7 371.3 --- 26.7 365.6 ± 38.8 349.4 ± 34.0 348.7 ± 35.4 330.3 ± 39.3 341.1 ± 33.6 351.8 +-- 25.2 327.2 --- 25.3

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(n (n (n (n (n (n (n (n (n (n (n (n (n (n (n (n (n (n

= = = = = = = = = = = = = = = = = =

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4) 513,0--- 136.9 8) 4 0 6 , 6 - 60.8 10)428.0 ± 100.8 9) 3 4 7 . 6 ± 62.8 7) 370.1 ± 59.3 5) 341.6 ± 65.8 8) 342.3 --- 46.1 4) 346.8 -+ 56.4 10) 339.5 - 36.8 5) 336.8 ± 43.8 4) 306.8 ± 22.4 5) 313.8 -+ 29.3 7) 335.0 ± 40,8 5) 325.0 ± 5.6 3) 306.7 ± 33.2 7) 346.9 --- 43.2 I) 352.0 ± 0 6) 343.8 ± 58.9

male (4 y e a r s old)

N100

rare

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100 200 300 female

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I

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.

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,

'~ 700

800

900

msec

Figure 1. ERPs and reaction time (RT) of a 4-year-old male and 13year.old female in the attending condition.

attending condition. N I 0 0 was seen in the responses to both rare and frequent tones, but N200 and P300 were recorded only for the rare tones. The latencies of all 3 potentials were longer in younger children, as expected. The reaction time also was longer and more variable in the 4-year-old than 13-year-old child. Figure 2 displays ERPs of a 5-year-old and 13-year-old male subject in the ignore condition. The latencies of P300 were longer in the younger child. Figure 3 displays the relationship between P300 and age in the attending and ignore conditions. The attending condition could not be tested reliably before the age of 4 years. P300 latencies in both conditions progressively shortened with age. In the ignore condition, the P300 latency was shortest at age 12 years; in the attending condition, it was shortest at age 15-17 years. Statistical model-fitting found that the relationship between age and P300 latencies in both conditions fit best with a curvilinear function: in the ignore condition, a significant secondorder polynomial regression (Y = 466.802 - 23.015X + 0,912X2; r 2 = 0,253, P < .001); in the attending condition, a significant second-order polynomial regression (Y = 510.41 - 17.518X + 0.429X2; r 2 = 0.437, P < .001).

The P300 latency in the ignore condition was shorter than that in the attending condition at any given age. The latency difference between the 2 conditions was greater at younger ages, progressively decreased toward 16-17 years of age, and approached identity in the late teens (Fig 4).

Ignore

m a l e (5 y e a r s old)

2

msec

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attending msec

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750

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0

• t : :• u,

300 ~

"TII•

w

0

5

10

I lOpV 0

1O0

200

300

400

500

mSec

Figure 2. ERPs of a 5-year-old male and 13-year-old male in the ignore condition.

Discussion The endogenous auditory P300 ERP has been used to distinguish depression from Alzheimer's dementia by its ability to evaluate cognitive functions [13-16]. The latency of P300 reflects the time to evaluate different stimuli, including the processes necessary for making taskrelevant decisions. Although a relevant task situation is generally used to elicit the P300, P300-1ike waveforms also can be obtained with procedures that do not involve an active, intentional discrimination task. Ritter et al. [17] and Roth [18] observed that auditory evoked potentials had a large positive potential with a latency of 200 to 300 ms when the first stimulus was presented in an unpredictable manner or when a repetitive series of auditory stimuli suddenly shifted in tone or quality. Predictable stimulus changes did not produce the same results. In this stimulus paradigm, the appearance of a positive deflection in the auditory evoked potential suggested that it was a functional component for an orienting response. Later, Squires et al. [19] delineated P3a and P3b components in P300. The earlier component, P3a, had a latency of about 240 ms, and could be elicited by infrequent, unpredictable shifts of either intensity or frequency

0

•

2501

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•

•

/°1",

3sol

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:,

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male (13 years old) N!oo

Y = 466.802 - 23.015 X + 0.912 X

750

~J •

w

•

S 15

•

"

• 20

age

Figure 3. Relationship between P300 and age in ignore and attending conditions.

in a train of tone pips, whether the subject was ignoring them by reading a book or attending to the tones by counting. The later component, P3b, had a mean latency of about 350 ms, and occurred only when the subject was actively attending to the tones [ 19]. An unexpected stimulus is perceived differently from a predicted stimulus. In the former condition, the subject is unable to ignore the stimulation because of its explicit nature or unexpected character. This type of forced attention is referred to as passive attention [20]. It contrasts msoc 80O

: attending 6oo

~

• : ignore

t 4oo

200

,o

~ 0

~ 2

, 4

I

' 6

' 8

' 10

' 12

~ 14

, , 16-17 20-21

age Figure 4. Age-related P300 latency differences between ignore and attending conditions.

Fuchigami et al: P300 From Two Conditions 27

with active attention, in which the subject voluntarily focuses on a designated task relevant to the stimulus. In our study, P300 in the ignore condition likely corresponds to P3a (passive attention), whereas conventional P300 corresponds to P3b (active attention). We were able to measure P300 in the ignore condition in 1-year-old subjects because no specific task was imposed in relation to the rare stimuli. However, P300 in the active condition could not be elicited in children 3 years old or younger because they could not understand our instructions. In the ignore condition, P300 latency shortened progressively until about age 12 years. The latency of taskrelevant P300 in ERPs gradually shortened from age 4 to about 16 years. Greater latency variabilities in younger children may parallel the greater variabilities in reaction time. The age at which P300 latency reached the adult level was earlier in the ignore than in the attending condition. Also, P300 latency in the ignore condition was shorter than in the attending condition at the same age. The latency difference between the 2 conditions was greater in younger children and progressively decreased, becoming identical in the late teens. The development of fundamental cognitive function like passive attention reaches the adult level at an earlier age than cognitive function like active attention. Polich reported P300 waves from a passive auditory paradigm in adults [6]. The passive sequence paradigm yielded P300 waveforms remarkably similar to those obtained from the active task. Our finding that the P300 latencies in the 2 conditions become identical in the late teens supports Polich's study in adults. References

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[4] Paul DD, Sutton S. Evoked potential correlates of response criteflon in auditory signal detection. Science 1972; 177:362-4. [5] Fuchigami T, Okubo O, Fujita Y, Okuni M, Noguchi Y, Yamada T. Auditory event-related potentials and reaction time in children: Evaluation of cognitive development. Dev Med Child Neurol 1993;35: 230-7. [6] Polich J. P300 from a passive auditory paradigm. Electroenceph Clin Neurophysiol 1989;74:312-20. [7] Goodin DS, Squires KC, Henderson BH, Start A. Age-related variations in evoked potentials to auditory stimuli in normal human subjects. Electroenceph Clin Neurophysiol 1978;44:447-58. [8] Courehesne E. Neurophysiological correlates of cognitive development: Changes in long-latency event-related potentials from childhood to adulthood. Electroenceph Clin Neurophysiol 1978;45:468-82. [9l Polieh J, Howard L, Start A. Effects of age on the P300 component of the event-related potentials from auditory stimuli: Peak definition, variation and measurement. J Gerontol 1985;40:721-6. [10] Finley WW, Faux SF, Hutcheson J, Amstutz L. Long-latency event-related potentials in evaluation of cognitive function in children. Neurology 1985;35:323-7. [11] Martin L, Barajas JJ, Fernandez R. Torres E. Auditory eventrelated potentials in well-characterized groups of children. Electroenceph Clin Neurophysiol 1988;71:375-81. [12] Pearce JW, Crowell DH, Tokioka A, Pachero GP. Childhood developmental changes in the auditory P300. J Child Neurol 1989;4: 100-6. [13] Goodin DS, Squires KC, Start A. Long-latency event-related components of the auditory evoked potential in dementia. Brain 1978; 101:635-48. [14] Goodin DS, Starr A, Chippendale T, Squires KC. Sequential changes in the P3 component of the auditory evoked potential in confusional states and dementing illnesses. Neurology 1983;33:1215-8. [15] Squires NK, Chippendale T, Wrege KW, Goodin DS, Starr A. Electrophysiological assessment of mental function in ageing and dementia. In: Poon L, ed. Ageing in the 1980s. Washington, DC: American Psychological Association, 1980:125-34. [16] Syndulko K, Hansch EC, Cohen SN, et al. Long-latency eventrelated potentials in normal aging and dementia. In: Courjon J, Maugiere F, Revol M, eds. Clinical applications of evoked potentials in neurology. New York: Raven Press, 1982:279-85. [17] Ritter W, Vaughan HG, Costa LD. Orienting and habituation to auditory stimuli: A study of short term changes in average evoked responses. Electroenceph Clin Neurophysiol 1968;25:550-6. [18] Roth WT. Auditory evoked responses to unpredictable stimuli. Psychophysiology 1973;10:125-38. [19] Squires NK, Squires KC, Hillyard SA. Two varieties of longlatency positive waves evoked by unpredictable auditory stimuli in men. Electroenceph Clin Neurophysiol 1975;38:387-401. [20] Ritter W, Vaughan HG. Average evoked responses in vigilance and discrimination: A reassessment. Science 1969;164:326-8.