Developmental changes in the human visual system as reflected by the latency of the pattern reversal VEP

Electroencephalography and clinical Neurophysiology, 1983, 56: 1-15

1

Elsevier Scientific Publishers Ireland, Ltd.

Clinical Section DEVELOPMENTAL CHANGES IN THE HUMAN VISUAL SYSTEM AS REFLECTED BY THE LATENCY OF THE PATI'ERN REVERSAL VEP A N N E M O S K O W I T Z and S A M U E L S O K O L i

Department of Ophthalmology, New England Medical Center, and Tufts University School of Medicine, 171 Harrison Avenue, Boston, Mass. 02111 (U.S.A.) (Accepted for publication: March 9, 1983)

Most visual evoked potential (VEP) studies of the maturing human visual system have used diffuse flashing light as a stimulus (Ellingson 1960; Engel and Butler 1963; Lodge et al. 1969; Ellingson et al. 1973; Barnet et al. 1980; Blom et al. 1980) and it is generally agreed that the latency of the flash VEP decreases with increasing age. Most investigators found that VEP latency reaches adult levels by 1-2 years of age (Lodge et al. 1969; Ellingson et al. 1973; Barnet et al. 1980), although Blom et al. (1980) did not find adult-like latency values until 4 years of age. More recently, pattern stimuli have been used to record VEPs from infants (Harter and Suitt 1970; Marg et al. 1976; Sokol and Dobson 1976; Harter et al. 1977; Pirchio et al. 1978; Sokol 1978). An advantage of the use of pattern stimuli is that the development of spatial mechanisms underlying visual function can be followed from as early as a few weeks of age. Studies of the adult pattern VEP have shown that the latency of the major components varies as a function of pattern element size. Small checks or high to intermediate spatial frequency gratings produce VEPs with latencies that are longer than VEPs obtained with large checks or low spatial frequency gratings (Parker and Salzen 1977a, b; Sokol 1982). Sokol and Jones (1979), using pattern reversal checkerboard stimuli, measured the latency of the first major positive component, PI, and found similar results with infants. Infants as young as 4-5 weeks of age showed VEPs with Pl latencies that increased as check size decreased. In addition,

Sokol and Jones found in a small group of infants and young children that P~ latency for checks larger than 30 min of arc reached adult levels by 4-5 months of age, while Pl latency for smaller checks did not reach adult levels until after 6 years of age. Similarly, Spekreijse (1978), who used onset-offset checkerboard stimulation, found that the latency of the first positive ('CI') and first negative ('CII') components of VEPs to small (9 rain) checks did not reach adult levels until about 10 years of age. De Vries-Khoe and Spekreijse (1982) also recorded pattern onset VEPs using 9 rain checks and found that the VEP wave form continued to develop up to puberty; the incidence of the component shown in adults to reflect foveal stimulation with small sharply focused patterns ('CII,' the first negative component) did not reach 100% until 8-12 years of age. Sokol and Jones (1979) found that the latency of the pattern VEP in infants shows much less variability than amplitude, both within and between subjects, and for that reason latency appears to be a more reliable index of visual maturation than amplitude. The present study adds to that of Sokol and Jones by testing a much larger group of subjects (439), by studying the maturation of both early and late pattern VEP components, and by examining the interactive effects of age, pattern element size and pattern form (checks vs. stripes).

i This research was supported by NEI Research Grant EY00926 and Career Development Award EY70275 to S.S.

Stimuli and subjects Pattern stimuli were generated by a black and

Methods

0013-4649/83/0000-0000/$03.00 © 1983 Elsevier Scientific Publishers Ireland, Ltd.

2 white TV monitor. The mean luminance of the screen was 1.9 log c d / m 2 and the contrast between dark and light pattern elements was 0.84. Binocular VEPs were recorded from 439 infants and young children ranging in age from 1 month to 5 years using checkerboard patterns. Three hundred and twenty of the subjects were tested at a distance of 75 cm from the TV screen using 60 a n d / o r 15 min of arc checks. The checks reversed at 1.88 alternations/see (0.94 Hz) and the field size at this distance was 15 × 18 °. One hundred and nineteen subjects, all between 2 and 6 months of age, were tested at a distance of 100 cm from the TV screen using 48 a n d / o r 12 min of arc checks. The checks reversed at either 1,88 alternat i o n s / s e e or 3.75 alternations/see (1.88 Hz); the field size at this distance was 11 × 14 °. We attempted to obtain data for both large (60 or 48 rain) and small (15 or 12 min) checks from each subject, but this was not always possible due to lack of sustained cooperation. Twelve infants were also tested longitudinally between the ages of 1 and 7 months using both square wave gratings and checkerboard patterns. The infants were tested at a distance of 75 cm from the TV screen with a series of stripes and checks with pattern elements subtending 7.5, 15, 30, 60, 120 and 240 min of arc. The patterns alternated at 1,88/sec; field size was 15 × 18 °.

VEP recording Binocular VEPs, were recorded using gold cup E E G electrodes. The active electrode was attached to the scalp a p p r o x i m ~ e l y 1 cm above the inion on the midline; one ear served as reference and the other as ground. The signals were led through a preamplifier with a bandpass of 1-35 Hz for the 1.88/see alternation rate and 1-50 Hz for the 3.75/sec alternation rate. The amplified signals were averaged by a minicomputer using a software program with an artifact rejection routine which examined each sweep and rejected sweeps containing artifacts, such as large DC shifts produced by head or body movement. During recording, either a single sweep or the cumulated response could be monitored on an oscilloscope. Because of the larger signal to noise ratio, 32 or 64 accumulations were usually sufficient to obtain

A. MOSKOWITZ, S. SOKOL measurable VEPs for the infants, while 64 or 128 accumulations were necessary for the toddlers and older children. The averaged responses were plotted with an X-Y recorder and stored on a floppy diskette for later retrieval and analysis. A software program which allowed the operator to place a cursor at any point on the VEP oscilloscope display was used to obtain peak latency measurements. Infants and young toddlers sat on their parent's lap during recording; older children sat alone. An observer standing behind the TV monitored the subject's fixation and operated a remote control switch to start and stop averaging. Averaging was initiated when the reflection of the stimulus field could be seen in the subject's pupils. If the subject looked away from the screen, averaging was stopped and then restarted when fixation was resumed. For the infants and toddlers, a control condition was presented at the end of each session. The monitor was switched to TV mode without an incoming video program, resulting in visual 'noise' (static). The components of the noise condition occurred randomly with respect to the sweep of the computer. Brain activity in response to the noise condition was recorded from each infant and toddler for the same number of accumulations that were obtained to pattern stimuli. Responses recorded when checks or stripes were presented which were not recognizably different from the response to the noise condition were not measured.

Results Fig. 1 shows representative VEP wave forms from individual subjects of several different ages, ranging from 1 month to 4 years, in response to large (60 min) and small (15 min) checks. VEPs from an adult are also shown for comparison. The adult responses for both large and small checks show an initial negative component at 85-95 msec (NL) and a prominent positive component at 100-120 msec (Pi)- The adult response to small checks also shows a second negative component at 140-160 msec (N 2) and a second positive compo-

HUMAN VISUAL DEVELOPMENT AS REFLECTED BY VEP LATENCY CHANGES

Lorge Checks I

$moll Checks

tive component in response to small checks shortens dramatically. By 4 years of age, the VEP records are very similar to those obtained from adults. Thus, with increasing age there is a sharpening of the peaks and an increase in the complexity of the VEP wave form. As seen in the records obtained from 1- to 9-month-old infants, this metamorphosis proceeds at a faster rate for large checks than for small checks. Fig. 2 shows VEP records for large (60 min) and small (15 min) checks from 5 representative subjects for each of 5 age groups: 3, 6 and 9 months and 1 and 4 years. The peak of the early positive component, Pj, occurs between 100 and 200 msec and is present in every record. The frequency of occurrence of the later positive components is more variable. For example, the wave forms from some subjects show no later positive components, others show a positive wave occurring between 200 and 300 msec ('P2'), and

1 mo.

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Fig. 1. VEP wave forms obtained from individual subjects ranging from 1 month to 4 years of age and for an adult in response to large (60 rain) and small (15 rain) checks. The checks reversed at a rate of 1.88 alternations/sec.

nent (1'2) at approximately 200 msec. The records in Fig. 1 obtained from infants and young children show that the latency of all components of the pattern reversal VEP, and most notably P=, decreases with increasing age. At 1 month, the VEP to large checks has a simpler wave form than that of an adult, consisting of only a slowly rising positive wave (Pi)- N o measurable response is obtained for small checks. At 2 months, the large positive wave in response to large checks is preceded and followed by negative potentials (N~ and N 2), and P~ has appeared in response to small checks. At 3 months, a late positive wave has emerged in the response to large checks, and by 9 months, late positive components are also present in the wave form for small checks. Between 9 months and 4 years, the latency of this late posi-

3 too.

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9 mo.

1 yr.

4 yr.

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Fig. 2. VEP records for large (60 rain) and small (15 rain) checks from 5 representative subjects for each of 5 age groups. Checks reversed at 1.88 alternations/sec. Note the variability of occurrence of later components (P2 and P3)-

4

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1 yr

Fig. 4. The frequency of occurrence of the 4 types of pattern reversal VEPs found in infants and young children. 'Neither' refers to the absence of P2 and P3 components; VEPs in this category contained only a P~ component.

Fig. 3. The 4 types of pattern reversal VEPs obtained from infants and young children. Pi was always present, a: no late positive components, b: a positive component occurring later

than 300 msec (I)3). c: a positive component occurring before 300 msec (I)2). d: both P2 and P3.

others show a wave occurring later than 300 msec ('P3'); in some cases, all 3 positive waves are present. Due to the variability of the later positive components, waves later than P~ were evaluated qualitatively. Fig. 3 gives examples of each type of pattern reversal VEP and the frequency of occurrence of each of these categories is shown in Fig. 4 for large (60 and 48 min) checks and small (15 and 12 min) checks for 1-6-month-old infants, 1- and 1-year-old children and adults. For large checks, P3 first appears at 2 months of age; its frequency of occurrence increases slightly at 3 months and by 1 year has decreased. Records obtained from adults do not show a I)3 component for large checks. By 6 months, nearly 50% of the infants show a P2 component, which is nearly equal to the propor-

tion of adults who have a P2 component. For small checks, no recordable signals were obtained for 1-month-old infants. At 3 months, the wave forms of only a small percentage of infants contain a P2 or P3 component. The proportion of infants showing these late positive components increases by 6 months, and at 1 year of age, only 5% of the infant wave forms lack later components. In adults, P2 is always present and, on occasion, is accompanied by P3- Thus, by 1 year of age, the frequency of occurrence of late positive components for large checks is more adult-like than for small checks. Quantitative analyses were carried out on the latency of the Pj component, which was consistently present in the VEP wave form for all age groups. First, the procedure of analysis of variance (ANOVA) for factorial designs was performed on the data from the 2-6-month-old infants to determine whether data for certain conditions could

H U M A N VISUAL DEVELOPMENT AS REFLECTED BY VEP LATENCY C H A N G E S

be combined. This was the age range for which records were obtained at two different distances (75 cm: 15 and 60 min checks; 100 cm: 12 and 48 min checks) and at two different alternation rates (1.88/sec and 3.75/sec). Data for the two small check sizes and for the two large check sizes were compared for each of the two alternation rates. Thus, 4 ANOVAs were carried out: (1) small checks (15 vs. 12 min), slow rate (1.88 alternations/sec); (2) small checks, fast rate (3.75 alternations/sec); (3) large checks (60 vs. 48 min), slow rate; and (4) large checks, fast rate. In each analysis, the dependent variable w a s Pl latency and the independent variables were check size and age. For small checks (15 and 12 min), the results for both alternation rates showed a significant age effect ( P < 0.001) but no effect due to check size and no check size by age interaction. Similarly, for large checks (60 and 48 min) at the 1.88/sec alternation rate there was a significant age effect ( P < 0.001), no effect due to check size and no check size by age interaction. Results of the ANOVA for large checks for 2-, 3- and 4-month-old infants at the 3.75/sec alternation rate, on the other hand, showed significant effects due to both age ( P < 0.001) and check size ( P < 0.025); there was no check size by age interaction, t tests carried out on these data showed that PI latency was significantly longer for 48 min checks than for 60 min checks for 2- and 3-monthold infants ( P < 0.02 and P < 0.05, respectively);

5

there was no significant difference at 4 months of age. Based on the results of the statistical analyses described above, data from the 2-6-month-old infants were combined for the following conditions for each age group: group 1 - - 15 and 12 min obtained at 1.88 alternations/sec; group 2 - 15 and 12 min obtained at 3.75 alternations/sec; and group 3 - - 60 and 48 rain obtained at 1.88 alternations/sec. Due to the significant effect of check size for large checks at 3.75 alternations/sec for 2- and 3-month-old infants, these data were excluded from subsequent statistical analyses. Next, the combined small check data for the two alternation rates (groups 1 and 2 above) were compared using an ANOVA for factorial designs. The dependent variable was Pt latency and the independent variables were alternation rate and age. The results showed a significant effect due to age ( P < 0.001), no effect due to alternation rate and no rate by age interaction. Consequently, data obtained for groups 1 and 2 were combined for each age group. This resulted in two categories of data: latencies obtained for small checks and latencies obtained for large checks. (All subjects older than 6 months of age were tested only with 15 a n d / o r 60 min checks alternating at 1.88/sec.) Mean P~ latency for small checks and large checks is given in Table I for 1-10-month-old infants and in Table II for l-5-year-old children. Fig. 5 shows P~ latency as a function of age

TABLE 1 PI latency (msec) for large and small checks for 1-10-month-old infants. Age Months

1 2 3 4 5 6 7 9 l0

Large checks Weeks

3-6 7 - I0 I 1-14 15-18 19-22 23-27 28- 32 33-37 38-42 43-47

Small checks (15 and 12 min)

(60 and 48 min)

220.5 i 78.1 140.6 119.1 114.3 112.5 l 17.0 113.9 113.9 108.8

S.D.

N

~

32.5 23.8 18.1 7.3 7.6 7.1 8.0 8.5 6.7 3.4

6 33 36 38 24 19 15 8 Il 6

208.0 152.9 143.7 134.5 131.5 129.9 128.0 135.9 135.2

S.D.

N

-

0 2 22 45 59 56 15 8 13 5

9.0 16.6 10.0 7.1 7.2 8.2 18.2 l 1.4

A. M O S K O W l T Z , S. SOKOL

6 T A B L E 11 PI latency (msec) for large and small checks for l-5-year-old children. Large checks (60 and 48 min)

Age Years

Months

1 2 3 4 5

12-23 24-35 36-47 48-59 60-71

Adults (20-25 yrs)

Small checks (15 and 12 rain) S.D.

N

~,

S.D.

N

109.2 108.9 107.1 108.3 108.5

3.8 6.6 5,1 6.1 5.1

20 25 13 19 21

120.1 119.2 t 17.6 116.6 119.1

6.1 6.3 6.0 6.2 6.2

20 25 29 40 43

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76

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76

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Fig. 5. Pn latency as a function of log age for large (left) and small (right) checks. Open circles show mean adult latency± 1 S.D. Hyperbolic curves were fit to the data by the procedure of least squares.

H U M A N VISUAL D E V E L O P M E N T AS R E F L E C T E D BY VEP L A T E N C Y C H A N G E S

(plotted on a logarithmic scale) for large checks (left) and small checks (right) for 439 subjects. Also shown is the mean P] latency for large (48 min) and small (12 min) checks for 76 adults ranging in age from 20 to 50 years obtained under the same stimulus and recording conditions in a previous study (Sokol et al. 1981). Hyperbolic curves were fit to the 1 month to 1 year data points for large checks and for small checks by the procedure of least squares. The asymptotes were determined mathematically for hyperbolic functions (see Lewis 1960, p. 56). For both check sizes, latency decreases rapidly during the first year of life and then gradually levels off. The variance is greatest for the younger infants (also evident in Table I). At all ages, small checks elicit signals with longer latencies than large checks. Fig. 6 shows the two hyperbolic curves and their corresponding equations plotted on the same set of axes. The curve for large checks shows a

220

|

210

7

much steeper decline during the first year of life than the curve for small checks. Also, the two curves reach their asymptotic values of 108 msec for large checks and 118 msec for small checks at different ages. By visual inspection, the large check curve appears to reach an asymptote at about 1 year of age, while the small check curve does not appear to reach an asymptote until about 2-3 years of age. The insert in Fig. 3 shows the log-log plots (i.e., the linear form of a hyperbola) of the two curves. The linear : plots for large and small checks show that latency reaches values which are within 1 msec of the asymptotes of their respective hyperbolic functions at 12 months for large Checks and at 37 months for small checks (dashed lines). A large sample z test for parallelism of slopes (Kleinbaum and Kupper 1978) indicated that the difference between slopes for large checks ( - 2.1339) and small checks ( - 1.3105) was significant (P<0.001). In other words, latency decreased significantly more rapidly for large checks than for small checks during the first year of life. Fig. 7 shows VEP wave forms for checks and stripes obtained from an 18-week-old infant for

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Fig. 6. The two hyperbolic curves fit to the data shown in Fig. 2 and their corresponding equations. The insert shows the log-log plot for each curve.

Fig. 7. VEP wave forms for checks (righ 0 and stripes (left) obtained from an 18-week-old infant. Angular subtense of the pattern elements increases from 7.5 min (top) to 240 rain (bottom). The checks reversed at a rate of 1.88 alternations/sec.

8

A. MOSKOWITZ, S. SOKOL

interaction ( P < 0.05): latency for 15 min checks was longer than latency for 15 min stripes, and the difference lessened with increasing age. For patterns with elements 30 min and larger, there was no effect due to pattern form and no form by age interaction. Thus, the data of Fig. 8 show that for small pattern elements (7.5 and 15 min) latency is significantly longer for checks than for stripes, while for large pattern elements (30 min and greater) there is no difference in latency between checks and stripes. Another way of comparing the data obtained with checks and stripes is based on an analysis of the Fourier components of the pattern stimuli. Kelly (1976) has shown that when check width and bar width (in rmnutes of arc) are equated, the

patterns with elements subtending 7.5-240 min of arc. While a response was obtained from this infant for 7.5 rain stripes, no measurable response was obtained for 7.5 min checks. The response to 15 min stripes has a shorter latency and larger amplitude than the response to 15 min checks. For patterns with larger elements (30-240 rain), no difference is seen between grating and checkerboard pattern VEPs. Fig. 8 shows the mean Pn latency for checks and stripes for the 12 infants tested longitudinally from 1 to 7 months of age. For patterns with 7.5 min elements, responses were not recordable until 3 months of age; for patterns with 15 min elements, responses were recordable by 2 months of age. For patterns with elements 30 min and larger, responses were obtained at all ages. An analysis of variance for factorial designs was performed on the data for each pattern element width; the independent variables were pattern form (checks and stripes) and age, and the dependent variable was Pn latency. Results showed that, for all 6 pattern element widths, there was a significant effect due to age ( P < 0.01 for 7.5 min and P < 0.001 for 15-240 min). For 7.5 rain, the effect of pattern form was significant ( P < 0.01), with checks yielding longer latencies than stripes; there was no form by age interaction. For 15 min, there was a significant effect due to pattern form ( P < 0.001) as well as a significant form by age

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AGE [momhsJ Fig. 8. Mean PI latency for checks (closed circles) and stripes (open circles) for patterns with elements ranging from 7:5 to 240 min for l-7-month-old infants tested longitudinally.

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Fig. 9. Mean P] latency :t: S.E. for 4-6-month-old infants (upper points) plotted as function of the fundamental spatial frequency of the pattern eliciUng the response, Also shown are data obtained from an adult subject. Closed circles represent checks and open circles represent Stripes. Each set of latency data is best fit by a singk function (infants, solid curve; adUlt, dashed curve).

H U M A N VISUAL DEVELOPMENT AS REFLECTED BY VEP LATENCY CHANGES

fundamental spatial frequency of a checkerboard is v~- higher than the fundamental frequency of a square wave grating. Thus, the fundamental frequencies for the stripes and checks used in the present study were (respectively for each pair): 0.125 and 0.175 c / d e g for 240 rain; 0.25 and 0.35 c / d e g for 120 min; 0.5 and 0.7 c / d e g for 60 min; 1.0 and 1.4 c / d e g for 30 rain; 2.0 and 2.4 c / d e g for 15 min; and 4.0 and 5.6 c / d e g for 7.5 min. In Fig. 9, mean P~ latency for 4-6-month-old infants is plotted as a function of the fundamental spatial frequency of the pattern stimulus. Also shown are data from an adult subject. Smooth curves were fit by eye to the latency data for checks and stripes for both the infants (solid curve) and the adult (dashed curve) and show that each set of data is best fit by a single function when the stimuli are expressed in terms of the fundamental frequency (in c / d e g ) rather than in terms of the visual angle of the checks or bars (in min). For both infant and adult subjects, there is no change in latency for spatial frequencies from 0.125 to 0.7 c/deg, a range encompassing 240-60 min checks and stripes. Latency then increases for spatial frequencies from 1.0 to 6 c / d e g , a range encompassing 30-7.5 min checks and stripes. Discussion

Qualitative analysis of the VEP records from 439 infaras and children ranging in age from 1 month to 5 years in response to reversing checkerboard patterns shows that a prominent positive wave occurring between 100 and 200 msec is consistently present at all ages for those check sizes which elicit a response which is recognizably different from activity recorded to visual 'noise.' The frequency of occurrence of later components is more variable, with some subjects showing no late waves, some showing a positive wave occurring between 200 and 300 msec (' P2'), some showing a positive wave occurring later than 300 msec ('P3') and some showing both later positive waves. Generally, the proportion of infants showing these late components increases with age. By 1 year, the frequency of occurrence of later components for large checks is more adult-like than for small checks.

9

The absence of later positive components in the VEP wave form of very young infants may be a reflection of less developed neural processing mechanisms than are present in older subjects. Alternatively, later components may actually be present but with latencies exceeding our 400 msec analysis time. Similarly, the apparent decrease in the frequency of occurrence of P3 and concomitant increase in the frequency of occurrence of P2 evident for large checks between 3 months and 1 year may also be a result of the general shortening of latency which occurs with increasing age: a 3month-old infant's 'P3' may, in actuality, be a long P2. However, the substantial proportion of infants showing both P2 and P3 at 1 year (40%) argues against this interpretation. In adults, a late positive component of the averaged evoked potential at 300-600 msec following stimulus onset occurs in response to novel, infrequent, unexpected or task-relevant stimuli (Sutton et al. 1965; Donchin et al., 1978). This component is often referred to as P300 or P3. Hofmann et al. (1981) recorded averaged evoked potentials from 3-month-old infants and observed an enhancement of the late positive component occurring between 300 and 600 msec following the onset of an infrequently presented stimulus (20% probability of occurrence) over that following a frequentl3/presented stimulus (80% probability of occurrence). Because our stimuli were repetitively presented with a 100% probability of occurrence, we do not believe that the positive wave reported here occurring later than 300 msec, and which we refer to as 'P3,' is the same as the enhanced positive component reported in response to novel stimuli (particularly in light of the fact that very few of the adult subjects showed a P3 component). Quantitative analysis of the latency of the P~ component shows a rapid decrease in latency during the first year of life, followed by a gradual leveling off during childhood. The time course of the latency change differs as a function of check size. At all ages, P~ latency is longer for small checks than for large checks. For large checks, Pi latency reached the adult level at about 1 year of age. The hyperbolic curve fit to our infant data for large checks had its asymptote at 108 msec, which is not significantly

10 different from the mean adult latency for large checks of 106 msec (S.D. = 5.2 msec). For small checks, the curve fit to our infant data reached an asymptotic level of 118 msec at about 2 - 3 years of age. However, this value is still significantly longer than the mean adult latency of 113 msec (S.D. = 6.2 msec) for small checks ( t = -5.070, df= 117, P < 0.001). Indeed, the data points in Fig. 2 (right) show that the majority of 3-5-year-old children (80%) had latencies which were longer than the adult mean (and 38% had latencies more than 1 S.D. longer than the adult mean). Thus, latency for small checks still has not reached adult levels by 5 years of age. To determine the age at which adult levels are finally reached, more children 6 years and older must be tested. In light of data indicating that selective attention influences the amplitude of the VEP (Harter and Previc 1978; Harter and Guido 1980), it is possible that the shorter latency for large checks than for small checks was due to differences in the infants' attention a n d / o r arousal when viewing the different check sizes. However, this is unlikely for several reasons. First, the order of presentation was random for subjects who were tested with both large and small checks; some subjects were tested with large checks first, others with small checks first. Second, fixation was carefully monitored during recording, and there were no noticeable differences between attention to large checks and to small cheeks. Further, VEPs were recorded only when the infant appeared to be attentive; averaging was interrupted when the infant's gaze was not directed toward the stimulus. Finally, while VEP amplitude may fluctuate with changes in the degree of attention or state of arousal, latency is much less affected by such factors. For example, if at certain times during a block of pattern reversals the infant, although apparently fixating, is actually not attending, the activity recorded during the unattended reversals contains either an absent or small amplitude signal. The final averaged wave form reflects this as a reduction in VEP amplitude, but the latency of each of the components of the wave form is not affected. Our results are in general agreement with earlier findings of Sokol and Jones (1979) obtained with a much smaller group of subjects (N = 36), They too

A. MOSKOWITZ, S. SOKOL found that the latency of pattern reversal VEPs for both large and small checks decreased rapidly during the first year of life. For small (15 min) checks, their latency values, like ours, continued to show a gradual decrease up to 5 - 6 years of age. Similarly, Spekreijse (1978) recorded VEPs to pattern onset stimulation and found that latency for small (9 min) checks did not reach adult levels until about t0 years of age. For large checks. however. Sokol and Jones (1979) estimated that adult-like latencies were reached by 4 - 5 months of age, which is earlier than the present finding that the adult level is not reached until about 12 months. In related studies (Sokol et al. 1981: Moskowitz et at. 1982), we have found that latency does not remain at asymptotic values throughout life. P~ latency in adults increases with advancing age, particularly after 50 years, and the rate of change is twice as fast for small checks (12 min) as for large checks (48 min). The present data raise the question of why latency for small pattern elements changes at a slower rate than latency for large pattern elements (see insert of Fig. 6). There are a number of underlying anatomical events following different time courses which take place in the developing infant visual system that may account for this difference. At birth, the infant's foveal cones are immature. It is not until 3 - 4 months of age, the point at which we were first able to record VEPs to small (i.e.. 7.5 mini pattern elements, that the macular cones are nearly mature (Last 1968; Mann 1969; Abramov et al. 1982). At the level of the lateral geniculate nucleus (LGN), Hickey (1977) reported that cells show a rapid increase in size during the first 6 - 1 2 months after birth and that there is a differential rate of growth, with the parvocellular layer developing at a faster rate than the magnoceltular layer. It is not until the end of the second postnatal year that all cells in the LGN have reached their adult size. Magoun and Robb (1981) have recently reported that there are continued increases in myelin in the optic nerve and tract up to 2 years of age, with small increases thereafter. This is contrary to previous reports that optic nerve myelinization is virtually complete by birth (Duke-Elder and Cook 1963) or soon thereafter (Yakovlev and Lecours 1967: Nakayama 1968).

H U M A N VISUAL DEVELOPMENT AS REFLECTED BY VEP LATENCY C H A N G E S

Data from two recent infant studies also relate to the differing time course of anatomical development in the human visual system. Regal (1981) used the forced-choice preferential looking technique (FPL) to trace the development of temporal processing in 1-3-month-old infants and found that critical flicker frequency (CFF) develops rapidly, reaching adult levels by 3 months of age. Moskowitz and Sokol (1980) investigated the development of and interaction between visual processing of temporal and spatial frequency information in 2-6-month-old infants using pattern reversal VEPs and found that the temporal tuning function for large checks (low spatial frequencies) reaches adult levels by 3-4 months of age, while the temporal tuning function for small checks (higher spatial frequencies) develops much more slowly. Also related to our findings is the substantial electrophysiological and anatomical evidence that the visual system of both cat and monkey contains two parallel pathways which process different aspects of the visual environment (Hoffmann et al. 1972; Bunt et al. 1975; Lennie 1980). One, the transient or Y-system, is made up of short latency cells with fast conducting axons and large receptive fields. This system is primarily responsible for the detection of movement and gross patterns. The other, the sustained or X-system, is comprised of long latency cells with slower conducting axons and small receptive fields. This system is found predominantly in the central retina and is believed to be responsible for the discrimination of fine patterns. Psychophysical evidence strongly suggests that these two systems are also present in the human visual system (Keesey 1972; Tolhurst 1973; Breitmeyer and Ganz 1976). It is possible that the absolute latency difference between large and small checks and the differential rate of development of latency to large and small checks is a reflection of the presence of transient and sustained systems in humans. The earlier appearance of short latency VEPs elicited by large pattern elements may reflect the activity of Y-cells and the later appearing, longer latency VEPs elicited by small checks may reflect the activity of X-cells. Typically, VEP studies have yielded higher estimates of visual acuity in infants than behav-

I1

ioral studies. VEP estimates indicate that infants have the equivalent of 20/20 Snellen acuity by 5-6 months of age (Marg et el. 1976; Sokol and Dobson 1976; Sokol 1978), while two recent behavioral studies of acuity, both using operant preferential looking techniques, have found that acuity does not reach adult levels until 4-5 years of age (Birch et al. 1983; Mayer and Dobson 1982). Dobson and Teller (1978) discuss possible reasons for the difference between VEP and behavioral acuity estimates, one being the difference in scoring techniques. For example, in preferential looking studies, a strict criterion of the pattern size required to produce 75~ correct performance by the observer is usually used, while in VEP studies, acuity is usually estimated as the pattern size yielding zero or just above zero VEP amplitude. If, instead, the attainment of adult-like latency values was used as the criterion, VEP acuity estimates would be much lower than those reported previously. The continuing decreases in VEP latency which occur beyond infancy for small checks may provide an electrophysiological correlate for the continuing improvement found in behaviorally determined visual acuity. An advantage of using the VEP to measure the time course of visual development is that the VEP, especially when latency is measured, is less encumbered by attentional, motivational and learning factors which can greatly affect the results of behavioral testing in infants and young children (Bradley and Freeman 1982). The results of our comparison of VEP latencies obtained from 1-7-month-old infants for checks versus stripes show that while there is no significant difference in latency for patterns with large elements (30-240 rain), latency for checks is significantly longer than latency for stripes when small (7.5 and 15 rain) pattern elements are used. These results can be explained on the basis of the fundamental frequency difference between checks and stripes, as illustrated in Fig. 9. The curves, both for infants and for an adult, show that latency is constant up to about 1.0 c / d e g and then increases with increasing spatial frequency. Parker and Salzen (1977a, b) showed a similar increase in the latency of the adult VEP in response to sinusoidal gratings as a function of increasing spatial frequency above 1.0 c/deg.

12

In addition to the spatial frequency difference between the checks and stripes used in the present study, there was also a difference in the orientation of the major Fourier components. The major spatial frequency components of a checkerboard are oriented at 45 ° to the check edges (Kelly 1976). Thus, the checkerboard patterns, which had vertically and horizontally oriented edges, had their major Fourier components at 45 ° and I35 ° , while the major Fourier components of the grating patterns were vertically oriented. Several behavioral studies in infants and children have shown a preference or an increased sensitivity for vertically and horizontally oriented gratings compared with obliquely oriented gratings (Leehey et al. 1975; Bornstein 1978; Gwiazda et al. 1978; Beazley et al. 1982). Similarly, numerous adult studies have shown that psychophysicaUy determined visual sensitivity (see Appelle 1972 for review) and VEP amplitude (Maffei and Campbell 1970; Fiorentini et al. 1972; Frost and Kaminer 1975; May et al. 1979; Zemon et al. 1980) are greater for vertical and horizontal gratings than for obliquely oriented gratings. However, no VEP latency differences have been reported as a function of stimulus orientation. Thus, we conclude that the difference in the orientation of the fundamental Fourier components between the gratings and checkerboards did not contribute to the latency differences we found. In summary, we have collected normative VEP latency data from a large number of subjects (N = 439) ranging in age from 1 month to 5 years. Our results show: (1) that PI, the first major positive component of the VEP wave form, is consistently present at all ages, while the frequency of occurrence of later components is more variable and generally increases with age; (2) that P1 latency decreases rapidly during the first year of life, for both large and small checks; (3) that the time course of the latency change differs as a function of check size, with VEPs to large checks attaining adult latency levels at a much earlier age than VEPs to small checks; and ( 4 ) t h a t for young infants (1-7 months), VEPs to small checks have significantly longer latencies than VEPs to small stripes of the same visual angle, most likely due to the fact that the fundamental spatial frequency is different between the two patterns. These results

A. MOSKOWITZ. S. SOKOL

have important practical implications in the clinical application of VEP latency. When determining the normality or abnormality of a patient's VEP latencms, age, pattern size and pattern type must be taken into account. Patients should always be compared with age-matched normals from whom VEPs were recorded using patterns of similar spatial frequencies. Since VEP latency decreases very rapidly during the first year of life, and since mean latency values are usually used in establishing norms, the age range for normative categories must be very small (i.e.. on the order of a few weeks) to insure that seemingly abnormal latencies are not merely a result of age differences between the patient and the normal control subjects.

Summary Pattern reversal visually evoked potentials (VEPs) were recorded from 439 infants and young children ranging in age from 1 month to 5 years in response to large and small checks. Qualitative analysis of the VEP wave form showed that the first major positive component, P~, is consistently present at all ages, while the frequency of occurrence of later positive components is more variable. The proportion of infants showing late positive components increases with age; by 1 year, the frequency of occurrence of late components for large checks is more adult-like than for small checks. The latency of PI was analyzed quantitatively. Results showed that PI latency decreases rapidly during the first year of life for both large and small checks and that the time course of the latency change differs as a function of check size. VEPs to large checks attain adult-like P~ latency values by about 1 year of age, while the P~ latency of VEPs to small checks has still not reached adult levels by 5 years of age. Data from 12 infants tested longitudinally between 1 and 7 months of age using both checkerboards and square wave gratings show no difference in P~ latency between checkerboards and gratings comprised of large (30-240 min) pattern elements, but for patterns with small (7.5 and 15 min) elements. P~ latency to checks is significantly

HUMAN VISUAL DEVELOPMENT AS REFLECTED BY VEP LATENCY CHANGES l o n g e r t h a n PI l a t e n c y to stripes. T h e s e results are e x p l a i n e d o n the basis of the difference in the f u n d a m e n t a l spatial f r e q u e n c y b e t w e e n checks a n d stripes.

R&sum6

Modifications du d~veloppement du systbme visuel chez l'homme refl~t~es par la latence du potentiel dvoquk visuel ~ une inversion de pattern O n a enregistr~ chez 439 nouveau-n~s et j e u n e s e n f a n t s d o n t l'fige variait de 1 mois /l 5 ans, les p o t e n t i e l s 6voqu6s visuels h une inversion d e p a t tern avec des 6chiquiers/l petites ou g r a n d e s cases. U n e a n a l y s e qualitative de la f o r m e des P E V a m o n t r 6 que la premi6re c o m p o s a n t e positive majeure, P1, est pr6sente de faqon stable ~ t o u s l e s gtges, alors que la fr6quence d ' a p p a r i t i o n des c o m p o s a n t e s positives tardives est plus variable. La p r o p o r t i o n d e nouveau-n6s p r 6 s e n t a n t des c o m p o s a n t e s positives tardives a u g m e n t e avec l'≥ /l 1 an, la fr6quence d~apparition des c o m p o s a n t e s tardives p o u r des 6 c h i q u i e r s / l larges cases est plus p r o c h e de celle des a d u l t e s que p o u r des 6chiquiers /t petites cases. L a latence de P~ a 6t6 analys6e q u a n t i t a t i v e m e n t . Les r6sultats o n t m o n t r 6 que la l a t e n c e de Pl d i m i n u e r a p i d e m e n t p e n d a n t la prem i e r e ann6e, que ce soit p o u r des 6chiquiers /l larges ou petites cases et que le d6cours t e m p o r e l des m o d i f i c a t i o n s de l a t e n c e varie en fonction de la taille des cases. Les PEV a t t e i g n e n t une config u r a t i o n s e m b l a b l e /l celle des a d u l t e s p o u r la l a t e n c e de P~ /l environ 1 an, alors que la latence d e P1 d a n s les P E V / t de petites cases n ' a toujours p a s atteint un niveau a d u l t e / l 5 ans. Les donn6es p r o v e n a n t de 12 nouveau-n6s testb,s l o n g i t u d i n a l e m e n t entre 1 et 7 mois en utilisant des 6chiquiers et des r6seaux rectangulaires o n t m o n t r 6 qu'il n'existe p a s de diff6rence p o u r la l a t e n c e de P~ e n t r e les 6chiquiers et les r6seaux form6s d'616ments larges (30 /l 240 min); m a i s p o u r des p a t t e r n s form6s de petits 616ments ( 7 , 5 / l 15 min), la latence de P~ est significativement plus l o n g u e p o u r l'6chiquier que p o u r les b a n d e s . Ces r6sultats sont interpr~t6s sur la b a s e des diff6rences d a n s la fr6quence spatiale f o n d a m e n tale entre 6chiquier et raies.

13

We would like to thank Dr. V.L. Towle, Dr. Adele Paul, Kathleen Jones and Alice Domar for their assistance in testing subjects.

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