Perceptiial and Moior Skills, 1976,43, 315-322. @ Perceptual and Motor Skills 1976 EFFECTS OF POSTNATAL STRESS ON VISUAL AND AUDITORY EVOKED POTENTIALSt
Mt.
CLARA TORDA School of Medicin2
Sinai
Summary.-Maturation of visual and auditory evoked potentials (mainly the Ps wave) of 10 controls and of 10 infants exposed to recurrent pstaaml stressful events (crying spells lacking organic basis) have been compared. The course of maturation of P3 waves may serve as indicator of growth and nature of cognitive processes (including perception). Recurrent crying spells seemed to delay appearance of visual P3 wave, prolonged its latency, and delayed appearance of visible differences in the shape of visual Pa wave upon exposure of the subjects to different visual experiences. A compensatory increase of maturation of the auditory Ps wave appeared. The results suggest that recurrent exposure to stressful events during the early postnatal period may delay the ability of the infant to use visual perception to register exogenous events and may create memory banks of auditory engrams with unusual contents (including memory traces of stresses), a potential basis for future auditory hallucinations. According to current concepts infants depend heavily o n hearing for perception of environmental stimuli during the first three postnatal months ( 1 2 ) . Perception through a sensory modality requires presence of a minimum memory bank of engrams of the same sensory modality, and intrauterine life permits only accumulation of auditory, not visual, engrams ( 1 6 ) . Accumulation of the minimum sufficient memory bank of visual engrams seems to require about 3 mo. i n infants under optimum conditions and coincides with substitution of a n adult-type of REM sleep for the neonatal type ( 1 2 ) . Present work attempted to ascertain whether substitution of visual perception for audicory is fully dependent o n a preprogrammed genetic process engrammed at birth o r also depends on postnaral processes that require mechanisms of intact and undisturbed cerebral functions, e.g., peace of mind, energy, etc. T h e process of maturation of visual and auditory cognitive processes (including perception) may be assayed by measurements of the latency and amplitude of the Ps wave of audicory and visual evoked potentials ( 3 , 7 , 16, 1 9 ) . T h e auditory and visual evoked potentials undergo an engrarnmed, species-dependent mat~uationconsisting of decreased latency of t h e various peaks and changes (increase in amplitude and complexity) of wave forms ( 1, 9, 11). T h e latency of the P3 waves averages 300 msec. (Fig. 3 ) in the adult. T h e auditory Pa peak usually becomes first detectable during the second postnatal week with a latency of over 800 msec. and the visual P3 peak becomes first measurable during the 'Presented at the First World Congress of Biological Psychiatry, September, 1974, Buenos Aires, Argentina. '10 E 100 Street, New York, N. Y. 10029.
3 16
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third week of life with a latency of about 800 msec. Animal experiments showed that auditory evoked potentials mature faster than visual ones (5, 14) and that exposure to recurrent postnatal stresses of special nature may delay the maturation of visual evoked potentials ( 15 ) . Attempts were made, therefore, to ascertain whether exposure to recurrent postnatal stressful events may significantly delay the early phases of maturation of the P3 wave of visual evoked potentials. Such delay may lead, theoretically, to accumulation of un,uual auditory memory engrams, a process that may precondition for auditory hallucinations. Naturally, every effort was made to avoid introduction of any stress into the life of infants. In the nurseries of large city hospitals several babies had been located, however, who lacked organic symptomatology (detectable by available clinical methods), but had a habit of crying daily, as much as half an hour before food intake. These crying spells are considered dinically to be stressful experiences of unknown etiology. Therefore, the maturation of the P3 wave of auditoty and visual evoked potentials of these infants and controls with uneventful growth were compared.
METHOD Subjects Twenty full-term neonates served as subjects. Ten subjects displayed recurrent crying spells, sometimes for half an hour before food intake. All available clinical tests failed to reveal any organic reason. These babies required prolonged feeding time to consume an adequate amount of nourishment. In spite of this, weight gain remained significantly below normal by the end of the third month of life. Ten subjects without somatic or behavioral difficulties served as controls. All infants were born to healthy parents of middle-class background. Boys and girls were nearly equally represented. All infants seemed to perform comparably well on functional and psychological tests 3 yr. later, without any symptom of cerebral malfunction, and had IQs above 110. Experimental Procedwes (3, 6, 18, 19) Between the second or third postnatal day and the end of the fourth month visual and auditory evoked potentials were recorded once a week. Each infant was held in the mother's lap in a soundproof insulated dark chamber of the research laboratory. During sleep, electrodes were fixed to the skull. Evoked potentials were recorded during wakefulness. In instances of crying data were discarded and the tests were repeated the next day. Electrodes.-Silver disk surface electrodes were fastened 2 cm above the inion, one electrode over the vertex. The reference electrode was fastened to one earlobe, the ground electrode above the top of the spine (back of the neck). Visual stimulatio7z.A white board of 150 cm2 area served as blank and a similar white board with a black circle of approximately 25 cm2 area painted at its
EFFECTS OF POSTNATAL STRESS ON EVOKED POTENTIALS
317
center served as stimulus. The boards were placed in a horizontal position approximately 40 cm from the infant's face and with the center of the board above the infant's eye. The boards were illuminated by Ionix flash units placed on the floor. Silent flashes were produced by a square wave of 20 msec. duration at 20 V, at a rate of one per 3 sec. This rate was chosen as the most likely to evoke a response ( 4 ) . At the plane of the white board the light intensity was 0.585 lu/m2. Twenty-five flashes were delivered during the exposure of the neonate to the blank or to the circle. The two boards were alternated following a Latin square design. The brain waves obtained during exposure of one type of stimulus were amplified by means of a Grass polygraph (Model 7 ) and the waves were fed into one or the other channel of a Computer of Average Transients (Mnemotron CAT 400). Depending on the tolerance of the neonate 25 to 100 flashes were three times alternated with 5-min. rest periods. Auditory stimulatiort.-Two pure tones ( 1,000 and 2,000 cycles per second) of 20 msec. duration were delivered once during 3 sec. The tone was generated by a Peekel electronic oscillator (Type 013 V ) and was amplified by a Philips loudspeaker (Type Ad 3800), suspended about 40 cm above the head of the infant. The sound generator was calibrated with a General Radio Sound Pressure Meter (Type 1881 A) to give a sound of 60 db above the background noise. Whenever possible, three groups of 65 pulses were alternated with a 5-min. rest period. Since the first 40 auditory evoked potentials (AEPs) may have been contaminated with waves of myogenic origin ( 8 ) , only the responses to the last 25 pulses were fed through the Grass amplifier to the CAT computer. Culcalation.-The averages of the responses to about 60 light flashes or 5 sound series of the same nature were displayed on an oscilloscope and were photographed. The statistical significance of the differences observed between the responses of controls and subjects with crying spells to the same type of stimuli were evaluated following two-tailed Wilcoxon matched-pairs signed-ranks tests ( 13). RESULTSAND DISCUSSION Visuul Evoked Pote~ztiuls(VEP) The average of VEPs obtained during the second or third postnatal days from controls and subjects with crying spells were similar and resembled in latency and wave-amplitudes the data reported in the literature ( 1, 5, 11 ) . For records of controls by the end of the third month the latency of P2 wave averaged 100 msec. The P3 peak became measurable by the end of the first month. At the end of the third month the latency of the Pa wave still exceeded 460 msec. The peak-latency decreased and the peak-amplitude increased (Fig. 1, Table 1) . The shape of the P3-N4 wave complex of the responses elicited by the blank and the circle started to differ by the end of the third postnatal month (Fig. 2 ) . For records of infants with crying spells the P3 peak became measurable only during the second or third postnatal month. Differences in the shape of the Pa
C TORDA
L
FIG. 1. Visual and auditory evoked potentials from maturing humans. (Mean of 10 control newborns and 10 babies with recurrent crying spells) : ( A ) Visual Evoked Potentials (VEP) are (X) Records taken from 10 control babies-[Dotted Line: Mean evoked potential taken during the second or third postnatal day h,n u , p, are peaks ( p u guessed). m, p, nu not marked; Solid Line: average of visual evoked potentials taken from the 10 infants at che end of the third postnatal month. Peaks marked: N1, PI, Na, P2, N3, Pa.] ( Y ) Records taken from infants with recurrent crying spellsDotted Line: VEPs recorded during the second or third postnatal days ( 1 0 infants) : b,nln are peaks; nl, p,nu peaks are not marked; pu not yet detectable. Solid Line: Average of VEP recorded from the 10 infants at the end of the third postnatal month. N1, PI, N1,P2, NJ, P3, N, mark peaks. (B) Auditory Evoked Potentials (AEP) are ( x ) Records taken from controls-Dotted Line: records taken at the end of the first postnatal week. Solid Line: average of AEP of 10 infants. Records taken at the end of third Line: average of month. ( y ) Records taken from infants with crying spells-Dotted AEP of 10 subjects, recorded at end of first week of life. Solid Line: Average of AEP of 10 infants recorded at end of third postnatal month. Horizontal bar: 100 msec. Vertical bar: 5pV
FIG. 2. Changes in the shape of visual Pa wave with age: (1) Visual evoked potential recorded from neonates with recurrent crying spells: row 1 shows VEP averaged during exposure to a blank; row 2 shows VEP averaged during exposure to a circle. (Horizontal bar: 1100 msec., verricle bar: 1 pV; 2 or 3 superimposed records taken the beginning of the fifth month from one neonate. The records were representative for the other neonates.) (2) Visual evoked potential recorded from a control neonate: row 1 shows VEP averaged during exposure to a blank; row 2, VEP averaged during exposure to a circle. (Horizontal bar: GOO msec., vertical bar: 2 pV; 2 or 3 superimposed records taken during the fourth month of postnatal life from one neonate. The records were representative for other neonate controls. )
EFFECTS OF POSTNATAL STRESS O N EVOKED POTENTIALS
319
TABLE 1 MEANS ( k SE OF MEAN)SHOWING hfATUUTION OF VISUALAND AUDITORY EVOKED POTENTIALS IN HLMAN INFANT Evoked Peak Exp. Potentials (n) D,Y 2 or 3
MO. 1
Postnatal Age Mo. 2
Mo. 3
Mo. 4
Latency (msec.) Visual Evoked Potentials Control Pa 10' 190219.5 Crying Pa 10 189f 18.7 Control Pa 10 Crying Pa 10 Auditory Evoked Potentials Control P. 10 185211.3 Crying Pa 10 184212.2 Control Pa 10 Crying Pa 10
8 5 k 8.8 90211.1 220215.5 2002 8.5
550220.2 1 5602 9.8 Amplitude (pV)
Visual Evoked Potential Control PrNa 10 5.0k1.0 Crying P r N l 10 6.9f 1.7 Control Pa-NI 10 Crying Pa-N, 10 Auditory Evoked Potentials Control PaNs 10 5.121.5 Crying PaNa 10 5.521.9 Control Pa-N. 10 Crying Pa-NI 10 *Mean of 3 values/exp., 10 infants= 3 x 10 values. t55% higher amplitude in crying infant (increase, P 0.005). $Crying infant had 56% longer latency (difference, P 0.001 ). §Crying infant had a 33% lower amplitude (difference, P 0.001).
<
Mt.
CLARA TORDA School of Medicin2
Sinai
Summary.-Maturation of visual and auditory evoked potentials (mainly the Ps wave) of 10 controls and of 10 infants exposed to recurrent pstaaml stressful events (crying spells lacking organic basis) have been compared. The course of maturation of P3 waves may serve as indicator of growth and nature of cognitive processes (including perception). Recurrent crying spells seemed to delay appearance of visual P3 wave, prolonged its latency, and delayed appearance of visible differences in the shape of visual Pa wave upon exposure of the subjects to different visual experiences. A compensatory increase of maturation of the auditory Ps wave appeared. The results suggest that recurrent exposure to stressful events during the early postnatal period may delay the ability of the infant to use visual perception to register exogenous events and may create memory banks of auditory engrams with unusual contents (including memory traces of stresses), a potential basis for future auditory hallucinations. According to current concepts infants depend heavily o n hearing for perception of environmental stimuli during the first three postnatal months ( 1 2 ) . Perception through a sensory modality requires presence of a minimum memory bank of engrams of the same sensory modality, and intrauterine life permits only accumulation of auditory, not visual, engrams ( 1 6 ) . Accumulation of the minimum sufficient memory bank of visual engrams seems to require about 3 mo. i n infants under optimum conditions and coincides with substitution of a n adult-type of REM sleep for the neonatal type ( 1 2 ) . Present work attempted to ascertain whether substitution of visual perception for audicory is fully dependent o n a preprogrammed genetic process engrammed at birth o r also depends on postnaral processes that require mechanisms of intact and undisturbed cerebral functions, e.g., peace of mind, energy, etc. T h e process of maturation of visual and auditory cognitive processes (including perception) may be assayed by measurements of the latency and amplitude of the Ps wave of audicory and visual evoked potentials ( 3 , 7 , 16, 1 9 ) . T h e auditory and visual evoked potentials undergo an engrarnmed, species-dependent mat~uationconsisting of decreased latency of t h e various peaks and changes (increase in amplitude and complexity) of wave forms ( 1, 9, 11). T h e latency of the P3 waves averages 300 msec. (Fig. 3 ) in the adult. T h e auditory Pa peak usually becomes first detectable during the second postnatal week with a latency of over 800 msec. and the visual P3 peak becomes first measurable during the 'Presented at the First World Congress of Biological Psychiatry, September, 1974, Buenos Aires, Argentina. '10 E 100 Street, New York, N. Y. 10029.
3 16
C TORDA
third week of life with a latency of about 800 msec. Animal experiments showed that auditory evoked potentials mature faster than visual ones (5, 14) and that exposure to recurrent postnatal stresses of special nature may delay the maturation of visual evoked potentials ( 15 ) . Attempts were made, therefore, to ascertain whether exposure to recurrent postnatal stressful events may significantly delay the early phases of maturation of the P3 wave of visual evoked potentials. Such delay may lead, theoretically, to accumulation of un,uual auditory memory engrams, a process that may precondition for auditory hallucinations. Naturally, every effort was made to avoid introduction of any stress into the life of infants. In the nurseries of large city hospitals several babies had been located, however, who lacked organic symptomatology (detectable by available clinical methods), but had a habit of crying daily, as much as half an hour before food intake. These crying spells are considered dinically to be stressful experiences of unknown etiology. Therefore, the maturation of the P3 wave of auditoty and visual evoked potentials of these infants and controls with uneventful growth were compared.
METHOD Subjects Twenty full-term neonates served as subjects. Ten subjects displayed recurrent crying spells, sometimes for half an hour before food intake. All available clinical tests failed to reveal any organic reason. These babies required prolonged feeding time to consume an adequate amount of nourishment. In spite of this, weight gain remained significantly below normal by the end of the third month of life. Ten subjects without somatic or behavioral difficulties served as controls. All infants were born to healthy parents of middle-class background. Boys and girls were nearly equally represented. All infants seemed to perform comparably well on functional and psychological tests 3 yr. later, without any symptom of cerebral malfunction, and had IQs above 110. Experimental Procedwes (3, 6, 18, 19) Between the second or third postnatal day and the end of the fourth month visual and auditory evoked potentials were recorded once a week. Each infant was held in the mother's lap in a soundproof insulated dark chamber of the research laboratory. During sleep, electrodes were fixed to the skull. Evoked potentials were recorded during wakefulness. In instances of crying data were discarded and the tests were repeated the next day. Electrodes.-Silver disk surface electrodes were fastened 2 cm above the inion, one electrode over the vertex. The reference electrode was fastened to one earlobe, the ground electrode above the top of the spine (back of the neck). Visual stimulatio7z.A white board of 150 cm2 area served as blank and a similar white board with a black circle of approximately 25 cm2 area painted at its
EFFECTS OF POSTNATAL STRESS ON EVOKED POTENTIALS
317
center served as stimulus. The boards were placed in a horizontal position approximately 40 cm from the infant's face and with the center of the board above the infant's eye. The boards were illuminated by Ionix flash units placed on the floor. Silent flashes were produced by a square wave of 20 msec. duration at 20 V, at a rate of one per 3 sec. This rate was chosen as the most likely to evoke a response ( 4 ) . At the plane of the white board the light intensity was 0.585 lu/m2. Twenty-five flashes were delivered during the exposure of the neonate to the blank or to the circle. The two boards were alternated following a Latin square design. The brain waves obtained during exposure of one type of stimulus were amplified by means of a Grass polygraph (Model 7 ) and the waves were fed into one or the other channel of a Computer of Average Transients (Mnemotron CAT 400). Depending on the tolerance of the neonate 25 to 100 flashes were three times alternated with 5-min. rest periods. Auditory stimulatiort.-Two pure tones ( 1,000 and 2,000 cycles per second) of 20 msec. duration were delivered once during 3 sec. The tone was generated by a Peekel electronic oscillator (Type 013 V ) and was amplified by a Philips loudspeaker (Type Ad 3800), suspended about 40 cm above the head of the infant. The sound generator was calibrated with a General Radio Sound Pressure Meter (Type 1881 A) to give a sound of 60 db above the background noise. Whenever possible, three groups of 65 pulses were alternated with a 5-min. rest period. Since the first 40 auditory evoked potentials (AEPs) may have been contaminated with waves of myogenic origin ( 8 ) , only the responses to the last 25 pulses were fed through the Grass amplifier to the CAT computer. Culcalation.-The averages of the responses to about 60 light flashes or 5 sound series of the same nature were displayed on an oscilloscope and were photographed. The statistical significance of the differences observed between the responses of controls and subjects with crying spells to the same type of stimuli were evaluated following two-tailed Wilcoxon matched-pairs signed-ranks tests ( 13). RESULTSAND DISCUSSION Visuul Evoked Pote~ztiuls(VEP) The average of VEPs obtained during the second or third postnatal days from controls and subjects with crying spells were similar and resembled in latency and wave-amplitudes the data reported in the literature ( 1, 5, 11 ) . For records of controls by the end of the third month the latency of P2 wave averaged 100 msec. The P3 peak became measurable by the end of the first month. At the end of the third month the latency of the Pa wave still exceeded 460 msec. The peak-latency decreased and the peak-amplitude increased (Fig. 1, Table 1) . The shape of the P3-N4 wave complex of the responses elicited by the blank and the circle started to differ by the end of the third postnatal month (Fig. 2 ) . For records of infants with crying spells the P3 peak became measurable only during the second or third postnatal month. Differences in the shape of the Pa
C TORDA
L
FIG. 1. Visual and auditory evoked potentials from maturing humans. (Mean of 10 control newborns and 10 babies with recurrent crying spells) : ( A ) Visual Evoked Potentials (VEP) are (X) Records taken from 10 control babies-[Dotted Line: Mean evoked potential taken during the second or third postnatal day h,n u , p, are peaks ( p u guessed). m, p, nu not marked; Solid Line: average of visual evoked potentials taken from the 10 infants at che end of the third postnatal month. Peaks marked: N1, PI, Na, P2, N3, Pa.] ( Y ) Records taken from infants with recurrent crying spellsDotted Line: VEPs recorded during the second or third postnatal days ( 1 0 infants) : b,nln are peaks; nl, p,nu peaks are not marked; pu not yet detectable. Solid Line: Average of VEP recorded from the 10 infants at the end of the third postnatal month. N1, PI, N1,P2, NJ, P3, N, mark peaks. (B) Auditory Evoked Potentials (AEP) are ( x ) Records taken from controls-Dotted Line: records taken at the end of the first postnatal week. Solid Line: average of AEP of 10 infants. Records taken at the end of third Line: average of month. ( y ) Records taken from infants with crying spells-Dotted AEP of 10 subjects, recorded at end of first week of life. Solid Line: Average of AEP of 10 infants recorded at end of third postnatal month. Horizontal bar: 100 msec. Vertical bar: 5pV
FIG. 2. Changes in the shape of visual Pa wave with age: (1) Visual evoked potential recorded from neonates with recurrent crying spells: row 1 shows VEP averaged during exposure to a blank; row 2 shows VEP averaged during exposure to a circle. (Horizontal bar: 1100 msec., verricle bar: 1 pV; 2 or 3 superimposed records taken the beginning of the fifth month from one neonate. The records were representative for the other neonates.) (2) Visual evoked potential recorded from a control neonate: row 1 shows VEP averaged during exposure to a blank; row 2, VEP averaged during exposure to a circle. (Horizontal bar: GOO msec., vertical bar: 2 pV; 2 or 3 superimposed records taken during the fourth month of postnatal life from one neonate. The records were representative for other neonate controls. )
EFFECTS OF POSTNATAL STRESS O N EVOKED POTENTIALS
319
TABLE 1 MEANS ( k SE OF MEAN)SHOWING hfATUUTION OF VISUALAND AUDITORY EVOKED POTENTIALS IN HLMAN INFANT Evoked Peak Exp. Potentials (n) D,Y 2 or 3
MO. 1
Postnatal Age Mo. 2
Mo. 3
Mo. 4
Latency (msec.) Visual Evoked Potentials Control Pa 10' 190219.5 Crying Pa 10 189f 18.7 Control Pa 10 Crying Pa 10 Auditory Evoked Potentials Control P. 10 185211.3 Crying Pa 10 184212.2 Control Pa 10 Crying Pa 10
8 5 k 8.8 90211.1 220215.5 2002 8.5
550220.2 1 5602 9.8 Amplitude (pV)
Visual Evoked Potential Control PrNa 10 5.0k1.0 Crying P r N l 10 6.9f 1.7 Control Pa-NI 10 Crying Pa-N, 10 Auditory Evoked Potentials Control PaNs 10 5.121.5 Crying PaNa 10 5.521.9 Control Pa-N. 10 Crying Pa-NI 10 *Mean of 3 values/exp., 10 infants= 3 x 10 values. t55% higher amplitude in crying infant (increase, P 0.005). $Crying infant had 56% longer latency (difference, P 0.001 ). §Crying infant had a 33% lower amplitude (difference, P 0.001).
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