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NICU infants are reported to have diminished social orientation and increased risk of socio-communicative disorders. In this eye tracking study, we used a preference for upright compared to inverted faces as a gauge of social interest in high medical risk full- and pre-term NICU infants. We examined the effects of facial motion and audio-visual redundancy on face and eye/mouth preferences across the first year. Upright and inverted baby faces were simultaneously presented in a paired-preference paradigm with motion and synchronized vocalization varied. NICU risk factors including birth weight, sex, and degree of CNS injury were examined. Overall, infants preferred the more socially salient upright faces, making this the first report, to our knowledge, of an upright compared to inverted face preference among high medical risk NICU infants. Infants with abnormalities on cranial ultrasound displayed lower social interest, i.e. less of a preferential interest in upright faces, when viewing static faces. However, motion selectively increased their upright face looking time to a level equal that of infants in other CNS injury groups. We also observed an age-related sex effect suggesting higher risk in NICU males. Females increased their attention to the mouth in upright faces across the first year, especially between 7-10 months, but males did not. Although vocalization increased diffuse attention toward the screen, contrary to our predictions, there was no evidence that the audio-visual redundancy embodied in a vocalizing face focused additional attention on upright faces or mouths. This unexpected result may suggest a vulnerability in response to talking faces among NICU infants that could potentially affect later verbal and socio-communicative development.

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Arousal effects on a 1-trial visual recognition paired-comparison task were studied at newborn, 1-month, and 4-month test ages. Infants were tested before and after feeding, with arousal assumed to be lower after feeding. Newborns and 1-month-olds shifted from a familiarity preference before feeding to a novelty preference after feeding. A control group tested only after feeding confirmed that this shift was not due to increased stimulus exposure from the prefeeding test. By 4 months, infants showed novelty preferences independent of feeding. This age by arousal interaction for recognition memory extends previous knowledge by including endogenous arousal with age, stimulus, and length of exposure as contributors to familiarity-novelty preferences. It also extends and provides converging evidence for arousal effects on visual attention in early infancy found previously with preferential looking. A shift from subcortical to cortical dominance is supported.

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CNS-compromised neonates are poor modulators tending to prefer less stimulation in all arousal conditions. Cocaine-exposed neonates also are poor modulators but tend to prefer more stimulation in all arousal conditions. Infants (N = 359, M = 4 months) were divided into 6 CNS injury groups and 1 cocaine-exposed, non-CNS-injured group and tested in three arousal conditions: less aroused (after feeding), more around-endogenous (before feeding), and more aroused-exogenous (after feeding with additional stimulation prior to each trial). Infants with CNS injuries still showed some degree of influence of arousal on attention that was now similar to that seen in normal neonates and 1-month-olds, while cocaine-exposed infants, 4-month-old normal and mild or moderate CNS-injury infants did not.

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The organization of arousal and attention as a function of intrauterine cocaine exposure was investigated in 180 normal nursery infants prior to hospital discharge and at 1 month of age. This was done by studying visual looking preferences when infants were in three arousal conditions: less aroused (after feeding); more aroused-endogenous (before feeding); and more aroused-exogenous (after feeding but including 8-Hz visual stimulation prior to each visual preference trial). The stimuli were light panels illuminated at three temporal frequencies between 1 and 8 Hz presented in pairs using a balanced presentation series of trials. Infants not exposed to cocaine demonstrated strong arousal-modulated attention, preferring faster frequencies when less aroused and slower frequencies when more aroused in both endogenous and exogenous conditions. In contrast, cocaine-exposed infants showed a lack of arousal-modulated attention and preferred faster frequencies of stimulation regardless of arousal condition. Similar differences in arousal-modulated attention as a function of cocaine exposure were obtained at 1 month after birth, indicating that these effects lasted longer than would be reasonable to attribute to the active presence of cocaine or its metabolites. This form of stimulus-seeking behavior was shown to be independent of confounding factors associated with prenatal cocaine exposure such as the absence of prenatal care, alcohol use, minority status, or gender, as well as mediating factors associated with growth such as birthweight. A direct and more chronic effect of intrauterine cocaine exposure on arousal-modulated attention and presumably on the developing CNS therefore was supported.

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To assess whether cocaine exposure in utero affected adrenocortical responsiveness in the neonatal period, salivary cortisol levels were compared between noncocaine-exposed (n = 35) and cocaine-exposed (n = 11) healthy preterm infants just prior to hospital discharge. Cortisol levels were measured under three conditions: Basal--120 min after no disrupting event or behavioral distress; Noninvasive Stressor--30 min after a neurobehavioral examination; Invasive Stressor--30 min after a heel-stick procedure. There were no differences in Basal cortisol levels between the noncocaine-exposed and cocaine-exposed infants, but the cocaine-exposed infants had significantly lower levels in both the Noninvasive and Invasive Stressor conditions. The suppressed cortisol responding to stressful events in cocaine-exposed infants suggests that these infants may have decreased modulation capability to normally stressful events, which could underlie some of the subtle state regulation problems reported.

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The relation of fetal growth and maternal oxygen transport as assessed by red blood cell 2,3-diphosphoglycerate, hemoglobin oxygen affinity, hemoglobin, pH, and PCO2 was evaluated in 21 pregnant women. The study was performed in the third trimester and each subject evaluated had sonographic evidence of fetal growth retardation without other obvious abnormalities. Decreased maternal 2,3-diphosphoglycerate/hemoglobin molar ratio and hemoglobin oxygen affinity were related linearly to the birth weight normalized for the expected sea level values of gestational age expressed as a birth weight (gestational age-normalized) Z score. The correlation coefficients and p values were r = 0.71, p less than 0.001 and r = 0.67, p less than 0.001, respectively. The ponderal index-normalized Z score correlated with the 2,3-diphosphoglycerate/hemoglobin molar ratio (r = 0.46, p less than 0.04), but the relation was not as strong as the birth weight-normalized Z score. The crown-heel length/head circumference ratio did not correlate with the 2,3-diphosphoglycerate/hemoglobin molar ratio (r = 0.29, NS). The birth weight (gestational age)-normalized Z score did not correlate with hemoglobin, PCO2, or pH. In the regulation of hemoglobin oxygen affinity, calculations indicated that the 2,3-diphosphoglycerate/hemoglobin molar ratio played a highly significant role (p less than 0.001), pH was minimally significant (p less than 0.025), but PCO2 had little or no significant effects in this study. It appears that fetal growth is related to the maternal red blood cell oxygen transport parameters 2,3-diphosphoglycerate/hemoglobin molar ratio and hemoglobin oxygen affinity. Moreover, the 2,3-diphosphoglycerate/hemoglobin molar ratio is the principal regulator of hemoglobin oxygen affinity.

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The relationship between cranial ultrasonograms (SONOs) and brain-stem auditory evoked responses (BAERs) was evaluated in 2 independent samples of newborn infants at risk for brain injury (n = 113 and 203). Features of the BAER wave forms subjected to stepwise linear discriminant analysis formed the basis of an algorithm used to detect and follow early brain injury. Using this algorithm, information derived from BAERs reliably predicted SONO abnormalities at least 82.3% of the time in the initial study which was replicated with the second sample (77.3%). The wave I component latency (CL) and the wave III-V inter-peak latency interval (IPL) were independent of each other, and both contributed to a prediction of SONO abnormality. Possible mechanisms for these BAER results include compromise to the cochlear membrane or to the auditory nerve itself as well as prolongation of transmission in the brain-stem due to brain-stem hemorrhage, edema, or compression. Normative BAER values and non-linear regression functions for the wave I, III and V CLs, and the I-III, III-V, and I-V IPLs were calculated across age using data from 109 infants who demonstrated normal BAER patterns and had no history of SONO abnormalities. Our analyses indicate BAER techniques, where a single higher intensity is used to produce the BAER wave form, are both valid and efficient for use in the evaluation of early brain injury.

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Eleven rats were subjected to graded compression of the brain stem at the cerebellopontine angle (CPA) following craniectomy and cerebellectomy. Clicks were delivered to the ear contralateral to the compression site, and brain-stem auditory evoked responses (BAER's) were collected before and during compression. With increasing compression, there was an increase in the latency and a decrease in the amplitude of the peaks of the BAER. The later peaks of the BAER (V and VI) demonstrated changes with minimal compression that progressed as compression increased, while changes in the amplitude and latency of the earlier peaks (II, III, and IV) occurred at the higher grades of compression. Following decompression of the brain stem, there was a decrease in the latencies of most of the BAER peaks. Peak amplitude remained depressed following brain-stem decompression. These experimental findings corroborate clinical reports of abnormal BAER's elicited from stimulation of the ear contralateral to a CPA tumor. The relative sensitivity of the later peaks of the BAER to even minimal brain-stem compression explains the prolonged III to V interpeak latency reported in the literature in patients with brain-stem compression from a CPA lesion. The possible mechanisms for the BAER changes that were observed contralateral to compression are discussed.

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An evoked potential (EP) test was developed to aid in the diagnostic evaluation of a 16-week-old infant of initially unknown pathology and degree of perceptual deficit. Patterned stimuli were presented at two repetition rates to challenge the infant's visual and auditory information processing capabilities. The data were compared to those obtained from a "normal" infant of the same age and sex and, where possible, to normative population data. The EP data indicated the following: (1) the "suspect" infant's occipital response to visual pattern was abnormal in terms of waveform characteristics and in the relationship of its amplitude to spatial frequency of pattern; (2) in comparing brain response to 1 Hz and 6 Hz stimulation rates, the "suspect" infant's occipital EPs were abnormally attenuated for the faster presentation rate when a patterned visual display was part of the stimulus complex; (3) an auditory speech sound produced equivalent EP effects in both infants. These data indicated that the "suspect" infant's perceptual deficit was restricted to the processing of visual pattern information, possibly due to abnormal functioning of the geniculo-striate system. Subsequent tests and the diagnosis of ocular albinism corroborated the results of the abnormalities suggested by the EP procedure.

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Multivariate discriminant analysis of brain stem auditory evoked response component latency intervals in patients with cerebellopontine angle tumors allowed accurate detection of 90% (35 of 39) of the tumor population with response data recordable from at least one ear. Eight-five per cent (23 of 27) of these could be detected by using information from the unaffected ear. One of 21 normal subjects was misclassified. Tumors significantly increased the I-III and III-V intervals on the side of the tumor. Increases in III-V interval latency were also observed on the unaffected side. The size of the tumor was significantly correlated with both discriminant scores derived from the analysis of the unaffected ear and delays in the III-V intervals from either the affected or the unaffected ear. These results were attributed to physiological factors and mechanical distortions of the brain stem. Regression equations derived from linear discriminant analysis for cerebellopontine angle tumors are presented and discussed in terms of their predictive validity.

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Preferential looking to stimuli varying in temporal frequency was examined in 11 prematurely born infants (X postconceptional age at testing = 37.6 weeks). The relationship between amount of looking and stimulus frequency yielded a significant linear trend, with the fastest frequency used (4 hertz) being most preferred. The results were interpreted as indicating that the mechanisms underlying temporal preferences differ from those underlying spatial preferences.

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