Nellie K. Laughlin

Effects of perinatal PCB exposure on discrimination-reversal learning in monkeys

Monkeys exposed to PCB mixtures during gestation and lactation were tested on two-choice discrimination-reversal learning (DR). In Experiment 1, offspring of mothers fed 1.0 ppm Aroclor 1248, and offspring born 1.5 years after maternal exposure to 2.5 ppm Aroclor 1248 ended did not differ from controls on spatial, color or shape DR problems. In Experiment 2, offspring of mothers fed 0.25 or 1.0 ppm Aroclor 1016 and offspring born 3 years after maternal exposure to 2.5 ppm Aroclor 1248 ended were tested on the same spatial, color and shape problems, but a spatial problem with color and shape as irrelevant cues was inserted after the initial spatial problem. Performance of the high dose Aroclor 1016 offspring was impaired on the initial spatial problem, and facilitated on the shape problem. Performance of the Aroclor 1248 postexposure offspring was facilitated on the shape problem. This apparently facilitatory effect may represent a failure of PCB-exposed monkeys to learn the irrelevancy of the shape cue when it was initially presented.

The effects of lead on otoacoustic emissions and auditory evoked potentials in monkeys

Auditory functioning was assessed in two groups of adult rhesus monkeys (11 years of age). One (n = 11) received modest exposure to lead early in life and the other (n = 8) served as controls and did not receive any lead supplementation. Two lead-exposed monkeys had abnormal distortion product otoacoustic emissions (DPEs) and smaller amplitude or absent evoked potentials. These monkeys had abnormal distortion product otoacoustic emission (DPEs) and smaller amplitude or absent evoked potentials. These monkeys had the highest blood levels recorded in their respective groups. For the remaining lead-exposed monkeys there was little difference between their DPEs and the DPEs of the control monkeys with one exception. DPE amplitudes of the control monkeys increased more rapidly as a function of stimulus level than those of the lead-exposed monkeys at most frequencies. There was also a significant but modest effect of lead exposure on the auditory brain stem evoked responses (ABRs) of these lead-exposed monkeys. There was no apparent effect on the middle latency evoked responses (MLRs), although that result could be due to the relatively greater variability of the MLR.

Lead exposure and diet: Differential effects on social development in the rhesus monkey

Infant rhesus monkeys ingested 0 or 1.0 mg/kg lead acetate daily from birth to one year postpartum in dietary milk. Half the monkeys in each group were offered milk ad lib, and half were given restricted quantities. Chow was available ad lib to all monkeys. Groups of 4 monkeys interacted for 1.5 h/day, 5 days/week beginning at approximately 2 months of age. The social sessions were moved to a larger arena at about 9 months postpartum. Ongoing behavior was observed during social sessions twice weekly beginning at about 3 months of age for 28 weeks, and again beginning at about 16 months of age for 11 weeks. Play behaviors were particularly susceptible to lead; social play was more severely disrupted than nonsocial play. Lead suppressed play in both test environments during the first year postpartum while self-stimulation and fearful behaviors increased. Lead-associated alterations in behavior were still present several months following termination of lead intake. Restriction of milk resulted in increased chow consumption but had little impact on behavior. Effects of lead may have been more profound in monkeys maintained on the restricted milk diet than in monkeys given milk ad lib.

Categorical perception for voicing contrasts in normal and lead-treated rhesus monkeys: Electrophysiological indices

Categorical perception of voicing contrasts was evaluated in rhesus monkeys. The monkeys had been chronically exposed to subclinical levels of lead either from conception to birth, or for approximately 6 months postnatally beginning at birth, or were never exposed to lead. Auditory evoked responses were recorded at 1 year of age from scalp electrodes placed over the left and right hemispheres during stimulus presentation. A late component of the brain responses recorded from the right temporal region of all monkeys discriminated between stimuli in a categorical manner. This pattern of responses was noted to be similar to that previously reported for humans. Categorical discriminations were also noted earlier in the waveforms for control monkeys and for monkeys exposed to lead prenatally, although this discrimination pattern shifted to the left hemisphere of the latter group. No such effects were noted for monkeys exposed to lead postnatally. These results suggest that the neurocortical mechanisms associated with categorical perception for voicing information may be similar across human and nonhuman primates. However, early exposure to lead appears to alter these processes.

Early undernutrition and later hippocampal damage: Effects on spontaneous behaviors and reversal learning

Rats from dams that were well fed or underfed (50% food reduction) during lactation received either large lesions of the dorsal hippocampus or sham operations at 60 days of age. The animals then were tested for open-field behavior, spontaneous alternation, spontaneous exploration, and spatial discrimination reversal learning. Main effects of nutrition were found in the open field and on the spatial learning and reversal tasks, as well as in body weight, eye opening, and time of appearance of body hair. Significant lesion effects were found in the open field and on spontaneous alternation and reversal learning. In contrast to two earlier studies, early diet had little effect on the response to later brain damage. These data show that the finding that early diet can affect the behavioral response to focal brain damage later in life may not generalize across all experimental conditions.

Neurobehavioral Consequences of Early Exposure to Lead in Rhesus Monkeys: Effects on Cognitive Behaviors

The present paper reports on a series of studies of rhesus monkeys exposed to low levels of lead administered daily throughout the first year of life. These lead-treated monkeys have provided an animal model directed at understanding childhood lead toxicity. The results to be described here focus on a cognitive test paradigm, reversal learning (RL), in which a reliable, lead-associated performance deficit was elicited and studied in several successive experiments. The emphasis of this report is on investigations of the RL test procedure designed to discover task parameters which elicited, enhanced, or sustained the lead-associated RL deficit, and which might identify the nature of the cognitive dysfunction responsible for the deficit.

Auditory evoked brainstem and middle latency responses in Macaca mulatta and humans

Early (ABRs) and middle (MLRs) surface-recorded auditory evoked potentials were compared in eight adult monkeys (Macaca mulatta) and eight adult humans. Responses whose probable generators were the cochlear nucleus and lateral lemniscus were of shorter latency and larger amplitude in monkeys. Relative to humans, ABR response latencies in monkeys were less affected by stimulus intensity, stimulus rate, and masker level. In contrast, monkey amplitudes were relatively more affected by those same stimulus parameters. The most prominent MLR wave was longer in latency and greater in amplitude in humans than the homologous wave in monkeys. The reduction in amplitude of that wave with increasing rate was greater for humans than monkeys. Temporal interactions (the effect of prior stimuli on the response to current stimulation) were investigated from a non-linear systems identification framework using maximum length sequences (MLSs). Both monkey and human auditory systems were second and probably third-order systems at the levels assessed. As the separations between the stimulus pulses decreased, evidence for temporal interactions became more prominent, reached a maximum, and then decreased with further decreases in stimulus pulse separation. At the highest stimulus rates presented, variations in temporal spacing among stimuli had less of an effect on monkey than human evoked responses.

The effects of early lead exposure on auditory function in rhesus monkeys

Thirty-one female rhesus monkeys were randomly assigned to three lead exposure conditions (none, birth to 1 year, and birth to 2 years). Blood lead levels were maintained at 35-40 microg/dl beginning shortly after birth and continuing for 1 or 2 years postnatally. Auditory function was assessed in these monkeys at least 1 year after exposure to lead. The outcome measures included tympanometry to assess middle ear function, otoacoustic emissions (OAEs) to assess cochlear function, and auditory brainstem-evoked responses (ABRs) to assess the auditory nerve and brainstem pathways. There were no significant differences among the three experimental groups for any of the tympanometric variables measured suggesting no effect of lead exposure on middle ear function. Suprathreshold and threshold distortion product OAEs (DPOAEs) were comparable among the three groups. Finally, the auditory-evoked response at levels from the auditory nerve to the cerebral cortex did not significantly differ as a function of lead exposure. The lead exposure in this study had little effect on auditory function.

Otoacoustic emission, evoked potential, and behavioral auditory thresholds in the rhesus monkey (Macaca mulatta).

Distortion product otoacoustic emission (DPOAE), auditory brainstem evoked response (ABR), and behavioral thresholds were recorded in a group of 15 adult rhesus monkeys with normal auditory function. DPOAE thresholds were recorded with stimulus parameters selected to maximize signal-to-noise ratio. Additional averaging at the lowest frequencies ensured comparable noise levels across frequencies. DPOAE thresholds decreased with increasing frequency (f(2)=0.5-16 kHz) and at 16 kHz were close to 0 dB SPL. ABR thresholds were best from 1 through 16 kHz (32-38 dB peSPL); higher at 0.5 (45 dB peSPL), 24 (39 dB peSPL), and 30 kHz (49 dB peSPL). At all levels including threshold, the early ABR waves (II and I) were more prominent at the high frequencies while the later waves (IV and V) were more prominent at the low frequencies. The behavioral thresholds recorded were similar to those reported by other researchers although elevated by about 10 dB presumably because of the complexity of the threshold task. DPOAE and ABR thresholds can be reliably and efficiently recorded in the rhesus monkey and provide information concerning site of processing in the auditory pathway not directly available from behavioral data.

The development of auditory event related potentials in the rhesus monkey (Macaca mulatta)

Auditory event related potentials were recorded from neonatal, 3-month, and 3-year old rhesus monkeys. Auditory brainstem evoked responses (ABRs) were reliably recorded at all ages. ABR latencies decreased with age. Age effects were greater the more centrally generated the wave. Wave I amplitude decreased with age, Wave II increased, and Wave IV remained about the same. Stimulus rate effects were greater in neonates than older monkeys. Stimulus frequency also affected the ABR, but not differentially as a function of age. Recording montage had a significant effect on the recorded waveform. Wave I tended to be larger in amplitude in horizontal recordings and front-back recordings, while the later waves were relatively more prominent in more vertical montages. Middle latency evoked responses and late potentials were less reliably recorded than the ABR. Their reproducibility improved with age. Auditory event related potentials are promising measures of auditory function for research requiring nonhuman primate models of the developing human.