Electrophysiological responses to auditory novelty in temperamentally different 9-month-old infants.

Behavioral reactivity to novel stimuli in the first half-year of life has been identified as a key aspect of early temperament and a significant precursor of approach and withdrawal tendencies to novelty in later infancy and early childhood. The current study examines the neural signatures of reactivity to novel auditory stimuli in 9-month-old infants in relation to prior temperamental reactivity. On the basis of the assessment of behavioral reactivity scores at 4 months of age, infants were classified into groups of high negatively reactive and high positively reactive infants. Along with an unselected control group, these groups of temperamentally different infants were given a three-stimulus auditory oddball task at 9 months of age which employed frequent standard and infrequent deviant tones as well as a set of complex novel sounds. In comparison to high positively reactive and control infants, high negatively reactive infants displayed increased amplitude of a positive slow wave in the ERP response to deviant tones compared to standard tones. In contrast, high positively reactive infants showed a larger novelty P3 to the complex novel sounds. Results are discussed in terms of optimal levels of novelty for temperamentally different infants.

Effects of early intervention on EEG power and coherence in previously institutionalized children in Romania.

Two groups of Romanian children were compared on spectral power and coherence in the electroencephalogram (EEG) in early childhood. One group consisted of previously institutionalized children who had been randomly assigned to a foster care intervention at a mean age of 23 months. The second group had been randomized to remain in institutional care. Because of a policy of noninterference, a number of these children also experienced placement into alternative family care environments. There were minimal group differences between the foster care and institutionalized groups in EEG power and coherence across all measured frequency bands at 42 months of age. However, age at foster care placement within the foster care group was correlated with certain measures of EEG power and coherence. Earlier age at foster care placement was associated with increased alpha power and decreased short-distance EEG coherence. Further analyses separating age at placement from duration of intervention suggest that this effect may be more robust for EEG coherence than EEG band power. Supplementary analyses examined whether the EEG measures mediated changes in intellectual abilities within the foster care children, but no clear evidence of mediation was observed.

Social competitiveness and plasticity of neuroendocrine function in old age: influence of neonatal novelty exposure and maternal care reliability.

Early experience is known to have a profound impact on brain and behavioral function later in life. Relatively few studies, however, have examined whether the effects of early experience remain detectable in the aging animal. Here, we examined the effects of neonatal novelty exposure, an early stimulation procedure, on late senescent rats' ability to win in social competition. During the first 3 weeks of life, half of each litter received daily 3-min exposures to a novel environment while the other half stayed in the home cage. At 24 months of age, pairs of rats competed against each other for exclusive access to chocolate rewards. We found that novelty-exposed rats won more rewards than home-staying rats, indicating that early experience exerts a life-long effect on this aspect of social dominance. Furthermore, novelty-exposed but not home-staying rats exhibited habituation of corticosterone release across repeated days of social competition testing, suggesting that early experience permanently enhances plasticity of the stress response system. Finally, we report a surprising finding that across individual rat families, greater effects of neonatal novelty exposure on stress response plasticity were found among families whose dams provided more reliable, instead of a greater total quantity of, maternal care.

An epigenetic induction of a right-shift in hippocampal asymmetry: selectivity for short- and long-term potentiation but not post-tetanic potentiation.

In humans, it is well established that major psychological functions are asymmetrically represented between the left and right cerebral cortices. The developmental origin of such functional lateralization remains unknown. Using the rat as a model system, we examined whether exposing neonates briefly to a novel environment can differentially affect synaptic plasticity in the left and right hippocampi during adulthood. During the first 3 weeks of life, one half of the pups from a litter spent 3 min daily away from their familiar home environment (Novel) while their littermates remained in that familiar environment (Home). At adulthood (7-months old), post-tetanic potentiation (PTP) of excitatory post-synaptic potentials (EPSPs), a very short-lasting form of plasticity, was greater among the Novel than the Home rats in both left and right hippocampi. In contrast, the novelty-induced increases in short- and long-term potentiation (STP, LTP), two relatively longer-lasting forms of plasticity, were found only in the right hippocampus. These findings demonstrate that a phase-selective asymmetry in hippocampal synaptic plasticity can be induced epigenetically by seemingly small systematic differences in early life environment. The selectivity of this asymmetry for the longer-lasting forms of synaptic plasticity suggests that the observed asymmetry in plasticity may contribute specifically to an asymmetric learning process which, in turn, may contribute to a functional asymmetry in the neocortex.

Programming social, cognitive, and neuroendocrine development by early exposure to novelty.

Mildly stressful early life experiences can potentially impact a broad range of social, cognitive, and physiological functions in humans, nonhuman primates, and rodents. Recent rodent studies favor a maternal-mediation hypothesis that considers maternal-care differences induced by neonatal stimulation as the cause of individual differences in offspring development. Using neonatal novelty exposure, a neonatal stimulation paradigm that dissociates maternal individual differences from a direct stimulation effect on the offspring, we investigated the effect of early exposures to novelty on a diverse range of psychological functions using several assessment paradigms. Pups that received brief neonatal novelty exposures away from the home environment showed enhancement in spatial working memory, social competition, and corticosterone response to surprise during adulthood compared with their home-staying siblings. These functional enhancements in novelty-exposed rats occurred despite evidence that maternal care was directed preferentially toward home-staying instead of novelty-exposed pups, indicating that greater maternal care is neither necessary nor sufficient for these early stimulation-induced functional enhancements. We suggest a unifying maternal-modulation hypothesis, which distinguishes itself from the maternal-mediation hypothesis in that (i) neonatal stimulation can have direct effects on pups, cumulatively leading to long-term improvement in adult offspring; and (ii) maternal behavior can attenuate or potentiate these effects, thereby decreasing or increasing this long-term functional improvement.

Effects of long-term estrogen replacement on social investigation and social memory in ovariectomized C57BL/6 mice.

Estrogen has been shown to play a role in modulating social recognition memory. However, the literature regarding the influence of estrogen on social memory is sparse and only covers two experimental manipulations: acute injections and receptor knockout. Long-term effects of estrogen replacement on social investigation and social recognition are unknown. Furthermore, existing social recognition protocols focus on memory of very short durations (<2 h). In the present study, we examined long-term effects of estrogen replacement on both short- (<30 min) and long-term (24 h) social recognition in ovariectomized female C57BL/6 mice by implanting 60-day time-release pellets containing physiological doses of estradiol (0, 0.18, or 0.72 mg of 17beta-estradiol). After 55 days of treatment, evidence of social recognition memory, measured by 24-h habituation, was found only in mice receiving the 0.72-mg pellet. This result is remarkable as previous reports indicate that individually-housed untreated rats and mice do not show habituation beyond 2 h. Our study further revealed that estrogen also increased frequencies of baseline social investigation without affecting general activity levels and decreased delayed post-swim-stress serum corticosterone concentration. Thus, these results suggest that long-term estrogen replacement increased the interest in social interaction as well as decreased stress responses. It is likely that the 24-h habituation observed in the estrogen replacement group is mediated jointly by the non-mnemonic effects of estrogen on the behavior displayed during the stage of memory encoding as well as mnemonic effects during the stage of memory consolidation.

Sex difference in temporal patterns of social interaction and its dependence upon neonatal novelty exposure.

Rodents have been an indispensable tool for the study of the neural mechanisms underlying a variety of emotional, social, and cognitive functions and dysfunctions. Surprisingly, little is known concerning sex difference in rodent social recognition memory and its sensitivity to neonatal stimulation. During the first 3 weeks of life, we exposed male and female neonates to a novel cage for 3-min per day while the matched littermate controls remained in the home cage. At 7 weeks and 7 months of age, we measured frequencies of social investigation over repeated social exposures and found that males showed greater habituation in social investigation than females during both juvenility and adulthood and that neonatal novelty exposure affected changes in the frequency of social investigation across multiple exposures in a sex-dependent manner. We speculate that these observed sex differences may reflect a sex difference in affinity for conspecific novelty rather than memory capability.

Developmentally stable sex-dependent modulation of turning asymmetry by neonatal novelty exposure.

In rats, early life stimulation can enhance learning and memory and induce parallel changes in brain asymmetry. Despite persistent interest in human brain asymmetry, relatively little is known in animal models about developmental stability of early-experience effects on asymmetry and how early-experience may affect males and females differently in asymmetry measures across developmental stages. We exposed male and female neonatal rats to a novel cage for 3min per day during the first 3 weeks of life and measured spontaneous turning behavior at juvenility (7 weeks of age) and adulthood (7 months of age). We found that (1) the effects of such neonatal novelty exposure on turning bias are developmentally stable, and (2) neonatal novelty exposure differentially modulates turning bias in males and females. We briefly discuss implications of these findings in terms of the role of brain asymmetry in modulating cognitive and emotional development.

Neonatal novelty exposure, dynamics of brain asymmetry, and social recognition memory.

Brief and transient early-life stimulation via neonatal handling and neonatal novelty exposure can lead to differential changes within the right and left brains. In rats, these lateralized changes have been demonstrated behaviorally, neuroanatomically, and neurophysiologically. Recently, we found that neonatal novelty exposure can prolong the duration of social recognition memory from less than 2 hr to at least 24 hr among male rats reared in social isolation and that this enhancement is associated with an initial right-turn preference in a novel testing cage. In contrast to stable forms of asymmetry, such as handedness, we show that this turning asymmetry is dynamic-decreasing as the animal adjusts to the novel testing environment over a 2-day period. This change in turning asymmetry was found only among animals that experienced neonatal novelty exposure during the first 3 weeks of their lives. Furthermore, individual differences in short-term social recognition memory for a conspecific can be predicted by this change in functional asymmetry.

Modification of social memory, hypothalamic-pituitary-adrenal axis, and brain asymmetry by neonatal novelty exposure.

Although corticosterone (a stress hormone) is known to influence social behavior and memory processes, little has been explored concerning its modulatory role in social recognition. In rats, social recognition memory for conspecifics typically lasts <2 hr when evaluated using a habituation paradigm. Using neonatal novelty exposure, a brief and transient early life stimulation method known to produce long-lasting changes in the hypothalamic-pituitary-adrenal axis, we found that social recognition memory was prolonged to at least 24 hr during adulthood. This prolonged social memory was paralleled by a reduction in the basal blood concentration of corticosterone. The same neonatal stimulation also resulted in a functional asymmetry expressed as a greater right-turn preference in a novel environment. Rats that preferred to turn right showed better social recognition memory. These inter-related changes in basal blood corticosterone concentration, turning asymmetry, and social recognition memory suggest that stress hormones and brain asymmetry are likely candidates for modulating social memory. Furthermore, given that neonatal stimulation has been shown to improve learning and memory performance primarily under aversive learning situations, the neonatal novelty exposure-induced enhancement in social recognition broadens the impact of early life stimulation to include the social domain.

Neonatal novelty exposure affects sex difference in open field disinhibition.

Neonatal stimulation induces sexually dimorphic changes at both the levels of behavior and neural systems. The effects of such stimulation on emotional reactivity measured by open field activity have been inconsistent. We found that among 23-day-old rats, neonatal novelty exposure induced an opposite pattern of sex difference in the initial open field disinhibition. This result suggests that the effect of early life stimulation on emotional reactivity is sex-dependent and that this early stimulation modulates the sexual dimorphism in emotional reactivity to a novel environment.

Independent components of magnetoencephalography: localization.

We applied second-order blind identification (SOBI), an independent component analysis method, to MEG data collected during cognitive tasks. We explored SOBI's ability to help isolate underlying neuronal sources with relatively poor signal-to-noise ratios, allowing their identification and localization. We compare localization of the SOBI-separated components to localization from unprocessed sensor signals, using an equivalent current dipole modeling method. For visual and somatosensory modalities, SOBI preprocessing resulted in components that can be localized to physiologically and anatomically meaningful locations. Furthermore, this preprocessing allowed the detection of neuronal source activations that were otherwise undetectable. This increased probability of neuronal source detection and localization can be particularly beneficial for MEG studies of higher-level cognitive functions, which often have greater signal variability and degraded signal-to-noise ratios than sensory activation tasks.