Persistent deficits in heart rate response habituation following neonatal binge ethanol exposure.

Cognitive outcomes associated with prenatal exposure to alcohol include low IQ, impaired short-term memory, problems with executive function, poor spatial abilities, and attention deficits. Longitudinal studies in humans prenatally exposed to alcohol have documented the persistence of such effects. Early exposure to alcohol can lead to developmental delays or more permanent impairments in neurocognitive functioning (Connor et al., 1999; Kerns et al., 1997; Korkman et al., 2003; Riley, 1990). Studies have found that although the physical abnormalities associated with prenatal alcohol exposure may normalize with maturation, impairments in attention, memory and executive function can persist into adulthood (Connor and Streissguth, 1999; Kodituwakku, 2007; Streissguth, 2007). Disturbances in attentional processes especially have been consistently reported across the lifespan of individuals with known prenatal exposure to alcohol. Such disruptions in attention have been noted as early as the first day of life (Streissguth et al., 1983), throughout childhood (Coles et al., 1997; Nanson and Hiscock, 1990; Streissguth et al., 1984), during adolescence (Brown et al., 1991; Coles et al., 2002; Korkman et al., 2003), and into adulthood (Connor et al., 1999; Kerns et al., 1997; Streissguth, 2007). Attentional problems are often noted as decreased focus, poor sustained attention and vigilance, and distractibility. Kerns et al. (1997) reported that adults with a diagnosis of fetal alcohol syndrome (FAS) were more distractible during a vigilance task. Distractibility may in part result from deficits in habituation to sensory stimuli outside the realm of the task, and such disturbances have often been described as a lack of ability to tune-out redundant and task-irrelevant information (Connor and Streissguth, 1999; Streissguth et al., 1989). Measurements of stimulus orienting have been powerful tools for examining attention, perception, learning and memory. The orienting response (OR) consists of a collection of central, autonomic, and behavioral reactions to the detection of a novel stimulus (e.g. Graham and Clifton, 1966; Sokolov, 1963). The most commonly used indices of orienting include behavioral orientation toward the source of stimulation and autonomic responses, such as changes in heart rate (Campbell et al., 1992; Lang et al., 1997). The heart rate component of the OR is defined as a decrease in rate (bradycardia), mediated primarily by activation of the parasympathetic nervous system (Graham, 1992; Hunt et al., 1994). Parasympathetic activation is functional in that it serves to reduce background noise, redistribute blood flow away from skeletal muscles to brain areas required for attention and vigilance, and can support faster reaction times (Lacey and Lacey, 1970). A fundamental property of the OR is its ability to undergo rapid habituation, which makes the OR suitable to the study of stimulus encoding and both short- and long-term recognition memory processes (e.g. Richardson and Campbell, 1991). The rate of response habituation has been considered by many as an index of cognitive development in humans and other animals, and rate of habituation assessed in infancy has been regarded as a predictor of later intelligence (e.g. Bornstein, 1989; Kavsek, 2004; McCall and Carriger, 1993). According to comparator theories (e.g. Sokolov, 1963), habituation of the orienting response reflects short-term nonassociative memory processes, as it involves the recognition that a stimulus has been encountered previously and is not biologically significant. Infant recognition memory performance also predicts later IQ (Fagan and Singer, 1983; Rose and Feldman, 1995). Indeed, McCall (1994) has proposed that inhibition is a common feature in habituation and recognition memory paradigms and that it is the propensity for inhibition that accounts for the predictive relationship between these measures and later intelligence test scores. Thus, habituation may be useful in identifying alcohol-induced cognitive deficits soon after birth that could be predictive of more complex and persistent problems that span at least into adolescence and early adulthood (Carmichael Olson et al., 1998; Kerns et al., 1997). Orienting responses have been examined in infants with a history of prenatal alcohol exposure. Coles et al. (1987) for example, reported that moderate gestational exposure to ethanol was correlated with reduced orienting and altered motor development in infants less than one month of age. Furthermore, these researchers found that the initial differences in orienting and motor competence were highly predictive of mental and motor performance assessed at 6 months. Streissguth et al. (1983) reported that infants exposed to moderate doses of ethanol during gestation exhibited reduced rates of response habituation to both auditory and visual stimuli when tested as early as 24 h after birth, with no obvious differences in initial orienting. This same cohort has been assessed repeatedly and deficits in attention and memory domains have consistently been reported (for review see Streissguth, 2007). Previous studies from our laboratory, using young rats, support the findings of Streissguth et al. (1983) in that ethanol-treated animals exhibit impaired response habituation with no observable change in stimulus orienting. Specifically, rats given ethanol on postnatal days (PD) 4-9, to model third-trimester gestational exposure in humans (Dobbing and Sands, 1979; Goodlett and Johnson, 1999), exhibit deficits in habituation of the heart rate orienting response to a novel olfactory stimulus (Hunt and Morasch, 2004; Hunt and Phillips, 2004). However, in these experiments the subjects were tested at only one age, shortly after the termination of the ethanol administration period, on PD 16. Given the well-documented persistence of attention and memory impairments observed in humans with prenatal exposure to ethanol, the purpose of the present experiment was to examine whether ethanol-induced attenuation in rate of response habituation would persist beyond the period of infancy.