Ongoing Studies

Infant Perceptual Abilities as Cognitive Precursors Research which aims to predict cognitive and linguistic abilities in later childhood based on early infant behavior implicates infant perceptual-cognitive abilities as likely analogs for childhood information-processing skills. These studies examine the specific relationship between early perceptual-cognitive abilities (as indexed by habituation, recognition memory, and cross-modal transfer) and later cognitive and linguistic development. Studies in infant monkeys have shown that lesions in the amygdala and thalamus can impair visual attention and recognition memory, including poor performance on preferential looking tasks. Performance on tasks requiring memory for location - in particular, delayed response tasks - is impaired in both monkey and human infants when damage to the caudate nucleus is sustained. Subcortical damage (due to interventricular hemorrhage) in preterm infants has been shown in a number of recent studies to affect habituation functions as well as recognition memory. Moreover, recent research also suggests that morphological abnormalities in the caudate and thalamus may play a part in temporal processing deficits. Speed of processing appears to be the critical factor in differential performance on perceptual-cognitive tasks. Measures of perceptual-cognitive abilities in infancy, such as habituation decrement and recognition memory, are in turn related to performance on childhood linguistic and cognitive tasks. Similarly, studies with language impaired children implicate a specific deficit in rate of sensory and perceptual information processing. Thus, this research examines the role of speed of processing in infant perceptual-cognitive abilities and its subsequent impact on later cognitive outcomes using a prospective longitudinal design. I have proposed a neurally plausible model to examine the hypothesis that the critical mechanism underlying "speed of encoding," as measured by rate and amount of habituation and novelty preference on recognition memory tests, may be temporal processing efficiency in infancy and that it is this mechanism which is specifically related to childhood language comprehension scores (receptive language) as well as to general language and IQ.   Rapid Auditory Processing in Infancy and Subsequent Relations with Early Language Development Specific Language Impairment (SLI) in children, also referred to as developmental dysphasia, is characterized by a relatively specific failure of normal language functions in the absence of such factors as deafness, mental retardation, motor disability, childhood schizophrenia, or infantile autism. Children with SLI have shown highly significant and persistent deficits in their abilities to process rapidly changing sequential non-verbal auditory stimuli. SLI children have been shown to be selectively impaired in their ability to perceive and produce those speech sounds which are characterized by brief or rapidly changing temporal cues. The degree of rapid temporal processing deficit has also proved to be highly correlated with the degree of language comprehension deficits over a broad age range of SLI individuals. This research is based on a neurobiological model of speech which emphasizes the "bottom-up" processing of incoming sensory percepts. The model posits that the primary deficit in specific language impairment (SLI) is the inability to integrate and discriminate two or more sensory events which enter the nervous system in rapid succession - in a time window of tens of milliseconds. Much of the sensory processing necessary for language comprehension and production occurs within a brief window of time. In order to process speech it is necessary to hear and respond to auditory cues that signal what words are being produced. In other words, processing proceeds in a "bottom-up" manner, with discrimination of basic acoustic properties supporting language acquisition. Problems decoding linguistic stimuli often co-occur with difficulties in non-speech rapid auditory processing. It has been hypothesized that the difficulties described above in processing brief, rapid, successive auditory cues could impair or delay the formation of distinct phonological representations and so possibly play a causal role in SLI (Benasich & Read, 1998; Tallal, Miller, Jenkins, & Merzenich, 1997). However, this hypothesis has not been universally supported (e.g. Martin, 1995; Mody, Studdert-Kennedy, & Brady, 1997; but see Denenberg, 1999, 2001; Leonard, 1998). At the heart of this theoretical controversy are issues of linguistic specificity and neural modularity for language development (Lieberman, 1996). In other words, are there dedicated neuroanatomical "modules" in the human brain that allow processing and computation of speech, or can more general sensory and learning mechanisms account for the development of language? Several recent studies support the association between auditory temporal processing abilities and SLI and dyslexia using more traditional psychophysical methodology (Kraus et al., 1996; Leonard, 1998; Lovegrove, 1991; Neville et al., 1993; Wright et al., 1997). For instance, Wright and colleagues (Wright et al., 1997) have shown that SLI children are severely impaired in their ability to separate successive rapid brief sounds of similar frequencies and also show excessive amounts of interference (auditory backward masking) when two auditory stimuli are presented in rapid succession. A variety of studies suggest that the neurons specialized for processing rapid transient stimuli (magnocellular neurons) in both visual and auditory thalamic regions are implicated in the temporal processing deficits seen in SLI and dyslexic subjects (Eden et al., 1995; Galaburda et al., 1994; Herman et al., 1995; Livingstone et al., 1991). Neuropathological and brain imaging (MRI) studies also suggest that the neuropathology implicated in SLI may occur early in life. Although the literature on temporal processing impairments as a function of brain lesions is limited, recent research suggests that morphological abnormalities in the caudate may play a part in temporal processing deficits. MRI studies have also shown atypical patterns of cerebral lateralization in SLI and dyslexic individuals as compared to controls. Specifically, a lack of the normal left-greater-than-right pattern is seen in the planum temporale as well as in the parietal and frontal regions (Jernigan et al., 1991; Larsonet al., 1990; Leonard et al., 1993). Errors in neuronal migration resulting in cortical cellular anomalies (i.e., ectopias, dysplasias, and microgyric lesions) have also been hypothesized as a primary deficit in SLI and dyslexia (Galaburda, et al., 1985; Humphreys et al., 1990). Such neuropathological deficits would originate prenatally during the period of neuronal migration. I have developed an assessment battery that is well tolerated by infants, and that has allowed us to demonstrate consistent and reliable rapid auditory temporal processing thresholds in normal infants as well as in infants at risk for developmental delays. Differences in infant discrimination of rapid auditory cues (a critical skill for decoding language) have been shown to be strongly and reliably related to differences in language comprehension and production in toddlers in three studies. In addition, current prospective studies of three samples of infants born into families with a history of language-based learning disorders suggest that ATP thresholds in about 50% of these infants differ from those of infants without such a family history (Benasich & Spitz, 1997) . Thus, a subset of infants with a family history of SLI are poor temporal processors and these same infants have lower achievement in language during the toddler years. Early processing is also being examined in other populations at risk for developmental delays including very low birthweight preterm infants, infants with repeated episodes of otitis media, and infants with focal lesions due to prenatal strokes. In sum, our data, to date, lend strong support to the notion that the ability to perform fine acoustic discriminations in early infancy is critically important to later language development. Our studies provide suggestive evidence that temporal processing deficits can serve as a behavioral "marker" of language-based learning impairments and could be of particular utility in the early identification of SLI. In addition, these findings suggest that the early processes that support general perceptual-cognitive abilities in infancy are also important for language acquisition and cognitive development in early childhood.   Recurrent Acute Otitis Media Recurrent Acute Otitis Media, or repeated ear infections with collection of fluid in the middle ear (middle ear effusion), during the first year can produce language and speech delays as a function of poor hearing. Many children go on to have normal hearing and normal language. However, a higher percentage of children who have repeated episodes of otitis media subsequently are found to have specific language impairment. Conversely, children with SLI and dyslexia are more likely to have a history of recurrent otitis media. It may be the case that the alteration of speech sounds caused by such cyclic hearing changes could produce learned deficits in auditory temporal processing. In essence, the fluctuating hearing loss during the early years may present the child with a speech signal that is more diffuse and thus more difficult to process. This may be particularly critical if it occurs in the first year, during which the infant is establishing speech and language categories (Kube, 1992; Menyuk, 1986). In a prospective longitudinal study, still underway, we are studying the temporal processing and language abilities of a cohort of infants with an early history (in the first six months) of repeated episodes of otitis media. Our findings thus far indicate that such children begin to "catch-up" to those without an early history of otitis media in their age groups by 24 months of age unless prematurity or a family history of language-based learning impairment is also present. However, we hypothesize that these "late talkers" will have a resurgence of difficulties in cognitive and language attainment once they reach school age.   Relationships Among Neurodevelopmental Delay, Behavioral/Emotional Disorders, and Language Development In collaboration with Dr. Paula Tallal (CMBN) and Dr. Susan Curtiss (UCLA), I have examined the interactions among neurodevelopmental delay, behavioral/emotional disorders, and language development and disorders. This work was an outgrowth of my interest in socioemotional development in toddlers, the enhanced incidence of behavior problems reported in children with language impairments, and the existence of a unique longitudinal cohort at University of California at San Diego (a large, quantitatively assessed group of children with specific developmental language impairment (SLI) and normal controls matched for age, IQ, race, and SES). It was possible that previous studies reporting a high incidence of psychiatric, behavioral, and/or emotional disturbance in SLI children failed to differentiate between neurodevelopmental delay and emotional disturbance, particularly in young SLI children. We were interested in whether socioemotional development in SLI children, as compared to normal boys and girls, would show quantitative and/or qualitative changes over time. In addition we wanted to examine the effect of the severity and course of the language disorder on behavioral/emotional outcomes. Our results suggest that behavior problems in language-impaired preschoolers are not necessarily an indication of underlying emotional disturbances. Rather, these behaviors may be part of the neurodevelopmental lags seen in these children at a number of levels. We also found that neither the severity nor the course of specific language impairment were good predictors of behavioral/emotional outcomes, at least across the age range we studied (4 through 8 years). We are presently examining the behavioral profiles of toddlers with a positive family history of SLI.   Effects Of Subependymal And Intraventricular Hemorrhages On Auditory Temporal Processing And Language Onset In VLBW Preterm Infants. It is well recognized that preterm, low birth weight infants are at high risk for cognitive, social and language delays as a result of prenatal and perinatal factors (IHDP, 1990; Washington, et al., 1986). Approximately 33% to 50% of all VLBW infants develop subependymal and intraventricular hemorrhage (IVH) in the immediate postnatal period (Papile, Burstein, & Burstein, 1978; Ross et al., 1991) Significant relations between the extent of hemorrhage and later developmental deficits have been reported (Papile et al., 1983; Shankaran et al., 1982; Volpe, 1995, 1991). IVH primarily originates in the subependymal germinal matrix, a cellular region immediately ventrolateral to the lateral ventricle with many delicate blood vessels making it vulnerable to hemorrhage. The germinal matrix provides a source of glioblasts which will develop into cerebral oligodendroglia and astrocytes in the third trimester; a hemorrhage here is likely to damage the matrix and thus its glial precursor cells. Damage may also occur to the caudate nucleus of the basal ganglia. The caudate develops from cells located at the base of the lateral ventricles into a body roughly paralleling the shape of the lateral ventricle and lying lateral to it. IVH may create lesions in the caudate nucleus, damaging not only the caudate, but also cells that would migrate to other sub-cortical structures, such as the amygdala and thalamus, and also to frontal and prefrontal cortical areas. The location of the hemorrhage is related to the gestational maturity of the vascular bed of the subependymal region. In infants at 24-28 weeks gestational age, hemorrhages are likely over the body of the caudate nucleus, whereas in infants from 28-32 weeks gestational age, hemorrhages are more likely to occur over the head of the caudate nucleus (Dietch, 1993) . Given the high incidence of language-based learning disorders in VLBW infants with IVH, and the potential impact of IVH on subcortical regions (such as the caudate nucleus, amygdala, and thalamus), research implicating these same subcortical regions in temporal processing disorders and subsequent language impairments is striking. The primary aims of this ongoing study are to examine the associations between the severity and location of subependymal and intraventricular hemorrhage (S/IVH) and infant auditory temporal processing abilities and between S/IVH and later cognitive and linguistic development in very low birth weight (VLBW) premature infants (<1500 grams and < 32 weeks gestational age). We are specifically focusing on temporal processing abilities, language outcomes (including both receptive and expressive abilities), and assessment of general cognitive outcomes using a prospective longitudinal design. A series of prospective longitudinal studies in our laboratory have characterized the temporal processing abilities underlying emerging language in infants. My research demonstrates that we can identify those infants, very early on, who are poor at processing rapid temporal cues in the auditory domain and that these differences in infant discrimination of rapid auditory cues (a critical skill for decoding language) are strongly and reliably related to differences in language comprehension and production in toddlers. We posit that infants with Grade I or Grade II hemorrhages in the areas of the lateral and/or fourth ventricles may be more likely to have auditory temporal processing deficits and subsequent specifically delayed language development given the likelihood of damage to the caudate nucleus and other subcortical structures. Infants with Grade III or Grade IV hemorrhages (involving the parenchyma) on the other hand are more likely to show generalized processing and cognitive delays as well as major neurological sequelae given the more extensive biological insult. We also hypothesize that "speed of encoding," as measured by auditory temporal processing, rate of habituation, and recognition memory performance in early infancy, will be significantly related to later neurodevelopmental, language, and cognitive outcomes in S/IVH infants as well as VLBW matched controls without S/IVH.   CMBN Rutgers Carter Center for Neurocognitive Research The Carter Center for Brain Research in Holoprosencephaly and Related Malformations at the Center for Molecular and Behavioral Neuroscience (CMBN) is not a clinical facility but focuses on basic research pertaining to the evaluation of early cognitive and language development in this population of often nonverbal and motor impaired children. Our primary objective is development of a prototype early assessment battery, the ' Early Cognitive Assessment Battery' that will: 1) allow evaluation of early cognitive and language development in nonverbal, motor impaired children, and 2) provide a means of assessing treatment and intervention protocols on an ongoing basis in order to assure that each child reaches his own full potential. Over the past year we have been pursuing a research program that has allowed us to translate our research techniques into a clinical battery that includes two interactive components: behavioral and electrophysiological (ERP's) as well as developing a series of innovative computer-based tasks. In the course of this longitudinal study, we will be collecting information that will allow us to adapt and expand the experimental nonverbal perceptual-cognitive assessment battery for infants, previously developed in our laboratory, for use with older children. The "Early Cognitive Assessment Battery" is designed to monitor progress in neurodevelopmental function, sensory processing, and cognitive and language development. It is aimed at testing children with generalized developmental delays from early brain insult and/or developmental disorders using simple techniques, such as eye gaze measures, to provide a window into the cognitive processes of preverbal/nonverbal infants and toddlers. A range of tasks are administered that are designed to provide information about different skills: speed and efficiency of information processing, short- and long-term memory, intrasensory integration, receptive vocabulary, comprehension of linguistic concepts, and phonemic discrimination. The test battery contains an assortment of nonstandardized behavioral tasks as well as items adapted from standardized scales with the potential to evaluate cognitive and language development using nonverbal behaviors. None of these assessments are ready for general clinical use but selected families with children diagnosed as having mild semilobar holoprosencephaly (identified by the HPE Clinical Centers or ascertained locally) or early brain insult from other causes will be invited to participate in our longitudinal study. (Carter Centers for Brain Research in Holoprosencephaly and Related Malformations) We are also pretesting other types of tasks including some new computer-based language assessments and high resolution EEG/ERP (Time-locked Cortical Evoked Potential) methods for assessing language development in children with motor disorders such as cerebral palsy. A number of our new experimental tasks have segments that show promise for use in an intervention/remediation setting and we have begun to investigate computer applications that could interface with these tasks. Early development of intervention strategies modeled on the innovative work of Dr. Paula Tallal and Dr. Michael Merzenich will also begin over the next year.   The Santa Fe Institute Consortium: Increasing Human Potential This cross-disciplinary cross-site project will allow the testing of hypotheses about the nature and time scale of changes in brain structure and function across development and will explore and attempt to link the behaviors that are thought to accompany such changes. At the CMBN, Rutgers site we will prospectively and longitudinally assess 80 healthy, normally developing infants at 6, 12, 24 and 36 months of age on measures of language, cognition, and social development. At each age, measures of brain structure, using structural Magnetic Resonance Imaging (MRIs), and brain function, employing event-related potentials (ERPs), will also be collected. (Parallel and matching assessments will take place with an equivalent sample and the same age groups at the University of Washington, Seattle, WA and the data sets will then be pooled to provide more statistical power.) Given the large number of subjects and the longitudinal strategy employed, this will be the most comprehensive data set of information collected, to date, about the developing and changing brain. The perceptual-cognitive infant assessment battery we will use provides a fine-grained "map" of the child's emerging behaviors across time and of the ages at which each child achieves developmental milestones. The battery includes a range of behavioral tasks designed to evaluate basic information processing abilities that are critically important for optimal development of language, cognitive, and social skills. Measures of the speed and efficiency of processing of auditory and visual information, short- and long-term memory, categorization, discrimination, and object permanence are included. In addition, the child's receptive and expressive vocabulary, symbolic skills, and phonemic discrimination (ability to discriminate between the building sounds of language) are assessed. Two converging techniques provide information about brain structure and function: ERPs to rapidly changing auditory temporal cues and to linguistic phonemes and MRIs that allow visualization of brain structures, fiber tracts, and myelination. The relations among the electrophysiological, imaging, and behavioral measures will be examined as a function of age and sociodemographic variables.

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