Silvia Ortiz-Mantilla

Understanding language and cognitive deficits in very low birth weight children.

Very-low-birth-weight infants are at much higher risk for cognitive and language delays but the nature of such deficits is not clearly understood. Given increasing rates of prematurity and infants born very-low-birth-weight, examination of mechanisms that underlie poorer developmental outcome is essential. We investigated language and cognitive abilities in very-low and normal birth-weight infants to determine whether performance differences were due to poorer global cognitive performance or to deficits in specific processing abilities. Thirty-two very-low and 32 normal birth-weight infants received visual and auditory-visual habituation recognition-memory tasks, and standardized language and cognitive assessments. Very-low-birth-weight infants performed more poorly on visual and auditory-visual habituation tasks and scored lower than controls on cognitive and language measures. These findings suggest that differences in language abilities in very-low-birth-weight children may be part of a global deficit that impacts many areas of cognitive functioning rather than a specific impairment in rapid auditory processing.

Pediatric neuroimaging in early childhood and infancy: challenges and practical guidelines

Structural and functional magnetic resonance imaging (fMRI) has been used increasingly to investigate typical and atypical brain development. However, in contrast to studies in school‐aged children and adults, MRI research in young pediatric age groups is less common. Practical and technical challenges occur when imaging infants and children, which presents clinicians and research teams with a unique set of problems. These include procedural difficulties (e.g., participant anxiety or movement restrictions), technical obstacles (e.g., availability of child‐appropriate equipment or pediatric MR head coils), and the challenge of choosing the most appropriate analysis methods for pediatric imaging data. Here, we summarize and review pediatric imaging and analysis tools and present neuroimaging protocols for young nonsedated children and infants, including guidelines and procedures that have been successfully implemented in research protocols across several research sites.

Regional Infant Brain Development: An MRI-Based Morphometric Analysis in 3 to 13 Month Olds

Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders.

Associations between the size of the amygdala in infancy and language abilities during the preschool years in normally developing children

Recently, structural MRI studies in children have been used to examine relations between brain volume and behavioral measures. However, most of these studies have been done in children older than 2 years of age. Obtaining volumetric measures in infants is considerably more difficult, as structures are less well defined and largely unmyelinated, making segmentation challenging. Moreover, it is still unclear whether individual anatomic variation across development, in healthy, normally developing infants, is reflected in the configuration and function of the mature brain and, as importantly, whether variation in infant brain structure might be related to later cognitive and linguistic abilities. In this longitudinal study, using T1 structural MRI, we identified links between amygdala volume in normally developing, naturally sleeping, 6-month infants and their subsequent language abilities at 2, 3 and 4 years. The images were processed and manually segmented using Cardviews to extract volumetric measures. Intra-rater reliability for repeated segmentation was 87.73% of common voxel agreement. Standardized language assessments were administered at 6 and 12 months and at 2, 3 and 4 years. Significant and consistent correlations were found between amygdala size and language abilities. Children with larger right amygdalae at 6 months had lower scores on expressive and receptive language measures at 2, 3, and 4 years. Associations between amygdala size and language outcomes have been reported in children with autism. The findings presented here extend this association to normally developing children, supporting the idea that the amygdalae might play an important but as yet unspecified role in mediating language acquisition.

Source localization of event-related potentials to pitch change mapped onto age-appropriate MRIs at 6 months of age

Auditory event-related potentials (ERPs) have been used to understand how the brain processes auditory input, and to track developmental change in sensory systems. Localizing ERP generators can provide invaluable insights into how and where auditory information is processed. However, age-appropriate infant brain templates have not been available to aid such developmental mapping. In this study, auditory change detection responses of brain ERPs were examined in 6-month-old infants using discrete and distributed source localization methods mapped onto age-appropriate magnetic resonance images. Infants received a passive oddball paradigm using fast-rate non-linguistic auditory stimuli (tone doublets) with the deviant incorporating a pitch change for the second tone. Data was processed using two different high-pass filters. When a 0.5 Hz filter was used, the response to the pitch change was a large frontocentral positive component. When a 3 Hz filter was applied, two temporally consecutive components associated with change detection were seen: one with negative voltage, and another with positive voltage over frontocentral areas. Both components were localized close to the auditory cortex with an additional source near to the anterior cingulate cortex. The sources for the negative response had a more tangential orientation relative to the supratemporal plane compared to the positive response, which showed a more lateral, oblique orientation. The results described here suggest that at 6 months of age infants generate similar response patterns and use analogous cortical areas to that of adults to detect changes in the auditory environment. Moreover, the source locations and orientations, together with waveform topography and morphology provide evidence in infants for feature-specific change detection followed by involuntary switching of attention.

Time course of ERP generators to syllables in infants: A source localization study using age-appropriate brain templates

Event-related potentials (ERPs) have become an important tool in the quest to understand how infants process perceptual information. Identification of the activation loci of the ERP generators is a technique that provides an opportunity to explore the neural substrates that underlie auditory processing. Nevertheless, as infant brain templates from healthy, non-clinical samples have not been available, the majority of source localization studies in infants have used non-realistic head models, or brain templates derived from older children or adults. Given the dramatic structural changes seen across infancy, all of which profoundly affect the electrical fields measured with EEG, it is important to use individual MRIs or age-appropriate brain templates and parameters to explore the localization and time course of auditory ERP sources. In this study 6-month-old infants were presented with a passive oddball paradigm using consonant-vowel (CV) syllables that differed in voice onset time. Dense-array EEG/ERPs were collected while the infants were awake and alert. In addition, MRIs were acquired during natural non-sedated sleep for a subset of the sample. Discrete dipole and distributed source models were mapped onto individual and averaged infant MRIs. The CV syllables elicited a positive deflection at about 200 ms followed by a negative deflection that peaked around 400 ms. The source models generated placed the dipoles at temporal areas close to auditory cortex for both positive and negative responses. Notably, an additional dipole for the positive peak was localized at the frontal area, at the anterior cingulate cortex (ACC) level. ACC activation has been reported in adults, but has not, to date, been reported in infants during processing of speech-related signals. The frontal ACC activation was earlier but smaller in amplitude than the left and right auditory temporal activations. These results demonstrate that in infancy the ERP generators to CV syllables are localized in cortical areas similar to that reported in adults, but exhibit a notably different temporal course. Specifically, ACC activation in infants significantly precedes auditory temporal activation, whereas in adults ACC activation follows that of temporal cortex. We suggest that these timing differences could be related to current maturational changes, to the ongoing construction of language-specific phonetic maps, and/or to more sensitive attentional switching as a response to speech signals in infancy.

Enhancement of Gamma Oscillations Indicates Preferential Processing of Native over Foreign Phonemic Contrasts in Infants

Young infants discriminate phonetically relevant speech contrasts in a universal manner, that is, similarly across languages. This ability fades by 12 months of age as the brain builds language-specific phonemic maps and increasingly responds preferentially to the infants native language. However, the neural mechanisms that underlie the development of infant preference for native over non-native phonemes remain unclear. Since gamma-band power is known to signal infants preference for native language rhythm, we hypothesized that it might also indicate preference for native phonemes. Using high-density electroencephalogram/event-related potential (EEG/ERP) recordings and source-localization techniques to identify and locate the ERP generators, we examined changes in brain oscillations while 6-month-old human infants from monolingual English settings listened to English and Spanish syllable contrasts. Neural dynamics were investigated via single-trial analysis of the temporal-spectral composition of brain responses at source level. Increases in 4–6 Hz (theta) power and in phase synchronization at 2–4 Hz (delta/theta) were found to characterize infants evoked responses to discrimination of native/non-native syllable contrasts mostly in the left auditory source. However, selective enhancement of induced gamma oscillations in the area of anterior cingulate cortex was seen only during native contrast discrimination. These results suggest that gamma oscillations support syllable discrimination in the earliest stages of language acquisition, particularly during the period in which infants begin to develop preferential processing for linguistically relevant phonemic features in their environment. Our results also suggest that by 6 months of age, infants already treat native phonemic contrasts differently from non-native, implying that perceptual specialization and establishment of enduring phonemic memory representations have been initiated.

Oscillatory support for rapid frequency change processing in infants.

Rapid auditory processing and auditory change detection abilities are crucial aspects of speech and language development, particularly in the first year of life. Animal models and adult studies suggest that oscillatory synchrony, and in particular low-frequency oscillations play key roles in this process. We hypothesize that infant perception of rapid pitch and timing changes is mediated, at least in part, by oscillatory mechanisms. Using event-related potentials (ERPs), source localization and time-frequency analysis of event-related oscillations (EROs), we examined the neural substrates of rapid auditory processing in 4-month-olds. During a standard oddball paradigm, infants listened to tone pairs with invariant standard (STD, 800-800 Hz) and variant deviant (DEV, 800-1200 Hz) pitch. STD and DEV tone pairs were first presented in a block with a short inter-stimulus interval (ISI) (Rapid Rate: 70 ms ISI), followed by a block of stimuli with a longer ISI (Control Rate: 300 ms ISI). Results showed greater ERP peak amplitude in response to the DEV tone in both conditions and later and larger peaks during Rapid Rate presentation, compared to the Control condition. Sources of neural activity, localized to right and left auditory regions, showed larger and faster activation in the right hemisphere for both rate conditions. Time-frequency analysis of the source activity revealed clusters of theta band enhancement to the DEV tone in right auditory cortex for both conditions. Left auditory activity was enhanced only during Rapid Rate presentation. These data suggest that local low-frequency oscillatory synchrony underlies rapid processing and can robustly index auditory perception in young infants. Furthermore, left hemisphere recruitment during rapid frequency change discrimination suggests a difference in the spectral and temporal resolution of right and left hemispheres at a very young age.

Involuntary switching of attention mediates differences in event-related responses to complex tones between early and late Spanish–English bilinguals

Most research with bilinguals has used speech stimuli to demonstrate differences in auditory processing abilities. Two main factors have been identified as modulators of such differences: proficiency and age of acquisition of the second language (L2). However, whether the bilingual brain differs from the monolingual in the efficient processing of non-verbal auditory events (known to be critical to the acoustic analysis of the speech stream) remains unclear. In this EEG/ERP study, using the mismatch negativity (MMN), P3a, and late negativity (LN), we examined differences in discrimination, involuntary switching of attention and reorienting of attention between monolinguals and bilinguals as they processed complex tones. Further, we examined the role that age of acquisition plays in modulating such responses. A group of English monolinguals and a group of proficient Spanish-English bilinguals were presented with a multiple-deviant oddball paradigm with four deviant conditions (duration, frequency, silent gap, and frequency modulation). Late bilinguals, who learned English after age 10, exhibited larger MMN and P3a responses than early bilinguals, across all deviant conditions. Significant associations were found between amplitude of the responses and both age of L2 acquisition and years of L2 experience. Individuals who acquired English at later ages and had fewer years of L2 experience had larger MMN, P3a, and LN responses than those who learned it earlier. These findings demonstrate that age of L2 acquisition is an important modulator of auditory responses in bilinguals even when processing non-speech signals. Involuntary attention switching is suggested as the main factor driving these differences.

Oscillatory Dynamics Underlying Perceptual Narrowing of Native Phoneme Mapping from 6 to 12 Months of Age

During the first months of life, human infants process phonemic elements from all languages similarly. However, by 12 months of age, as language-specific phonemic maps are established, infants respond preferentially to their native language. This process, known as perceptual narrowing, supports neural representation and thus efficient processing of the distinctive phonemes within the sound environment. Although oscillatory mechanisms underlying processing of native and non-native phonemic contrasts were recently delineated in 6-month-old infants, the maturational trajectory of these mechanisms remained unclear. A group of typically developing infants born into monolingual English families, were followed from 6 to 12 months and presented with English and Spanish syllable contrasts varying in voice-onset time. Brain responses were recorded with high-density electroencephalogram, and sources of event-related potential generators identified at right and left auditory cortices at 6 and 12 months and also at frontal cortex at 6 months. Time-frequency analyses conducted at source level found variations in both θ and γ ranges across age. Compared with 6-month-olds, 12-month-olds responses to native phonemes showed smaller and faster phase synchronization and less spectral power in the θ range, and increases in left phase synchrony as well as induced high-γ activity in both frontal and left auditory sources. These results demonstrate that infants become more automatized and efficient in processing their native language as they approach 12 months of age via the interplay between θ and γ oscillations. We suggest that, while θ oscillations support syllable processing, γ oscillations underlie phonemic perceptual narrowing, progressively favoring mapping of native over non-native language across the first year of life. SIGNIFICANCE STATEMENT During early language acquisition, typically developing infants gradually construct phonemic maps of their native language in auditory cortex. It is well known that, by 12 months of age, human infants move from universal discrimination of most linguistic phonemic contrasts to phonemic expertise in their native language. This perceptual narrowing occurs at the expense of the ability to process non-native phonemes. However, the neural mechanisms underlying this process are still poorly understood. Here we demonstrate that perceptual narrowing is, at least in part, accomplished by decreasing power and phase coherence in the θ range while increasing activity in high-γ in left auditory cortex. Understanding the normative neural mechanisms that support early language acquisition is crucial to understanding and perhaps ameliorating developmental language disorders.