Infants' brain responses to social interaction predict future language growth.

In face-to-face interactions with infants, human adults exhibit a species-specific communicative signal. Adults present a distinctive "social ensemble": they use infant-directed speech (parentese), respond contingently to infants' actions and vocalizations, and react positively through mutual eye-gaze and smiling. Studies suggest that this social ensemble is essential for initial language learning. Our hypothesis is that the social ensemble attracts attentional systems to speech and that sensorimotor systems prepare infants to respond vocally, both of which advance language learning. Using infant magnetoencephalography (MEG), we measure 5-month-old infants' neural responses during live verbal face-to-face (F2F) interaction with an adult (social condition) and during a control (nonsocial condition) in which the adult turns away from the infant to speak to another person. Using a longitudinal design, we tested whether infants' brain responses to these conditions at 5 months of age predicted their language growth at five future time points. Brain areas involved in attention (right hemisphere inferior frontal, right hemisphere superior temporal, and right hemisphere inferior parietal) show significantly higher theta activity in the social versus nonsocial condition. Critical to theory, we found that infants' neural activity in response to F2F interaction in attentional and sensorimotor regions significantly predicted future language development into the third year of life, more than 2 years after the initial measurements. We develop a view of early language acquisition that underscores the centrality of the social ensemble, and we offer new insight into the neurobiological components that link infants' language learning to their early brain functioning during social interaction.

Parent coaching from 6 to 18 months improves child language outcomes through 30 months of age.

Interventions focused on the home language environment have been shown to improve a number of child language outcomes in the first years of life. However, data on the longer-term effects of the intervention are still somewhat limited. The current study examines child vocabulary and complex speech outcomes (N = 59) during the year following completion of a parent-coaching intervention, which was previously found to increase the quantity of parent-child conversational turns and to improve child language outcomes through 18 months of age. Measures of parental language input, child speech output, and parent-child conversational turn-taking were manually coded from naturalistic home recordings (Language Environment Analysis System, LENA) at regular 4-month intervals when children were 6- to 24-months old. Child language skills were assessed using the MacArthur-Bates Communicative Development Inventory (CDI) at four time-points following the final intervention session (at 18, 24, 27, and 30 months). Vocabulary size and growth from 18 to 30 months was greater in the intervention group, even after accounting for differences in child language ability during the intervention period. The intervention group also scored higher on measures of speech length and grammatical complexity, and these effects were mediated by 18-month vocabulary. Intervention was associated with increased parent-child conversational turn-taking in home recordings at 14 months, and mediation analysis suggested that 14-month conversational turn-taking accounted for intervention-related differences in subsequent vocabulary. Together, the results suggest enduring, positive effects of parental language intervention and underscore the importance of interactive, conversational language experience during the first 2 years of life. RESEARCH HIGHLIGHTS: Parent coaching was provided as part of a home language intervention when children were 6-18 months of age. Naturalistic home language recordings showed increased parent-child conversational turn-taking in the intervention group at 14 months of age. Measures of productive vocabulary and complex speech indicated more advanced expressive language skills in the intervention group through 30 months of age, a full year after the final intervention session. Conversational turn-taking at 14 months predicted subsequent child vocabulary and accounted for differences in vocabulary size across the intervention and control groups.

Language Experience during Infancy Predicts White Matter Myelination at Age 2 Years.

Parental input is considered a key predictor of language achievement during the first years of life, yet relatively few studies have assessed the effects of parental language input and parent-infant interactions on early brain development. We examined the relationship between measures of parent and child language, obtained from naturalistic home recordings at child ages 6, 10, 14, 18, and 24 months, and estimates of white matter myelination, derived from quantitative MRI at age 2 years (mean = 26.30 months, SD = 1.62, N = 22). Analysis of the white matter focused on dorsal pathways associated with expressive language development and long-term language ability, namely, the left arcuate fasciculus (AF) and superior longitudinal fasciculus (SLF). Frequency of parent-infant conversational turns (CT) uniquely predicted myelin density estimates in both the AF and SLF. Moreover, the effect of CT remained significant while controlling for total adult speech and child speech-related utterances, suggesting a specific role for interactive language experience, rather than simply speech exposure or production. An exploratory analysis of 18 additional tracts, including the right AF and SLF, indicated a high degree of anatomic specificity. Longitudinal analyses of parent and child language variables indicated an effect of CT as early as 6 months of age, as well as an ongoing effect over infancy. Together, these results link parent-infant conversational turns to white matter myelination at age 2 years, and suggest that early, interactive experiences with language uniquely contribute to the development of white matter associated with long-term language ability.SIGNIFICANCE STATEMENT Children's earliest experiences with language are thought to have profound and lasting developmental effects. Recent studies suggest that intervention can increase the quality of parental language input and improve children's learning outcomes. However, important questions remain about the optimal timing of intervention, and the relationship between specific aspects of language experience and brain development. We report that parent-infant turn-taking during home language interactions correlates with myelination of language related white matter pathways through age 2 years. Effects were independent of total speech exposure and infant vocalizations and evident starting at 6 months of age, suggesting that structured language interactions throughout infancy may uniquely support the ongoing development of brain systems critical to long-term language ability.

Language input in late infancy scaffolds emergent literacy skills and predicts reading related white matter development.

Longitudinal studies provide the unique opportunity to test whether early language provides a scaffolding for the acquisition of the ability to read. This study tests the hypothesis that parental language input during the first 2 years of life predicts emergent literacy skills at 5 years of age, and that white matter development observed early in the 3rd year (at 26 months) may help to account for these effects. We collected naturalistic recordings of parent and child language at 6, 10, 14, 18, and 24 months using the Language ENvironment Analysis system (LENA) in a group of typically developing infants. We then examined the relationship between language measures during infancy and follow-up measures of reading related skills at age 5 years, in the same group of participants (N = 53). A subset of these children also completed diffusion and quantitative MRI scans at age 2 years (N = 20). Within this subgroup, diffusion tractography was used to identify white matter pathways that are considered critical to language and reading development, namely, the arcuate fasciculus (AF), superior and inferior longitudinal fasciculi, and inferior occipital-frontal fasciculus. Quantitative macromolecular proton fraction (MPF) mapping was used to characterize myelin density within these separately defined regions of interest. The longitudinal data were then used to test correlations between early language input and output, white matter measures at age 2 years, and pre-literacy skills at age 5 years. Parental language input, child speech output, and parent-child conversational turns correlated with pre-literacy skills, as well as myelin density estimates within the left arcuate and superior longitudinal fasciculus. Mediation analyses indicated that the left AF accounted for longitudinal relationships between infant home language measures and 5-year letter identification and letter-sound knowledge, suggesting that the left AF myelination at 2 years may serve as a mechanism by which early language experience supports emergent literacy.

Brain myelination at 7 months of age predicts later language development.

Between 6 and 12 months of age there are dramatic changes in infants' processing of language. The neurostructural underpinnings of these changes are virtually unknown. The objectives of this study were to (1) examine changes in brain myelination during this developmental period and (2) examine the relationship between myelination during this period and later language development. Macromolecular proton fraction (MPF) was used as a marker of myelination. Whole-brain MPF maps were obtained with 1.25 mm3 isotropic spatial resolution from typically developing children at 7 and 11 months of age. Effective myelin density was calculated from MPF based on a linear relationship known from the literature. Voxel-based analyses were used to identify longitudinal changes in myelin density and to calculate correlations between myelin density at these ages and later language development. Increases in myelin density were more predominant in white matter than in gray matter. A strong predictive relationship was found between myelin density at 7 months of age, language production at 24 and 30 months of age, and rate of language growth. No relationships were found between myelin density at 11 months, or change in myelin density between 7 and 11 months of age, and later language measures. Our findings suggest that critical changes in brain structure may precede periods of pronounced change in early language skills.

Neurobiological underpinnings of rapid white matter plasticity during intensive reading instruction.

Diffusion MRI is a powerful tool for imaging brain structure, but it is challenging to discern the biological underpinnings of plasticity inferred from these and other non-invasive MR measurements. Biophysical modeling of the diffusion signal aims to render a more biologically rich image of tissue microstructure, but the application of these models comes with important caveats. A separate approach for gaining biological specificity has been to seek converging evidence from multi-modal datasets. Here we use metrics derived from diffusion kurtosis imaging (DKI) and the white matter tract integrity (WMTI) model along with quantitative MRI measurements of T1 relaxation to characterize changes throughout the white matter during an 8-week, intensive reading intervention (160 total hours of instruction). Behavioral measures, multi-shell diffusion MRI data, and quantitative T1 data were collected at regular intervals during the intervention in a group of 33 children with reading difficulties (7-12 years old), and over the same period in an age-matched non-intervention control group. Throughout the white matter, mean 'extra-axonal' diffusivity was inversely related to intervention time. In contrast, model estimated axonal water fraction (AWF), overall diffusion kurtosis, and T1 relaxation time showed no significant change over the intervention period. Both diffusion and quantitative T1 based metrics were correlated with pre-intervention reading performance, albeit with distinct anatomical distributions. These results are consistent with the view that rapid changes in diffusion properties reflect phenomena other than widespread changes in myelin density. We discuss this result in light of recent work highlighting non-axonal factors in experience-dependent plasticity and learning.

Diffusional Kurtosis Imaging in the Diffusion Imaging in Python Project.

Diffusion-weighted magnetic resonance imaging (dMRI) measurements and models provide information about brain connectivity and are sensitive to the physical properties of tissue microstructure. Diffusional Kurtosis Imaging (DKI) quantifies the degree of non-Gaussian diffusion in biological tissue from dMRI. These estimates are of interest because they were shown to be more sensitive to microstructural alterations in health and diseases than measures based on the total anisotropy of diffusion which are highly confounded by tissue dispersion and fiber crossings. In this work, we implemented DKI in the Diffusion in Python (DIPY) project-a large collaborative open-source project which aims to provide well-tested, well-documented and comprehensive implementation of different dMRI techniques. We demonstrate the functionality of our methods in numerical simulations with known ground truth parameters and in openly available datasets. A particular strength of our DKI implementations is that it pursues several extensions of the model that connect it explicitly with microstructural models and the reconstruction of 3D white matter fiber bundles (tractography). For instance, our implementations include DKI-based microstructural models that allow the estimation of biophysical parameters, such as axonal water fraction. Moreover, we illustrate how DKI provides more general characterization of non-Gaussian diffusion compatible with complex white matter fiber architectures and gray matter, and we include a novel mean kurtosis index that is invariant to the confounding effects due to tissue dispersion. In summary, DKI in DIPY provides a well-tested, well-documented and comprehensive reference implementation for DKI. It provides a platform for wider use of DKI in research on brain disorders and in cognitive neuroscience.

Myelin development in cerebral gray and white matter during adolescence and late childhood.

Myelin development during adolescence is becoming an area of growing interest in view of its potential relationship to cognition, behavior, and learning. While recent investigations suggest that both white matter (WM) and gray matter (GM) undergo protracted myelination during adolescence, quantitative relations between myelin development in WM and GM have not been previously studied. We quantitatively characterized the dependence of cortical GM, WM, and subcortical myelin density across the brain on age, gender, and puberty status during adolescence with the use of a novel macromolecular proton fraction (MPF) mapping method. Whole-brain MPF maps from a cross-sectional sample of 146 adolescents (age range 9-17 years) were collected. Myelin density was calculated from MPF values in GM and WM of all brain lobes, as well as in subcortical structures. In general, myelination of cortical GM was widespread and more significantly correlated with age than that of WM. Myelination of GM in the parietal lobe was found to have a significantly stronger age dependence than that of GM in the frontal, occipital, temporal and insular lobes. Myelination of WM in the temporal lobe had the strongest association with age as compared to WM in other lobes. Myelin density was found to be higher in males as compared to females when averaged across all cortical lobes, as well as in a bilateral subcortical region. Puberty stage was significantly correlated with myelin density in several cortical areas and in the subcortical GM. These findings point to significant differences in the trajectories of myelination of GM and WM across brain regions and suggest that cortical GM myelination plays a dominant role during adolescent development.

Supporting Interprofessional Engagement in Serious Illness Conversations: An Adapted Resource.

Communication is vital to quality palliative care nursing particularly when caring for someone with a chronic life-limiting illness and their family. Conversations about future decline and preferred care are considered challenging and difficult and are often avoided, resulting in missed opportunities for improving care. To support more, earlier, better conversations, health care organizations in British Columbia, Canada, adopted the Serious Illness Care Program inclusive of the Serious Illness Conversation Guide developed by Ariadne Labs. Workshops for interprofessional team members have been held throughout the province. Nurses and allied health identified the need for more guidance in using the guide in the contexts of their clinical practice. Specifically challenging has been prognosis communication that falls within the scope of practice for each profession. Informed by workshop feedback, an expert team of nurse clinicians and educators tailored an interprofessional clinician reference guide to optimize the guide's use across health care settings. In this article, we present the adaptations focusing on (1) the role of nurses and allied health in serious illness communication, (2) prognosis communication, and (3) a range of role-play scenarios specific to nonphysician practice for serious illness conversations that may arise within the process of care.

Increased Right Posterior STS Recruitment Without Enhanced Directional-Tuning During Tactile Motion Processing in Early Deaf Individuals.

Upon early sensory deprivation, the remaining modalities often exhibit cross-modal reorganization, such as primary auditory cortex (PAC) recruitment for visual motion processing in early deafness (ED). Previous studies of compensatory plasticity in ED individuals have given less attention to tactile motion processing. In the current study, we aimed to examine the effects of early auditory deprivation on tactile motion processing. We simulated four directions of tactile motion on each participant's right index finger and characterized their tactile motion responses and directional-tuning profiles using population receptive field analysis. Similar tactile motion responses were found within primary (SI) and secondary (SII) somatosensory cortices between ED and hearing control groups, whereas ED individuals showed a reduced proportion of voxels with directionally tuned responses in SI contralateral to stimulation. There were also significant but minimal responses to tactile motion within PAC for both groups. While early deaf individuals show significantly larger recruitment of right posterior superior temporal sulcus (pSTS) region upon tactile motion stimulation, there was no evidence of enhanced directional tuning. Greater recruitment of right pSTS region is consistent with prior studies reporting reorganization of multimodal areas due to sensory deprivation. The absence of increased directional tuning within the right pSTS region may suggest a more distributed population of neurons dedicated to processing tactile spatial information as a consequence of early auditory deprivation.

Intensive Summer Intervention Drives Linear Growth of Reading Skill in Struggling Readers.

A major achievement of reading research has been the development of effective intervention programs for struggling readers. Most intervention studies employ a pre-post design, to examine efficacy, but this precludes the study of growth curves over the course of the intervention program. Determining the time-course of improvement is essential for cost-effective, evidence-based decisions on the optimal intervention dosage. The goal of this study was to analyze reading growth curves during an intensive summer intervention program. A cohort of 31 children (6-12 years) with reading difficulties (N = 21 with dyslexia diagnosis) were enrolled in 160 h of intervention occurring over 8 weeks of summer vacation. We collected behavioral measures over 4 sessions assessing decoding, oral reading fluency, and comprehension. Mixed-effects modeling of longitudinal measurements revealed a linear dose-response relationship between hours of intervention and improvement in reading ability; there was significant linear growth on every measure of reading skill and none of the measures showed non-linear growth trajectories. Decoding skills showed substantial growth [Cohen's d = 0.85 (WJ Basic Reading Skills)], with fluency and comprehension growing more gradually [d = 0.41 (WJ Reading Fluency)]. These results highlight the opportunity to improve reading skills over an intensive, short-term summer intervention program, and the linear dose-response relationship between duration and gains enables educators to set reading level goals and design a treatment plan to achieve them.

Responses in area hMT+ reflect tuning for both auditory frequency and motion after blindness early in life.

Previous studies report that human middle temporal complex (hMT+) is sensitive to auditory motion in early-blind individuals. Here, we show that hMT+ also develops selectivity for auditory frequency after early blindness, and that this selectivity is maintained after sight recovery in adulthood. Frequency selectivity was assessed using both moving band-pass and stationary pure-tone stimuli. As expected, within primary auditory cortex, both moving and stationary stimuli successfully elicited frequency-selective responses, organized in a tonotopic map, for all subjects. In early-blind and sight-recovery subjects, we saw evidence for frequency selectivity within hMT+ for the auditory stimulus that contained motion. We did not find frequency-tuned responses within hMT+ when using the stationary stimulus in either early-blind or sight-recovery subjects. We saw no evidence for auditory frequency selectivity in hMT+ in sighted subjects using either stimulus. Thus, after early blindness, hMT+ can exhibit selectivity for auditory frequency. Remarkably, this auditory frequency tuning persists in two adult sight-recovery subjects, showing that, in these subjects, auditory frequency-tuned responses can coexist with visually driven responses in hMT+.

Early Blindness Shapes Cortical Representations of Auditory Frequency within Auditory Cortex.

Early loss of vision is classically linked to large-scale cross-modal plasticity within occipital cortex. Much less is known about the effects of early blindness on auditory cortex. Here, we examine the effects of early blindness on the cortical representation of auditory frequency within human primary and secondary auditory areas using fMRI. We observe that 4 individuals with early blindness (2 females), and a group of 5 individuals with anophthalmia (1 female), a condition in which both eyes fail to develop, have lower response amplitudes and narrower voxelwise tuning bandwidths compared with a group of typically sighted individuals. These results provide some of the first evidence in human participants for compensatory plasticity within nondeprived sensory areas as a result of sensory loss.SIGNIFICANCE STATEMENT Early blindness has been linked to enhanced perception of the auditory world, including auditory localization and pitch perception. Here we used fMRI to compare neural responses with auditory stimuli within auditory cortex across sighted, early blind, and anophthalmic individuals, in whom both eyes fail to develop. We find more refined frequency tuning in blind subjects, providing some of the first evidence in human subjects for compensation within nondeprived primary sensory areas as a result of blindness early in life.

Applying microstructural models to understand the role of white matter in cognitive development.

Diffusion MRI (dMRI) holds great promise for illuminating the biological changes that underpin cognitive development. The diffusion of water molecules probes the cellular structure of brain tissue, and biophysical modeling of the diffusion signal can be used to make inferences about specific tissue properties that vary over development or predict cognitive performance. However, applying these models to study development requires that the parameters can be reliably estimated given the constraints of data collection with children. Here we collect repeated scans using a typical multi-shell diffusion MRI protocol in a group of children (ages 7-12) and use two popular modeling techniques to examine individual differences in white matter structure. We first assess scan-rescan reliability of model parameters and show that axon water faction can be reliably estimated from a relatively fast acquisition, without applying spatial smoothing or de-noising. We then investigate developmental changes in the white matter, and individual differences that correlate with reading skill. Specifically, we test the hypothesis that previously reported correlations between reading skill and diffusion anisotropy in the corpus callosum reflect increased axon water fraction in poor readers. Both models support this interpretation, highlighting the utility of these approaches for testing specific hypotheses about cognitive development.

Word selectivity in high-level visual cortex and reading skill.

Word-selective neural responses in human ventral occipito-temporal cortex (VOTC) emerge as children learn to read, creating a visual word form area (VWFA) in the literate brain. It has been suggested that the VWFA arises through competition between pre-existing selectivity for other stimulus categories, changing the topography of VOTC to support rapid word recognition. Here, we hypothesized that competition between words and objects would be resolved as children acquire reading skill. Using functional magnetic resonance imaging (fMRI), we examined the relationship between responses to words and objects in VOTC in two ways. First, we defined the VWFA using a words > objects contrast and found that only skilled readers had a region that responded more to words than objects. Second, we defined the VWFA using a words > faces contrast and examined selectivity for words over objects in this region. We found that word selectivity strongly correlated with reading skill, suggesting reading skill-dependent tuning for words. Furthermore, we found that low word selectivity in struggling readers was not due to a lack of response to words, but to a high response to objects. Our results suggest that the fine-tuning of word-selective responses in VOTC is a critical component of skilled reading.

Rapid and widespread white matter plasticity during an intensive reading intervention.

White matter tissue properties are known to correlate with performance across domains ranging from reading to math, to executive function. Here, we use a longitudinal intervention design to examine experience-dependent growth in reading skills and white matter in grade school-aged, struggling readers. Diffusion MRI data were collected at regular intervals during an 8-week, intensive reading intervention. These measurements reveal large-scale changes throughout a collection of white matter tracts, in concert with growth in reading skill. Additionally, we identify tracts whose properties predict reading skill but remain fixed throughout the intervention, suggesting that some anatomical properties stably predict the ease with which a child learns to read, while others dynamically reflect the effects of experience. These results underscore the importance of considering recent experience when interpreting cross-sectional anatomy-behavior correlations. Widespread changes throughout the white matter may be a hallmark of rapid plasticity associated with an intensive learning experience.

Who Benefits from Chronic Opioid Therapy? Rethinking the Question of Opioid Misuse Risk.

Beginning in the late 1990s, a movement began within the pain management field focused upon the underutilization of opioids, thought to be a potentially safe and effective class of pain medication. Concern for addiction and misuse were present at the start of this shift within pain medicine, and an emphasis was placed on developing reliable and valid methods and measures of identifying those at risk for opioid misuse. Since that time, the evidence for the safety and effectiveness of chronic opioid therapy (COT) has not been established. Rather, the harmful, dose-dependent deleterious effects have become clearer, including addiction, increased risk of injuries, respiratory depression, opioid induced hyperalgesia, and death. Still, many individuals on low doses of opioids for long periods of time appear to have good pain control and retain social and occupational functioning. Therefore, we propose that the question, "Who is at risk of opioid misuse?" should evolve to, "Who may benefit from COT?" in light of the current evidence.

Evaluation of the Utility of the Edmonton Symptom Assessment System (revised) Scale on a Tertiary Palliative Care Unit.

AIM: The aim of this study was to evaluate the utility of the Edmonton Symptom Assessment System (ESAS-r) Scale on a tertiary palliative care unit. METHOD: There were 92 admitted patients who participated in the study; the scale was administered to those able to participate on day 1 (n = 35, 38 percent), on day 4 (n = 20, 21 percent), and weekly. Patient comfort level with the ESAS-r tool was assessed using a 5-point Likert scale (strongly disagree to strongly agree) on day 4. Nurses' and physicians' perceptions of clinical assessment pre- and postimplementation of the scale were surveyed using a 5-point Likert scale. RESULTS: Of the participating physicians, 75 percent (n = 3) found that the ESAS-r Scale did not enhance clinical assessment; the proportion of nurses with that response was 37.5 percent (n = 6). Among these care providers, 50 percent of the physicians (n = 2) and 62 percent of the nurses (n = 10) thought that the scale was burdensome to patients; but 60 percent of the patients who were able to complete the comfort-level survey (n = 12) indicated that they did not find the scale burdensome. CONCLUSION: Patient acuity, team expertise, perceived burden to patients, and time commitment all influenced staff's recommendation not to implement the ESAS-r tool on the palliative care unit.

A lack of experience-dependent plasticity after more than a decade of recovered sight.

In 2000, monocular vision was restored to M. M., who had been blind between the ages of 3 and 46 years. Tests carried out over 2 years following the surgery revealed impairments of 3-D form, object, and face processing and an absence of object- and face-selective blood-oxygen-level-dependent responses in ventral visual cortex. In the present research, we reexamined M. M. to test for experience-dependent recovery of visual function. Behaviorally, M. M. remains impaired in 3-D form, object, and face processing. Accordingly, we found little to no evidence of the category-selective organization within ventral visual cortex typically associated with face, body, scene, or object processing. We did observe remarkably normal object selectivity within lateral occipital cortex, consistent with M. M.'s previously reported shape-discrimination performance. Together, these findings provide little evidence for recovery of high-level visual function after more than a decade of visual experience in adulthood.