Katherine Travis

All Publications

• Maternal mental health and engagement in developmental care activities with preterm infants in the NICU. Journal of perinatology : official journal of the California Perinatal Association Dubner, S. E., Morales, M. C., Marchman, V. A., Shaw, R. J., Travis, K. E., Scala, M. 2023

  Abstract

  To examine associations between maternal mental health and involvement in developmental care in the NICU.Mothers of infants born <32 weeks gestation (n = 135) were approached to complete mental health screening questionnaires at two weeks after admission. Mothers who completed screening (n = 55) were further classified as with (n = 19) and without (n = 36) elevated scores. Mothers' frequency, rate, and duration of developmental care activities were documented in the electronic health record.35% of screened mothers scored above the cutoff for clinical concern on ≥1 measure. No significant differences between the 3 groups were identified for rates, frequency, or amount of all developmental care, kangaroo care, and swaddled holding.Elevated scores on maternal mental health questionnaires did not relate to developmental care. Maternal developmental care engagement may not indicate mental health status. Universal screening for psychological distress is required to accurately detect symptoms in mothers of hospitalized preterm infants.

  View details for DOI 10.1038/s41372-023-01661-0

  View details for PubMedID 37046070

  View details for PubMedCentralID 8552262

• Inpatient Kangaroo Care Predicts Early Cognitive Development at 6 and 12 Months in Infants Born Very Preterm. medRxiv : the preprint server for health sciences Lazarus, M. F., Marchman, V. A., Brignoni-Perez, E., Dubner, S., Feldman, H. M., Scala, M., Travis, K. E. 2023

  Abstract

  Background: Limited research links hospital-based experiences of Kangaroo Care (KC), or skin-to-skin holding to longer-term neurodevelopmental outcomes in preterm children. The present study examined relations between inpatient KC and cognitive abilities measured at 6- and 12-months of age in a sample of very preterm (VPT) infants.Methods: Retrospective study reviewing medical records of 132 (54% male) VPT infants (<32 weeks gestational age (GA)). We calculated KC frequency (instances/day), KC rate (minutes/day), and KC duration (minutes/instance). Scores on the Cognitive-Adaptive Test were available as part of routine follow-up care at 6 ( n =77) and 12 ( n = 37) months.Results: Families engaged in KC about 2 days/week, 20 minutes/day, and 70 minutes/session, on average, although there was substantial variability. Variation in KC was positively associated with cognitive outcomes at both 6 (frequency: r=0.32; rate: r=0.29) and 12 (frequency: r=0.53; rate: r=0.59; duration: r=0.38) months. KC significantly predicted 7 to 27% unique variance in 6- and 12-month cognitive outcomes, after controlling for GA, socioeconomic status, health acuity, visitation frequency, and prior cognitive scores. Small increases in KC frequency (e.g., 1 day/week), rate (e.g., 20 minutes/day) or duration (e.g., 20 minutes/instance) were associated with 0.5 to 1.0 SD increases in cognitive outcomes at 12 months. SES, GA, and infant health acuity did not moderate these relations.Conclusion: VPT infants with more KC during hospitalization demonstrated higher scores on 6- and 12- month assessments of cognitive development. Results provide strong evidence that KC may confer neuroprotection on VPT infants through the first year of life.Article Summary: Variation in family-delivered Kangaroo Care in the NICU predicted infants' higher cognitive performance at 6 and 12 months, beyond visitation, clinical, and demographic factors.What is Known on This Subject: Kangaroo Care is a developmental care practice associated with positive short-term outcomes for preterm infants. Kangaroo Care is thought to mitigate adverse neurodevelopmental outcomes associated with preterm birth, but direct evidence of effects beyond hospital discharge is limited.What This Study adds: In this retrospective cohort study, frequency, amount, and duration of family-delivered Kangaroo Care in the NICU predicted cognitive abilities at 6 and 12 months. Kangaroo care may be a long-term neuroprotective clinical strategy for infants born preterm.

  View details for DOI 10.1101/2023.04.06.23288260

  View details for PubMedID 37066271

• Disparities in Kangaroo Care for Premature Infants in the Neonatal Intensive Care Unit. Journal of developmental and behavioral pediatrics : JDBP Brignoni-Perez, E., Scala, M., Feldman, H. M., Marchman, V. A., Travis, K. E. 2021

  Abstract

  OBJECTIVE: The aim of this study was to investigate whether preterm infants whose families have lower socioeconomic status (SES) or communicate with clinical staff in a language other than English experience differences in the rate, frequency, and duration of kangaroo care (KC) in the neonatal intensive care unit (NICU) compared with preterm infants of higher SES or primarily English-speaking families.METHODS: Participants were infants born <32 weeks' gestational age (GA), N = 116. We defined SES by the infants' health insurance (private/higher vs public/lower) and language by the language mothers used to communicate with clinical staff (English vs Other language). SES or language groups were compared on (1) rate of KC infants experienced during hospitalization per visitation days, (2) frequency of KC per visitation days, and (3) duration of KC events per day.RESULTS: Infants in the lower SES and Other language groups experienced KC in reduced amounts, lower frequencies, and shorter durations than infants in either the higher SES or English language groups. SES and language group differences remained significant after controlling for family visitation and GA at birth. After controlling for SES, language group differences in KC duration remained significant.CONCLUSION: Our findings revealed disparities in the rate, frequency, and duration of KC experienced in the NICU as a function of both SES and language. Such disparities reduced infants' access to this developmental care practice shown to stabilize clinical status and promote neurodevelopment. We recommend that hospital nurseries implement policies that minimize these disparities.

  View details for DOI 10.1097/DBP.0000000000001029

  View details for PubMedID 34723932

• Impact of the COVID-19 pandemic on developmental care practices for infants born preterm. Early human development Scala, M., Marchman, V. A., Brignoni-Perez, E., Morales, M. C., Dubner, S. E., Travis, K. E. 2021; 163: 105483

  Abstract

  OBJECTIVES: To assess the impact of the COVID-19 pandemic on rates of hospital visitation and rates and durations of developmental care practices for infants born preterm.METHODS: We analyzed electronic medical record data from 129 infants born at less than 32weeks gestational age (GA) cared for in the Lucile Packard Children's Hospital neonatal intensive care unit (NICU) in a COVID-19-affected period (March 8, 2020 to Nov 30, 2020, n=67) and the analogous period in 2019 (n=62). Rates of family visitation and of family- and clinical staff-delivered developmental care were compared across cohorts, adjusting for covariates.RESULTS: Families of infants visited the hospital at nearly half of the rate during 2020 as during 2019 (p=0.001). Infants experienced developmental care less frequently in 2020 vs. 2019 (3.0 vs. 4.3 activities per day; p=0.001), resulting in fewer minutes per day (77.5 vs. 130.0; p=0.001). In 2020, developmental care activities were 5min shorter, on average, than in 2019, p=0.001. Similar reductions occurred in both family- and staff-delivered developmental care. Follow-up analyses indicated that effects persisted and even worsened as the pandemic continued through fall 2020, despite relaxation of hospital visitation policies.CONCLUSIONS: The COVID-19 pandemic has negatively impacted family visitation and preterm infant developmental care practices in the NICU, both experiences associated with positive health benefits. Hospitals should create programs to improve family visitation and engagement, while also increasing staff-delivered developmental care. Careful attention should be paid to long-term follow up of preterm infants and families.

  View details for DOI 10.1016/j.earlhumdev.2021.105483

  View details for PubMedID 34649193

• Neonatal white matter tract microstructure and 2-year language outcomes after preterm birth. NeuroImage. Clinical Dubner, S. E., Rose, J. n., Bruckert, L. n., Feldman, H. M., Travis, K. E. 2020; 28: 102446

  Abstract

  To determine whether variability in diffusion MRI (dMRI) white matter tract metrics, obtained in a cohort of preterm infants prior to neonatal hospital discharge, would be associated with language outcomes at age 2 years, after consideration of age at scan and number of major neonatal complications.30 children, gestational age 28.9 (2.4) weeks, underwent dMRI at mean post menstrual age 36.4 (1.4) weeks and language assessment with the Bayley Scales of Infant Development-III at mean age 22.2 (1.7) months chronological age. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for 5 white matter tracts. Hierarchical linear regression assessed associations between tract FA, moderating variables, and language outcomes.FA of the left inferior longitudinal fasciculus accounted for 17% (p = 0.03) of the variance in composite language and FA of the posterior corpus callosum accounted for 19% (p = 0.02) of the variance in composite language, beyond that accounted for by post-menstrual age at scan and neonatal medical complications. The number of neonatal medical complications moderated the relationship between language and posterior corpus callosum FA but did not moderate the association in the other tract.Language at age 2 is associated with white matter metrics in early infancy in preterm children. The different pattern of associations by fiber group may relate to the stage of brain maturation and/or the nature and timing of medical complications related to preterm birth. Future studies should replicate these findings with a larger sample size to assure reliability of the findings.

  View details for DOI 10.1016/j.nicl.2020.102446

  View details for PubMedID 33035964

• More than myelin: Probing white matter differences in prematurity with quantitative T1 and diffusion MRI. NeuroImage. Clinical Travis, K. E., Castro, M. R., Berman, S., Dodson, C. K., Mezer, A. A., Ben-Shachar, M., Feldman, H. M. 2019; 22: 101756

  Abstract

  OBJECTIVE: We combined diffusion MRI (dMRI) with quantitative T1 (qT1) relaxometry in a sample of school-aged children born preterm and full term to determine whether reduced fractional anisotropy (FA) within the corpus callosum of the preterm group could be explained by a reduction in myelin content, as indexed by R1 (1/T1) from qT1 scans.METHODS: 8-year-old children born preterm (n = 29; GA 22-32 weeks) and full term (n = 24) underwent dMRI and qT1 scans. Four subdivisions of the corpus callosum were segmented in individual native space according to cortical projection zones (occipital, temporal, motor and anterior-frontal). Fractional anisotropy (FA) and R1 were quantified along the tract trajectory of each subdivision and compared across two birth groups.RESULTS: Compared to controls, preterm children demonstrated significantly decreased FA in 3 of 4 analyzed corpus callosum subdivisions (temporal, motor, and anterior frontal segments) and decreased R1 in only 2 of 4 corpus callosum subdivisions (temporal and motor segments). FA and RD were significantly associated with R1 within temporal but not anterior frontal subdivisions of the corpus callosum in the term group; RD correlated with R1 in the anterior subdivision in the preterm group only.CONCLUSIONS: Myelin content, as indexed by R1, drives some but not all of the differences in white matter between preterm and term born children. Other factors, such as axonal diameter and directional coherence, likely contributed to FA differences in the anterior frontal segment of the corpus callosum that were not well explained by R1.

  View details for PubMedID 30901711

• White matter microstructure and cognitive outcomes in relation to neonatal inflammation in 6-year-old children born preterm. NeuroImage. Clinical Dubner, S. E., Dodson, C. K., Marchman, V. A., Ben-Shachar, M. n., Feldman, H. M., Travis, K. E. 2019; 23: 101832

  Abstract

  Cognitive outcomes in preterm (PT) children have been associated with microstructural properties of white matter. PT children who experienced neonatal inflammatory conditions have poorer cognitive outcomes than those who did not. The goal of this study was to contrast white matter microstructure and cognitive outcomes after preterm birth in relation to the presence or absence of severe inflammatory conditions in the neonatal period.PT children (n = 35), born at gestational age 22-32 weeks, were classified as either PT+ (n = 12) based on a neonatal history of inflammatory conditions, including bronchopulmonary dysplasia, necrotizing enterocolitis or culture positive sepsis, or PT- (n = 23) based on the absence of the three inflammatory conditions. Full term (FT) children (n = 43) served as controls. Participants underwent diffusion MRI and cognitive testing (intelligence, reading, and executive function) at age 6 years. The corpus callosum was segmented into 7 regions using deterministic tractography and based on the cortical projection zones of the callosal fibers. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for each segment. General linear models with planned contrasts assessed group differences in FA, MD and cognitive outcomes. Pearson correlations assessed associations of white matter metrics and cognitive outcome measures.FA was significantly lower and MD was significantly higher in PT+ compared to PT- or FT groups in multiple callosal segments, even after adjusting for gestational age. Executive function scores, but not intelligence or reading scores, were less favorable in PT+ than in PT- groups. Among the entire sample, occipital FA was significantly correlated with IQ (r = 0.25, p < 0.05), reading (r = 0.32, p < 0.01), and executive function (r = -0.28, p < 0.05) measures. Anterior frontal FA and superior parietal FA were significantly correlated with executive function (r = -0.25, r = 0.23, respectively, p < 0.05).We observed differences in the white matter microstructure of the corpus callosum and in the cognitive skills of 6-year-old PT children based on their history of neonatal inflammation. Neonatal inflammation is one medical factor that may contribute to variation in long-term neurobiological and neuropsychological outcomes in PT samples.

  View details for PubMedID 31075555

• White matter microstructure and cognitive outcomes in relation to neonatal inflammation in 6-year-old children born preterm NEUROIMAGE-CLINICAL Dubner, S. E., Dodson, C. K., Marchman, V. A., Ben-Shachar, M., Feldman, H. M., Travis, K. E. 2019; 23

  View details for DOI 10.1016/j.nicl.2019.101832

  View details for Web of Science ID 000485804400037

• More than myelin: Probing white matter differences in prematurity with quantitative T1 and diffusion MRI NEUROIMAGE-CLINICAL Travis, K. E., Castro, M. H., Berman, S., Dodson, C. K., Mezer, A. A., Ben-Shachar, M., Feldman, H. M. 2019; 22

  View details for DOI 10.1016/j.nicl.2019.101756

  View details for Web of Science ID 000470123000081

• Microstructural properties of white matter pathways in relation tosubsequent reading abilities in children: a longitudinal analysis. Brain structure & function Borchers, L. R., Bruckert, L., Dodson, C. K., Travis, K. E., Marchman, V. A., Ben-Shachar, M., Feldman, H. M. 2018

  Abstract

  Microstructural properties of white matter pathways are associated with concurrent reading abilities in children. In this longitudinal study, we asked whether properties of white matter pathways at the onset of learning to read would be associated with reading abilities at older ages. Children (N=37) with a wide range of reading abilities completed standardized measures of language and phonological awareness and diffusion MRI at age 6years. Mean tract-fractional anisotropy (FA) was extracted from reading-related pathways. At age 8, the same children were re-assessed using a standardized reading measure. Using linear regressions, we examined the contribution of tract-FA at age 6 to reading outcome at age 8, beyond known demographic and pre-literacy predictors of reading. Tract-FA of the left arcuate, left and right superior longitudinal fasciculus (SLF), and left inferior cerebellar peduncle (ICP) made unique contributions to reading outcome after consideration of sex and family history of reading delays. Tract-FA of the left and right SLF and left ICP made unique contributions to reading outcome after the addition of pre-literacy skills. Thus, cerebellar and bilateral cortical pathways represented a network associated with subsequent reading abilities. Early white matter properties may be associated with other neuropsychological functions that predict reading or may influence reading development, independent of reading-related abilities. Tract FA at early stages of learning to read may serve as a biomarker of later reading abilities.

  View details for PubMedID 30539288

• White matter properties associated with pre-reading skills in 6-year-old children born preterm and at term. Developmental medicine and child neurology Dodson, C. K., Travis, K. E., Borchers, L. R., Marchman, V. A., Ben-Shachar, M., Feldman, H. M. 2018

  Abstract

  AIM: To assess associations between white matter properties and pre-reading skills (phonological awareness and receptive and expressive language) in children born preterm and at term at the onset of reading acquisition.METHOD: Six-year-old children born preterm (n=36; gestational age 22-32wks) and at term (n=43) underwent diffusion magnetic resonance imaging and behavioural assessments. Tracts were selected a priori based on findings from a study of 6-year-old children born at term: the left-hemisphere arcuate fasciculus and superior longitudinal fasciculus, and right-hemisphere uncinate fasciculus. Using linear regression, we assessed associations between fractional anisotropy of tracts and phonological awareness and receptive and expressive language scores. We investigated whether associations were moderated by prematurity.RESULTS: Fractional anisotropy of the left-hemisphere arcuate fasciculus contributed unique variance to phonological awareness across birth groups. The association between fractional anisotropy of the right-hemisphere uncinate fasciculus and receptive and expressive language was significantly moderated by prematurity.INTERPRETATION: A left-hemisphere tract was associated with phonological awareness in both birth groups. A right-hemisphere tract was associated with language only in the term group, suggesting that expressive and receptive language is mediated by different white matter pathways in 6-year-old children born preterm. These findings provide novel insights into similarities and differences of the neurobiology of pre-reading skills between children born preterm and at term at reading onset.WHAT THIS PAPER ADDS: White matter properties and pre-reading abilities were associated in children born preterm at the onset of reading. The neurobiology of phonological awareness was similar in children born preterm versus children born at term at 6 years. The neurobiology of language was different in children born preterm versus children born at term at 6 years.

  View details for PubMedID 29722009

• White matter properties differ in 6-year old Readers and Pre-readers BRAIN STRUCTURE & FUNCTION Travis, K. E., Adams, J. N., Kovachy, V. N., Ben-Shachar, M., Feldman, H. M. 2017; 222 (4): 1685-1703

  Abstract

  Reading, an essential life skill in modern society, is typically learned during childhood. Adults who can read show white matter differences compared to adults who never learned to read. Studies have not established whether children who can read show similar white matter differences compared to children who cannot read. We compared 6-year old children who could decode written English words and pseudowords (n = 31; Readers) and 6-year old children who could not decode pseudowords and had a standard score <100 on a task for reading single words (n = 11; Pre-readers). We employed diffusion MRI and tractography to extract fractional anisotropy (FA) along the trajectory of six bilateral intra-hemispheric tracts and two posterior subdivisions of the corpus callosum. Readers demonstrated significantly increased FA within the left anterior segment of the superior longitudinal fasciculus (aSLF-L) and the right uncinate fasciculus (UF-R) compared to Pre-readers. FA in the aSLF-L was significantly correlated with phonological awareness; FA in the UF-R was significantly correlated with language. Correlations in the UF-R but not the aSLF-L remained significant after controlling for reading ability, revealing that UF-R group differences were related to both children's language and reading abilities. Taken together, these findings demonstrate new evidence showing that individual differences in white matter structure relate to whether children have begun to read.

  View details for DOI 10.1007/s00429-016-1302-1

  View details for Web of Science ID 000400186400010

• White matter properties differ in 6-year old Readers and Pre-readers. Brain structure & function Travis, K. E., Adams, J. N., Kovachy, V. N., Ben-Shachar, M., Feldman, H. M. 2016: -?

  Abstract

  Reading, an essential life skill in modern society, is typically learned during childhood. Adults who can read show white matter differences compared to adults who never learned to read. Studies have not established whether children who can read show similar white matter differences compared to children who cannot read. We compared 6-year old children who could decode written English words and pseudowords (n = 31; Readers) and 6-year old children who could not decode pseudowords and had a standard score <100 on a task for reading single words (n = 11; Pre-readers). We employed diffusion MRI and tractography to extract fractional anisotropy (FA) along the trajectory of six bilateral intra-hemispheric tracts and two posterior subdivisions of the corpus callosum. Readers demonstrated significantly increased FA within the left anterior segment of the superior longitudinal fasciculus (aSLF-L) and the right uncinate fasciculus (UF-R) compared to Pre-readers. FA in the aSLF-L was significantly correlated with phonological awareness; FA in the UF-R was significantly correlated with language. Correlations in the UF-R but not the aSLF-L remained significant after controlling for reading ability, revealing that UF-R group differences were related to both children's language and reading abilities. Taken together, these findings demonstrate new evidence showing that individual differences in white matter structure relate to whether children have begun to read.

  View details for PubMedID 27631434

• Case Series: Fractional Anisotropy Profiles of the Cerebellar Peduncles in Adolescents Born Preterm With Ventricular Dilation JOURNAL OF CHILD NEUROLOGY Travis, K. E., Leitner, Y., Ben-Shachar, M., Yeom, K. W., Feldman, H. M. 2016; 31 (3): 321-327

  Abstract

  This case series assesses white matter microstructure of the cerebellar peduncles in 4 adolescents born preterm with enlarged ventricles and reduced white matter volume in the cerebrum but no apparent injury to the cerebellum. Subjects (ages 12-17 years, gestational age 26-32 weeks, birth weight 825-2211 g) were compared to a normative sample of 19 full-term controls (9-17 years, mean gestational age 39 weeks, mean birth weight 3154 g). Tract profiles for each of the cerebellar peduncles were generated by calculating fractional anisotropy at 30 points along the central portion of each tract. One or more case subjects exhibited higher fractional anisotropy beyond the 90th percentile in the inferior, middle, and superior cerebellar peduncles. Findings demonstrate that differences in cerebellar white matter microstructure can be detected in the absence of macrostructural cerebellar abnormalities.

  View details for DOI 10.1177/0883073815592223

  View details for PubMedID 26116381

• Variations in the neurobiology of reading in children and adolescents born full term and preterm NEUROIMAGE-CLINICAL Travis, K. E., Ben-Shachar, M., Myall, N. J., Feldman, H. M. 2016; 11: 555-565

  Abstract

  Diffusion properties of white matter tracts have been associated with individual differences in reading. Individuals born preterm are at risk of injury to white matter. In this study we compared the associations between diffusion properties of white matter and reading skills in children and adolescents born full term and preterm. 45 participants, aged 9-17 years, included 26 preterms (born < 36 weeks' gestation) and 19 full-terms. Tract fractional anisotropy (FA) profiles were generated for five bilateral white matter tracts previously associated with reading: anterior superior longitudinal fasciculus (aSLF), arcuate fasciculus (Arc), corticospinal tract (CST), uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF). Mean scores on reading for the two groups were in the normal range and were not statistically different. In both groups, FA was associated with measures of single word reading and comprehension in the aSLF, AF, CST, and UF. However, correlations were negative in the full term group and positive in the preterm group. These results demonstrate variations in the neurobiology of reading in children born full term and preterm despite comparable reading skills. Findings suggest that efficient information exchange required for strong reading abilities may be accomplished via a different balance of neurobiological mechanisms in different groups of readers.

  View details for DOI 10.1016/j.nicl.2016.04.003

  View details for PubMedID 27158588

• Tract Profiles of the Cerebellar White Matter Pathways in Children and Adolescents CEREBELLUM Leitner, Y., Travis, K. E., Ben-Shachar, M., Yeom, K. W., Feldman, H. M. 2015; 14 (6): 613-623

  Abstract

  Intact development of cerebellar connectivity is essential for healthy neuromotor and neurocognitive development. To date, limited knowledge about the microstructural properties of the cerebellar peduncles, the major white matter tracts of the cerebellum, is available for children and adolescents. Such information would be useful as a comparison for studies of normal development, clinical conditions, or associations of cerebellar structures with cognitive and motor functions. The goal of the present study was to evaluate the variability in diffusion measures of the cerebellar peduncles within individuals and within a normative sample of healthy children. Participants were 19 healthy children and adolescents, aged 9-17 years, mean age 13.0 ± 2.3. We analyzed diffusion magnetic resonance imaging (dMRI) data with deterministic tractography. We generated tract profiles for each of the cerebellar peduncles by extracting four diffusion properties (fractional anisotropy (FA) and mean, radial, and axial diffusivity) at 30 equidistant points along each tract. We were able to identify the middle cerebellar peduncle and the bilateral inferior and superior cerebellar peduncles in all participants. The results showed that within each of the peduncles, the diffusion properties varied along the trajectory of the tracts. However, the tracts showed consistent patterns of variation across individuals; the coefficient of variation for FA across individual profiles was low (≤20 %) for each tract. We observed no systematic variation of the diffusion properties with age. These cerebellar tract profiles of the cerebellar peduncles can serve as a reference for future studies of children across the age range and for children and adolescents with clinical conditions that affect the cerebellum.

  View details for DOI 10.1007/s12311-015-0652-1

  View details for PubMedID 25648754

• Cerebellar White Matter Pathways are Associated With Reading Skills in Children and Adolescents HUMAN BRAIN MAPPING Travis, K. E., Leitner, Y., Feldman, H. M., Ben-Shachar, M. 2015; 36 (4): 1536-1553

  Abstract

  Reading is a critical life skill in the modern world. The neural basis of reading incorporates a distributed network of cortical areas and their white matter connections. The cerebellum has also been implicated in reading and reading disabilities. However, little is known about the contribution of cerebellar white matter pathways to major component skills of reading. We used diffusion magnetic resonance imaging (dMRI) with tractography to identify the cerebellar peduncles in a group of 9- to 17-year-old children and adolescents born full term (FT, n = 19) or preterm (PT, n = 26). In this cohort, no significant differences were found between fractional anisotropy (FA) measures of the peduncles in the PT and FT groups. FA of the cerebellar peduncles correlated significantly with measures of decoding and reading comprehension in the combined sample of FT and PT subjects. Correlations were negative in the superior and inferior cerebellar peduncles and positive in the middle cerebellar peduncle. Additional analyses revealed that FT and PT groups demonstrated similar patterns of reading associations within the left superior cerebellar peduncle, middle cerebellar peduncle, and left inferior cerebellar peduncle. Partial correlation analyses showed that distinct sub-skills of reading were associated with FA in segments of different cerebellar peduncles. Overall, the present findings are the first to document associations of microstructure of the cerebellar peduncles and the component skills of reading. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.

  View details for DOI 10.1002/hbm.22721

  View details for PubMedID 25504986

• Decreased and Increased Anisotropy along Major Cerebral White Matter Tracts in Preterm Children and Adolescents PLoS One Travis, K. E., Adams, J. N., Ben-Shachar, M., Feldman, H. M. 2015

  View details for DOI 10.1371/journal.pone.0142860

• Decreased and Increased Anisotropy along Major Cerebral White Matter Tracts in Preterm Children and Adolescents. PloS one Travis, K. E., Adams, J. N., Ben-Shachar, M., Feldman, H. M. 2015; 10 (11): e0142860

  Abstract

  Premature birth is highly prevalent and associated with neurodevelopmental delays and disorders. Adverse outcomes, particularly in children born before 32 weeks of gestation, have been attributed in large part to white matter injuries, often found in periventricular regions using conventional imaging. To date, tractography studies of white matter pathways in children and adolescents born preterm have evaluated only a limited number of tracts simultaneously. The current study compares diffusion properties along 18 major cerebral white matter pathways in children and adolescents born preterm (n = 27) and full term (n = 19), using diffusion magnetic resonance imaging and tractography. We found that compared to the full term group, the preterm group had significantly decreased FA in segments of the bilateral uncinate fasciculus and anterior segments of the right inferior fronto-occipital fasciculus. Additionally, the preterm group had significantly increased FA in segments of the right and left anterior thalamic radiations, posterior segments of the right inferior fronto-occipital fasciculus, and the right and left inferior longitudinal fasciculus. Increased FA in the preterm group was generally associated with decreased radial diffusivity. These findings indicate that prematurity-related white matter differences in later childhood and adolescence do not affect all tracts in the periventricular zone and can involve both decreased and increased FA. Differences in the patterns of radial diffusivity and axial diffusivity suggest that the tissue properties underlying group FA differences may vary within and across white matter tracts. Distinctive diffusion properties may relate to variations in the timing of injury in the neonatal period, extent of white matter dysmaturity and/or compensatory processes in childhood.

  View details for DOI 10.1371/journal.pone.0142860

  View details for PubMedID 26560745

• Abnormal white matter properties in adolescent girls with anorexia nervosa. NeuroImage. Clinical Travis, K. E., Golden, N. H., Feldman, H. M., Solomon, M., Nguyen, J., Mezer, A., Yeatman, J. D., Dougherty, R. F. 2015; 9: 648-659

  Abstract

  Anorexia nervosa (AN) is a serious eating disorder that typically emerges during adolescence and occurs most frequently in females. To date, very few studies have investigated the possible impact of AN on white matter tissue properties during adolescence, when white matter is still developing. The present study evaluated white matter tissue properties in adolescent girls with AN using diffusion MRI with tractography and T1 relaxometry to measure R1 (1/T1), an index of myelin content. Fifteen adolescent girls with AN (mean age = 16.6 years ± 1.4) were compared to fifteen age-matched girls with normal weight and eating behaviors (mean age = 17.1 years ± 1.3). We identified and segmented 9 bilateral cerebral tracts (18) and 8 callosal fiber tracts in each participant's brain (26 total). Tract profiles were generated by computing measures for fractional anisotropy (FA) and R1 along the trajectory of each tract. Compared to controls, FA in the AN group was significantly decreased in 4 of 26 white matter tracts and significantly increased in 2 of 26 white matter tracts. R1 was significantly decreased in the AN group compared to controls in 11 of 26 white matter tracts. Reduced FA in combination with reduced R1 suggests that the observed white matter differences in AN are likely due to reductions in myelin content. For the majority of tracts, group differences in FA and R1 did not occur within the same tract. The present findings have important implications for understanding the neurobiological factors underlying white matter changes associated with AN and invite further investigations examining associations between white matter properties and specific physiological, cognitive, social, or emotional functions affected in AN.

  View details for DOI 10.1016/j.nicl.2015.10.008

  View details for PubMedID 26740918

• Spatiotemporal Neural Dynamics of Word Understanding in 12- to 18-Month-Old-Infants CEREBRAL CORTEX Travis, K. E., Leonard, M. K., Brown, T. T., Hagler, D. J., Curran, M., Dale, A. M., Elman, J. L., Halgren, E. 2011; 21 (8): 1832-1839

  Abstract

  Learning words is central in human development. However, lacking clear evidence for how or where language is processed in the developing brain, it is unknown whether these processes are similar in infants and adults. Here, we use magnetoencephalography in combination with high-resolution structural magnetic resonance imaging to noninvasively estimate the spatiotemporal distribution of word-selective brain activity in 12- to 18-month-old infants. Infants watched pictures of common objects and listened to words that they understood. A subset of these infants also listened to familiar words compared with sensory control sounds. In both experiments, words evoked a characteristic event-related brain response peaking ∼400 ms after word onset, which localized to left frontotemporal cortices. In adults, this activity, termed the N400m, is associated with lexico-semantic encoding. Like adults, we find that the amplitude of the infant N400m is also modulated by semantic priming, being reduced to words preceded by a semantically related picture. These findings suggest that similar left frontotemporal areas are used for encoding lexico-semantic information throughout the life span, from the earliest stages of word learning. Furthermore, this ontogenetic consistency implies that the neurophysiological processes underlying the N400m may be important both for understanding already known words and for learning new words.

  View details for DOI 10.1093/cercor/bhq259

  View details for Web of Science ID 000293076300012

  View details for PubMedID 21209121

• Investigating relations between the NICU speech environment and weight gain in infants born very preterm. American journal of perinatology Kumar, K., Marchman, V. A., Morales, M. C., Scala, M., Travis, K. E. 2023

  Abstract

  Children born preterm, especially those born very preterm (< 32 weeks gestational age, GA), are at risk for poor growth and adverse neurodevelopmental outcomes. Adverse growth and neurodevelopmental outcomes in preterm children have been attributed, in part, to the aversive sounds and relative speech paucity of the neonatal intensive care unit (NICU). Experimental studies that directly expose preterm infants to speech sounds in the NICU find significant improvements in health factors relevant for neurodevelopment. Few studies have examined whether natural variations in the speech environment of the NICU are related to short-term health outcomes in preterm infants. Such data are important for optimizing the sound environment of the NICU.Examine relations between the NICU speech environment and rate of weight gain during hospitalization.Participants were infants born very preterm (n = 20). The speech environment of each infant was assessed at 32-36 weeks postmenstrual age using an automatic speech-counting device. Average rates of weight gain (g/kg/day) were ascertained over the same period. Calories were derived from charted intake (kcals/kg/day). Linear regressions examined caloric intake and speech counts as predictors of infant weight gain.Infant weight gain was significantly predicted by caloric intake and speech exposure, each uniquely accounting for ~27% variance (Total R2 = 60.2%; p < .001). Speech counts were uncorrelated with rates of family visitation, time in incubator, or health acuity.While future research should establish causality and direction of effects, enhancing speech exposure in the NICU may be beneficial for physical growth. NICU care plans should consider opportunities to increase speech exposure.

  View details for DOI 10.1055/a-2023-8813

  View details for PubMedID 36720260

• EFFECTS OF POSTNATAL GLUCOCORTICOIDS ON BRAIN STRUCTURE IN PRETERM INFANTS, A SCOPING REVIEW. Neuroscience and biobehavioral reviews Robles, I., Eidsness, M. A., Travis, K. E., Feldman, H. M., Dubner, S. E. 2023: 105034

  Abstract

  Glucocorticoids (GC) are used in neonatal intensive care units to prevent or reduce the severity of chronic lung disease in preterm infants and have been implicated in impaired neurodevelopment. Our objective was to identify what is known about the effects of postnatal GC treatment in human preterm infants on structural brain development and to identify gaps in the literature. Following Arksey and O'Malley's scoping review methodological framework, we searched scientific literature databases for original research on human preterm infants, postnatal GCs, and brain structure. 11 studies assessed the effects of GCs on structural brain outcomes. 56 studies reported brain injury, but not structure. Dexamethasone was consistently associated with decreased total and regional brain volumes, including cerebellar volumes. Hydrocortisone was often, but not always associated with absence of brain volume differences. No studies examined the impact of inhaled GC on brain structure. Additional research on the effects of neonatal GCs after preterm birth on a variety of structural brain measures is required for understanding contributions to neurodevelopment and informing practice guidelines.

  View details for DOI 10.1016/j.neubiorev.2023.105034

  View details for PubMedID 36608916

• White matter properties underlying reading abilities differ in 8-year-old children born full term and preterm: A multi-modal approach NEUROIMAGE Brignoni-Perez, E., Dubner, S. E., Ben-Shachar, M., Berman, S., Mezer, A. A., Feldman, H. M., Travis, K. E. 2022; 256

  View details for DOI 10.1016/j.neuroimage.2022.119246

  View details for Web of Science ID 000830858700002

• White matter properties underlying reading abilities differ in 8-year-old children born full term and preterm: A multi-modal approach. NeuroImage Brignoni-Perez, E., Dubner, S. E., Ben-Shachar, M., Berman, S., Mezer, A. A., Feldman, H. M., Travis, K. E. 2022: 119240

  Abstract

  Many diffusion magnetic resonance imaging (dMRI) studies document associations between reading skills and fractional anisotropy (FA) within brain white matter, suggesting that efficient transfer of information across the brain contributes to individual differences in reading. Use of complementary imaging methods can determine if these associations relate to myelin content of white matter tracts. Compared to children born at term (FT), children born preterm (PT) are at risk for reading deficits. We used two MRI methods to calculate associations of reading and white matter properties in FT and PT children. Participants (N=79: 36 FT and 43 PT) were administered the Gray's Oral Reading Test at age 8. We segmented three dorsal (left arcuate and bilateral superior longitudinal fasciculus) and four ventral (bilateral inferior longitudinal fasciculus and bilateral uncinate) tracts and quantified (1) FA from dMRI and (2) R1 from quantitative T1 relaxometry. We examined correlations between reading scores and these metrics along the trajectories of the tracts. Reading positively correlated with FA in segments of left arcuate and bilateral superior longitudinal fasciculi in FT children; no FA associations were found in PT children. Reading positively correlated with R1 in segments of the left superior longitudinal, right uncinate, and left inferior longitudinal fasciculi in PT children; no R1 associations were found in FT children. Birth group significantly moderated the associations of reading and white matter metrics. Myelin content of white matter may contribute to individual differences in PT but not FT children.

  View details for DOI 10.1016/j.neuroimage.2022.119240

  View details for PubMedID 35490913

• Spatiotemporal changes in along-tract profilometry of cerebellar peduncles in cerebellar mutism syndrome. NeuroImage. Clinical Toescu, S. M., Bruckert, L., Jabarkheel, R., Yecies, D., Zhang, M., Clark, C. A., Mankad, K., Aquilina, K., Grant, G. A., Feldman, H. M., Travis, K. E., Yeom, K. W. 2022: 103000

  Abstract

  Cerebellar mutism syndrome, characterised by mutism, emotional lability and cerebellar motor signs, occurs in up to 39% of children following resection of medulloblastoma, the most common malignant posterior fossa tumour of childhood. Its pathophysiology remains unclear, but prior studies have implicated damage to the superior cerebellar peduncles. In this study, the objective was to conduct high-resolution spatial profilometry of the cerebellar peduncles and identify anatomic biomarkers of cerebellar mutism syndrome. In this retrospective study, twenty-eight children with medulloblastoma (mean age 8.8±3.8years) underwent diffusion MRI at four timepoints over one year. Forty-nine healthy children (9.0±4.2years), scanned at a single timepoint, served as age- and sex-matched controls. Automated Fibre Quantification was used to segment cerebellar peduncles and compute fractional anisotropy (FA) at 30 nodes along each tract. Thirteen patients developed cerebellar mutism syndrome. FA was significantly lower in the distal third of the left superior cerebellar peduncle pre-operatively in all patients compared to controls (FA in proximal third 0.228, middle and distal thirds 0.270, p=0.01, Cohen's d=0.927). Pre-operative differences in FA did not predict cerebellar mutism syndrome. However, post-operative reductions in FA were highly specific to the distal left superior cerebellar peduncle, and were most pronounced in children with cerebellar mutism syndrome compared to those without at the 1-4month follow up (0.325 vs 0.512, p=0.042, d=1.36) and at the 1-year follow up (0.342, vs 0.484, p=0.038, d=1.12). High spatial resolution cerebellar profilometry indicated a site-specific alteration of the distal segment of the superior cerebellar peduncle seen in cerebellar mutism syndrome which may have important surgical implications in the treatment of these devastating tumours of childhood.

  View details for DOI 10.1016/j.nicl.2022.103000

  View details for PubMedID 35370121

• Neonatal Inflammation, Corpus Callosum Microstructure, and Language Skills in 2-Year-Old Children Born Preterm Dubner, S. E., Sproul, D., Rickerich, L., Robles, I., Feldman, H., Travis, K. LIPPINCOTT WILLIAMS & WILKINS. 2022: E140-E141

  View details for Web of Science ID 000797424900075

• Associations of Behavioral Problems and White Matter Properties of the Cerebellar Peduncles in Boys and Girls Born Full Term and Preterm. Cerebellum (London, England) Hosoki, M., Bruckert, L., Borchers, L. R., Marchman, V. A., Travis, K. E., Feldman, H. M. 2022

  Abstract

  Accumulating evidence suggests that the role of cerebellum includes regulation of behaviors; cerebellar impairment may lead to behavioral problems. Behavioral problems differ by sex: internalizing problems are more common in girls, externalizing problems in boys. Behavioral problems are also elevated in children born preterm (PT) compared to children born full term (FT). The current study examined internalizing and externalizing problems in 8-year-old children in relation to sex, birth-group, fractional anisotropy (FA) of the three cerebellar peduncles (superior, middle, and inferior), and interactions among these predictor variables. Participants (N = 78) were 44 boys (28 PT) and 34 girls (15 PT). We assessed behavioral problems via standardized parent reports and FA of the cerebellar peduncles using deterministic tractography. Internalizing problems were higher in children born PT compared to children born FT (p = .032); the interaction of sex and birth-group was significant (p = .044). When considering the contribution of the mean-tract FA of cerebellar peduncles to behavioral problems, there was a significant interaction of sex and mean-tract FA of the inferior cerebellar peduncle (ICP) with internalizing problems; the slope was negative in girls (p = .020) but not in boys. In boys, internalizing problems were only associated with mean-tract FA ICP in those born preterm (p = .010). We found no other significant associations contributing to internalizing or externalizing problems. Thus, we found sexual dimorphism and birth-group differences in the association of white matter metrics of the ICP and internalizing problems in school-aged children. The findings inform theories of the origins of internalizing behavioral problems in middle childhood and may suggest approaches to treatment at school age.

  View details for DOI 10.1007/s12311-022-01375-7

  View details for PubMedID 35138604

• Listening to Mom in the NICU: effects of increased maternal speech exposure on language outcomes and white matter development in infants born very preterm. Trials Brignoni-Perez, E., Morales, M. C., Marchman, V. A., Scala, M., Feldman, H. M., Yeom, K., Travis, K. E. 2021; 22 (1): 444

  Abstract

  BACKGROUND: Infants born very preterm (<32weeks gestational age (GA)) are at risk for developmental language delays. Poor language outcomes in children born preterm have been linked to neurobiological factors, including impaired development of the brain's structural connectivity (white matter), and environmental factors, including decreased exposure to maternal speech in the neonatal intensive care unit (NICU). Interventions that enhance preterm infants' exposure to maternal speech show promise as potential strategies for improving short-term health outcomes. Intervention studies have yet to establish whether increased exposure to maternal speech in the NICU offers benefits beyond the newborn period for brain and language outcomes.METHODS: This randomized controlled trial assesses the long-term effects of increased maternal speech exposure on structural connectivity at 12months of age (age adjusted for prematurity (AA)) and language outcomes between 12 and 18months of age AA. Study participants (N=42) will include infants born very preterm (24-31weeks 6/7days GA). Newborns are randomly assigned to the treatment (n=21) or standard medical care (n=21) group. Treatment consists of increased maternal speech exposure, accomplished by playing audio recordings of each baby's own mother reading a children's book via an iPod placed in their crib/incubator. Infants in the control group have the identical iPod setup but are not played recordings. The primary outcome will be measures of expressive and receptive language skills, obtained from a parent questionnaire collected at 12-18months AA. The secondary outcome will be measures of white matter development, including the mean diffusivity and fractional anisotropy derived from diffusion magnetic resonance imaging scans performed at around 36weeks postmenstrual age during the infants' routine brain imaging session before hospital discharge and 12months AA.DISCUSSION: The proposed study is expected to establish the potential impact of increased maternal speech exposure on long-term language outcomes and white matter development in infants born very preterm. If successful, the findings of this study may help to guide NICU clinical practice for promoting language and brain development. This clinical trial has the potential to advance theoretical understanding of how early language exposure directly changes brain structure for later language learning.TRIAL REGISTRATION: NIH Clinical Trials (ClinicalTrials.gov) NCT04193579 . Retrospectively registered on 10 December 2019.

  View details for DOI 10.1186/s13063-021-05385-4

  View details for PubMedID 34256820

• Retrospective Cohort Study of Early Postnatal Hydrocortisone in Infants Born Extremely Preterm and 12 Month Outcomes Dubner, S. E., Scala, M., Feldman, H. M., Travis, K. E. LIPPINCOTT WILLIAMS & WILKINS. 2021: S22

  View details for Web of Science ID 000670615500076

• Associations of Attention Problems, Behavior Problems, Social Competence, and Academic Skills in a School Aged Children Born Preterm and Term Hosoki, M., Travis, K. E., Feldman, H. M. LIPPINCOTT WILLIAMS & WILKINS. 2021: S18

  View details for Web of Science ID 000656627200061

• Disparities in Kangaroo Care in the Neonatal Intensive Care Unit as a function of Mother's Language Brignoni-Perez, E., Scala, M., Marchman, V. A., Feldman, H. M., Travis, K. E. LIPPINCOTT WILLIAMS & WILKINS. 2021: S24-S25

  View details for Web of Science ID 000656627200082

• Retrospective Cohort Study of Early Postnatal Hydrocortisone in Infants Born Extremely Preterm and 12 Month Outcomes Dubner, S. E., Scala, M., Feldman, H. M., Travis, K. E. LIPPINCOTT WILLIAMS & WILKINS. 2021: S22

  View details for Web of Science ID 000656627200076

• Associations of Attention Problems, Behavior Problems, Social Competence, and Academic Skills in a School Aged Children Born Preterm and Term Hosoki, M., Travis, K. E., Feldman, H. M. LIPPINCOTT WILLIAMS & WILKINS. 2021: S18

  View details for Web of Science ID 000670615500061

• Disparities in Kangaroo Care in the Neonatal Intensive Care Unit as a function of Mother's Language Brignoni-Perez, E., Scala, M., Marchman, V. A., Feldman, H. M., Travis, K. E. LIPPINCOTT WILLIAMS & WILKINS. 2021: S24-S25

  View details for Web of Science ID 000670615500082

• Associations of Reading Efficiency with White Matter Properties of the Cerebellar Peduncles in Children. Cerebellum (London, England) Bruckert, L., Travis, K. E., Mezer, A. A., Ben-Shachar, M., Feldman, H. M. 2020

  Abstract

  Reading in children has been associated with microstructural properties of the cerebellar peduncles, the white matter pathways connecting the cerebellum to the cerebrum. In this study, we used two independent neuroimaging modalities to assess which features of the cerebellar peduncles would be associated with reading. Twenty-three 8-year-old children were evaluated on word reading efficiency and imaged using diffusion MRI (dMRI) and quantitative T1 relaxometry (qT1). We segmented the superior (SCP), middle, and inferior cerebellar peduncles and extracted two metrics: fractional anisotropy (FA) from dMRI and R1 from qT1. Tract-FA was significantly correlated with tract-R1 in left and right SCPs (left: rP(21)=.63, right: rP(21)=.76, p≤.001) suggesting that FA of these peduncles, at least in part, indexed myelin content. Tract-FA and tract R1 were not correlated in the other cerebellar peduncles. Reading efficiency negatively correlated with tract-FA of the left (rP(21)=-.43, p=.040) and right SCP (rP(21)=-.37, p=.079). Reading efficiency did not correlate with tract-R1 in the SCPs. The negative association of reading efficiency with tract-FA and the lack of association of reading efficiency with tract-R1 implicate properties other than myelin content as relevant to the information flow between the cerebellum and the cerebrum for individual differences in reading skills in children.

  View details for DOI 10.1007/s12311-020-01162-2

  View details for PubMedID 32642932

• Assessing speech exposure in the NICU: Implications for speech enrichment for preterm infants. Journal of perinatology : official journal of the California Perinatal Association Scala, M. L., Marchman, V. A., Godenzi, C. n., Gao, C. n., Travis, K. E. 2020

  Abstract

  Quantify NICU speech exposure over multiple days in relation to NICU care practices.Continuous measures of speech exposure were obtained for preterm infants (n = 21; 12 M) born <34 weeks gestational age in incubators (n = 12) or open cribs (n = 9) for 5-14 days. Periods of care (routine, developmental) and delivery source (family, medical staff, cuddler) were determined through chart review.Infants spent 13% of their time in Care, with >75% of care time reflecting developmental care. Speech counts were higher during care than no care, for mature vs. immature infants, and for infants in open cribs vs. incubators. Family participation in care ranged widely, with the highest speech counts occurring during periods of intentional voice exposure.Care activities represent a small portion of NICU experiences. Speech exposure during Developmental Care, especially with intentional voice exposure, may be an important source of stimulation. Implications for care practices are discussed.

  View details for DOI 10.1038/s41372-020-0672-7

  View details for PubMedID 32362660

• Age-Dependent White Matter Characteristics of the Cerebellar Peduncles from Infancy Through Adolescence CEREBELLUM Bruckert, L., Shpanskaya, K., McKenna, E. S., Borchers, L. R., Yablonski, M., Blecher, T., Ben-Shachar, M., Travis, K. E., Feldman, H. M., Yeom, K. W. 2019; 18 (3): 372–87

  View details for DOI 10.1007/s12311-018-1003-9

  View details for Web of Science ID 000468112900008

• White Matter Plasticity in Reading-Related Pathways Differs in Children Born Preterm and at Term: A Longitudinal Analysis FRONTIERS IN HUMAN NEUROSCIENCE Bruckert, L., Borchers, L. R., Dodson, C. K., Marchman, V. A., Travis, K. E., Ben-Shachar, M., Feldman, H. M. 2019; 13

  View details for DOI 10.3389/fnhum.2019.00139

  View details for Web of Science ID 000467472300001

• White Matter Plasticity in Reading-Related Pathways Differs in Children Born Preterm and at Term: A Longitudinal Analysis. Frontiers in human neuroscience Bruckert, L., Borchers, L. R., Dodson, C. K., Marchman, V. A., Travis, K. E., Ben-Shachar, M., Feldman, H. M. 2019; 13: 139

  Abstract

  Children born preterm (PT) are at risk for white matter injuries based on complications of prematurity. They learn to read but on average perform below peers born full term (FT). Studies have yet to establish whether properties of white matter pathways at the onset of learning to read are associated with individual variation later in reading development in PT children. Here, we asked whether fractional anisotropy (FA) at age 6 years is associated with reading outcome at age 8 years in PT children in the same pathways as previously demonstrated in a sample of FT children. PT (n = 34, mean gestational age = 29.5 weeks) and FT children (n = 37) completed diffusion MRI and standardized measures of non-verbal IQ, language, and phonological awareness at age 6 years. Reading skills were assessed at age 8 years. Mean tract-FA was extracted from pathways that predicted reading outcome in children born FT: left arcuate fasciculus (Arc), bilateral superior longitudinal fasciculus (SLF), and left inferior cerebellar peduncle (ICP). We explored associations in additional pathways in the PT children: bilateral inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus. Linear regression models examined whether the prediction of reading outcome at age 8 years based on mean tract-FA at age 6 years was moderated by birth group. Children born PT and FT did not differ significantly in tract-FA at age 6 years or in reading at age 8 years. Sex, socioeconomic status, and non-verbal IQ at age 6 years were associated with reading outcome and were included as covariates in all models. Birth group status significantly moderated associations between reading outcome and mean tract-FA only in the left Arc, right SLF, and left ICP, before and after consideration of pre-literacy skills. Microstructural properties of these cerebral and cerebellar pathways predicted later reading outcome in FT but not in PT children. Children born PT may rely on alternative pathways to achieve fluent reading. These findings have implications for plasticity of neural organization after early white matter injury.

  View details for DOI 10.3389/fnhum.2019.00139

  View details for PubMedID 31139064

  View details for PubMedCentralID PMC6519445

• Predicting text reading skills at age 8 years in children born preterm and at term EARLY HUMAN DEVELOPMENT Borchers, L. R., Bruckert, L., Travis, K. E., Dodson, C. K., Loe, I. M., Marchman, V. A., Feldman, H. M. 2019; 130: 80–86

  View details for DOI 10.1016/j.earlhumdev.2019.01.012

  View details for Web of Science ID 000462801000013

• Predicting text reading skills at age 8 years in children born preterm and at term. Early human development Borchers, L. R., Bruckert, L., Travis, K. E., Dodson, C. K., Loe, I. M., Marchman, V. A., Feldman, H. M. 2019; 130: 80–86

  Abstract

  BACKGROUND: Children born preterm are at risk for developing reading difficulties and for decrements in other cognitive skills compared to children born at term.AIMS: To assess how domains of function, often negatively impacted by preterm birth, predict reading development in children born preterm and at term.STUDY DESIGN: Longitudinal descriptive cohort study.SUBJECTS: Preterm (n = 48; gestational age 22-32 weeks, 30 males) and term (n = 41, 18 males) participants were assessed at age 6 years on a battery of verbal and non-verbal cognitive skills and reassessed at age 8 using the Gray Oral Reading Tests-5. Linear regressions assessed the contributions of phonological awareness, language, executive function, and non-verbal IQ at age 6 to reading outcome at age 8.RESULTS: Children born preterm had lower scores than children born at term on all measures (Cohen's d from 0.46 to 1.08, all p < .05). Phonological awareness and language abilities predicted reading in both groups (accounting for 19.9% and 25.0% of variance, respectively, p < .001). Birth group did not moderate the association. By contrast, the association between executive function and non-verbal intelligence and reading outcome was moderated by birth group (interaction accounted for 3.9-6.7% of variance, respectively, p < .05). Positive predictions to reading from executive function and non-verbal IQ were found only in children born preterm.CONCLUSIONS: Non-verbal cognitive skills improved the prediction of reading outcome only in the preterm group, suggesting that reading decrements represent a component of global deficits. These findings have implications for evaluation of children born preterm at school entry and treatment of reading difficulties.

  View details for PubMedID 30708270

• Age-Dependent White Matter Characteristics of the Cerebellar Peduncles from Infancy Through Adolescence. Cerebellum (London, England) Bruckert, L., Shpanskaya, K., McKenna, E. S., Borchers, L. R., Yablonski, M., Blecher, T., Ben-Shachar, M., Travis, K. E., Feldman, H. M., Yeom, K. W. 2019

  Abstract

  Cerebellum-cerebrum connections are essential for many motor and cognitive functions and cerebellar disorders are prevalent in childhood. The middle (MCP), inferior (ICP), and superior cerebellar peduncles (SCP) are the major white matter pathways that permit communication between the cerebellum and the cerebrum. Knowledge about the microstructural properties of these cerebellar peduncles across childhood is limited. Here, we report on a diffusion magnetic resonance imaging tractography study to describe age-dependent characteristics of the cerebellar peduncles in a cross-sectional sample of infants, children, and adolescents from newborn to 17years of age (N=113). Scans were collected as part of clinical care; participants were restricted to those whose scans showed no abnormal findings and whose history and exam had no risk factors for cerebellar abnormalities. A novel automated tractography protocol was applied. Results showed that mean tract-FA increased, while mean tract-MD decreased from infancy to adolescence in all peduncles. Rapid changes were observed in both diffusion measures in the first 24months of life, followed by gradual change at older ages. The shape of the tract profiles was similar across ages for all peduncles. These data are the first to characterize the variability of diffusion properties both across and within cerebellar white matter pathways that occur from birth through later adolescence. The data represent a rich normative data set against which white matter alterations seen in children with posterior fossa conditions can be compared. Ultimately, the data will facilitate the identification of sensitive biomarkers of cerebellar abnormalities.

  View details for PubMedID 30637673

• White matter microstructure of 6-year old children born preterm and full term NEUROIMAGE-CLINICAL Dodson, C. K., Travis, K. E., Ben-Shachar, M., Feldman, H. M. 2017; 16: 268–75

  Abstract

  We previously observed a complex pattern of differences in white matter (WM) microstructure between preterm-born (PT) and full-term-born (FT) children and adolescents age 9-17 years. The aim of this study was to determine if the same differences exist as early as age 6 years.We obtained diffusion MRI (dMRI) scans in children born PT at age 6 years (n = 20; 11 males) and FT (n = 38; 14 males), using two scanning protocols: 30 diffusion directions (b = 1000 s/mm2) and 96 diffusion directions (b = 2500 s/mm2). We used deterministic tractography and analyzed fractional anisotropy (FA) along bilateral cerebral WM pathways that demonstrated differences in the older sample.Compared to the FT group, the PT group showed (1) significantly decreased FA in the uncinate fasciculi and forceps major and (2) significantly increased FA in the right anterior thalamic radiation, inferior fronto-occipital fasciculi, and inferior longitudinal fasciculi. This pattern of group differences resembles findings in the previous study of older PT and FT participants. Group differences were similar across dMRI acquisition protocols.The underlying neurobiology driving the pattern of PT-FT differences in FA is present as early as age 6 years. Generalization across dMRI acquisition protocols demonstrates the robustness of group differences in FA. Future studies will use quantitative neuroimaging techniques to understand the tissue properties that give rise to this consistent pattern of WM differences after PT birth.

  View details for PubMedID 28840098

• Abnormal white matter properties in adolescent girls with anorexia nervosa Neuroimage:Clinical Travis, K. E., Golden, N. H., Feldman, H. M., Solomon, M., Nguyen, J., Mezer, A., Yeatman, J. D., Dougherty, R. F. 2015

  View details for DOI 10.1016/j.nicl.2015.10.008

• Abnormal white matter properties in adolescent girls with anorexia nervosa NEUROIMAGE-CLINICAL Travis, K. E., Golden, N. H., Feldman, H. M., Solomon, M., Jenny Nguyen, J., Mezer, A., Yeatman, J. D., Dougherty, R. F. 2015; 9: 648-659

  Abstract

  Anorexia nervosa (AN) is a serious eating disorder that typically emerges during adolescence and occurs most frequently in females. To date, very few studies have investigated the possible impact of AN on white matter tissue properties during adolescence, when white matter is still developing. The present study evaluated white matter tissue properties in adolescent girls with AN using diffusion MRI with tractography and T1 relaxometry to measure R1 (1/T1), an index of myelin content. Fifteen adolescent girls with AN (mean age = 16.6 years ± 1.4) were compared to fifteen age-matched girls with normal weight and eating behaviors (mean age = 17.1 years ± 1.3). We identified and segmented 9 bilateral cerebral tracts (18) and 8 callosal fiber tracts in each participant's brain (26 total). Tract profiles were generated by computing measures for fractional anisotropy (FA) and R1 along the trajectory of each tract. Compared to controls, FA in the AN group was significantly decreased in 4 of 26 white matter tracts and significantly increased in 2 of 26 white matter tracts. R1 was significantly decreased in the AN group compared to controls in 11 of 26 white matter tracts. Reduced FA in combination with reduced R1 suggests that the observed white matter differences in AN are likely due to reductions in myelin content. For the majority of tracts, group differences in FA and R1 did not occur within the same tract. The present findings have important implications for understanding the neurobiological factors underlying white matter changes associated with AN and invite further investigations examining associations between white matter properties and specific physiological, cognitive, social, or emotional functions affected in AN.

  View details for DOI 10.1016/j.nicl.2015.10.008

  View details for Web of Science ID 000373188400069

• Speech-Specific Tuning of Neurons in Human Superior Temporal Gyrus CEREBRAL CORTEX Chan, A. M., Dykstra, A. R., Jayaram, V., Leonard, M. K., Travis, K. E., Gygi, B., Baker, J. M., Eskandar, E., Hochberg, L. R., Halgren, E., Cash, S. S. 2014; 24 (10): 2679-2693

  Abstract

  How the brain extracts words from auditory signals is an unanswered question. We recorded approximately 150 single and multi-units from the left anterior superior temporal gyrus of a patient during multiple auditory experiments. Against low background activity, 45% of units robustly fired to particular spoken words with little or no response to pure tones, noise-vocoded speech, or environmental sounds. Many units were tuned to complex but specific sets of phonemes, which were influenced by local context but invariant to speaker, and suppressed during self-produced speech. The firing of several units to specific visual letters was correlated with their response to the corresponding auditory phonemes, providing the first direct neural evidence for phonological recoding during reading. Maximal decoding of individual phonemes and words identities was attained using firing rates from approximately 5 neurons within 200 ms after word onset. Thus, neurons in human superior temporal gyrus use sparse spatially organized population encoding of complex acoustic-phonetic features to help recognize auditory and visual words.

  View details for DOI 10.1093/cercor/bht127

  View details for Web of Science ID 000343408200014

  View details for PubMedID 23680841

• Age-related Changes in Tissue Signal Properties Within Cortical Areas Important for Word Understanding in 12-to 19-Month-Old Infants CEREBRAL CORTEX Travis, K. E., Curran, M. M., Torres, C., Leonard, M. K., Brown, T. T., Dale, A. M., Elman, J. L., Halgren, E. 2014; 24 (7): 1948-1955

  Abstract

  Recently, our laboratory has shown that the neural mechanisms for encoding lexico-semantic information in adults operate functionally by 12-18 months of age within left frontotemporal cortices (Travis et al., 2011. Spatiotemporal neural dynamics of word understanding in 12- to 18-month-old-infants. Cereb Cortex. 8:1832-1839). However, there is minimal knowledge of the structural changes that occur within these and other cortical regions important for language development. To identify regional structural changes taking place during this important period in infant development, we examined age-related changes in tissue signal properties of gray matter (GM) and white matter (WM) intensity and contrast. T1-weighted surface-based measures were acquired from 12- to 19-month-old infants and analyzed using a general linear model. Significant age effects were observed for GM and WM intensity and contrast within bilateral inferior lateral and anterovental temporal regions, dorsomedial frontal, and superior parietal cortices. Region of interest (ROI) analyses revealed that GM and WM intensity and contrast significantly increased with age within the same left lateral temporal regions shown to generate lexico-semantic activity in infants and adults. These findings suggest that neurophysiological processes supporting linguistic and cognitive behaviors may develop before cellular and structural maturation is complete within associative cortices. These results have important implications for understanding the neurobiological mechanisms relating structural to functional brain development.

  View details for DOI 10.1093/cercor/bht052

  View details for Web of Science ID 000338110900021

• Independence of Early Speech Processing from Word Meaning CEREBRAL CORTEX Travis, K. E., Leonard, M. K., Chan, A. M., Torres, C., Sizemore, M. L., Qu, Z., Eskandar, E., Dale, A. M., Elman, J. L., Cash, S. S., Halgren, E. 2013; 23 (10): 2370-2379

  Abstract

  We combined magnetoencephalography (MEG) with magnetic resonance imaging and electrocorticography to separate in anatomy and latency 2 fundamental stages underlying speech comprehension. The first acoustic-phonetic stage is selective for words relative to control stimuli individually matched on acoustic properties. It begins ∼60 ms after stimulus onset and is localized to middle superior temporal cortex. It was replicated in another experiment, but is strongly dissociated from the response to tones in the same subjects. Within the same task, semantic priming of the same words by a related picture modulates cortical processing in a broader network, but this does not begin until ∼217 ms. The earlier onset of acoustic-phonetic processing compared with lexico-semantic modulation was significant in each individual subject. The MEG source estimates were confirmed with intracranial local field potential and high gamma power responses acquired in 2 additional subjects performing the same task. These recordings further identified sites within superior temporal cortex that responded only to the acoustic-phonetic contrast at short latencies, or the lexico-semantic at long. The independence of the early acoustic-phonetic response from semantic context suggests a limited role for lexical feedback in early speech perception.

  View details for DOI 10.1093/cercor/bhs228

  View details for Web of Science ID 000325760200009

  View details for PubMedID 22875868

• Signed Words in the Congenitally Deaf Evoke Typical Late Lexicosemantic Responses with No Early Visual Responses in Left Superior Temporal Cortex JOURNAL OF NEUROSCIENCE Leonard, M. K., Ramirez, N. F., Torres, C., Travis, K. E., Hatrak, M., Mayberry, R. I., Halgren, E. 2012; 32 (28): 9700-9705

  Abstract

  Congenitally deaf individuals receive little or no auditory input, and when raised by deaf parents, they acquire sign as their native and primary language. We asked two questions regarding how the deaf brain in humans adapts to sensory deprivation: (1) is meaning extracted and integrated from signs using the same classical left hemisphere frontotemporal network used for speech in hearing individuals, and (2) in deafness, is superior temporal cortex encompassing primary and secondary auditory regions reorganized to receive and process visual sensory information at short latencies? Using MEG constrained by individual cortical anatomy obtained with MRI, we examined an early time window associated with sensory processing and a late time window associated with lexicosemantic integration. We found that sign in deaf individuals and speech in hearing individuals activate a highly similar left frontotemporal network (including superior temporal regions surrounding auditory cortex) during lexicosemantic processing, but only speech in hearing individuals activates auditory regions during sensory processing. Thus, neural systems dedicated to processing high-level linguistic information are used for processing language regardless of modality or hearing status, and we do not find evidence for rewiring of afferent connections from visual systems to auditory cortex.

  View details for DOI 10.1523/JNEUROSCI.1002-12.2012

  View details for Web of Science ID 000306526800027

  View details for PubMedID 22787055

• Spatial Organization of Neurons in the Frontal Pole Sets Humans Apart from Great Apes CEREBRAL CORTEX Semendeferi, K., Teffer, K., Buxhoeveden, D. P., Park, M. S., Bludau, S., Amunts, K., Travis, K., Buckwalter, J. 2011; 21 (7): 1485-1497

  Abstract

  Few morphological differences have been identified so far that distinguish the human brain from the brains of our closest relatives, the apes. Comparative analyses of the spatial organization of cortical neurons, including minicolumns, can aid our understanding of the functionally relevant aspects of microcircuitry. We measured horizontal spacing distance and gray-level ratio in layer III of 4 regions of human and ape cortex in all 6 living hominoid species: frontal pole (Brodmann area [BA] 10), and primary motor (BA 4), primary somatosensory (BA 3), and primary visual cortex (BA 17). Our results identified significant differences between humans and apes in the frontal pole (BA 10). Within the human brain, there were also significant differences between the frontal pole and 2 of the 3 regions studied (BA 3 and BA 17). Differences between BA 10 and BA 4 were present but did not reach significance. These findings in combination with earlier findings on BA 44 and BA 45 suggest that human brain evolution was likely characterized by an increase in the number and width of minicolumns and the space available for interconnectivity between neurons in the frontal lobe, especially the prefrontal cortex.

  View details for DOI 10.1093/cercor/bhq191

  View details for Web of Science ID 000291750400003

  View details for PubMedID 21098620

• Language Proficiency Modulates the Recruitment of Non-Classical Language Areas in Bilinguals PLOS ONE Leonard, M. K., Torres, C., Travis, K. E., Brown, T. T., Hagler, D. J., Dale, A. M., Elman, J. L., Halgren, E. 2011; 6 (3)

  Abstract

  Bilingualism provides a unique opportunity for understanding the relative roles of proficiency and order of acquisition in determining how the brain represents language. In a previous study, we combined magnetoencephalography (MEG) and magnetic resonance imaging (MRI) to examine the spatiotemporal dynamics of word processing in a group of Spanish-English bilinguals who were more proficient in their native language. We found that from the earliest stages of lexical processing, words in the second language evoke greater activity in bilateral posterior visual regions, while activity to the native language is largely confined to classical left hemisphere fronto-temporal areas. In the present study, we sought to examine whether these effects relate to language proficiency or order of language acquisition by testing Spanish-English bilingual subjects who had become dominant in their second language. Additionally, we wanted to determine whether activity in bilateral visual regions was related to the presentation of written words in our previous study, so we presented subjects with both written and auditory words. We found greater activity for the less proficient native language in bilateral posterior visual regions for both the visual and auditory modalities, which started during the earliest word encoding stages and continued through lexico-semantic processing. In classical left fronto-temporal regions, the two languages evoked similar activity. Therefore, it is the lack of proficiency rather than secondary acquisition order that determines the recruitment of non-classical areas for word processing.

  View details for DOI 10.1371/journal.pone.0018240

  View details for Web of Science ID 000288811500031

  View details for PubMedID 21455315

• Spatiotemporal dynamics of bilingual word processing NEUROIMAGE Leonard, M. K., Brown, T. T., Travis, K. E., Gharapetian, L., Hagler, D. J., Dale, A. M., Elman, J. L., Halgren, E. 2010; 49 (4): 3286-3294

  Abstract

  Studies with monolingual adults have identified successive stages occurring in different brain regions for processing single written words. We combined magnetoencephalography and magnetic resonance imaging to compare these stages between the first (L1) and second (L2) languages in bilingual adults. L1 words in a size judgment task evoked a typical left-lateralized sequence of activity first in ventral occipitotemporal cortex (VOT: previously associated with visual word-form encoding) and then ventral frontotemporal regions (associated with lexico-semantic processing). Compared to L1, words in L2 activated right VOT more strongly from approximately 135 ms; this activation was attenuated when words became highly familiar with repetition. At approximately 400 ms, L2 responses were generally later than L1, more bilateral, and included the same lateral occipitotemporal areas as were activated by pictures. We propose that acquiring a language involves the recruitment of right hemisphere and posterior visual areas that are not necessary once fluency is achieved.

  View details for DOI 10.1016/j.neuroimage.2009.12.009

  View details for Web of Science ID 000274064500039

  View details for PubMedID 20004256

• Somatodendritic Kv7/KCNQ/M channels control interspike interval in hippocampal interneurons JOURNAL OF NEUROSCIENCE Lawrence, J. J., Saraga, F., Churchill, J. F., Statland, J. M., Travis, K. E., Skinner, F. K., McBain, C. J. 2006; 26 (47): 12325-12338

  Abstract

  The M-current (I(M)), comprised of Kv7 channels, is a voltage-activated K+ conductance that plays a key role in the control of cell excitability. In hippocampal principal cells, I(M) controls action potential (AP) accommodation and contributes to the medium-duration afterhyperpolarization, but the role of I(M) in control of interneuron excitability remains unclear. Here, we investigated I(M) in hippocampal stratum oriens (SO) interneurons, both from wild-type and transgenic mice in which green fluorescent protein (GFP) was expressed in somatostatin-containing interneurons. Somatodendritic expression of Kv7.2 or Kv7.3 subunits was colocalized in a subset of GFP+ SO interneurons, corresponding to oriens-lacunosum moleculare (O-LM) cells. Under voltage clamp (VC) conditions at -30 mV, the Kv7 channel antagonists linopirdine/XE-991 abolished the I(M) amplitude present during relaxation from -30 to -50 mV and reduced the holding current (I(hold)). In addition, 0.5 mM tetraethylammonium reduced I(M), suggesting that I(M) was composed of Kv7.2-containing channels. In contrast, the Kv7 channel opener retigabine increased I(M) amplitude and I(hold). When strongly depolarized in VC, the linopirdine-sensitive outward current activated rapidly and comprised up to 20% of the total current. In current-clamp recordings from GFP+ SO cells, linopirdine induced depolarization and increased AP frequency, whereas retigabine induced hyperpolarization and arrested firing. In multicompartment O-LM interneuron models that incorporated I(M), somatodendritic placement of Kv7 channels best reproduced experimentally measured I(M). The models suggest that Kv3- and Kv7-mediated channels both rapidly activate during single APs; however, Kv3 channels control rapid repolarization of the AP, whereas Kv7 channels primarily control the interspike interval.

  View details for DOI 10.1523/JNEUROSCI.3521-06.2006

  View details for Web of Science ID 000242387800026

  View details for PubMedID 17122058

• Regional dendritic variation in neonatal human cortex: A quantitative Golgi study DEVELOPMENTAL NEUROSCIENCE Travis, K., Ford, K., Jacobs, B. 2005; 27 (5): 277-287

  Abstract

  The present study quantitatively compared the basilar dendritic/spine systems of lamina V pyramidal neurons across four hierarchically arranged regions of neonatal human neocortex. Tissue blocks were removed from four Brodmann's areas (BAs) in the left hemisphere of four neurologically normal neonates (mean age=41+/- 40 days): primary (BA4 and BA3-1-2), unimodal (BA18), and supramodal cortices (BA10). Tissue was stained with a modified rapid Golgi technique. Ten cells per region (N=160) were quantified. Despite the small sample size, significant differences in dendritic/spine extent obtained across cortical regions. Most apparent were substantial differences between BA4 and BA10: total dendritic length was 52% greater in BA4 than BA10, and dendritic spine number was 67% greater in BA4 than BA10. Neonatal patterns were compared to adult patterns, revealing that the relative regional pattern of dendritic complexity in the neonate was roughly the inverse of that established in the adult, with BA10 rather than BA4 being the most complex area in the adult. Overall, regional dendritic patterns suggest that the developmental time course of basilar dendritic systems is heterochronous and is more protracted for supramodal BA10 than for primary or unimodal regions (BA4, BA3-1-2, BA18).

  View details for DOI 10.1159/000086707

  View details for Web of Science ID 000231701800001

  View details for PubMedID 16137985