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Laura R. Ment

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8 papers

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YNICL Journal 2019 Journal Article

Amygdala functional connectivity is associated with social impairments in preterm born young adults

Christina B. Johns
Cheryl Lacadie
Betty Vohr
Laura R. Ment
Dustin Scheinost

Survivors of preterm birth experience long-lasting behavioral problems characterized by increased risk of depression, anxiety, and impairments in social functioning. The amygdala is a key region for social functioning and alterations in amygdala structure and connectivity are thought to underlie social functioning deficits in many disorders, including preterm birth. However, functional connectivity of the amygdala and its association with social impairments is not well-studied in preterm participants (PTs). In a group of late adolescents born very PT (600-1250 g birth weight), measures of social and emotional development were examined using the Child Behavior Checklist (CBCL) administered at age 16 (66 term and 161 preterm participants), the Youth Self Report (YSR) administered at age 16 (56 term and 45 preterm participants), and the Vineland Adaptive Behavior Scales (VABS) administered at age 18 (71 term and 190 preterm participants). Amygdala functional connectivity was also examined using resting-state functional magnetic resonance imaging at age 20 (17 term and 19 preterm participants). By parent report, preterm-born adolescents demonstrate increased social impairment compared to their term-born peers. Amygdala connectivity is altered for those prematurely-born, and markers of social functioning correlate with altered amygdala-PCC connectivity. These findings add to knowledge regarding the developmental trajectory of amygdala connectivity in PT and suggest a possible neural underpinning for the well-characterized social impairment experienced by prematurely-born individuals.

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YNICL Journal 2016 Journal Article

Language at rest: A longitudinal study of intrinsic functional connectivity in preterm children

Megan A. Rowlands
Dustin Scheinost
Cheryl Lacadie
Betty Vohr
Fangyong Li
Karen C. Schneider
R. Todd Constable
Laura R. Ment

BACKGROUND: Preterm (PT) children show early cognitive and language deficits and display altered cortical connectivity for language compared to term (T) children. Developmentally, functional connectivity networks become more segregated and integrated, through the weakening of short-range and strengthening of long-range connections. METHODS: Longitudinal intrinsic connectivity distribution (ICD) values were assessed in PT (n = 13) compared to T children (n = 12) at ages 8 vs. 16 using a Linear Mixed Effects model. Connectivity values in regions generated by the group × age interaction analysis were then correlated to scores on full IQ (FSIQ), verbal IQ (VIQ), verbal comprehension IQ (VCIQ), performance IQ (PIQ), Peabody picture vocabulary test-revised (PPVT-R), and Rapid Naming Composite (RDRL_Cmp). RESULTS: Nine regions were generated by the group × age interaction analysis. PT connectivity significantly increased over time in all but two regions, and they ultimately displayed greater relative connectivity at age 16 than Ts in all areas except the left occipito-temporal cortex (OTC). PTs underwent significant connectivity reductions in the left OTC, which corresponded with worse performance on FSIQ, VIQ, and PIQ. These findings differed from Ts, who did not undergo any significant changes in connectivity over time. CONCLUSIONS: These findings suggest that the developmental alterations in connectivity in PT children at adolescence are both pervasive and widespread. The persistent and worsening cognitive and language deficits noted in the PT subjects may be attributed to the loss of connections in the left OTC.

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YNICL Journal 2016 Journal Article

Prenatal stress alters amygdala functional connectivity in preterm neonates

Dustin Scheinost
Soo Hyun Kwon
Cheryl Lacadie
Gordon Sze
Rajita Sinha
R. Todd Constable
Laura R. Ment

Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p < 0.05). Similarly, when compared to extremely preterm neonates without exposure to prenatal stress, extremely preterm neonates with exposure to prenatal stress show significantly less connectivity between the left amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p < 0.05). Exploratory analysis of the combined cohorts suggests additive effects of prenatal stress on alterations in amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

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YNIMG Journal 2015 Journal Article

Adaptive mechanisms of developing brain: Cerebral lateralization in the prematurely-born

Soo Hyun Kwon
Dustin Scheinost
Cheryl Lacadie
Gordon Sze
Karen C. Schneider
Feng Dai
R. Todd Constable
Laura R. Ment

Preterm birth results in alterations in neural connectivity, but the impact of prematurity on the functional organization of the developing brain has yet to be explored. To test the hypothesis that preterm birth alters cortical organization during the late second and third trimesters of gestation, we interrogated cerebral lateralization at rest in 26 very preterm subjects (birth weight 500–1500g) with no evidence of brain injury and 25 healthy term control subjects at term equivalent age. Employing an unbiased voxel-based measure of functional connectivity, these data demonstrated that cerebral lateralization is impaired in the prematurely-born. At term equivalent age, preterm neonates showed significantly less lateralization in regions subserving both receptive and expressive language, left Brodmann (BA) areas insula–BA22–BA21 and L BA45–BA47 (p <0. 05 corrected for multiple comparisons for both). Exploratory region of interest analyses demonstrated significantly less inter-hemispheric connectivity from L BA22 to R BA22 in preterm infants compared to term controls (p <0. 005) and from R BA22 to its homolog (p <0. 005). L BA22, Wernicke's area, was more strongly connected to R BA39, foreshadowing neural networks for language in preterm subjects at school age, adolescence and young adulthood. For these very preterm neonates born at less than 30weeks' PMA, the degree of prematurity had no influence on lateralization in these differential regions.

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YNIMG Journal 2013 Journal Article

A left cerebellar pathway mediates language in prematurely-born young adults

R. Todd Constable
Betty R. Vohr
Dustin Scheinost
Jennifer R. Benjamin
Robert K. Fulbright
Cheryl Lacadie
Karen C. Schneider
Karol H. Katz

Preterm (PT) subjects are at risk for developmental delay, and task-based studies suggest that developmental disorders may be due to alterations in neural connectivity. Since emerging data imply the importance of right cerebellar function for language acquisition in typical development, we hypothesized that PT subjects would have alternate areas of cerebellar connectivity, and that these areas would be responsible for differences in cognitive outcomes between PT subjects and term controls at age 20years. Nineteen PT and 19 term control young adults were prospectively studied using resting-state functional MRI (fMRI) to create voxel-based contrast maps reflecting the functional connectivity of each tissue element in the grey matter through analysis of the intrinsic connectivity contrast degree (ICC-d). Left cerebellar ICC-d differences between subjects identified a region of interest that was used for subsequent seed-based connectivity analyses. Subjects underwent standardized language testing, and correlations with cognitive outcomes were assessed. There were no differences in gender, hand preference, maternal education, age at study, or Peabody Picture Vocabulary Test (PPVT) scores. Functional connectivity (FcMRI) demonstrated increased tissue connectivity in the biventer, simple and quadrangular lobules of the L cerebellum (p<0. 05) in PTs compared to term controls; seed-based analyses from these regions demonstrated alterations in connectivity from L cerebellum to both R and L inferior frontal gyri (IFG) in PTs compared to term controls. For PTs but not term controls, there were significant positive correlations between these connections and PPVT scores (R IFG: r=0. 555, p=0. 01; L IFG: r=0. 454, p=0. 05), as well as Verbal Comprehension Index (VCI) scores (R IFG: r=0. 472, p=0. 04). These data suggest the presence of a left cerebellar language circuit in PT subjects at young adulthood. These findings may represent either a delay in maturation or the engagement of alternative neural pathways for language in the developing PT brain.

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YNIMG Journal 2011 Journal Article

Preterm birth results in alterations in neural connectivity at age 16 years

Katherine M. Mullen
Betty R. Vohr
Karol H. Katz
Karen C. Schneider
Cheryl Lacadie
Michelle Hampson
Robert W. Makuch
Allan L. Reiss

Very low birth weight preterm (PT) children are at high risk for brain injury. Employing diffusion tensor imaging (DTI), we tested the hypothesis that PT adolescents would demonstrate microstructural white matter disorganization relative to term controls at 16years of age. Forty-four PT subjects (600–1250g birth weight) without neonatal brain injury and 41 term controls were evaluated at age 16years with DTI, the Wechsler Intelligence Scale for Children—III (WISC), the Peabody Picture Vocabulary Test—Revised (PPVT), and the Comprehensive Test of Phonological Processing (CTOPP). PT subjects scored lower than term subjects on WISC full scale (p =0. 003), verbal (p =0. 043), and performance IQ tests (p =0. 001), as well as CTOPP phonological awareness (p =0. 004), but scored comparably to term subjects on PPVT and CTOPP Rapid Naming tests. PT subjects had lower fractional anisotropy (FA) values in multiple regions including bilateral uncinate fasciculi (left: p =0. 01; right: p =0. 004), bilateral external capsules (left: p <0. 001; right: p <0. 001), the splenium of the corpus callosum (p =0. 008), and white matter serving the inferior frontal gyrus bilaterally (left: p <0. 001; right: p =0. 011). FA values in both the left and right uncinate fasciculi correlated with PPVT scores (a semantic language task) in the PT subjects (left: r =0. 314, p =0. 038; right: r =0. 336, p =0. 026). FA values in the left and right arcuate fasciculi correlated with CTOPP Rapid Naming scores (a phonologic task) in the PT subjects (left: r =0. 424, p =0. 004; right: r =0. 301, p =0. 047). These data support for the first time that dual pathways underlying language function are present in PT adolescents. The striking bilateral dorsal correlations for the PT group suggest that prematurely born subjects rely more heavily on the right hemisphere than typically developing adults for performance of phonological language tasks. These findings may represent either a delay in maturation or the engagement of alternative neural pathways for language in the developing PT brain.

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YNIMG Journal 2010 Journal Article

Functional connectivity to a right hemisphere language center in prematurely born adolescents

Eliza H. Myers
Michelle Hampson
Betty Vohr
Cheryl Lacadie
Stephen J. Frost
Kenneth R. Pugh
Karol H. Katz
Karen C. Schneider

Prematurely born children are at increased risk for language deficits at school age and beyond, but the neurobiological basis of these findings remains poorly understood. Thirty-one PT adolescents (600–1250g birth weight) and 36 T controls were evaluated using an fMRI passive language task and neurodevelopmental assessments including: the Wechsler Intelligence Scale for Children-III (WISC-III), the Peabody Picture Vocabulary Test-Revised (PPVT-R), the Comprehensive Test of Phonological Processing (CTOPP) and the Test of Word Reading Efficiency (TOWRE) at 16years of age. Neural activity was assessed for language processing and the data were evaluated for connectivity and correlations to cognitive outcomes. PT subjects scored significantly lower on all components of the WISC-III (p <0. 05) compared to term subjects, but there was no significant difference in PPVT-R scores between the groups. Functional connectivity (fcMRI) between Wernicke's area (left BA 22) and the right supramarginal gyrus (BA 40) was increased in preterm subjects relative to term controls (p =0. 03), and the strength of this connection was inversely related to performance on both the PPVT-R (R 2 =0. 553, p =0. 002), and the verbal comprehension index (R 2 =0. 439, p =0. 019). Preterm adolescents engage a dorsal right hemisphere region for language at age 16years. Those with the greatest cognitive deficits demonstrate increasing reliance on this alternate pathway.

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YNIMG Journal 2009 Journal Article

Alterations in neural connectivity in preterm children at school age

Yeisid Gozzo
Betty Vohr
Cheryl Lacadie
Michelle Hampson
Karol H. Katz
Jill Maller-Kesselman
Karen C. Schneider
Bradley S. Peterson

Converging data suggest recovery from injury in the preterm brain. We used functional magnetic resonance imaging (fMRI) to test the hypothesis that cerebral connectivity involving Wernicke's area and other important cortical language regions would differ between preterm (PT) and term (T) control school age children during performance of an auditory language task. Fifty-four PT children (600–1250 g birth weight) and 24 T controls were evaluated using an fMRI passive language task and neurodevelopmental assessments including: the Wechsler Intelligence Scale for Children — III (WISC-III), the Peabody Individual Achievement Test — Revised (PIAT-R) and the Peabody Picture Vocabulary Test — Revised (PPVT-R) at 8 years of age. Neural activity was assessed for language processing and the data were evaluated for connectivity and correlations to cognitive outcomes. We found that PT subjects scored significantly lower on all components of the WISC-III (p <0. 009), the PIAT-R Reading Comprehension test (p =0. 013), and the PPVT-R (p =0. 001) compared to term subjects. Connectivity analyses revealed significantly stronger neural circuits in PT children between Wernicke's area and the right inferior frontal gyrus (R IFG, Broca's area homologue) and both the left and the right supramarginal gyri (SMG) components of the inferior parietal lobules (p ≤0. 02 for all). We conclude that PT subjects employ neural systems for auditory language function at school age differently than T controls; these alterations may represent a delay in maturation of neural networks or the engagement of alternate circuits for language processing.

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