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Janet E. Lainhart

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6 papers
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6

YNICL Journal 2023 Journal Article

Gray matter microstructure differences in autistic males: A gray matter based spatial statistics study

  • Marissa A. DiPiero
  • Olivia J. Surgent
  • Brittany G. Travers
  • Andrew L. Alexander
  • Janet E. Lainhart
  • Douglas C. Dean III

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition. Understanding the brain's microstructure and its relationship to clinical characteristics is important to advance our understanding of the neural supports underlying ASD. In the current work, we implemented Gray-Matter Based Spatial Statistics (GBSS) to examine and characterize cortical microstructure and assess differences between typically developing (TD) and autistic males. METHODS: A multi-shell diffusion MRI (dMRI) protocol was acquired from 83 TD and 70 autistic males (5-to-21-years) and fit to the DTI and NODDI models. GBSS was performed for voxelwise analysis of cortical gray matter (GM). General linear models were used to investigate group differences, while age-by-group interactions assessed age-related differences between groups. Within the ASD group, relationships between cortical microstructure and measures of autistic symptoms were investigated. RESULTS: All dMRI measures were significantly associated with age across the GM skeleton. Group differences and age-by-group interactions are reported. Group-wise increases in neurite density in autistic individuals were observed across frontal, temporal, and occipital regions of the right hemisphere. Significant age-by-group interactions of neurite density were observed within the middle frontal gyrus, precentral gyrus, and frontal pole. Negative relationships between neurite dispersion and the ADOS-2 Calibrated Severity Scores (CSS) were observed within the ASD group. DISCUSSION: Findings demonstrate group and age-related differences between groups in neurite density in ASD across right-hemisphere brain regions supporting cognitive processes. Results provide evidence of altered neurodevelopmental processes affecting GM microstructure in autistic males with implications for the role of cortical microstructure in the level of autistic symptoms. CONCLUSION: Using dMRI and GBSS, our findings provide new insights into group and age-related differences of the GM microstructure in autistic males. Defining where and when these cortical GM differences arise will contribute to our understanding of brain-behavior relationships of ASD and may aid in the development and monitoring of targeted and individualized interventions.

YNIMG Journal 2021 Journal Article

A 16-year study of longitudinal volumetric brain development in males with autism

  • Molly B.D. Prigge
  • Nicholas Lange
  • Erin D. Bigler
  • Jace B. King
  • Douglas C. Dean
  • Nagesh Adluru
  • Andrew L. Alexander
  • Janet E. Lainhart

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with unknown brain etiology. Our knowledge to date about structural brain development across the lifespan in ASD comes mainly from cross-sectional studies, thereby limiting our understanding of true age effects within individuals with the disorder that can only be gained through longitudinal research. The present study describes FreeSurfer-derived volumetric findings from a longitudinal dataset consisting of 607 T1-weighted magnetic resonance imaging (MRI) scans collected from 105 male individuals with ASD (349 MRIs) and 125 typically developing male controls (258 MRIs). Participants were six to forty-five years of age at their first scan, and were scanned up to 5 times over a period of 16 years (average inter-scan interval of 3.7 years). Atypical age-related volumetric trajectories in ASD included enlarged gray matter volume in early childhood that approached levels of the control group by late childhood, an age-related increase in ventricle volume resulting in enlarged ventricles by early adulthood and reduced corpus callosum age-related volumetric increase resulting in smaller corpus callosum volume in adulthood. Larger corpus callosum volume was related to a lower (better) ADOS score at the most recent study visit for the participants with ASD. These longitudinal findings expand our knowledge of volumetric brain-based abnormalities in males with ASD, and highlight the need to continue to examine brain structure across the lifespan and well into adulthood.

YNIMG Journal 2021 Journal Article

Evidence for normal extra-axial cerebrospinal fluid volume in autistic males from middle childhood to adulthood

  • Madeline Peterson
  • Molly B.D. Prigge
  • Erin D. Bigler
  • Brandon Zielinski
  • Jace B. King
  • Nicholas Lange
  • Andrew Alexander
  • Janet E. Lainhart

Autism spectrum disorder has long been associated with a variety of organizational and developmental abnormalities in the brain. An increase in extra-axial cerebrospinal fluid volume in autistic individuals between the ages of 6 months and 4 years has been reported in recent studies. Increased extra-axial cerebrospinal fluid volume was predictive of the diagnosis and severity of the autistic symptoms in all of them, irrespective of genetic risk for developing the disorder. In the present study, we explored the trajectory of extra-axial cerebrospinal fluid volume from childhood to adulthood in both autism and typical development. We hypothesized that an elevated extra-axial cerebrospinal fluid volume would be found in autism persisting throughout the age range studied. We tested the hypothesis by employing an accelerated, multi-cohort longitudinal data set of 189 individuals (97 autistic, 92 typically developing). Each individual had been scanned between 1 and 5 times, with scanning sessions separated by 2-3 years, for a total of 439 T1-weighted MRI scans. A linear mixed-effects model was used to compare developmental, age-related changes in extra-axial cerebrospinal fluid volume between groups. Inconsistent with our hypothesis, we found no group differences in extra-axial cerebrospinal fluid volume in this cohort of individuals 3 to 42 years of age. Our results suggest that extra-axial cerebrospinal fluid volume in autistic individuals is not increased compared with controls beyond four years of age.

YNIMG Journal 2010 Journal Article

Microstructural connectivity of the arcuate fasciculus in adolescents with high-functioning autism

  • P. Thomas Fletcher
  • Ross T. Whitaker
  • Ran Tao
  • Molly B. DuBray
  • Alyson Froehlich
  • Caitlin Ravichandran
  • Andrew L. Alexander
  • Erin D. Bigler

The arcuate fasciculus is a white matter fiber bundle of great importance in language. In this study, diffusion tensor imaging (DTI) was used to infer white matter integrity in the arcuate fasciculi of a group of subjects with high-functioning autism and a control group matched for age, handedness, IQ, and head size. The arcuate fasciculus for each subject was automatically extracted from the imaging data using a new volumetric DTI segmentation algorithm. The results showed a significant increase in mean diffusivity (MD) in the autism group, due mostly to an increase in the radial diffusivity (RD). A test of the lateralization of DTI measurements showed that both MD and fractional anisotropy (FA) were less lateralized in the autism group. These results suggest that white matter microstructure in the arcuate fasciculus is affected in autism and that the language specialization apparent in the left arcuate of healthy subjects is not as evident in autism, which may be related to poorer language functioning.

YNIMG Journal 2009 Journal Article

A study of diffusion tensor imaging by tissue-specific, smoothing-compensated voxel-based analysis

  • Jee Eun Lee
  • Moo K. Chung
  • Mariana Lazar
  • Molly B. DuBray
  • Jinsuh Kim
  • Erin D. Bigler
  • Janet E. Lainhart
  • Andrew L. Alexander

Voxel-based analysis (VBA) is commonly used for statistical analysis of image data, including the detection of significant signal differences between groups. Typically, images are co-registered and then smoothed with an isotropic Gaussian kernel to compensate for image misregistration, to improve the signal-to-noise ratio (SNR), to reduce the number of multiple comparisons, and to apply random field theory. Problems with typical implementations of VBA include poor tissue specificity from image misregistration and smoothing. In this study, we developed a new tissue-specific, smoothing-compensated (T-SPOON) method for the VBA of diffusion tensor imaging (DTI) data with improved tissue specificity and compensation for image misregistration and smoothing. When compared with conventional VBA methods, the T-SPOON method introduced substantially less errors in the normalized and smoothed DTI maps. Another confound of the conventional DTI-VBA is that it is difficult to differentiate between differences in morphometry and DTI measures that describe tissue microstructure. T-SPOON VBA decreased the effects of differential morphometry in the DTI VBA studies. T-SPOON and conventional VBA were applied to a DTI study of white matter in autism. T-SPOON VBA results were found to be more consistent with region of interest (ROI) measurements in the corpus callosum and temporal lobe regions. The T-SPOON method may be also applicable to other quantitative imaging maps such as T1 or T2 relaxometry, magnetization transfer, or PET tracer maps.

YNIMG Journal 2007 Journal Article

Diffusion tensor imaging of the corpus callosum in Autism

  • Andrew L. Alexander
  • Jee Eun Lee
  • Mariana Lazar
  • Rebecca Boudos
  • Molly B. DuBray
  • Terrence R. Oakes
  • Judith N. Miller
  • Jeffrey Lu

The corpus callosum is the largest commissural white matter pathway that connects the hemispheres of the human brain. In this study, diffusion tensor imaging (DTI) was performed on subject groups with high-functioning autism and controls matched for age, handedness, IQ, and head size. DTI and volumetric measurements of the total corpus callosum and subregions (genu, body and splenium) were made and compared between groups. The results showed that there were significant differences in volume, fractional anisotropy, mean diffusivity, and radial diffusivity between groups. These group differences appeared to be driven by a subgroup of the autism group that had small corpus callosum volumes, high mean diffusivity, low anisotropy, and increased radial diffusivity. This subgroup had significantly lower performance IQ measures than either the other individuals with autism or the control subjects. Measurements of radial diffusivity also appeared to be correlated with processing speed measured during the performance IQ tests. The subgroup of autism subjects with high mean diffusivity and low fractional anisotropy appeared to cluster with the highest radial diffusivities and slowest processing speeds. These results suggest that the microstructure of the corpus callosum is affected in autism, which may be related to nonverbal cognitive performance.

v2026.09.13