Examination of Cerebellar Grey-Matter Volume in Children with Neurodevelopmental Disorders: a Coordinated Analysis Using the ACAPULCO Algorithm

Valenzuela-Fernández, Leslier; Burmester, Alex; Duque, Juan Dominguez; Silk, Timothy J.; Hyde, Christian; Kirkovski, Melissa; Enticott, Peter G.; Caeyenberghs, Karen

doi:10.1007/s12311-022-01503-3

Cited by 6 publications

(5 citation statements)

References 13 publications

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“…53 As such, ADHD-related volume deficits would be expected throughout all phases of injury in our sample. 35 However, our results demonstrated significantly greater deficits in subregional cerebellar volume in the chronic phase of injury, suggesting that ADHD was not a confounding factor.…”

Section: Potential Confoundsmentioning

confidence: 47%

“…Raw 3D T1-weighted MR images were processed using the ENIGMA Cerebellum Pipeline, which is based on the Automatic Cerebellum Anatomical Parcellation using U-Net with Locally Constrained Optimization (ACAPULCO; v 0.2.1) workflow. 5,35,36 Image processing, segmentation, and quality review were conducted at the University of Utah. The cerebellum was segmented into 28 subregions (Figure 1).…”

Section: Image Acquisition Processing and Quality Controlmentioning

confidence: 99%

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Multimodal Analysis of Secondary Cerebellar Alterations after Pediatric Traumatic Brain Injury

Keleher

Lindsey

Kerestes

et al. 2022

Preprint

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While traditionally ignored as a region purely responsible for motor function, the cerebellum is increasingly being appreciated for its contributions to higher-order functions through cerebro-cerebellar networks. Traumatic brain injury (TBI) research generally focuses on the cerebrum, in part because of the frequency of acute pathology. Acute pathology is an important predictor of outcome, but neural disruption evolves over time in ways that influence daily-life functioning. We examine these changes in a multi-modal, multi-cohort study. Combining 12 datasets from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Pediatric msTBI (moderate-severe TBI) working group, we measured volume of the total cerebellum and 17 subregions using a state-of-the-art, deep learning-based approach for automated parcellation in 598 children and adolescents with or without TBI (msTBI; n = 314 | non-TBI; n = 284; age M = 14.0 +/- 3.1 years). Further, we investigated brain-behavior relations between cerebellar volumes and a measure of executive functioning (Behavioral Rating Inventory of Executive Function). In a subsample with longitudinal data (n = 80), we assessed associations between late changes in cerebellar volume and early white matter (WM) microstructure using diffusion tensor imaging (DTI). Significantly smaller total cerebellar volume was observed in the msTBI group (Cohens d = -0.37). In addition, smaller volume was found in posterior lobe regions including crus II, lobule VIIB and VIIIB, and vermis VII and IX (Cohens d range = -0.22 to -0.43). These alterations were primarily driven by participants in the chronic phase of injury (> 6 months). Smaller cerebellum volumes were associated with more parent-reported executive function problems. In a subset of participants with longitudinal data, we found evidence of altered growth in total cerebellum volume, with younger msTBI participants showing secondary degeneration (volume reductions), and older participants showing disrupted development (slower growth rates). Changes in total cerebellum volume over time were also associated with WM microstructure in the first months post-injury, such that poorer WM organization in the first months post-injury was associated with decreases in volume longitudinally. Pediatric msTBI was characterized by smaller cerebellar volumes, primarily in the posterior lobe and vermis. The course of these alterations, along with group differences in longitudinal volume changes and injury-specific associations between DTI measures and volume changes, suggests secondary cerebellar atrophy, possibly related to supratentorial lesions, and/or disruption in cerebellar structural and functional circuits. Moreover, evidence for brain-behavior relationships underscore the potential cognitive and behavioral consequences of cerebellar disruption during a critical period of brain development.

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Section: Potential Confoundsmentioning

confidence: 47%

Section: Image Acquisition Processing and Quality Controlmentioning

confidence: 99%

Multimodal Analysis of Secondary Cerebellar Alterations after Pediatric Traumatic Brain Injury

Keleher

Lindsey

Kerestes

et al. 2022

Preprint

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“…Previous studies using MRI in children with ADHD have observed structural changes in cerebellum and specifically in the vermis ( Castellanos et al, 1996 ; Berquin et al, 1998 ; Mackie et al, 2007 ). A section of the executive/non-motor portion of the cerebellum, the left Crus I result has been shown to have a lower grey-matter volume in ADHD children compared to healthy controls ( Fernandez et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Neurocognitive and cerebellar function in ADHD, autism and spinocerebellar ataxia

Cundari,

Vestberg,

Gustafsson

et al. 2023

Front. Syst. Neurosci.

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The cerebellum plays a major role in balance, motor control and sensorimotor integration, but also in cognition, language, and emotional regulation. Several neuropsychiatric disorders such as attention deficit-hyperactivity disorder (ADHD), autism spectrum disorder (ASD), as well as neurological diseases such as spinocerebellar ataxia type 3 (SCA3) are associated with differences in cerebellar function. Morphological abnormalities in different cerebellar subregions produce distinct behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. The specific contribution of the cerebellum to typical development may therefore involve the optimization of the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains. Here, we review cerebellar structural and functional differences between healthy and patients with ADHD, ASD, and SCA3, and explore how disruption of cerebellar networks affects the neurocognitive functions in these conditions. We discuss how cerebellar computations contribute to performance on cognitive and motor tasks and how cerebellar signals are interfaced with signals from other brain regions during normal and dysfunctional behavior. We conclude that the cerebellum plays a role in many cognitive functions. Still, more clinical studies with the support of neuroimaging are needed to clarify the cerebellum’s role in normal and dysfunctional behavior and cognitive functioning.

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“…Methods are reviewed here with additional detail in eMethods in Supplement 1. Raw 3-dimensional T1-weighted MR images were processed using the ENIGMA Cerebellum Pipeline, based on Automatic Cerebellum Anatomical Parcellation using U-Net with Locally Constrained Optimization (ACAPULCO version 0.2.1; Johns Hopkins University) . Image processing, segmentation, and quality review occurred at the University of Utah.…”

Section: Methodsmentioning

confidence: 99%

“…Raw 3-dimensional T1-weighted MR images were processed using the ENIGMA Cerebellum Pipeline, based on Automatic Cerebellum Anatomical Parcellation using U-Net with Locally Constrained Optimization (ACAPULCO version 0.2.1; Johns Hopkins University). 4,43,44 Image processing, segmentation, and quality review occurred at the University of Utah. The cerebellum was segmented into 28 subregions (eFigure 1 in Supplement 1).…”

Section: Image Acquisition Processing and Quality Controlmentioning

confidence: 99%

Multimodal Analysis of Secondary Cerebellar Alterations After Pediatric Traumatic Brain Injury

Keleher,

Lindsey,

Kerestes

et al. 2023

JAMA Netw Open

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ImportanceTraumatic brain injury (TBI) is known to cause widespread neural disruption in the cerebrum. However, less is known about the association of TBI with cerebellar structure and how such changes may alter executive functioning.ObjectiveTo investigate alterations in subregional cerebellum volume and cerebral white matter microstructure after pediatric TBI and examine subsequent changes in executive function.Design, Setting, and ParticipantsThis retrospective cohort study combined 12 data sets (collected between 2006 and 2020) from 9 sites in the Enhancing Neuroimaging Genetics Through Meta-Analysis Consortium Pediatric TBI working group in a mega-analysis of cerebellar structure. Participants with TBI or healthy controls (some with orthopedic injury) were recruited from trauma centers, clinics, and institutional trauma registries, some of which were followed longitudinally over a period of 0.7 to 1.9 years. Healthy controls were recruited from the surrounding community. Data analysis occurred from October to December 2022.ExposureAccidental mild complicated-severe TBI (msTBI) for those in the TBI group. Some controls received a diagnosis of orthopedic injury.Main Outcomes and MeasuresVolume of 18 cerebellar lobules and vermal regions were estimated from 3-dimensional T1-weighted magnetic resonance imaging (MRI) scans. White matter organization in 28 regions of interest was assessed with diffusion tensor MRI. Executive function was measured by parent-reported scores from the Behavior Rating Inventory of Executive Functioning.ResultsA total of 598 children and adolescents (mean [SD] age, 14.05 [3.06] years; range, 5.45-19.70 years; 386 male participants [64.5%]; 212 female participants [35.5%]) were included in the study, with 314 participants in the msTBI group, and 284 participants in the non-TBI group (133 healthy individuals and 151 orthopedically injured individuals). Significantly smaller total cerebellum volume (d = −0.37; 95% CI, −0.52 to −0.22; P &lt; .001) and subregional cerebellum volumes (eg, corpus medullare; d = −0.43; 95% CI, −0.58 to −0.28; P &lt; .001) were observed in the msTBI group. These alterations were primarily seen in participants in the chronic phase (ie, &gt;6 months postinjury) of injury (total cerebellar volume, d = −0.55; 95% CI, −0.75 to −0.35; P &lt; .001). Smaller cerebellum volumes were associated with higher scores on the Behavior Rating Inventory of Executive Functioning Global Executive Composite score (β = −208.9 mm3; 95% CI, −319.0 to −98.0 mm3; P = .008) and Metacognition Index score (β = −202.5 mm3; 95% CI, −319.0 to −85.0 mm3; P = .02). In a subset of 185 participants with longitudinal data, younger msTBI participants exhibited cerebellum volume reductions (β = 0.0052 mm3; 95% CI, 0.0013 to 0.0090 mm3; P = .01), and older participants slower growth rates. Poorer white matter organization in the first months postinjury was associated with decreases in cerebellum volume over time (β=0.52 mm3; 95% CI, 0.19 to 0.84 mm3; P = .005).Conclusions and RelevanceIn this cohort study of pediatric msTBI, our results demonstrated robust cerebellar volume alterations associated with pediatric TBI, localized to the posterior lobe. Furthermore, longitudinal cerebellum changes were associated with baseline diffusion tensor MRI metrics, suggesting secondary cerebellar atrophy. These results provide further understanding of secondary injury mechanisms and may point to new opportunities for intervention.

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Examination of Cerebellar Grey-Matter Volume in Children with Neurodevelopmental Disorders: a Coordinated Analysis Using the ACAPULCO Algorithm

Cited by 6 publications

References 13 publications

Multimodal Analysis of Secondary Cerebellar Alterations after Pediatric Traumatic Brain Injury

Multimodal Analysis of Secondary Cerebellar Alterations after Pediatric Traumatic Brain Injury

Neurocognitive and cerebellar function in ADHD, autism and spinocerebellar ataxia

Multimodal Analysis of Secondary Cerebellar Alterations After Pediatric Traumatic Brain Injury

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