Harmonizing PTSD severity scales across instruments and sites.

Kennedy, Eamonn; Dennis, Emily; Lindsey, Hannah M.; deRoon‐Cassini, Terri; Plessis, Stéfan du; Fani, Negar; Kaufman, Milissa L.; Koen, Nastassja; Larson, Christine L.; Laskowitz, Sarah; Lebois, Lauren A. M.; Morey, Rajendra A.; Newsome, Mary R.; Palermo, Cori A.; Pastorek, Nicholas J.; Powers, Abigail; Scheibel, Randall S.; Seedat, Soraya; Seligowski, Antonia V.; Stein, Dan J.; Stevens, Jennifer; Sun, Delin; Thompson, Paul M.; Troyanskaya, Maya; Rooij, Sanne J.H. van; Watts, Amanda A; Tomas, Carissa W.; Williams, Wright; Hillary, Frank G.; Pugh, Mary Jo; Wilde, Elisabeth A.; Tate, David F.

doi:10.1037/neu0000823

Cited by 8 publications

(11 citation statements)

References 37 publications

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“…The ComBat-GAM algorithm (13) was implemented to correct for site-specific variations such as differences in inclusion/exclusion criteria (Supplementary Table S2) while explicitly preserving real covariate effects (e.g., age) for further analysis as described elsewhere (4). Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Appropriate harmonization transforms data in ways that preserve its core relationships (4). For this study, these relationships include the associations between scores and ability, between scores and covariates (e.g., age-related memory decline), and the measurement of the underlying cognitive construct.…”

Section: Discussionmentioning

confidence: 99%

“…While analyses of large datasets can provide unparalleled statistical power, data aggregation without robust harmonization can mask and even introduce flaws and biases (3). This is a critical consideration in the behavioral sciences, where multi-site collaboration often requires the synthesis of non-identical cognitive measures (4)(5)(6). For example, verbal memory/recall is a core cognitive function, and deficits in learning and memory are one of the most common and widely assessed patient complaints (7).…”

Section: Introductionmentioning

confidence: 99%

“…To address these limitations, emerging data harmonization approaches offer new ways to perform data transformations that remove unwanted influences in aggregated data while preserving meaning (12). Data harmonization of large and heterogeneous AVLT data sources represents an appropriate framework for the development of cross-AVLT score conversion tools, but such efforts come with analytical and organizational challenges (1, 4, 16, 17).…”

Section: Main Text Introductionmentioning

confidence: 99%

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Bridging Big Data: Procedures for Combining Non-equivalent Cognitive Measures from the ENIGMA Consortium

Kennedy

Vadlamani

Lindsey

et al. 2023

Preprint

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Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subjects latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Main Text Introductionmentioning

confidence: 99%

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Bridging Big Data: Procedures for Combining Non-equivalent Cognitive Measures from the ENIGMA Consortium

Kennedy

Vadlamani

Lindsey

et al. 2023

Preprint

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“…Work is on-going in the ENIGMA Brain Injury working group to harmonize scales within the same domain. 39 The Behavior Rating Inventory of Executive Function (BRIEF) is one of the most widely used parent/informant questionnaire measures of executive functioning in children. 40…”

Section: Neurobehavioral Measuresmentioning

confidence: 99%

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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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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Harmonizing PTSD severity scales across instruments and sites.

Cited by 8 publications

References 37 publications

Bridging Big Data: Procedures for Combining Non-equivalent Cognitive Measures from the ENIGMA Consortium

Bridging Big Data: Procedures for Combining Non-equivalent Cognitive Measures from the ENIGMA Consortium

Multimodal Analysis of Secondary Cerebellar Alterations after Pediatric Traumatic Brain Injury

Multimodal Analysis of Secondary Cerebellar Alterations After Pediatric Traumatic Brain Injury

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