White Matter Hyperintensities and Mild TBI in Post-9/11 Veterans and Service Members.

INTRODUCTION: The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. MATERIALS AND METHODS: The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median postinjury interval of 8 years) or negative mTBI history (n = 198), were examined. RESULTS: White matter hyperintensities were present in both mTBI and comparison groups at similar rates (39% and 37%, respectively). There was an age-by-diagnostic group interaction, such that older Veterans and Service Members with a history of mTBI demonstrated a significant increase in the number of WMHs present compared to those without a history of mTBI. Additional associations between an increase in the number of WMHs and service-connected disability, insulin-like growth factor-1 levels, and worse performance on tests of episodic memory and executive functioning-processing speed were found. CONCLUSIONS: Subtle but important clinical relationships are identified when larger samples of mTBI participants are used to examine the relationship between history of head injury and radiological findings. Future studies should use follow-up magnetic resonance imaging and longitudinal neurobehavioral assessments to evaluate the long-term implications of WMHs following mTBI.

Scheltens ratings, clinical white matter hyperintensities and executive functioning in the Cache County Memory Study.

OBJECTIVE: Examine the association between neuropsychologically assessed executive function and clinically identifiable white matter burden from magnetic resonance imaging, using a visual rating system (Scheltens Rating System) applied to the Cache County Memory Study (CCMS) archival database. METHOD: We used the Scheltens Ratings Scale to quantify white matter lesion burden in the CCMS sample and used this metric as a predictor of executive function. The sample included 60 individuals with dementia and 13 healthy controls. RESULTS: Higher Scheltens ratings were associated with poorer task performance on an Executive Function composite score of common neuropsychological tests. This association held true for both controls and dementing cases. CONCLUSIONS: The current findings support extensive prior literature demonstrating the association between brain vascular health determined by white matter burden and clinical outcomes based on neuropsychological assessment of cognitive performance.

Cognitive Sparing in Proton versus Photon Radiotherapy for Pediatric Brain Tumor Is Associated with White Matter Integrity: An Exploratory Study.

Radiotherapy for pediatric brain tumors is associated with reduced white matter structural integrity and neurocognitive decline. Superior cognitive outcomes have been reported following proton radiotherapy (PRT) compared to photon radiotherapy (XRT), presumably due to improved sparing of normal brain tissue. This exploratory study examined the relationship between white matter change and late cognitive effects in pediatric brain tumor survivors treated with XRT versus PRT. Pediatric brain tumor survivors treated with XRT (n = 10) or PRT (n = 12) underwent neuropsychological testing and diffusion weighted imaging >7 years post-radiotherapy. A healthy comparison group (n = 23) was also recruited. Participants completed age-appropriate measures of intellectual functioning, visual-motor integration, and motor coordination. Tractography was conducted using automated fiber quantification (AFQ). Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were extracted from 12 tracts of interest. Overall, both white matter integrity (FA) and neuropsychological performance were lower in XRT patients while PRT patients were similar to healthy control participants with respect to both FA and cognitive functioning. These findings support improved long-term outcomes in PRT versus XRT. This exploratory study is the first to directly support for white matter integrity as a mechanism of cognitive sparing in PRT.

Consideration of different scoring approaches for a verbal incidental learning measure from the WAIS-IV using hippocampal volumes.

Objective: While Spencer's verbal incidental learning (IL) task-from Vocabulary and Similarities subtests of the WAIS-has been validated relative to traditional memory measures and Alzheimer's disease (AD) pathology, the effectiveness of the particular scoring method used has not been assessed relative to alternative scoring weightings. The purpose of this study was to compare original and alternative scoring methods of this IL task by using an AD biomarker-benchmark to arrive at an optimal approach. Methods: Fifty-five memory-clinic patients aged 59-87 received neuropsychological assessment, measures of IL, and quantitative brain imaging. Partial correlation coefficients with total hippocampal volume-controlling for age, sex, and intracranial volume-were assessed across several IL scoring methods, and partial correlations with measures of memory were examined to evaluate convergent validity.Results: IL scoring methods maximizing the contribution of paired-associate-recall-performance were significantly correlated with both hippocampal volumes and traditional memory measures, whereas discrimination-emphasized scoring methods were not.Conclusions: IL scoring methods emphasizing memory paired-associate recall appeared to be preferable to those emphasizing memory discrimination. Administration of the IL- Similarities subtest alone, without IL- Vocabulary, may strike a balance between strength of relationships with both hippocampal volumes and standard memory measures, while also limiting administration time.

Advanced brain age in deployment-related traumatic brain injury: A LIMBIC-CENC neuroimaging study.

OBJECTIVE: To determine if history of mild traumatic brain injury (mTBI) is associated with advanced or accelerated brain aging among the United States (US) military Service Members and Veterans. METHODS: Eight hundred and twenty-two participants (mean age = 40.4 years, 714 male/108 female) underwent MRI sessions at eight sites across the US. Two hundred and one participants completed a follow-up scan between five months and four years later. Predicted brain ages were calculated using T1-weighted MRIs and then compared with chronological ages to generate an Age Deviation Score for cross-sectional analyses and an Interval Deviation Score for longitudinal analyses. Participants also completed a neuropsychological battery, including measures of both cognitive functioning and psychological health. RESULT: In cross-sectional analyses, males with a history of deployment-related mTBI showed advanced brain age compared to those without (t(884) = 2.1, p = .038), while this association was not significant in females. In follow-up analyses of the male participants, severity of posttraumatic stress disorder (PTSD), depression symptoms, and alcohol misuse were also associated with advanced brain age. CONCLUSION: History of deployment-related mTBI, severity of PTSD and depression symptoms, and alcohol misuse are associated with advanced brain aging in male US military Service Members and Veterans.

Preliminary Validation of the Learning Ratio for the HVLT-R and BVMT-R in Older Adults.

BACKGROUND: The learning slope is typically represented as the raw difference between the final score and the score of the first learning trial. A new method for calculating the learning slope, the learning ratio (LR), was recently developed; it is typically represented as the number of items that are learned after the first trial divided by the number of items that are yet to be learned. OBJECTIVE: To evaluate the convergent and criterion validity of the LR in order to understand its sensitivity to Alzheimer disease (AD) pathology. METHOD: Fifty-six patients from a memory clinic underwent standard neuropsychological assessment and quantitative brain imaging. LR scores were calculated from the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised and were compared with both standard memory measures and total hippocampal volumes, as well as between individuals with AD and those with mild cognitive impairment. RESULTS: Lower LR scores were consistently associated with poorer performances on standard memory measures and smaller total hippocampal volumes, generally more so than traditional learning slope scores. The LR scores of the AD group were smaller than those of the group with mild cognitive impairment. Furthermore, the aggregation of LR scores into a single metric was partially supported. CONCLUSION: The LR is sensitive to AD pathology along the AD continuum. This result supports previous claims that the LR score can reflect learning capacity better than traditional learning calculations can by considering the amount of information that is learned at trial 1.

Developmental Alterations in Cortical Organization and Socialization in Adolescents Who Sustained a Traumatic Brain Injury in Early Childhood.

This study investigated patterns of cortical organization in adolescents who had sustained a traumatic brain injury (TBI) during early childhood to determine ways in which early head injury may alter typical brain development. Increased gyrification in other patient populations is associated with polymicrogyria and aberrant development, but this has not been investigated in TBI. Seventeen adolescents (mean age = 14.1 ± 2.4) who sustained a TBI between 1-8 years of age, and 17 demographically-matched typically developing children (TDC) underwent a high-resolution, T1-weighted 3-Tesla magnetic resonance imaging (MRI) at 6-15 years post-injury. Cortical white matter volume and organization was measured using FreeSurfer's Local Gyrification Index (LGI). Despite a lack of significant difference in white matter volume, participants with TBI demonstrated significantly increased LGI in several cortical regions that are among those latest to mature in normal development, including left parietal association areas, bilateral dorsolateral and medial frontal areas, and the right posterior temporal gyrus, relative to the TDC group. Additionally, there was no evidence of increased surface area in the regions that demonstrated increased LGI. Higher Vineland-II Socialization scores were associated with decreased LGI in right frontal and temporal regions. The present results suggest an altered pattern of expected development in cortical gyrification in the TBI group, with changes in late-developing frontal and parietal association areas. Such changes in brain structure may underlie cognitive and behavioral deficits associated with pediatric TBI. Alternatively, increased gyrification following TBI may represent a compensatory mechanism that allows for typical development of cortical surface area, despite reduced brain volume.

Examining the Relationship between a Verbal Incidental Learning Measure from the WAIS-IV and Neuroimaging Biomarkers for Alzheimer's Pathology.

Convergent validation of a verbal incidental learning (IL) task from the WAIS-IV using neuroimaging biomarkers is warranted to understand its sensitivity to Alzheimer's disease (AD) pathology. Fifty-five memory clinic patients aged 59 to 87 years received neuropsychological assessment, and measures of IL and quantitative brain imaging. Worse IL-Total Score and IL-Similarities performances were significantly associated with smaller hemispheric hippocampal volumes. IL measures were not significantly correlated with cerebral ß-amyloid burden, though a trend was present and effect sizes were mild. These hippocampal volume results suggest that this IL task may be sensitive to AD pathology along the AD continuum.

Post-Acute Cortical Thickness in Children with Mild Traumatic Brain Injury versus Orthopedic Injury.

Studies of brain morphometry may illuminate the effects of pediatric mild traumatic brain injury (TBI; e.g., concussion). However, no published studies have examined cortical thickness in the early injury phases of pediatric mild TBI using an appropriate comparison group. The current study used an automated approach (i.e., FreeSurfer) to determine whether cortical thickness differed in children following a mild TBI or a mild orthopedic injury (OI), and to examine whether post-acute cortical thickness predicted post-acute and chronic post-concussive symptoms (PCS). Children ages 8.00-16.99 years with mild TBI (n = 136) or OI (n = 70) were recruited at emergency department visits to two children's hospitals, during which parents rated children's pre-injury symptoms retrospectively. Children completed a post-acute (3-24 days post-injury) assessment, which included a 3 Tesla MRI, and 3- and 6-month post-injury assessments. Parents and children rated PCS at each assessment. Cortical thickness was estimated using FreeSurfer. Linear mixed effects and multi-variable negative binomial regression models were used to test study aims, with false discovery rate (FDR) correction for multiple comparisons. Groups differed significantly on left parietal cortical thickness (TBI > OI) after FDR correction. Cortical thickness also varied by brain subregion and age, but not sex. Groups differed significantly on PCS post-acutely (TBI > OI), but not at 3 or 6 months. Right frontal thickness was positively related to post-acute PCS in both groups. Right cingulum thickness predicted chronic PCS in the OI group only. Results highlight the complexity of predicting outcomes of pediatric mild TBI from post-acute neuroimaging biomarkers.

Post-acute white matter microstructure predicts post-acute and chronic post-concussive symptom severity following mild traumatic brain injury in children.

INTRODUCTION: Mild traumatic brain injury (TBI) is a global public health concern that affects millions of children annually. Mild TBI tends to result in subtle and diffuse alterations in brain tissue, which challenges accurate clinical detection and prognostication. Diffusion tensor imaging (DTI) holds promise as a diagnostic and prognostic tool, but little research has examined DTI in post-acute mild TBI. The current study compared post-acute white matter microstructure in children with mild TBI versus those with mild orthopedic injury (OI), and examined whether post-acute DTI metrics can predict post-acute and chronic post-concussive symptoms (PCS). MATERIALS AND METHODS: Children aged 8-16.99 years with mild TBI (n = 132) or OI (n = 69) were recruited at emergency department visits to two children's hospitals, during which parents rated children's pre-injury symptoms retrospectively. Children completed a post-acute (<2 weeks post-injury) assessment, which included a 3T MRI, and 3- and 6-month post-injury assessments. Parents and children rated PCS at each assessment. Mean diffusivity (MD) and fractional anisotropy (FA) were derived from diffusion-weighted MRI using Automatic Fiber Quantification software. Multiple multivariable linear and negative binomial regression models were used to test study aims, with False Discovery Rate (FDR) correction for multiple comparisons. RESULTS: No significant group differences were found in any of the 20 white matter tracts after FDR correction. DTI metrics varied by age and sex, and site was a significant covariate. No interactions involving group, age, and sex were significant. DTI metrics in several tracts robustly predicted PCS ratings at 3- and 6-months post-injury, but only corpus callosum genu MD was significantly associated with post-acute PCS after FDR correction. Significant group by DTI metric interactions on chronic PCS ratings indicated that left cingulum hippocampus and thalamic radiation MD was positively associated with 3-month PCS in the OI group, but not in the mild TBI group. CONCLUSIONS: Post-acute white matter microstructure did not differ for children with mild TBI versus OI after correcting for multiple comparisons, but was predictive of post-acute and chronic PCS in both injury groups. These findings support the potential prognostic utility of this advanced DTI technique.

FreeSurfer 5.3 versus 6.0: are volumes comparable? A Chronic Effects of Neurotrauma Consortium study.

Automated neuroimaging methods like FreeSurfer ( https://surfer.nmr.mgh.harvard.edu/ ) have revolutionized quantitative neuroimaging analyses. Such analyses provide a variety of metrics used for image quantification, including magnetic resonance imaging (MRI) volumetrics. With the release of FreeSurfer version 6.0, it is important to assess its comparability to the widely-used previous version 5.3. The current study used data from the initial 249 participants in the ongoing Chronic Effects of Neurotrauma Consortium (CENC) multicenter observational study to compare the volumetric output of versions 5.3 and 6.0 across various regions of interest (ROI). In the current investigation, the following ROIs were examined: total intracranial volume, total white matter volume, total ventricular volume, total gray matter volume, and right and left volumes for the thalamus, pallidum, putamen, caudate, amygdala and hippocampus. Absolute ROI volumes derived from FreeSurfer 6.0 differed significantly from those obtained using version 5.3. We also employed a clinically-based evaluation strategy to compare both versions in their prediction of age-mediated volume reductions (or ventricular increase) in the aforementioned structures. Statistical comparison involved both general linear modeling (GLM) and random forest (RF) methods, where cross-validation error was significantly higher using segmentations from FreeSurfer version 5.3 versus version 6.0 (GLM: t = 4.97, df = 99, p value = 2.706e-06; RF: t = 4.85, df = 99, p value = 4.424e-06). Additionally, the relative importance of ROIs used to predict age using RFs differed between FreeSurfer versions, indicating substantial differences in the two versions. However, from the perspective of correlational analyses, fitted regression lines and their slopes were similar between the two versions, regardless of version used. While absolute volumes are not interchangeable between version 5.3 and 6.0, ROI correlational analyses appear to yield similar results, suggesting the interchangeability of ROI volume for correlational studies.

Structural neuroimaging in mild traumatic brain injury: A chronic effects of neurotrauma consortium study.

OBJECTIVES: The chronic effects of neurotrauma consortium (CENC) observational study is a multisite investigation designed to examine the long-term longitudinal effects of mild traumatic brain injury (mTBI). All participants in this initial CENC cohort had a history of deployment in Operation Enduring Freedom (Afghanistan), Operation Iraqi Freedom (Iraq), and/or their follow-on conflicts (Operation Freedom's Sentinel). All participants undergo extensive medical, neuropsychological, and neuroimaging assessments and either meet criteria for any lifetime mTBI or not. These assessments are integrated into six CENC core studies-Biorepository, Biostatistics, Data and Study Management, Neuroimaging, and Neuropathology. METHODS: The current study outlines the quantitative neuroimaging methods managed by the Neuroimaging Core using FreeSurfer automated software for image quantification. RESULTS: At this writing, 319 participants from the CENC observational study have completed all baseline assessments including the imaging protocol and tertiary data quality assurance procedures. CONCLUSIONS/DISCUSSION: The preliminary findings of this initial cohort are reported to describe how the Neuroimaging Core manages neuroimaging quantification for CENC studies.

Methylphenidate Treatment of Cognitive Dysfunction in Adults After Mild to Moderate Traumatic Brain Injury: Rationale, Efficacy, and Neural Mechanisms.

Positive effects of methylphenidate (MPH) on attention and cognitive processing speed have been reported in studies of patients with moderate to severe traumatic brain injury (TBI). Studies which have acquired functional brain imaging before and while using MPH have also found alteration of brain activation while performing a cognitive task; in some studies, this alteration of activation in selective brain regions was also related to improved performance on cognitive tests administered outside of the scanning environment. Enhanced cognitive performance has been reported after single doses of MPH and after daily treatment over durations of up to and exceeding 1 month. Preclinical research and both positron emission tomography and single photon emission tomography of humans have shown that MPH increases extracellular dopamine and norepinephrine; the dose effects of MPH have an inverted U-shaped function where high doses may cause insomnia, nervousness, and increased heart rate among other symptoms and impair cognitive performance, whereas too low a dose fails to improve cognitive performance. In the past 5 years, small clinical trials, and experimental pilot studies have found therapeutic effects of single and repeated low doses of MPH in patients with mild TBI who reported cognitive dysfunction. This literature also suggests that MPH may interact with concurrent cognitive interventions to enhance their effects. This focused review will critically evaluate the recent literature on MPH effects on cognitive dysfunction after mild to moderate TBI. To elucidate the neural mechanisms of MPH effects, this review will also include recent imaging research, preclinical, and experimental human studies.

The mentalizing network and theory of mind mediate adjustment after childhood traumatic brain injury.

Childhood traumatic brain injury (TBI) affects over 600 000 children per year in the United States. Following TBI, children are vulnerable to deficits in psychosocial adjustment and neurocognition, including social cognition, which persist long-term. They are also susceptible to direct and secondary damage to related brain networks. In this study, we examine whether brain morphometry of the mentalizing network (MN) and theory of mind (ToM; one component of social cognition) mediates the effects of TBI on adjustment. Children with severe TBI (n = 15, Mage = 10.32), complicated mild/moderate TBI (n = 30, Mage = 10.81) and orthopedic injury (OI; n = 42, Mage = 10.65) completed measures of ToM and executive function and underwent MRI; parents rated children's psychosocial adjustment. Children with severe TBI demonstrated reduced right-hemisphere MN volume, and poorer ToM, vs children with OI. Ordinary least-squares path analysis indicated that right-hemisphere MN volume and ToM mediated the association between severe TBI and adjustment. Parallel analyses substituting the central executive network and executive function were not significant, suggesting some model specificity. Children at greatest risk of poor adjustment after TBI could be identified based in part on neuroimaging of social brain networks and assessment of social cognition and thereby more effectively allocate limited intervention resources.

Assessment of quantitative magnetic resonance imaging metrics in the brain through the use of a novel phantom.

OBJECTIVE: Multisite and longitudinal neuroimaging studies are important in uncovering trajectories of recovery and neurodegeneration following traumatic brain injury (TBI) and concussion through the use of diffusion tensor imaging (DTI) and other imaging modalities. This study assessed differences in anisotropic diffusion measurement across four scanners using a human and a novel phantom developed in conjunction with the Chronic Effects of Neurotrauma Consortium. METHOD: Human scans provided measurement within biological tissue, and the novel physical phantom provided measures of anisotropic intra-tubular diffusion to serve as a model for intra-axonal water diffusion. Intra- and inter-scanner measurement variances were compared, and the impact on effect size was calculated. RESULTS: Intra-scanner test-retest reliability estimates for fractional anisotropy (FA) demonstrated relative stability over testing intervals. The human tissue and phantom showed similar FA ranges, high linearity and large within-device effect sizes. However, inter-scanner measures of FA indicated substantial differences, some of which exceeded typical DTI effect sizes in mild TBI. CONCLUSION: The diffusion phantom may be used to better elucidate inter-scanner variability in DTI-based measurement and provides an opportunity to better calibrate results obtained from scanners used in multisite and longitudinal studies. Novel solutions are being evaluated to understand and potentially overcome these differences.

Functional brain connectivity and cortical thickness in relation to chronic pain in post-911 veterans and service members with mTBI.

OBJECTIVES: Investigate the relation of chronic pain interference to functional connectivity (FC) of brain regions and to cortical thickness in post-911 Veterans and Service Members (SMs) who sustained a mild traumatic brain injury (mTBI). METHODS: This is an observational study with cross-sectional analyses. A sample of 65 enrollees completing initial evaluation at a single site of the Chronic Effects of Neurotrauma Consortium (CENC) reported pain interference ratings on the TBI QOL. Functional connectivity and cortical thickness were measured. RESULTS: Severity of pain interference was negatively related to FC of the default mode network (DMN), i.e., participants who reported more severe pain interference had less FC between mesial prefrontal cortex and posterior regions of the DMN including posterior cingulate cortex and precuneus. Cortical thickness of specific regions was positively related to severity of pain interference. CONCLUSION: The more that pain was perceived to interfere with daily life, the less the FC between regions in a network associated with self-referential thought and mind wandering. Although cortical thickness in specific brain regions was positively related to severity of pain interference, follow-up longitudinal data, control group data, and study of individual differences in this cohort will expand this initial report and replicate these findings.

Cortical thickness in pediatric mild traumatic brain injury including sports-related concussion.

This investigation explored whether differences in cortical thickness could be detected in children who sustained a mild traumatic brain injury (mTBI) compared to those with orthopedic injury (OI) and whether cortical thickness related parental reporting of symptoms. To achieve this objective, FreeSurfer®-based cortical thickness measures were obtained in 330 children, 8 to 15 years of age, with either a history of mTBI or OI. Imaging was performed in all participants with the same 3 Tesla MRI scanner at six-months post-injury, where a parent-rated Post-Concussion Symptom Inventory (PCSI) was also obtained. Robust age-mediated reductions in cortical thickness were observed, but no consistent group-based differences between the mTBI and OI groups were observed. Also, the relation between mechanism of injury (i.e., sports-related, recreational, fall, motor vehicle accident or other) and cortical thickness was examined. Injuries associated with any type of abuse were excluded and children with OI could not have experienced a MVA. Mechanism of injury did not differentially relate to cortical thickness, although in the fall group, parental rating using the PCSI showed increased symptom reporting to be associated with reduced cortical thickness in the left interior frontal, temporal pole and lateral temporal lobe as well as in the right temporal pole. Results from these preliminary findings are discussed in terms of injury variables and developmental factors associated with mTBI in childhood.

ENIGMA MILITARY BRAIN INJURY: A COORDINATED META-ANALYSIS OF DIFFUSION MRI FROM MULTIPLE COHORTS.

Traumatic brain injury (TBI) is a significant cause of morbidity in military Veterans and Service Members. While most individuals recover fully from mild injuries within weeks, some continue to experience symptoms including headaches, disrupted sleep, and other cognitive, behavioral or physical symptoms. Diffusion magnetic resonance imaging (dMRI) shows promise in identifying areas of structural disruption and predicting outcomes. Although some studies suggest widespread structural disruption after brain injury, dMRI studies of military brain injury have yielded mixed results so far, perhaps due to the subtlety of mild injury, individual differences in injury location, severity and mechanism, and comorbidity with other disorders such as post-traumatic stress disorder (PTSD), depression, and substance abuse. We present preliminary dMRI results from the ENIGMA (Enhancing Neuroimaging Genetics through Meta-Analysis) military brain injury working group. We found higher fractional anisotropy (FA) in participants with a history of TBI. Understanding the injury and recovery process, along with factors that influence these, will lead to improved diagnosis and treatment.

High correlations between MRI brain volume measurements based on NeuroQuant® and FreeSurfer.

NeuroQuant® (NQ) and FreeSurfer (FS) are commonly used computer-automated programs for measuring MRI brain volume. Previously they were reported to have high intermethod reliabilities but often large intermethod effect size differences. We hypothesized that linear transformations could be used to reduce the large effect sizes. This study was an extension of our previously reported study. We performed NQ and FS brain volume measurements on 60 subjects (including normal controls, patients with traumatic brain injury, and patients with Alzheimer's disease). We used two statistical approaches in parallel to develop methods for transforming FS volumes into NQ volumes: traditional linear regression, and Bayesian linear regression. For both methods, we used regression analyses to develop linear transformations of the FS volumes to make them more similar to the NQ volumes. The FS-to-NQ transformations based on traditional linear regression resulted in effect sizes which were small to moderate. The transformations based on Bayesian linear regression resulted in all effect sizes being trivially small. To our knowledge, this is the first report describing a method for transforming FS to NQ data so as to achieve high reliability and low effect size differences. Machine learning methods like Bayesian regression may be more useful than traditional methods.