| Examining the validity of the use of ratio IQs in psychological assessments | IQ tests are amongst the most used psychological assessments, both in research and clinical settings. For participants who cannot complete IQ tests normed for their age, ratio IQ scores (RIQ) are routinely computed and used as a proxy of IQ, especially in large research databases to avoid missing data points. However, because it has never been scientifically validated, this practice is questionable. In the era of big data, it is important to examine the validity of this widely used practice. In this paper, we use the case of autism to examine the differences between standard full-scale IQ (FSIQ) and RIQ. Data was extracted from four databases in which ages, FSIQ scores and subtests raw scores were available for autistic participants between 2 and 17 years old. The IQ tests included were the MSEL (N=12033), DAS-II early years (N=1270), DAS-II school age (N=2848), WISC-IV (N=471) and WISC-V (N=129). RIQs were computed for each participant as well as the discrepancy (DSC) between RIQ and FSIQ. We performed two linear regressions to respectively assess the effect of FSIQ and of age on the DSC for each IQ test, followed by additional analyses comparing age subgroups as well as FSIQ subgroups on DSC. Participants at the extremes of the FSIQ distribution tended to have a greater DSC than participants with average FSIQ. Furthermore, age significantly predicted the DSC, with RIQ superior to FSIQ for younger participants while the opposite was found for older participants. These results question the validity of this widely used alternative scoring method, especially for individuals at the extremes of the normal distribution, with whom RIQs are most often employed. | 162/17423 | Secondary Analysis | Shared |
| Clinical significance of diffusion tensor imaging in metachromatic leukodystrophy | Background Metachromatic leukodystrophy (MLD) is a lysosomal enzyme deficiency disorder leading to progressive demyelination and, consecutively, to cognitive and motor decline. Brain magnetic resonance imaging (MRI) can detect affected white matter as T2 hyperintense areas but cannot quantify the gradual microstructural process of demyelination more accurately. Our study aimed to investigate the value of routine MR diffusion tensor imaging in assessing disease progression.
Methods MR diffusion parameters (apparent diffusion coefficient [ADC] and fractional anisotropy [FA]) were in the frontal white matter, central region (CR), and posterior limb of the internal capsule in 111 MR datasets from a natural history study of 83 patients (age: 0.5–39.9 years; 35 late-infantile, 45 juvenile, 3 adult, with clinical diffusion sequences of different scanner manufacturers) as well as 120 controls. Results were correlated with clinical parameters reflecting motor and cognitive function.
Results ADC values increase and FA values decrease depending on disease stage/severity. They show region-specific correlations with clinical parameters of motor and cognitive symptoms, respectively. Higher ADC levels in CR at diagnosis predicted a disease course with more rapid motor deterioration in juvenile MLD patients. In highly organized tissues such as the corticospinal tract, in particular, diffusion MR parameters were highly sensitive to MLD-associated changes and did not correlate with the visual quantification of T2 hyperintensities.
Conclusion Our results show that diffusion MRI can deliver valuable, robust, clinically meaningful, and easily obtainable/accessible/available parameters in the assessment of prognosis and progression of MLD. Therefore, it provides additional quantifiable information to established methods such as T2 hyperintensity. | 210/211 | Secondary Analysis | Shared |
| The effect of intrathecal recombinant arylsulfatase A therapy on structural brain MRI in children with metachromatic leukodystrophy | Introduction: Metachromatic leukodystrophy (MLD) is a rare neurometabolic disorder caused by deficient activity of arylsulfatase A (ASA), resulting in sulfatide accumulation, demyelination and rapid neurological deterioration. A phase 1/2 study (NCT01510028) recently assessed the safety of intrathecal (IT) recombinant human ASA (SHP611; rhASA) in the late-infantile (LI) form of MLD. This analysis investigated the effect of IT rhASA on brain tissue changes in patients with LI-MLD using MRI volumetric and diffusion parameters.
Methods: 170 MRIs of 24 patients with LI-MLD treated with IT rhASA were compared with 56 MRIs of 12 patients with LI-MLD treated with intravenous (IV) rhASA, 43 MRIs of 33 untreated patients with LI-MLD and 238 MRIs of 156 healthy controls (C-MIND database: https://nda.nih.gov/edit_collection.html?id=2329). Automated segmentation of gray matter (GM) and white matter (WM) volumes was performed using T1- and T2-weighted sequences. Fractional anisotropy (FA) was calculated from diffusion tensor imaging in the frontal WM and part of the pyramidal tract.
Results: GM volume, brain volume and FA in all regions were decreased in patients with LI-MLD vs age-matched healthy controls. The most pronounced effects were visible for total brain and GM volume, and FA in the pyramidal tract, with greater decreases in the untreated and IV rhASA compared with the IT rhASA group (p<0.05). Patients who were clinical responders to IT rhASA had significantly improved MRI parameters compared with non-responders.
Conclusion: GM volume and microstructural changes in the pyramidal tract deteriorated over the clinical course in patients with LI-MLD. IT rhASA treatment had a positive effect on tissue changes. These MRI parameters correlated with clinical response to IT rhASA treatment. | 211/211 | Secondary Analysis | Shared |
| Age attenuates noise and increases symmetry of head movements during sleep resting-state fMRI in healthy neonates, infants, and toddlers | Newborns produce spontaneous movements during sleep that are functionally important for their future development.
This nuance has been previously studied using animal models and more recently using movement data from sleep
resting-state fMRI (rs-fMRI) scans. Age-related trajectory of statistical features of spontaneous movements of the head
is under-examined. This study quantitatively mapped a developmental trajectory of spontaneous head movements
during an rs-fMRI scan acquired during natural sleep in 91 datasets from healthy children from ~birth to 3 years old,
using the Open Science Infancy Research upcycling protocol. The youngest participants studied, 2-3 week-old
neonates, showed increased noise-to-signal levels as well as lower symmetry features of their movements; noise-tosignal
levels were attenuated and symmetry was increased in the older infants and toddlers (all Spearman’s rank-order
correlations, P< 0.05). Thus, statistical features of spontaneous head movements become more symmetrical and less
noisy from birth to ~3 years in children. Because spontaneous movements during sleep in early life may trigger new
neuronal activity in the cortex, the key outstanding question for in-vivo, non-invasive neuroimaging studies in young
children is not “How can we correct head movement better?” but rather: How can we represent all important sources of
neuronal activity that shape functional connections in the still-developing human central nervous system? | 35/86 | Secondary Analysis | Shared |
| Resting-state fMRI effective connectivity of deep grey motor networks in children with developmental movement disorders | INTRODUCTION/HYPOTHESIS/SCIENTIFIC PREMISE
Developmental movement disorders, such as dystonic cerebral palsy (CP-D), can dramatically influence quality of life and functioning and are often refractory to treatment. Pediatric movement disorders are increasingly conceptualized as brain network disorders- particularly dysfunction involving basal ganglia networks – which may be targeted for treatment. However, little is known about the nature of cortical and subcortical motor network disturbances involved, nor the causal relationships expected within these networks in typically developing children. This contributes to the difficulty in treating CP-D. In this study, we use resting state fMRI (RS) to develop a preliminary model of normal effective connectivity within pediatric basal ganglia motor networks and compare the normal model to models of children with developmental movement disorders.
METHODS/APPROACH
We used the (RS) scans from 19 participants of the Cincinnati MR Imaging of NeuroDevelopment (C-MIND) database to build a normal pediatric model. Data were pre-processed using a standard pipeline in Statistical Parametric Mapping (SPM12). The CAT12 toolbox in SPM was used to draw the following regions of interest in each hemisphere: primary motor cortex (M1), thalamus, sub-thalamic nucleus (STN), striatum, globus pallidus internus (GPi), and contralateral cerebellum. Dynamic causal modelling (DCM) in SPM was then used to create a directional model between these regions for each hemisphere. These models were then averaged across the normal group, resulting in two models (left, right). Patient data were collected as a part of clinical treatment at Phoenix Children's Hospital and their DCM models were individually compared to the averaged normal DCM models for each hemisphere.
RESULTS
The averaged normal DCM models were largely symmetrical between hemispheres, though causal connections were more pronounced in the left hemisphere model. All modulatory signals toward the STN were inhibitory. Modulations from the cerebellum were inhibitory toward all other regions. In the right hemisphere, GPi was inhibitory toward M1 and cerebellum, but in the left it was inhibitory toward thalamus. The GPi is thought to be crucial in inhibiting unwanted movement and is the primary target of interventions such as deep brain stimulation in CP-D.
CONCLUSIONS/DISCUSSION
The preliminary DCM for normal basal ganglia motor networks in children are consistent with anatomically known and functionally hypothesized relationships in adults. In particular, there was overall inhibition toward bilateral STN. Additionally, GPi had an inhibitory effect on regions that initiate movement, however, the specific regions differed between hemisphere.
| 19/19 | Secondary Analysis | Shared |
