Ellen Grant
Harvard University
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Featured researches published by Ellen Grant.
NeuroImage | 2006
Kristina T. Ciesielski; Paul G. Lesnik; Robert L. Savoy; Ellen Grant; Seppo P. Ahlfors
The prefrontal and temporal networks subserving object working memory tasks in adults have been reported as immature in young children; yet children are adequately capable of performing such tasks. We investigated the basis of this apparent contradiction using a complex object working memory task, a Categorical n-back (CN-BT). We examined whether the neural networks engaged by the CN-BT in children consist of the same brain regions as those in adults, but with a different magnitude of activation, or whether the networks are qualitatively different. Event-related fMRI was used to study differences in brain activation between healthy children ages 6 and 10 years, and young adults (20-28 years). Performance accuracy and RTs in 10-year-olds and adults were comparable, but the performance in 6-year-olds was lower. In adults, the CN-BT was highly effective in engaging the bilateral (L>R) ventral prefrontal cortex, the bilateral fusiform gyrus, posterior cingulate and precuneus, thus suggesting an involvement of the ventral visual stream, with related feature extraction and semantic labeling strategies. In children, the brain networks were distinctly different. They involved the premotor and parietal cortex, anterior insula, caudate/putamen, and the cerebellum, thus suggesting a predominant involvement of the visual dorsal and sensory-motor pathways, with related visual-spatial and action cognitive strategies. The findings indicate engagement of developmental networks in children reflecting task-effective brain activation. The age-related pattern of fMRI activation suggests a working hypothesis of a developmental shift from reliance on the dorsal visual stream and premotor/striatal/cerebellar networks in young children to reliance on the ventral prefrontal and inferior temporal networks in adults.
American Journal of Neuroradiology | 2009
Florian Eichler; Wolfgang Grodd; Ellen Grant; Maria Sessa; Alessandra Biffi; Annette Bley; Alfried Kohlschuetter; Daniel J. Loes; Inge Kraegeloh-Mann
BACKGROUND AND PURPOSE: Metachromatic leukodystrophy (MLD) is a devastating demyelinating disease for which novel therapies are being tested. We hypothesized that MR imaging of brain lesion involvement in MLD could be quantified along a scale. MATERIALS AND METHODS: Thirty-four brain MR images in 28 patients with proved biochemical and genetic defects for MLD were reviewed: 10 patients with late infantile, 16 patients with juvenile, and 2 patients with adult MLD. All MR images were reviewed by experienced neuroradiologists and neurologists (2 readers in Germany, 2 readers in the United States) for global disease burden, as seen on the T2 and fluid-attenuated inversion recovery images. A visual scoring method was based on a point system (range, 0–34) derived from the location of white matter involvement and the presence of global atrophy, analogous to the scoring system developed for adrenoleukodystrophy. The readers were blinded to the neurologic findings. RESULTS: Thirty-three of 34 MR images showed confluent T2 hyperintensities of white matter. The inter-rater reliability coefficient was 0.988. Scores between readers were within 2 points of each other. Serial MR imaging studies in 6 patients showed significant progressive disease in 3 patients (initial score average, 4; mean follow-up, 24.3) and no change or 1 point progression in 3 patients (initial score average, 12; mean follow-up, 12.66). Projection fibers and the cerebellum tended to be involved only in advanced stages of disease. CONCLUSIONS: The MLD MR severity scoring method can be used to provide a measure of brain MR imaging involvement in MLD patients.
Journal of Neurology | 2010
Anne Gallagher; Ellen Grant; Neel Madan; Delma Y. Jarrett; David A. Lyczkowski; Elizabeth A. Thiele
Cortical tubers are very common in tuberous sclerosis complex (TSC) and widely vary in size, appearance and location. The relationship between tuber features and clinical phenotype is unclear. The aim of the study is to propose a classification of tuber types along a spectrum of severity, using magnetic resonance imaging (MRI) characteristics in 35 patients with TSC and history of epilepsy, and to investigate the relationship between tuber types and genetics, as well as clinical manifestations. Three types of tubers were identified based on the MRI signal intensity of their subcortical white matter component. (1) Tubers Type A are isointense on volumetric T1 images and subtly hyperintense on T2 weighted and fluid-attenuated inversion recovery (FLAIR); (2) Type B are hypointense on volumetric T1 images and homogeneously hyperintense on T2 weighted and FLAIR; (3) Type C are hypointense on volumetric T1 images, hyperintense on T2 weighted, and heterogeneous on FLAIR characterized by a hypointense central region surrounded by a hyperintense rim. Based on the dominant tuber type present, three distinct patient groups were also identified: Patients with Type A tuber dominance have a milder phenotype. Patients with Type C tuber dominance have more MRI abnormalities such as subependymal giant cell tumors, and were more likely to have an autism spectrum disorder, a history of infantile spasms, and a higher frequency of epileptic seizures, compared to patients who have a dominance in Type B tubers, and especially to those with a Type A dominance.
JAMA Psychiatry | 2016
Debra D'Angelo; Sébastien Lebon; Qixuan Chen; Sandra Martin-Brevet; LeeAnne Green Snyder; Loyse Hippolyte; Ellen Hanson; Anne M. Maillard; W. Andrew Faucett; Aurélien Macé; Aurélie Pain; Raphael Bernier; Samuel Chawner; Albert David; Joris Andrieux; Elizabeth H. Aylward; Genevieve Baujat; Ines Caldeira; Philippe Conus; Carrina Ferrari; Francesca Forzano; Marion Gerard; Robin P. Goin-Kochel; Ellen Grant; Jill V. Hunter; Bertrand Isidor; Aurélia Jacquette; Aia Elise Jønch; Boris Keren; Didier Lacombe
IMPORTANCE The 16p11.2 BP4-BP5 duplication is the copy number variant most frequently associated with autism spectrum disorder (ASD), schizophrenia, and comorbidities such as decreased body mass index (BMI). OBJECTIVES To characterize the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits and to understand the specificity of these effects by systematically comparing results in duplication carriers and reciprocal deletion carriers, who are also at risk for ASD. DESIGN, SETTING, AND PARTICIPANTS This international cohort study of 1006 study participants compared 270 duplication carriers with their 102 intrafamilial control individuals, 390 reciprocal deletion carriers, and 244 deletion controls from European and North American cohorts. Data were collected from August 1, 2010, to May 31, 2015 and analyzed from January 1 to August 14, 2015. Linear mixed models were used to estimate the effect of the duplication and deletion on clinical traits by comparison with noncarrier relatives. MAIN OUTCOMES AND MEASURES Findings on the Full-Scale IQ (FSIQ), Nonverbal IQ, and Verbal IQ; the presence of ASD or other DSM-IV diagnoses; BMI; head circumference; and medical data. RESULTS Among the 1006 study participants, the duplication was associated with a mean FSIQ score that was lower by 26.3 points between proband carriers and noncarrier relatives and a lower mean FSIQ score (16.2-11.4 points) in nonproband carriers. The mean overall effect of the deletion was similar (-22.1 points; P < .001). However, broad variation in FSIQ was found, with a 19.4- and 2.0-fold increase in the proportion of FSIQ scores that were very low (≤40) and higher than the mean (>100) compared with the deletion group (P < .001). Parental FSIQ predicted part of this variation (approximately 36.0% in hereditary probands). Although the frequency of ASD was similar in deletion and duplication proband carriers (16.0% and 20.0%, respectively), the FSIQ was significantly lower (by 26.3 points) in the duplication probands with ASD. There also were lower head circumference and BMI measurements among duplication carriers, which is consistent with the findings of previous studies. CONCLUSIONS AND RELEVANCE The mean effect of the duplication on cognition is similar to that of the reciprocal deletion, but the variance in the duplication is significantly higher, with severe and mild subgroups not observed with the deletion. These results suggest that additional genetic and familial factors contribute to this variability. Additional studies will be necessary to characterize the predictors of cognitive deficits.
JAMA Neurology | 2008
Eva Ratai; Trina Kok; Christopher J. Wiggins; Graham C. Wiggins; Ellen Grant; Borjan Gagoski; Gilmore O'Neill; Elfar Adalsteinsson; Florian Eichler
BACKGROUND Adults with X-linked adrenoleukodystrophy (X-ALD) remain at risk for progressive neurological deterioration. Phenotypes vary in their pathology, ranging from axonal degeneration to inflammatory demyelination. The severity of symptoms is poorly explained by conventional imaging. OBJECTIVE To test the hypothesis that neurochemistry in normal-appearing brains differs in adult phenotypes of X-ALD and that neurochemical changes correlate with the severity of symptoms. PATIENTS AND METHODS Using a 7-Tesla scanner, we performed structural and proton magnetic resonance spectroscopic imaging in 13 adult patients with X-ALD: 4 patients with adult cerebral ALD, 5 patients with adrenomyeloneuropathy (AMN), and 4 female heterozygotes. Nine healthy controls were included. RESULTS Among adult X-ALD phenotypes, the myo-inositol to creatine ratio was 46% higher and the choline to creatine ratio was 21% higher in normal-appearing white matter of those with adult cerebral ALD compared with those with AMN (P < .05). Both N-acetylaspartate to creatine (P = .03) and glutamate to creatine (P = .04) ratios were lower in AMN patients than in controls. There were no significant differences between patients with AMN and female heterozygotes. In the cortex, patients with adult cerebral ALD had lower N-acetylaspartate to creatine ratios compared with female heterozygotes and controls (P = .02). The global myo-inositol to creatine ratio demonstrated a significant association with Expanded Disability Status Scale score (Spearman rho = 0.66, P = .04). CONCLUSIONS Seven-Tesla proton magnetic resonance spectroscopic imaging reveals differences in the neurochemistry of adult cerebral ALD but cannot distinguish AMN patients from female heterozygotes. Myo-inositol to creatine ratio correlates with the severity of the symptoms and may be a meaningful biomarker in adult X-ALD.
IEEE Transactions on Biomedical Engineering | 2014
Erin M. Buckley; Pei-Yi Lin; Katherine Hagan; Angela Fenoglio; Mathieu Dehaes; Ellen Grant; Maria Angela Franceschini
In order to better understand the injured neonatal brain, we quantify cerebral oxygenation, blood flow, and oxygen metabolism in healthy neonates during the first days of life using non-invasive optical spectroscopies.
IEEE Transactions on Biomedical Engineering | 2014
Erin M. Buckley; Stefan A. Carp; Pei-Yi Lin; Haruo Nakaji; Jay Dubb; Dennis M. Hueber; Mathieu Dehaes; Ellen Grant; David A. Boas; Maria Angela Franceschini
Frequency domain near-infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) use near-infrared light to quantify static and dynamic properties of brain tissue. We present a novel FDNIRS-DCS system and characterize its performance.
Clinical Neurology and Neurosurgery | 2008
Darlene Gabeau-Lacet; Ellen Grant; Anat Stemmer-Rachamimov; Torunn I. Yock; Nancy J. Tarbell
Non-pituitary lesions account for a minority of sellar region abnormalities. We report the unusual occurrence of non-pituitary sellar/suprasellar lesions in a mother and her two daughters. Each of these cases was diagnosed and managed differently, illustrating the relative importance of radiographic imaging, tumor markers and histopathologic examination in the diagnosis and treatment of intracranial disease. The mother had histologically confirmed Rathkes cleft cyst (RCC) with typical radiographic and histologic appearance. One daughter was treated presumptively for germinoma based on characteristic radiographic studies and slightly elevated tumor marker. The other daughters lesion exhibited radiographic characteristics concerning for pituitary macroadenoma but with slightly elevated germ cell tumor marker, raising the suspicion for germinoma. Biopsy of the intrasellar mass revealed only proteinaceous material and normal anterior pituitary, consistent with cyst content without evidence of neoplasm. Without a clear unifying diagnosis it is difficult to posit an underlying pathology or genetic mechanisms in this unusual set of cases. At least two of the patients had benign cysts. The diagnosis of the third patient is unclear as there was no tissue biopsy. However, it is highly improbable that three female first-degree relatives would develop such lesions in the same brain region simply by chance.
Other repository | 2016
Silvina L. Ferradal; Borjan Gagoski; Rutvi Vyas; Christopher Ha; Divya S. Bolar; Henry H. Cheng; Jane W. Newburger; Maria Angela Franceschini; Ellen Grant; Jeffrey N. Stout; Elfar Adalsteinsson
IEEE Transactions on Biomedical Engineering | 2010
Bernhard B. Zimmermann; Nadege Roche-Labarbe; Andrea Surova; David A. Boas; Ellen Grant; Maria Angela Franceschini