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Allenstown Elementary School, NH, United States

Krivitzky L.S.,George Washington University | Roebuck-Spencer T.M.,University of Oklahoma | Roth R.M.,Brain Imaging Laboratory | Blackstone K.,George Washington University | And 2 more authors.
Journal of the International Neuropsychological Society | Year: 2011

The current pilot study examined functional magnetic resonance imaging (fMRI) activation in children with mild traumatic brain injury (mTBI) during tasks of working memory and inhibitory control, both of which are vulnerable to impairment following mTBI. Thirteen children with symptomatic mTBI and a group of controls completed a version of the Tasks of Executive Control (TEC) during fMRI scanning. Both groups showed greater prefrontal activation in response to increased working memory load. Activation patterns did not differ between groups on the working memory aspects of the task, but children with mTBI showed greater activation in the posterior cerebellum with the addition of a demand for inhibitory control. Children with mTBI showed greater impairment on symptom report and "real world" measures of executive functioning, but not on traditional "paper and pencil" tasks. Likewise, cognitive testing did not correlate significantly with imaging results, whereas increased report of post-concussive symptoms were correlated with increased cerebellar activation. Overall, results provide some evidence for the utility of symptom report as an indicator of recovery and the hypothesis that children with mTBI may experience disrupted neural circuitry during recovery. Limitations of the study included a small sample size, wide age range, and lack of in-scanner accuracy data. © Copyright The International Neuropsychological Society 2011.

Fadul C.E.,Dartmouth Hitchcock Medical Center | Fadul C.E.,Norris Cotton Cancer Center | Hampton T.H.,Dartmouth Hitchcock Medical Center | Lallana E.C.,Dartmouth Hitchcock Medical Center | And 7 more authors.
Journal of Immunotherapy | Year: 2011

Patients with glioblastoma multiforme (GBM) are profoundly immunosuppressed and may benefit from restoration of an antitumor immune response in combination with conventional radiation therapy and temozolomide (TMZ). The optimal strategies to evaluate clinically relevant immune responses to treatment have yet to be determined. The primary objective of our study was to determine immunologic response to cervical intranodal vaccination with autologous tumor lysate-loaded dendritic cells (DCs) in patients with GBM after radiation therapy and TMZ. We used a novel hierarchical clustering analysis of immune parameters measured before and after vaccination. Secondary objectives were to assess treatment feasibility and to correlate immune response with progression-free survival (PFS) and overall survival. Ten eligible patients received vaccination. Tumor-specific cytotoxic T-cell response measured after vaccination was enhanced for the precursor frequency of CD4+ T and CD4+ interferon γ-producing cells. Hierarchical clustering analysis of multiple functional outcomes discerned 2 groups of patients according to their immune response, and additionally showed that patients in the top quintile for at least one immune function parameter had improved survival. There were no serious adverse events related to DC vaccination. All patients were alive at 6 months after diagnosis and the 6-month PFS was 90%. The median PFS was 9.5 months and overall survival was 28 months. In patients with GBM, immune therapy with DC vaccination after radiation and TMZ resulted in tumor-specific immune responses that were associated with prolonged survival. Our data suggest that DC vaccination in combination with radiation and chemotherapy in patients with GBM is feasible, safe, and may induce tumor-specific immune responses. © 2011 by Lippincott Williams and Wilkins.

Dumas J.A.,University of Vermont | McDonald B.C.,Indiana University | Saykin A.J.,Indiana University | McAllister T.W.,Brain Imaging Laboratory | And 3 more authors.
Menopause | Year: 2010

Objective: The cholinergic system has been shown to modulate estrogen effects on cognitive performance in postmenopausal women. In an effort to further understand cholinergic contributions to cognition after menopause, this pilot study investigated the effects of two receptor-specific anticholinergic drugs on brain activation and episodic memory encoding in postmenopausal women not taking estrogen. Methods: Six healthy postmenopausal women took part in three drug challenges using the antimuscarinic drug scopolamine (2.5 μg/kg IV), the antinicotinic drug mecamylamine (20 mg PO), and placebo. During functional magnetic resonance imaging, participants performed a visual-verbal continuous recognition memory test that allowed for the separation of encoding and recognition processes. Results: Functional magnetic resonance imaging results showed greater hippocampal and frontal activation and less occipital activation during encoding relative to retrieval conditions. This pattern of activation was similar under both drug challenges. Conclusions: These results suggest that the changes in the cholinergic system may, in part, be responsible for menopause-related increases in brain activation. © 2010 by The North American Menopause Society.

Sloan C.D.,Computational Genetics Laboratory | Shen L.,Indiana University | West J.D.,Indiana University | Wishart H.A.,Brain Imaging Laboratory | And 12 more authors.
American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics | Year: 2010

Hierarchical clustering is frequently used for grouping results in expression or haplotype analyses. These methods can elucidate patterns between measures that can then be applied to discerning their validity in discriminating between experimental conditions. Here a hierarchical clustering method is used to analyze the results of an imaging genetics study using multiple brain morphology and cognitive testing endpoints for older adults with amnestic mild cognitive impairment (MCI) or cognitive complaints (CC) compared to healthy controls (HC). The single nucleotide polymorphisms (SNPs) are a subset of those included on a larger array that are found in a reported Alzheimer's disease (AD) and neurodegeneration pathway. The results indicate that geneticmodels within the endpoints cluster together, while there are 4 distinct sets of SNPs that differentiate between the endpoints, with most significant results associated with morphology endpoints rather than cognitive testing of patients' reported symptoms. The genes found in at least one cluster are ABCB1, APBA1, BACE1, BACE2, BCL2, BCL2L1, CASP7, CHAT, CST3, DRD3, DRD5, IL6, LRP1, NAT1, and PSEN2. The greater associations with morphology endpoints suggests that changes in brain structure can be influenced by an individual's genetic background in the absence of dementia and in some cases (Cognitive Complaints group) even without those effects necessarily being detectable on commonly used clinical tests of cognition. The results are consistent with polygenic influences on early neurodegenerative changes and demonstrate the effectiveness of hierarchical clustering in identifying genetic associations among multiple related phenotypic endpoints. © 2010 Wiley-Liss, Inc.

Wang Y.,Indiana University | West J.D.,Indiana University | Flashman L.A.,Brain Imaging Laboratory | Wishart H.A.,Brain Imaging Laboratory | And 6 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2012

Background: White matter changes measured using diffusion tensor imaging have been reported in Alzheimer's disease and amnestic mild cognitive impairment, but changes in earlier pre-mild cognitive impairment stages have not been fully investigated. Methods: In a cross-sectional analysis, older adults with mild cognitive impairment (n. = 28), older adults with cognitive complaints but without psychometric impairment (n. = 29) and healthy controls (n. = 35) were compared. Measures included whole-brain diffusion tensor imaging, T1-weighted structural magnetic resonance imaging, and neuropsychological assessment. Diffusion images were analyzed using Tract-Based Spatial Statistics. Voxel-wise fractional anisotropy and mean, axial, and radial diffusivities were assessed and compared between groups. Significant tract clusters were extracted in order to perform further region of interest comparisons. Brain volume was estimated using FreeSurfer based on T1 structural images. Results: The mild cognitive impairment group showed lower fractional anisotropy and higher radial diffusivity than controls in bilateral parahippocampal white matter. When comparing extracted diffusivity measurements from bilateral parahippocampal white matter clusters, the cognitive complaint group had values that were intermediate to the mild cognitive impairment and healthy control groups. Group difference in diffusion tensor imaging measures remained significant after controlling for hippocampal atrophy. Across the entire sample, diffusion tensor imaging indices in parahippocampal white matter were correlated with memory function. Conclusions: These findings are consistent with previous results showing changes in parahippocampal white matter in Alzheimer's disease and mild cognitive impairment compared to controls. The intermediate pattern found in the cognitive complaint group suggests the potential of diffusion tensor imaging to contribute to earlier detection of neurodegenerative changes during prodromal stages. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease. © 2011 Elsevier B.V.

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