Publications (19) View all
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Article: Left anterior temporal lobe sustains naming in Alzheimer's dementia and mild cognitive impairment.
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ABSTRACT: Cognitive decline in degenerative dementia is paralleled by progressive brain atrophy, with the localization of atrophy reflecting specific cognitive impairment. Confrontation naming deficits are frequently observed in dementia across etiologies. In this study we aimed to identify the brain regions underlying this deficit. In patients with clinically diagnosed dementia or mild cognitive impairment (MCI) we investigated the relationship between gray matter volume (GMV) and performance on a standardized confrontation naming test. 268 patients with one of three probable etiologies were included: Alzheimer's Dementia (AD), AD with signs of cerebrovascular pathology, and frontotemporal dementia. Applying voxel-based morphometry using a diffeomorphic registration algorithm we contrasted GMV of patients performing within the normal range with those of patients with pathological performance. Further, differential effects of gray matter atrophy on impaired performance in AD versus MCI of AD type were investigated. Results revealed significantly reduced GMV in the left anterior temporal lobe (ATL) in pathological performers compared to normal performers. The subgroup analysis confined to MCI of AD type and AD patients confirmed this relationship. While left ATL atrophy is known to be implicated in naming deficits in semantic dementia, our data confirm the same in AD and MCI of AD type.Current Alzheimer research 05/2011; 8(8):893-901. · 4.97 Impact Factor -
Article: Alterations in functional connectivity of the amygdala in unilateral mesial temporal lobe epilepsy.
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ABSTRACT: The aim of this work was to evaluate the relationship between ipsilateral amygdala dysfunction in unilateral mesial temporal lobe epilepsy (MTLE) and remote temporal, frontal, and parietal brain structures and to identify their association with theory of mind (ToM) abilities. Functional magnetic resonance imaging (fMRI) data were acquired from MTLE patients with unilateral hippocampal sclerosis (n = 28; 16 left-sided) and healthy controls (HC, n = 18) watching an animated fearful face paradigm. To explore functional connectivity, we used independent component analysis (ICA) of fMRI data to characterize possible amygdala network alterations that may be caused by lateralized amygdala dysfunction. We furthermore investigated the relationship between activation within the amygdala network and ToM task performance. The pattern of amygdalar BOLD activation observed in response to an animated fearful face paradigm was bilateral amygdalar activation in HC and amygdala activation lateralized to the contralateral side in MTLE patients. In HC, a hemispheric asymmetry of the amygdala network was present with amygdala co-activation in predominantly left temporolateral and frontal brain structures. In MTLE patients, the observed asymmetry of amygdala connectivity was modulated by the side of pathology and the extent of amygdalar connectivity to the parahippocampal gyrus and insula was related to ToM test performance. These findings suggest that ipsilateral amygdalar dysfunction in MTLE is associated with alterations in remote temporal and frontal brain areas. The study of psychiatric and neurological disorders via network analysis allows for a shift of focus away from viewing dysfunctions of individual structures to a pathological network that possibly gives rise to a variety of symptoms.Journal of Neurology 06/2012; · 3.47 Impact Factor -
Article: A comparison of different automated methods for the detection of white matter lesions in MRI data.
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ABSTRACT: White matter hyperintensities (WMH) are the focus of intensive research and have been linked to cognitive impairment and depression in the elderly. Cumbersome manual outlining procedures make research on WMH labour intensive and prone to subjective bias. This study compares fully automated supervised detection methods that learn to identify WMH from manual examples against unsupervised approaches on the combination of FLAIR and T1 weighted images. Data were collected from ten subjects with mild cognitive impairment and another set of ten individuals who fulfilled diagnostic criteria for dementia. Data were split into balanced groups to create a training set used to optimize the different methods. Manual outlining served as gold standard to evaluate performance of the automated methods that identified each voxel either as intact or as part of a WMH. Otsu's approach for multiple thresholds which is based only on voxel intensities of the FLAIR image produced a high number of false positives at grey matter boundaries. Performance on an independent test set was similarly disappointing when simply applying a threshold to the FLAIR that was found from training data. Among the supervised methods, precision-recall curves of support vector machines (SVM) indicated advantages over the performance achieved by K-nearest-neighbor classifiers (KNN). The curves indicated a clear benefit from optimizing the threshold of the SVM decision value and the voting rule of the KNN. Best performance was reached by selecting training voxels according to their distance to the lesion boundary and repeated training after replacing the feature vectors from those voxels that did not form support vectors of the SVM. The study demonstrates advantages of SVM for the problem of detecting WMH at least for studies that include only FLAIR and T1 weighted images. Various optimization strategies are discussed and compared against each other.NeuroImage 07/2011; 57(2):416-22. · 5.89 Impact Factor -
Article: Quantifying change in individual subjects affected by frontotemporal lobar degeneration using automated longitudinal MRI volumetry.
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ABSTRACT: A novel method of automated MRI volumetry was used to study regional atrophy and disease progression in repeated MRI measurements of patients with frontotemporal lobar degeneration (FTLD). Fifty-nine structural MRI data sets of 17 clinically diagnosed FTLD patients were acquired over up to 30 months in intervals of 6 months and compared with data of 30 age-matched healthy controls. Patients were further subgrouped into behavioral variant FTLD (bvFTLD), progressive nonfluent aphasia (PNFA), and semantic dementia (SemD). Gray matter (GM) volumes of frontal lobes (FL) and temporal lobes (TL) were determined by voxel-based volumetry based on SPM5 algorithms and a probabilistic brain atlas. MRI volumetry revealed frontal and temporal GM atrophy across FTLD patients, with further progression over time. Significant side asymmetry of TL volumes was found in SemD. The ratio of TL to FL volumes was significantly reduced in SemD and increased in bvFTLD. Using this ratio, 6/7 SemD patients and 5/6 bvFTLD patients could be correctly differentiated. TL/FL ratios in bvFTLD and SemD further diverged significantly over a time span of only 6 months. Rates of temporal GM loss per 6 months were 3-4% in SemD, and 2.5% for frontal GM loss in bvFTLD, and thereby clearly exceeded published cerebral volume loss in healthy elderly subjects. The study presents a fully automated, observer-independent volumetric assessment of regional atrophy which allows differentiation of FTLD subgroups. Its sensitivity for atrophy progression--even in such short intervals like 6 months--might benefit future clinical trials as treatment outcome measure.Human Brain Mapping 05/2011; 33(7):1526-35. · 5.88 Impact Factor -
Article: Reduced precuneus deactivation during object naming in patients with mild cognitive impairment, Alzheimer's disease, and frontotemporal lobar degeneration.
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ABSTRACT: The precuneus is part of the default network of the human brain, which exhibits a high level of activity during the resting state and lower activity during task-related behavior. Typically, the posterior midline areas show this characteristic response in functional magnetic resonance imaging (fMRI) studies. In Alzheimer's disease (AD) and mild cognitive impairment (MCI), subjects exhibit a lack of this typical deactivation. The interpretation of these findings, however, is obfuscated by the presence of local pathology and atrophy in AD. In contrast to AD, in patients with early frontotemporal lobar degeneration (FTLD), the precuneus is virtually free of local neuropathology. In this study, we demonstrate reduced fMRI signal in the precuneus in a group of patients with FTLD during a confrontation naming task. We show that this effect in FTLD patients was (1) similar to that observed in AD and MCI and (2) not related to the degree of gray matter atrophy in the precuneus. We hypothesize that reduced deactivation of the default network is not related to local pathology but to a lack of connectivity, which decreases in both FTLD and AD, the major cortical dementias.Dementia and Geriatric Cognitive Disorders 10/2010; 30(4):334-43. · 2.14 Impact Factor
