Predicting behavioral variant frontotemporal dementia with pattern classification in multi-center structural MRI data.
LIFE Adult

Abstract (Expand)

PURPOSE: Frontotemporal lobar degeneration (FTLD) is a common cause of early onset dementia. Behavioral variant frontotemporal dementia (bvFTD), its most common subtype, is characterized by deep … alterations in behavior and personality. In 2011, new diagnostic criteria were suggested that incorporate imaging criteria into diagnostic algorithms. The study aimed at validating the potential of imaging criteria to individually predict diagnosis with machine learning algorithms. MATERIALS & METHODS: Brain atrophy was measured with structural magnetic resonance imaging (MRI) at 3 Tesla in a multi-centric cohort of 52 bvFTD patients and 52 healthy control subjects from the German FTLD Consortium's Study. Beside group comparisons, diagnosis bvFTD vs. controls was individually predicted in each subject with support vector machine classification in MRI data across the whole brain or in frontotemporal, insular regions, and basal ganglia known to be mainly affected based on recent meta-analyses. Multi-center effects were controlled for with a new method, "leave one center out" conjunction analyses, i.e. repeatedly excluding subjects from each center from the analysis. RESULTS: Group comparisons revealed atrophy in, most consistently, the frontal lobe in bvFTD beside alterations in the insula, basal ganglia and temporal lobe. Most remarkably, support vector machine classification enabled predicting diagnosis in single patients with a high accuracy of up to 84.6%, where accuracy was highest in a region-of-interest approach focusing on frontotemporal, insular regions, and basal ganglia in comparison with the whole brain approach. CONCLUSION: Our study demonstrates that MRI, a widespread imaging technology, can individually identify bvFTD with high accuracy in multi-center imaging data, paving the road to personalized diagnostic approaches in the future.

Authors: S. Meyer, K. Mueller, K. Stuke, S. Bisenius, J. Diehl-Schmid, F. Jessen, J. Kassubek, J. Kornhuber, A. C. Ludolph, J. Prudlo, A. Schneider, K. Schuemberg, I. Yakushev, M. Otto, M. L. Schroeter

Date Published: 29th Mar 2017

Publication Type: Journal article

Human Diseases: frontotemporal dementia

Atrophy and structural covariance of the cholinergic basal forebrain in primary progressive aphasia.
LIFE Adult

Abstract (Expand)

Primary progressive aphasia (PPA) is characterized by profound destruction of cortical language areas. Anatomical studies suggest an involvement of cholinergic basal forebrain (BF) in PPA syndromes, … particularly in the area of the nucleus subputaminalis (NSP). Here we aimed to determine the pattern of atrophy and structural covariance as a proxy of structural connectivity of BF nuclei in PPA variants. We studied 62 prospectively recruited cases with the clinical diagnosis of PPA and 31 healthy older control participants from the cohort study of the German consortium for frontotemporal lobar degeneration (FTLD). We determined cortical and BF atrophy based on high-resolution magnetic resonance imaging (MRI) scans. Patterns of structural covariance of BF with cortical regions were determined using voxel-based partial least square analysis. We found significant atrophy of total BF and BF subregions in PPA patients compared with controls [F(1, 82) = 20.2, p < .001]. Atrophy was most pronounced in the NSP and the posterior BF, and most severe in the semantic variant and the nonfluent variant of PPA. Structural covariance analysis in healthy controls revealed associations of the BF nuclei, particularly the NSP, with left hemispheric predominant prefrontal, lateral temporal, and parietal cortical areas, including Broca's speech area (p < .001, permutation test). In contrast, the PPA patients showed preserved structural covariance of the BF nuclei mostly with right but not with left hemispheric cortical areas (p < .001, permutation test). Our findings agree with the neuroanatomically proposed involvement of the cholinergic BF, particularly the NSP, in PPA syndromes. We found a shift from a structural covariance of the BF with left hemispheric cortical areas in healthy aging towards right hemispheric cortical areas in PPA, possibly reflecting a consequence of the profound and early destruction of cortical language areas in PPA.

Authors: S. Teipel, T. Raiser, L. Riedl, I. Riederer, M. L. Schroeter, S. Bisenius, A. Schneider, J. Kornhuber, K. Fliessbach, A. Spottke, M. J. Grothe, J. Prudlo, J. Kassubek, A. Ludolph, B. Landwehrmeyer, S. Straub, M. Otto, A. Danek

Date Published: 11th Aug 2016

Publication Type: Journal article

Human Diseases: aphasia

Frontomedian cortex is central for moral deficits in behavioural variant frontotemporal dementia.
LIFE Adult

Abstract

Not specified

Authors: M. L. Schroeter, D. Bzdok, S. B. Eickhoff, J. Neumann

Date Published: 25th Sep 2014

Publication Type: Not specified

Human Diseases: frontotemporal dementia

Conceptualizing neuropsychiatric diseases with multimodal data-driven meta-analyses - the case of behavioral variant frontotemporal dementia.
LIFE Adult

Abstract (Expand)

INTRODUCTION: Uniform coordinate systems in neuroimaging research have enabled comprehensive systematic and quantitative meta-analyses. Such approaches are particularly relevant for neuropsychiatric … diseases, the understanding of their symptoms, prediction and treatment. Behavioral variant frontotemporal dementia (bvFTD), a common neurodegenerative syndrome, is characterized by deep alterations in behavior and personality. Investigating this 'nexopathy' elucidates the healthy social and emotional brain. METHODS: Here, we combine three multimodal meta-analyses approaches - anatomical and activation likelihood estimates and behavioral domain profiles - to identify neural correlates of bvFTD in 417 patients and 406 control subjects and to extract mental functions associated with this disease by meta-analyzing functional activation studies in the comprehensive probabilistic functional brain atlas of the BrainMap database. RESULTS: The analyses identify the frontomedian cortex, basal ganglia, anterior insulae and thalamus as most relevant hubs, with a regional dissociation between atrophy and hypometabolism. Neural networks affected by bvFTD were associated with emotion and reward processing, empathy and executive functions (mainly inhibition), suggesting these functions as core domains affected by the disease and finally leading to its clinical symptoms. In contrast, changes in theory of mind or mentalizing abilities seem to be secondary phenomena of executive dysfunctions. CONCLUSIONS: The study creates a novel conceptual framework to understand neuropsychiatric diseases by powerful data-driven meta-analytic approaches that shall be extended to the whole neuropsychiatric spectrum in the future.

Authors: M. L. Schroeter, A. R. Laird, C. Chwiesko, C. Deuschl, E. Schneider, D. Bzdok, S. B. Eickhoff, J. Neumann

Date Published: 26th Apr 2014

Publication Type: Not specified

Human Diseases: frontotemporal dementia

Structural and functional MRI study of the brain, cognition and mood in long-term adequately treated Hashimoto's thyroiditis.
LIFE Adult

Abstract (Expand)

The current study investigated neuropsychological and underlying structural and functional brain alterations in long-term adequately treated patients with Hashimoto's thyroiditis in order to examine … much discussed residual complaints in patients in relation to possible long-term neural alterations with a specific interest in the underlying autoimmune process. Eighteen patients with treated hypothyroidism due to Hashimoto's thyroiditis (mean age 32, range 18-54 years; two males; mean treatment duration 4.4 years) and 18 healthy matched control subjects underwent 3-Tesla magnetic resonance imaging (MRI). Voxel-based morphometry was used to investigate grey matter density, resting-state functional MRI to analyse the brain connectivity of areas known to be altered in hypothyroidism and event-related functional MRI to examine brain activity during associative memory encoding. Neuropsychological assessment included memory, working memory, psychomotor speed and attention. We previously reported subclinically reduced mood in this study population and investigated its neural correlates here. Thyroid stimulating hormone, free triiodthyronine, free thyroxine and thyroid peroxidase antibodies were measured in serum. We did not find cognitive deficits or alterations in grey matter density, functional connectivity or associative memory-related brain activity in comparison to the control group and cognition was unrelated to thyroid serum measures in the patient group. Thyroid peroxidase antibodies in the patient group correlated with increased grey matter density in right amygdala and enhanced connectivity between subcallosal and parahippocampal areas. Treatment duration was associated with brain structure in frontal and occipital cortex and connectivity between left amygdala and frontal cortex. Mood correlated with brain areas associated with distinct functional networks, but not with those most prominently affected in depression. In conclusion, no cognitive or neural alterations were detected in this young and otherwise healthy cohort of patients in comparison to a healthy control group and current mood status could not be related to depression-related networks. However, autoimmune activity and treatment duration showed a relationship with depression and hypothyroidism-related brain structure and function. They are thus promising factors to further investigate residual complaints despite biochemically adequate treatment in patients with Hashimoto's thyroiditis. Given the small sample size, all findings require replication.

Authors: E. M. Quinque, S. Karger, K. Arelin, M. L. Schroeter, J. Kratzsch, A. Villringer

Date Published: 19th Mar 2014

Publication Type: Not specified

Human Diseases: autoimmune thyroiditis, hypothyroidism

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