Multiclass prediction of different dementia syndromes based on multi-centric volumetric MRI imaging

IntroductionDementia syndromes can be difficult to diagnose. We aimed at building a classifier for multiple dementia syndromes using magnetic resonance imaging (MRI).MethodsAtlas-based volumetry was performed on T1-weighted MRI data of 426 patients and 51 controls from the multi-centric German Research Consortium of Frontotemporal Lobar Degeneration including patients with behavioral variant frontotemporal dementia, Alzheimer’s disease, the three subtypes of primary progressive aphasia, i.e., semantic, logopenic and nonfluent-agrammatic variant, and the atypical parkinsonian syndromes progressive supranuclear palsy and corticobasal syndrome. Support vector machine classification was used to classify each patient group against controls (binary classification) and all seven diagnostic groups against each other in a multi-syndrome classifier (multiclass classification).ResultsThe binary classification models reached high prediction accuracies between 71 and 95% with a chance level of 50%. Feature importance reflected disease-specific atrophy patterns. The multi-syndrome model reached accuracies of more than three times higher than chance level but was far from 100%. Multi-syndrome model performance was not homogenous across dementia syndromes, with better performance in syndromes characterized by regionally specific atrophy patterns. Whereas diseases generally could be classified vs controls more correctly with increasing severity and duration, differentiation between diseases was optimal in disease-specific windows of severity and duration.DiscussionResults suggest that automated methods applied to MR imaging data can support physicians in diagnosis of dementia syndromes. It is particularly relevant for orphan diseases beside frequent syndromes such as Alzheimer’s disease

Evidence-Based PET for Neurological Diseases

Over the past two decades, one of the major breakthroughs for the approach to neurological diseases both in the clinical and research settings has been represented by the validation of diagnostic biomarkers able to demonstrate the presence of pathological mechanisms, alteration in neurotransmission as well as to predict disease progression [1, 2]. The use of PET with different tracers as well as other imaging biomarkers support the etiological diagnosis of neurological disorders in vivo. This approach is particularly relevant in the field of neurodegenerative diseases. In fact, neurodegenerative diseases are characterized by the progressive degeneration and death of neurons. They represent a heterogeneous group of conditions characterized by different etiologies, different neuropathological and neurochemical alterations leading to different clinical pictures and courses [3]. Indeed, an early accurate diagnosis allows to tackle the disease with available or experimental intervention, lifestyle changes, or logistical arrangements, before disability has developed. Early intervention is expected to have greater clinical impact, extend independent and active life, improve its quality, and decrease the burden and costs of the disease [4]. However, the validation of PET tracers in neurological disease is still ongoing, and evidence on its comparative and combined diagnostic value with respect to other biomarkers is incomplete [4, 5]. As a matter of fact, the increasing pressure for cost-effectiveness requires systematic assessment and validation of all biomarker performance in the clinical settings. Similarly only an evidence-based approach to new PET tracers can allow to select the most promising tracers for PET imaging in the research field both for pathophysiological investigations and for upcoming diagnostic approaches

Conscious perception and the modulatory role of dopamine: no effect of the dopamine D2 agonist cabergoline on visual masking, the attentional blink, and probabilistic discrimination

Rationale Conscious perception is thought to depend on global amplification of sensory input. In recent years, striatal dopamine has been proposed to be involved in gating information and conscious access, due to its modulatory influence on thalamocortical connectivity. Objectives Since much of the evidence that implicates striatal dopamine is correlational, we conducted a double-blind crossover pharmacological study in which we administered cabergoline—a dopamine D2 agonist—and placebo to 30 healthy participants. Under both conditions, we subjected participants to several well-established experimental conscious-perception paradigms, such as backward masking and the attentional blink task. Results We found no evidence in support of an effect of cabergoline on conscious perception: key behavioral and event-related potential (ERP) findings associated with each of these tasks were unaffected by cabergoline. Conclusions Our results cast doubt on a causal role for dopamine in visual perception. It remains an open possibility that dopamine has causal effects in other tasks, perhaps where perceptual uncertainty is more prominent

Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta-analyses

Recently, diagnostic clinical and imaging criteria for primary progressive aphasia (PPA) have been revised by an international consortium (Gorno-Tempini et al. Neurology 2011;76:1006-14). The aim of this study was to validate the specificity of the new imaging criteria and investigate whether different imaging modalities [magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET)] require different diagnostic subtype-specific imaging criteria. Anatomical likelihood estimation meta-analyses were conducted for PPA subtypes across a large cohort of 396 patients: firstly, across MRI studies for each of the three PPA subtypes followed by conjunction and subtraction analyses to investigate the specificity, and, secondly, by comparing results across MRI vs. FDG-PET studies in semantic dementia and progressive nonfluent aphasia. Semantic dementia showed atrophy in temporal, fusiform, parahippocampal gyri, hippocampus, and amygdala, progressive nonfluent aphasia in left putamen, insula, middle/superior temporal, precentral, and frontal gyri, logopenic progressive aphasia in middle/superior temporal, supramarginal, and dorsal posterior cingulate gyri. Results of the disease-specific meta-analyses across MRI studies were disjunct. Similarly, atrophic and hypometabolic brain networks were regionally dissociated in both semantic dementia and progressive nonfluent aphasia. In conclusion, meta-analyses support the specificity of new diagnostic imaging criteria for PPA and suggest that they should be specified for each imaging modality separately

Identifying neural correlates of visual consciousness with ALE meta-analyses

Neural correlates of consciousness (NCC) have been a topic of study for nearly two decades. In functional imaging studies, several regions have been proposed to constitute possible candidates for NCC, but as of yet, no quantitative summary of the literature on NCC has been done. The question whether single (striate or extrastriate) regions or a network consisting of extrastriate areas that project directly to fronto-parietal regions are necessary and sufficient neural correlates for visual consciousness is still highly debated [e.g., Rees et al., 2002, Nat Rev. Neurosci 3, 261–270; Tong, 2003, Nat Rev. Neurosci 4, 219–229]. The aim of this work was to elucidate this issue and give a synopsis of the present state of the art by conducting systematic and quantitative meta-analyses across functional magnetic resonance imaging (fMRI) studies using several standard paradigms for conscious visual perception. In these paradigms, consciousness is operationalized via perceptual changes, while the visual stimulus remains invariant. An activation likelihood estimation (ALE) meta-analysis was performed, representing the best approach for voxel-wise meta-analyses to date. In addition to computing a meta-analysis across all paradigms, separate meta-analyses on bistable perception and masking paradigms were conducted to assess whether these paradigms show common or different NCC. For the overall meta-analysis, we found significant clusters of activation in inferior and middle occipital gyrus; fusiform gyrus; inferior temporal gyrus; caudate nucleus; insula; inferior, middle, and superior frontal gyri; precuneus; as well as in inferior and superior parietal lobules. These results suggest a subcortical-extrastriate-fronto-parietal network rather than a single region that constitutes the necessary NCC. The results of our exploratory paradigm-specific meta-analyses suggest that this subcortical-extrastriate-fronto-parietal network might be differentially activated as a function of the paradigms used to probe for NCC