Improved Parkinson’s disease classification from diffusion MRI data by Fisher vector descriptors

in Improved Parkinson’s disease classification from diffusion MRI data by Fisher vector descriptors (2015, October)

Due to the complex clinical picture of Parkinson’s disease (PD), the reliable diagnosis of patients is still challenging. A promising approach is the structural characterization of brain areas affected in ... [more ▼]

Due to the complex clinical picture of Parkinson’s disease (PD), the reliable diagnosis of patients is still challenging. A promising approach is the structural characterization of brain areas affected in PD by diffusion magnetic resonance imaging (dMRI). Standard classification methods depend on an accurate non-linear alignment of all images to a common reference template, and are challenged by the resulting huge dimensionality of the extracted feature space. Here, we propose a novel diagnosis pipeline based on the Fisher vector algorithm. This technique allows for a precise encoding into a high-level descriptor of standard diffusion measures like the fractional anisotropy and the mean diffusivity, extracted from the regions of interest (ROIs) typically involved in PD. The obtained low dimensional, fixed-length descriptors are independent of the image alignment and boost the linear separability of the problem in the description space, leading to more efficient and accurate diagnosis. In a test cohort of 50 PD patients and 50 controls, the implemented methodology outperforms previous methods when using a logistic linear regressor for classification of each ROI independently, which are subsequently combined into a single classification decision. [less ▲]

Failing as Doorman and Disc Jockey at the Same Time: Amygdalar Dysfunction in Parkinson’s Disease

in Movement Disorders (2015), 00(00),

In Braak’s model of ascending degeneration in Parkinson’s disease (PD), involvement of the amygdala occurs simultaneously with substantia nigra degeneration. However, the clinical manifestations of ... [more ▼]

In Braak’s model of ascending degeneration in Parkinson’s disease (PD), involvement of the amygdala occurs simultaneously with substantia nigra degeneration. However, the clinical manifestations of amygdalar involvement in PD have not been fully delineated. Considered a multitask manager, the amygdala is a densely connected “hub,” coordinating and integrating tasks ranging from prompt, multisensorial emotion recognition to adequate emotional responses and emotional tuning of memories. Although phylogenetically predisposed to handle fear, the amygdala handles both aversive and positive emotional inputs. In PD, neuropathological and in vivo studies suggest primarily amygdalar hypofunction. However, as dopamine acts as an inverted U-shaped amygdalar modulator, medicationinduced hyperactivity of the amygdala can occur.We propose that amygdalar (network) dysfunction contributes to reduced recognition of negative emotional face expressions, impaired theory of mind, reactive hypomimia, and impaired decision making. Similarly, impulse control disorders in predisposed individuals, hallucinations, anxiety, and panic attacks may be related to amygdalar dysfunction. When available, we discuss amygdala-independent trigger mechanisms of these symptoms. Although dopaminergic agents have mostly an activation effect on amygdalar function, adaptive and compensatory network changes may occur as well, but these have not been sufficiently explored. In conclusion, our model of amygdalar involvement brings together several elements of Parkinson’s disease phenomenology heretofore left unexplained and provides a framework for testable hypotheses in patients during life and in autopsy analyses. VC 2015 International Parkinson and Movement Disorder Society [less ▲]

Are patients with Parkinson’s disease blind to blindsight?

in Brain : A Journal of Neurology (2014)

In Parkinson’s disease, visual dysfunction is prominent. Visual hallucinations can be a major hallmark of late stage disease, but numerous visual deficits also occur in early stage Parkinson’s disease ... [more ▼]

In Parkinson’s disease, visual dysfunction is prominent. Visual hallucinations can be a major hallmark of late stage disease, but numerous visual deficits also occur in early stage Parkinson’s disease. Specific retinopathy, deficits in the primary visual pathway and the secondary ventral and dorsal pathways, as well as dysfunction of the attention pathways have all been posited as causes of hallucinations in Parkinson’s disease. We present data from patients with Parkinson’s disease that contrast with a known neuro-ophthalmological syndrome, termed ‘blindsight’. In this syndrome, there is an absence of conscious object identification, but preserved ‘guess’ of the location of a stimulus, preserved reflexive saccades and motion perception and preserved autonomical and expressive reactions to negative emotional facial expressions. We propose that patients with Parkinson’s disease have the converse of blindsight, being ‘blind to blindsight’. As such they preserve conscious vision, but show erroneous ‘guess’ localization of visual stimuli, poor saccades and motion perception, and poor emotional face perception with blunted autonomic reaction. Although a large data set on these deficits in Parkinson’s disease has been accumulated, consolidation into one specific syndrome has not been proposed. Focusing on neuropathological and physiological data from two phylogenetically old and subconscious pathways, the retino-colliculo-thalamo-amygdala and the retino-geniculo-extrastriate pathways, we propose that aberrant function of these systems, including pathologically inhibited superior colliculus activity, deficient corollary discharges to the frontal eye fields, dysfunctional pulvinar, claustrum and amygdaloid subnuclei of the amygdala, the latter progressively burdened with Lewy bodies, underlie this syndrome. These network impairments are further corroborated by the concept of the ‘silent amygdala’. Functionally being ‘blind to blindsight’ may facilitate the highly distinctive ‘presence’ or ‘passage’ hallucinations of Parkinson’s disease and can help to explain handicaps in driving capacities and dysfunctional ‘theory of mind’. We propose this synthesis to prompt refined neuropathological and neuroimaging studies on the pivotal nuclei in these pathways in order to better understand the networks underpinning this newly conceptualized syndrome in Parkinson’s disease. [less ▲]

Integrating Pathways of Parkinson's Disease in a Molecular Interaction Map

in Molecular Neurobiology (2014)

Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is ... [more ▼]

Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is rapidly increasing and needs to be efficiently organized, so that the resulting data is available for exploration and analysis. Here we introduce a computationally tractable, comprehensive molecular interaction map of PD. This map integrates pathways implicated in PD pathogenesis such as synaptic and mitochondrial dysfunction, impaired protein degradation, alpha-synuclein pathobiology and neuroinflammation. We also present bioinformatics tools for the analysis, enrichment and annotation of the map, allowing the research community to open new avenues in PD research. The PD map is accessible at http://minerva.uni.lu/pd_map . [less ▲]

The hallmarks of Parkinson's disease.

in FEBS Journal (2013)

Since the discovery of dopamine as a neurotransmitter in the 1950s, Parkinson's disease (PD) research has generated a rich and complex body of knowledge, revealing PD to be an age-related multifactorial ... [more ▼]

Since the discovery of dopamine as a neurotransmitter in the 1950s, Parkinson's disease (PD) research has generated a rich and complex body of knowledge, revealing PD to be an age-related multifactorial disease, influenced by both genetic and environmental factors. The tremendous complexity of the disease is increased by a non-linear progression of the pathogenesis between molecular, cellular, and organic systems. In this mini-review, we explore the complexity of PD and propose a systems-based approach, organizing the available information around cellular disease hallmarks. We encourage our peers to adopt this cell-based view with the aim of improving communication in interdisciplinary research endeavors targeting the molecular events, modulatory cell-to-cell signaling pathways, and emerging clinical phenotypes related to PD. This article is protected by copyright. All rights reserved. [less ▲]

Autosomal dominant mutations in POLG and C10orf2: association with late onset chronic progressive external ophthalmoplegia and Parkinsonism in two patients

in Journal of Neurology (2013), 260

Constructing a comprehensive map of Parkinson’s disease to elucidate underlying mechanisms of its multifaceted molecular pathology

Poster (2012, August)

Parkinson's disease: Acquired frailty of archaic neural networks?

in Journal of the Neurological Sciences (2012), 314(1-2), 143-51

In Parkinson's disease (PD) many motor and non-motor symptoms are difficult to explain in terms of a purely ascending degeneration process as described by Braak. This essay proposes phylogenetic ... [more ▼]

In Parkinson's disease (PD) many motor and non-motor symptoms are difficult to explain in terms of a purely ascending degeneration process as described by Braak. This essay proposes phylogenetic considerations for consolidating the multidimensional elements of PD. Subtle clinical analysis paired with ethological comparisons as well as patho-anatomical data suggests that disrupted automatic gait control, olfactory deficits, selected visual deficits, impaired emotional face recognition, and REM sleep behavior disorder could be due to dysfunction of phylogenetically ancient networks. Neuroanatomical and behavioral findings lead to a reconsideration of the basal ganglia, to be viewed as the nuclear core of a widely distributed neural network that arborizes throughout the primordial core of the neuraxis, including the brainstem. Fragility of the resulting multiple, closed, ancillary loops that link brainstem and forebrain components of the basal ganglia may be a nodal point, pivotal to the pathogenesis of PD. Other primitive neural networks, such as those located at cardiac or gastro-intestinal levels, may share the same vulnerability. Such a network-based hypothesis overrides the need of a fixed temporal ordering of symptoms based on putative caudal–cephalic propagation patterns of pathological lesions. It also creates testable, secondary hypotheses such as differential gene expression in different neural networks, potential early epigenetic influences, concepts of “overuse” or maladaptation of primitive networks to the constraints of adult life, and system frailty due to irreparable mitochondrial “exhaustion” in highly energy consuming postmitotic cells [less ▲]

Discriminative power of different nonmotor signs in early Parkinson's disease. A case-control study

in Movement Disorders (2010), 25(7), 882-887

The objective of this study was to evaluate the discriminative power of different nonmotor signs for early diagnosis of Parkinson's disease (PD). Thirty patients with PD with <or=3 years of disease ... [more ▼]

The objective of this study was to evaluate the discriminative power of different nonmotor signs for early diagnosis of Parkinson's disease (PD). Thirty patients with PD with <or=3 years of disease duration were compared with 30 healthy controls. Six deficit domains (DD) were defined: hyposmia, sleep abnormalities, dysautonomia, visual deficits, executive dysfunction, and depression. Plotting of Receiver operating characteristic (ROC) curves and exact conditional logistic modeling, followed by manual stepwise descending procedure were used to identify a model for nonmotor signs that detects early PD. Patients with PD and controls did not differ in terms of age, gender, and educational level. Several DD discriminated patients with PD from healthy controls. Visual deficits showed the largest area under the ROC curve (0.83), followed by hyposmia (0.81) and dysautonomia (0.80). When combining the DD visual deficits and dysautonomia, the best residual model was obtained; it maximized both sensitivity and specificity for PD at a level of 0.77. At an early disease stage, several nonmotor domains were already able to discriminate patients with PD from healthy controls. Visual deficits had the best discriminatory power. Being brief and inexpensive, visual tests should be further investigated in larger cohorts as potential screening tool for early PD. [less ▲]

Progressive sleep 'destructuring' in Parkinson's disease. A polysomnographic study in 46 patients.

in Sleep Medicine (2005), 6(4), 313-8

BACKGROUND: Sleep abnormalities in Parkinson's disease (PD) are frequent, but it is unknown whether or not there is progressive loss of physiological sleep architecture or what the causes could be ... [more ▼]

BACKGROUND: Sleep abnormalities in Parkinson's disease (PD) are frequent, but it is unknown whether or not there is progressive loss of physiological sleep architecture or what the causes could be. METHODS: Retrospective review of medical records and polysomnographic data from 46 non-demented PD patients. RESULTS: Sleep latency was correlated with disease duration (F1,44=4.87, P=0.03). Total sleep time (F1,44=8.54, P=0.005), deep sleep time (F1,44=4.06, P=0.05), REM sleep time (F1,44=9.15, P=0.004) and sleep efficiency (SE) (F1,44=10.20, P=0.003) were inversely correlated with disease duration. The same sleep parameters were independent from the degree of motor impairment, dosage of the dopaminergic medications, and age. Subjective sleep complaints could only partially predict abnormalities in polysomnographic (PSG) studies. CONCLUSION: In PD nocturnal sleep 'destructuring' is linked to disease duration and evolves independently from other major disease parameters. [less ▲]