Speech Prosody Across Stimulus Types for Individuals with Parkinson's Disease

Up to 89% of the individuals with Parkinson's disease (PD) experience speech problem over the course of the disease. Speech prosody and intelligibility are two of the most affected areas in hypokinetic dysarthria. However, assessment of these areas could potentially be problematic as speech prosody and intelligibility could be affected by the type of speech materials employed. Objective: To comparatively explore the effects of different types of speech stimulus on speech prosody and intelligibility in PD speakers. Methods: Speech prosody and intelligibility of two groups of individuals with varying degree of dysarthria resulting from PD was compared to that of a group of control speakers using sentence reading, passage reading and monologue. Acoustic analysis including measures on fundamental frequency (F0), intensity and speech rate was used to form a prosodic profile for each individual. Speech intelligibility was measured for the speakers with dysarthria using direct magnitude estimation. Results: Difference in F0 variability between the speakers with dysarthria and control speakers was only observed in sentence reading task. Difference in the average intensity level was observed for speakers with mild dysarthria to that of the control speakers. Additionally, there were stimulus effect on both intelligibility and prosodic profile. Conclusions: The prosodic profile of PD speakers was different from that of the control speakers in the more structured task, and lower intelligibility was found in less structured task. This highlighted the value of both structured and natural stimulus to evaluate speech production in PD speakers. 2015-IOS Press and the authors.casl5pub3998pub

Eye typing in application: A comparison of two systems with ALS patients

A variety of eye typing systems has been developed during the last decades. Such systems can provide support for people who lost the ability to communicate, e.g. patients suffering from motor neuron diseases such as amyotrophic lateral sclerosis (ALS). In the current retrospective analysis, two eye typing applications were tested (EyeGaze, GazeTalk) by ALS patients (N = 4) in order to analyze objective performance measures and subjective ratings. An advantage of the EyeGaze system was found for most of the evaluated criteria. The results are discussed in respect of the special target population and in relation to requirements of eye tracking devices

Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells

Clonogenic neural stem cells (NSCs) are self-renewing cells that maintain the capacity to differentiate into brain-specific cell types, and may also replace or repair diseased brain tissue. NSCs can be directly isolated from fetal or adult nervous tissue, or derived from embryonic stem cells. Here, we describe the efficient conversion of human adult bone marrow stromal cells (hMSC) into a neural stem cell-like population (hmNSC, for human marrow-derived NSC-like cells). These cells grow in neurosphere-like structures, express high levels of early neuroectodermal markers, such as the proneural genes NeuroD1, Neurog2, MSl1 as well as otx1 and nestin, but lose the characteristics of mesodermal stromal cells. In the presence of selected growth factors, hmNSCs can be differentiated into the three main neural phenotypes: astroglia, oligodendroglia and neurons. Clonal analysis demonstrates that individual hmNSCs are multipotent and retain the capacity to generate both glia and neurons. Our cell culture system provides a powerful tool for investigating the molecular mechanisms of neural differentiation in adult human NSCs. hmNSCs may therefore ultimately help to treat acute and chronic neurodegenerative diseases

Cerebrospinal fluid promotes survival and astroglial differentiation of adult human neural progenitor cells but inhibits proliferation and neuronal differentiation

<p>Abstract</p> <p>Background</p> <p>Neural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. Growing evidence suggests an important role of cerebrospinal fluid (CSF) not only on neuroectodermal cells during brain development but also on the survival, proliferation and fate specification of NSCs in the adult brain. Existing <it>in vitro </it>studies focused on embryonic cell lines and embryonic CSF. We therefore studied the effects of adult human leptomeningeal CSF on the behaviour of adult human NSCs (ahNSCs).</p> <p>Results</p> <p>Adult CSF increased the survival rate of adult human NSCs compared to standard serum free culture media during both stem cell maintenance and differentiation. The presence of CSF promoted differentiation of NSCs leading to a faster loss of their self-renewal capacity as it is measured by the proliferation markers Ki67 and BrdU and stronger cell extension outgrowth with longer and more cell extensions per cell. After differentiation in CSF, we found a larger number of GFAP⁺astroglial cells compared to differentiation in standard culture media and a lower number of β-tubulin III⁺neuronal cells.</p> <p>Conclusions</p> <p>Our data demonstrate that adult human leptomeningeal CSF creates a beneficial environment for the survival and differentiation of adult human NSCs. Adult CSF is <it>in vitro </it>a strong glial differentiation stimulus and leads to a rapid loss of stem cell potential.</p

Emerging role of LRRK2 in human neural progenitor cell cycle progression, survival and differentiation

Despite a comprehensive mapping of the Parkinson's disease (PD)-related mRNA and protein leucine-rich repeat kinase 2 (LRRK2) in the mammalian brain, its physiological function in healthy individuals remains enigmatic. Based on its structural features and kinase properties, LRRK2 may interact with other proteins involved in signalling pathways. Here, we show a widespread LRRK2 mRNA and/or protein expression in expanded or differentiated human mesencephalic neural progenitor cells (hmNPCs) and in post-mortem substantia nigra PD patients. Using small interfering RNA duplexes targeting LRRK2 in hmNPCs following their differentiation into glia and neurons, we observed a reduced number of dopaminergic neurons due to apoptosis in LRRK2 knockdown samples. LRRK2-deficient hmNPCs exhibited elevated cell cycle- and cell death-related markers. In conclusion, a reduction of LRRK2 expression in hmNPCs severely impaired dopaminergic differentiation and/or survival of dopaminergic neurons most likely via preserving or reactivating the cell cycle

Non-Motor Symptoms in Patients Suffering from Motor Neuron Diseases.

The recently postulated "disease spreading hypothesis" has gained much attention, especially for Parkinson's disease (PD). The various non-motor symptoms (NMS) in neurodegenerative diseases would be much better explained by this hypothesis than by the degeneration of disease-specific cell populations. Motor neuron disease (MND) is primarily known as a group of diseases with a selective loss of motor function. However, recent evidence suggests disease spreading into non-motor brain regions also in MND. The aim of this study was to comprehensively detect NMS in patients suffering from MND. We used a self-rating questionnaire including 30 different items of gastrointestinal, autonomic, neuropsychiatric, and sleep complaints [NMS questionnaire (NMSQuest)], which is an established tool in PD patients. 90 MND patients were included and compared to 96 controls. In total, MND patients reported significantly higher NMS scores (median: 7 points) in comparison to controls (median: 4 points). Dribbling, impaired taste/smelling, impaired swallowing, weight loss, loss of interest, sad/blues, falling, and insomnia were significantly more prevalent in MND patients compared to controls. Interestingly, excessive sweating was more reported in the MND group. Correlation analysis revealed an increase of total NMS score with disease progression. NMS in MND patients seemed to increase with disease progression, which would fit with the recently postulated "disease spreading hypothesis." The total NMS score in the MND group significantly exceeded the score for the control group, but only 8 of the 30 single complaints of the NMSQuest were significantly more often reported by MND patients. Dribbling, impaired swallowing, weight loss, and falling could primarily be connected to motor neuron degeneration and declared as motor symptoms in MND.S

Data from an Observational Study

Introduction Effective management and development of new treatment strategies for response fluctuations in advanced Parkinson’s disease (PD) largely depends on clinical rating instruments such as the PD home diary. The Parkinson’s kinetigraph (PKG) measures movement accelerations and analyzes the spectral power of the low frequencies of the accelerometer data. New algorithms convert each hour of continuous PKG data into one of the three motor categories used in the PD home diary, namely motor Off state and On state with and without dyskinesia. Objective To compare quantitative motor state assessment in fluctuating PD patients using the PKG with motor state ratings from PD home diaries. Methods Observational cohort study on 24 in-patients with documented motor fluctuations who completed diaries by rating motor Off, On without dyskinesia, On with dyskinesia, and asleep for every hour for 5 consecutive days. Simultaneously collected PKG data (recorded between 6 am and 10 pm) were analyzed and calibrated to the patient’s individual thresholds for Off and dyskinetic state by novel algorithms classifying the continuous accelerometer data into these motor states for every hour between 6 am and 10 pm. Results From a total of 2,040 hours, 1,752 hours (87.4%) were available for analyses from calibrated PKG data (7.5% sleeping time and 5.1% unclassified motor state time were excluded from analyses). Distributions of total motor state hours per day measured by PKG showed moderate-to-strong correlation to those assessed by diaries for the different motor states (Pearson’s correlations coefficients: 0.404–0.658), but inter-rating method agreements on the single- hour-level were only low-to-moderate (Cohen’s κ: 0.215–0.324). Conclusion The PKG has been shown to capture motor fluctuations in patients with advanced PD. The limited correlation of hour-to-hour diary and PKG recordings should be addressed in further studies

Chronic–Progressive Dopaminergic Deficiency Does Not Induce Midbrain Neurogenesis

Background: Consecutive adult neurogenesis is a well-known phenomenon in the ventricular–subventricular zone of the lateral wall of the lateral ventricles (V–SVZ) and has been controversially discussed in so-called “non-neurogenic” brain areas such as the periventricular regions (PVRs) of the aqueduct and the fourth ventricle. Dopamine is a known modulator of adult neural stem cell (aNSC) proliferation and dopaminergic neurogenesis in the olfactory bulb, though a possible interplay between local dopaminergic neurodegeneration and induction of aNSC proliferation in mid/hindbrain PVRs is currently enigmatic. Objective/Hypothesis: To analyze the influence of chronic–progressive dopaminergic neurodegeneration on both consecutive adult neurogenesis in the PVRs of the V–SVZ and mid/hindbrain aNSCs in two mechanistically different transgenic animal models of Parkinson´s disease (PD). Methods: We used Thy1-m[A30P]h α synuclein mice and Leu9′Ser hypersensitive α4* nAChR mice to assess the influence of midbrain dopaminergic neuronal loss on neurogenic activity in the PVRs of the V–SVZ, the aqueduct and the fourth ventricle. Results: In both animal models, overall proliferative activity in the V–SVZ was not altered, though the proportion of B2/activated B1 cells on all proliferating cells was reduced in the V–SVZ in Leu9′Ser hypersensitive α4* nAChR mice. Putative aNSCs in the mid/hindbrain PVRs are known to be quiescent in vivo in healthy controls, and dopaminergic deficiency did not induce proliferative activity in these regions in both disease models. Conclusions: Our data do not support an activation of endogenous aNSCs in mid/hindbrain PVRs after local dopaminergic neurodegeneration. Spontaneous endogenous regeneration of dopaminergic cell loss through resident aNSCs is therefore unlikely