Ilona Eliasova

Non-invasive brain stimulation of the right inferior frontal gyrus may improve attention in early Alzheimer's disease: A pilot study

INTRODUCTION Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool for modulating cortical activity. OBJECTIVES In this pilot study, we evaluated the effects of high frequency rTMS applied over the right inferior frontal gyrus (IFG) on cognitive functions in patients with amnestic mild cognitive impairment (MCI) or incipient dementia due to Alzheimers disease (AD). METHODS Ten patients (6 men; 4 women, mean age of 72 ± 8 years; MMSE 23 ± 3.56) were enrolled in a randomized, placebo-controlled study with a crossover design. All participants received 2 sessions of 10 Hz rTMS over the non-dominant right hemisphere in random order: IFG (active stimulation site) and vertex (control stimulation site). Intensities were adjusted to 90% of resting motor threshold. A total of 2250 pulses were applied in a session. The Trail Making Test (TMT), the Stroop test, and the complex visual scene encoding task (CVSET) were administered before and immediately after each session. The Wilcoxon paired test was used for data analysis. RESULTS Stimulation applied over the IFG induced improvement in the TMT parts A (p = 0.037) and B (p = 0.049). No significant changes were found in the Stroop test or the CVSET after the IFG stimulation. We observed no significant cognitive aftereffects of rTMS applied over the vertex. CONCLUSIONS High frequency rTMS of the right IFG induced significant improvement of attention and psychomotor speed in patients with MCI/mild dementia due to AD. This pilot study is part of a more complex protocol and ongoing research.

Robust and complex approach of pathological speech signal analysis

This paper presents a study of the approaches in the state-of-the-art in the field of pathological speech signal analysis with a special focus on parametrization techniques. It provides a description of 92 speech features where some of them are already widely used in this field of science and some of them have not been tried yet (they come from different areas of speech signal processing like speech recognition or coding). As an original contribution, this work introduces 36 completely new pathological voice measures based on modulation spectra, inferior colliculus coefficients, bicepstrum, sample and approximate entropy and empirical mode decomposition. The significance of these features was tested on 3 (English, Spanish and Czech) pathological voice databases with respect to classification accuracy, sensitivity and specificity. To our best knowledge the introduced approach based on complex feature extraction and robust testing outperformed all works that have been published already in this field. The results (accuracy, sensitivity and specificity equal to 100.0 ? 0.0 % ) are discussable in the case of Massachusetts Eye and Ear Infirmary (MEEI) database because of its limitation related to a length of sustained vowels, however in the case of Principe de Asturias (PdA) Hospital in Alcala de Henares of Madrid database we made improvements in classification accuracy ( 82.1 ? 3.3 % ) and specificity ( 83.8 ? 5.1 % ) when considering a single-classifier approach. Hopefully, large improvements may be achieved in the case of Czech Parkinsonian Speech Database (PARCZ), which are discussed in this work as well. All the features introduced in this work were identified by Mann-Whitney U test as significant ( p < 0.05 ) when processing at least one of the mentioned databases. The largest discriminative power from these proposed features has a cepstral peak prominence extracted from the first intrinsic mode function ( p = 6.9443 i? 10 - 32 ) which means, that among all newly designed features those that quantify especially hoarseness or breathiness are good candidates for pathological speech identification. The paper also mentions some ideas for the future work in the field of pathological speech signal analysis that can be valuable especially under the clinical point of view.

Prosodic analysis of neutral, stress-modified and rhymed speech in patients with Parkinson's disease

BACKGROUND AND OBJECTIVE Hypokinetic dysarthria (HD) is a frequent speech disorder associated with idiopathic Parkinsons disease (PD). It affects all dimensions of speech production. One of the most common features of HD is dysprosody that is characterized by alterations of rhythm and speech rate, flat speech melody, and impairment of speech intensity control. Dysprosody has a detrimental impact on speech naturalness and intelligibility. METHODS This paper deals with quantitative prosodic analysis of neutral, stress-modified and rhymed speech in patients with PD. The analysis of prosody is based on quantification of monopitch, monoloudness, and speech rate abnormalities. Experimental dataset consists of 98 patients with PD and 51 healthy speakers. For the purpose of HD identification, sequential floating feature selection algorithm and random forests classifier is used. In this paper, we also introduce a concept of permutation test applied in the field of acoustic analysis of dysarthric speech. RESULTS Prosodic features obtained from stress-modified reading task provided higher classification accuracies compared to the ones extracted from reading task with neutral emotion demonstrating the importance of stress in speech prosody. Features calculated from poem recitation task outperformed both reading tasks in the case of gender-undifferentiated analysis showing that rhythmical demands can in general lead to more precise identification of HD. Additionally, some gender-related patterns of dysprosody has been observed. CONCLUSIONS This paper confirms reduced variation of fundamental frequency in PD patients with HD. Interestingly, increased variability of speech intensity compared to healthy speakers has been detected. Regarding speech rate disturbances, our results does not report any particular pattern. We conclude further development of prosodic features quantifying the relationship between monopitch, monoloudness and speech rate disruptions in HD can have a great potential in future PD analysis.

Addenbrooke's Cognitive Examination and Individual Domain Cut-Off Scores for Discriminating between Different Cognitive Subtypes of Parkinson's Disease

Objective. The main aim of this study was to verify the sensitivity and specificity of Addenbrookes Cognitive Examination-Revised (ACE-R) in discriminating between Parkinsons disease (PD) with normal cognition (PD-NC) and PD with mild cognitive impairment (PD-MCI) and between PD-MCI and PD with dementia (PD-D). We also evaluated how ACE-R correlates with neuropsychological cognitive tests in PD. Methods. We examined three age-matched groups of PD patients diagnosed according to the Movement Disorder Society Task Force criteria: PD-NC, PD-MCI, and PD-D. ROC analysis was used to establish specific cut-off scores of ACE-R and its domains. Correlation analyses were performed between ACE-R and its subtests with relevant neuropsychological tests. Results. Statistically significant differences between groups were demonstrated in global ACE-R scores and subscores, except in the language domain. ACE-R cut-off score of 88.5 points discriminated best between PD-MCI and PD-NC (sensitivity 0.68, specificity 0.91); ACE-R of 82.5 points distinguished best between PD-MCI and PD-D (sensitivity 0.70, specificity 0.73). The verbal fluency domain of ACE-R demonstrated the best discrimination between PD-NC and PD-MCI (cut-off score 11.5; sensitivity 0.70, specificity 0.73) while the orientation/attention subscore was best between PD-MCI and PD-D (cut-off score 15.5; sensitivity 0.90, specificity 0.97). ACE-R scores except for ACE-R language correlated with specific cognitive tests of interest.

Assessing progress of Parkinson's disease using acoustic analysis of phonation

This paper deals with a complex acoustic analysis of phonation in patients with Parkinsons disease (PD) with a special focus on estimation of disease progress that is described by 7 different clinical scales (e. g. Unified Parkinsons disease rating scale or Beck depression inventory). The analysis is based on parametrization of 5 Czech vowels pronounced by 84 PD patients. Using classification and regression trees we estimated all clinical scores with maximal error lower or equal to 13 %. Best estimation was observed in the case of Mini-mental state examination (MAE = 0.77, estimation error 5.50 %). Finally, we proposed a binary classification based on random forests that is able to identify Parkinsons disease with sensitivity SEN = 92.86% (SPE = 85.71 %). The parametrization process was based on extraction of 107 speech features quantifying different clinical signs of hypokinetic dysarthria present in PD.

Distinct Pattern of Gray Matter Atrophy in Mild Alzheimer’s Disease Impacts on Cognitive Outcomes of Noninvasive Brain Stimulation

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is a promising tool to study and modulate brain plasticity. OBJECTIVE Our aim was to investigate the effects of rTMS on cognitive functions in patients with mild cognitive impairment and Alzheimers disease (MCI/AD) and assess the effect of gray matter (GM) atrophy on stimulation outcomes. METHODS Twenty MCI/AD patients participated in the proof-of-concept controlled study. Each patient received three sessions of 10 Hz rTMS of the right inferior frontal gyrus (IFG), the right superior temporal gyrus (STG), and the vertex (VTX, a control stimulation site) in a randomized order. Cognitive functions were tested prior to and immediately after each session. The GM volumetric data of patients were: 1) compared to healthy controls (HC) using source-based morphometry; 2) correlated with rTMS-induced cognitive improvement. RESULTS The effect of the stimulated site on the difference in cognitive scores was statistically significant for the Word part of the Stroop test (ST-W, p = 0.012, linear mixed models). As compared to the VTX stimulation, patients significantly improved after both IFG and STG stimulation in this cognitive measure. MCI/AD patients had significant GM atrophy in characteristic brain regions as compared to HC (p = 0.029, Bonferroni corrected). The amount of atrophy correlated with the change in ST-W scores after rTMS of the STG. CONCLUSION rTMS enhanced cognitive functions in MCI/AD patients. We demonstrated for the first time that distinct pattern of GM atrophy in MCI/AD diminishes the cognitive effects induced by rTMS of the temporal neocortex.

Parkinson Disease Detection from Speech Articulation Neuromechanics

Aim: The research described is intended to give a description of articulation dynamics as a correlate of the kinematic behavior of the jaw-tongue biomechanical system, encoded as a probability distribution of an absolute joint velocity. This distribution may be used in detecting and grading speech from patients affected by neurodegenerative illnesses, as Parkinson Disease. Hypothesis: The work hypothesis is that the probability density function of the absolute joint velocity includes information on the stability of phonation when applied to sustained vowels, as well as on fluency if applied to connected speech. Methods: A dataset of sustained vowels recorded from Parkinson Disease patients is contrasted with similar recordings from normative subjects. The probability distribution of the absolute kinematic velocity of the jaw-tongue system is extracted from each utterance. A Random Least Squares Feed-Forward Network (RLSFN) has been used as a binary classifier working on the pathological and normative datasets in a leave-one-out strategy. Monte Carlo simulations have been conducted to estimate the influence of the stochastic nature of the classifier. Two datasets for each gender were tested (males and females) including 26 normative and 53 pathological subjects in the male set, and 25 normative and 38 pathological in the female set. Results: Male and female data subsets were tested in single runs, yielding equal error rates under 0.6% (Accuracy over 99.4%). Due to the stochastic nature of each experiment, Monte Carlo runs were conducted to test the reliability of the methodology. The average detection results after 200 Montecarlo runs of a 200 hyperplane hidden layer RLSFN are given in terms of Sensitivity (males: 0.9946, females: 0.9942), Specificity (males: 0.9944, females: 0.9941) and Accuracy (males: 0.9945, females: 0.9942). The area under the ROC curve is 0.9947 (males) and 0.9945 (females). The equal error rate is 0.0054 (males) and 0.0057 (females). Conclusions: The proposed methodology avails that the use of highly normalized descriptors as the probability distribution of kinematic variables of vowel articulation stability, which has some interesting properties in terms of information theory, boosts the potential of simple yet powerful classifiers in producing quite acceptable detection results in Parkinson Disease.

Quantitative Analysis of Relationship Between Hypokinetic Dysarthria and the Freezing of Gait in Parkinson’s Disease

Hypokinetic dysarthria (HD) and freezing of gait (FOG) are both axial symptoms that occur in patients with Parkinson’s disease (PD). It is assumed they have some common pathophysiological mechanisms and therefore that speech disorders in PD can predict FOG deficits within the horizon of some years. The aim of this study is to employ a complex quantitative analysis of the phonation, articulation and prosody in PD patients in order to identify the relationship between HD and FOG, and establish a mathematical model that would predict FOG deficits using acoustic analysis at baseline. We enrolled 75 PD patients who were assessed by 6 clinical scales including the Freezing of Gait Questionnaire (FOG–Q). We subsequently extracted 19 acoustic measures quantifying speech disorders in the fields of phonation, articulation and prosody. To identify the relationship between HD and FOG, we performed a partial correlation analysis. Finally, based on the selected acoustic measures, we trained regression models to predict the change in FOG during a 2-year follow-up. We identified significant correlations between FOG–Q scores and the acoustic measures based on formant frequencies (quantifying the movement of the tongue and jaw) and speech rate. Using the regression models, we were able to predict a change in particular FOG–Q scores with an error of between 7.4 and 17.0 %. This study is suggesting that FOG in patients with PD is mainly linked to improper articulation, a disturbed speech rate and to intelligibility. We have also proved that the acoustic analysis of HD at the baseline can be used as a predictor of the FOG deficit during 2 years of follow-up. This knowledge enables researchers to introduce new cognitive systems that predict gait difficulties in PD patients.

Vowel Articulation Distortion in Parkinson’s Disease

Neurodegenerative pathologies produce important distortions in speech. Parkinson’s Disease (PD) leaves marks in fluency, prosody, articulation and phonation. Certain measurements based in configurations of the articulation organs inferred from formant positions, as the Vocal Space Area (VSA) or the Formant Centralization Ratio (FCR) have been classically used in this sense, but these markers represent mainly the static positions of sustained vowels on the vowel triangle. The present study proposes a measurement based on the mutual information contents of kinematic correlates derived from formant dynamics. An absolute kinematic velocity associated to the position of the articulation organs, involving the jaw and tongue is estimated and modelled statistically. The distribution of this feature is rather different in PD patients than in normative speakers when sustained vowels are considered. Therefore, articulation failures may be detected even in single sustained vowels. The study has processed a limited database of 40 female and 54 male PD patients, contrasted to a very selected and stable set of normative speakers. Distances based on Kullback-Leibler’s Divergence have shown to be sensitive to PD articulation instability. Correlation measurements show that the distance proposed shows statistically relevant relationship with certain motor and non-motor behavioral observations, as freezing of gait, or sleep disorders. These results point out to the need of defining scoring scales specifically designed for speech-based diagnose and monitoring methodologies in degenerative diseases of neuromotor origin.

Identification of hypokinetic dysarthria using acoustic analysis of poem recitation

Up to 90% of patients with Parkinsons disease (PD) suffer from hypokinetic dysarthria (HD). In this work, we analysed the power of conventional speech features quantifying imprecise articulation, dysprosody, speech dysfluency and speech quality deterioration extracted from a specialized poem recitation task to discriminate dysarthric and healthy speech. For this purpose, 152 speakers (53 healthy speakers, 99 PD patients) were examined. Only mildly strong correlation between speech features and clinical status of the speakers was observed. In case of univariate classification analysis, sensitivity of 62.63 % (imprecise articulation), 61.62% (dysprosody), 71.72% (speech dysfluency) and 59.60% (speech quality deterioration) was achieved. Multivariate classification analysis improved the classification performance. Sensitivity of 83.42% using only two features describing imprecise articulation and speech quality deterioration in HD was achieved. We showed the promising potential of the selected speech features and especially the use of poem recitation task to quantify and identify HD in PD.