Levodopa may modulate specific speech impairment in Parkinson's disease: an fMRI study.

Hypokinetic dysarthria (HD) is a difficult-to-treat symptom affecting quality of life in patients with Parkinson's disease (PD). Levodopa may partially alleviate some symptoms of HD in PD, but the neural correlates of these effects are not fully understood. The aim of our study was to identify neural mechanisms by which levodopa affects articulation and prosody in patients with PD. Altogether 20 PD patients participated in a task fMRI study (overt sentence reading). Using a single dose of levodopa after an overnight withdrawal of dopaminergic medication, levodopa-induced BOLD signal changes within the articulatory pathway (in regions of interest; ROIs) were studied. We also correlated levodopa-induced BOLD signal changes with the changes in acoustic parameters of speech. We observed no significant changes in acoustic parameters due to acute levodopa administration. After levodopa administration as compared to the OFF dopaminergic condition, patients showed task-induced BOLD signal decreases in the left ventral thalamus (p = 0.0033). The changes in thalamic activation were associated with changes in pitch variation (R = 0.67, p = 0.006), while the changes in caudate nucleus activation were related to changes in the second formant variability which evaluates precise articulation (R = 0.70, p = 0.003). The results are in line with the notion that levodopa does not have a major impact on HD in PD, but it may induce neural changes within the basal ganglia circuitries that are related to changes in speech prosody and articulation.

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.

Speech prosody impairment predicts cognitive decline in Parkinson's disease.

BACKGROUND: Impairment of speech prosody is characteristic for Parkinson's disease (PD) and does not respond well to dopaminergic treatment. OBJECTIVES: We assessed whether baseline acoustic parameters, alone or in combination with other predominantly non-dopaminergic symptoms may predict global cognitive decline as measured by the Addenbrooke's cognitive examination (ACE-R) and/or worsening of cognitive status as assessed by a detailed neuropsychological examination. METHODS: Forty-four consecutive non-depressed PD patients underwent clinical and cognitive testing, and acoustic voice analysis at baseline and at the two-year follow-up. Influence of speech and other clinical parameters on worsening of the ACE-R and of the cognitive status was analyzed using linear and logistic regression. RESULTS: The cognitive status (classified as normal cognition, mild cognitive impairment and dementia) deteriorated in 25% of patients during the follow-up. The multivariate linear regression model consisted of the variation in range of the fundamental voice frequency (F0VR) and the REM Sleep Behavioral Disorder Screening Questionnaire (RBDSQ). These parameters explained 37.2% of the variability of the change in ACE-R. The most significant predictors in the univariate logistic regression were the speech index of rhythmicity (SPIR; p = 0.012), disease duration (p = 0.019), and the RBDSQ (p = 0.032). The multivariate regression analysis revealed that SPIR alone led to 73.2% accuracy in predicting a change in cognitive status. Combining SPIR with RBDSQ improved the prediction accuracy of SPIR alone by 7.3%. CONCLUSIONS: Impairment of speech prosody together with symptoms of RBD predicted rapid cognitive decline and worsening of PD cognitive status during a two-year period.

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 Parkinson's 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.

Impact of Parkinson's disease and levodopa on resting state functional connectivity related to speech prosody control.

BACKGROUND: Impaired speech prosody is common in Parkinson's disease (PD). We assessed the impact of PD and levodopa on MRI resting-state functional connectivity (rs-FC) underlying speech prosody control. METHODS: We studied 19 PD patients in the OFF and ON dopaminergic conditions and 15 age-matched healthy controls using functional MRI and seed partial least squares correlation (PLSC) analysis. In the PD group, we also correlated levodopa-induced rs-FC changes with the results of acoustic analysis. RESULTS: The PLCS analysis revealed a significant impact of PD but not of medication on the rs-FC strength of spatial correlation maps seeded by the anterior cingulate (p = 0.006), the right orofacial primary sensorimotor cortex (OF_SM1; p = 0.025) and the right caudate head (CN; p = 0.047). In the PD group, levodopa-induced changes in the CN and OF_SM1 connectivity strengths were related to changes in speech prosody. CONCLUSIONS: We demonstrated an impact of PD but not of levodopa on rs-FC within the brain networks related to speech prosody control. When only the PD patients were taken into account, the association between treatment-induced changes in speech prosody and changes in rs-FC within the associative striato-prefrontal and motor speech networks was found.

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 Addenbrooke's Cognitive Examination-Revised (ACE-R) in discriminating between Parkinson's 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.

Independent origin of sex chromosomes in two species of the genus Silene.

Here we introduce a new model species, Silene colpophylla, that could facilitate research of sex chromosome evolution and sex-determining systems. This species is related to the well-established dioecious plant model Silene latifolia. Our results show that S. colpophylla is, similarly to S. latifolia, a male heterogametic species, but its sex chromosomes have evolved from a different pair of autosomes than in S. latifolia. The results of our phylogenetic study and mapping of homologs of S. latifolia X-linked genes indicate that the sex determination system in S. colpophylla evolved independently from that in S. latifolia. We assert that this model species pair will make it possible to study two independent patterns of sex chromosome evolution in related species.