Short-term effects of transcranial direct current stimulation on motor speech in Parkinson's disease: a pilot study.

INTRODUCTION: Hypokinetic dysarthria (HD) is a common motor speech symptom of Parkinson's disease (PD) which does not respond well to PD treatments. We investigated short-term effects of transcranial direct current stimulation (tDCS) on HD in PD using acoustic analysis of speech. Based on our previous studies we focused on stimulation of the right superior temporal gyrus (STG) - an auditory feedback area. METHODS: In 14 PD patients with HD, we applied anodal, cathodal and sham tDCS to the right STG using a cross-over design. A protocol consisting of speech tasks was performed prior to and immediately after each stimulation session. Linear mixed models were used for the evaluation of the effects of each stimulation condition on the relative change of acoustic parameters. We also performed a simulation of the mean electric field induced by tDCS. RESULTS: Linear mixed model showed a statistically significant effect of the stimulation condition on the relative change of median duration of silences longer than 50 ms (p = 0.015). The relative change after the anodal stimulation (mean = -5.9) was significantly lower as compared to the relative change after the sham stimulation (mean = 12.8), p = 0.014. We also found a correlation between the mean electric field magnitude in the right STG and improvement of articulation precision after anodal tDCS (R = 0.637; p = 0.019). CONCLUSIONS: The exploratory study showed that anodal tDCS applied over the auditory feedback area may lead to shorter pauses in a speech of PD patients.

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.

A Pilot Study on the Functional Stability of Phonation in EEG Bands After Repetitive Transcranial Magnetic Stimulation in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative condition with constantly increasing prevalence rates, affecting strongly life quality in terms of neuromotor and cognitive performance. PD symptoms include voice and speech alterations, known as hypokinetic dysarthria (HD). Unstable phonation is one of the manifestations of HD. Repetitive transcranial magnetic stimulation (rTMS) is a rehabilitative treatment thathas been shown to improve some motor and non-motor symptoms of persons with PD (PwP). This study analyzed the phonation functional behavior of 18 participants (13 males, 5 females) with PD diagnosis before (one pre-stimulus) and after (four post-stimulus) evaluation sessions of rTMS treatment, to assess the extent of changes in their phonation stability. Participants were randomized 1:1 to receive either rTMS or sham stimulation. Voice recordings of a sustained vowel [a:] taken immediately before and after the treatment, and at follow-up evaluation sessions (immediately after, at six, ten, and fourteen weeks after the baseline assessment) were processed by inverse filtering to estimate a biomechanical correlate of vocal fold tension. This estimate was further band-pass filtered into EEG-related frequency bands. Log-likelihood ratios (LLRs) between pre- and post-stimulus amplitude distributions of each frequency band showed significant differences in five cases actively stimulated. Seven cases submitted to the sham protocol did not show relevant improvements in phonation instability. Conversely, four active cases did not show phonation improvements, whereas two sham cases did. The study provides early preliminary insights into the capability of phonation quality assessment by monitoring neuromechanical activity from acoustic signals in frequency bands aligned with EEG ones.

Comparison of CNN-Learned vs. Handcrafted Features for Detection of Parkinson's Disease Dysgraphia in a Multilingual Dataset.

Parkinson's disease dysgraphia (PDYS), one of the earliest signs of Parkinson's disease (PD), has been researched as a promising biomarker of PD and as the target of a noninvasive and inexpensive approach to monitoring the progress of the disease. However, although several approaches to supportive PDYS diagnosis have been proposed (mainly based on handcrafted features (HF) extracted from online handwriting or the utilization of deep neural networks), it remains unclear which approach provides the highest discrimination power and how these approaches can be transferred between different datasets and languages. This study aims to compare classification performance based on two types of features: features automatically extracted by a pretrained convolutional neural network (CNN) and HF designed by human experts. Both approaches are evaluated on a multilingual dataset collected from 143 PD patients and 151 healthy controls in the Czech Republic, United States, Colombia, and Hungary. The subjects performed the spiral drawing task (SDT; a language-independent task) and the sentence writing task (SWT; a language-dependent task). Models based on logistic regression and gradient boosting were trained in several scenarios, specifically single language (SL), leave one language out (LOLO), and all languages combined (ALC). We found that the HF slightly outperformed the CNN-extracted features in all considered evaluation scenarios for the SWT. In detail, the following balanced accuracy (BACC) scores were achieved: SL-0.65 (HF), 0.58 (CNN); LOLO-0.65 (HF), 0.57 (CNN); and ALC-0.69 (HF), 0.66 (CNN). However, in the case of the SDT, features extracted by a CNN provided competitive results: SL-0.66 (HF), 0.62 (CNN); LOLO-0.56 (HF), 0.54 (CNN); and ALC-0.60 (HF), 0.60 (CNN). In summary, regarding the SWT, the HF outperformed the CNN-extracted features over 6% (mean BACC of 0.66 for HF, and 0.60 for CNN). In the case of the SDT, both feature sets provided almost identical classification performance (mean BACC of 0.60 for HF, and 0.58 for CNN).

Shannon entropy: A novel parameter for quantifying pentagon copying performance in non-demented Parkinson's disease patients.

INTRODUCTION: Impaired copy of intersecting pentagons from the Mini-Mental State Examination (MMSE), has been used to assess dementia in Parkinson's disease (PD). We used a digitizing tablet during the pentagon copying test (PCT) as a potential tool for evaluating early cognitive deficits in PD without major cognitive impairment. We also aimed to uncover the neural correlates of the identified parameters using whole-brain magnetic resonance imaging (MRI). METHODS: We enrolled 27 patients with PD without major cognitive impairment and 25 age-matched healthy controls (HC). We focused on drawing parameters using a digitizing tablet. Parameters with between-group differences were correlated with cognitive outcomes and were used as covariates in the whole-brain voxel-wise analysis using voxel-based morphometry; familywise error (FWE) threshold p < 0.001. RESULTS: PD patients differed from HC in attention domain z-scores (p < 0.0001). In terms of tablet parameters, the groups differed in Shannon entropy (horizontal in-air, p = 0.003), which quantifies the movements between two strokes. In PD, a correlation was found between the median of Shannon entropy (horizontal in-air) and attention z-scores (R = -0.55, p = 0.006). The VBM revealed an association between our drawing parameter of interest and gray matter (GM) volume variability in the right superior parietal lobe (SPL). CONCLUSION: Using a digitizing tablet during the PCT, we identified a novel entropy-based parameter that differed between the nondemented PD and HC groups. This in-air parameter correlated with the level of attention and was linked to GM volume variability of the region engaged in spatial attention.

Non-invasive brain stimulation for speech in Parkinson's disease: A randomized controlled trial.

BACKGROUND: Hypokinetic dysarthria is a common but difficult-to-treat symptom of Parkinson's disease (PD). OBJECTIVES: We evaluated the long-term effects of multiple-session repetitive transcranial magnetic stimulation on hypokinetic dysarthria in PD. Neural mechanisms of stimulation were assessed by functional MRI. METHODS: A randomized parallel-group sham stimulation-controlled design was used. Patients were randomly assigned to ten sessions (2 weeks) of real (1 Hz) or sham stimulation over the right superior temporal gyrus. Stimulation effects were evaluated at weeks 2, 6, and 10 after the baseline assessment. Articulation, prosody, and speech intelligibility were quantified by speech therapist using a validated tool (Phonetics score of the Dysarthric Profile). Activations of the speech network regions and intrinsic connectivity were assessed using 3T MRI. Linear mixed models and post-hoc tests were utilized for data analyses. RESULTS: Altogether 33 PD patients completed the study (20 in the real stimulation group and 13 in the sham stimulation group). Linear mixed models revealed significant effects of time (F(3, 88.1) = 22.7, p < 0.001) and time-by-group interactions: F(3, 88.0) = 2.8, p = 0.040) for the Phonetics score. Real as compared to sham stimulation led to activation increases in the orofacial sensorimotor cortex and caudate nucleus and to increased intrinsic connectivity of these regions with the stimulated area. CONCLUSIONS: This is the first study to show the long-term treatment effects of non-invasive brain stimulation for hypokinetic dysarthria in PD. Neural mechanisms of the changes are discussed.

Mozart effect in epilepsy: Why is Mozart better than Haydn? Acoustic qualities-based analysis of stereoelectroencephalography.

BACKGROUND AND PURPOSE: We aimed to confirm the Mozart effect in epileptic patients using intracerebral electroencephalography recordings and the hypothesis that the reduction of epileptiform discharges (EDs) can be explained by the music's acoustic properties. METHODS: Eighteen epilepsy surgery candidates were implanted with depth electrodes in the temporal medial and lateral cortex. Patients listened to the first movement of Mozart's Sonata for Two Pianos K. 448 and to the first movement of Haydn's Symphony No. 94. Musical features from each composition with respect to rhythm, melody, and harmony were analyzed. RESULTS: Epileptiform discharges in intracerebral electroencephalography were reduced by Mozart's music. Listening to Haydn's music led to reduced EDs only in women; in men, the EDs increased. The acoustic analysis revealed that nondissonant music with a harmonic spectrum and decreasing tempo with significant high-frequency parts has a reducing effect on EDs in men. To reduce EDs in women, the music should additionally be gradually less dynamic in terms of loudness. Finally, we were able to demonstrate that these acoustic characteristics are more dominant in Mozart's music than in Haydn's music. CONCLUSIONS: We confirmed the reduction of intracerebral EDs while listening to classical music. An analysis of the musical features revealed that the acoustic characteristics of music are responsible for suppressing brain epileptic activity. Based on our study, we suggest studying the use of musical pieces with well-defined acoustic properties as an alternative noninvasive method to reduce epileptic activity in patients with epilepsy.

Articulatory network reorganization in Parkinson's disease as assessed by multimodal MRI and acoustic measures.

INTRODUCTION: Hypokinetic dysarthria (HD) is common in Parkinson's disease (PD). Our objective was to evaluate articulatory networks and their reorganization due to PD pathology in individuals without overt speech impairment using a multimodal MRI protocol and acoustic analysis of speech. METHODS: A total of 34 PD patients with no subjective HD complaints and 25 age-matched healthy controls (HC) underwent speech task recordings, structural MRI, and reading task-induced and resting-state fMRI. Grey matter probability maps, task-induced activations, and resting-state functional connectivity within the regions engaged in speech production (ROIs) were assessed and compared between groups. Correlation with acoustic parameters was also performed. RESULTS: PD patients as compared Tto HC displayed temporal decreases in speech loudness which were related to BOLD signal increases in the right-sided regions of the dorsal language pathway/articulatory network. Among those regions, activation of the right anterior cingulate was increased in PD as compared to HC. We also found bilateral posterior superior temporal gyrus (STG) GM loss in PD as compared to HC that was strongly associated with diadochokinetic (DDK) irregularity in the PD group. Task-induced activations of the left STG were increased in PD as compared to HC and were related to the DDK rate control. CONCLUSIONS: The results provide insight into the neural correlates of speech production control and distinct articulatory network reorganization in PD apparent already in patients without subjective speech impairment.

Patterns of diffusion kurtosis changes in Parkinson's disease subtypes.

BACKGROUND: Diffusion kurtosis imaging has been applied to evaluate white matter and basal ganglia microstructure in mixed Parkinson's disease (PD) groups with inconclusive results. OBJECTIVES: To evaluate specific patterns of kurtosis changes in PD and to assess the utility of diffusion imaging in differentiating between healthy subjects and cognitively normal PD, and between PD with and without mild cognitive impairment. METHODS: Diffusion scans were obtained in 92 participants using 3T MRI. Differences in white matter were tested by tract-based spatial statistics. Gray matter was evaluated in basal ganglia, thalamus, hippocampus, and motor and premotor cortices. Brain atrophy was also assessed. Multivariate logistic regression was used to identify a combination of diffusion parameters with the highest discrimination power between groups. RESULTS: Diffusion kurtosis metrics showed a significant increase in substantia nigra (p = 0.037, Hedges' g = 0.89), premotor (p = 0.009, Hedges' g = 0.85) and motor (p = 0.033, Hedges' g = 0.87) cortices in PD with normal cognition compared to healthy participants. Combined diffusion markers in gray matter reached 81% accuracy in differentiating between both groups. Significant white matter microstructural changes, and kurtosis decreases in the cortex were present in cognitively impaired versus cognitively normal PD. Diffusion parameters from white and gray matter differentiated between both PD phenotypes with 78% accuracy. CONCLUSIONS: Increased kurtosis in gray matter structures in cognitively normal PD reflects increased hindrance to water diffusion caused probably by alpha-synuclein-related microstructural changes. In cognitively impaired PD, the changes are mostly driven by decreased white matter integrity. Our results support the utility of diffusion kurtosis imaging for PD diagnostics.