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.
- MeSH
- antiparkinsonika škodlivé účinky MeSH
- dysartrie etiologie komplikace MeSH
- kvalita života MeSH
- levodopa * škodlivé účinky MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- Parkinsonova nemoc * komplikace diagnostické zobrazování farmakoterapie MeSH
- poruchy řeči diagnostické zobrazování etiologie MeSH
- řeč fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
White Matter Lesions (WML) are a radiological finding common in aged subjects. We explored the impact of WML on underlying neurodegenerative processes. We focused on the impact of WML on two neurodegenerative diseases with different pathology. In this cross-sectional study of 137 subjects (78 female, 59 men, mean age 67.2; 43-87 years), we compared WML in healthy controls (HC; n = 55), patients with Alzheimer's disease and amnestic Mild Cognitive Impairment (aMCI), and Parkinson's disease patients with normal cognition and with MCI. Subjects with AD and aMCI were treated as one group (n = 40), subjects with PD and PDMCI were another group (n = 42). MRI T2_FLAIR sequences were analyzed. WML were divided into periventricular (pWML) or subcortical (sWML) depending on their distance from the ventricles. Subjects from the AD + aMCI group, had a significantly greater volume of WML than both HC and the PD + PDMCI group. The volume of WML was greater in the PD + PDMCI than in HC but the difference was not significant. In AD + aMCI subjects, sWML and not pWML were related to a decrease in global cognitive functioning despite greater volume of pWML. In PD + PDMCI, pWML correlate with decline in executive functions and working memory. In HC, pWML correlated with the multidomain decrease corresponding with the aging. This points to a difference between normal aging and pathological aging due to AD and PD brain pathology. The WML location together with underlying disease related neurodegeneration may play a role in determining the effect of WML on cognition. Our results suggest that the impact of WML is not uniform in all patients; rather, their volume, location and cognitive effect may be disease-specific.
- MeSH
- Alzheimerova nemoc * komplikace diagnostické zobrazování patologie MeSH
- bílá hmota * diagnostické zobrazování patologie MeSH
- kognice MeSH
- kognitivní dysfunkce * komplikace etiologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- nemoci nervového systému * MeSH
- neuropsychologické testy MeSH
- Parkinsonova nemoc * komplikace diagnostické zobrazování patologie MeSH
- progrese nemoci MeSH
- průřezové studie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The volume of the hippocampus decreases more slowly than the volume of the cortex during normal aging. We explored changes in the hippocampus-to-cortex volume (HV:CTV) ratio with increasing age in non-demented Parkinson's disease (PD) patients as compared to healthy controls (HC). We also evaluated the association between the HV:CTV ratio and cognitive outcomes. Altogether 130 participants without dementia aged 51-88 years were consecutively enrolled, including 54 PD patients (mean age 67, standard deviation (SD) 8 years) and 76 HC (mean age 69, SD 7 years). All participants underwent structural magnetic resonance examination and psychological evaluation. Hippocampal and cortex volumes were determined from T1 and FLAIR scans using FreeSurfer software, and the HV:CTV ratio was calculated. Regression lines for age-dependence of the HV:CTV ratio for PD and HC groups were calculated. We further assessed the association between the HV:CTV ratio and cognitive tests examining hippocampus-related cognitive functions. PD patients and age-matched HC showed a significant difference in age-dependence of HV:CTV ratio (p value = 0.012), with a decreasing slope in PD and increasing slope in HC. In the PD group, a significant correlation (R = 0.561, p = 0.024) was observed between the HV:CTV ratio and the Digit Symbol-Coding test. The reduction of HV:CTV ratio is accelerated in pathological aging due to PD pathology. The HV:CTV ratio was associated with impaired processing speed, i.e., the cognitive function that is linked to subcortical alterations of both associated basal ganglia circuitry and the hippocampus.
The vertex has been used as a suitable control stimulation site in repetitive transcranial magnetic stimulation studies. The objectives of this study are (1) to assess cognitive performance (CP) after theta burst stimulation (TBS); (2) to evaluate whether clinically relevant cortical areas might be reached by vertex stimulation and how that might influence CP. Twenty young healthy subjects performed a cognitive task prior to and immediately after intermittent TBS (iTBS) and continuous TBS (cTBS) of two active cortical stimulation sites and the vertex. We used the Wilcoxon signed-rank test to compare the pre- and post-stimulation reaction times (RTs) and a mixed ANOVA analysis to evaluate the effect of the stimulation on changes in RTs. A three-dimensional finite-element model (FEM) was used to calculate the vertex TBS-induced electrical field (E-field) in the adjacent regions of interest (ROIs). Correlation analyses were performed between E-fields in the ROIs and cognitive outcomes. We found a significant effect only of the stimulation time factor (F (1,12) = 65.37, p < 0.001) on RT shortening, with no superiority of the active site stimulation compared to the vertex stimulation. In 73.5% of vertex TBS sessions, a significant E-field was induced in at least one ROI. We found a negative association between the magnitude of the iTBS-induced E-fields and RT changes (R = - 0.54, p = 0.04). TBS protocols may lead to changes in CP when applied over the craniometrically targeted vertex. We therefore suggest not using a conventional approach as a vertex targeting method.
- MeSH
- hlava * MeSH
- lidé MeSH
- reakční čas MeSH
- theta rytmus EEG MeSH
- transkraniální magnetická stimulace * metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Several neurological diseases are accompanied by rhythmic oscillatory dysfunctions in various frequency ranges and disturbed cross-frequency relationships on regional, interregional, and whole brain levels. Knowledge of these disease-specific oscillopathies is important mainly in the context of deep brain stimulation (DBS) therapy. Electrophysiological biomarkers have been used as input signals for adaptive DBS (aDBS) as well as preoperative outcome predictors. As movement disorders, particularly Parkinson's disease (PD), are among the most frequent DBS indications, the current research of DBS is the most advanced in the movement disorders field. We reviewed the literature published mainly between 2010 and 2020 to identify the most important findings concerning the current evolution of electrophysiological biomarkers in DBS and to address future challenges for prospective research.
- MeSH
- biologické markery MeSH
- hluboká mozková stimulace * MeSH
- lidé MeSH
- mozek MeSH
- Parkinsonova nemoc * terapie MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB-Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.
The complex phenomenological understanding of dystonia has transcended from the clinics to genetics, imaging and neurophysiology. One way in which electrophysiology will impact into the clinics are cases wherein a dystonic clinical presentation may not be typical or a "forme fruste" of the disorder. Indeed, the physiological imprints of dystonia are present regardless of its clinical manifestation. Underpinnings in the understanding of dystonia span from the peripheral, segmental and suprasegmental levels to the cortex, and various electrophysiological tests have been applied in the course of time to elucidate the origin of dystonia pathophysiology. While loss of inhibition remains to be the key finding in this regard, intricacies and variabilities exist, thus leading to a notion that perhaps dystonia should best be gleaned as network disorder. Interestingly, the complex process has now spanned towards the understanding in terms of networks related to the cerebellar circuitry and the neuroplasticity. What is evolving towards a better and cohesive view will be neurophysiology attributes combined with structural dynamic imaging. Such a sound approach will significantly lead to better therapeutic modalities in the future.
- MeSH
- dystonické poruchy * MeSH
- dystonie * MeSH
- lidé MeSH
- mozeček MeSH
- mozková kůra MeSH
- neurofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
We evaluated the therapeutic effects of non-pharmacological interventions (cognitive training, physical activity, and non-invasive brain stimulation) on cognitive symptoms in Parkinson's disease. A comprehensive literature search for non-pharmacological intervention randomized controlled trials was performed and effect sizes were calculated for each suitable study intervention approach and cognitive domain. Despite the heterogeneity of the study results, we report level B evidence for the probable efficacy of cognitive training in improving or maintaining attention/working memory and memory domains. Level C (possible efficacy) evidence was found for specific physical training types with respect to enhancing executive functions. Non-invasive brain stimulation techniques and combinatorial approaches show preliminary but promising results. Prediction markers evaluating distinct treatment responses should be identified that would help to choose the best candidates for specific treatment strategies and cognitive symptoms. Future directions and recommendations are discussed.
Although deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) is generally a successful therapy, adverse events and insufficient clinical effect can complicate the treatment in some patients. We studied clinical parameters and cortical oscillations related to STN-DBS to identify patients with suboptimal responses. High-density EEG was recorded during a visual oddball three-stimuli paradigm in DBS "off" and "on" conditions in 32 PD patients with STN-DBS. Pre-processed data were reconstructed into the source space and the time-frequency analysis was evaluated. We identified a subgroup of six patients with longer reaction times (RT) during the DBS "on" state than in the DBS "off" state after target stimuli. These subjects had lower motor responsiveness to DBS and decreased memory test results compared to the other subjects. Moreover, the alpha and beta power decrease (event-related desynchronizations, ERD), known as an activation correlate linked to motor and cognitive processing, was also reduced in the DBS "on" condition in these patients. A subgroup of PD patients with a suboptimal response to STN-DBS was identified. Evaluation of RT could potentially serve as a biomarker for responsiveness to STN-DBS.
- MeSH
- hluboká mozková stimulace * MeSH
- kognice MeSH
- lidé MeSH
- nucleus subthalamicus * MeSH
- Parkinsonova nemoc * terapie MeSH
- reakční čas MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hypokinetic dysarthria is a multidimensional impairment affecting all main speech subsystems with variable patterns and severity across individual Parkinson's disease (PD) patients. We can thus assume that inter-individual abnormal speech patterns are related to the various clinical subtypes of PD with different prominent motor symptoms. The aim of this cross-sectional study was to compare speech disorder between patients with the postural instability/gait difficulty (PIGD) and tremor-dominant (TD) motor phenotypes of PD. Speech samples were acquired from a total of 63 participants, including 21 PIGD patients, 21 TD patients, and 21 healthy controls. Quantitative acoustic vocal assessment of 12 unique speech dimensions related to phonation, vocal tremor, oral diadochokinesis, articulation, prosody and speech timing was performed. Speech impairment was more pronounced in the PIGD group than in the TD group, with an area under the curve of 0.76. Patients in the PIGD group manifested abnormalities in pitch breaks, articulatory decay, decreased rate of follow-up speech segments and inappropriate silences, apart from monopitch and irregular AMR that were affected in TD group as well. An abnormal vocal tremor was present in only 10% of PD patients, with no differences between the PD phenotypes. We found a correlation between non-motor symptom severity and speech timing (r = - 0.40, p = 0.009). The present study demonstrates that speech disorder reflects the underlying motor phenotypes. Vocal tremor appeared to be an isolated phenomenon that does not share similar pathophysiology with limb tremor.
- MeSH
- chůze (způsob) MeSH
- lidé MeSH
- neurologické poruchy chůze * MeSH
- Parkinsonova nemoc * komplikace MeSH
- poruchy hlasu * etiologie MeSH
- posturální rovnováha MeSH
- průřezové studie MeSH
- řeč MeSH
- tremor komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
