BACKGROUND: This study investigated the subthalamic nucleus (STN) function and deep brain stimulation (DBS) effects on single-unit activity (SUA) in Parkinson's disease (PD) patients with dysarthria. METHODS: After presurgical speech analysis, we recorded STN neuronal activities while PD patients (n = 16) articulated Chinese Pinyin consonants. The Pinyin consonants were categorized by the manner and place of articulation for SUA cluster analysis. The cohort was then divided into normal articulation and dysarthria groups based on diadochokinetic (DDK) assessments. The STN SUA patterns, represented by the mean firing rate (FR), peak time, and response intensity during articulation, were analyzed and compared between the two groups. Finally, a stimulation cohort of 7 PD patients was included to test articulation and SUA pattern changes following intraoperative DBS. RESULTS: Clustering analysis of STN neuronal firing patterns demonstrated that neurons encode articulation by grouping consonants with the same manner of articulation into distinct clusters. Using k-means clustering, we further classified SUAs into two waveform types: negative spikes (type 1) and positive spikes (type 2). Dysarthria patients exhibited an increased mean FR of type 1 spikes and a reduced response intensity of type 2 spikes. During intraoperative stimulation, PD patients showed accelerated DDK, accompanied by a decrease in type 1 mean FR and an increase in type 2 mean FR. CONCLUSION: Our findings indicate the crucial role of the STN in consonant encoding and dysarthria at the single-unit level. Both SUA firing patterns in the STN and DDK performance can be modulated by DBS.
- MeSH
- akční potenciály fyziologie MeSH
- dysartrie * etiologie patofyziologie MeSH
- hluboká mozková stimulace * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- neurony * fyziologie MeSH
- nucleus subthalamicus * patofyziologie MeSH
- Parkinsonova nemoc * patofyziologie komplikace terapie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The aim of this work was to study the effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) on the subnetwork of subcortical and cortical motor regions and on the whole brain connectivity using the functional connectivity analysis in Parkinson's disease (PD). The high-density source space EEG was acquired and analyzed in 43 PD subjects in DBS on and DBS off stimulation states (off medication) during a cognitive-motor task. Increased high gamma band (50-100 Hz) connectivity within subcortical regions and between subcortical and cortical motor regions was significantly associated with the Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III improvement after DBS. Whole brain neural correlates of cognitive performance were also detected in the high gamma (50-100 Hz) band. A whole brain multifrequency connectivity profile was found to classify optimal and suboptimal responders to DBS with a positive predictive value of 0.77, negative predictive value of 0.55, specificity of 0.73, and sensitivity of 0.60. Specific connectivity patterns related to PD, motor symptoms improvement after DBS, and therapy responsiveness predictive connectivity profiles were uncovered.
- MeSH
- elektroencefalografie metody MeSH
- hluboká mozková stimulace * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozek patofyziologie diagnostické zobrazování MeSH
- nucleus subthalamicus * patofyziologie MeSH
- Parkinsonova nemoc * terapie patofyziologie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cognitive decline represents a severe non-motor symptom of Parkinson's disease (PD) that can significantly reduce the benefits of subthalamic deep brain stimulation (STN DBS). Here, we aimed to describe post-surgery cognitive decline and identify pre-surgery cognitive profile associated with faster decline in STN DBS-treated PD patients. A retrospective observational study of 126 PD patients treated by STN DBS combined with oral dopaminergic therapy followed for 3.54 years on average (SD = 2.32) with repeated assessments of cognition was conducted. Pre-surgery cognitive profile was obtained via a comprehensive neuropsychological examination and data analysed using exploratory factor analysis and Bayesian generalized linear mixed models. On the whole, we observed a mild annual cognitive decline of 0.90 points from a total of 144 points in the Mattis Dementia Rating Scale (95% posterior probability interval [-1.19, -0.62]) with high inter-individual variability. However, true score changes did not reach previously reported reliable change cut-offs. Executive deficit was the only pre-surgery cognitive variable to reliably predict the rate of post-surgery cognitive decline. On the other hand, exploratory analysis of electrode localization did not yield any statistically clear results. Overall, our data and models imply mild gradual average annual post-surgery cognitive decline with high inter-individual variability in STN DBS-treated PD patients. Nonetheless, patients with worse long-term cognitive prognosis can be reliably identified via pre-surgery examination of executive functions. To further increase the utility of our results, we demonstrate how our models can help with disentangling true score changes from measurement error in future studies of post-surgery cognitive changes.
- MeSH
- hluboká mozková stimulace * metody MeSH
- kognice fyziologie MeSH
- kognitivní dysfunkce * etiologie terapie patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- neuropsychologické testy MeSH
- nucleus subthalamicus * MeSH
- Parkinsonova nemoc * terapie patofyziologie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
BACKGROUND AND OBJECTIVES: The intricate relationship between deep brain stimulation (DBS) in Parkinson's disease (PD) and cognitive impairment has lately garnered substantial attention. The presented study evaluated pre-DBS structural and microstructural cerebral patterns as possible predictors of future cognitive decline in PD DBS patients. METHODS: Pre-DBS MRI data in 72 PD patients were combined with neuropsychological examinations and follow-up for an average of 2.3 years after DBS implantation procedure using a screening cognitive test validated for diagnosis of mild cognitive impairment in PD in a Czech population - Dementia Rating Scale 2. RESULTS: PD patients who would exhibit post-DBS cognitive decline were found to have, already at the pre-DBS stage, significantly lower cortical thickness and lower microstructural complexity than cognitively stable PD patients. Differences in the regions directly related to cognition as bilateral parietal, insular and cingulate cortices, but also occipital and sensorimotor cortex were detected. Furthermore, hippocampi, putamina, cerebellum and upper brainstem were implicated as well, all despite the absence of pre-DBS differences in cognitive performance and in the position of DBS leads or stimulation parameters between the two groups. CONCLUSIONS: Our findings indicate that the cognitive decline in the presented PD cohort was not attributable primarily to DBS of the subthalamic nucleus but was associated with a clinically silent structural and microstructural predisposition to future cognitive deterioration present already before the DBS system implantation.
- MeSH
- hluboká mozková stimulace * škodlivé účinky MeSH
- kognitivní dysfunkce * etiologie diagnostické zobrazování patofyziologie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- neuropsychologické testy MeSH
- nucleus subthalamicus * diagnostické zobrazování MeSH
- Parkinsonova nemoc * terapie diagnostické zobrazování patologie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: In this study we evaluated the impact of location of deep brain stimulation electrode active contact in different parts of the subthalamic nucleus on improvement of non-motor symptoms in patients with Parkinson's disease. METHODS: The subthalamic nucleus was divided into two (dorsolateral/ventromedial) and three (dorsolateral, medial, ventromedial) parts. 37 deep brain stimulation electrodes were divided according to their active contact location. Correlation between change in non-motor symptoms before and one and four months after deep brain stimulation electrode implantation and the location of active contact was made. RESULTS: In dividing the subthalamic nucleus into three parts, no electrode active contact was placed ventromedially, 28 active contacts were located in the medial part and 9 contacts were placed dorsolaterally. After one and four months, no significant difference was found between medial and dorsolateral positions. In the division of the subthalamic nucleus into two parts, 13 contacts were located in the ventromedial part and 24 contacts were placed in the dorsolateral part. After one month, significantly greater improvement in the Non-motor Symptoms Scale for Parkinson's disease (P=0.045) was found on dorsolateral left-sided stimulation, but no significant differences between the ventromedial and dorsolateral positions were found on the right side. CONCLUSION: This study demonstrated the relationship between improvement of non-motor symptoms and the side (hemisphere, left/right) of the deep brain stimulation electrode active contact, rather than its precise location within specific parts of the subthalamic nucleus in patients treated for advanced Parkinson's disease.
- MeSH
- elektrody MeSH
- hluboká mozková stimulace * MeSH
- lidé MeSH
- nucleus subthalamicus * fyziologie MeSH
- Parkinsonova nemoc * terapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: This study aimed to evaluate whether long-term averaged spectrum (LTAS) descriptors for reading and monologue are suitable to detect worsening of dysarthria in patients with Parkinson's disease (PD) treated with subthalamic nucleus deep brain stimulation (STN-DBS) with potential effect of ON and OFF stimulation conditions and types of connected speech. METHOD: Four spectral moments based on LTAS were computed for monologue and reading passage collected from 23 individuals with PD treated with bilateral STN-DBS and 23 age- and gender-matched healthy controls. Speech performance of patients with PD was compared in ON and OFF STN-DBS conditions. RESULTS: All LTAS spectral moments including mean, standard deviation, skewness, and kurtosis across both monologue and reading passage were able to significantly distinguish between patients with PD in both stimulation conditions and control speakers. The spectral mean was the only LTAS measure sensitive to capture better speech performance in STN-DBS ON, as compared to the STN-DBS OFF stimulation condition (p < .05). Standardized reading passage was more sensitive compared to monologue in detecting dysarthria severity via LTAS descriptors with an area under the curve of up to 0.92 obtained between PD and control groups. CONCLUSIONS: Our findings confirmed that LTAS is a suitable approach to objectively describe changes in speech impairment severity due to STN-DBS therapy in patients with PD. We envisage these results as an important step toward a continuum development of technological solutions for the automated assessment of stimulation-induced dysarthria. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21644798.
Little is known about the minimum sample length required for the stable acoustic assessment of speech in Parkinson's disease (PD). This study aimed to investigate the effect of the duration of the reading passage on the determination of reliable acoustic patterns in individuals with PD treated with subthalamic nucleus deep brain stimulation. A phonetically balanced reading text of 313 words was collected from 32 Czech persons with PD, and 32 age- and sex-matched healthy controls. The reading passage was segmented to produce ten sub-texts of increasing length ranging from a one- to a ten-segment-long sub-text. An error rate analysis was used to estimate the required stabilization value by evaluating the differences between the sub-texts and the entire text across seven hypokinetic dysarthria features. The minimum length of a reading passage equal to 128 words was found to be necessary for acoustic assessment, with similar lengths being required for the controls (120 words) and the two PD subgroups, including Parkinsonian individuals with a mild (126 words) and moderate (128 words) dysarthria severity. The current study provides important guidelines for the necessary sample length for future expert instrumental dysarthria assessments and assists in decreasing the time required for clinical speech evaluations.
- MeSH
- akustika MeSH
- čtení MeSH
- dysartrie MeSH
- hluboká mozková stimulace * MeSH
- lidé MeSH
- nucleus subthalamicus * MeSH
- Parkinsonova nemoc * diagnóza terapie MeSH
- řeč MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Functional MRI (fMRI) has become an important tool for probing network-level effects of deep brain stimulation (DBS). Previous DBS-fMRI studies have shown that electrical stimulation of the ventrolateral (VL) thalamus can modulate sensorimotor cortices in a frequency and amplitude dependent manner. Here, we investigated, using a swine animal model, how the direction and orientation of the electric field, induced by VL-thalamus DBS, affects activity in the sensorimotor cortex. Adult swine underwent implantation of a novel 16-electrode (4 rows x 4 columns) directional DBS lead in the VL thalamus. A within-subject design was used to compare fMRI responses for (1) directional stimulation consisting of monopolar stimulation in four radial directions around the DBS lead, and (2) orientation-selective stimulation where an electric field dipole was rotated 0°-360° around a quadrangle of electrodes. Functional responses were quantified in the premotor, primary motor, and somatosensory cortices. High frequency electrical stimulation through leads implanted in the VL thalamus induced directional tuning in cortical response patterns to varying degrees depending on DBS lead position. Orientation-selective stimulation showed maximal functional response when the electric field was oriented approximately parallel to the DBS lead, which is consistent with known axonal orientations of the cortico-thalamocortical pathway. These results demonstrate that directional and orientation-selective stimulation paradigms in the VL thalamus can tune network-level modulation patterns in the sensorimotor cortex, which may have translational utility in improving functional outcomes of DBS therapy.
- MeSH
- elektrická stimulace metody MeSH
- hluboká mozková stimulace * metody MeSH
- magnetická rezonanční tomografie metody MeSH
- motorické korové centrum fyziologie MeSH
- nervové dráhy fyziologie MeSH
- nuclei ventrales thalami fyziologie MeSH
- nucleus subthalamicus fyziologie MeSH
- prasata MeSH
- thalamus fyziologie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
The degree of response to subthalamic nucleus deep brain stimulation (STN-DBS) is individual and hardly predictable. We hypothesized that DBS-related changes in cortical network organization are related to the clinical effect. Network analysis based on graph theory was used to evaluate the high-density electroencephalography (HDEEG) recorded during a visual three-stimuli paradigm in 32 Parkinson's disease (PD) patients treated by STN-DBS in stimulation "off" and "on" states. Preprocessed scalp data were reconstructed into the source space and correlated to the behavioral parameters. In the majority of patients (n = 26), STN-DBS did not lead to changes in global network organization in large-scale brain networks. In a subgroup of suboptimal responders (n = 6), identified according to reaction times (RT) and clinical parameters (lower Unified Parkinson's Disease Rating Scale [UPDRS] score improvement after DBS and worse performance in memory tests), decreased global connectivity in the 1-8 Hz frequency range and regional node strength in frontal areas were detected. The important role of the supplementary motor area for the optimal DBS response was demonstrated by the increased node strength and eigenvector centrality in good responders. This response was missing in the suboptimal responders. Cortical topologic architecture is modified by the response to STN-DBS leading to a dysfunction of the large-scale networks in suboptimal responders.
- MeSH
- elektroencefalografie MeSH
- hluboká mozková stimulace * MeSH
- hodnocení výsledků zdravotní péče MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozková kůra patofyziologie MeSH
- nervová síť patofyziologie MeSH
- nucleus subthalamicus patofyziologie MeSH
- Parkinsonova nemoc patofyziologie terapie MeSH
- psychomotorický výkon fyziologie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
It has been suggested that slow oscillations in the subthalamic nucleus (STN) reflect top-down inputs from the medial prefrontal cortex, thus implementing behavior control. It is unclear, however, whether the STN oscillations are related to cortical activity in a bottom-up manner. To assess resting-state subcortico-cortical interactions, we recorded simultaneous scalp electroencephalographic activity and local field potentials in the STN (LFP-STN) in 11 patients with Parkinson's disease implanted with deep brain stimulation electrodes in the on-medication state during rest. We assessed the cross-structural phase-amplitude coupling (PAC) between the STN and cortical activity within a wide frequency range of 1 to 100 Hz. The PAC was dominant between the δ/θ STN phase and β/γ cortical amplitude in most investigated scalp regions and between the δ cortical phase and θ/α STN amplitude in the frontal and temporal regions. The cross-frequency linkage between the slow oscillations of the LFP-STN activity and the amplitude of the scalp-recorded cortical activity at rest was demonstrated, and similar involvement of the left and right STNs in the coupling was observed. Our results suggest that the STN plays a role in both bottom-up and top-down processes within the subcortico-cortical circuitries of the human brain during the resting state. A relative left-right symmetry in the STN-cortex functional linkage was suggested. Practical treatment studies would be necessary to assess whether unilateral stimulation of the STN might be sufficient for treatment of Parkinson's disease.
- MeSH
- elektroencefalografie MeSH
- hluboká mozková stimulace * MeSH
- lidé MeSH
- nucleus subthalamicus * MeSH
- Parkinsonova nemoc * terapie MeSH
- skalp MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
