Tools for post-operative localization of deep brain stimulation (DBS) electrodes may be of major benefit in the evaluation of the stimulation area. However, little is known about their precision. This study compares 3 different software packages used for DBS electrode localization. T1-weighted MRI images before and after the implantation of the electrodes into the subthalamic nucleus for DBS in 105 Parkinson's disease patients were processed using the pipelines implemented in Lead-DBS, SureTune4, and Brainlab. Euclidean distance between active contacts determined by individual software packages and in repeated processing by the same and by a different operator was calculated. Furthermore, Dice coefficient for overlap of volume of tissue activated (VTA) was determined for Lead-DBS. Medians of Euclidean distances between estimated active contact locations in inter-software package comparison ranged between 1.5 mm and 2 mm. Euclidean distances in within-software package intra- and inter-rater assessments were 0.6-1 mm and 1-1.7 mm, respectively. Median intra- and inter-rater Dice coefficients for VTAs were 0.78 and 0.75, respectively. Since the median distances are close to the size of the target nucleus, any clinical use should be preceded by careful review of the outputs.

• MeSH
• Deep Brain Stimulation * methods   instrumentation   MeSH
• Electrodes, Implanted * MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Subthalamic Nucleus surgery   MeSH
• Parkinson Disease * therapy   MeSH
• Aged MeSH
• Software MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Research on the possible influence of lateralised basal ganglia dysfunction on speech in Parkinson's disease is scarce. This study aimed to compare speech in de-novo, drug-naive patients with Parkinson's disease (PD) with asymmetric nigral dopaminergic dysfunction, predominantly in either the right or left hemisphere. METHODS: Acoustic analyses of reading passages were performed. Asymmetry of nigral dysfunction was defined using dopamine transporter-single-photon emission CT (DAT-SPECT). RESULTS: From a total of 135 de novo patients with PD assessed, 47 patients had a lower right and 36 lower left DAT availability in putamen based on DAT-SPECT. Patients with PD with lower left DAT availability had higher dysarthria severity via composite dysarthria index compared with patients with lower right DAT availability (p=0.01). CONCLUSION: Our data support the crucial role of DAT availability in the left putamen in speech. This finding might provide important clues for managing speech following deep brain stimulation.

• MeSH
• Basal Ganglia * physiopathology   diagnostic imaging   MeSH
• Dysarthria physiopathology   diagnostic imaging   etiology   MeSH
• Functional Laterality * physiology   MeSH
• Tomography, Emission-Computed, Single-Photon MeSH
• Middle Aged MeSH
• Humans MeSH
• Parkinson Disease * physiopathology   diagnostic imaging   complications   MeSH
• Dopamine Plasma Membrane Transport Proteins metabolism   MeSH
• Putamen diagnostic imaging   metabolism   physiopathology   MeSH
• Speech * physiology   MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Temporal interference stimulation (TIS) is a novel noninvasive electrical stimulation technique to focally modulate deep brain regions; a minimum of two high-frequency signals (f1 and f2 > 1 kHz) interfere to create an envelope-modulated signal at a deep brain target with the frequency of modulation equal to the difference frequency: Δf = |f2 - f1|. OBJECTIVE: The goals of this study were to verify the capability of TIS to modulate the subthalamic nucleus (STN) with Δf and to compare the effect of TIS and conventional deep brain stimulation (DBS) on the STN beta oscillations in patients with Parkinson's disease (PD). METHODS: DBS leads remained externalized after implantation, allowing local field potentials (LFPs) recordings in eight patients with PD. TIS was performed initially by two pairs (f1 = 9.00 kHz; f2 = 9.13 kHz, 4 mA peak-peak per pair maximum) of scalp electrodes placed in temporoparietal regions to focus the envelope signal maximum (Δf = 130 Hz) at the motor part of the STN target. RESULTS: The comparison between the baseline LFPs and recordings after TIS and conventional DBS sessions showed substantial suppression of high beta power peak after both types of stimulation in all patients. CONCLUSIONS: TIS has the potential to effectively modulate the STN and reduce the beta oscillatory activity in a completely noninvasive manner, as is traditionally possible only with intracranial DBS. Future studies should confirm the clinical effectiveness of TIS and determine whether TIS could be used to identify optimal DBS candidates and individualize DBS targets. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

• MeSH
• Beta Rhythm * physiology   MeSH
• Deep Brain Stimulation * methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Subthalamic Nucleus * physiopathology   MeSH
• Parkinson Disease * therapy   physiopathology   MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Temporal interference (TI) is a method of non-invasive brain stimulation using transcutaneous electrodes which allows the targeting and modulation of deeper brain structures, not normally associated with non-invasive simulation, while avoiding unwanted stimulation of shallower cortical structures. The properties of TI have been previously demonstrated, however, the problem of decoupling stimulation focality from stimulation intensity has not yet been well addressed. In this paper, we provide a possible novel solution, multipolar TI (mTI), which allows increased independent control over both the size of the stimulated region and the stimulation intensity. The mTI method uses multiple carrier frequencies to create multiple overlapping amplitude-modulated envelopes, rather than using one envelope as in standard TI. The study presents an explanation of the concept of mTI along with experimental data gathered from Rhesus macaques and mice. We improved the focality at depth in anesthetized mice and monkeys, and using the new focality in awake monkeys, evoked targeted activity at depth in the superior colliculus. The mTI method could be an interesting and potentially useful new tool alongside other forms of non-invasive brain stimulation. Teaser Multipolar Temporal Interference Stimulation can produce a more focal brain stimulation at depth compared to Temporal Interference.

• Publication type
• Journal Article MeSH

INTRODUCTION: Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is a well-established, effective treatment for dystonia. Substantial variability of therapeutic success has been the one of the drivers of an ongoing debate about proper stimulation site and settings, with several indications of the notional sweet spot pointing to the lower GPi or even subpallidal area. METHODS: The presented patient-blinded, random-order study with cross-sectional verification against healthy controls enrolled 17 GPi DBS idiopathic, cervical or generalised dystonia patients to compare the effect of the stimulation in the upper and lower GPi area, with the focus on sensorimotor network connectivity and local activity measured using functional magnetic resonance. RESULTS: Stimulation brought both these parameters to levels closer to the state detected in healthy controls. This effect was much more pronounced during the stimulation in the lower GPi area or beneath it than in slightly higher positions, with stimulation-related changes detected by both metrics of interest in the sensorimotor cortex, striatum, thalamus and cerebellum. CONCLUSIONS: All in all, this study not only replicated the results of previous studies on GPi DBS as a modality restoring sensorimotor network connectivity and local activity in dystonia towards the levels in healthy population, but also showed that lower GPi area or even subpallidal structures, be it white matter or even small, but essential nodes in the zona incerta as nucleus basalis of Meynert, are important regions to consider when programming DBS in dystonia patients.

• MeSH
• Adult MeSH
• Dystonic Disorders therapy   physiopathology   diagnostic imaging   MeSH
• Dystonia therapy   physiopathology   diagnostic imaging   MeSH
• Globus Pallidus * diagnostic imaging   physiopathology   MeSH
• Deep Brain Stimulation * methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Cross-Sectional Studies MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

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
• Action Potentials physiology   MeSH
• Dysarthria * etiology   physiopathology   MeSH
• Deep Brain Stimulation * methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neurons * physiology   MeSH
• Subthalamic Nucleus * physiopathology   MeSH
• Parkinson Disease * physiopathology   complications   therapy   MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article 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
• Electroencephalography methods   MeSH
• Deep Brain Stimulation * methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Brain physiopathology   diagnostic imaging   MeSH
• Subthalamic Nucleus * physiopathology   MeSH
• Parkinson Disease * therapy   physiopathology   MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Electrical stimulation involving temporal interference of two different kHz frequency sinusoidal electric fields (temporal interference (TI)) enables non-invasive deep brain stimulation, by creating an electric field that is amplitude modulated at the slow difference frequency (within the neural range), at the target brain region. OBJECTIVE: Here, we investigate temporal interference neural stimulation using square, rather than sinusoidal, electric fields that create an electric field that is pulse-width, but not amplitude, modulated at the difference frequency (pulse-width modulated temporal interference, (PWM-TI)). METHODS/RESULTS: We show, using ex-vivo single-cell recordings and in-vivo calcium imaging, that PWM-TI effectively stimulates neural activity at the difference frequency at a similar efficiency to traditional TI. We then demonstrate, using computational modelling, that the PWM stimulation waveform induces amplitude-modulated membrane potential depolarization due to the membrane's intrinsic low-pass filtering property. CONCLUSIONS: PWM-TI can effectively drive neural activity at the difference frequency. The PWM-TI mechanism involves converting an envelope amplitude-fixed PWM field to an amplitude-modulated membrane potential via the low-pass filtering of the passive neural membrane. Unveiling the biophysics underpinning the neural response to complex electric fields may facilitate the development of new brain stimulation strategies with improved precision and efficiency.

• MeSH
• Electric Stimulation MeSH
• Brain * MeSH
• Computer Simulation MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Hluboká mozková stimulace (DBS) u Parkinsonovy nemoci (PN) je standardní léčebnou metodou pozdního a intermediálního stádia. Vývoj PN je spojen s rozvojem řady non-motorických symptomů, které v klinickém obraze mnohdy dominují, a které se mohou během DBS STN významně zhoršit. Mezi „tvrdá“ kritéria, na základě kterých bývá pacient z indikačního procesu DBS obvykle vyloučen, jsou projevy atypických parkinsonských syndromů, symptomy u PN s klinickým obrazem demence, floridní deprese, opakovanými psychotickými stavy, posturální nestabilitou nebo poruchou chůze a to i přes optimálně vedenou dopaminergní léčbu. „Měkká“ vylučovací kritéria jsou spojena s vyšším biologickým věkem, výskytem mírné kognitivní poruchy, anamnézou sporadických pre-psychotických symptomů či předchozí úzkostně-depresivní epizodou. Záměrem předkládaného projektu je snaha prověřit stávající měkká indikační kritéria s cílem stanovit důležitost jednotlivých ukazatelů v predikci budoucího úspěchu DBS STN současně se snahou doplnit je o kritéria nová, opřená o multimodální předoperační nálezy.; Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a common treatment for intermediate and late stages of Parkinson’s disease (PD). The development of PD is associated with the progression of several non-motor symptoms that may predominate the clinical picture and which may substantially worsen in the course of STN DBS. Among the ‘hard’ criteria that exclude patients from the DBS program are atypical parkinsonian syndromes, dementia, actual depression, recurrent psychotic conditions, and postural instability with gait disorder despite optimal dopaminergic therapy. On the other hand, ‘soft’ exclusion criteria are associated with axial motor symptoms, higher biological age, the occurrence of mild cognitive impairment, a history of sporadic pre-psychotic symptoms, or a preceding anxiety-depressive episode. The aim of this project is to challenge the ‘soft’ criteria and to establish the importance of individual indicators in predicting the future of a STN DBS outcome as well as to define new additional criteria based on multi-modal preoperative testing.

• Keywords
• biomarkery, biomarkers, Parkinsonova nemoc, Parkinson Disease, mírná kognitivní porucha, mild cognitive impairment, řeč, subthalamic nucleus, hluboká mozková stimulace, deep brain stimulation, Oční pohyby, Eye movements, subtalamické jádro, resting state fMRI, mikroregistrace, non-motorické příznaky, axiální příznaky, DBS, resting state fMRI, speech production, microrecording, non-motor symptoms, axial symptoms, DBS,

• NML Publication type
• závěrečné zprávy o řešení grantu AZV MZ ČR

Navrhovaný projekt se zaměřuje na predikci efektu neurostimulačních metod (vagové stimulace, hluboké mozkové stimulace) u pacientů s epilepsií. V současnosti je známo, že neurostimulační metody vedou k významné redukci záchvatů cca u 50% implantovaných pacientů. Dosud však nejsme schopni pacienty, kteří profitují z implantace neurostimulátoru, identifikovat na základě jejich předimplantačních dat. Našemu kolektivu se podařilo vyvinout statistický model, který predikuje efekt vagové stimulace na základě rutinního EEG, které bylo natočeno před implantací. Tento statistický model predikuje efekt vagové stimulace s vysokou sensitivitou a specificitou. Nynější projekt vychází z tohoto statistického modelu, snahou je vytvořit obdobný model pro děti s implantovaný vagovým stimulátorem a pro pacienty s hlubokou mozkovou stimulací. Současně si rovněž uvědomujeme nutnost otestovat statistický model na externích datech, toto testování vnímáme jako zásadní pro jeho klinické využití. Projekt se zaměřuje na zlepšení péče o pacienty s farmakorezistentní epilepsií.; Proposed project is focused on the prediction of neurostimulation methods (vagal nerve stimulation, deep brain stimulation) efficacy in patients with epilepsy. Neurostimulation leads to significant seizure reduction in approximately 50% of implanted patient. By now, we are not able to identify patients who can benefit from implantation of neurostimulator pre-operatively. We managed to develop a statistic mode, which is able to predict efficacy of vagal nerve stimulation based on routine pre-implantation EEG. This statistic model predict efficacy of vagal nerve stimulation with high sensitivity and specificity. Proposed project is based on this statistic model, we would like to develop similar model for children with implanted vagal nerve stimulator and for patients with deep brain stimulation. At the same time, we realize the necessity to verify our statistic model on independent external data set, which we supposed to be crucial for the clinical application. The project is focused on the improvement of medical care in patients with drug-resistant epilepsy.

• Keywords
• epilepsie, epilepsy, neurostimulace, Neurostimulation, hluboká mozková stimulace, deep brain stimulation, stimulace vagového nervu, predikce efektu, statistický model, vagal nerve stimulation, efficacy prediction, statistic model,

• NML Publication type
• závěrečné zprávy o řešení grantu AZV MZ ČR