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High-quality eye-tracking data are crucial in behavioral sciences and medicine. Even with a solid understanding of the literature, selecting the most suitable algorithm for a specific research project poses a challenge. Empowering applied researchers to choose the best-fitting detector for their research needs is the primary contribution of this paper. We developed a framework to systematically assess and compare the effectiveness of 13 state-of-the-art algorithms through a unified application interface. Hence, we more than double the number of algorithms that are currently usable within a single software package and allow researchers to identify the best-suited algorithm for a given scientific setup. Our framework validation on retrospective data underscores its suitability for algorithm selection. Through a detailed and reproducible step-by-step workflow, we hope to contribute towards significantly improved data quality in scientific experiments.
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Algoritmos , Tecnologia de Rastreamento Ocular , Humanos , Software , Confiabilidade dos Dados , Movimentos Oculares/fisiologia , Reprodutibilidade dos TestesRESUMO
Parkinson's disease (PD) is characterized by the disruption of repetitive, concurrent and sequential motor actions due to compromised timing-functions principally located in cortex-basal ganglia (BG) circuits. Increasing evidence suggests that motor impairments in untreated PD patients are linked to an excessive synchronization of cortex-BG activity at beta frequencies (13-30 Hz). Levodopa and subthalamic nucleus deep brain stimulation (STN-DBS) suppress pathological beta-band reverberation and improve the motor symptoms in PD. Yet a dynamic tuning of beta oscillations in BG-cortical loops is fundamental for movement-timing and synchronization, and the impact of PD therapies on sensorimotor functions relying on neural transmission in the beta frequency-range remains controversial. Here, we set out to determine the differential effects of network neuromodulation through dopaminergic medication (ON and OFF levodopa) and STN-DBS (ON-DBS, OFF-DBS) on tapping synchronization and accompanying cortical activities. To this end, we conducted a rhythmic finger-tapping study with high-density EEG-recordings in 12 PD patients before and after surgery for STN-DBS and in 12 healthy controls. STN-DBS significantly ameliorated tapping parameters as frequency, amplitude and synchrony to the given auditory rhythms. Aberrant neurophysiologic signatures of sensorimotor feedback in the beta-range were found in PD patients: their neural modulation was weaker, temporally sluggish and less distributed over the right cortex in comparison to controls. Levodopa and STN-DBS boosted the dynamics of beta-band modulation over the right hemisphere, hinting to an improved timing of movements relying on tactile feedback. The strength of the post-event beta rebound over the supplementary motor area correlated significantly with the tapping asynchrony in patients, thus indexing the sensorimotor match between the external auditory pacing signals and the performed taps. PD patients showed an excessive interhemispheric coherence in the beta-frequency range during the finger-tapping task, while under DBS-ON the cortico-cortical connectivity in the beta-band was normalized. Ultimately, therapeutic DBS significantly ameliorated the auditory-motor coupling of PD patients, enhancing the electrophysiological processing of sensorimotor feedback-information related to beta-band activity, and thus allowing a more precise cued-tapping performance.
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Ritmo beta , Sincronização Cortical , Estimulação Encefálica Profunda , Dedos , Levodopa , Córtex Motor , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Estimulação Encefálica Profunda/métodos , Idoso , Ritmo beta/fisiologia , Córtex Motor/fisiopatologia , Córtex Motor/fisiologia , Sincronização Cortical/fisiologia , Levodopa/uso terapêutico , Núcleo Subtalâmico/fisiopatologia , Antiparkinsonianos/uso terapêutico , EletroencefalografiaRESUMO
High-frequency, conventional deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) is usually applied bilaterally under the assumption of additive effects due to interhemispheric crosstalk. Theta burst stimulation (TBS-DBS) represents a new patterned stimulation mode with 5 Hz interburst and 200 Hz intraburst frequency, whose stimulation effects in a bilateral mode compared to unilateral are unknown. This single-center study evaluated acute motor effects of the most affected, contralateral body side in 17 PD patients with unilateral subthalamic TBS-DBS and 11 PD patients with bilateral TBS-DBS. Compared to therapy absence, both unilateral and bilateral TBS-DBS significantly improved (p < 0.05) lateralized Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) scores. Bilateral TBS-DBS revealed only slight, but not significant additional effects in comparison to unilateral TBS-DBS on total lateralized motor scores, but on the subitem lower limb rigidity. These results indicate that bilateral TBS-DBS has limited additive beneficial effects compared to unilateral TBS-DBS in the short term.
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The parkinsonian gait disorder and freezing of gait are therapeutically demanding symptoms with considerable impact on quality of life. The aim of this study was to assess the role of subthalamic and nigral neurons in the parkinsonian gait control using intraoperative microelectrode recordings of basal ganglia neurons during a supine stepping task. Twelve male patients (56 ± 7 years) suffering from moderate idiopathic Parkinson's disease (disease duration 10 ± 3 years, Hoehn and Yahr stage 2), undergoing awake neurosurgery for deep brain stimulation, participated in the study. After 10 s resting, stepping at self-paced speed for 35 s was followed by short intervals of stepping in response to random 'start' and 'stop' cues. Single- and multi-unit activity was analysed offline in relation to different aspects of the stepping task (attentional 'start' and 'stop' cues, heel strikes, stepping irregularities) in terms of firing frequency, firing pattern and oscillatory activity. Subthalamic nucleus and substantia nigra neurons responded to different aspects of the stepping task. Of the subthalamic nucleus neurons, 24% exhibited movement-related activity modulation as an increase of the firing rate, suggesting a predominant role of the subthalamic nucleus in motor aspects of the task, while 8% of subthalamic nucleus neurons showed a modulation in response to the attentional cues. In contrast, responsive substantia nigra neurons showed activity changes exclusively associated with attentional aspects of the stepping task (15%). The firing pattern of subthalamic nucleus neurons revealed gait-related firing regularization and a drop of beta oscillations during the stepping performance. During freezing episodes instead, there was a rise of beta oscillatory activity. This study shows for the first time specific, task-related subthalamic nucleus and substantia nigra single-unit activity changes during gait-like movements in humans with differential roles in motor and attentional control of gait. The emergence of perturbed firing patterns in the subthalamic nucleus indicates a disrupted information transfer within the gait network, resulting in freezing of gait.
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Estimulação Encefálica Profunda , Transtornos Neurológicos da Marcha , Doença de Parkinson , Transtornos Parkinsonianos , Humanos , Masculino , Estimulação Encefálica Profunda/métodos , Marcha/fisiologia , Transtornos Neurológicos da Marcha/etiologia , Neurônios/fisiologia , Doença de Parkinson/terapia , Qualidade de Vida , Substância NegraRESUMO
The aim of this study was to assess the effects of novel stimulation algorithms of deep brain stimulation (short pulse and directional stimulation) in the ventrointermediate thalamus and posterior subthalamic area (VIM/PSA-DBS) on tremor in Parkinson's disease (PD) and to compare the effects with those in essential tremor (ET). We recruited six PD patients (70.8 ± 10.4 years) and seven ET patients (64.4 ± 9.9 years) with implanted VIM/PSA-DBS in a stable treatment condition (> 3 months postoperatively). Tremor severity and ataxia were assessed in four different stimulation conditions in a randomized order: DBS switched off (STIM OFF), omnidirectional stimulation with 60 µs (oDBS60), omnidirectional stimulation with 30 µs (oDBS30), directional stimulation at the best segment with 60 µs (dDBS60). In both patient groups, all three DBS stimulation modes reduced the total tremor score compared to STIM OFF, whereas stimulation-induced ataxia was reduced by oDBS30 and partially by dDBS60 compared to oDBS60. Tremor reduction was more pronounced in PD than in ET due to a limited DBS effect on intention and action-specific drawing tremor in ET. In PD and ET tremor, short pulse or directional VIM/PSA-DBS is an effective and well tolerated therapeutic option.Trial registration: The study was registered in the DRKS (ID DRKS00025329, 18.05.2021, German Clinical Trials Register, DRKS-Deutsches Register Klinischer Studien).
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Estimulação Encefálica Profunda , Tremor Essencial , Doença de Parkinson , Ataxia , Estimulação Encefálica Profunda/efeitos adversos , Tremor Essencial/etiologia , Tremor Essencial/terapia , Humanos , Masculino , Doença de Parkinson/etiologia , Doença de Parkinson/terapia , Antígeno Prostático Específico , Tálamo/fisiologia , Resultado do Tratamento , Tremor/terapiaRESUMO
BACKGROUND: Freezing of gait (FOG) is among the most common and disabling symptoms of Parkinson's disease (PD). Studies show that deep brain stimulation (DBS) of the subthalamic nucleus (STN) can reduce FOG severity. However, there is uncertainty about pathways that need to be modulated to improve FOG. OBJECTIVE: To investigate whether STN-DBS effectively reduces FOG postoperatively and whether structural connectivity of the stimulated tissue explains variance of outcomes. METHODS: We investigated 47 patients with PD and preoperative FOG. Freezing prevalence and severity was primarily assessed using the Freezing of Gait Questionnaire (FOG-Q). In a subset of 18 patients, provoked FOG during a standardized walking course was assessed. Using a publicly available model of basal-ganglia pathways we determined stimulation-dependent connectivity associated with postoperative changes in FOG. A region-of-interest analysis to a priori defined mesencephalic regions was performed using a disease-specific normative connectome. RESULTS: Freezing of gait significantly improved six months postoperatively, marked by reduced frequency and duration of freezing episodes. Optimal stimulation volumes for improving FOG structurally connected to motor areas, the prefrontal cortex and to the globus pallidus. Stimulation of the lenticular fasciculus was associated with worsening of FOG. This connectivity profile was robust in a leave-one-out cross-validation. Subcortically, stimulation of fibers crossing the pedunculopontine nucleus and the substantia nigra correlated with postoperative improvement. CONCLUSION: STN-DBS can alleviate FOG severity by modulating specific pathways structurally connected to prefrontal and motor cortices. More differentiated FOG assessments may allow to differentiate pathways for specific FOG subtypes in the future.
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Estimulação Encefálica Profunda , Transtornos Neurológicos da Marcha , Doença de Parkinson , Núcleo Subtalâmico , Marcha/fisiologia , Transtornos Neurológicos da Marcha/complicações , Transtornos Neurológicos da Marcha/terapia , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiologiaRESUMO
INTRODUCTION: The preoperative evaluation of Parkinson's Disease (PD) patients for subthalamic nucleus deep brain stimulation (STN-DBS) includes the assessment of the neuropsychological status of the patient. A widely used preoperative test is the Mattis Dementia rating scale (MDRS). However, the Montreal cognitive assessment (MoCA) has also been proven to be a sensitive, time-sparing tool with high diagnostic validity in PD. We evaluate the utility of the MoCA as a preoperative screening test for PD patients undergoing bilateral STN-DBS. METHODS: In this single-centre, retrospective study, we analysed pre- and postoperative assessments of MoCA, MDRS, Movement disorder society-Unified PD Rating Scale-motor examination, PD Questionnaire-39 and levodopa equivalent daily dose. Longitudinal outcome changes were analysed using paired t-test, Pearson's correlation coefficient, linear regression and CHAID (chi-square automatic interaction detector) regression tree model. RESULTS: Clinical motor and cognitive scores of 59 patients (61.05±7.73 years, 24 females) were analysed. The MoCA, but not the MDRS, identified significant postoperative cognitive decline in PD patients undergoing STN-DBS. The preoperative MoCA score correlated with postoperative quality of life improvement, whereas the MDRS did not. PD patients with a MoCA score ≤ 23 points had a significant decline of quality of life after DBS surgery compared to patients > 23 points. CONCLUSION: This study identifies the MoCA as an alternative test within the preoperative evaluation of PD patients for the detection of neuropsychological deficits and prediction of the postoperative improvement of quality of life.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Feminino , Humanos , Testes de Estado Mental e Demência , Doença de Parkinson/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Núcleo Subtalâmico/fisiologia , Resultado do TratamentoRESUMO
Background: The preferable position of Deep Brain Stimulation (DBS) electrodes is proposed to be located in the dorsolateral subthalamic nucleus (STN) to improve general motor performance. The optimal DBS electrode localization for the post-operative improvement of balance and gait is unknown. Methods: In this single-center, retrospective analyses, 66 Parkinson's disease (PD) patients (24 female, age 63 ± 7 years) were assessed pre- and post-operatively (8.45 ± 4.2 months after surgery) by using MDS-UPDRS, freezing of gait (FoG) score, Giladi's gait and falls questionnaire and Berg balance scale. The clinical outcome was related to the DBS electrode coordinates in x, y, z plane as revealed by image-based reconstruction (SureTune™). Binomial generalized linear mixed models with fixed-effect variables electrode asymmetry, parkinsonian subtype, medication, age class and clinical DBS induced changes were analyzed. Results: Subthalamic nucleus-deep brain stimulation improved all motor, balance and FoG scores in MED OFF condition, however there were heterogeneous results in MED ON condition. DBS electrode reconstructed coordinates impacted the responsiveness of axial symptoms. FoG and balance responders showed slightly more medially located STN electrode coordinates and less medio-lateral asymmetry of the electrode reconstructed coordinates across hemispheres compared to non-responders. Conclusion: Deep brain stimulation electrode reconstructed coordinates, particularly electrode asymmetry on the medio-lateral axis affected the post-operative responsiveness of balance and FoG symptoms in PD patients.
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Background: Freezing of gait (FoG) is a disabling burden for Parkinson's disease (PD) patients with poor response to conventional therapies. Combined deep brain stimulation of the subthalamic nucleus and substantia nigra (STN+SN DBS) moved into focus as a potential therapeutic option to treat the parkinsonian gait disorder and refractory FoG. The mechanisms of action of DBS within the cortical-subcortical-basal ganglia network on gait, particularly at the cortical level, remain unclear. Methods: Twelve patients with idiopathic PD and chronically-implanted DBS electrodes were assessed on their regular dopaminergic medication in a standardized stepping in place paradigm. Patients executed the task with DBS switched off (STIM OFF), conventional STN DBS and combined STN+SN DBS and were compared to healthy matched controls. Simultaneous high-density EEG and kinematic measurements were recorded during resting-state, effective stepping, and freezing episodes. Results: Clinically, STN+SN DBS was superior to conventional STN DBS in improving temporal stepping variability of the more affected leg. During resting-state and effective stepping, the cortical activity of PD patients in STIM OFF was characterized by excessive over-synchronization in the theta (4-8 Hz), alpha (9-13 Hz), and high-beta (21-30 Hz) band compared to healthy controls. Both active DBS settings similarly decreased resting-state alpha power and reduced pathologically enhanced high-beta activity during resting-state and effective stepping compared to STIM OFF. Freezing episodes during STN DBS and STN+SN DBS showed spectrally and spatially distinct cortical activity patterns when compared to effective stepping. During STN DBS, FoG was associated with an increase in cortical alpha and low-beta activity over central cortical areas, while with STN+SN DBS, an increase in high-beta was prominent over more frontal areas. Conclusions: STN+SN DBS improved temporal aspects of parkinsonian gait impairment compared to conventional STN DBS and differentially affected cortical oscillatory patterns during regular locomotion and freezing suggesting a potential modulatory effect on dysfunctional cortical-subcortical communication in PD.
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Gait disorders in patients with Parkinson's disease (PD) impact their mobility and self-dependence. Gait training and dual-task (DT)-training improve gait quality. This study aims to assess the feasibility of a specific, gradually intensified DT-training for PD patients with a special focus on gait performance under single task (ST) and DT conditions. Correlations to Freezing of Gait (FoG) were examined. 17 PD patients (70.1 ± 7.4 years, H&Y Stadium 2-3, FoG-Q 9.0 ± 5.5) participated in a four-week DT-training (1x/week, 60 min) with progressively increasing task difficulty and number of tasks. Gait performance (spatiotemporal parameters) was assessed during ST and DT conditions. The training improved DT gait performance, especially gait velocity + 0.11 m/s; (F(2,16) = 7.163; p = .0171; η2part = .309) and step length (+ 5.73 cm). Also, physical well-being and absolved walking distance improved significantly. Correlation analyses of the FoG score at baseline with relative change of gait metrics post-training revealed significant correlations with training-induced changes of step length and improvement of gait velocity. Overall, the developed DT-training was feasible and effective. Further studies should examine the long-term benefits and the optimal setting to achieve the highest impact. The study was registered in the DRKS (ID DRKS00018084, 23.1.20).
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Terapia por Exercício/métodos , Transtornos Neurológicos da Marcha/reabilitação , Marcha/fisiologia , Doença de Parkinson/reabilitação , Desempenho Psicomotor/fisiologia , Idoso , Cognição , Estudos de Viabilidade , Feminino , Análise da Marcha/estatística & dados numéricos , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Teste de Stroop , Resultado do TratamentoRESUMO
BACKGROUND: Gait disturbances and balance remain challenging issues in Parkinsonian patients (PD) with deep brain stimulation (DBS). Short pulse deep brain stimulation (spDBS) increases the therapeutic window in PD patients, yet the effect on gait and postural symptoms remains unknown. OBJECTIVE: We assessed the efficacy of spDBS compared to conventional DBS (cDBS) within the subthalamic nucleus (STN) on Parkinsonian gait. METHODS: The study was a single-centre, randomized, double-blind, clinical short-term trial. 20 PD patients were studied postoperatively in three different conditions (DBS stimulation switched off (off DBS), spDBS with 40µs pulse width, cDBS with 60µs pulse width) on regular medication. The primary endpoint was the relative difference of gait velocity at self-paced speed during quantitative gait analysis between stimulation conditions. Secondary endpoints were changes of further measures of quantitative gait analysis, Ziegler course, Berg balance scale, FOG questionnaire, MDS-UPDRS, PDQ-39, and HADS. Mixed-model analysis and post-hoc t-tests were performed. RESULTS: Both spDBS and cDBS improved gait velocity at self-paced speed compared to off DBS, however, there was no significant difference between both stimulation modes. Still, 40% of the patients preferred spDBS over cDBS subjectively. Both stimulation modes were equally effective in improving secondary endpoints of gait, balance, motor and non-motor performances. CONCLUSION: The use of spDBS and cDBS is equally effective in improving gait and balance in PD and might be beneficial in specified cohorts of PD patients.
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Estimulação Encefálica Profunda , Transtornos Neurológicos da Marcha , Transtornos Parkinsonianos , Estimulação Encefálica Profunda/métodos , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/terapia , Humanos , Transtornos Parkinsonianos/fisiopatologia , Transtornos Parkinsonianos/terapia , Núcleo Subtalâmico/fisiologia , Resultado do TratamentoRESUMO
Background: The Parkinsonian [i.e., Parkinson's disease (PD)] gait disorder represents a therapeutical challenge with residual symptoms despite the use of deep brain stimulation of the subthalamic nucleus (STN DBS) and medical and rehabilitative strategies. The aim of this study was to assess the effect of different DBS modes as combined stimulation of the STN and substantia nigra (STN+SN DBS) and environmental rehabilitative factors as footwear on gait kinematics. Methods: This single-center, randomized, double-blind, crossover clinical trial assessed shod and unshod gait in patients with PD with medication in different DBS conditions (i.e., STIM OFF, STN DBS, and STN+SN DBS) during different gait tasks (i.e., normal gait, fast gait, and gait during dual task) and compared gait characteristics to healthy controls. Notably, 15 patients participated in the study, and 11 patients were analyzed after a dropout of four patients due to DBS-induced side effects. Results: Gait was modulated by both factors, namely, footwear and DBS mode, in patients with PD. Footwear impacted gait characteristics in patients with PD similarly to controls with longer step length, lower cadence, and shorter single-support time. Interestingly, DBS exerted specific effects depending on gait tasks with increased cognitive load. STN+SN DBS was the most efficient DBS mode compared to STIM OFF and STN DBS with intense effects as step length increment during dual task. Conclusion: The PD gait disorder is a multifactorial symptom, impacted by environmental factors as footwear and modulated by DBS. DBS effects on gait were specific depending on the gait task, with the most obvious effects with STN+SN DBS during gait with increased cognitive load.
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Abnormally sustained beta-frequency synchronisation between the motor cortex and subthalamic nucleus (STN) is associated with motor symptoms in Parkinson's disease (PD). It is currently unclear whether STN neurons have a preference for beta-frequency input (12-35 Hz), rather than cortical input at other frequencies, and how such a preference would arise following dopamine depletion. To address this question, we combined analysis of cortical and STN recordings from awake human PD patients undergoing deep brain stimulation surgery with recordings of identified STN neurons in anaesthetised rats. In these patients, we demonstrate that a subset of putative STN neurons is strongly and selectively sensitive to magnitude fluctuations of cortical beta oscillations over time, linearly increasing their phase-locking strength with respect to the full range of instantaneous amplitude in the beta-frequency range. In rats, we probed the frequency response of STN neurons in the cortico-basal-ganglia-network more precisely, by recording spikes evoked by short bursts of cortical stimulation with variable frequency (4-40 Hz) and constant amplitude. In both healthy and dopamine-depleted rats, only beta-frequency stimulation led to a progressive reduction in the variability of spike timing through the stimulation train. This suggests, that the interval of beta-frequency input provides an optimal window for eliciting the next spike with high fidelity. We hypothesize, that abnormal activation of the indirect pathway, via dopamine depletion and/or cortical stimulation, could trigger an underlying sensitivity of the STN microcircuit to beta-frequency input.
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Comportamento Animal/fisiologia , Ritmo beta/fisiologia , Estimulação Encefálica Profunda , Córtex Motor/fisiopatologia , Doença de Parkinson/fisiopatologia , Animais , Estimulação Encefálica Profunda/métodos , Neurônios/fisiologia , Doença de Parkinson/terapia , Ratos , Núcleo Subtalâmico/fisiologia , Núcleo Subtalâmico/fisiopatologiaRESUMO
Changes in personality are one of the main concerns Parkinson's disease (PD) patients raise when facing the decision to undergo neurosurgery for deep brain stimulation (DBS) of the subthalamic nucleus (STN). While clinical instruments for monitoring functional changes following DBS surgery are well-established in the daily therapeutic routine, personality issues are far less systematically encompassed. Moreover, while sex disparities in the outcomes of STN-DBS therapy have been reported, little is known about the different effects that DBS treatment may have on mood and personality traits in female and male patients. To this aim, the effect of STN-DBS on personality traits was assessed in 46 PD patients (12 women and 34 men) by means of the Freiburg Personality Inventory. The Becks Depression Inventory (BDI-I) and the Parkinson's Disease Questionnaire were used to evaluate patients' level of depression and quality of life (QoL). Patients completed the questionnaires a few days before, within the first year, and 2 years after surgery. The 12 personality traits defined by the FPI-R questionnaire did not change significantly after STN-DBS surgery (p = 0.198). Women declared higher depression scores through all study stages (p = 0.009), but also showed a stronger QoL amelioration after surgery than male patients (p = 0.022). The BDI-I scores of female patients clearly correlated with their levodopa equivalent daily dose (LEDD; r = 0.621, p = 0.008). Remarkably, in both male and female patients, higher pre-operative LEDDs were related to worse post-operative QoL scores (p = 0.034). These results mitigate the concerns about systematic personality changes due to STN-DBS treatment in PD patients and encourage an early DBS approach, before severe levodopa-induced sequelae may irreparably compromise the patients' QoL. In the future, more focus should lie on sex-related effects, since female patients seem to profit more than male patients from STN-DBS, in terms of reduced depressive symptoms associated with a reduction of the LEDD and amelioration of QoL. These aspects may help to redress the sex imbalance in PD patients treated with DBS, given that women are still strongly under-represented.
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BACKGROUND AND OBJECTIVES: The purpose of this study was to assess efficacy and safety of a new patterned theta burst stimulation algorithm of DBS with the aim of expanding the therapeutic window and clinical benefit in PD. METHODS: In this single-center, randomized, double-blind, clinical short-term trial, unilateral conventional subthalamic DBS was compared with unilateral patterned stimulation algorithms with intraburst high- or low-frequency theta burst stimulation in 17 PD patients. RESULTS: There were no serious adverse events with theta burst stimulation. During monopolar review, conventional subthalamic DBS and high-frequency theta burst stimulation were comparable, but low-frequency theta burst stimulation differed by requiring higher stimulation amplitudes for symptom reduction, but a larger therapeutic window. High- and low-frequency theta burst stimulation with adapted stimulation amplitude were effective in PD symptom reduction with differential effects on akinesia and tremor, depending on the theta burst stimulation mode. CONCLUSIONS: Theta burst stimulation is a safe and effective stimulation mode with potential future application opportunities. © 2020 International Parkinson and Movement Disorder Society.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/terapia , Estimulação Magnética Transcraniana , Resultado do Tratamento , TremorRESUMO
OBJECTIVES: Dysphagia is a frequent and highly relevant symptom in Parkinson's disease (PD) due to high associated morbidity and mortality. To compare the effect of simultaneous stimulation of the subthalamic nucleus (STN) and substantia nigra (SNr) with conventional STN-stimulation on swallowing function in Parkinson's disease. METHODS: In this controlled, randomized, double-blind, cross-over clinical trial, 15 PD patients were assessed with DBS switched off (STIM OFF), STN-DBS, STN + SNr-DBS. Patients and 32 age-matched healthy controls were examined clinically and by flexible-endoscopic evaluation of swallowing (FEES) to evaluate the swallowing function. The primary endpoint was the assessment of residues, secondary endpoints were penetration/aspiration, leakage, retained pharyngeal secretions, drooling, and assessments of the patient's self-perception of swallowing on a visual analog scale. RESULTS: Compared with healthy controls PD patients showed significantly more pharyngeal residues in STIM OFF and both DBS modes. Residues or aspiration events were found in 80% of the patients under STN-stimulation. Simultaneous STN + SNr-stimulation had no additional positive effect on objective dysphagia and self-reported swallowing function compared to STN-DBS. INTERPRETATION: Simultaneous STN + SNr-stimulation seems to have no additional beneficial effects on dysphagia when compared with conventional STN-stimulation, but did not deteriorate the swallowing function. If STN + SNr-stimulation is planned to be applied for the improvement of axial symptoms and gait disorders in PD patients, it can be considered safe in terms of dysphagia.
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Estimulação Encefálica Profunda , Transtornos de Deglutição/terapia , Doença de Parkinson/terapia , Substância Negra , Núcleo Subtalâmico , Idoso , Estudos Cross-Over , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/métodos , Transtornos de Deglutição/etiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Doença de Parkinson/complicaçõesRESUMO
BACKGROUND: Deep brain stimulation (DBS) within the pallidum represents an effective and well-established treatment for isolated dystonia. However, clinical outcome after surgery may be variable with limited response in 10-25% of patients. The effect of lead location on clinical improvement is still under debate. OBJECTIVE: To identify stimulated brain regions associated with the most beneficial clinical outcome in dystonia patients. METHODS: 18 patients with cervical and generalized dystonia with chronic DBS of the internal pallidum were investigated. Patients were grouped according to their clinical improvement into responders, intermediate responders and non-responders. Magnetic resonance and computed tomography images were co-registered, and the volume of tissue activated (VTA) with respect to the pallidum of individual patients was analysed. RESULTS: VTAs in responders (n = 11), intermediate responders (n = 3) and non-responders (n = 4) intersected with the posterior internal (GPi) and external (GPe) pallidum and the subpallidal area. VTA heat maps showed an almost complete overlap of VTAs of responders, intermediate and non-responders. VTA coverage of the GPi was not higher in responders. In contrast, VTAs of intermediate and non-responders covered the GPi to a significantly larger extent in the left hemisphere (p < 0.01). CONCLUSIONS: DBS of ventral parts of the posterior GPi, GPe and the adjacent subpallidal area containing pallidothalamic output projections resulted in favourable clinical effects. Of note, non-responders were also stimulated within the same area. This suggests that factors other than mere lead location (e.g., clinical phenotype, genetic background) have determined clinical outcome in the present cohort.
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Estimulação Encefálica Profunda , Distúrbios Distônicos/terapia , Eletrodos Implantados , Globo Pálido/anatomia & histologia , Avaliação de Resultados em Cuidados de Saúde , Torcicolo/terapia , Adolescente , Adulto , Idoso , Estimulação Encefálica Profunda/métodos , Distúrbios Distônicos/diagnóstico por imagem , Distúrbios Distônicos/genética , Feminino , Globo Pálido/diagnóstico por imagem , Globo Pálido/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Torcicolo/diagnóstico por imagem , Torcicolo/genética , Adulto JovemRESUMO
Beta frequency oscillations (15 to 35 Hz) in cortical and basal ganglia circuits become abnormally synchronized in Parkinson's disease (PD). How excessive beta oscillations emerge in these circuits is unclear. We addressed this issue by defining the firing properties of basal ganglia neurons around the emergence of cortical beta bursts (ß bursts), transient (50 to 350 ms) increases in the beta amplitude of cortical signals. In PD patients, the phase locking of background spiking activity in the subthalamic nucleus (STN) to frontal electroencephalograms preceded the onset and followed the temporal profile of cortical ß bursts, with conditions of synchronization consistent within and across bursts. Neuronal ensemble recordings in multiple basal ganglia structures of parkinsonian rats revealed that these dynamics were recapitulated in STN, but also in external globus pallidus and striatum. The onset of consistent phase-locking conditions was preceded by abrupt phase slips between cortical and basal ganglia ensemble signals. Single-unit recordings demonstrated that ensemble-level properties of synchronization were not underlain by changes in firing rate but, rather, by the timing of action potentials in relation to cortical oscillation phase. Notably, the preferred angle of phase-locked action potential firing in each basal ganglia structure was shifted during burst initiation, then maintained stable phase relations during the burst. Subthalamic, pallidal, and striatal neurons engaged and disengaged with cortical ß bursts to different extents and timings. The temporal evolution of cortical and basal ganglia synchronization is cell type-selective, which could be key for the generation/ maintenance of excessive beta oscillations in parkinsonism.
Assuntos
Gânglios da Base/fisiopatologia , Ritmo beta/fisiologia , Córtex Cerebral/fisiopatologia , Doença de Parkinson/fisiopatologia , Potenciais de Ação , Idoso , Animais , Eletroencefalografia , Feminino , Humanos , Masculino , Neurônios/fisiologia , Ratos , Fatores de TempoRESUMO
It is well documented that there is a strong relationship between gait asymmetry and the freezing of gait (FOG) in Parkinson's Disease. The purpose of this pilot study was to find a "virtual reality (VR)- based" gait manipulation strategy to improve gait symmetry by equalizing step length. Fifteen male PD patients (mean age of 67.6 years) with FOG were assessed on a GAITRite® walkway. Natural gait was compared with walking conditions during "VR-based" gait modulation tasks that aimed at equalizing gait symmetry using visual or proprioceptive signals. Compared to natural gait, VR manipulation tasks significantly increased step width and swing time variability for both body sides. Within the VR conditions, only the task with "proprioceptive-visual dissociation" by artificial backward shifting of the foot improved spatial asymmetry significantly with comparable step lengths of both sides. Specific, hypothesis-driven VR tasks represent an efficient tool to manipulate gait features as gait symmetry in PD potentially preventing FOG. This pilot study offers promising "VR-based" approaches for rehabilitative training strategies to achieve gait symmetry and prevent FOG.
Assuntos
Marcha/fisiologia , Doença de Parkinson/fisiopatologia , Realidade Virtual , Idoso , Simulação por Computador , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
BACKGROUND: Stimulation of the subthalamic area (STA) is an effective treatment in essential tremor patients, but limited by stimulation induced adverse effects. The aim of this study was to determine the spatial distribution of stimulus related tremor suppression, ataxia induction and paresthesia of the upper limb in the subthalamic area (STA) of essential tremor patients. METHODS: We recruited eight patients with essential tremor in a stable postoperative condition (>3 months after surgery). Stimulation-induced effects were assessed with suprathreshold stimulation. Tremor severity was assessed with the Fahn-Tolosa-Marin tremor rating scale (TRS) and cerebellar impairment was evaluated using the international cooperative ataxia rating scale (ICARS). Patients rated paresthesia intensity with a visual analog scale. Linear regression analysis was performed to associate stereotactic coordinates with tremor, ataxia and paresthesia. RESULTS: Suprathreshold stimulation significantly decreased tremor and elicited ataxia and paresthesia in all patients (Pâ¯<â¯0.001). Tremor rating scale (TRS) total score was positively correlated with y-coordinates (râ¯=â¯0.44, Pâ¯<â¯0.05), i.e. anterior stimulation sites were more effective to suppress tremor. Concerning adverse effects, ataxia induction was positively correlated with z-coordinates almost reaching statistical significance (râ¯=â¯0.50, Pâ¯=â¯0.07), i.e. inferior stimulation sites elicit stronger ataxia. Furthermore, paresthesia was positively correlated with y-coordinates (râ¯=â¯0.66; Pâ¯<â¯0.01) and to a lesser degree with x-coordinates (râ¯=â¯0.32; Pâ¯=â¯0.08), i.e. posterior and lateral stimulation sites within the STA caused more paresthesia. CONCLUSION: Antero-dorso-medial stimulation site in the STA were associated with less tremor and adverse effects in our small single-center cohort of ET patients with thalamic DBS.