Temporal Evolution of Oscillations and Synchrony in GPi/Muscle Pairs in Parkinson's Disease

2005 ◽  
Vol 93 (3) ◽  
pp. 1569-1584 ◽  
Author(s):  
José M. Hurtado ◽  
Leonid L. Rubchinsky ◽  
Karen A. Sigvardt ◽  
Vicki L. Wheelock ◽  
Conrad T. E. Pappas

Both standard spectral analysis and time-dependent phase correlation techniques were applied to 27 pairs of tremor-related single units in the globus pallidus internus (GPi) and EMG of patients with Parkinson's disease (PD) undergoing stereotactic neurosurgery. Over long time-scales (∼60 s), GPi tremor-related units were statistically coherent with restricted regions of the peripheral musculature displaying tremor. The distribution of pooled coherence across all pairs supports a classification of GPi cell/EMG oscillatory pairs into coherent or noncoherent. Analysis using ∼2-s sliding windows shows that oscillatory activity in both GPi tremor units and muscles occurs intermittently over time. For brain/muscle pairs that are coherent, there is partial overlap in the times of oscillatory activity but, in most cases, no significant correlation between the times of oscillatory subepisodes in the two signals. Phase locking between coherent pairs occurs transiently; however, the phase delay is similar for different phase-locking subepisodes. Noncoherent pairs also show episodes of transient phase locking, but they occurred less frequently, and no preferred phase delay was seen across subepisodes. Tremor oscillations in pallidum and EMGs are punctuated by phase slips, which were classified as synchronizing or desynchronizing depending on their effect on phase locking. In coherent pairs, the incidence of synchronizing slips is higher than desynchronizing slips, whereas no significant difference was seen for noncoherent pairs. The results of this quantitative characterization of parkinsonian tremor provide a foundation for hypotheses about the structure and dynamical functioning of basal ganglia motor control networks involved in tremor generation.

2019 ◽  
Author(s):  
Lucas A. Koelman ◽  
Madeleine M. Lowery

AbstractThe aim of this study was to understand the relative role of autonomous oscillations and patterning by exogenous oscillatory inputs in the generation of pathological oscillatory activity within the subthalamic nucleus (STN) - external globus pallidus (GPe) network in Parkinson’s disease. A biophysically detailed model that accounts for the integration of synaptic currents and their interaction with intrinsic membrane currents in dendritic structures within the STN and GPe was developed. The model was used to investigate the development of beta-band synchrony and bursting within the STN-GPe network by changing the balance of excitation and inhibition in both nuclei, and by adding exogenous oscillatory inputs with varying phase relationships through the hyperdirect cortico-subthalamic and indirect striato-pallidal pathways. The model showed an intrinsic susceptibility to beta-band oscillations that was manifest in weak autonomously generated oscillations within the STN-GPe network and in selective amplification of exogenous beta-band synaptic inputs near the network’s endogenous oscillation frequency. The resonant oscillation frequency was determined by the net level of excitatory drive in the loop. Intrinsically generated oscillations were too weak to support a pacemaker role for the STN-GPe network, however, they were considerably amplified by sparse cortical beta inputs when their frequency range overlapped and were further amplified by striatal beta inputs that promoted anti-phase firing of the cortex and GPe, resulting in maximum transient inhibition of STN neurons. The model elucidates a mechanism of cortical patterning of the STN-GPe network through feedback inhibition whereby intrinsic susceptibility to beta-band oscillations can lead to phase locked spiking under parkinsonian conditions. These results point to resonance of endogenous oscillations with exogenous patterning of the STN-GPe network as a mechanism of pathological synchronization, and a role for the pallido-striatal feedback loop in amplifying beta oscillations.Author summaryExaggerated beta-frequency neuronal synchrony is observed throughout the basal ganglia in Parkinson’s disease and is reduced with medication and during deep brain stimulation. The power of beta-band oscillations is increasingly used as a biomarker to guide antiparkinsonian therapies. Despite their importance as a clinical target, the mechanisms by which pathological beta-band oscillations are generated are not yet clearly understood. In vitro electrophysiological recordings support a theory of enhanced phase locking of the reciprocally connected subthalamo-pallidal network to beta-band cortical inputs but this has not yet been clearly demonstrated in a model. We present a new model of the subthalamo-pallidal network consisting of biophysically detailed cell models that captures the interaction between synaptic and intrinsic currents in dendritic structures. The model shows how phase locking of subthalamic and pallidal neurons and exaggerated bursting in subthalamic neurons can arise from the interaction of these currents when the balance of excitation and inhibition is changed and how phase locking is amplified under specific phase relationships between cortical and striatal beta inputs.


2020 ◽  
Vol 132 (4) ◽  
pp. 1234-1242 ◽  
Author(s):  
Paolo Belardinelli ◽  
Ramin Azodi-Avval ◽  
Erick Ortiz ◽  
Georgios Naros ◽  
Florian Grimm ◽  
...  

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for symptomatic Parkinson’s disease (PD); the clinical benefit may not only mirror modulation of local STN activity but also reflect consecutive network effects on cortical oscillatory activity. Moreover, STN-DBS selectively suppresses spatially and spectrally distinct patterns of synchronous oscillatory activity within cortical-subcortical loops. These STN-cortical circuits have been described in PD patients using magnetoencephalography after surgery. This network information, however, is currently not available during surgery to inform the implantation strategy.The authors recorded spontaneous brain activity in 3 awake patients with PD (mean age 67 ± 14 years; mean disease duration 13 ± 7 years) during implantation of DBS electrodes into the STN after overnight withdrawal of dopaminergic medication. Intraoperative propofol was discontinued at least 30 minutes prior to the electrophysiological recordings. The authors used a novel approach for performing simultaneous recordings of STN local field potentials (LFPs) and multichannel electroencephalography (EEG) at rest. Coherent oscillations between LFP and EEG sensors were computed, and subsequent dynamic imaging of coherent sources was performed.The authors identified coherent activity in the upper beta range (21–35 Hz) between the STN and the ipsilateral mesial (pre)motor area. Coherence in the theta range (4–6 Hz) was detected in the ipsilateral prefrontal area.These findings demonstrate the feasibility of detecting frequency-specific and spatially distinct synchronization between the STN and cortex during DBS surgery. Mapping the STN with this technique may disentangle different functional loops relevant for refined targeting during DBS implantation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyoungwon Baik ◽  
Seon Myeong Kim ◽  
Jin Ho Jung ◽  
Yang Hyun Lee ◽  
Seok Jong Chung ◽  
...  

AbstractWe investigated the efficacy of donepezil for mild cognitive impairment in Parkinson’s disease (PD-MCI). This was a prospective, non-randomized, open-label, two-arm study. Eighty PD-MCI patients were assigned to either a treatment or control group. The treatment group received donepezil for 48 weeks. The primary outcome measures were the Korean version of Mini-Mental State Exam and Montreal Cognitive Assessment scores. Secondary outcome measures were the Clinical Dementia Rating, Unified Parkinson’s Disease Rating Scale part III, Clinical Global Impression scores. Progression of dementia was assessed at 48-week. Comprehensive neuropsychological tests and electroencephalography (EEG) were performed at baseline and after 48 weeks. The spectral power ratio of the theta to beta2 band (TB2R) in the electroencephalogram was analyzed. There was no significant difference in the primary and secondary outcome measures between the two groups. However, the treatment group showed a significant decrease in TB2R at bilateral frontotemporoparietal channels compared to the control group. Although we could not demonstrate improvements in the cognitive functions, donepezil treatment had a modulatory effect on the EEG in PD-MCI patients. EEG might be a sensitive biomarker for detecting changes in PD-MCI after donepezil treatment.


Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 137
Author(s):  
Tina Levstek ◽  
Sara Redenšek ◽  
Maja Trošt ◽  
Vita Dolžan ◽  
Katarina Trebušak Podkrajšek

Telomeres, which are repetitive sequences that cap the end of the chromosomes, shorten with each cell division. Besides cellular aging, there are several other factors that influence telomere length (TL), in particular, oxidative stress and inflammation, which play an important role in the pathogenesis of neurodegenerative brain diseases including Parkinson’s disease (PD). So far, the majority of studies have not demonstrated a significant difference in TL between PD patients and healthy individuals. However, studies investigating the effect of TL on the symptomatology and disease progression of PD are scarce, and thus, warranted. We analyzed TL of peripheral blood cells in a sample of 204 PD patients without concomitant autoimmune diseases and analyzed its association with several PD related phenotypes. Monochrome multiplex quantitative PCR (mmqPCR) was used to determine relative TL given as a ratio of the amount of DNA between the telomere and albumin as the housekeeping gene. We found a significant difference in the relative TL between PD patients with and without dementia, where shorter TL presented higher risk for dementia (p = 0.024). However, the correlation was not significant after adjustment for clinical factors (p = 0.509). We found no correlations between TLs and the dose of dopaminergic therapy when the analysis was adjusted for genetic variability in inflammatory or oxidative factors. In addition, TL influenced time to onset of motor complications after levodopa treatment initiation (p = 0.0134), but the association did not remain significant after adjustment for age at inclusion and disease duration (p = 0.0781). Based on the results of our study we conclude that TL contributes to certain PD-related phenotypes, although it may not have a major role in directing the course of the disease. Nevertheless, this expends currently limited knowledge regarding the association of the telomere attrition and the disease severity or motor complications in Parkinson’s disease.


2021 ◽  
Vol 11 (8) ◽  
pp. 687
Author(s):  
Valentina Varalta ◽  
Paola Poiese ◽  
Serena Recchia ◽  
Barbara Montagnana ◽  
Cristina Fonte ◽  
...  

Background: Parkinson’s disease (PD) is characterized by motor and cognitive dysfunctions that can usually be treated by physiotherapy or cognitive training, respectively. The effects of consecutive physiotherapy and cognitive rehabilitation programs on PD deficits are less investigated. Objective: We investigated the effects of 3 months of physiotherapy (physiotherapy treatment group) or consecutive physiotherapy and cognitive (physiotherapy and cognitive treatment group) rehabilitation programs on cognitive, motor, and psychological aspects in 20 PD patients. Methods: The two groups switched programs and continued rehabilitation for another 3 months. The outcomes were score improvement on cognitive (Montreal Cognitive Assessment, Frontal Assessment Battery, Trail Making Test, Verbal Phonemic Fluency, Digit Span, and Rey Auditory Verbal Learning), motor (Unified Parkinson’s Disease Rating Scale-III, Berg Balance Scale, Two-Minute Walking Test, and Time Up and Go), and psychological (Beck Depression Inventory and State-Trait Anxiety Inventory) scales. Results: Between-group comparison revealed a significant difference in functional mobility between the two rehabilitation programs. Improvements in walking abilities were noted after both interventions, but only the patients treated with consecutive training showed better performance on functional mobility and memory tasks. Conclusion: Our findings support the hypothesis that consecutive physiotherapy plus cognitive rehabilitation may have a greater benefit than physiotherapy alone in patients with PD.


2021 ◽  
pp. 000313482198903
Author(s):  
Mitsuru Ishizuka ◽  
Norisuke Shibuya ◽  
Kazutoshi Takagi ◽  
Hiroyuki Hachiya ◽  
Kazuma Tago ◽  
...  

Objective To explore the impact of appendectomy history on emergence of Parkinson’s disease (PD). Background Although there are several studies to investigate the relationship between appendectomy history and emergence of PD, the results are still controversial. Methods We performed a comprehensive electronic search of the literature (the Cochrane Library, PubMed, and the Web of Science) up to April 2020 to identify studies that had employed databases allowing comparison of emergence of PD between patients with and those without appendectomy history. To integrate the impact of appendectomy history on emergence of PD, a meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI) for the selected studies, and heterogeneity was analyzed using I2 statistics. Results Four studies involving a total of 6 080 710 patients were included in this meta-analysis. Among 1 470 613 patients with appendectomy history, 1845 (.13%) had emergences of PD during the observation period, whereas among 4 610 097 patients without appendectomy history, 6743 (.15%) had emergences of PD during the observation period. These results revealed that patients with appendectomy history and without appendectomy had almost the same emergence of PD (RR, 1.02; 95% CI, .87-1.20; P = .83; I2 = 87%). Conclusion This meta-analysis has demonstrated that there was no significant difference in emergence of PD between patients with and those without appendectomy history.


2011 ◽  
Vol 111 (2) ◽  
pp. 443-448 ◽  
Author(s):  
J. T. Groothuis ◽  
R. A. J. Esselink ◽  
J. P. H. Seeger ◽  
M. J. H. van Aalst ◽  
M. T. E. Hopman ◽  
...  

The pathophysiology of orthostatic hypotension in Parkinson's disease (PD) is incompletely understood. The primary focus has thus far been on failure of the baroreflex, a central mediated vasoconstrictor mechanism. Here, we test the role of two other possible factors: 1) a reduced peripheral vasoconstriction (which may contribute because PD includes a generalized sympathetic denervation); and 2) an inadequate plasma volume (which may explain why plasma volume expansion can manage orthostatic hypotension in PD). We included 11 PD patients with orthostatic hypotension (PD + OH), 14 PD patients without orthostatic hypotension (PD − OH), and 15 age-matched healthy controls. Leg blood flow was examined using duplex ultrasound during 60° head-up tilt. Leg vascular resistance was calculated as the arterial-venous pressure gradient divided by blood flow. In a subset of 9 PD + OH, 9 PD − OH, and 8 controls, plasma volume was determined by indicator dilution method with radiolabeled albumin (125I-HSA). The basal leg vascular resistance was significantly lower in PD + OH (0.7 ± 0.3 mmHg·ml−1·min) compared with PD − OH (1.3 ± 0.6 mmHg·ml−1·min, P < 0.01) and controls (1.3 ± 0.5 mmHg·ml−1·min, P < 0.01). Leg vascular resistance increased significantly during 60° head-up tilt with no significant difference between the groups. Plasma volume was significantly larger in PD + OH (3,869 ± 265 ml) compared with PD − OH (3,123 ± 377 ml, P < 0.01) and controls (3,204 ± 537 ml, P < 0.01). These results indicate that PD + OH have a lower basal leg vascular resistance in combination with a larger plasma volume compared with PD − OH and controls. Despite the increase in leg vascular resistance during 60° head-up tilt, PD + OH are unable to maintain their blood pressure.


2016 ◽  
Vol 46 (4) ◽  
pp. 292-300 ◽  
Author(s):  
Lauren Hirsch ◽  
Nathalie Jette ◽  
Alexandra Frolkis ◽  
Thomas Steeves ◽  
Tamara Pringsheim

Background: Parkinson's disease (PD) is a common neurodegenerative disorder. Epidemiological studies on the incidence of PD are important to better understand the risk factors for PD and determine the condition's natural history. Objective: This systematic review and meta-analysis examine the incidence of PD and its variation by age and gender. Methods: We searched MEDLINE and EMBASE for epidemiologic studies of PD from 2001 to 2014, as a previously published systematic review included studies published until 2001. Data were analyzed separately for age group and gender, and meta-regression was used to determine whether a significant difference was present between groups. Results: Twenty-seven studies were included in the analysis. Meta-analysis of international studies showed rising incidence with age in both men and women. Significant heterogeneity was observed in the 80+ group, which may be explained by methodological differences between studies. While males had a higher incidence of PD in all age groups, this difference was only statistically significant for those in the age range 60-69 and 70-79 (p < 0.05). Conclusion: PD incidence generally increases with age, although it may stabilize in those who are 80+.


Author(s):  
Jéssica A. Moratelli ◽  
Kettlyn H. Alexandre ◽  
Leonessa Boing ◽  
Alessandra Swarowsky ◽  
Clynton L. Corrêa ◽  
...  

Background: Evidence-based practices involving dance modalities found in binary (two-beat rhythm) or quaternary (four-beat rhythm) show that dance positively influences the motor aspects of disease.Aim: This randomized clinical trial aimed to analyze the effect of two dance rhythm (binary and quaternary) on the balance, gait, and mobility in individuals with Parkinson’s disease (PD). Methods: Thirty-one individuals with PD were randomized into the binary group (n = 18) and the quaternary group (n = 13). Both groups participated in different dance rhythms lasting 12 weeks, twice a week, for 45 minutes. Results: The binary group showed a significant difference in balance (p = 0.003), freezing of gait (p = 0.007), as well as in the motor aspects of MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), with emphasis on the total values with a score change of 3.23. In the quaternary group, significant differences were found in balance (p = 0.021) with a score change of -2.54 and in the motor aspects of the MDS-UPDRS Part III where the total values stood out with a change of 3.54. Discussion: When comparing the possible effects of binary and quaternary rhythms on the motor symptoms of individuals with PD, it was demonstrated that binary rhythm improved balance, freezing gait, and UPDRSIII. As for the quaternary rhythm, the benefits were in balance and the UPDRSIII. Conclusion: The binary and the quaternary rhythm dance protocols positively influenced the motor symptoms of individuals with PD after 12 weeks of intervention.


Sign in / Sign up

Export Citation Format

Share Document