scholarly journals Effect of Stimulation of Subthalamic Nucleus onbeta Oscillations and Thalamus Tremor Activity in aComputational Model of Parkinson’s Disease  

Author(s):  
Seyed-Mojtaba Alavi ◽  
Amin Mirzaei ◽  
Alireza Valizadeh ◽  
Reza Ebrahimpour

Abstract Parkinson’s disease (PD) is associated with abnormal b band oscillations (13-30 Hz) in the cortico-basal ganglia circuits.Abnormally increased striato-pallidal inhibition and strengthening the synaptic coupling between subthalamic nucleus (STN)and globus pallidus externa (GPe), due to the loss of dopamine, are accounted as the potential sources of b oscillations in thebasal ganglia. Deep brain stimulation (DBS) of the basal ganglia subregions is known as a way to reduce the pathological boscillations and motor deficits related to PD. Despite the success of the DBS, its underlying mechanism is poorly understoodand, there is controversy about the inhibitory or excitatory role of the DBS in the literature. Here, we utilized a computationalnetwork model of basal ganglia which consists STN, GPe, globus pallidus interna (GPi), and thalamus neuronal population.This model can capture healthy and pathological b oscillations as what has been observed in experimental studies. Using thismodel, we investigated the effect of DBS to understand whether its effect is excitatory or inhibitory. Our results show that theexcitatory DBS (EDBS) is able to quench the pathological synchrony and b oscillations, while, applying inhibitory DBS (IDBS)failed to quench the PD signs. In addition, the EDBS ameliorated the thalamic activity related to tremor in the model, while,the IDBS outperformed. However, with the help of the model results, we conclude that the effect of the DBS on its target isexcitatory

2020 ◽  
Author(s):  
Seyed Mojtaba Alavi ◽  
Amin Mirzaei ◽  
Alireza Valizadeh ◽  
Reza Ebrahimpour

Parkinson's disease (PD) is associated with abnormal β band oscillations (13-30 Hz) in the cortico-basal ganglia circuits. Abnormally increased striato-pallidal inhibition and strengthening the synaptic coupling between subthalamic nucleus (STN) and globus pallidus externa (GPe), due to the loss of dopamine, are considered as the potential sources of β oscillations in the basal ganglia. Deep brain stimulation (DBS) of the basal ganglia subregions is known as a way to reduce the pathological β oscillations and motor deficits related to PD. Despite the success of the DBS, its underlying mechanism is poorly understood and, there is controversy about the inhibitory or excitatory role of the DBS in the literature. Here, we utilized a computational network model of basal ganglia which consists of STN, GPe, globus pallidus interna (GPi), and thalamic neuronal population. This model can reproduce healthy and pathological β oscillations similar to what has been observed in experimental studies. Using this model, we investigated the effect of DBS to understand whether its effect is excitatory or inhibitory. Our results show that the excitatory DBS (EDBS) is able to quench the pathological synchrony and β oscillations, while, applying inhibitory DBS (IDBS) failed to quench the PD signs. In light of simulation results, we conclude that the effect of the DBS on its target is excitatory.


2017 ◽  
Author(s):  
Amin Mirzaei ◽  
Arvind Kumar ◽  
Daniel Leventhal ◽  
Nicolas Mallet ◽  
Ad Aertsen ◽  
...  

AbstractBrief epochs of beta oscillations have been implicated in sensorimotor control in the basal ganglia of task-performing healthy animals. However, which neural processes underlie their generation and how they are affected by sensorimotor processing remains unclear. To determine the mechanisms underlying transient beta oscillations in the local field potential (LFP), we combined computational modeling of the subthalamo-pallidal network for the generation of beta oscillations with realistic stimulation patterns derived from single unit data. The single unit data were recorded from different basal ganglia subregions in rats performing a cued choice task. In the recordings we found distinct firing patterns in the striatum, globus pallidus and subthalamic nucleus related to sensory and motor events during the behavioral task. Using these firing patterns to generate realistic inputs to our network model lead to transient beta oscillations with the same time course as the rat LFP data. In addition, our model can account for further non-intuitive aspects of beta modulation, including beta phase resets following sensory cues and correlations with reaction time. Overall, our model can explain how the combination of temporally regulated sensory responses of the subthalamic nucleus, ramping activity of the subthalamic nucleus, and movement-related activity of the globus pallidus, leads to transient beta oscillations during behavior.Significance StatementTransient beta oscillations emerge in the normal functioning cortico-basal ganglia loop during behavior. In this work we employ a unique approach connecting a computational model closely with experimental data. In this way we achieve a simulation environment for our model that mimics natural input patterns in awake behaving animals. Using this approach we demonstrate that a computational model for beta oscillations in Parkinson’s disease can also account for complex patterns of transient beta oscillations in healthy animals. Therefore, we propose that transient beta oscillations in healthy animals share the same mechanism with pathological beta oscillations in Parkinson’s disease. This important result connects functional and pathological roles of beta oscillations in the basal ganglia.


2004 ◽  
Vol 18 (2/3) ◽  
pp. 130-139 ◽  
Author(s):  
Guillermo Paradiso ◽  
Danny Cunic ◽  
Robert Chen

Abstract Although it has long been suggested that the basal ganglia and thalamus are involved in movement planning and preparation, there was little direct evidence in humans to support this hypothesis. Deep brain stimulation (DBS) is a well-established treatment for movement disorders such as Parkinson's disease, tremor, and dystonia. In patients undergoing DBS surgery, we recorded simultaneously from scalp contacts and from electrodes surgically implanted in the subthalamic nucleus (STN) of 13 patients with Parkinson's disease and in the “cerebellar” thalamus of 5 patients with tremor. The aim of our studies was to assess the role of the cortico-basal ganglia-thalamocortical loop through the STN and the cerebello-thalamocortical circuit through the “cerebellar” thalamus in movement preparation. The patients were asked to perform self-paced wrist extension movements. All subjects showed a cortical readiness potential (RP) with onset ranging between 1.5 to 2s before the onset of movement. Subcortical RPs were recorded in 11 of 13 with electrodes in the STN and in 4 of 5 patients with electrodes in the thalamus. The onset time of the STN and thalamic RPs were not significantly different from the onset time of the scalp RP. The STN and thalamic RPs were present before both contralateral and ipsilateral hand movements. Postoperative MRI studies showed that contacts with maximum RP amplitude generally were inside the target nucleus. These findings indicate that both the basal ganglia and the cerebellar circuits participate in movement preparation in parallel with the cortex.


2008 ◽  
Vol 100 (5) ◽  
pp. 2515-2524 ◽  
Author(s):  
F. Steigerwald ◽  
M. Pötter ◽  
J. Herzog ◽  
M. Pinsker ◽  
F. Kopper ◽  
...  

We recorded resting-state neuronal activity from the human subthalamic nucleus (STN) during functional stereotactic surgeries. By inserting up to five parallel microelectrodes for single- or multiunit recordings and applying statistical spike-sorting methods, we were able to isolate a total of 351 single units in 65 patients with Parkinson's disease (PD) and 33 single units in 9 patients suffering from essential tremor (ET). Among these were 93 pairs of simultaneously recorded neurons in PD and 17 in ET, which were detected either by the same ( n = 30) or neighboring microelectrodes ( n = 80). Essential tremor is a movement disorder without any known basal ganglia pathology and with normal dopaminergic brain function. By comparing the neuronal activity of the STN in patients suffering from PD and ET we intended to characterize, for the first time, changes of basal ganglia activity in the human disease state that had previously been described in animal models of Parkinson's disease. We found a significant increase in the mean firing rate of STN neurons in PD and a relatively larger fraction of neurons exhibiting burstlike activity compared with ET. The overall proportion of neurons exhibiting intrinsic oscillations or interneuronal synchronization as defined by significant spectral peaks in the auto- or cross-correlations functions did not differ between PD and ET when considering the entire frequency range of 1–100 Hz. The distribution of significant oscillations across the theta (1–8 Hz), alpha (8–12 Hz), beta (12–35 Hz), and gamma band (>35 Hz), however, was uneven in ET and PD, as indicated by a trend in Fisher's exact test ( P = 0.05). Oscillations and pairwise synchronizations within the 12- to 35-Hz band were a unique feature of PD. Our results confirm the predictions of the rate model of Parkinson's disease. In addition, they emphasize abnormalities in the patterning and dynamics of neuronal discharges in the parkinsonian STN, which support current concepts of abnormal motor loop oscillations in Parkinson's disease.


Author(s):  
Azari H ◽  

Background: Deep Brain Stimulation (DBS) is regarded as a viable therapeutic choice for Parkinson’s Disease (PD). The two most common sites for DBS are the Subthalamic Nucleus (STN) and Globus Pallidus (GPi). In this study, the clinical effectiveness of these two targets was compared. Methods: A systematic literature search in electronic databases were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies that evaluated the Unified Parkinson’s Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) had at least three months follow-up period; (2) compared both GPi and STN DBS; (3) at least five participants in each group; (4) conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale. Results: 3577 potentially relevant articles were identified 3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). Majority of studies reported no statistically significant between-group difference for improvements in UPDRS III scores. Conclusions: Although there were some results in terms of action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice or regarding the adverse effects, GPi seemed better; but it cannot be concluded that one target is superior. Other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for stimulation and imposes fewer adverse effects on the patients.


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