Excitatory Deep Brain Stimulation Quenches Parkinsonian Signs in the Basal Ganglia and Thalamus

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.

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

10.21203/rs.3.rs-125807/v1 ◽

2020 ◽

Author(s):

Seyed-Mojtaba Alavi ◽

Amin Mirzaei ◽

Alireza Valizadeh ◽

Reza Ebrahimpour

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Globus Pallidus ◽

Subthalamic Nucleus ◽

Experimental Studies ◽

Underlying Mechanism ◽

Motor Deficits ◽

Synaptic Coupling

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

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INVESTIGATING DIFFERENT TARGETS IN DEEP BRAIN STIMULATION ON PARKINSON'S DISEASE USING A MEAN-FIELD MODEL OF THE BASAL GANGLIA-THALAMOCORTICAL SYSTEM

Journal of Mechanics in Medicine and Biology ◽

10.1142/s0219519412400040 ◽

2012 ◽

Vol 12 (02) ◽

pp. 1240004 ◽

Cited By ~ 1

Author(s):

ALIREZA NAHVI ◽

FARIBA BAHRAMI ◽

SAMIRA HEMMATI

Keyword(s):

Parkinson’S Disease ◽

Deep Brain Stimulation ◽

Basal Ganglia ◽

Globus Pallidus ◽

Brain Stimulation ◽

Field Model ◽

Mean Field ◽

Mean Field Model ◽

Thalamocortical System ◽

Deep Brain

In this paper, we investigated effects of deep brain stimulation (DBS) on Parkinson's disease (PD) when different target sites in the basal ganglia are stimulated. The targets which are investigated are subthalamic nucleus (STN), globus pallidus interna (GPi), and globus pallidus externa (GPe). For this purpose we used a computational model of the basal ganglia-thalamocortical system (BGTCS) with parameters calculated for mean field. This model is able to reproduce both the normal and Parkinsonian activities of basal ganglia, thalamus and cortex in a unified structure. In the present study, we used a mean-field model of the BGTCS, allowing a more complete framework to simulate DBS and to interpret its effects in the BGTCS. Our results suggest that DBS in the STN and GPe could restore the thalamus relay activity, while DBS in the GPi could inhibit it. Our results are compatible with the experimental and the clinical outcomes about the effects of DBS of different targets.

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Patterned low-frequency deep brain stimulation induces motor deficits and modulates cortex-basal ganglia neural activity in healthy rats

Journal of Neurophysiology ◽

10.1152/jn.00929.2017 ◽

2018 ◽

Vol 120 (5) ◽

pp. 2410-2422 ◽

Cited By ~ 5

Author(s):

Chintan S. Oza ◽

David T. Brocker ◽

Christina E. Behrend ◽

Warren M. Grill

Keyword(s):

Deep Brain Stimulation ◽

Basal Ganglia ◽

Brain Stimulation ◽

Movement Disorders ◽

Neural Activity ◽

Low Frequency ◽

Oscillatory Activity ◽

Motor Deficits ◽

Motor Symptoms ◽

Deep Brain

Deep brain stimulation (DBS) is an effective therapy for movement disorders, including Parkinson’s disease (PD), although the mechanisms of action remain unclear. Abnormal oscillatory neural activity is correlated with motor symptoms, and pharmacological or DBS treatment that alleviates motor symptoms appears to suppress abnormal oscillations. However, whether such oscillatory activity is causal of motor deficits such as tremor remains unclear. Our goal was to generate abnormal oscillatory activity in the cortex-basal ganglia loop using patterned subthalamic nucleus DBS and to quantify motor behavior in awake healthy rats. Stimulation patterns were designed via model-based optimization to increase power in the low-frequency (7–11 Hz) band because these oscillations are associated with the emergence of motor symptoms in the 6-hydroxydopamine lesioned rat model of parkinsonism. We measured motor activity using a head-mounted accelerometer, as well as quantified neural activity in cortex and globus pallidus (GP), in response to 5 stimulation patterns that generated a range of 7- to 11-Hz spectral power. Stimulation patterns induced oscillatory activity in the low-frequency band in the cortex and GP and caused tremor, whereas control patterns and regular 50-Hz DBS did not generate any such effects. Neural and motor-evoked responses observed during stimulation were synchronous and time-locked to stimulation bursts within the patterns. These results identified elements of irregular patterns of stimulation that were correlated with tremor and tremor-related neural activity in the cortex and basal ganglia and may lead to the identification of the oscillatory activity and structures associated with the generation of tremor activity. NEW & NOTEWORTHY Subthalamic nucleus deep brain stimulation is a promising therapy for movement disorders such as Parkinson’s disease. Several groups reported correlation between suppression of abnormal oscillatory activity in the cortex-basal ganglia and motor symptoms, but it remains unclear whether such oscillations play a causal role in the emergence of motor symptoms. We demonstrate generation of tremor and pathological oscillatory activity in otherwise healthy rats by stimulation with patterns that produced increases in low-frequency oscillatory activity.

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Deep brain stimulation in the treatment of dyskinesia and dystonia

Neurosurgical FOCUS ◽

10.3171/foc.2004.17.1.2 ◽

2004 ◽

Vol 17 (1) ◽

pp. 9-13 ◽

Cited By ~ 38

Author(s):

Hiroki Toda ◽

Clement Hamani ◽

Andres Lozano

Keyword(s):

Deep Brain Stimulation ◽

Basal Ganglia ◽

Globus Pallidus ◽

Brain Stimulation ◽

Movement Disorders ◽

Improved Outcomes ◽

Generalized Dystonia ◽

Clinical Conditions ◽

Better Than ◽

Deep Brain

Deep brain stimulation (DBS) has become a mainstay of treatment for patients with movement disorders. This modality is directed at modulating pathological activity within basal ganglia output structures by stimulating some of their nuclei, such as the subthalamic nucleus (STN) and the globus pallidus internus (GPi), without making permanent lesions. With the accumulation of experience, indications for the use of DBS have become clearer and the effectiveness and limitations of this form of therapy in different clinical conditions have been better appreciated. In this review the authors discuss the efficacy of DBS in the treatment of dystonia and levodopa-induced dyskinesias. The use of DBS of the STN and GPi is very effective for the treatment of movement disorders induced by levodopa. The relative benefits of using the GPi as opposed to the STN as a target are still being investigated. Bilateral GPi stimulation is gaining importance in the therapeutic armamentarium for the treatment of dystonia. The DYT1 forms of generalized dystonia and cervical dystonias respond to DBS better than secondary dystonia does. Discrimination between the diverse forms of dystonia and a better understanding of the pathophysiological features of this condition will serve as a platform for improved outcomes.

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10 / Anaesthetic considerations in a patient with kernicterus for stereotactic bilateral insertion of deep brain stimulation (DBS) electrodes into internal globus pallidus (GPi) nuclei.

10.26226/morressier.5aeb0ac907b0d6001a79a69e ◽

2018 ◽

Author(s):

Sofia Diaz

Keyword(s):

Deep Brain Stimulation ◽

Globus Pallidus ◽

Brain Stimulation ◽

Internal Globus Pallidus ◽

Deep Brain

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Faculty Opinions recommendation of Deep brain stimulation of anteromedial globus pallidus interna for severe Tourette's syndrome.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717953861.793459545 ◽

2012 ◽

Author(s):

Shailesh Jain

Keyword(s):

Deep Brain Stimulation ◽

Globus Pallidus ◽

Brain Stimulation ◽

Tourette's Syndrome ◽

Tourette’S Syndrome ◽

Deep Brain ◽

Stimulation Of

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Inhibitory Control on a Stop Signal Task in Tourette Syndrome before and after Deep Brain Stimulation of the Internal Segment of the Globus Pallidus

Brain Sciences ◽

10.3390/brainsci11040461 ◽

2021 ◽

Vol 11 (4) ◽

pp. 461

Author(s):

Francesca Morreale ◽

Zinovia Kefalopoulou ◽

Ludvic Zrinzo ◽

Patricia Limousin ◽

Eileen Joyce ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Tourette Syndrome ◽

Globus Pallidus ◽

Brain Stimulation ◽

Stop Signal ◽

Stop Signal Task ◽

Healthy Controls ◽

Reactive Inhibition ◽

Double Blind ◽

Deep Brain

As part of the first randomized double-blind trial of deep brain stimulation (DBS) of the globus pallidus (GPi) in Tourette syndrome, we examined the effect of stimulation on response initiation and inhibition. A total of 14 patients with severe Tourette syndrome were recruited and tested on the stop signal task prior to and after GPi-DBS surgery and compared to eight age-matched healthy controls. Tics were significantly improved following GPi-DBS. The main measure of reactive inhibition, the stop signal reaction time did not change from before to after surgery and did not differ from that of healthy controls either before or after GPi-DBS surgery. This suggests that patients with Tourette syndrome have normal reactive inhibition which is not significantly altered by GPi-DBS.

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Deep brain stimulation of the subthalamic nucleus reestablishes neuronal information transmission in the 6-OHDA rat model of parkinsonism

Journal of Neurophysiology ◽

10.1152/jn.00713.2013 ◽

2014 ◽

Vol 111 (10) ◽

pp. 1949-1959 ◽

Cited By ~ 29

Author(s):

Alan D. Dorval ◽

Warren M. Grill

Keyword(s):

Deep Brain Stimulation ◽

Basal Ganglia ◽

Information Transmission ◽

Brain Stimulation ◽

Rat Model ◽

Information Transfer ◽

Firing Pattern ◽

Signal Propagation ◽

Neuronal Firing ◽

Deep Brain

Pathophysiological activity of basal ganglia neurons accompanies the motor symptoms of Parkinson's disease. High-frequency (>90 Hz) deep brain stimulation (DBS) reduces parkinsonian symptoms, but the mechanisms remain unclear. We hypothesize that parkinsonism-associated electrophysiological changes constitute an increase in neuronal firing pattern disorder and a concomitant decrease in information transmission through the ventral basal ganglia, and that effective DBS alleviates symptoms by decreasing neuronal disorder while simultaneously increasing information transfer through the same regions. We tested these hypotheses in the freely behaving, 6-hydroxydopamine-lesioned rat model of hemiparkinsonism. Following the onset of parkinsonism, mean neuronal firing rates were unchanged, despite a significant increase in firing pattern disorder (i.e., neuronal entropy), in both the globus pallidus and substantia nigra pars reticulata. This increase in neuronal entropy was reversed by symptom-alleviating DBS. Whereas increases in signal entropy are most commonly indicative of similar increases in information transmission, directed information through both regions was substantially reduced (>70%) following the onset of parkinsonism. Again, this decrease in information transmission was partially reversed by DBS. Together, these results suggest that the parkinsonian basal ganglia are rife with entropic activity and incapable of functional information transmission. Furthermore, they indicate that symptom-alleviating DBS works by lowering the entropic noise floor, enabling more information-rich signal propagation. In this view, the symptoms of parkinsonism may be more a default mode, normally overridden by healthy basal ganglia information. When that information is abolished by parkinsonian pathophysiology, hypokinetic symptoms emerge.

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