Subthalamic–pallidal interactions are critical in determining normal and abnormal functioning of the basal ganglia

Gillies, Andrew; Willshaw, David; Li, Zhaoping

doi:10.1098/rspb.2001.1817

Cited by 114 publications

(102 citation statements)

References 33 publications

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“…Low-frequency oscillations observed in organotypic cultures of this circuit (Plenz and Kitai, 1999) have been captured by these models (Humphries and Gurney, 2001;Gillies et al, 2002;Terman et al, 2002) and are consistent with the residual oscillations seen in the in vivo recordings of Magill et al (2001). The combined results of the current and previous modeling studies thus provide considerable support for the proposal that the isolated STN-GP loop forms a low-frequency pacemaker circuit (Plenz and Kitai, 1999;Bevan et al, 2002).…”

Section: Relationship To Other Bg Modelssupporting

confidence: 68%

A Physiologically Plausible Model of Action Selection and Oscillatory Activity in the Basal Ganglia

Humphries

Stewart²,

Gurney³

2006

J. Neurosci.

341

439

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The basal ganglia (BG) have long been implicated in both motor function and dysfunction. It has been proposed that the BG form a centralized action selection circuit, resolving conflict between multiple neural systems competing for access to the final common motor pathway. We present a new spiking neuron model of the BG circuitry to test this proposal, incorporating all major features and many physiologically plausible details. We include the following: effects of dopamine in the subthalamic nucleus (STN) and globus pallidus (GP), transmission delays between neurons, and specific distributions of synaptic inputs over dendrites. All main parameters were derived from experimental studies. We find that the BG circuitry supports motor program selection and switching, which deteriorates under dopamine-depleted and dopamine-excessive conditions in a manner consistent with some pathologies associated with those dopamine states. We also validated the model against data describing oscillatory properties of BG. We find that the same model displayed detailed features of both ␥-band

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Section: Relationship To Other Bg Modelssupporting

confidence: 68%

A Physiologically Plausible Model of Action Selection and Oscillatory Activity in the Basal Ganglia

Humphries

Stewart²,

Gurney³

2006

J. Neurosci.

341

439

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“…Such connections are not present in our model, because we judged that the evidence for such connections (Hammond and Yelnik, 1983;Sato et al, 2000b) was not strong enough to consider that they play a prominent role in information transmission in the basal ganglia. We think that the reason why Gillies et al (2002) did not find oscillations without these connections is that they did not consider transmission delays between STN and GPe, and our results (Eq. 9) imply that these delays must exist for the oscillations to be present.…”

Section: Discussionmentioning

confidence: 52%

“…Relationship to other models There have been a number of other modeling studies that investigated the oscillations present in the basal ganglia (Gillies et al, 2002;Terman et al, 2002;Humphries et al, 2006;Leblois et al, 2006). Two of those studies (Gillies et al, 2002;) also focused on the STN-GPe circuit and found that it can generate oscillatory activity, but the mechanisms that generated these oscillations were very different from our model, as we now describe.…”

Section: Discussionmentioning

confidence: 62%

“…Two of those studies (Gillies et al, 2002;) also focused on the STN-GPe circuit and found that it can generate oscillatory activity, but the mechanisms that generated these oscillations were very different from our model, as we now describe. Gillies et al (2002) developed a firing rate model of the STN-GPe circuit that was simple enough to be studied analytically. They found that their model could produce oscillations only if the strength of connections from STN neurons to other STN neurons was increased.…”

Section: Discussionmentioning

confidence: 96%

“…To shed light on the origin of oscillations associated with Parkinson's disease, many computational models have been proposed (Gillies et al, 2002;Terman et al, 2002;Frank, 2006;Humphries et al, 2006;Leblois et al, 2006;Gillies and Willshaw, 2007;van Albada and Robinson, 2009). These models provide interesting conclusions and explain experimentally observed phenomena; however, most have a drawback in that the complexity of the equations used in the model make them unsuitable for mathematical analysis.…”

Section: Introductionmentioning

confidence: 99%

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Conditions for the Generation of Beta Oscillations in the Subthalamic Nucleus–Globus Pallidus Network

Nevado‐Holgado¹,

Terry²,

Bogacz³

2010

J. Neurosci.

249

292

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The advance of Parkinson's disease is associated with the existence of abnormal oscillations within the basal ganglia with frequencies in the beta band (13-30 Hz). While the origin of these oscillations remains unknown, there is some evidence suggesting that oscillations observed in the basalgangliaariseduetointeractionsoftwonuclei:thesubthalamicnucleus(STN)andtheglobuspallidusparsexterna(GPe).Toinvestigatethis hypothesis, we develop a computational model of the STN-GPe network based upon anatomical and electrophysiological studies. Significantly, our study shows that for certain parameter regimes, the model intrinsically oscillates in the beta range. Through an analytical study of the model, we identify a simple set of necessary conditions on model parameters that guarantees the existence of beta oscillations. These conditions for generation of oscillations are described by a set of simple inequalities and can be summarized as follows: (1) The excitatory connections from STN to GPe and the inhibitory connections from GPe to STN need to be sufficiently strong. (2) The time required by neurons to react to their inputs needs to be short relative to synaptic transmission delays. (3) The excitatory input from the cortex to STN needs to be high relative to the inhibition from striatum to GPe. We confirmed the validity of these conditions via numerical simulation. These conditions describe changes in parameters that are consistent with those expected as a result of the development of Parkinson's disease, and predict manipulations that could inhibit the pathological oscillations.

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Systems approaches to optimizing deep brain stimulation therapies in Parkinson’s disease

Santaniello

Gale

Sarma

2018

WIREs Mechanisms of Disease

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Over the last 30 years, deep brain stimulation (DBS) has been used to treat chronic neurological diseases like dystonia, obsessive-compulsive disorders, essential tremor, Parkinson's disease, and more recently, dementias, depression, cognitive disorders, and epilepsy. Despite its wide use, DBS presents numerous challenges for both clinicians and engineers. One challenge is the design of novel, more efficient DBS therapies, which are hampered by the lack of complete understanding about the cellular mechanisms of therapeutic DBS. Another challenge is the existence of redundancy in clinical outcomes, that is, different DBS programs can result in similar clinical benefits but very little information (e.g., predictive models, longitudinal data, metrics, etc.) is available to select one program over another. Finally, there is high variability in patients' responses to DBS, which forces clinicians to carefully adjust the stimulation settings to each patient via lengthy programming sessions. Researchers in neural engineering and systems biology have been tackling these challenges over the past few years with the specific goal of developing novel DBS therapies, design methodologies, and computational tools that optimize the therapeutic effects of DBS in each patient. Furthermore, efforts are being made to automatically adapt the DBS treatment to the fluctuations of disease symptoms. A review of the quantitative approaches currently available for the treatment of Parkinson's disease is presented here with an emphasis on the contributions that systems theoretical approaches have provided to understand the global dynamics of complex neuronal circuits in the brain under DBS. This article is categorized under: Translational, Genomic, and Systems Medicine > Therapeutic Methods Analytical and Computational Methods > Computational Methods Analytical and Computational Methods > Dynamical Methods Physiology > Mammalian Physiology in Health and Disease.

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Subthalamic–pallidal interactions are critical in determining normal and abnormal functioning of the basal ganglia

Cited by 114 publications

References 33 publications

A Physiologically Plausible Model of Action Selection and Oscillatory Activity in the Basal Ganglia

A Physiologically Plausible Model of Action Selection and Oscillatory Activity in the Basal Ganglia

Conditions for the Generation of Beta Oscillations in the Subthalamic Nucleus–Globus Pallidus Network

Systems approaches to optimizing deep brain stimulation therapies in Parkinson’s disease

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