A Cortico- Basal Ganglia Model for choosing an optimal rehabilitation strategy in Hemiparetic Stroke

Narayanamurthy, Rukhmani; Jayakumar, Samyukta; Elango, Sundari; Muralidharan, Vignesh; Chakravarthy, V. Srinivasa

doi:10.1038/s41598-019-49670-4

Cited by 8 publications

(5 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…

in Equation (8) represents the value of the current position of the arm at time ‘ t ’ and is obtained as the probabilistic gradient ascent over the value function [ 22 , 55 ] performed by the BG, as given in Equation (9) below.

and

are the current arm position obtained from the PC and the target goal position obtained from the PFC, respectively.…”

Section: Methodsmentioning

confidence: 99%

A Computational Model of Deep Brain Stimulation for Parkinson’s Disease Tremor and Bradykinesia

Nair,

Chakravarthy

2024

Brain Sciences

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions, and its impact extends beyond physical abnormalities into emotional well-being and cognitive symptoms. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) leads to an array of dysfunctions in the functioning of the basal ganglia (BG) circuitry that manifests into PD. While active research is being carried out to find the root cause of SNc cell death, various therapeutic techniques are used to manage the symptoms of PD. The most common approach in managing the symptoms is replenishing the lost dopamine in the form of taking dopaminergic medications such as levodopa, despite its long-term complications. Another commonly used intervention for PD is deep brain stimulation (DBS). DBS is most commonly used when levodopa medication efficacy is reduced, and, in combination with levodopa medication, it helps reduce the required dosage of medication, prolonging the therapeutic effect. DBS is also a first choice option when motor complications such as dyskinesia emerge as a side effect of medication. Several studies have also reported that though DBS is found to be effective in suppressing severe motor symptoms such as tremors and rigidity, it has an adverse effect on cognitive capabilities. Henceforth, it is important to understand the exact mechanism of DBS in alleviating motor symptoms. A computational model of DBS stimulation for motor symptoms will offer great insights into understanding the mechanisms underlying DBS, and, along this line, in our current study, we modeled a cortico-basal ganglia circuitry of arm reaching, where we simulated healthy control (HC) and PD symptoms as well as the DBS effect on PD tremor and bradykinesia. Our modeling results reveal that PD tremors are more correlated with the theta band, while bradykinesia is more correlated with the beta band of the frequency spectrum of the local field potential (LFP) of the subthalamic nucleus (STN) neurons. With a DBS current of 220 pA, 130 Hz, and a 100 microsecond pulse-width, we could found the maximum therapeutic effect for the pathological dynamics simulated using our model using a set of parameter values. However, the exact DBS characteristics vary from patient to patient, and this can be further studied by exploring the model parameter space. This model can be extended to study different DBS targets and accommodate cognitive dynamics in the future to study the impact of DBS on cognitive symptoms and thereby optimize the parameters to produce optimal performance effects across modalities. Combining DBS with rehabilitation is another frontier where DBS can reduce symptoms such as tremors and rigidity, enabling patients to participate in their therapy. With DBS providing instant relief to patients, a combination of DBS and rehabilitation can enhance neural plasticity. One of the key motivations behind combining DBS with rehabilitation is to expect comparable results in motor performance even with milder DBS currents.

show abstract

“…

and

are the current arm position obtained from the PC and the target goal position obtained from the PFC, respectively.…”

Section: Methodsmentioning

confidence: 99%

A Computational Model of Deep Brain Stimulation for Parkinson’s Disease Tremor and Bradykinesia

Nair,

Chakravarthy

2024

Brain Sciences

View full text Add to dashboard Cite

show abstract

“…The output of the BG performs a stochastic hill-climbing over the value function (Chakravarthy and Moustafa, 2018 ; Narayanamurthy et al, 2019 ) and drives the MC to facilitate the arm in reaching the target. The value difference (δ V ) which is computed by comparing the current and previous values is given as,…”

Section: Methodsmentioning

confidence: 99%

“…where, X targ is the target goal position, X arm is the current endeffector position of the arm, σ V is the spatial range over which the value function is sensitive for that particular target. The output of the BG performs a stochastic hill-climbing over the value function (Chakravarthy and Moustafa, 2018;Narayanamurthy et al, 2019) and drives the MC to facilitate the arm in reaching the target. The value difference (δ V ) which is computed by comparing the current and previous values is given as,…”

Section: Value Computation and Stochastic Hill Climbingmentioning

confidence: 99%

A Multiscale, Systems-Level, Neuropharmacological Model of Cortico-Basal Ganglia System for Arm Reaching Under Normal, Parkinsonian, and Levodopa Medication Conditions

Nair

Muddapu

Chakravarthy

2022

Front. Comput. Neurosci.

Self Cite

View full text Add to dashboard Cite

In order to understand the link between substantia nigra pars compacta (SNc) cell loss and Parkinson's disease (PD) symptoms, we developed a multiscale computational model that can replicate the symptoms at the behavioural level by incorporating the key cellular and molecular mechanisms underlying PD pathology. There is a modelling tradition that links dopamine to reward and uses reinforcement learning (RL) concepts to model the basal ganglia. In our model, we replace the abstract representations of reward with the realistic variable of extracellular DA released by a network of SNc cells and incorporate it in the RL-based behavioural model, which simulates the arm reaching task. Our results successfully replicated the impact of SNc cell loss and levodopa (L-DOPA) medication on reaching performance. It also shows the side effects of medication, such as wearing off and peak dosage dyskinesias. The model demonstrates how differential dopaminergic axonal degeneration in basal ganglia results in various cardinal symptoms of PD. It was able to predict the optimum L-DOPA medication dosage for varying degrees of cell loss. The proposed model has a potential clinical application where drug dosage can be optimised as per patient characteristics.

show abstract

“…The output of the BG performs a stochastic hill climbing over the value function (Chakravarthy and Moustafa, 2018;Narayanamurthy et al, 2019) and drives the MC to facilitate the arm in reaching the target. The value difference ( ) which is computed by comparing the current and previous values is given as,…”

Section: Value Computation and Stochastic Hill Climbingmentioning

confidence: 99%

A Multiscale, Systems-level, Neuropharmacological Model of Cortico-Basal Ganglia System for Arm Reaching under Normal, Parkinsonian and Levodopa Medication Conditions

Nair

2021

Preprint

Self Cite

View full text Add to dashboard Cite

The root cause of Parkinson's disease (PD) is the death of dopaminergic neurons in Substantia Nigra pars compacta (SNc). The exact cause of this cell death is still not known. Loss of SNc cells manifest as the cardinal symptoms of PD, including tremor, rigidity, bradykinesia, and postural imbalance. To investigate the PD condition in detail and understand the link between loss of cells in SNc and PD symptoms, it is important to have an integrated multiscale computational model that can replicate the symptoms at the behavioural level by evoking the key cellular and molecular underlying mechanisms that contribute to the pathology. In line with this objective, we present a multiscale integrated model of cortico-basal ganglia motor circuitry for arm reaching task, incorporating a detailed biophysical model of SNc dopaminergic neuron. Earlier researchers have shown that fluctuations in dopamine (DA) signals are analogous to reward/punishment signals, thereby prompting application of concepts from reinforcement learning (RL) to modelling the basal ganglia system. In our model, we replace the abstract representations of reward with the realistic variable of extracellular DA released by a network of SNc cells and incorporate it with the RL-based behavioural model, which simulates the arm reaching task. Our results showed that as SNc cell loss increases, the percentage success rate to reach the target decreases, and average time to reach the target increases. With levodopa (L-DOPA) medication, both the success rate and the average time to reach the target improved significantly. The proposed model also exhibits how differential dopaminergic axonal degeneration in basal ganglia results in various cardinal symptoms of PD as manifest in reaching movements. From the model results, we were able to show the side effects of L-DOPA mediation, such as wearing off and peak dosage dyskinesias. Moreover, from the results, we were able to predict the optimum dosage for varying degrees of cell loss and L-DOPA medication. The proposed model has a potential clinical application where drug dosage can be optimized as per patient characteristics. We conclude that our model presents a realistic and efficient way of simulating the PD pathology conditions and the effect of levodopa medication, thereby giving a reliable indicator towards the optimization of the drug dosage.

show abstract

A Cortico- Basal Ganglia Model for choosing an optimal rehabilitation strategy in Hemiparetic Stroke

Cited by 8 publications

References 48 publications

A Computational Model of Deep Brain Stimulation for Parkinson’s Disease Tremor and Bradykinesia

A Computational Model of Deep Brain Stimulation for Parkinson’s Disease Tremor and Bradykinesia

A Multiscale, Systems-Level, Neuropharmacological Model of Cortico-Basal Ganglia System for Arm Reaching Under Normal, Parkinsonian, and Levodopa Medication Conditions

A Multiscale, Systems-level, Neuropharmacological Model of Cortico-Basal Ganglia System for Arm Reaching under Normal, Parkinsonian and Levodopa Medication Conditions

Contact Info

Product

Resources

About