| || Models ||Description|
Cognitive and motor cortico-basal ganglia interactions during decision making (Guthrie et al 2013)
||This is a re-implementation of Guthrie et al 2013 by Topalidou and Rougier 2015. The original study investigated how multiple level action selection
could be performed by the basal ganglia.
Cortex-Basal Ganglia-Thalamus network model (Kumaravelu et al. 2016)
||" ... We developed a biophysical network model comprising of the closed loop cortical-basal ganglia-thalamus circuit representing the healthy and parkinsonian rat brain. The network properties of the model were validated by comparing responses evoked in basal ganglia (BG) nuclei by cortical (CTX) stimulation to published experimental results. A key emergent property of the model was generation of low-frequency network oscillations. Consistent with their putative pathological role, low-frequency oscillations in model BG neurons were exaggerated in the parkinsonian state compared to the healthy condition. ..."
Cortical oscillations and the basal ganglia (Fountas & Shanahan 2017)
||"Although brain oscillations involving the basal ganglia (BG) have been
the target of extensive research, the main focus lies
disproportionally on oscillations generated within the BG circuit
rather than other sources, such as cortical areas. We remedy this here
by investigating the influence of various cortical frequency bands on
the intrinsic effective connectivity of the BG, as well as the role of
the latter in regulating cortical behaviour. To do this, we construct
a detailed neural model of the complete BG circuit based on fine-tuned
spiking neurons, with both electrical and chemical synapses as well as
short-term plasticity between structures. As a measure of effective
connectivity, we estimate information transfer between nuclei by means
of transfer entropy. Our model successfully reproduces firing and
oscillatory behaviour found in both the healthy and Parkinsonian
BG. We found that, indeed, effective connectivity changes dramatically
for different cortical frequency bands and phase offsets, which are
able to modulate (or even block) information flow in the three major
BG pathways. ..."
Excitotoxic loss of dopaminergic cells in PD (Muddapu et al 2019)
couple of the proposed mechanisms, however, show
potential for the
development of a novel line of PD (Parkinson's disease) therapeutics. One of these
mechanisms is the peculiar metabolic vulnerability of SNc (Substantia Nigra pars compacta) cells
compared to other dopaminergic clusters; the other is the SubThalamic
Nucleus (STN)-induced excitotoxicity in SNc. To investigate the latter
hypothesis computationally, we developed a spiking neuron
network-model of SNc-STN-GPe system. In the model, prolonged
stimulation of SNc cells by an overactive STN leads to an increase in
‘stress’ variable; when the stress in a SNc neuron exceeds a stress
threshold, the neuron dies. The model shows that the interaction
between SNc and STN involves a positive-feedback due to which, an
initial loss of SNc cells that crosses a threshold causes a
runaway-effect, leading to an inexorable loss of SNc cells, strongly
resembling the process of neurodegeneration. The model further
suggests a link between the two aforementioned mechanisms of SNc cell
loss. Our simulation results show that the excitotoxic cause of SNc
cell loss might initiate by weak-excitotoxicity mediated by energy
deficit, followed by strong-excitotoxicity, mediated by a disinhibited
STN. A variety of conventional therapies were simulated to test their
efficacy in slowing down SNc cell loss. Among them, glutamate
inhibition, dopamine restoration, subthalamotomy and deep brain
stimulation showed superior neuroprotective-effects in the proposed
High frequency stimulation of the Subthalamic Nucleus (Rubin and Terman 2004)
||" ... Using a computational model, this paper considers the hypothesis that DBS works by replacing pathologically rhythmic
basal ganglia output with tonic, high frequency firing.
In our simulations of parkinsonian conditions, rhythmic inhibition from GPi to the thalamus compromises the ability of thalamocortical relay (TC) cells to respond to depolarizing inputs, such as sensorimotor signals.
High frequency stimulation of STN regularizes GPi firing, and this restores TC responsiveness, despite the increased frequency and amplitude of GPi inhibition to thalamus that result.
We provide a mathematical phase plane analysis of the mechanisms that determine TC relay capabilities in
normal, parkinsonian, and DBS states in a reduced model.
This analysis highlights the differences in deinactivation of the low-threshold calcium T -current that we observe in TC cells in these different conditions. ..."
Investigation of different targets in deep brain stimulation for Parkinson`s (Pirini et al. 2009)
||"We investigated by a computational model of the basal ganglia the different network effects of deep brain stimulation (DBS) for Parkinson’s disease (PD) in different target sites in the subthalamic nucleus (STN), the globus pallidus pars interna (GPi), and the globus pallidus pars externa (GPe).
A cellular-based model of the basal ganglia system (BGS), based on the model proposed by Rubin and Terman (J Comput Neurosci 16:211–235, 2004), was developed.
Our results suggest that DBS in the STN could functionally restore the TC relay activity, while DBS in the GPe and in the GPi could functionally over-activate and inhibit it, respectively.
Our results are consistent with the experimental and the clinical evidences on the network effects of DBS."