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Investigating irregularly patterned deep brain stimulation signal design using biophysical models.

Summerson SR, Aazhang B, Kemere C - Front Comput Neurosci (2015)

Bottom Line: Biological models are an important tool for gaining insights into neural function and, in this case, serve as effective tools for investigating innovative new DBS paradigms.We show that antidromic spiking from DBS of the subthalamic nucleus (STN) has a significant impact on cortical neural activity, which is frequency dependent and additionally modulated by the regularity of the stimulus pulse train used.Irregular spacing between stimulus pulses, where the amount of variability added is bounded, is shown to increase diversification of response of basal ganglia neurons and reduce entropic noise in cortical neurons, which may be fundamentally important to restoration of information flow in the motor circuit.

View Article: PubMed Central - PubMed

Affiliation: Department of Electrical Engineering and Computer Science, University of California, Berkeley Berkeley, CA, USA.

ABSTRACT
Parkinson's disease (PD) is a neurodegenerative disorder which follows from cell loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), a nucleus in the basal ganglia (BG). Deep brain stimulation (DBS) is an electrical therapy that modulates the pathological activity to treat the motor symptoms of PD. Although this therapy is currently used in clinical practice, the sufficient conditions for therapeutic efficacy are unknown. In this work we develop a model of critical motor circuit structures in the brain using biophysical cell models as the base components and then evaluate performance of different DBS signals in this model to perform comparative studies of their efficacy. Biological models are an important tool for gaining insights into neural function and, in this case, serve as effective tools for investigating innovative new DBS paradigms. Experiments were performed using the hemi-parkinsonian rodent model to test the same set of signals, verifying the obedience of the model to physiological trends. We show that antidromic spiking from DBS of the subthalamic nucleus (STN) has a significant impact on cortical neural activity, which is frequency dependent and additionally modulated by the regularity of the stimulus pulse train used. Irregular spacing between stimulus pulses, where the amount of variability added is bounded, is shown to increase diversification of response of basal ganglia neurons and reduce entropic noise in cortical neurons, which may be fundamentally important to restoration of information flow in the motor circuit.

No MeSH data available.


Related in: MedlinePlus

Cortical unit computational model. The output layer, Layer V, of the motor cortex is modeled using a population of cortical units, where each cortical unit is formed using a pyramidal cell (PY) and interneuron (IN) in a feedback architecture. The axon of the PY cell projects to the STN, while an axonal branch projects to the IN cell. In turn, the IN cell synapses onto the PY cell providing an inhibitory input.
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Figure 1: Cortical unit computational model. The output layer, Layer V, of the motor cortex is modeled using a population of cortical units, where each cortical unit is formed using a pyramidal cell (PY) and interneuron (IN) in a feedback architecture. The axon of the PY cell projects to the STN, while an axonal branch projects to the IN cell. In turn, the IN cell synapses onto the PY cell providing an inhibitory input.

Mentions: The two main cell types that make up the cortex are excitatory pyramidal cells (PY) and inhibitory interneurons (IN). Both cell types are modeled here using single compartment models based on prior work (Destexhe et al., 1998), but with parameters tuned to match in vivo data. A recurrent network architecture, shown in Figure 1, is formed using a PY and IN model to replicate physiological findings. Stimulation of STN neurons excites both cell types: the PY cell body directly and the IN cell synaptically via the PY axonal branch.


Investigating irregularly patterned deep brain stimulation signal design using biophysical models.

Summerson SR, Aazhang B, Kemere C - Front Comput Neurosci (2015)

Cortical unit computational model. The output layer, Layer V, of the motor cortex is modeled using a population of cortical units, where each cortical unit is formed using a pyramidal cell (PY) and interneuron (IN) in a feedback architecture. The axon of the PY cell projects to the STN, while an axonal branch projects to the IN cell. In turn, the IN cell synapses onto the PY cell providing an inhibitory input.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4481153&req=5

Figure 1: Cortical unit computational model. The output layer, Layer V, of the motor cortex is modeled using a population of cortical units, where each cortical unit is formed using a pyramidal cell (PY) and interneuron (IN) in a feedback architecture. The axon of the PY cell projects to the STN, while an axonal branch projects to the IN cell. In turn, the IN cell synapses onto the PY cell providing an inhibitory input.
Mentions: The two main cell types that make up the cortex are excitatory pyramidal cells (PY) and inhibitory interneurons (IN). Both cell types are modeled here using single compartment models based on prior work (Destexhe et al., 1998), but with parameters tuned to match in vivo data. A recurrent network architecture, shown in Figure 1, is formed using a PY and IN model to replicate physiological findings. Stimulation of STN neurons excites both cell types: the PY cell body directly and the IN cell synaptically via the PY axonal branch.

Bottom Line: Biological models are an important tool for gaining insights into neural function and, in this case, serve as effective tools for investigating innovative new DBS paradigms.We show that antidromic spiking from DBS of the subthalamic nucleus (STN) has a significant impact on cortical neural activity, which is frequency dependent and additionally modulated by the regularity of the stimulus pulse train used.Irregular spacing between stimulus pulses, where the amount of variability added is bounded, is shown to increase diversification of response of basal ganglia neurons and reduce entropic noise in cortical neurons, which may be fundamentally important to restoration of information flow in the motor circuit.

View Article: PubMed Central - PubMed

Affiliation: Department of Electrical Engineering and Computer Science, University of California, Berkeley Berkeley, CA, USA.

ABSTRACT
Parkinson's disease (PD) is a neurodegenerative disorder which follows from cell loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), a nucleus in the basal ganglia (BG). Deep brain stimulation (DBS) is an electrical therapy that modulates the pathological activity to treat the motor symptoms of PD. Although this therapy is currently used in clinical practice, the sufficient conditions for therapeutic efficacy are unknown. In this work we develop a model of critical motor circuit structures in the brain using biophysical cell models as the base components and then evaluate performance of different DBS signals in this model to perform comparative studies of their efficacy. Biological models are an important tool for gaining insights into neural function and, in this case, serve as effective tools for investigating innovative new DBS paradigms. Experiments were performed using the hemi-parkinsonian rodent model to test the same set of signals, verifying the obedience of the model to physiological trends. We show that antidromic spiking from DBS of the subthalamic nucleus (STN) has a significant impact on cortical neural activity, which is frequency dependent and additionally modulated by the regularity of the stimulus pulse train used. Irregular spacing between stimulus pulses, where the amount of variability added is bounded, is shown to increase diversification of response of basal ganglia neurons and reduce entropic noise in cortical neurons, which may be fundamentally important to restoration of information flow in the motor circuit.

No MeSH data available.


Related in: MedlinePlus