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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

LFP power spectra. The LFP was filtered using a zero-phase FIR filter with passband 0–200 Hz and the power spectrum of the LFP signal was estimated using multitaper methods (Chronux 2.0) with 9 Slepian data tapers. Power spectra shown are for activity in the lesioned hemisphere of the subjects without stimulation and with four different stimulation signals: 40 Hz with regularly and irregularly space pulse trains, and 130 Hz DBS with regularly and irregularly spaced pulse trains.
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Figure 7: LFP power spectra. The LFP was filtered using a zero-phase FIR filter with passband 0–200 Hz and the power spectrum of the LFP signal was estimated using multitaper methods (Chronux 2.0) with 9 Slepian data tapers. Power spectra shown are for activity in the lesioned hemisphere of the subjects without stimulation and with four different stimulation signals: 40 Hz with regularly and irregularly space pulse trains, and 130 Hz DBS with regularly and irregularly spaced pulse trains.

Mentions: The power spectrum of the observed LFP data during stimulation was computed in order to identify effects of the STN DBS in the rodent model on beta band activity, since increased beta band activity has been correlated with motor symptoms associated with PD (Brown et al., 2001). The averaged normalized spectrum is presented in Figure 7. With increasing stimulation frequency, beta band power was found to be increasingly attenuated (One-Way ANOVA: p < 0.05; post-hoc LSD: p < 0.025). Also, irregular stimulation dampened peak beta band power more than regular stimulation (post-hoc LSD: p < 0.05). These results confirm that pathological activity was reduced with high frequency, irregular stimulus pulse trains, as indicated by the computational model.


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

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

LFP power spectra. The LFP was filtered using a zero-phase FIR filter with passband 0–200 Hz and the power spectrum of the LFP signal was estimated using multitaper methods (Chronux 2.0) with 9 Slepian data tapers. Power spectra shown are for activity in the lesioned hemisphere of the subjects without stimulation and with four different stimulation signals: 40 Hz with regularly and irregularly space pulse trains, and 130 Hz DBS with regularly and irregularly spaced pulse trains.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 7: LFP power spectra. The LFP was filtered using a zero-phase FIR filter with passband 0–200 Hz and the power spectrum of the LFP signal was estimated using multitaper methods (Chronux 2.0) with 9 Slepian data tapers. Power spectra shown are for activity in the lesioned hemisphere of the subjects without stimulation and with four different stimulation signals: 40 Hz with regularly and irregularly space pulse trains, and 130 Hz DBS with regularly and irregularly spaced pulse trains.
Mentions: The power spectrum of the observed LFP data during stimulation was computed in order to identify effects of the STN DBS in the rodent model on beta band activity, since increased beta band activity has been correlated with motor symptoms associated with PD (Brown et al., 2001). The averaged normalized spectrum is presented in Figure 7. With increasing stimulation frequency, beta band power was found to be increasingly attenuated (One-Way ANOVA: p < 0.05; post-hoc LSD: p < 0.025). Also, irregular stimulation dampened peak beta band power more than regular stimulation (post-hoc LSD: p < 0.05). These results confirm that pathological activity was reduced with high frequency, irregular stimulus pulse trains, as indicated by the computational model.

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