Adaptive Parameter Selection for Deep Brain Stimulation in Parkinson’s Disease

Each year, around 60,000 people are diagnosed with Parkinson’s disease (PD) and the economic burden of PD is at least $14.4 billion a year in the United States. Pharmaceutical costs for a Parkinson’s patient can be reduced from$12,000 to $6,000 per year with the addition of neuromodulation therapies such as Deep Brain Stimulation (DBS), transcranial Direct Current Stimulation (tDCS), Transcranial Magnetic Stimulation (TMS), etc. In neurodegenerative disorders such as PD, deep brain stimulation (DBS) is a desirable approach when the medication is less effective for treating the symptoms. DBS incorporates transferring electrical pulses to a specific tissue of the central nervous system and obtaining therapeutic results by modulating the neuronal activity of that region. The hyperkinetic symptoms of PD are associated with the ensembles of interacting oscillators that cause excess or abnormal synchronous behavior within the Basal Ganglia (BG) circuitry. Delayed feedback stimulation is a closed loop technique shown to suppress this synchronous oscillatory activity. Deep Brain Stimulation via delayed feedback is known to destabilize the complex intermittent synchronous states. Computational models of the BG network are often introduced to investigate the effect of delayed feedback high frequency stimulation on partially synchronized dynamics. In this work, we developed several computational models of four interacting nuclei of the BG as well as considering the Thalamo-Cortical local effects on the oscillatory dynamics. These models are able to capture the emergence of 34 Hz beta band oscillations seen in the Local Field Potential (LFP) recordings of the PD state. Traditional High Frequency Stimulations (HFS) has shown deficiencies such as strengthening the synchronization in case of highly fluctuating neuronal activities, increasing the energy consumed as well as the incapability of activating all neurons in a large-scale network. To overcome these drawbacks, we investigated the effects of the stimulation waveform and interphase delays on the overall efficiency and efficacy of DBS. We also propose a new feedback control variable based on the filtered and linearly delayed LFP recordings. The proposed control variable is then used to modulate the frequency of the stimulation signal rather than its amplitude. In strongly coupled networks, oscillations reoccur as soon as the amplitude of the stimulus signal declines. Therefore, we show that maintaining a fixed amplitude and modulating the frequency might ameliorate the desynchronization process, increase the battery lifespan and activate substantial regions of the administered DBS electrode. The charge balanced stimulus pulse itself is embedded with a delay period between its charges to grant robust desynchronization with lower amplitude needed. The efficiency and efficacy of the proposed Frequency Adjustment Stimulation (FAS) protocol in a delayed feedback method might contribute to further investigation of DBS modulations aspired to address a wide range of abnormal oscillatory behaviors observed in neurological disorders. Adaptive stimulation can open doors towards simultaneous stimulation with MRI recordings. We additionally propose a new pipeline to investigate the effect of Transcranial Magnetic Stimulation (TMS) on patient specific models. The pipeline allows us to generate a full head segmentation based on each individual MRI data. In the next step, the neurosurgeon can adaptively choose the proper location of stimulation and transmit accurate magnetic field with this pipeline

A Hyperbolic Model of Neuronal Spiking Patterns in Parkinson’s Disease

This poster was also presented on 2015-04-30 at Northeast Section American Society for Engineering Education 2015 in Boston, MA.To investigate how different types of neurons in brain can produce well known spiking patterns, a new computationally efficient model is proposed in this poster. The model can demonstrate various neuronal behavior observed in vivo such as abnormal pattern of subthalamic nucleus (STN) in Parkinson’s disease. The irregular and arrhythmic behavior of STN firing pattern under normal conditions can easily be transformed to those caused by Parkinson’s disease through simple parameter modifications. This model can explicitly show the change of neuronal activity patterns in Parkinson’s disease, which may eventually lead to effective bio-chip designs that can be used to assist in the control, treatment, and ultimately, the cure of the disease

A Superposed Quantum Model of Brain Spiking Neurons

© ASEE 2015In all mammalian brain billions of neurons exist and these neurons are working together through synapses and spike responses. A big question stand still in the field of neuroscience. Why a neuron can produce different types of spikes under same conditions? We showed that unknown and random behavior of neuronal spikes through time can be described by this quantum fact that a neuron can be in many states at a same time, therefore any spike patterns or combination of spike patterns can be understandable. Based on neuronal spikes patterns, sometimes we observed an unknown pattern can be explained by this phenomena that a neuron can exist partially in a physical state but when it’s response to an stimuli is recorded the result would be only one of the possible states or a linear combination of some states

Robust desynchronization of Parkinson’s disease pathological oscillations by frequency modulation of delayed feedback deep brain stimulation

The hyperkinetic symptoms of Parkinson’s Disease (PD) are associated with the ensembles of interacting oscillators that cause excess or abnormal synchronous behavior within the Basal Ganglia (BG) circuitry. Delayed feedback stimulation is a closed loop technique shown to suppress this synchronous oscillatory activity. Deep Brain Stimulation (DBS) via delayed feedback is known to destabilize the complex intermittent synchronous states. Computational models of the BG network are often introduced to investigate the effect of delayed feedback high frequency stimulation on partially synchronized dynamics. In this study, we develop a reduced order model of four interacting nuclei of the BG as well as considering the Thalamo-Cortical local effects on the oscillatory dynamics. This model is able to capture the emergence of 34 Hz beta band oscillations seen in the Local Field Potential (LFP) recordings of the PD state. Train of high frequency pulses in a delayed feedback stimulation has shown deficiencies such as strengthening the synchronization in case of highly fluctuating neuronal activities, increasing the energy consumed as well as the incapability of activating all neurons in a large-scale network. To overcome these drawbacks, we propose a new feedback control variable based on the filtered and linearly delayed LFP recordings. The proposed control variable is then used to modulate the frequency of the stimulation signal rather than its amplitude. In strongly coupled networks, oscillations reoccur as soon as the amplitude of the stimulus signal declines. Therefore, we show that maintaining a fixed amplitude and modulating the frequency might ameliorate the desynchronization process, increase the battery lifespan and activate substantial regions of the administered DBS electrode. The charge balanced stimulus pulse itself is embedded with a delay period between its charges to grant robust desynchronization with lower amplitudes needed. The efficiency of the proposed Frequency Adjustment Stimulation (FAS) protocol in a delayed feedback method might contribute to further investigation of DBS modulations aspired to address a wide range of abnormal oscillatory behavior observed in neurological disorders.https://doi.org/10.1371/journal.pone.020776

EEG Signal Analysis for Effective Classification of Brain States

EEG (Electroencephalogram) is a non-stationary signal that has been well established to be used for studying various states of the brain, in general, and several disorders, in particular. This work presents efficient signal processing and classification of the EEG signal. The digital filters used during decomposition of the input EEG signal have transfer functions which are simple and easily realizable on digital signal processors (DSP) and embedded systems. The features selected in this study; energy, entropy and variance; are among the most efficient and informative to analyze the EEG signal strength and distribution for detecting brain disorders such as seizure. Training and testing of the extracted features are performed using linear kernel (Support Vector Machine) SVM and thresholding in DSP algorithms and hardware, respectively. The experimental results for the digital signal processing algorithms show a high classification accuracy of 95% in the occurrence of seizure in epileptic patients. The techniques in this work are also under investigation for classifying other brain states/disorders such as sleep stages, sleep apnea and multiple sclerosis

Hyperbolic Modeling of Subthalamic Nucleus Cells to Investigate the Effect of Dopamine Depletion

To investigate how different types of neurons can produce well-known spiking patterns, a new computationally efficient model is proposed in this paper. This model can help realize the neuronal interconnection issues. The model can demonstrate various neuronal behaviors observed in vivo through simple parameter modification. The behaviors include tonic and phasic spiking, tonic and phasic bursting, class 1 and class 2 excitability, rebound spike, rebound burst, subthreshold oscillation, and accommodated spiking along with inhibition neuron responses. Here, we investigate the neuronal spiking patterns in Parkinson’s disease through our proposed model. Abnormal pattern of subthalamic nucleus in Parkinson’s disease can be studied through variations in the shape and frequency of firing patterns. Our proposed model introduces mathematical equations, where these patterns can be derived and clearly differentiated from one another. The irregular and arrhythmic behaviors of subthalamic nucleus firing pattern under normal conditions can easily be transformed to those caused by Parkinson’s disease through simple parameter modifications in the proposed model. This model can explicitly show the change of neuronal activity patterns in Parkinson’s disease, which may eventually lead to effective treatment with deep brain stimulation devices

Computational Stimulation of the Basal Ganglia Neurons with Cost Effective Delayed Gaussian Waveforms

Deep brain stimulation (DBS) has compelling results in the desynchronization of the basal ganglia neuronal activities and thus, is used in treating the motor symptoms of Parkinson's disease (PD). Accurate definition of DBS waveform parameters could avert tissue or electrode damage, increase the neuronal activity and reduce energy cost which will prolong the battery life, hence avoiding device replacement surgeries. This study considers the use of a charge balanced Gaussian waveform pattern as a method to disrupt the firing patterns of neuronal cell activity. A computational model was created to simulate ganglia cells and their interactions with thalamic neurons. From the model, we investigated the effects of modified DBS pulse shapes and proposed a delay period between the cathodic and anodic parts of the charge balanced Gaussian waveform to desynchronize the firing patterns of the GPe and GPi cells. The results of the proposed Gaussian waveform with delay outperformed that of rectangular DBS waveforms used in in-vivo experiments. The Gaussian Delay Gaussian (GDG) waveforms achieved lower number of misses in eliciting action potential while having a lower amplitude and shorter length of delay compared to numerous different pulse shapes. The amount of energy consumed in the basal ganglia network due to GDG waveforms was dropped by 22% in comparison with charge balanced Gaussian waveforms without any delay between the cathodic and anodic parts and was also 60% lower than a rectangular charged balanced pulse with a delay between the cathodic and anodic parts of the waveform. Furthermore, by defining a Synchronization Level metric, we observed that the GDG waveform was able to reduce the synchronization of GPi neurons more effectively than any other waveform. The promising results of GDG waveforms in terms of eliciting action potential, desynchronization of the basal ganglia neurons and reduction of energy consumption can potentially enhance the performance of DBS devices

Closed Loop Deep Brain Stimulation for Parkinson’s disease with Frequency Modulation

Neural oscillations within the Basal Ganglia (BG) circuitry are associated with Parkinson’s Disease (PD) and are observable through the Local Field Potential (LFP) of the Subthalamic Nucleus (STN) or Globus Pallidus externa (GPe) neurons. LFP amplitude modulation in a delayed feedback protocol for Deep Brain Stimulation (DBS) is shown to destabilize the complex intermittent synchronous states. However, traditional High Frequency Stimulations (HFS) often intensify the synchronization of highly fluctuating neurons, are less efficient in activating all neurons in large scale networks and consume more battery of the DBS device. Here, we investigate the partially synchronous dynamics of a STN-GPe coupling network to examine the effect of frequency adjustment in the stimulation signal. The frequency of the stimulation signal is adjusted according to the nonlinear delayed feedback LFP of the STN population. Frequency adjustment protocol with a fixed stimulation amplitude is shown to increase the desynchronization efficiency and neuronal activation by 25% and 16.2%, respectively, while reducing the energy consumption by 31.5% compared to amplitude modulation methods for stimulation of large networks (1000 neurons)

supporting data.mat

<p>data is the supplementary information for this article " Robust desynchronization of Parkinson's disease pathological oscillations by frequency modulation of delayed feedback deep brain stimulation".</p

A system dynamics model for optimal allocation of natural gas to various demand sectors

The final publication is available at Elsevier via https://doi.org/10.1016/j.compchemeng.2019.05.040. © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Natural gas is the most promising fossil fuel in the transition to a low-carbon energy future, and many countries have long term plans to increase its share in their energy supply mix through pricing regulations. While these policies encourage substitution of natural gas with more polluting fossil fuels, its over consumption and inefficient use can lead to misallocation of resources and CO2 emission increase. This paper develops a supply-demand model to optimally allocate natural gas to various demand sectors through determining a price path for each sector. The dynamic effects of price on demand, and income on supply are modeled using system dynamics. The model is applied to a case study on the optimal consumption share of each demand sector according to economic and environmental criteria. The results show that the residential sector should have a much smaller and export much larger share of the recommended consumption mix in 2040