A Neural Model-based Study Of Deep Brain Stimulation Control In Alzheimer's Disease

Deep brain stimulation（DBS）has been clinically used in the treatment of diseases such as Parkinson’s disease and epilepsy,and the treatment effect of DBS is remarkable.DBS has a good application prospect.In recent years,DBS has been gradually applied to the treatment of Alzheimer’s disease（AD）.AD is a degenerative disease of the nervous system with insidious onset.Clinical studies and animal experiments have shown that DBS plays an important role in the regulation of AD,but the selection of targets,the regulation of stimulus parameters,and the related biophysical mechanisma need to be resolved urgently.In view of this,based on neural computing models,this work combines neural dynamics and control theory to explore the regulation and control effect of DBS on AD.The main content and conclusions of the work are as follows:1.Study the control effect of thalamic relay nucleus DBS on AD.First,based on the physiological structure and experimental data of the cortex and thalamus,a thalamic-cortex-thalamic（TCT）neurological quality model related to AD under the action of DBS was constructed.Then,we simulate the neuropathological state of AD synapse loss by reducing the strength of synaptic connections from thalamic interneurons to the thalamus relay nucleus.Further,DBS was introduced into the thalamus relay nucleus to explore the effect of DBS on the pathological state of AD.Combined with power spectrum analysis and phase space analysis,it is found that the relative power of the theta band of the model decreases and the relative power of the alpha band increases.This is consistent with the reversal of the EEG in the AD drug efficacy comparison test,which means that the EEG rhythm is gradually restored.At the same time,the phase space transitions from the point attractor to the limit cycle mode,and the membrane potential changes from the non-discharge state to the discharge state.These results indicate that DBS can significantly alleviate the pathological symptoms of AD.Finally,adjust the amplitude A,cycle P and duration D of DBS in the parameter space.It is found that within the appropriate parameter range,DBS can effectively improve the pathological symptoms of AD and has a better control effect on AD.2.Study the regulation of hippocampal DBS on AD.First,according to the physiological structure and synaptic connections of hippocampal CA1 area,a neuronal network model of hippocampal CA1 area related to AD under the regulation of DBS was constructed.Then,by enhancing M current IM of pyramidal,the potassium ion current IAHP activated by calcium ions to simulate the pathological state of cholinergic deficiency in AD,and we simulate the pathological state of beta amyloid（Aβ）deposition in AD by enhancing the delayed rectifier K+current IK.Finally,in the pathological state of AD,using power spectrum analysis and phase space analysis,it is found that proper adjustment of the amplitude A,period P,and duration D of the DBS can reduce the relative power in theta frequency band of the network model,and the membrane potential gradually returns to the oscillating state from the resting state.The space has also changed from point attractor mode to limit cycle mode,which indicates that the pathological symptoms of AD are alleviated,which means that DBS can effectively control AD.In this work,the relay nucleus of the thalamus and the CA1 area of the hippocampus are used as targets of DBS.By establishing a neural computing model related to AD,it is revealed that DBS with appropriate parameters can effectively control AD theoretically.This study highlights the potential role of DBS in the treatment of AD.The selection of targets and the suitable range of DBS parameters in this work provide theoretical basis and reference for animal experiments and clinical research,and are of great significance for the development of DBS in the treatment of AD.