Investigating the Neural Correlates of Pathological Cortical Networks in Alzheimer's Disease Using Heterogeneous Neuronal Models

Abstract

This paper describes an investigation into the pathophysiological causes of abnormal cortical oscillations in Alzheimer's disease (AD) using two heterogeneous neuronal network models. The effect of excitatory circuit disruption on the beta band power (13-30 Hz) using a conductance-based network model of 200 neurons is assessed. Then, the neural correlates of abnormal cortical oscillations in different frequency bands based on a larger network model of 1000 neurons consisting of different types of cortical neurons are also analyzed. EEG studies in AD patients have shown that beta band power (13-30 Hz) decreased in the early stages of the disease with a parallel increase in theta band power (4-7 Hz). This abnormal change progresses with the later stages of the disease but with decreased power spectra in other fast frequency bands plus an increase in delta band power (1-3 Hz). Our results show that, despite the heterogeneity of the network models, the beta band power is significantly affected by excitatory neural and synaptic loss. Second, the results of modeling a functional impairment in the excitatory circuit shows that beta band power exhibits the most decrease compared with other bands. Previous biological experiments on different types of cultural excitatory neurons show that cortical neuronal death is mediated by dysfunctional ionic behavior that might specifically contribute to the pathogenesis of β-amyloid-peptide-induced neuronal death in AD. Our study also shows that beta band power was the first affected component when the modeled excitatory circuit begins to lose neurons and synapses.

Model-based bifurcation and power spectral analyses of thalamocortical alpha rhythm slowing in Alzheimer's Disease

“…The output of the model is the membrane potential of the TCR cell 1 It is worth mentioning here that the delta (1-3 Hz), theta (3-7 Hz) and beta (13)(14)(15)(16)(17)(18)(19)(20) bands are also well known to be affected in AD (see [53,54] for a model-based study on these EEG frequency bands). However, we ignore these in the present work for brevity and confine our investigation to the alpha band only.…”

Integration of Network Topological and Connectivity Properties for Neuroimaging Classification

“…In the literature, it has been shown that many neurological and psychiatric disorders can be categorized as dysconnectivity/hyperconnectivity syndromes, which are commonly associated with the disrupted synchronization or the abnormal integration of different brain regions [9], [10]. Rapid advances in neuroimaging techniques have provided an efficient and noninvasive way for studying the structural and functional connectivity of human brain [11].…”

A VLSI Circuit Emulation of Chemical Synaptic Transmission Dynamics and Postsynaptic DNA Transcription

“…The proposed VLSI implementation thus provides an emulation platform for computational neuroscience at the molecular level. Future effort may include the use of this model to simulate at molecular level, neurological disorders that are related to synaptic transmission process, such as Alzheimer's disease [64]. In addition, future expansion of this research may include the circuit model of molecular interactions in the biochemical pathways (extending from the cytosol to the nucleus of the neuron) that are activated by the translated proteins from postsynaptic DNA transcription.…”