Control analysis of deep brain stimulation and optogenetics for Alzheimer's disease under the computational cortex...

Abnormal τ and β-amyloid (Aβ) deposition in the brains of patients with Alzheimer's disease (AD) is significantly associated with cognitive decline. This abnormal deposition has been reported to be linked to increased excitatory and inhibitory time constants in neural circuits. In this paper, we focus on three typical electroencephalography (EEG) slowdowns clinically reported in association with AD, including decreased dominant frequency, decreased α rhythmic activity, and increased δ + θ rhythmic activity. Firstly, we demonstrate that changes in excitatory time constant, inhibitory time constants, and synaptic connection strength can induce the phenomenon of EEG slowdowns in early AD. Then, we are interested in the regulation of AD by traditional deep brain stimulation (DBS) and emerging optogenetic stimulation. High-frequency, high-pulse width, and high-amplitude DBS are more effective in reversing brain rhythm in AD, supporting the experiment that cortical high-frequency DBS may be an effective therapeutic way for dementia-related diseases. In particular, as a modification of traditional DBS, we find that oscillatory bursty stimulation can compensate for the shortcomings of DBS at low amplitude. However, it is physiologically difficult to target inhibitory interneurons with conventional electrical stimulation. Optogenetics is able to precisely stimulate pyramidal neurons and inhibitory interneurons observed in animal experiments. Our numerical results indicate that medium and low-frequency stimulation can better eliminate AD pathology. It should be noted that stimulation of inhibitory interneurons requires greater light intensity than stimulation of pyramidal neurons. Finally, we propose two optimization intermittent optogenetic stimulation protocols. These modeling results can reproduce some experimental phenomena and are expected to reveal the underlying pathological mechanisms and control strategies associated with cognitive dysfunction such as AD.