Mechanism Of Brain Network In Gamma Oscillation Absence In Working Memory Dysfunction

Alzheimer’s disease(AD) is a common neurodegenerative disorder that gradually induces cognitive deficit in the elderly. It is not only a serious threat to the patient’s health, but also brings heavy burdens to society. With the advent of the aging society, the incidence of AD is keep increasing every year. At present, China has entered the aging society, with the largest aging population in the world. Therefore,studying on the pathogenesis of AD has important academic meaning, clinical application significance and social benefits.Working memory dysfunction was typically observed in AD clinical practice.Working memory, defined as a system for the temporary holding and manipulation of information important for a range of cognitive tasks, is the foundation of the higher cognitive functions such as planning behavior, comprehension, reasoning and decision making. Studying on working memory dysfunction in AD may yield important insights into the pathogenesis of AD.Gamma oscillations play an important role in various cognitive functions. The synchronized gamma oscillations are essential for the successful execution of working memory. Research on the gamma oscillation mechanism of working memory dysfunction in AD is one of the hot spots in the field of pathogenesis of AD.Recently, the concept of networked brain has been widely proposed. It is beneficial for the investigation of cognitive functions as well as cognitive disorders, and thus provides a new idea for the mechanism investigation of neural system diseases.Based on the above, the questions raised here: What is the pattern of gamma oscillation in working memory dysfunction? What is the mechanism of gamma oscillation absence from the view of brain network?According to the above questions, in the present thesis, we employed the awake animal in vivo implantable electrodes recording technique and obtained local field potentials(LFPs) from multi-electrodes implanted in prefrontal cortex of the rats(control group and Aβ-injected group) when they performed a Y-maze working memory task. The thesis aims to investigate the characteristic patterns of gamma oscillation among LFPs in working memory dysfunction and the mechanism of brain network in gamma oscillation absence in working memory dysfunctionThe main work of this thesis are as follows:1. Establishment and identification of Aβ1–42-induced rat model with working memory dysfunctionSprague-Dawley(SD) rats(male, 2.5 months) were divided randomly into two groups: working memory dysfunction group, comprised of Aβ1–42-induced toxicity rats; control group, comprised of healthy rats. 36h-Incubated Aβ1–42(5 μl, 1 μg/μl)was injected into DG of dorsal hippocampus bilaterally. 14 days after Aβ1–42 injection,the rats with subsequent working memory deficits on Y-maze were identified as Aβ1–42-induced toxicity rat model. We first investigated whether Aβ1–42 could be detected in rat hippocampus with Aβ1–42 intra-hippocampal injection. Using immunohistochemistry, we found a number of Aβ1–42 positive immunostaining in the working memory dysfunction group.2. Behavioral performance in the two groupsThe correct percent and latency of the two groups during a Y-maze working memory task were analyzed to investigate the characteristic patterns of behavioral performance in working memory dysfunction group.3. Acquisition of 16-channel LFPs from rat PFC during the working memory taskWe employed the in vivo implantable electrodes recording technique for awake animal and recorded neuronal activity from multi-electrodes implanted in rat PFC when they performed a Y-maze working memory task.The recorded neural activity was filtered(<500 Hz) to obtain the 16-channel LFPs. LFPs was then preprocessed to remove the baseline drift and power-line interference.We recorded LFPs from 16 rats(8 rats,120 trials for the control group; 8 rats,120 trials for working memory dysfunction group) while they performed the Y-maze working memory task.4. Gamma oscillation absence in the working memory dysfunction group(1) Time and frequency of Gamma oscillation absence in the working memory dysfunction groupThe short-time Fourier transform(STFT) was applied to calculate the power spectrum of LFPs during the working memory task. We found that the gamma(30-60Hz) power increased significantly and peaked before the referance point in the control group, indicating the gamma oscillation emerged during working memory;while the gamma power in the working memory dysfunction group never experience such changes.(2) Synchronous Gamma oscillation absence in the working memory dysfunction groupThe coherence analysis was applied to estimate the gamma oscillation during the working memory task. We found that the coherence value in the gamma band increased significantly and peaked before the referance point in the control group,indicating the gamma oscillation emerged during working memory; while the coherence value in the working memory dysfunction group never experience such changes, indicating the synchronous gamma oscillation absence.5. Mechanism of brain network in gamma oscillation absence in working memory dysfunctionWe then applied the Granger causal analysismethod to estimate the direct transform function among LFPs(gamma-band) during the working memory task in the two groups. Causal network was constructed based on the DTF matrix.(1) Gamma network defect in working memory dysfunctionWe respectively employed DTFij and averaged DTF of all DTFij to quantify the connection strength from node j to node i and the overall connection strength in the causal network.The results show that:The averaged DTF value in the control group increased and peaked before the rats arrived the referance point during the working memory task; while the one in the working memory dysfunction group never experience such changes.The averaged DTF value in working memory in the control group was definitely higher than that in the working memory dysfunction group indicating the gamma network defect in the working memory dysfunction(2) Mechanism of brain network in gamma oscillation absence in working memory dysfunctionIn the control group, the peak time of DTF value was prior to the peak time of gamma coherence during working memory, indicating the the strengthened gamma oscillation may emerge from the enhanced network connectivity. In the working memory dysfunction group, there was no obvious gamma oscillation and enhanced network connectivity.The thesis provides new insights and methods for the mechanism study of working memory dysfunction...