| Part I:The research of the structural characteristics of NREM,REM stage and sleep transition period in patients with chronic insomnia disorder based on EEG signalObjective:In this paper,we studied the sleep structure characteristics of patients with chronic insomnia disorder(CID)and good sleeper(GS)during NREM,REM period and sleep transition by analyzing and comparing the characteristics of EEG spectrum density during sleep period,we aimed to explore the biological markers from EEG signals of patients with CID.Methods:Twenty-six chronic insomnia disorder patients(15 female/11 male,47.0±6.0 years)and twenty-three good sleeper(15 female/8 male,46.3±4.3 years)were underwent a polysomnography(PSG)recordings for 3 consecutive nights(one adaptation night,two test nights)in the sleep lab.The EEG density characteristics in the sleep onset period(SOP,within 5 mins before and after the first sleep spindle wave),the sleep maintenance stage(10 mins of stable NREM 2,NREM 3,REM in the first sleep cycle)and the sleep transition(5 mins before and after the first REM sleep)were analyzed by using the Fast Fourier Transform(FFT)method.Results:1.Compared with the GS group,the CID group saw the following changes:the total sleep time(TST)shortened(t=4.682,P<0.001);the sleep efficiency(SE)decreased;the sleep latency(SL)extended(t=-6.46,P<0.001);the proportion of the Stage N2 increased(t=-4.0,P<0.001)while that of the Stage N3(t=6.8,P<0.001)decreased;the sleep time of the Stage N3 decreased(t=-2.933,P=0.003)and the time of Waking After Sleep Onset(WASO)increased(t=-4.350,P<0.001);the arousal index increased(t=2.150,P=0.011).2.We found that there was no significant difference between two groupsin EEG power spectrum density of Delta(1-4Hz),Theta(4-8Hz),Alpha(8-12Hz),Sigma(12-16Hz),Beta-1(16-20Hz)and Beta-2(20-32Hz)in the SOP period.However,there were the following differences between them:the CID group saw a lower increase rate respectively in the Theta within the first 5 mins of SOP and in the Sigma within the last 5 mins of SOP,and a lower drop rate in the Beta-1 within the last 5 mins of SOP.In the Stage N2 of the sleep maintenance period there was no significant differences between them,but Delta in the Stage N3 for the CID group was obviously lower than that for the other group.In the REM period,Alfa for the CID group was apparently higher that for the GS group.In the sleep transition,the Alpha,Sigma,Beta-1 and Beta-2 for the CID group were significantly higher in frequency than the GS group.Conclusion:During the sleep onset period,the dynamic differences between the CID group and the GS group in Theta,Beta-1 and Sigma may suggest that patients with CID have the hyper cortical arousal.In the sleep transition,the CID EEG recordings related to the CID group showed an increase of Sigma,Alpha,Beta-1 and Beta-2 in frequency,probably implying that waking-promoting and sleep-protecting neural activities can be activated simultaneously.Besides,there may be energies that cause sleep to transit from one stage to another stage.Sigma in the sleep spindles may play a key role in affecting the brain network mechanism of sleep.Part II:The Study on the Correlations between Cognitive functions between Slow-wave Sleep and Sleep Spindle of Patients with Chronic Insomnia DisorderObjective:To study and analyze the correlation of spindle features and slow-wave sleep with cognitive functions in the stages N2 and N3 of patients with CID and GSs and further to explore how the cognitive impairment occurs due to CID.Methods:15 patients with CID,10 females and 5 males,ages 35-55,and 15 good sleepers(GS),9 females and 6 males,were selected to undergo a polysomnography(PSG)test for 3 nights(one adaptation night,two test nights)in the sleep lab.First,we respectively analyzed the sleep structure of CID patients and GSs;second,we analyzed the number and density of sleep spindles in stages N2 and N3 as well as their density in such two stages when the sleep is stable in the first sleep cycle.We used the Nine Box Maze Test to evaluate the spatial working memory and the declarative memory of subjects.We also utilized the Wechsler Memory Scale to measure the long-term memory,the short-term memory,the instantaneous memory,and the concentration.Finally,we analyzed the correlation between cognitive functions and the slow-wave sleep and sleep spindles.Results:1.Compared with the GS group,the CID group saw the following differences:the total sleep time(TST)shortened(z=3.997,P<0.001);the sleep efficiency(SE%)decreased(t=-5.35,p<0.001);the sleep latency extended(SL)(z=-3.901,p<0.001);the time of the Stage N3(z=-3.13,p=0.002)and stages N2+N3(z=-3.15,p=0.003)shortened;and the time of Waking After Sleep Onset(WASO)(t=-3.629,p<0.001)and the arousal index increased(t=-2.975,p=0.006).2.There was no significant differences between both groups in the number of sleep spindles in the Stage N2(z=-1.742,p=0.081),but the number of sleep spindles of the CID group in the Stage N3 dropped sharply(z=-0.344,p=0.019).Evens so,statistically,the total number of sleep spindles in stages N2 and N3(z=-1.98,p=0.63)and the sleep spindle destiny in the NREM period for both groups were almost the same.Compared with the CID group,the destiny of the sleep spindle M in the stages N2 and N3 within 10 mins of the first NREM dropped(z=-2.24,p=0,025)3.We found that,compared with the GS group,that the CID group had its cognitive function damaged seriously in such aspects as the spatial working memory,the long-term memory,the short-term memory and the concentration In terms of the spatial working memory,abilities of the object memory(z=-3.15,p=0.002),the spatial memory(z=-2.192,p=0.028)and the object recognition decreased(z=-2.19,p=0.028).Besides,the long-term memory(z=-2.352,p=0.028),the short-term memory(z=-2.10,p=)and the concentration showed great differences from those of the GS group4.Based on the studies on correlation between the PSG sleep structural parameters and cognitive functions,we found that the sleep time in the Stage N3 had a negative correlation with the spatial working memory(r=-0.439,p=0.015)and the object recognition(r=-0.433,p=0.017),the sleep efficiency also had the same correlation with the object memory(r=-0.373,p=0.042),and the sleep latency had a positive correlation with the spatial working memory(r=-0.393,p=0.032).As for the Stage R,the sleep latency and the WTAS were both positively correlated to the object memory(r=0.508,p=0.017,and r=0.447,p-0.013),the sleep efficiency was positively corelated to long-term memory(r=0.49,p=0.006),short-term memory(r=0.455,p=0.013),concentration(r=0.501,p=0.005)and the memory quotient(r=0.541,p=0.002),the sleep latency had a negative correlation with the long-term memory(r=-0.371,p=0.0.043)and the memory quotient(r=-0.383,p=0.037);and the WTAS was negatively correlated to the long-term memory(r=-3.81,p=0.038),the concentration(r=-0.435,p=0.016)and the memory quotient(r=-0.415,p=0.022).5.Based on the studies on correlation between the sleep spindles and the cognitive functions,we found that the absolute value(r=-0.386,p=0.035)of the number of sleep spindles in the Stage N3 were negatively corelated to object recognition;the destiny of sleep spindles in the Stage N2 within 10 mins of the stable sleep in the first NREM period was negatively correlated to object recognition(r=-0.509,p=0.004)and the object working memory(r=-0.520,p=0.003).Conclusion:Cognitive impairment of patients with CID,especially,the spatial working memory impairment,may result from decrease of SWS and sleep spindles,probably symbolizing the unbalance of brain synapse remodeling.Such unbalance becomes the main reason causing the cognitive impairment of patients with CID,especially deteriorating their spatial working memory and the concentration.Part Ⅲ:The Resting-state EEG Function Connectivity-based Analysis on the Brain Network Mechanism of Patients with CIDObjective:To analyze the correlation between brain functional connectivity and cognitive functions of stable sleep in the NREM period of patients with chronic insomnia disorder(CID)and good sleepers(GS)so as to explore the brain network mechanism with cognitive impairment resulting from CID.Methods:15 patients with CID,10 females and 5 males,aged at 45,and 15 good sleepers,9 females and 6 males,aged at 45,were selected to undergo the polysomnographic(PSG)test.The WPLI was adopted to analyze the topological distribution characteristics of functional connectivity indices of Delta,Theta,Alpha,Sigma and Beta in stages N2,N3 and R.The Nine Box Maze Test and the Wechsler Memory Scale were also used to measure the spatial working memory,the long-term memory,the short-term memory,the instantaneous memory,and concentration.At last,the correlation was conducted between the WPLI analysis results and the measuring results of the Nine Box Maze Test and the Wechsler Memory Scale.Results:1.Functional connectivity of the resting-state EEG brain network was used to compare the WPLI results by pair and to analyze the difference between patients with CID and good sleepers in the functional connectivity of the brain network.The analysis results are shown below:in the Stage N2 the connectivity of all frequency spectrums of patients with CID became stronger,especially the connectivity for Beta rhythm between the prefrontal lobe in the two cerebral hemispheres and the parietal lobe.The connectivity between the frontal lobe and the parietal lobe for Sigma of the GS group changed most.In the Stage N3,Theta of the CID group distributed more broadly while Delta and Sigma of the GS group saw stronger connectivity.The central zone on the left top was mainly involved in.In the Stage R,Beta and Sigma for both groups experienced the same change.However,only Alpha of the CID group had its connectivity between the frontal lobe and the occipital lobe become stronger and spread more widely.2.According to the research on the correlation between WPLI and cognitive domain,the connectivity of Sigma in F3-C3 in the Stage N2(r=0.386,p<0.05)was positively correlated to the short-term memory;the F3-C3 connectivity was positively correlated to the memory quotient(r=0.410,p<0.05).In the Stage N3,the F3-C3 connectivity of Sigma had a negative correlation with the times of misidentifying objects in the spatial memory(r=-0.412,p<0.05)and had a positive correlation respectively with the short-term memory(r=0.393,p<0.05),the memory quotient(r=0.450,p<0.05)and the concentration(r=0.349,p<0.05).In the Stage REM,the connectivity between the bilateral frontal lobe and partial lobe and bilateral occipital lobes in the Alpha was significantly strengthened.Lead F3-01 showed that its connectivity was positively correlated to the times of misidentifying objects in the memory(r=0.42,P<0.05)and to the times of misidentifying objects in the spatial memory(r=0.497,p<0.05);it also showed that its connectivity was positively related to the times of misidentifying the reference objects(r=0.40,p<0.05)and the times of misidentifying objects in the special memory(r=0.039,p<0.05).Lead F4-02 showed that its connectivity was positively correlated to the times of misidentifying objects in the spatial memory(r=0.518,p<0.05).Lead C3-03 showed that its connectivity had a positive correlation with the times of misidentifying the reference objects(r=0.508,p<0.05).Lead C4-03 showed that its connectivity was positively correlated to the times of misidentifying objects in the spatial memory(r=0.507,p<0.05)and negatively correlated to the long-term memory(r=-0.514,p<0.05)and the concentration(r=-0.384,p<0.05).Conclusion:We found that the connectivity of Sigma between the frontal lobe and the parietal lobe in the stages NREM and REM in the first sleep circle of patients with CID became weaker,suggesting that the sleep-protecting mechanism of insomniacs is impaired.Such impairment may prevent insomniacs from entering their SWS sleep,make such sleep unstable,and further damage their memories,especially spatial working memory,the short-term memory and concentration.We also found that the connectivity of Alpha in the Stage REM between the parietal lobe and the occipital region became stronger due to dreaminess and multiple awakenings,thus impairing concentration,the spatial working memory and the long-term memory... |
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