Brain Network Of Working Memory Dysfunction In TLE With Depression

ObjectiveTemporal lobe epilepsy(TLE)is a common refractory epilepsy and about 50%of the TLE patients suffer from comorbid depression.Comorbid depression in TLE patients leads to cognitive disorder,reduced quality of life and increased risk of suicide.TLE with depression patients are often accompanied with the dysfunction in working memory(WM),which serves as a foundation for complex cognitive functions,such as learning,language comprehension and logical reasoning.Therefore,it is of great importance to explore the mechanism underlying WM disorder in TLE with depression.The study examined the behavioral manifestations and analyzed the characteristics inneuraloscillationandbrainnetworkbasedonthemulti-channel electroencephalographs(EEGs)of TLE patients with depression during a WM task,to explore the neural mechanisms of WM dysfunction in TLE with depression.It is expected to gain new insight for mechanism exploration and provide a theoretical support for the diagnosis and treatment of TLE with depression.Methods1.Behavioral performance(1)Subjects:TLE patients were divided into two groups:TLE with depression and TLE without depression,according to the Beck Depression Inventory II(BD-II)and the Hamilton’s Depression Scale(HAMD)-17 score.Matched healthy controls were also included(10 subjects in each group).(2)Behavioral data acquisition and analysis:reaction time(RT)and accuracy for all groups was recorded and analyzed during a visual WM task.2.Pattern changes of theta oscillation in WM delay period(1)Experimental data:34-channel EEGs were recorded from the three groups(10subjects in each group)while the subjects performed the visual WM task.(2)EEG preprocessing:Artifacts caused by electrooculography,50 Hz noise and baseline drift were excluded from the original EEGs.(3)Time-frequency analysis:Short-time Fourier transform(STFT)was used to obtain the time-frequency distribution and the principal frequency band and key time period for WM was determined.(4)Topographical maps in the principal frequency band and key time period were respectively presented and the differences of the three groups were statistically compared.3.Funtional connectivity changes of gamma network in WM delay period(1)Directed transfer function was employed to calculate the funtional connectivity among the 34 channels EEGs during the WM delay periord and the causal networks were constructed.(2)The functional connectivity strengths of the brain network were calculated.The patterns in different frequency bands were analyzed and the principal frequency band for WM was determined.(3)The topographies of functional connectivity in the principal frequency band were analyzed.The differences in the functional connectivity strength were statistically compared among the three groups.Results1.Behavioral performance(1)The accuracy of control,TLE and TLE with depression was 97.35±0.70%,92.01±1.31%,91.28±1.13%,respectively(P<0.01).The RT of control,TLE and TLE withdepressionwas699.78±29.64ms,930.95±41.23ms,1092.43±41.38ms,respectively(P<0.001).Compared with controls,the accuracy of TLE patients with depression decreased obviously(P<0.001).Compared with controls and TLE patients,the reaction time of TLE patients with depression increased significantly(P<0.001).2.Pattern changes of theta oscillation in WM delay period(1)The EEGs power for the controls mainly concentrated on theta band,therefore,theta band was selected as the principal band for WM.(2)The percentage of theta power in TLE patients with depression was significantly decreased during the delay period,compared with those in the other two groups,(P<0.05).(3)The topographical of maps presented the power mainly concentrant on frontal middle region.The theta power in frontal lobe(especially in Fz)(frontal 0.0586±0.0188μV~2/Hz;Fz 0.2036±0.0189μV~2/Hz)in TLE patients with depression were decreased,compared with the TLE patients without depression(frontal0.2139±0.0070μV~2/Hz;Fz0.2895±0.0178μV~2/Hz)andcontrols(frontal0.2869±0.0117μV~2/Hz;Fz 0.3642±0.0185μV~2/Hz)(P<0.05).3.Funtional connectivity changes of gamma network in WM delay period(1)The connectivity strengths for all group peak in the delay period in gamma band(30-80Hz),and the gamma band presented the strongest connectivity strength(P<0.05).Therefore,gamma band was determined as the principal band for WM.(2)In TLE patients with depression,the averaged causal connectivity strength in gamma network was significantly lower during the delay period(P<0.05).(3)Topographies of gamma network showed the strong connectivity in frontal area,especially in Fz.Compared with the control(frontal 0.0023±0.0001;Fz0.0195±0.0010)and TLE groups(frontal 0.0012±0.0001;Fz0.0114±0.0007~),the connectivity strength in the TLE patients with depression group(frontal0.0004±0.0001;Fz 0.0075±0.0007)was significantly decreased(P<0.05).Conclusion1.The TLE patients with depression suffered from WM dysfunction,with declined accuracy and increased reaction time.2.Absence of theta oscillation in WM dysfunction in TLE with depression(1)Theta oscillation plays an important role in WM.(2)The frontal area(Fz,in particular)is one of the key responsible areas for WM;(3)The absence of theta oscillation in frontal area(especially in Fz)during the delay period may provide a potential neural mechanism for WM dysfunction in TLE with depression.3.Absence of gamma brain network in WM dysfunction in TLE with depression(1)Gamma oscillation brain network is closely related to WM.(2)The frontal area(Fz,in particular)is one of the key responsible areas for WM gamma brain network;(3)The absence of gamma brain network in frontal area(especially in Fz)during the delay period may be responsible for WM dysfunction in TLE with depression.