The Neural Mechanism For Electroconvulsive Therapy Modulating Emotion And Memory

Background Depression is a common chronic mood disorder with unknown etiology.Although antidepressants and psychological therapies were applied in the treatment of depression at first line for several decades,there are approximately 30% of patients resistant to drugs and psychological therapies.Besides,patients with severe suicidal tendencies need a rapid response,which cannot be acquired by drugs and psychological therapies.For these patients,electroconvulsive therapy(ECT)is a satisfactory treatment with rapid and efficient antidepressive effect.ECT is a treatment involving induction of seizures through electrodes placed at the surface of the skull.Although the antidepressive efficacy of ECT is well documented,the precise mechanism of benefit is still unclear.In addition,ECT frequently causes cognitive side-effects,mainly the memory impairment.The neural substrate is also still obscure.The advance of neuroscience and neuroimaging provide tools to reveal the neural substrate underling regulatory effect of ECT on emotion and memory.Indexes based on the resting state functional Magnetic Resonance Imaging(RS-f MRI)could represent the brain local activity and inter-region cooperation.These methods help to reveal the neural substrate underling depression and regulatory effect of ECT on neural circuits.ObjectiveBased on the special hypothesis,we aimed to explore the neural substrate underling regulatory effect of ECT on emotion and memory with methods of cognitive behavior and RS-f MRI.(1)Substantial studies have indicated that emotional memory bias(bias toward the negative and bias from the positive)play a vital role in the onset and poor prognosis of depression.Based on the memory-impairment effect of ECT,present study aimed to explore the modulatory of ECT on the emotional memory bias in depressed patients.(2)As a crucial regions in memory function,hippocampus also are involved in the emotional processing.Evidences have suggested that hippocampus has multiple subregions,corresponding to memory and emotion progressing,respectively.Present study mainly wants to evaluate the relationship between hippocampal-subregion alterations following ECT and the regulatory effect of ECT on emotion and memory.(3)In addition to hippocampus and other limbic cortex,prefrontal cortex is another key node for regulating emtion processing.Dysfunctional prefrontal cortex is vital for the onset of depression.Previous studies have implied the key role of the dorsal prefrontal cortex in the antidepressive effect of ECT.However,there is still ubiquitous inconsistency across these studies,partly due to several confounding effects induced by the use of different samples.Studies with independent samples are necessary for validations to minimize confounding effects to explore the role of prefrontal function in regulatory effect of ECT on emotion.Methods(1)In this study,the incidental memory task with emotional pictures was applied to evaluate the emotional memory of twenty depressed patients at pre and post-ECT compared to twenty healthy controls.The depressive symptoms were evaluated using the Hamilton Depression Rating Scale(HDRS).The correlation between the change of emotional memory and the change of HDRS was conducted.(2)Resting-state functional connectivity(RSFC)based on the seeds of hippocampal subregions were investigated in 45 pre-and post-ECT depressed patients.Structural connectivity between hippocampal subregions and corresponding functionally abnormal regions was also conducted using probabilistic tractography(n = 38).Antidepressant effects and cognitive impairments were measured by the Hamilton Depressive Rating Scale(HDRS)and the Category Verbal Fluency Test(CVFT),respectively.Their relationships with hippocampal-subregions alterations were examined.(3)In the current study,resting-state magnetic resonance imaging of 84 participants was collected using two scanners and two types of scanning parameters.One sample consisted of 28 patients and 23 healthy controls,and the other sample consisted of 33 patients.The local activity(indexed by the amplitude of low-frequency fluctuations)and functional connectivity were used to examine prefrontal function in the two independent samples before and after ECT.Results(1)Before ECT,patients showed decreased recognition memory for positive pictures compared to controls and remembered negative pictures more easily than positive pictures in the recognition task.In patients,the main effect of session(pre-ECT and post-ECT)was significant for both recognition and recall memory with reduced memory performance.The interaction between valence(positive,neutral and negative)and session was significant for recognition memory,indicating that negative memory was impaired more severely than positive memory.There was no significant correlation between the changes of emotional memory and the improvement of depressive symptoms severity.(2)After ECT,patients showed increased RSFC in the hippocampal emotional subregion(HIPe)with the left middle occipital gyrus(LMOG)and right medial temporal gyrus(RMTG).Decreased HDRS was associated with increased HIPe-RMTG RSFC significantly and increased HIPe-LMOG RSFC at trend level(r =.In contrast,the hippocampal cognitive subregion showed decreased RSFC with the bilateral angular gyrus,and was correlated with decreased CVFT.No significant changes were found in structural connectivity.(3)Both samples showed increased local activity of the dorsomedial prefrontal cortex(DMPFC)and enhanced connectivity of the DMPFC with the posterior cingulate cortex(PCC)following ECT.The enhanced connectivity between the DMPFC and PCC was positively associated with depressive symptoms improvement for both samples.Conclusion(1)Our results indicate that ECT relieves depressive symptoms and regulates emotional memory through more severe impairment on memory for negative stimuli.(2)The hippocampal-subregions functional alterations may be specially associated with the regulatory effect of ECT on emotion and memory.(3)These findings provide relatively strong evidence to support the function of the dorsomedial prefrontal cortex in depression and reorganization by ECT.The function of the DMPFC-PCC connection may underlie regulatory effect of ECT on emotion.Above findings with the methods of neuroscience and resting-state neuroimaging revealed the neural substrate underling regulatory effect of ECT on emotion.Besides,based on the functional changes of hippocampal subregions,our results also revealed the neural substrate underling regulatory effect of ECT on memory.A better understanding of these processes is needed to fine-tune ECT in order to induce less negative side effects band thus enhance the positive attitudes among patients who may benefit from it.