| Memory is the basis of various cognitive abilities of human beings.Research shows that memory is a dynamically process.The consolidation of memory will make it in an unstable state,providing a window period for individuals to actively modify or suppress it.In daily life,recalling happy memories can make people feel physically and mentally happy,but some cues related to painful experiences may trigger the invasion of unwanted memories.In order to reduce the negative impact of painful memories,individuals can disrupt the recall of unwanted memories through active inhibition.This ability is called memory suppression ability.It is mainly measured in the laboratory by the Think/No-Think(TNT)paradigm.The TNT paradigm first requires the subjects to form a high-strength association between the cue stimulus and the target memory,so that when they perceive the cue stimulus,they would involuntarily recall the target memory.This involuntary recall was used to simulate the intrusion of unwanted memories in everyday life.The subsequent TNT stage required the subjects to suppress the target memory.Numerous studies have found that memories that are required to be suppressed are less recalled relative to memories that do not appear during the TNT phase,indicating a significant suppression-induced forgetting effect.Follow-up studies have shown that the subjects can not only actively suppress the memory of neutral words,but also the memory of emotional materials,such as traumatic pictures,fear memories of the future,etc.These studies demonstrate the protective effect of memory suppression ability on the mental health of individuals.Functional magnetic resonance imaging(f MRI)studies have shown that memory suppression is an active process involving increased activation of brain regions related to executive control(the dorsolateral prefrontal cortex)and decreased activation of brain regions involved in memory recall(hippocampus).The follow-up dynamic causal model and physiologicalpsychological interaction analysis showed that the dorsolateral prefrontal cortex downregulated hippocampal activation during memory suppression,and the degree of hippocampal activation down-regulation could predict the memory suppression ability of the subjects.These studies suggest that memory suppression involves the disruption of memory representations by executive control functions.While other studies have found an increase in coupling within the prefrontal cortex during memory suppression which in order to support executive control functions.Some studies have also shown that the impairment of memory suppression ability in patients with intrusive memory as the main clinical feature,such as depression,anxiety,and post-traumatic stress disorder.However,most previous studies on the memory suppression have mainly focused on the interactions between a few brain regions of interest,such as the prefrontal cortex as the source of inhibition and the hippocampus as the target of inhibition.However,memory suppression may involve activation or deactivation in many brain regions.For example,in addition to the hippocampus,significant decreases in activation were also observed in the primary visual cortex,fusiform gyrus,and parahippocampus during memory suppression.In addition to the dorsolateral prefrontal cortex,other prefrontal cortex regions,such as the superior frontal gyrus and inferior frontal gyrus,also observed a large-scale increase in activation during memory suppression.Systematic profiling of whole-brain activation patterns during memory suppression can deepen our understanding of the neural mechanisms of memory suppression from a broader perspective.In addition,the brain regions activated during memory suppression are not independent of each other,but there is extensive communication between those regions.Previous studies mainly focused on the changes in the connectivity between the dorsolateral prefrontal cortex and the hippocampus during memory suppression,and paid less attention to the coupling between other brain regions.Studies have shown that different executive control-related networks(dorsal attention network,ventral attention network,frontoparietal control network)are responsible for different functions when performing cognitive control tasks,and the coupling between them would also change according to the purpose of the task.How executive control-related brain networks interact during active forgetting still needs further exploration.On the other hand,successful memory retrieval does not only depend on the activation of the hippocampus,but also on the communication between the hippocampus and the neocortex,such as the visual cortex,parahippocampus,etc.Therefore,we can expect that successful memory suppression may not only reduce the activation of the hippocampus,but also disrupt the connection between the hippocampus and the neocortex.Finally,previous studies have shown that patients(depression,post-traumatic stress disorder,etc.)with intrusive memory as the main feature have impaired memory suppression ability,but the neural mechanism behind it has yet to be explored.By comparing the differences in the neural mechanisms of memory suppression between subthreshold depressed subjects and normal subjects,it can help us better understand the reasons for the impairment of memory suppression ability in depressed patients.,and promote clinical diagnosis and treatment.In summary,this study intends to explore the above issues through three sub-studies.From the perspective of group level(134 people),study 1 divides the brain into different networks and regions(visual network,motor network,dorsal attention network,ventral attention network,limbic system,frontoparietal control network,default network,amygdala,hippocampus,basal ganglia,thalamus)and systematically characterize the whole brain activation and connectivity pattern.Through graph theory,we also explore the relationship between connectivity and activation during memory suppression.The results showed that during memory suppression,the activation of frontoparietal control network and dorsal attention network increased,while the activation of visual network,motor network and hippocampus decreased.Functional connectivity analysis shown that during memory suppression,the functional connectivity between the frontoparietal control network and the ventral attention network and the functional connectivity within the dorsal attention network were increased,while the functional connectivity within the visual network and default network were decreased.Graph theory analysis showed that nodes with lower activation(visual cortex)tended to form negative connectivity with nodes related to executive control.The above results suggest that memory suppression involves increased activation of brain regions related to executive control(prefrontal cortex)and that the coupling between these regions also increases.On the other hand,the brain regions related to memory representation(visual cortex,hippocampus)exhibit decreased of activation,and the coupling between those regions also been reduced.In Study 1,we found a significant decrease in activation of memory representation brain regions other than the hippocampus,such as the visual cortex.Connectivity analysis revealed a wide range of functional connectivity changes during memory suppression.In Study 2,from the perspective of individual differences,we used wholebrain predictive model and seed-based predictive model to predict subject’s memory suppression ability based on functional connectivity changes during memory suppression.The results showed that the whole brain functional connectivity could not effectively predict the subject’s memory suppression ability.On the other hand,the functional connectivity change between hippocampus and visual cortex,nucleus accumbens could effectively predict subject’s memory suppression ability.Subsequent validation analysis showed that this result was not affected by head movement,crossvalidation strategies,regression methods,and feature selection thresholds,and could be generalized by using different brain atlas.This result suggest that the decreased activation of visual cortex and hippocampus may not independent of each other.Memory suppression not only reduces the activation of the hippocampus,but also reduces the communication between the hippocampus and other brain regions,thereby promoting forgetting.The subjects in study 1 and study 2 were all normal subjects.Previous studies have shown that memory suppression is impaired in patients with depression.Therefore,in study 3,by constructing a multivariate classifier,we tried to explore the neural mechanism behind the impairment of memory suppression ability in depression.The results show that,during suppression of negative memory,compared with normal subjects,subthreshold depression subjects shown more positive connectivity between hippocampus,parahippocampus and prefrontal cortex.This result indicated that subthreshold depression subjects could not effectively mobilize the executive control function of the prefrontal cortex to suppress unwanted memories.On other hand,we also found that compared to normal subjects,subthreshold depression subjects exhibit lower functional connectivity between prefrontal cortex and parietal lobe,indicated the deficit of executive control function.To sum up,our results show that during memory suppression,the activation of executive control-related regions(prefrontal cortex)were increased and accompanied by increased connectivity between those regions(connectivity between frontoparietal control network and ventral attention network,within functional connectivity of attention network).On the contrary,the activation of brain regions related to memory representation(visual cortex,hippocampus)is decreased.Through prediction analysis,we shown that systemic memory suppression involves more than the modulation of hippocampal activity—it alters functional connectivity patterns between the hippocampus and visual cortex,leading to successful forgetting.Furthermore,by comparing the differences in neural mechanisms in memory suppression between subthreshold depressed subjects and normal subjects,we show that subthreshold depressed subjects could not effectively recruit the executive control function of the prefrontal cortex to suppress the activation of memory representation areas such as the hippocampus and parahippocampus,resulting in inferior memory suppression ability.Future research can explore how to enhance the individual’s memory suppression ability through behavioral or neural training. |
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