The recollection of childhood memories is affected by the subjects involved, such as father and mother, and by the context. This study aimed to clarify the neural influence of autobiographical memory related to the parent-child relationship on psychological health in adulthood. Twenty-nine healthy volunteers participated in a functional magnetic resonance imaging experiment using a childhood memory recollection task, in which they appraised the emotion a parent would have provided in a given situation. Whole-brain univariate and psychophysiological interaction analyses were performed. Neuroimaging results indicated notable involvement of the caudal anterior cingulate cortex and precuneus in autobiographical memory related to the parent-child relationship, and their activities were closely associated with the level of depression and self-esteem, respectively. The functional connectivity results indicated increased connectivity between the caudal anterior cingulate cortex and fusiform gyrus for the father-positive condition compared to the mother-positive condition and there was a positive correlation between the strength of connectivity between the two regions and the anxiety level. Our findings suggest the processing of negative affect and the personalness of autobiographical memories are distinctly engaged depending on the parent in question and the situational valence. The present study illuminates the impact of autobiographical memory processes on various dimensions of psychological health. Like the saying, “no health without mental health,” promoted by the WHO, psychological health or psychological well-being is a fundamental factor contributing to quality of life . There aThe retrospective perceptions of the parent-child relationship are based on an individual’s autobiographical memory. The development of autobiographical memory is a social process that is influenced by the reminiscing style of parents, and thus an integral part of the developing sense of self and interpersonal relatedness ,7. AutobPsychological health is very closely related to memory encoding and retrieval, and there is evidence supporting its influence on neural activities related to autobiographical memory. Numerous studies have also shown the connection between psychological health and selective memory bias. The representation, recall, and maintenance of autobiographical memories have shown to be disturbed by individuals with poor psychological well-being, where they are systematically biased for negative information . Memory Self-esteem is a facet of personality that affects perception of social standing and modulates the salience of social interaction. Previous studies have shown that the midline cortical structures, such as the medial prefrontal cortex (PFC), ACC, posterior cingulate cortex (PCC), and precuneus that mediate self-referential processing are also closely involved in the expression of self-esteem . Global The level of self-esteem may be related to the manifestation of depression through memory biases . Many stPathological anxiety has also been associated with negative memory bias . Like deAlthough behavioral and neurobiological studies indicate the impact of the psychological dimensions on the encoding and retrieval of autobiographical memories, the way in which psychological health affects memory processes in the general population is still unknown. The importance of the parent-child relationship in child development has been well documented. When looking at the way parents interact with a child, mothers are often more caring and nurturing, whereas fathers engage in more playful interactions . NaturalIn this study of the general population, we sought to identify the neural substrates of the impression of parents while participants recalled childhood memories. For this purpose, we examined how fathers and mothers are perceived differently and whether the valence of memory influences this perception, and surveyed the effects of psychological health  on the memory process. As childhood memories of parents triggered by various situations are inherently charged with emotions, we hypothesized that regions often involved in an autobiographical memory, such as the ACC, IFG, amygdala, and hippocampus, would be engaged differently depending on the parent and the valence of situation, and would be modulated by a person’s psychological health.Twenty-nine normal volunteers were recruited through an advertisement at a local hospital and via the internet. All participants were right-handed, as assessed by the Annett Handedness Inventory . ExclusiWe used the Parent-Adolescent Communication Inventory (PACI) , which cParticipants performed a task where they were asked to imagine what their parents’ facial expression looked like in a given situation during their childhood. Visual stimuli with a grey background included black words presenting a situation in the upper part and four black and white faces of the same person expressing different emotions  in the lower part . The numt-test.In order to evaluate the validity of the presented words, the vividness of memory associated with the situation, the intensity of reaction received from a parent in the situation, and the current degree of arousal caused by the recollection of the situation were assessed for each situation in 24 volunteers who did not participate in the fMRI experiment . Similar to the fMRI task, each situation was presented with either word “Father” or “Mother” on top of a page, then the volunteers were instructed to visualize an image of a parent during their childhood. All three items  were measured on a 9-point scale . Analysis was conducted using repeated measures analysis of variance (ANOVA) for parent (Father and Mother) and valence of situation  and post-hoc paired http://surfer.nmr.mgh.harvard.edu/optseq/) to ensure that events in this mixed design could be statistically separated and to verify that the neural responses for each pair of stimuli were mutually orthogonal.A total of ten blocks were presented in the task, and each block lasted for 30 sec with a 16 sec rest period between the blocks. Half of the blocks included a male face and the other half of the blocks included a female face. Participants were instructed to regard the man as their father and the woman as their mother. The 30 situations were presented in five blocks for the father condition and all of these situations were repeated in five blocks for the mother condition. Each block included two positive, two negative, and two neutral trials. Each trial lasted for 3 sec and the inter-stimulus interval was jittered between 0.5 sec and 3.0 sec. We randomly assigned the two block conditions in the whole sequence, the six situations in each block, and the four facial emotions in each trial. The timing and distribution of trials were optimized by optseq2  to represent the imagined emotion. In order to verify the validity of facial stimuli, we asked participants who finished scanning to rate the valence of each face on a 4-point Likert scale, anchored at 2 = very positive and -2 = very negative.t-test was subsequently performed to investigate the difference in imagined emotion scores between the father and mother conditions in each of the positive, negative, and neutral situations.The imagined emotion score and reaction time (RT) were counted for behavioral analysis. The ANOVA was used to identify the main effect of parents (father and mother) and situation  and the interaction effect between them. A paired MRI data were acquired on a 3T scanner . Functional images were acquired using a T2*-weighted gradient echo-planar imaging sequence . Imaging slices were obtained at a tilted angle of 30° from the anterior commissure-posterior commissure line to minimize signal loss in the orbitofrontal cortex. An additional structural image using a 3D T1-weighted gradient echo sequence  was obtained from each participant after the functional runs.Data preprocessing and analysis were performed using SPM12 . Images remaining after discarding the first six images from the dummy scan were used for further preprocessing. Differences in the slice acquisition time were corrected, and realignment was performed to correct for head motion. These functional images were coregistered on the T1-weighted image. The T1-weighted images were spatially normalized to the standard template, and the resulting transformation matrices were applied to the coregistered functional images. The normalized images were smoothed with a Gaussian kernel of 6 mm full-width at half-maximum.post-hoc paired t-test to investigate the main and interaction effects of parents and situation. Statistical inferences were conducted at a threshold of a corrected p < 0.05, which corresponds to the family-wise error (FWE) corrected significance at the cluster level with a cluster-defining threshold of p < 0.001. In addition, correlation analysis was conducted between parameter estimates from the significant clusters showing the interaction effect and psychological scale scores. Parameter estimates were extracted from 6-mm spherical regions of interest (ROIs) centered on the peak voxel of significant clusters using the MarsBaR toolbox.Preprocessed images were analyzed using a general linear model. A series of events as regressors of interest was modeled by convolving the event-train of stimulus onsets with the canonical hemodynamic response function. Trials were modeled based on the onset of stimulus presentation, specified as zero-duration events. With movement parameters as regressors of no-interest, left-hand and right-hand button pressing during the task period were also included as additional regressors. The positive and negative situations were contrasted with the neutral situations in each of the father and mother conditions for each participant on first-level analysis. At this first stage of analysis, the neutral situation was chosen as a control to subtract out general effects involving visual process and recall. Subsequently, four main contrasts for the positive and negative emotional situations in the father and mother conditions were created and used for the second-level analysis using a flexible factorial model and a p < 0.05, with an initially voxel-level uncorrected p < 0.001. Finally, correlation analyses were conducted between the strength of functional coupling of the seed with the coupled region and the psychological scale scores. The MarsBaR toolbox was used to extract mean PPI coefficients from the first-level single-subject contrasts using the target area used for PPI analyses.Functional connectivity analyses were implemented with psychophysiological interaction (PPI) analyses, in which the seed region was defined as a cluster showing the interaction effect in the second-level analysis. The time course from a 6-mm sphere in each seed region was extracted. Results were reported at a cluster-level FWE-corrected F1,23 = 7.63, p = 0.011), but not in a main effect of situation  and an interaction effect . In post-hoc analysis, the vividness was significantly greater in the mother condition than in the father condition . The response intensity showed significant results in a main effect of parent  and a main effect of situation , but not in an interaction effect . Post-hoc analysis revealed that the response intensity was significantly higher in the mother condition than in the father condition  and significantly higher in the positive situation and negative condition than in the neutral situation . The arousal showed significant results in a main effect of parent  and a main effect of situation , but not in an interaction effect . In post-hoc analysis, the arousal was significantly higher in the mother condition than in the father condition , and in the positive and negative conditions than in the neutral condition .Results from the assessment of the vividness, response intensity, and arousal of the 30 word stimuli are presented in F2,47 = 408.28, p < 0.001], but not a main effect of parents  and a significant parents × situation interaction . Post-hoc analyses showed that the scores for the positive situations were significantly higher than those for the negative  and neutral situations , and the scores for the negative situations were significantly lower than those for the neutral situations .F2,47 = 45.42, p < 0.001] and a significant parents × situation interaction , but not a main effect of parents . Post-hoc analyses showed that the RTs for the positive situations were significantly shorter than those for the negative situations  and the neutral situations , and there was no significant difference between the negative and neutral situations . The RTs in the father-negative condition were significantly longer than those in the father-neutral condition , whereas there was no significant difference between the mother-negative and mother-neutral conditions .The RTs also showed a main effect of situation . There are many factors that influence psychological health in adulthood, and one of the most central determinants is the parent-child relationship [2]. The relationship between a parent and child becomes the template for other interpersonal relationships because attachment bonding allows a person to understand their environment and establish a sense of security . An examination of the association between the retrospective perceptions of the parent-child relationship and emotional health in adulthood showed that daily emotional and psychological distress are closely related to how one perceives the quality of the parent-child relationship, and the retrospective perceptions of father-child and mother-child relationships contribute to different dimensions of emotional health [5]. Therefore, the perceptions of the childhood relationship with parents are important in the overall well-being, even as adults.The retrospective perceptions of the parent-child relationship are based on an individual’s autobiographical memory. The development of autobiographical memory is a social process that is influenced by the reminiscing style of parents, and thus an integral part of the developing sense of self and interpersonal relatedness . Autobiographical memory represents the self and shapes emotional states of our everyday lives . In general, memories are highly intertwined with features like self-referential processing and emotion [9]. Functional neuroimaging studies have examined autobiographical memories in reference to other types of memories. For instance, a recent study that compared the difference between autobiographical memory and simple recognition memory found that when a task required retrieval of life memories, default-mode areas were engaged more, whereas a simple recollection of memories engaged the parietal memory network [10]. Since autobiographical memory retrieval relies heavily on self-reference and emotion, retrieval of autobiographical memories has been shown to employ various cortical and subcortical regions, including the prefrontal and parietal cortices, anterior cingulate cortex (ACC), precuneus, medial temporal cortex, hippocampus, and amygdala [11-14]. In particular, the amygdala has been implicated in the encoding of emotional memories [15] as well as retrieval of autobiographical memories [16]. Previous studies also found coactivation of the amygdala, hippocampus, and inferior frontal gyrus (IFG) during the retrieval of autobiographical memories [17] and neural responses in the dorsal to caudal ACC and IFG elicited by the retrieval of painful autobiographical memories [18]. These reports consistently show a close relationship between autobiographical memory and emotional memory.Psychological health is very closely related to memory encoding and retrieval, and there is evidence supporting its influence on neural activities related to autobiographical memory. Numerous studies have also shown the connection between psychological health and selective memory bias. The representation, recall, and maintenance of autobiographical memories have shown to be disturbed by individuals with poor psychological well-being, where they are systematically biased for negative information [11]. Memory bias and negative interpretations of events contribute to a vicious cycle, where one’s psychological health contributes to the tendency toward negative interpretation of memories, and this bias also maintains low self-esteem, depression, or anxiety [19-21]. In fact, there is a consensus that self-esteem, anxiety, and depression are core elements of psychological health [22-24]. The importance of these elements has spurred researchers to study the close associations between self-esteem, anxiety and depression, and quality of life in numerous fields [25-28].Self-esteem is a facet of personality that affects perception of social standing and modulates the salience of social interaction. Previous studies have shown that the midline cortical structures, such as the medial prefrontal cortex (PFC), ACC, posterior cingulate cortex (PCC), and precuneus that mediate self-referential processing are also closely involved in the expression of self-esteem [29]. Global self-esteem, which includes self-competence and self-liking, is related to selective memory, especially toward a negatively salient stimulus [19]. Individuals with lower self-esteem tend to be more concerned with how others perceive them, and this makes heightened negative events more memorable. Lower self-esteem predicts an increase in ventral ACC and medial PFC activity in response to positive versus negative social feedback, indicating the relationship between self-esteem and the salience processing [30]. On the other hand, a positivity bias for events that involve self-evaluations is stronger for individuals with higher self-esteem, suggesting that this bias affecting autobiographical memory is part of psychological mechanisms for maintaining a positive self-image [31]. The underlying neural substrates of a positive self-evaluation include the medial ventral and dorsolateral PFC and hippocampus, reflecting cognitive effort and emotional involvement for the positivity bias [32]. In addition, it has been reported that the lateral PFC, dorsal ACC, posterior cingulate cortex (PCC), precuneus, and caudate are involved in negative or positive character feedback associated with self-esteem [33].The level of self-esteem may be related to the manifestation of depression through memory biases [34]. Many studies have reported that overall autobiographical memory predicts the onset or course of depression and thus is considered to be a risk factor for depression . Depression contributes to the deviant reactivation of neural areas associated with autobiographical memory retrieval [37]. Neural correlates of autobiographical memory deficits in depressed patients have been known to involve a wide range of brain regions, such as the IFG, lateral orbitofrontal cortex (OFC), dorsomedial and ventrolateral PFC, ACC, precuneus, temporoparietal cortex, insula, hippocampus, and amygdala [38-40]. Pathological anxiety has also been associated with negative memory bias [41]. Like depression, anxiety disorders are also characterized by maladaptive emotional responses and retrieval of memories [42]. In particular, negative autobiographical memory bias is prominent in individuals high in social anxiety [43]. Increased state anxiety decreases the ability to retrieve specific autobiographical memory [44]. Previous studies of patients with anxiety disorders have reported functional impairments of structures linked to the experience and regulation of emotion, such as the PFC, ACC, insula, and amygdala [45-47].Although behavioral and neurobiological studies indicate the impact of the psychological dimensions on the encoding and retrieval of autobiographical memories, the way in which psychological health affects memory processes in the general population is still unknown. The importance of the parent-child relationship in child development has been well documented. When looking at the way parents interact with a child, mothers are often more caring and nurturing, whereas fathers engage in more playful interactions [48]. Naturally, since the relationship between a father and child is different from the relationship between a mother and child, the autobiographical memories of parents in adulthood must be different. This difference is also observed in the brain response. For example, faces of mothers elicited more activity in the face processing network including the fusiform gyrus, whereas faces of fathers elicited more activity in the striatal region [49]. Despite the importance of the parent-child relationship and its difference between parents, no study has provided neurobiological evidence for how perceptions change depending on the parent and the valence of memories.Also, explaining more in-depth of the specific brain regions associated with the recall of autobiographical memories, emotional memories, since this is the specific task participants will be engaging in.Reply:As suggested, additional explanations regarding autobiographical memory and emotional memory were added to a separate paragraph.Revision:In ‘the second paragraph’ of the Introduction sectionThe retrospective perceptions of the parent-child relationship are based on an individual’s autobiographical memory. The development of autobiographical memory is a social process that is influenced by the reminiscing style of parents, and thus an integral part of the developing sense of self and interpersonal relatedness . Autobiographical memory represents the self and shapes emotional states of our everyday lives . In general, memories are highly intertwined with features like self-referential processing and emotion [9]. Functional neuroimaging studies have examined autobiographical memories in reference to other types of memories. For instance, a recent study that compared the difference between autobiographical memory and simple recognition memory found that when a task required retrieval of life memories, default-mode areas were engaged more, whereas a simple recollection of memories engaged the parietal memory network [10]. Since autobiographical memory retrieval relies heavily on self-reference and emotion, retrieval of autobiographical memories has been shown to employ various cortical and subcortical regions, including the prefrontal and parietal cortices, anterior cingulate cortex (ACC), precuneus, medial temporal cortex, hippocampus, and amygdala [11-14]. In particular, the amygdala has been implicated in the encoding of emotional memories [15] as well as retrieval of autobiographical memories [16]. Previous studies also found coactivation of the amygdala, hippocampus, and inferior frontal gyrus (IFG) during the retrieval of autobiographical memories [17] and neural responses in the dorsal to caudal ACC and IFG elicited by the retrieval of painful autobiographical memories [18]. These reports consistently show a close relationship between autobiographical memory and emotional memory.Also, the hypothesis of this paper are also not clear. For example, “We predicted that emotional ratings would be correlated with psychological health facets.” What emotional ratings are being referenced? Rating of the specific parental facial expressions expressed by a parent during a given encounter or the valence of the memory in general. Furthermore, there was no justification for why they hypothesized different activity in memory regions based on parent or emotion.Reply:We sincerely apologize for the confusion. To answer the first part, the “emotional ratings” we mentioned in the hypothesis was the in-scan behavior data. In the revised manuscript, the hypothesis was updated to avoid the confusion.Revision:In ‘the last paragraph’ of the Introduction sectionIn this study of the general population, we sought to identify the neural substrates of the impression of parents while participants recalled childhood memories. For this purpose, we examined how fathers and mothers are perceived differently and whether the valence of memory influences this perception, and surveyed the effects of psychological health  on the memory process. As childhood memories of parents triggered by various situations are inherently charged with emotions, we hypothesized that regions often involved in an autobiographical memory, such as the ACC, IFG, amygdala, and hippocampus, would be engaged differently depending on the parent and the valence of situation, and would be modulated by a person’s psychological health.Methods: A concern of the study is whether participants actually engaged in autobiographical memory recall rather than imagination or simply an impression. First, there is substantial research showing that retrieving specific autobiographical memories takes more time than 3 seconds in response to a cue word ! In addition, participants were not actually instructed to retrieve a memory, but rather to imagine their parents’ facial expression. This type of task will be heavily influenced by current/recent experiences with their parents’ facial expression. Lastly, I’m not sure it is possible to both retrieve a memory and make the facial judgment within 3 seconds. Because participants were forced to respond so quickly (and did so looking at the RT’s), this task is best interpreted as an impression task. Do the authors have any evidence to support their interpretation of the task?Reply:We are sincerely grateful for this particular point. As indicated, 3 seconds can actually be a very short time to remember an autobiographical memory. Our manuscript had no basis to properly answer this pointed problem. Now, following your recommendations at the end, we provided clarity data for task stimuli after the additional experiment. As shown in the newly added Table 1, the vividness of memory associated with the situation and the intensity of reaction received from a parent in all situations indicated 4 or greater, which means ‘above moderately.’ We think these results may explain to an extent to what you have expressed concerns. In the revised manuscript, we added this comment in the discussion.Revision:In ‘the first paragraph’ of the Discussion sectionThe three seconds given for the task may have been too short to remember an autobiographical memory. However, since the vividness and reaction intensity in the stimulus assessments were rated as moderately or higher, we can say that the task was to evoke an autobiographical memory rather than an imagination or a simple impression.The authors also report using a linear mixed model to analyze the behavior. First, this model is quite complex and much more information is needed regarding how the model was set up  and why this model was chosen over an ANOVA.Reply:As pointed out, it seems that LMM was not necessary, and thus ANOVA was applied to the revised manuscript. As the analysis method changed, it was adjusted accordingly to the statistical values of the results.Revision:In ‘Behavioral task and analysis’ of the Methods sectionThe ANOVA was used to identify the main effect of parents (father and mother) and situation  and the interaction effect between them.In ‘Behavioral results’ of the RESULTS sectionFigure 2 illustrates the mean imagined emotion score and mean RT in each condition during the task. The imagined emotion scores showed a main effect of situation , but not a main effect of parents  and a significant parents × situation interaction . Post-hoc analyses showed that the scores for the positive situations were significantly higher than those for the negative  and neutral situations , and the scores for the negative situations were significantly lower than those for the neutral situations .The RTs also showed a main effect of situation  and a significant parents × situation interaction , but not a main effect of parents . Post-hoc analyses showed that the RTs for the positive situations were significantly shorter than those for the negative situations  and the neutral situations , and there was no significant difference between the negative and neutral situations . The RTs in the father-negative condition were significantly longer than those in the father-neutral condition , whereas there was no significant difference between the mother-negative and mother-neutral conditions .Results: The authors should report all results and all p-values e.g. …”” (p. 9); “but showed no parent effect and a significant parents × situation interaction.” (p. 8) Can the authors also show figures of the main effects? The authors also do not appropriately describe the interactions (which are based on differences between conditions). The authors’ worded the interaction as main effects (“ACC activity was significantly greater in the father condition than in the mother condition”), which were inaccurate.Reply:As suggested, we added statistics for the results without significance. Since the differences among the positive, negative, and neutral conditions were so similar between the father and mother conditions, we did not add a graph of the main effect to avoid the duplication. In terms of the interaction effect, we agree with the comment that our reports were inaccurate. In the revised results, we changed them into an appropriate form.Revision:In ‘Behavioral results’ of the RESULTS sectionFigure 2 illustrates the mean imagined emotion score and mean RT in each condition during the task. The imagined emotion scores showed a main effect of situation , but not a main effect of parents  and a significant parents × situation interaction . Post-hoc analyses showed that the scores for the positive situations were significantly higher than those for the negative  and neutral situations , and the scores for the negative situations were significantly lower than those for the neutral situations .The RTs also showed a main effect of situation  and a significant parents × situation interaction , but not a main effect of parents . Post-hoc analyses showed that the RTs for the positive situations were significantly shorter than those for the negative situations  and the neutral situations , and there was no significant difference between the negative and neutral situations . The RTs in the father-negative condition were significantly longer than those in the father-neutral condition , whereas there was no significant difference between the mother-negative and mother-neutral conditions .In ‘Imaging results’ of the RESULTS sectionThere was an interaction effect in the right caudal ACC and right precuneus. As shown in Figure 3A, right caudal ACC activity in the father condition was significantly greater in the negative situation than in the positive situation , whereas that in the mother condition was not significant but greater in the positive condition than in the negative condition . Figure 3B also shows that right precuneus activity in the father condition was significantly greater in the negative situation than in the positive situation , whereas that in the mother condition was not significant but greater in the positive condition than in the negative condition .The authors should reconsider the names of their regions and interpretation. The ACC activity they found is better characterized as mid cingulate cortex. It is a bit too posterior to be considered dACC activity.Reply:We agree with this comment. I have two significant results in the ACC. In the revised manuscript, the first one in the main effect of situation was named the dorsal ACC, and the second one in the interaction effect was regarded as the caudal ACC. As a result of this separation, the interpretation in the discussion was changed accordingly.Revision:In ‘Imaging results’ of the Results sectionThere was an interaction effect in the right caudal ACC and right precuneus.In ‘3rd and 4th paragraphs’ of the Discussion sectionFrom the neuroimaging data, we saw intriguing neural responses to each condition from the right caudal ACC and precuneus, in particular. In the result of the caudal ACC, there was a particular bias toward father-negative and mother-positive, suggesting that in the autobiographical memory of emotional events, different forms of brain reactions occur depending on the parent's gender. Attention on the caudal ACC has risen in recent years and studies have indicated that the region contributes significantly to negative affect and pain processing [56-58]. This region receives an ample amount of emotion-related and voluntary movement signals , and has been suggested as a pivotal site for the emotional and voluntary interaction [58]. In a fascinating investigation on pain processing in self and others, it was seen that the caudal ACC was activated in response to self-experienced pain, but not when perceiving pain in others [56]. Furthermore, this region was shown to increase in response to negatively charged autobiographical memories [61]. On the other hand, its involvement in other-experienced pain processing has also been reported. A meta-analysis on empathy-related regions indicates that this region is part of the pain empathy network, and is engaged when pain was anticipated [62]. Regardless, it is clear that the caudal ACC plays a role in processing negative affect.In light of these caudal ACC functions, our results may be linked to mothers taking on the role of primary caretaker more so than the fathers. In many cultures, traditional gender roles have determined the roles and expectations for parents, which usually assumes fathers as breadwinners and mothers as the primary caretaker in child rearing . This point can be related to our results of the stimulus assessment. The analysis of the stimulus assessments indicated that the responses that fathers gave were less intense in all situations than those given by mothers; and the imagination of fathers’ appearances were less vivid and evoked less arousal than that of the mothers. In these respects, it is possible that caudal ACC activity may be a response to the stoic and emotionally distant perception of fathers. Meanwhile, the importance of memory to the mother can be seen in our result of negative correlation between caudal ACC activity in the mother-positive condition and depression score. There was a report that pathological changes in this region may be related to major depressive disorder [65]. A study on the behavioral adaptation to unpleasant environment showed the involvement of the caudal ACC to be critical in the ability to regulate the behavior [66]. It has been suggested that the region might contribute to defending one from developing depression [67]. Taken together, our result of the negative correlation in the mother-positive condition may suggest that through the function of the caudal ACC, autobiographical memories of positive events with the mother may act as a factor that prevents depression.Motivation for the correlations do not make sense. For example, the authors found activity in the “ACC” that was driven by valence differences in the father condition, and yet found a correlation between depression and brain activity in this region in the mother-positive condition! Same with the other correlation. This implies that the authors assessed all possible correlations, regardless as to whether they made sense which would be at least 24 tests , thus inflating false positives. Not only should these correlations not be trusted , but they also were not hypothesized.Reply:As defined in the introduction, we hypothesized that a person’s psychological health  would be modulated by neural regions including the ACC, IFG, hippocampus, amygdala, and other areas associated with autobiographical memory recall. Since the regions of interest  result from the interaction effect, we considered their activity meaningful in every condition. We saw that if there was a difference in the father condition, there was also a meaning of no difference in the mother condition, and vice versa. Of course, as pointed out, it is a problem that the likelihood of false positives increases. We added this problem in the limitation of the study in the discussion.Revision:In the 9th paragraph of the DISCUSSION sectionSecond, since the correlation analysis was performed between three scale scores and regional activity under each condition, the possibility of false positives should be considered in interpreting the results.Discussion: The major issue in the discussion is that the authors over-interpret their findings and use a lot of reverse inferencing to do so. As one example, the authors claim that the dACC activity represents conflict processing. First, I am not convinced that the dACC was activated at all. However, even if this were to be the dACC, the dACC is one of the most active areas and does not indicate that conflict processing has occurred. The authors would benefit from reading Poldrack, R. A. (2011). Inferring mental states from neuroimaging data: from reverse inference to large-scale decoding. Neuron, 72(5), 692-697. Another example is that the authors claim that they can “therefore infer that the perceptions of fathers were more personal and vivid than those of mothers, especially during reminiscence of negative situations.” Again, none of this can actually be inferred without actual ratings of vividness or “personalness”. Because the Discussion is primarily comprised of entirely reverse inferencing and over-interpretation, it would have to be rewritten and I am convinced that nothing can be firmly concluded without additional data.One source of evidence of over-interpretation is again the interpretation of conflict monitoring. Decades of research has shown that conflict comes with a cost in response times. And yet, this “conflict monitoring” that occurs only for fathers and not mothers is not borne out in the RT ratings.Reply:We agree with the comments that our discussion contained too much of over-interpretation. As suggested, we included additional behavioral data in order to clarify certain claims that we made. We also edited our claims to eliminate reverse inferencing and over-interpretation as much as possible. Additionally, we changed the dACC region significant from the interaction effect to the caudal ACC. Accordingly, the discussion section of the revised manuscript was rewritten entirely.Revision:In ‘the 3rd to 8th paragraphs’ of the Discussion sectionFrom the neuroimaging data, we saw intriguing neural responses to each condition from the right caudal ACC and precuneus, in particular. In the result of the caudal ACC, there was a particular bias toward father-negative and mother-positive, suggesting that in the autobiographical memory of emotional events, different forms of brain reactions occur depending on the parent's gender. Attention on the caudal ACC has risen in recent years and studies have indicated that the region contributes significantly to negative affect and pain processing [56-58]. This region receives an ample amount of emotion-related and voluntary movement signals , and has been suggested as a pivotal site for the emotional and voluntary interaction [58]. In a fascinating investigation on pain processing in self and others, it was seen that the caudal ACC was activated in response to self-experienced pain, but not when perceiving pain in others [56]. Furthermore, this region was shown to increase in response to negatively charged autobiographical memories [61]. On the other hand, its involvement in other-experienced pain processing has also been reported. A meta-analysis on empathy-related regions indicates that this region is part of the pain empathy network, and is engaged when pain was anticipated [62]. Regardless, it is clear that the caudal ACC plays a role in processing negative affect.In light of these caudal ACC functions, our results may be linked to mothers taking on the role of primary caretaker more so than the fathers. In many cultures, traditional gender roles have determined the roles and expectations for parents, which usually assumes fathers as breadwinners and mothers as the primary caretaker in child rearing . This point can be related to our results of the stimulus assessment. The analysis of the stimulus assessments indicated that the responses that fathers gave were less intense in all situations than those given by mothers; and the imagination of fathers’ appearances were less vivid and evoked less arousal than that of the mothers. In these respects, it is possible that caudal ACC activity may be a response to the stoic and emotionally distant perception of fathers. Meanwhile, the importance of memory to the mother can be seen in our result of negative correlation between caudal ACC activity in the mother-positive condition and depression score. There was a report that pathological changes in this region may be related to major depressive disorder [65]. A study on the behavioral adaptation to unpleasant environment showed the involvement of the caudal ACC to be critical in the ability to regulate the behavior [66]. It has been suggested that the region might contribute to defending one from developing depression [67]. Taken together, our result of the negative correlation in the mother-positive condition may suggest that through the function of the caudal ACC, autobiographical memories of positive events with the mother may act as a factor that prevents depression.The precuneus, a central hub of the default mode network, also exhibited a similar interaction effect between the parent and situation during the childhood memory recollection task. The precuneus has been thought to play a critical role in episodic memory , source monitoring [70], and self-referential processing [71]. Recently, a multivariate analysis method, representational similarity analysis, demonstrated that the precuneus is a key region engaged during the subjective experience of vivid autobiographical memory reminiscence [72]. Other experiments have confirmed its prominent involvement in the vividness of self-related memories . In addition, right lateralization of the precuneus has been shown for highly personal and vivid reminiscence of autobiographical events [72]. Right lateralization is corroborated by the present study, which required participants not only to visualize a given circumstance, but also to delineate the facial expression by either parent. Our results indicate overall greater activation of the right precuneus during recollection of fathers than mothers, and more specifically, its activity was higher when recollecting fathers in negative compared to positive situations. It is interesting to note that despite lower vividness score in the stimulus assessments for fathers than mothers, these findings were observed, suggesting that the perceptions of fathers may be more personal than those of mothers, especially during reminiscence of negative situations. These may indicate the saliency of childhood memories of fathers and particularly how fathers responded during negative circumstances. In conjunction with activity of the caudal ACC, we cautiously conclude that memories of fathers in negative situations have a more adverse effect as the negative impression of fathers is more permanently embedded. This interpretation can also be linked to the results of correlation with self-esteem. Studies report that the neural structure of personal semantic memories serves as a neural correlate of self-esteem . It is postulated that due to its role in using autobiographical memories to choose the applicable self-relevant information, activation of the precuneus is closely related to self-esteem and how one processes given information . The current study confirmed the established association between self-esteem and precuneus activity, as we found a negative relationship between one’s self-esteem and precuneus activity during autobiographical reminiscence of fathers in negative events. Recently, the precuneus was identified to correlate positively with evaluation sensitivity, measured by a change in state self-esteem [75]. Together with the evidence supporting the precuneus’ affiliation with evaluation sensitivity, as well as the tendency for individuals with lower self-esteem to be more affected by negative information [76], our result seems to suggest that the heightened activation observed in individuals with lower self-esteem may be due to the saliency of negative memories during recollection and their tendency to be more influenced by negative information.  Our PPI analysis revealed significant increases in functional connectivity of the caudal ACC with the fusiform gyrus and postcentral gyrus for the father-positive condition compared to the mother-positive condition. Given that the fusiform gyrus processes facial identity [78] and emotion [79], our finding may indicate that a greater sense of negative affect was involved while processing facial expressions of fathers than mothers in positive childhood events. This raises the possibility that the negative affect arisen from processing emotional face expressions may be particularly different between the parent in a positive context. Going back to the stimulus assessments, we saw lower vividness, response intensity, and arousal from fathers than mothers. Again, this may be since, generally, mothers are primary caregivers who spend more time with children; thus, one may have more readily available positive memories involving mothers than fathers to access on demand.Previously, individuals with high trait anxiety have shown to hyperactivate the fusiform gyrus while processing uncertain cues and angry faces . Consistent with the activation study, our study revealed that the connectivity strengths between the cingulate cortex and fusiform gyrus during the father-positive versus mother-positive condition correlated positively with the severity of anxiety symptoms. These results may provide the neurobiological influence of trait anxiety in the retrieval of memory and the perception of fathers. In addition to emotional face processing, greater connectivity between the cingulate area and postcentral gyrus was witnessed for the father-positive than mother-positive condition. Functional connectivity between these two regions has been implicated in posttraumatic stress disorder (PTSD), where patients with PTSD showed stronger connectivity than the control group, and also was positively correlated with the severity of symptoms [82]. As part of the sensorimotor network [83], the coupling of the caudal ACC and postcentral or paracentral gyri has been shown to be involved in shock processing [84] and other emotional memory tasks [85]. Based on the evidence, we postulate that the caudal ACC may relay negatively valenced affective information to the sensorimotor area more for fathers than mothers when processing facial expressions.Lastly, the authors do indicate one of the major limitations is not being able to analyze sex differences due to the small sample size (which I agree with), but the authors may not realize how much of a problem this actually is. Because the authors have already chosen to differentially investigate effect mother vs. father effects, the relationship and memory biases that one might have will surely depend on the sex of the individual. The net result is an average set of brain activity that may not represent either the men or women .Reply:We whole-heartedly agree with this comment on the importance of exploring the sex differences in this study. Because we couldn't do it because of the small number of samples, we added the reviewer's point as an additional description to the limitation of the study.Revision:In the 9th paragraph of the DISCUSSION sectionFirst, in the relationship with parents, the degree of intimacy or memory biases can vary between father and mother, depending on the individual's sex. Because of the small sample size, however, the effect of sex variation was not analyzed.Recommendations: In the end, I would highly recommend testing a new set of participants behaviorally in the same task, but with additional probing to test whether they actually retrieved a memory, to rate the vividness of that memory, assess the degree of conflict they experienced, and any other rating to support the inferences the authors are making. Making claims of cognitive processing based on the neuroimaging findings alone without such support is a critical and known inferencing flaw in the neuroimaging community.Reply:We greatly appreciate this suggestion on conducting additional tests. In fact, before the experiment, we had performed a preliminary test to survey the intensity of reaction given by a parent, the vividness of each stimulus, and the level of arousal to ensure the validity of the task. However, due to the small number of subjects, the results were not included in the manuscript. In response to the reviewer’s recommendation, we carried out additional experiment to increase the number of subjects, and the data has been included in the method and results to the revised manuscript. We believe the results helped to mitigate the over-interpretation and reverse-inference problem, and we thank you again for the comment.Revision:In ‘Task stimuli’ of the Methods sectionParticipants performed a task where they were asked to imagine what their parents’ facial expression looked like in a given situation during their childhood. Visual stimuli with a grey background included black words presenting a situation in the upper part and four black and white faces of the same person expressing different emotions  in the lower part . The number of situations used in the task was 30, including ten positive , ten negative , and ten neutral . All actual situations used are shown in Supplementary Table S1. In order to evaluate the validity of the presented words, the vividness of memory associated with the situation, the intensity of reaction received from a parent in the situation, and the current degree of arousal caused by the recollection of the situation were assessed for each situation in 24 volunteers who did not participate in the fMRI experiment . Similar to the fMRI task, each situation was presented with either word “Mother” or “Father” on top of a page, then the volunteers were instructed to visualize an image of a parent during their childhood. All three items  were measured on a 9-point scale . Analysis was conducted using repeated measures ANOVA for parent (Mother and Father) and valence of situation  and post-hoc paired t-test.In ‘Stimulus assessment results’ of the Results sectionResults from the assessment of the vividness, response intensity, and arousal of the 30 word stimuli are presented in Table 1. The vividness showed a significant result in a main effect of parent , but not in a main effect of situation  and an interaction effect . In post-hoc analysis, the vividness was significantly greater in the mother condition than in the father condition . The response intensity showed significant results in a main effect of parent  and a main effect of situation , but not in an interaction effect . Post-hoc analysis revealed that the response intensity was significantly higher in the mother condition than in the father condition  and significantly higher in the positive situation and negative condition than in the neutral situation . The arousal showed significant results in a main effect of parent  and a main effect of situation , but not in an interaction effect . In post-hoc analysis, the arousal was significantly higher in the mother condition than in the father condition , and in the positive and negative conditions than in the neutral condition .Reviewer #2: Thank you very much for the possibility to review the manuscript titled "The neural influence of autobiographical memory related to the parent-child relationship on psychological health in adulthood". I think that this study contributes a lot to the literature and should be published in this journal if the authors want to review some aspects of the article that are lacking. This study investigates the neural influence on autobiographical memories; however, the introductory section refers to several concepts not explored in this work: emotional regulation, parent-child attachment. I think it may be important to review the whole introductory section in order to better focus the present work. In fact, the authors are invited to review studies related to the parent-child relationship  and to deepen the literature on autobiographical memory.For example, the authors are recommended to deepen their knowledge of the following works, which would greatly enrich this manuscript:Fivush, R., & Haden, C. A. (Eds.). (2003). Autobiographical memory and the construction of a narrative self: Developmental and cultural perspectives. Psychology Press.Fivush, R. et al. (1996). Remembering, recounting, and reminiscing: The development of autobiographical memory in social context.Cimino, S. et al. (2020). Dialogues about Emotional Events between Mothers with Anxiety, Depression, Anorexia Nervosa, and No Diagnosis and Their Children. Parenting, 20(1), 69-82.Reply:We would like to express our gratitude for your optimistic evaluation of our research and for drawing our attention to an important point. In the revised manuscript, descriptions of emotion regulation and attachment were deleted because they were not directly related to the research purpose. Instead, we added additional information to the introduction to clarify autobiographical memory-related contents, including the references that you suggested. Consequently, the introduction was entirely rewritten.Revision:In ‘the 1st to 3rd paragraphs’ of the Introduction sectionLike the saying, “no health without mental health,” promoted by the WHO, psychological health or psychological well-being is a fundamental factor contributing to quality of life [1]. There are many factors that influence psychological health in adulthood, and one of the most central determinants is the parent-child relationship [2]. The relationship between a parent and child becomes the template for other interpersonal relationships because attachment bonding allows a person to understand their environment and establish a sense of security . An examination of the association between the retrospective perceptions of the parent-child relationship and emotional health in adulthood showed that daily emotional and psychological distress are closely related to how one perceives the quality of the parent-child relationship, and the retrospective perceptions of father-child and mother-child relationships contribute to different dimensions of emotional health [5]. Therefore, the perceptions of the childhood relationship with parents are important in the overall well-being, even as adults.The retrospective perceptions of the parent-child relationship are based on an individual’s autobiographical memory. The development of autobiographical memory is a social process that is influenced by the reminiscing style of parents, and thus an integral part of the developing sense of self and interpersonal relatedness . Autobiographical memory represents the self and shapes emotional states of our everyday lives . In general, memories are highly intertwined with features like self-referential processing and emotion [9]. Functional neuroimaging studies have examined autobiographical memories in reference to other types of memories. For instance, a recent study that compared the difference between autobiographical memory and simple recognition memory found that when a task required retrieval of life memories, default-mode areas were engaged more, whereas a simple recollection of memories engaged the parietal memory network [10]. Since autobiographical memory retrieval relies heavily on self-reference and emotion, retrieval of autobiographical memories has been shown to employ various cortical and subcortical regions, including the prefrontal and parietal cortices, anterior cingulate cortex (ACC), precuneus, medial temporal cortex, hippocampus, and amygdala [11-14]. In particular, the amygdala has been implicated in the encoding of emotional memories [15] as well as retrieval of autobiographical memories [16]. Previous studies also found coactivation of the amygdala, hippocampus, and inferior frontal gyrus (IFG) during the retrieval of autobiographical memories [17] and neural responses in the dorsal to caudal ACC and IFG elicited by the retrieval of painful autobiographical memories [18]. These reports consistently show a close relationship between autobiographical memory and emotional memory.Psychological health is very closely related to memory encoding and retrieval, and there is evidence supporting its influence on neural activities related to autobiographical memory. Numerous studies have also shown the connection between psychological health and selective memory bias. The representation, recall, and maintenance of autobiographical memories have shown to be disturbed by individuals with poor psychological well-being, where they are systematically biased for negative information [11]. Memory bias and negative interpretations of events contribute to a vicious cycle, where one’s psychological health contributes to the tendency toward negative interpretation of memories, and this bias also maintains low self-esteem, depression, or anxiety [19-21]. In fact, there is a consensus that self-esteem, anxiety, and depression are core elements of psychological health [22-24]. The importance of these elements has spurred researchers to study the close associations between self-esteem, anxiety and depression, and quality of life in numerous fields [25-28].Again with regard to the introductory section, the authors are invited to define more clearly the objectives of the work and the hypotheses, consistent with the results and discussions.Reply:As suggested, we revised the objective and hypothesis.Revision:In ‘the last paragraph’ of the Introduction sectionIn this study of the general population, we sought to identify the neural substrates of the impression of parents while participants recalled childhood memories. For this purpose, we examined how fathers and mothers are perceived differently and whether the valence of memory influences this perception, and surveyed the effects of psychological health  on the memory process. As childhood memories of parents triggered by various situations are inherently charged with emotions, we hypothesized that regions often involved in an autobiographical memory, such as the ACC, IFG, amygdala, and hippocampus, would be engaged differently depending on the parent and the valence of situation, and would be modulated by a person’s psychological health.Discussions can also be reviewed in the light of the cited literature and authors are invited to use an editing service for English language.Reply:As suggested, we have completely revised the discussion and the manuscript was reviewed by a native speaker for English expression.Revision:In ‘the 1st to 8th paragraphs’ of the Discussion sectionThe present study examined the neural relationship between the perception of a parent and the valence of an autobiographical memory, then explored how it is modulated by one’s psychological health. We measured perception by inciting imagination of the facial expression a parent had made in a given situation. The three seconds given for the task may have been too short to remember an autobiographical memory. However, since the vividness and reaction intensity in the stimulus assessments were rated as moderately or higher, we can say that the task was to evoke an autobiographical memory rather than an imagination or a simple impression. From our behavioral data, we saw a rank in imagined emotion scores among the valences of childhood memories, where positive situations elicited the highest imagined emotion score, followed by neutral situations and negative situations. In conjunction with the RT results, we could infer a sense of hesitation in choosing an appropriate expression especially for negative childhood situations compared to positive situations. The quality of communication between parents and children is an excellent indicator of the quality of a parent-child relationship. Studies suggest that open communication with parents allows children to learn skills that are closely related to healthy coping skills and problem-solving strategies . Thus, we assessed whether the quality of the relationship with parents affects the impression of parents during childhood. As expected, we found that more open communication with either father or mother was correlated with a greater emotion score in positive emotion situations for both parents. On the other hand, negative correlations were seen between communication problem scale scores (father/mother) and the imagined emotion ratings for the respective parent-positive conditions. Altogether, these findings convey that relationship quality directly affects the recollection of one’s parents in positive contexts, but not necessarily in negative situations. Moreover, the results also revealed that one’s level of self-esteem positively influences the perception of one’s father, particularly in positive situations. This finding further highlighted the influence of self-esteem on how positively one perceives his or her father for positive memories, rather than rumination on exaggerated negative affects seen in previous patient studies . From the neuroimaging data, we saw intriguing neural responses to each condition from the right caudal ACC and precuneus, in particular. In the result of the caudal ACC, there was a particular bias toward father-negative and mother-positive, suggesting that in the autobiographical memory of emotional events, different forms of brain reactions occur depending on the parent's gender. Attention on the caudal ACC has risen in recent years and studies have indicated that the region contributes significantly to negative affect and pain processing [56-58]. This region receives an ample amount of emotion-related and voluntary movement signals , and has been suggested as a pivotal site for the emotional and voluntary interaction [58]. In a fascinating investigation on pain processing in self and others, it was seen that the caudal ACC was activated in response to self-experienced pain, but not when perceiving pain in others [56]. Furthermore, this region was shown to increase in response to negatively charged autobiographical memories [61]. On the other hand, its involvement in other-experienced pain processing has also been reported. A meta-analysis on empathy-related regions indicates that this region is part of the pain empathy network, and is engaged when pain was anticipated [62]. Regardless, it is clear that the caudal ACC plays a role in processing negative affect.In light of these caudal ACC functions, our results may be linked to mothers taking on the role of primary caretaker more so than the fathers. In many cultures, traditional gender roles have determined the roles and expectations for parents, which usually assumes fathers as breadwinners and mothers as the primary caretaker in child rearing . This point can be related to our results of the stimulus assessment. The analysis of the stimulus assessments indicated that the responses that fathers gave were less intense in all situations than those given by mothers; and the imagination of fathers’ appearances were less vivid and evoked less arousal than that of the mothers. In these respects, it is possible that caudal ACC activity may be a response to the stoic and emotionally distant perception of fathers. Meanwhile, the importance of memory to the mother can be seen in our result of negative correlation between caudal ACC activity in the mother-positive condition and depression score. There was a report that pathological changes in this region may be related to major depressive disorder [65]. A study on the behavioral adaptation to unpleasant environment showed the involvement of the caudal ACC to be critical in the ability to regulate the behavior [66]. It has been suggested that the region might contribute to defending one from developing depression [67]. Taken together, our result of the negative correlation in the mother-positive condition may suggest that through the function of the caudal ACC, autobiographical memories of positive events with the mother may act as a factor that prevents depression.The precuneus, a central hub of the default mode network, also exhibited a similar interaction effect between the parent and situation during the childhood memory recollection task. The precuneus has been thought to play a critical role in episodic memory , source monitoring [70], and self-referential processing [71]. Recently, a multivariate analysis method, representational similarity analysis, demonstrated that the precuneus is a key region engaged during the subjective experience of vivid autobiographical memory reminiscence [72]. Other experiments have confirmed its prominent involvement in the vividness of self-related memories . In addition, right lateralization of the precuneus has been shown for highly personal and vivid reminiscence of autobiographical events [72]. Right lateralization is corroborated by the present study, which required participants not only to visualize a given circumstance, but also to delineate the facial expression by either parent. Our results indicate overall greater activation of the right precuneus during recollection of fathers than mothers, and more specifically, its activity was higher when recollecting fathers in negative compared to positive situations. It is interesting to note that despite lower vividness score in the stimulus assessments for fathers than mothers, these findings were observed, suggesting that the perceptions of fathers may be more personal than those of mothers, especially during reminiscence of negative situations. These may indicate the saliency of childhood memories of fathers and particularly how fathers responded during negative circumstances. In conjunction with activity of the caudal ACC, we cautiously conclude that memories of fathers in negative situations have a more adverse effect as the negative impression of fathers is more permanently embedded. This interpretation can also be linked to the results of correlation with self-esteem. Studies report that the neural structure of personal semantic memories serves as a neural correlate of self-esteem . It is postulated that due to its role in using autobiographical memories to choose the applicable self-relevant information, activation of the precuneus is closely related to self-esteem and how one processes given information . The current study confirmed the established association between self-esteem and precuneus activity, as we found a negative relationship between one’s self-esteem and precuneus activity during autobiographical reminiscence of fathers in negative events. Recently, the precuneus was identified to correlate positively with evaluation sensitivity, measured by a change in state self-esteem [75]. Together with the evidence supporting the precuneus’ affiliation with evaluation sensitivity, as well as the tendency for individuals with lower self-esteem to be more affected by negative information [76], our result seems to suggest that the heightened activation observed in individuals with lower self-esteem may be due to the saliency of negative memories during recollection and their tendency to be more influenced by negative information.  Our PPI analysis revealed significant increases in functional connectivity of the caudal ACC with the fusiform gyrus and postcentral gyrus for the father-positive condition compared to the mother-positive condition. Given that the fusiform gyrus processes facial identity [78] and emotion [79], our finding may indicate that a greater sense of negative affect was involved while processing facial expressions of fathers than mothers in positive childhood events. This raises the possibility that the negative affect arisen from processing emotional face expressions may be particularly different between the parent in a positive context. Going back to the stimulus assessments, we saw lower vividness, response intensity, and arousal from fathers than mothers. Again, this may be since, generally, mothers are primary caregivers who spend more time with children; thus, one may have more readily available positive memories involving mothers than fathers to access on demand.Previously, individuals with high trait anxiety have shown to hyperactivate the fusiform gyrus while processing uncertain cues and angry faces . Consistent with the activation study, our study revealed that the connectivity strengths between the cingulate cortex and fusiform gyrus during the father-positive versus mother-positive condition correlated positively with the severity of anxiety symptoms. These results may provide the neurobiological influence of trait anxiety in the retrieval of memory and the perception of fathers. In addition to emotional face processing, greater connectivity between the cingulate area and postcentral gyrus was witnessed for the father-positive than mother-positive condition. Functional connectivity between these two regions has been implicated in posttraumatic stress disorder (PTSD), where patients with PTSD showed stronger connectivity than the control group, and also was positively correlated with the severity of symptoms [82]. As part of the sensorimotor network [83], the coupling of the caudal ACC and postcentral or paracentral gyri has been shown to be involved in shock processing [84] and other emotional memory tasks [85]. Based on the evidence, we postulate that the caudal ACC may relay negatively valenced affective information to the sensorimotor area more for fathers than mothers when processing facial expressions.AttachmentResponses to Reviewers 0316_HEK.docxSubmitted filename: Click here for additional data file. 27 Mar 2020The neural influence of autobiographical memory related to the parent-child relationship on psychological health in adulthoodPONE-D-19-30869R1Dear Authors,We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.Within one week, you will receive an e-mail containing information on the amendments required prior to publication. 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Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact With kind regards,Luca Cerniglia, PhDAcademic EditorPLOS ONEAdditional Editor Comments :The authors were responsive to all comments. I think the manuscript can be published in the present version.Reviewers' comments: 31 Mar 2020PONE-D-19-30869R1 The neural influence of autobiographical memory related to the parent-child relationship on psychological health in adulthood Dear Dr. Kim:I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. 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Purpose: The aim of this paper was to show the usefulness of imagery in better documenting the pathology of the anterior segment. Methods: The article comprises clinical cases, insisting on how imagery was essential in establishing the diagnosis or the therapeutic plan.Results: Lack of imagery would have made establishing a proper diagnosis much more difficult.Conclusions: Although clinical examination is simple and offers a fairly good amount of information, some particular cases of anterior segment pathology need additional investigations, every method having its indications and limits. The ophthalmologist can consider himself fortunate for having chosen this particular medical specialty because in most cases the doctor can readily observe the disease just by using his own eyes. Nevertheless, sometimes, with the help of modern biomicroscopes – with good illumination and different levels of magnification – ophthalmologists can have an even better view of the pathological process. This is especially true for anterior segment pathology. The cornea, the anterior chamber and the iris can be easily approached and the diagnosis rarely needs additional investigations. However, there are clinical situations when the ophthalmologist has doubts and certain imaging investigations may help him.1,2]. Limitations in current clinical imaging revealed the need to provide the maximum achievable resolution while also making it possible for the ultrasound beam to penetrate the ocular structures. The greater the frequency, the greater the resolution. For instance, for a 60 microns resolution, an operating frequency of 60 MHz is needed. The price to be paid for the increase in resolution is the loss of penetration. Human tissues have an ultrasound attenuation coefficient that increases with frequency. A frequency of 10 MHz allows a penetration of 50 millimeters, but, for 60 MHz, the penetration is only 5 millimeters.The use of high frequencies, with a range between 20 to 100 MHz, has improved the resolution of ultrasound images and allows the visualization of the cornea and anterior segment. The first device for clinical use was introduced by Devlin and colleagues from the laboratory of Stuart Foster at the University of Toronto and the authors named this examination method ultrasound biomicroscopy .UBM has been helpful in uncovering the mechanism of angle-closure glaucoma, due to its ability to show all the angle components and also the ciliary body. It also made it possible to study the behavior of the iris under different illumination conditions [6].In trauma cases, UBM can reveal the cyclodialysis cleft even when the anterior chamber is shallow and it is not obvious with gonioscopy. UBM can make the state of the anterior chamber apparent under traumatic opacities and detect and assess the position of foreign bodies that are difficult to view using conventional techniques [7].The evaluation of iris tumors can be improved by using UBM, especially in the case of angle tumors, where it can provide measurements of the tumors, including the height, that can be used for follow-up [8].UBM can assess corneal and conjunctival tumors, along with the depth of the conjunctival, limbal and corneal lesions. This is especially useful for corneal involvement, where UBM can determine the thickness of the tumor and which corneal layers are involved . Optical coherence tomography (OCT) is a high-resolution imaging technique that uses low coherence interferometry to obtain axial resolution in the range of 3-20 microns. Anterior segment optical coherence tomography (AS-OCT) was first demonstrated in 1994 by Izzat, using light with a wavelength of 830 nm, used mainly for the posterior pole examination. However, this wavelength does not have good penetration through the sclera, whereas the wavelength of 1310 nm allows deeper penetration and imaging of the anterior chamber, including the angle .AS-OCT can be useful in the diagnosis and follow-up of different corneal diseases: dystrophies, degenerations, inflammatory pathology – corneal infiltrations, ulcers, scars. For corneal ulcers, the depth and extent obtained by AS-OCT is more accurate to that of anterior segment photography [12].AS-OCT provides different tools for measuring structures of the anterior segment: accurate measurements of the angle, calipers that can measure anterior chamber depth and width and also corneal thickness. In keratoconus management, AS-OCT can document the corneal thickness and also provide good imaging of intracorneal rings . In endothelial keratoplasty, AS-OCT can visualize and monitor the graft attachment.In corneal transplantation, AS-OCT provides images of the host-graft junction and of retrocorneal membranes [14]. It can be used to distinguish between appositional and synechial closure, and it can also assess the result of laser iridotomy – showing whether iridectomy has increased the depth of the anterior chamber and the width of the angle [15]. AS-OCT has a role in the visualization of the anterior segment anatomy when suspecting malignant glaucoma and can also be used in the evaluation of the filtration bleb after trabeculectomy.In glaucoma, AS-OCT provides direct visualization of the anterior chamber angle. Many studies showed that AS-OCT measurement of the angle is reliable and correlated to gonioscopy [Case 1Fig. 1).We presented the case of a patient who underwent a penetrating keratoplasty for bullous keratopathy 30 days before admission. A retrocorneal membrane covered all the surface behind the graft, apart from a small region, situated temporally. There was a distance of about 1,5 millimeters between the cornea and the membrane and the same distance between the membrane and the iris .UBM emphasized that the retrocorneal membrane arose at the graft-host junction and covered the entire circumference, except for a small temporal region. The thickness of the membrane appeared to be 10-15% of that of the cornea .AS-OCT showed the same modifications, but better assessed the thickness of the very thin membrane .The diagnosis of retained host Descemet’s membrane was established and surgical removal was performed with good functional results .The second case was that of a patient who suffered a car accident and had multiple glass foreign bodies removed from his cornea in the emergency department. The patient was then referred to our clinic for a deep corneal foreign body, as well as for an intraocular foreign body .UBM provided information regarding the location of the intraocular foreign body, which was without contact with the iris. The foreign body was removed through a corneal incision with no corneal, iris or lens damage. AS-OCT could not obtain a good view of the angle .Regarding the corneal foreign body, UBM showed a hyperreflective lesion in the corneal stroma; it was difficult to assess how deep the foreign body was .AS-OCT showed a hyperreflective area with a shadow effect in the anterior stroma, quite superficially; it was removed without complications .AS-OCT better assessed the corneal scars and the corneal trajectory of the intraocular foreign body, information impossible to obtain by using UBM . The lesion was pigmented, near the angle, about 2 millimeters in diameter, between the 8 and 9 o’clock positions. It was difficult to assess the elevation using the biomicroscope due to the reflection of light in the peripheral cornea. Gonioscopy showed a pigmented lesion, which did not appear prominent.A glaucoma patient who underwent trabeculectomy and phacoemulsification with intraocular lens implantation 12 months before in another clinic, came for a pigmented lesion that had appeared 6 months before and seemed to have become darker and to have increased in dimensions .UBM was performed to evaluate the depth and the extension of the lesion, but surprisingly it showed that at the level of the lesion the thickness of the iris was significantly reduced (to more than 70%) .In this case, the patient presented with a prominent, pigmented lesion of the bulbar conjunctiva, which also involved the limbus and the cornea . UBM showed a hyperreflective lesion at the level of the limbus and cornea; there was a line of demarcation between the lesion and the cornea. There was no intraocular extension of the lesion, the anterior chamber angle being free .AS- OCT could not assess the structures beneath the tumor that was opaque to light (As it can be seen, although the lesions were very accessible to direct visualization, the comprehensive assessment requires imagistic methods. Both the UBM and the AS-OCT have advantages, but also limitations. UBM can examine through opaque media – pigmented lesion, as in case 4 -, corneal scars, corneal edema. It can also visualize retroirian structures. However, it is difficult to obtain good quality images, the procedure is time-consuming and needs topical anesthesia; it is a contact method, not very pleasant for the patient and sometimes corneal erosions may occur. AS-OCT is a non-contact method; the images are taken very quickly and it is easier to obtain good quality images. A follow-up can be achieved more accurately than with UBM, because some anatomical structures – nevi, vessels – can be used as landmark points. The method is more accurate in assessing corneal lesions, but only in clear corneas. The main disadvantage is that it cannot examine through opaque media – tumors, scars, pterygium – or behind the iris.


Recently, the rapid development of the Internet of Things (IoT) has led to an increasing exponential growth of non-scalar data . Local services are far from satisfying storage requirements, and the cloud computing fails to effectively support heterogeneous distributed IoT environments, such as wireless sensor network. To effectively provide smart privacy protection for video data storage, we take full advantage of three patterns  of edge computing to design the hierarchical edge computing architecture, and propose a low-complexity and high-secure scheme based on it. The video is divided into three parts and stored in completely different facilities. Specifically, the most significant bits of key frames are directly stored in local sensor devices while the least significant bits of key frames are encrypted and sent to the semi-trusted cloudlets. The non-key frame is compressed with the two-layer parallel compressive sensing and encrypted by the 2D logistic-skew tent map and then transmitted to the cloud. Simulation experiments and theoretical analysis demonstrate that our proposed scheme can not only provide smart privacy protection for big video data storage based on the hierarchical edge computing, but also avoid increasing additional computation burden and storage pressure. Cloud computing was introduced in Search Engine Strategies 2006 in order to tackle the constraints of the Internet of Things (IoT) in management, storage, computing and processing, and was formally defined by National Institute of Standards and Technology . Since tHowever, cloud computing cannot efficiently support big multimedia data storage in distributed IoT environments because of the following reasons . First, Generally speaking, edge computing includes three patterns, that is, multi-access edge computing (MEC) ,10, clouHowever, various security issues have always been potential threats to the cloud storage. Each user has his/her own data ranging from GB’s to TB’s and the local storage fails to achieve this huge demand alone. Thus, deploying a low-complexity and high-secure cloud storage service has become an inevitable trend. In other words, the cloud provider who supports smart edge computing-based IoT applications with higher security degrees will attract more individuals. In this paper, we propose a novel distributed compressive video sensing (DCVS) coding  and the We make full use of the respective advantages of MEC, cloudlets and fog computing to design the hierarchical edge computing architecture to support distributed IoT application environments.The most significant bits (MSB) of the key frame (KF) are completely controlled by users so that our proposed scheme has higher degrees of security. Meanwhile, the least significant (LSB) bits of KF are directly encrypted via MSB to avoid unnecessary computation burden of edge computing and extra storage pressure of local sensor devices.The two-layer parallel compressive sensing is used to compress the non-key frame (NKF) so as to minimize the storage burden on cloud services.The remainder of this paper is organized as follows. S is the key stream with the same size O. The inverse operation in the decryption process can be expressed byDiffusion can significantly change statistical characteristics of the input plain-frame and spread the influence of each bit to the cipher-frame. The principle is to diffuse the corresponding pixel of the current frame through the value of the key stream . In ordei column of an original 2D signal and i column of the measurement value via linear projection of the measurement matrix Compressive sensing (CS) has two promising advantages: compress and sample simultaneously; the sampling rate is much lower than the Nyqvist-Shannon criterion. Both of them facilitate CS to be used in relevant fields widely since its emergence . HoweverLyu et al. proposed a privacy-preservation system for fog-based aggregation in Smart Grid with differential privacy so as to enable the intermediate fog nodes to safely collect data from connected smart meters . Wang etHowever, to the best of our knowledge, this study is the first to take full advantage of MEC, cloudlets and fog computing to design the hierarchical edge computing architecture and propose a smart and low-complexity privacy protection scheme for big video data storage based on it. Besides, the cloud space does not mean unlimited storage resources so that we also consider compression.Bonomi et al. argued that the features of fog computing make it suitable for many critical Internet of Things services and applications, namely, connected vehicle, smart grid, cloud computing and wireless sensors networks . Hu et aMora-Gimeno et al. presented a security model for the externalization of application execution in multi-tier MEC environments, which produces a minimal overhead, especially for computationally intensive applications . Lee et The above researches related with the edge computing schemes can be classified as the three-level architecture, including the local individual layer, the edge computing layer and the cloud computing layer. Specifically, the edge computing layer is refined as the MEC layer. However, although MEC brings computing power and storage resources to the edge of the mobile network, limited computation resources of mobile edge nodes may not be sufficient to serve excessive offloading tasks exceeding the computation capacities of themselves. Further, we can take advantage of the lower latency of MEC to distinguish KF from NKF in real time while receiving the video. Meanwhile, all frames are encrypted or compressed by fog computing, which has relatively stronger computing resources compared with MEC. In addition, considering the local storage resources are limited and individuals do not want the key information of the video to be stored by completely un-trusted cloud, we use the independent encoding - joint decoding DCVS coding to divide the video data into three parts. MSB of KF is stored by local devices while LSB of KF is transmitted to the semi-trusted cloudlets. The rest, NFK, which must be reconstructed better via referring to KF, should be stored to the cloud after a series of processing. This is why we design a novel hierarchical edge computing architecture to provide smart private protection for big video data storage with low latency.The overall scheme of using the hierarchical edge computing architecture to protect big video data storage privacy is shown in Video is not a simple combination of pictures, and there are strong correlations among frames. That is, the selection of KF often determines the whole recovery performance of NKF from the same GOP. Thus, GOP selection has profound significance for video sampling. However, service objects of the cloud consist of intelligent users, ocean monitoring and so on, as shown in Fixed GOP values: If a certain scenario needs to analyze complex or important videos, the small values should be selected to ensure reconstruction performance, while the large values could be considered to reduce the overall sampling rate of videos and handle massive data.Adaptive GOP selection: In order to improve encoding efficiency and decoding performance, the adaptive GOP selection based on the perceptual hash algorithm was applied for DCVS . Though In a word, we should make a concrete analysis of concrete conditions. MEC receives the video stream from the nearest local devices and then the separated KF and NKF are transmitted to different layers of fog computing.Take 1st frame of “News(CIF)” as an example. The whole scheme of encoding KF is shown in M and N are the width and the length of the KF The MSB Then, the binary matrix As encoding of KF only involves encryption, decoding is the inverse process of encoding. In brief, To further improve the security level and achieve better accuracy of the NKF reconstruction, we do not directly perform coding but extract deviations between NKF and KF of the same GOP at first in the first layer of fog computing. Then taking the 2nd frame of “News(CIF)” as an example, as shown in x (DBBD)  is adoptSet initial values l iterated values to avoid transient effects byIterate Discretize Rearrange Exchange the pixel Finally, transmit the encrypted NKF to the cloud.The decoding process of NKF is decryption-then-reconstruction. Decryption and encryption are inter-reversible and the secret key  (TVAL3)  is used In this paper, our proposed scheme is encoded and decoded by MATLAB 2016a programming software. Hall(CIF), News(CIF) and Foreman(CIF) with different motion types are applied to simulate our scheme reliably. The security analysis of video data storage based on the hierarchical edge computing can be analyzed from two aspects. From the perspective of KF, although the local individuals have full control over the edge computing devices and can rely on the cloudlets to manage data, cipher-data are stored to prevent an attacker who obtains the data by force. In the field of reversible data hiding, the LSB layers of the cover image are usually replaced by significant information to ensure that no change in the cover image is visible to the naked eye. It indicates that the important data of an image is located in the MSB layers. Based on this principle, we divide KF into the MSB layers and LSB layers equally. Compared with the random matrix generated by the key to diffuse the LSB layers, directly regarding the MSB layers as the key stream is far more secure and even does not need to provide the extra space to store the key. Besides, two secret keys with only one bit difference can encrypt a certain frame into two different cipher-frames by bit adaptive diffusion. So our secure scheme for KF has strong capability of resisting famous attacks, such as differential attack and chosen-plaintext attack.The NKF, which occupies a large part of videos, have to be stored in the completely untrusted public cloud. So the privacy and compression should be considered at the same time. In order to achieve the above goal without increasing computation complexity, we directly adopt the two-layer PCS with controlled sampling rates. To be more specific, in the first compression process, the three-layer RGB employs different sampling rates so that the correct composition proportion of the 1D plane formed by combination could not be known absolutely. To further reduce the storage, the second compression is adopted. Besides, instead of processing NKF directly, the main information is removed by subtraction in order to avoid the sensitive data leakage. We also use 2D logistic-skew tent map to encrypt measurement values further to improve the performance of privacy preservation.In short, our proposed scheme not only provides effective and efficient privacy protection for big video storage based on the hierarchical edge computing, but also does not add additional burden from both computation and storage aspects of edge computing and the public cloud.In this paper, we take full advantage of three patterns  of edge computing to design the hierarchical edge computing. Based on this architecture, we further propose a novel smart privacy preservation scheme for big video data storage. For KF, MSB are stored directly in local sensor devices while LSB are encrypted by MSB and then sent to cloudlets. For NKF, two-layer PCS and encryption are performed at first, and finally transmitted to the cloud service. Experimental results and theoretical analysis prove that our proposed scheme is effective, efficient and lower-complexity, which provides smart privacy-protection for video contents.