You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Anterior insula volume and guilt: neurobehavioral markers of recurrence after early childhood major depressive disorder.
Abstract 1:
IMPORTANCE This is the first study to date to examine volumetric alterations in the anterior insula ( AI ) as a potential biomarker for the course of childhood major depressive disorder ( MDD ) . OBJECTIVES To examine whether children with a history of preschool-onset ( PO ) MDD show reduced AI volume , whether a specific symptom of PO MDD ( pathological guilt ) is related to AI volume reduction ( given the known relationship between AI and guilt processing ) , and whether AI volumes predict subsequent likelihood of having an episode of MDD . DESIGN , SETTING , AND PARTICIPANTS In a prospect i ve longitudinal study , 306 children ( age range , 3.00 - 5.11 years ) and caregivers completed DSM diagnostic assessment s at 6 annual time points during 10 years as part of the Preschool Depression Study .  Magnetic resonance imaging was completed on a subset of 145 school-age children ( age range , 6.11 - 12.11 years ) . MAIN OUTCOMES AND MEASURES Whole-brain-adjusted AI volume measured using magnetic resonance imaging at school age and children 's diagnosis of MDD any time after their imaging . RESULTS Compared with children without a history of PO MDD , school-age children previously diagnosed as having PO MDD had smaller left and right AI volumes ( Wilks Λ = 0.94 , F2,124 = 3.37 , P = .04 , Cohen d = 0.23 ) . However , the effect of PO MDD on reduced AI volumes was better explained by children 's experience of pathological guilt during preschool ( Λ = 0.91 , F2,120 = 6.17 , P = .003 , d = .30 ) . When covarying for children 's lifetime history of MDD episodes , their experience of pathological guilt during preschool , as well as their sex and age at the time of imaging , schoolchildren 's right-side AI volume was a significant predictor of being diagnosed as having an MDD episode after imaging ( odds ratio , 0.96 ; 95 % CI , 0.01 - 0.75 ; P = .03 ) . CONCLUSIONS AND RELEVANCE These results provide evidence that structural abnormalities in AI volume are related to the neurobiology of depressive disorders starting in early childhood . The present findings are consistent with mounting research in adult MDD suggesting that insula function and structure may be a target biomarker for major depression


Title 2:
Effect of subjective perspective taking during simulation of action: a PET investigation of agency
Abstract 2:
Perspective taking is an essential component in the mechanisms that account for intersubjectivity and agency . Mental simulation of action can be used as a natural protocol to explore the cognitive and neural processing involved in agency . Here we took PET measurements while  subjects simulated actions with either a first-person or a third-person perspective .  Both conditions were associated with common activation in the SMA , the pre central gyrus , the precuneus and the MT/V5 complex . When compared to the first-person perspective , the third-person perspective recruited right inferior parietal , precuneus , posterior cingulate and frontopolar cortex . The opposite contrast revealed activation in left inferior parietal and somatosensory cortex . We suggest that the right inferior parietal , precuneus and somatosensory cortex are specifically involved in distinguishing self-produced actions from those generated by others


Title 3:
Modeling other minds
Abstract 3:
Nine normal volunteers performed a ‘ theory of mind ’ task while their regional brain blood flow pattern was recorded using the PET [15O]H2O technique . Control conditions induced subjects to attend to the visual and semantic attributes of known objects . In a third condition , subjects had to infer the function of an unfamiliar object from its form . In the ‘ theory of mind ’ condition , subjects had to infer function based on the form of both familiar and unfamiliar objects and in addition , model the knowledge and rationality of another mind about the function of these objects . Performance during the ‘ theory of mind ’ condition evoked the activation of a distributed set of neural networks with prominent activation of the left medial frontal lobe ( Brodmann area 9 ) and left temporal lobe ( Brodmann areas 21 , 39/19 , 38 ) . This result suggests that when inferential reasoning depends on constructing a mental model about the beliefs and intentions of others , the participation of the prefrontal cortex is required . When access to such knowledge is affected by central nervous system dysfunction , such as that found in autism , modeling other minds may prove difficult


Title 4:
Caught in the act: The impact of audience on the neural response to morally and socially inappropriate behavior
Abstract 4:
We examined the impact of witnesses on the neural response to moral and social transgressions  using fMRI . In this study , participants ( N=16 ) read short vignettes describing moral and social transgressions in the presence or absence of an audience . In line with our hypothesis , ventrolateral ( BA 47 ) and dorsomedial ( BA 8) frontal cortex showed increased BOLD responses to moral transgressions regardless of audience and to social transgressions in the presence of an audience relative to neutral situations . These findings are consistent with the suggestion that these regions of prefrontal cortex modify behavioral responses in response to social cues . Greater activity was observed in left temporal-parietal junction , medial prefrontal cortex and temporal poles to moral and to a lesser extent social transgressions relative to neutral stories , regardless of audience . These regions have been implicated in the representation of the mental states of others ( Theory of Mind ) . The presence of an audience was associated with increased left amygdala activity across all conditions


Title 5:
The neural correlates of maternal and romantic love
Abstract 5:
Romantic and maternal love are highly rewarding experiences . Both are linked to the perpetuation of the species and therefore have a closely linked biological function of crucial evolutionary importance . Yet almost nothing is known about their neural correlates in the human . We therefore used fMRI to measure brain activity in mothers while they viewed pictures of their own and of acquainted children , and of their best friend and of acquainted adults as additional controls . The activity specific to maternal attachment was compared to that associated to romantic love described in our earlier study and to the distribution of attachment-mediating neurohormones established by other studies . Both types of attachment activated regions specific to each , as well as overlapping regions in the brain 's reward system that coincide with areas rich in oxytocin and vasopressin receptors . Both deactivated a common set of regions associated with negative emotions , social judgment and ' mentalizing ' , that is , the assessment of other people 's intentions and emotions . We conclude that human attachment employs a push-pull mechanism that overcomes social distance by deactivating networks used for critical social assessment and negative emotions , while it bonds individuals through the involvement of the reward circuitry , explaining the power of love to motivate and exhilarate


Title 6:
Emotional arousal and activation of the visual cortex: an fMRI analysis.
Abstract 6:
Functional activity in the visual cortex was assessed using functional magnetic resonance imaging technology while participants viewed a series of pleasant , neutral , or unpleasant pictures . Coronal images at four different locations in the occipital cortex were acquired during each of eight 12-s picture presentation periods ( on ) and 12-s interpicture interval ( off ) . The extent of functional activation was larger in the right than the left hemisphere and larger in the occipital than in the occipitoparietal regions during processing of all picture contents compared with the interpicture intervals . More importantly , functional activity was significantly greater in all sample d brain regions when processing emotional ( pleasant or unpleasant ) pictures than when processing neutral stimuli . In Experiment 2 , a hypothesis that these differences were an artifact of differential eye movements was ruled out . Whereas both emotional and neutral pictures produced activity centered on the calcarine fissure ( Area 17 ) , only emotional pictures also produced sizable clusters bilaterally in the occipital gyrus , in the right fusiform gyrus , and in the right inferior and superior parietal lobules


Title 7:
Remembering the past: two facets of episodic memory explored with positron emission tomography.
Abstract 7:
OBJECTIVE This study used positron emission tomography to examine two kinds of personal memory that are used in psychiatric evaluation : focused episodic memory ( recall of past experience , employed in " taking a history " ) and r and om episodic memory ( uncensored thinking about experience , examined during analytic therapy using free association ) . For comparison , a third memory task was used to tap impersonal memory that represents general information about the world ( " semantic memory " ) . METHOD Thirteen subjects were studied using the [15O]H2O method to obtain quantitative measurements of cerebral blood flow . The three conditions were subtracted and their relative relationships examined . RESULTS The r and om episodic condition produced activations in widely distributed association cortex ( right and left frontal , parietal , angular/supramarginal , and posterior inferior temporal regions ) . Focused episodic memory engaged a network that included the medial inferior frontal regions , precuneus/retrosplenial cingulate , anterior cingulate , thalamus , and cerebellum . The use of medial frontal regions and the precuneus/retrosplenial cingulate was common to both focused and r and om episodic memory . The major difference between semantic and episodic memory was activation of Broca 's area and the left frontal operculum by semantic memory . CONCLUSIONS These results indicate that free-ranging mental activity ( r and om episodic memory ) produces large activations in association cortex and may reflect both active retrieval of past experiences and planning of future experiences . Focused episodic memory shares some components of this circuit ( inferior frontal and precuneus ) , which may reflect the time-linked components of both aspects of episodic memory , and which permit human beings to experience personal identity , consciousness , and self-awareness


Title 8:
Movement and Mind: A Functional Imaging Study of Perception and Interpretation of Complex Intentional Movement Patterns
Abstract 8:
We report a functional neuroimaging study with positron emission tomography ( PET ) in which six healthy adult volunteers were  scanned  while watching silent computer-presented animations . The characters in the animations were simple geometrical shapes whose movement patterns selectively evoked mental state attribution or simple action description . Results showed increased activation in association with mental state attribution in four main regions : medial prefrontal cortex , temporoparietal junction ( superior temporal sulcus ) , basal temporal regions ( fusiform gyrus and temporal poles adjacent to the amygdala ) , and extrastriate cortex ( occipital gyrus ) . Previous imaging studies have implicated these regions in self-monitoring , in the perception of biological motion , and in the attribution of mental states using verbal stimuli or visual depictions of the human form . We suggest that these regions form a network for processing information about intentions , and speculate that the ability to make inferences about other people 's mental states evolved from the ability to make inferences about other creatures ' actions


Title 9:
Reflecting upon Feelings: An fMRI Study of Neural Systems Supporting the Attribution of Emotion to Self and Other
Abstract 9:
Underst and ing one 's own and other individual 's emotional states is essential for maintaining emotional equilibrium and strong social bonds . Although the neural substrates supporting reflection upon one 's own feelings have been investigated , no studies have directly examined attributions about the internal emotional states of others to determine whether common or distinct neural systems support these abilities . The present study sought to directly compare brain regions involved in judging one 's own , as compared to another individual 's , emotional state . Thirteen participants viewed mixed valence blocks of photos drawn from the International Affective Picture System while whole-brain fMRI data were collected . Preblock cues instructed participants to evaluate either their emotional response to each photo  , the emotional state of the central figure in each photo , or ( in a baseline condition ) whether the photo was taken indoors or outdoors .  Contrasts indicated ( 1 ) that both self and other judgments activated the medial prefrontal cortex ( MPFC ) , the superior temporal gyrus , and the posterior cingulate/precuneus , ( 2 ) that self judgments selectively activated subregions of the MPFC and the left temporal cortex , whereas ( 3 ) other judgments selectively activated the left lateral prefrontal cortex ( including Broca 's area ) and the medial occipital cortex . These results suggest ( 1 ) that self and other evaluation of emotion rely on a network of common mechanisms centered on the MPFC , which has been hypothesized to support mental state attributions in general , and ( 2 ) that medial and lateral PFC regions selectively recruited by self or other judgments may be involved in attention to , and elaboration of , internally as opposed to externally generated information


Title 10:
Brain activation associated with evaluative processes of guilt and embarrassment: an fMRI study
Abstract 10:
We aim ed to investigate the neural substrates associated with evaluative process of moral emotions . Using functional magnetic resonance imaging ( fMRI ) , we examined the similarities and differences between evaluative process of guilt and that of embarrassment at the neural basis level . Study of the neural basis of judgments of moral emotions might contribute to a better underst and ing of the amoral behavior observed in neurological and psychiatric disorders . Nineteen healthy volunteers were studied . The participants read sentences carrying neutral , guilty , or embarrassing contents during the scans . Both guilt and embarrassment conditions commonly activated the medial prefrontal cortex ( MPFC ) , left posterior superior temporal sulcus ( STS ) , and visual cortex . Compared to guilt condition , embarrassment condition produced greater activation in the right temporal cortex ( anterior ) , bilateral hippocampus , and visual cortex . Most of these regions have been implicated in the neural substrate of social cognition or Theory of Mind ( ToM ) . Our results support the idea that both are self-conscious emotions , which are social emotions requiring the ability to represent the mental states of others . At the same time , our functional fMRI data are in favor of the notion that evaluative process of embarrassment might be a more complex process than that of guilt
MACM demonstrated that regions associated with guilt are highly interconnected .
Our analysis identified a distributed neural network of left-lateralized regions associated with guilt .
While voxel-based FDR-corrected results should be considered exploratory , the dorsal cingulate was robustly associated with guilt .
We speculate that this network integrates cognitive and emotional processes involved in the experience of guilt , including self-representation , theory of mind , conflict monitoring and moral values .