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1.  The Neural Architecture of Music-Evoked Autobiographical Memories 
Cerebral Cortex (New York, NY)  2009;19(11):2579-2594.
The medial prefrontal cortex (MPFC) is regarded as a region of the brain that supports self-referential processes, including the integration of sensory information with self-knowledge and the retrieval of autobiographical information. I used functional magnetic resonance imaging and a novel procedure for eliciting autobiographical memories with excerpts of popular music dating to one's extended childhood to test the hypothesis that music and autobiographical memories are integrated in the MPFC. Dorsal regions of the MPFC (Brodmann area 8/9) were shown to respond parametrically to the degree of autobiographical salience experienced over the course of individual 30 s excerpts. Moreover, the dorsal MPFC also responded on a second, faster timescale corresponding to the signature movements of the musical excerpts through tonal space. These results suggest that the dorsal MPFC associates music and memories when we experience emotionally salient episodic memories that are triggered by familiar songs from our personal past. MPFC acted in concert with lateral prefrontal and posterior cortices both in terms of tonality tracking and overall responsiveness to familiar and autobiographically salient songs. These findings extend the results of previous autobiographical memory research by demonstrating the spontaneous activation of an autobiographical memory network in a naturalistic task with low retrieval demands.
PMCID: PMC2758676  PMID: 19240137
emotion; episodic memory; fMRI; medial prefrontal cortex; tonality
2.  Neural representations of close others in collectivistic brains 
Our recent work showed that close relationships result in shared cognitive and neural representations of the self and one’s mother in collectivistic individuals (Zhu et al., 2007, Neuroimage, 34, 1310–7). However, it remains unknown whether close others, such as mother, father and best friend, are differentially represented in collectivistic brains. Here, using functional magnetic resonance imaging and a trait judgment task, we showed evidence that, while trait judgments of the self and mother generated comparable activity in the medial prefrontal cortex (MPFC) and anterior cingulate (ACC) of Chinese adults, trait judgments of mother induced greater MPFC/ACC activity than trait judgments of father and best friend. Our results suggest that, while neural representations of the self and mother overlapped in the MPFC/ACC, close others such as mother, father and best friend are unequally represented in the MPFC/ACC of collectivistic brains.
PMCID: PMC3277373  PMID: 21382966
close other; self; medial prefrontal cortex; anterior cingulate; fMRI
3.  Default Network Deactivations Are Correlated with Psychopathic Personality Traits 
PLoS ONE  2010;5(9):e12611.
The posteromedial cortex (PMC) and medial prefrontal cortex (mPFC) are part of a network of brain regions that has been found to exhibit decreased activity during goal-oriented tasks. This network is thought to support a baseline of brain activity, and is commonly referred to as the “default network”. Although recent reports suggest that the PMC and mPFC are associated with affective, social, and self-referential processes, the relationship between these default network components and personality traits, especially those pertaining to social context, is poorly understood.
Methodology/Principal Findings
In the current investigation, we assessed the relationship between PMC and mPFC deactivations and psychopathic personality traits using fMRI and a self-report measure. We found that PMC deactivations predicted traits related to egocentricity and mPFC deactivations predicted traits related to decision-making.
These results suggest that the PMC and mPFC are associated with processes involving self-relevancy and affective decision-making, consistent with previous reports. More generally, these findings suggest a link between default network activity and personality traits.
PMCID: PMC2935364  PMID: 20830290
4.  Functional Neuroimaging of Self-Referential Encoding with Age 
Neuropsychologia  2010;48(1):211-219.
Aging impacts memory formation and the engagement of frontal and medial temporal regions. However, much of the research to date has focused on the encoding of neutral verbal and visual information. The present fMRI study investigated age differences in a social encoding task while participants made judgments about the self or another person. Although previous studies identified an intact self-reference effect with age, subserved by robust engagement of medial prefrontal cortex (mPFC) by both young and older adults, we identified a number of age differences. In regions including superior mPFC, inferior prefrontal cortex, and anterior and posterior cingulate cortex, young and older adults exhibited reversals in the pattern of activity for self and other conditions. Whereas young primarily evidenced subsequent forgetting effects in the self-reference condition, older adults demonstrated subsequent memory effects in the other-reference condition. These results indicate fundamental differences across the age groups in the engagement of elaborative encoding processes. We suggest that older adults may encode information about the self in a more normative manner, whereas young adults focus on encoding the unique aspects of the self and distinguishing the self from others.
PMCID: PMC2794905  PMID: 19765600
Aging; self; long-term memory; prefrontal cortex; cognition; fMRI
5.  The World According to Me: Personal Relevance and the Medial Prefrontal Cortex 
More than a decade of neuroimaging research has established that anterior and posterior cortical midline regions are consistently recruited during self-referential thinking. These regions are engaged under conditions of directed cognition, such as during explicit self-reference tasks, as well as during spontaneous cognition, such as under conditions of rest. One of the many issues that remain to be clarified regarding the relationship between self-referential thinking and cortical midline activity is the functional specificity of these regions with regard to the nature of self-representation and processing. The functional profile associated with the medial prefrontal cortex (mPFC) is the focus of the current article. What is specifically explored is the idea that personal relevance or personal significance is a central factor that impacts how brain activity is modulated within this cortical midline region. The proactive, imaginative, and predictive nature of function in the mPFC is examined by evaluating studies of spontaneously directed cognition, which is triggered by stimulus-associated personal relevance.
PMCID: PMC3698455  PMID: 23847510
self-referential thinking; spontaneous cognition; reality-fiction distinction; default mode network; self relevance
6.  The role of medial prefrontal cortex in early social cognition 
One major function of our brain is to enable us to behave with respect to socially relevant information. Much research on how the adult human brain processes the social world has shown that there is a network of specific brain areas, also called the social brain, preferentially involved during social cognition. Among the specific brain areas involved in the adult social brain, functional activity in prefrontal cortex (PFC), particularly the medial prefrontal cortex (mPFC), is of special importance for human social cognition and behavior. However, from a developmental perspective, it has long been thought that PFC is functionally silent during infancy (first year of life), and until recently, little was known about the role of PFC in the early development of social cognition. I shall present an emerging body of recent neuroimaging studies with infants that provide evidence that mPFC exhibits functional activation much earlier than previously thought, suggesting that the mPFC is involved in social information processing from early in life. This review will highlight work examining infant mPFC function across a range of social contexts. The reviewed findings will illustrate that the human brain is fundamentally adapted to develop within a social context.
PMCID: PMC3701864  PMID: 23847509
infancy; development; prefrontal cortex; social cognition; fNIRS
7.  Anxiety Dissociates Dorsal and Ventral Medial Prefrontal Cortex Functional Connectivity with the Amygdala at Rest 
Cerebral Cortex (New York, NY)  2010;21(7):1667-1673.
Anxiety is linked to compromised interactions between the amygdala and the dorsal and ventral medial prefrontal cortex (mPFC). While numerous task-based neuroimaging studies show that anxiety levels predict amygdala–mPFC connectivity and response magnitude, here we tested the hypothesis that anxiety would predict functional connectivity between these brain regions even during rest. Resting-state functional magnetic resonance imaging scans and self-reported measures of anxiety were acquired from healthy subjects. At rest, individuals with high anxiety were characterized by negatively correlated amygdala–ventral mPFC functional connectivity, while low anxious subjects showed positively correlated activity. Further, high anxious subjects showed amygdala–dorsal mPFC activity that was uncorrelated, while low anxious subjects showed negatively correlated activity. These data show that amygdala–mPFC connectivity at rest indexes normal individual differences in anxiety.
PMCID: PMC3116741  PMID: 21127016
amygdala; anxiety; functional connectivity; medial prefrontal cortex; resting-state fMRI
8.  Development and neurophysiology of mentalizing. 
The mentalizing (theory of mind) system of the brain is probably in operation from ca. 18 months of age, allowing implicit attribution of intentions and other mental states. Between the ages of 4 and 6 years explicit mentalizing becomes possible, and from this age children are able to explain the misleading reasons that have given rise to a false belief. Neuroimaging studies of mentalizing have so far only been carried out in adults. They reveal a system with three components consistently activated during both implicit and explicit mentalizing tasks: medial prefrontal cortex (MPFC), temporal poles and posterior superior temporal sulcus (STS). The functions of these components can be elucidated, to some extent, from their role in other tasks used in neuroimaging studies. Thus, the MPFC region is probably the basis of the decoupling mechanism that distinguishes mental state representations from physical state representations; the STS region is probably the basis of the detection of agency, and the temporal poles might be involved in access to social knowledge in the form of scripts. The activation of these components in concert appears to be critical to mentalizing.
PMCID: PMC1693139  PMID: 12689373
9.  A Meta-Analysis of Functional Neuroimaging Studies of Self and Other Judgments Reveals a Spatial Gradient for Mentalizing in Medial Prefrontal Cortex 
Journal of cognitive neuroscience  2012;24(8):1742-1752.
The distinction between processes used to perceive and understand the self and others has received considerable attention in psychology and neuroscience. Brain findings highlight a role for various regions, in particular the medial prefrontal cortex (mPFC), in supporting judgments about both the self and others. We performed a meta-analysis of 107 neuroimaging studies of self- and other-related judgments using Multilevel Kernel Density Analysis (MKDA; Kober & Wager, 2010). We sought to determine what brain regions are reliably involved in each judgment type, and in particular, what the spatial and functional organization of mPFC is with respect to them. Relative to non-mentalizing judgments, both self and other judgments were associated with activity in mPFC, ranging from ventral to dorsal extents, as well as common activation of the left temporoparietal junction (TPJ) and posterior cingulate. A direct comparison between self and other judgments revealed that ventral mPFC (vmPFC), as well as left ventrolateral PFC and left insula, were more frequently activated by self-related judgments, whereas dorsal mPFC (dmPFC), in addition to bilateral TPJ and cuneus, were more frequently activated by other-related judgments. Logistic regression analyses revealed that ventral and dorsal mPFC lay at opposite ends of a functional gradient: the z-coordinates reported in individual studies predicted whether the study involved self- or other-related judgments, which were associated with increasingly ventral or dorsal portions of mPFC, respectively. These results argue for a distributed rather than localizationist account of mPFC organization and support an emerging view on the functional heterogeneity of mPFC.
PMCID: PMC3806720  PMID: 22452556
10.  Self-esteem Modulates Medial Prefrontal Cortical Responses to Evaluative Social Feedback 
Cerebral Cortex (New York, NY)  2010;20(12):3005-3013.
Self-esteem is a facet of personality that influences perception of social standing and modulates the salience of social acceptance and rejection. As such, self-esteem may bias neural responses to positive and negative social feedback across individuals. During functional magnetic resonance imaging scanning, participants (n = 42) engaged in a social evaluation task whereby they ostensibly received feedback from peers indicating they were liked or disliked. Results demonstrated that individuals with low self-esteem believed that they received less positive feedback from others and showed enhanced activity to positive versus negative social feedback in the ventral anterior cingulate cortex/medial prefrontal cortex (vACC/mPFC). By contrast, vACC/mPFC activity was insensitive to positive versus negative feedback in individuals with high self-esteem, and these individuals consistently overestimated the amount of positive feedback received from peers. Voxelwise analyses supported these findings; lower self-esteem predicted a linear increase in vACC/mPFC response to positive versus negative social feedback. Taken together, the present findings propose a functional role for the vACC/mPFC in representing the salience of social feedback and shaping perceptions of relative social standing.
PMCID: PMC2978246  PMID: 20351022
anterior cingulate cortex; fMRI; medial prefrontal cortex; self-esteem; social
11.  Three Ways in Which Midline Regions Contribute to Self-Evaluation 
An integration of existing research and newly conducted psychophysiological interaction (PPI) connectivity analyses suggest a new framework for understanding the contribution of midline regions to social cognition. Recent meta-analyses suggest that there are no midline regions that are exclusively associated with self-processing. Whereas medial prefrontal cortex (MPFC) is broadly modulated by self-processing, subdivisions within MPFC are differentially modulated by the evaluation of close others (ventral MPFC: BA 10/32) and the evaluation of other social targets (dorsal MPFC: BA 9/32). The role of DMPFC in social cognition may also be less uniquely social than previously thought; it may be better characterized as a region that indexes certainty about evaluation rather than previously considered social mechanisms (i.e., correction of self-projection). VMPFC, a region often described as an important mediator of socioemotional significance, may instead perform a more cognitive role by reflecting the type of information brought to bear on evaluations of people we know well. Furthermore, the new framework moves beyond MPFC and hypothesizes that two other midline regions, ventral anterior cingulate cortex (VACC: BA 25) and medial orbitofrontal cortex (MOFC: BA 11), aid motivational influences on social cognition. Despite the central role of motivation in psychological models of self-perception, neural models have largely ignored the topic. Positive connectivity between VACC and MOFC may mediate bottom-up sensitivity to information based on its potential for helping us evaluate ourselves or others the way we want. As connectivity becomes more positive with striatum and less positive with middle frontal gyrus (BA 9/44), MOFC mediates top-down motivational influences by adjusting the standards we bring to bear on evaluations of ourselves and other people.
PMCID: PMC3731671  PMID: 23935580
self; optimistic bias; social cognition; frontal lobe; self-projection; motivation; person perception
12.  Functional connectivity during a social emotion task in adolescents and in adults 
The European Journal of Neuroscience  2009;29(6):1294-1301.
In this fMRI study we investigated functional connectivity between components of the mentalising system during a social emotion task, using psychophysiological interaction (PPI) analysis. Ten adults (22–32 years) and 18 adolescents (11–18 years) were scanned while thinking about scenarios in which a social or a basic emotion would be experienced. Unlike basic emotions (such as disgust and fear), social emotions (such as embarrassment and guilt) require the representation of another’s mental states. In both adults and adolescents, an anterior rostral region of medial prefrontal cortex (arMPFC) involved in mentalising showed greater connectivity with the posterior superior temporal sulcus (pSTS) bordering on the temporo-parietal junction (TPJ) and with anterior temporal cortex (ATC) during social than during basic emotion. This result provides novel evidence that components of the mentalising system interact functionally during a social emotion task. Furthermore, functional connectivity differed between adolescence and adulthood. The adolescent group showed stronger connectivity between arMPFC and pSTS/TPJ during social relative to basic emotion than did the adult group, suggestive of developmental changes in functional integration within the mentalising system.
PMCID: PMC2695858  PMID: 19302165
functional integration; medial prefrontal cortex; mentalising network; PPIs; social brain; social cognition; theory of mind
13.  Computerized Cognitive Training Restores Neural Activity within the Reality Monitoring Network in Schizophrenia 
Neuron  2012;73(4):842-853.
Schizophrenia patients suffer from severe cognitive deficits, such as impaired reality monitoring. Reality monitoring is the ability to distinguish the source of internal experiences from outside reality. During reality monitoring tasks, schizophrenia patients make errors identifying “I made it up” items, and even during accurate performance, they show abnormally low activation of the medial prefrontal cortex (mPFC), a region that supports self-referential cognition. We administered 80 hours of computerized training of cognitive processes to schizophrenia patients and found improvement in reality monitoring that correlated with increased mPFC activity. In contrast, patients in a computer games control condition did not show any behavioral or neural improvements. Notably, recovery in mPFC activity after training was associated with improved social functioning six months later. These findings demonstrate that a serious behavioral deficit in schizophrenia, and its underlying neural dysfunction, can be improved by well-designed computerized cognitive training, resulting in better quality of life.
PMCID: PMC3295613  PMID: 22365555
14.  Medial prefrontal activity differentiates self from close others 
A key question in psychology and neuroscience is the extent to which the neural representation of others is incorporated with, or is distinct from, our concept of self. Recent neuroimaging research has emphasized the importance of a region in the medial prefrontal cortex [MPFC; Brodmann's area (BA) 10] when performing self-referent tasks. Specifically, previous studies have reported selective MPFC recruitment when making judgments about the self relative to a familiar but personally unknown other. The present event-related functional magnetic resonance imaging study extends these findings to judgments about personally known others. Subjects were imaged while making trait adjective judgments in one of the three conditions: (i) whether the adjective described the self; (ii) whether the adjective described an intimate other (i.e., a best friend); or (iii) whether the adjective was presented in uppercase letters. Making judgments about the self relative to an intimate other selectively activated the MPFC region previously implicated in the self-processing literature. These results suggest that while we may incorporate intimate others into our self-concept, the neural correlates of the self remain distinct from intimate and non-intimate others.
PMCID: PMC2555408  PMID: 18985097
self; social cognition; memory; medial prefrontal cortex; fMRI
15.  Neurobiological dissociation of retrieval and reconsolidation of cocaine-associated memory 
Drug use is provoked by the presentation of drug-associated cues, even following long periods of abstinence. Disruption of these learned associations would therefore limit relapse susceptibility. Drug-associated memories are susceptible to long-term disruption during retrieval and shortly after, during memory reconsolidation. Recent evidence reveals that retrieval and reconsolidation are dependent on β-adrenergic receptor (β-AR) activation. Despite this, whether retrieval and reconsolidation are dependent on identical or distinct neural mechanisms is unknown. The prelimbic medial prefrontal cortex (PL-mPFC) and basolateral amygdala (BLA) have been implicated in the expression and reconsolidation of associative memories. Therefore, we investigated the necessity of β-AR activation within the PL-mPFC and BLA for cocaine-associated memory retrieval and reconsolidation in rats. Before or immediately after a cocaine-induced conditioned place preference (CPP) retrieval trial, β-AR antagonists were infused into the PL-mPFC or BLA, followed by daily testing. PL-mPFC infusions before, but not after, a CPP trial disrupted CPP memory retrieval and induced a persistent deficit in retrieval during subsequent trials. In contrast, BLA β-AR blockade had no effect on initial CPP memory retrieval, but prevented CPP expression during subsequent trials indicative of reconsolidation disruption. Our results reveal a distinct dissociation between the neural mechanisms required for cocaine-associated memory retrieval and reconsolidation. Using patch-clamp electrophysiology, we also show that application of a β-AR antagonist prevents NE-induced potentiation of PL-mPFC pyramidal and GABAergic neuronal excitability. Thus, targeted β-AR blockade could induce long-term deficits in drug-associated memory retrieval by reducing neuronal excitability, providing a novel method of preventing cue-elicited drug seeking and relapse.
PMCID: PMC3564635  PMID: 23325262
noradrenergic beta-receptor; norepinephrine; prelimbic medial prefrontal cortex; basolateral amygdala; intrinsic excitability; relapse; drug abuse
16.  Inactivation Or Inhibition Of Neuronal Activity In The Medial Prefrontal Cortex Largely Reduces Pup Retrieval And Grouping in Maternal Rats 
Brain research  2010;1325C:77-88.
Previous research suggests that the maternal medial prefrontal cortex (mPFC) may play a role in maternal care and that cocaine sensitization before pregnancy can affect neuronal activity within this region. The present work was carried out to test whether the mPFC does actually play a role in the expression of maternal behaviors in the rats and to understand what specific behaviors this cortical area may modulate. In the first experiment, tetrodotoxin (TTX) was used to chemically inactivate the mPFC during tests for maternal behavior latencies. Lactating rats were tested on postpartum day 7–9. The results of this first experiment indicate that there is a large effect of TTX-induced inactivation on retrieval behavior latencies. TTX nearly abolished the expression of maternal retrieval of pups without significantly impairing locomotor activity. In the second experiment, GABA-mediated inhibition was used to test maternal behavior latencies and durations of maternal and other behaviors in postpartum dams. In agreement with experiment 1, it was observed that dams capable of retrieving are rendered incapable by inhibition in the mPFC. GABA-mediated inhibition in the mPFC largely reduced retrieval without altering other indices of maternal care and non-specific behavior such as ambulation time, self-grooming, and inactivity. Moreover, in both experiments dams were able to establish contact with pups within seconds. The overall results indicate that the mPFC may play an active role in modulating maternal care, particularly retrieval behavior. External factors that affect the function of the frontal cortical site may result in significant impairments in maternal goal-directed behavior as reported in our earlier work.
PMCID: PMC2848891  PMID: 20156425
Maternal behavior; Medial Prefrontal Cortex; Prelimbic Cortex; Anterior Cingulate Cortex; Pup Retrieval; mPFC; Motivation; Emotion; Reward; Site-specific Injections
17.  Segregation of the human medial prefrontal cortex in social cognition 
While the human medial prefrontal cortex (mPFC) is widely believed to be a key node of neural networks relevant for socio-emotional processing, its functional subspecialization is still poorly understood. We thus revisited the often assumed differentiation of the mPFC in social cognition along its ventral-dorsal axis. Our neuroinformatic analysis was based on a neuroimaging meta-analysis of perspective-taking that yielded two separate clusters in the ventral and dorsal mPFC, respectively. We determined each seed region's brain-wide interaction pattern by two complementary measures of functional connectivity: co-activation across a wide range of neuroimaging studies archived in the BrainMap database and correlated signal fluctuations during unconstrained (“resting”) cognition. Furthermore, we characterized the functions associated with these two regions using the BrainMap database. Across methods, the ventral mPFC was more strongly connected with the nucleus accumbens, hippocampus, posterior cingulate cortex, and retrosplenial cortex, while the dorsal mPFC was more strongly connected with the inferior frontal gyrus, temporo-parietal junction, and middle temporal gyrus. Further, the ventral mPFC was selectively associated with reward related tasks, while the dorsal mPFC was selectively associated with perspective-taking and episodic memory retrieval. The ventral mPFC is therefore predominantly involved in bottom-up-driven, approach/avoidance-modulating, and evaluation-related processing, whereas the dorsal mPFC is predominantly involved in top–down-driven, probabilistic-scene-informed, and metacognition-related processing in social cognition.
PMCID: PMC3665907  PMID: 23755001
social cognition; medial prefrontal cortex; meta-analytic connectivity modeling; resting state connectivity; functional decoding; data-mining
18.  Switching language switches mind: linguistic effects on developmental neural bases of ‘Theory of Mind’ 
Theory of mind (ToM)—our ability to predict behaviors of others in terms of their underlying intentions—has been examined through false-belief (FB) tasks. We studied 12 Japanese early bilingual children (8−12 years of age) and 16 late bilingual adults (18−40 years of age) with FB tasks in Japanese [first language (L1)] and English [second language (L2)], using fMRI. Children recruited more brain regions than adults for processing ToM tasks in both languages. Moreover, children showed an overlap in brain activity between the L1 and L2 ToM conditions in the medial prefrontal cortex (mPFC). Adults did not show such a convergent activity in the mPFC region, but instead, showed brain activity that varied depending on the language used in the ToM task. The developmental shift from more to less ToM specific brain activity may reflect increasing automatization of ToM processing as people age. These results also suggest that bilinguals recruit different resources to understand ToM depending on the language used in the task, and this difference is greater later in life.
PMCID: PMC2569814  PMID: 19015096
fMRI; theory of mind; cognitive development; language; bilingualism; medial prefrontal cortex
19.  The development of brain systems associated with successful memory retrieval of scenes 
Neuroanatomical and psychological evidence suggests prolonged maturation of declarative memory systems in the human brain from childhood into young adulthood. Here, we examined functional brain development during successful memory retrieval of scenes in children, adolescents, and young adults ages 8-21 via functional magnetic resonance imaging. Recognition memory improved with age, specifically for accurate identification of studied scenes (hits). Successful retrieval (correct old-new decisions for studied vs. unstudied scenes) was associated with activations in frontal, parietal, and medial-temporal lobes (MTL) regions. Activations associated with successful retrieval increased with age in left parietal cortex (BA7), bilateral prefrontal, and bilateral caudate regions. In contrast, activations associated with successful retrieval did not change with age in the MTL. Psycho-physiological interaction (PPI) analysis revealed that there were, however, age-relate changes in differential connectivity for successful retrieval between MTL and prefrontal regions. These results suggest that neocortical regions related to attentional or strategic control show the greatest developmental changes for memory retrieval for scenes. Further, these results suggest that functional interactions between MTL and prefrontal regions during memory retrieval also develop into young adulthood. The developmental increase of memory-related activations in frontal and parietal regions for retrieval of scenes and the absence of such an increase in MTL regions parallels what has been observed for memory encoding of scenes.
PMCID: PMC3507540  PMID: 22815515
Declarative memory; Children; Cognitive Development; Functional Magnetic Resonance Imaging (fMRI); Functional connectivity; PPI
20.  Neural Correlates of Direct and Reflected Self-Appraisals in Adolescents and Adults: When Social Perspective-Taking Informs Self-Perception 
Child development  2009;80(4):1016-1038.
Classic theories of self-development suggest people define themselves in part through internalized perceptions of other people’s beliefs about them, known as reflected self-appraisals. This study uses functional magnetic resonance imaging to compare the neural correlates of direct and reflected self-appraisals in adolescence (N = 12, ages 11–14 years) and adulthood (N = 12, ages 23–30 years). During direct self-reflection, adolescents demonstrated greater activity than adults in networks relevant to self-perception (medial prefrontal and parietal cortices) and social-cognition (dorsomedial prefrontal cortex, temporal–parietal junction, and posterior superior temporal sulcus), suggesting adolescent self-construals may rely more heavily on others’ perspectives about the self. Activity in the medial fronto-parietal network was also enhanced when adolescents took the perspective of someone more relevant to a given domain.
PMCID: PMC3229828  PMID: 19630891
21.  Self-appraisal decisions evoke dissociated dorsal—ventral aMPFC networks 
NeuroImage  2005;30(3):1050-1058.
The anterior medial prefrontal cortex (aMPFC) is consistently active during personally salient decisions, yet the differential contributory processes of this region along the dorsal—ventral axis are less understood. Using a self-appraisal decision-making task and functional magnetic resonance imaging, we demonstrated task-dependent connectivity of ventral aMPFC with amygdala, insula, and nucleus accumbens, and dorsal aMPFC connectivity with dorsolateral PFC and bilateral hippocampus. These aMPFC networks appear to subserve distinct contributory processes inherent to self-appraisal decisions, specifically a dorsally mediated cognitive and a ventrally mediated affective/self-relevance network.
PMCID: PMC2627777  PMID: 16326117
22.  Autistic traits are associated with diminished neural response to affective touch 
‘Social brain’ circuitry has recently been implicated in processing slow, gentle touch targeting a class of slow-conducting, unmyelinated nerves, CT afferents, which are present only in the hairy skin of mammals. Given the importance of such ‘affective touch’ in social relationships, the current functional magnetic resonance imaging (fMRI) study aimed to replicate the finding of ‘social brain’ involvement in processing CT-targeted touch and to examine the relationship between the neural response and individuals’ social abilities. During an fMRI scan, 19 healthy adults received alternating blocks of slow (CT-optimal) and fast (non-optimal) brushing to the forearm. Relative to fast touch, the slow touch activated contralateral insula, superior temporal sulcus (STS), medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC) and amygdala. Connectivity analyses revealed co-activation of the mPFC, insula and amygdala during slow touch. Additionally, participants’ autistic traits negatively correlated with the response to slow touch in the OFC and STS. The current study replicates and extends findings of the involvement of a network of ‘social brain’ regions in processing CT-targeted affective touch, emphasizing the multimodal nature of this system. Variability in the brain response to such touch illustrates a tight coupling of social behavior and social brain function in typical adults.
PMCID: PMC3624948  PMID: 22267520
affective touch; autistic traits; CT-afferent; fMRI; social brain
23.  Error effects in anterior cingulate cortex reverse when error likelihood is high 
Strong error-related activity in medial prefrontal cortex (mPFC) has been shown repeatedly with neuroimaging and event-related potential studies for the last several decades. Multiple theories have been proposed to account for error effects, including comparator models and conflict detection models, but the neural mechanisms that generate error signals remain in dispute. Typical studies use relatively low error rates, confounding the expectedness and the desirability of an error. Here we show with a gambling task and fMRI that when losses are more frequent than wins, the mPFC error effect disappears, and moreover, exhibits the opposite pattern by responding more strongly to unexpected wins than losses. These findings provide perspective on recent ERP studies and suggest that mPFC error effects result from a comparison between actual and expected outcomes.
PMCID: PMC2841347  PMID: 20203206
prediction error; fMRI; cognitive control; decision making; risky choice; medial prefrontal cortex
24.  Self-specific processing in the default network: a single-pulse TMS study 
In examining neural processing specific to the self, primarily by contrasting self-related stimuli with non-self-related stimuli (i.e., self vs. other), neuroimaging studies have activated a consistent set of regions, including medial prefrontal cortex (MPFC), precuneus, and right and left inferior parietal cortex. However, criticism has arisen that this network may not be specific to self-related processing, but instead reflects a more general aspect of cortical processing. For example, it is almost identical to the active network of the resting state, the “default” mode, when the subject is free to think about anything at all. We tested the self-specificity of this network by using transcranial magnetic stimulation (TMS) to briefly disrupt local cortical processing while subjects rated adjectives as like or unlike themselves or their best friend. Healthy volunteers show a self-reference effect (SRE) in this task, in which performance with self-related items is superior to that with other-related items. As individual adjectives appeared on a monitor, single-pulse TMS was applied at five different times relative to stimulus onset (SOA: stimulus onset asynchrony) ranging from 0 to 480 ms. In 18 subjects, TMS to left parietal cortex suppressed the SRE from 160 to 480 ms. SRE suppression occurred at later SOA with TMS to the right parietal cortex. In contrast, no effects were seen with TMS to MPFC. Together with our previous work, these results provide evidence for a self-specific processing system in which midline and lateral inferior parietal cortices, as elements of the default network, play a role in ongoing self-awareness.
PMCID: PMC3008414  PMID: 20878395
TMS; Self; Parietal cortex; Default network
25.  The Influence of Prior Knowledge on Memory: A Developmental Cognitive Neuroscience Perspective 
Across ontogenetic development, individuals gather manifold experiences during which they detect regularities in their environment and thereby accumulate knowledge. This knowledge is used to guide behavior, make predictions, and acquire further new knowledge. In this review, we discuss the influence of prior knowledge on memory from both the psychology and the emerging cognitive neuroscience literature and provide a developmental perspective on this topic. Recent neuroscience findings point to a prominent role of the medial prefrontal cortex (mPFC) and of the hippocampus (HC) in the emergence of prior knowledge and in its application during the processes of successful memory encoding, consolidation, and retrieval. We take the lateral PFC into consideration as well and discuss changes in both medial and lateral PFC and HC across development and postulate how these may be related to the development of the use of prior knowledge for remembering. For future direction, we argue that, to measure age differential effects of prior knowledge on memory, it is necessary to distinguish the availability of prior knowledge from its accessibility and use.
PMCID: PMC3792618  PMID: 24115923
lifespan development; child development; hippocampus; medial prefrontal cortex; semantic memory; prior knowledge; lateral prefrontal cortex; episodic memory

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