RESUMO
Trust is the glue of society. While the trust we place in close others is crucial for our wellbeing, trust in strangers is important to fulfill needs that families and friends cannot provide. Adolescence is an important phase for the development of trust in strangers, because the social world of adolescents expands tremendously. We provide an overview of the development of trust in adolescence by reviewing studies that used the trust game, an experimental paradigm to measure trust between dyads during monetary exchange. We start from the notion that trust is a form of social reinforcement learning in which prior beliefs about the trustworthiness of others are continuously updated by new information. Within this framework, development in adolescence is characterized by increasing uncertainty of prior beliefs, a greater tolerance of uncertainty, and a greater tendency to seek and use new information. Accordingly, there is evidence for an increase in initial trust and better adaptation of trust during repeated interactions. Childhood psychological and social-economic adversity may impact this development negatively. To further our understanding of these individual differences, we suggest ways in which the trust game can be enriched to capture trust dilemmas that are relevant to youth with diverse backgrounds.
RESUMO
Research has shown that adolescents - particularly girls - who mature relatively early often experience more internalizing problems. This effect is thought to be partially driven by psychosocial mechanisms, but previous research based relative pubertal maturation on complete samples or population standards, instead of considering the adolescents' direct peer environment. In the current study the level of adolescents' pubertal development was assessed relative to their classmates in order to examine relative pubertal maturation. The effects of adolescents' relative pubertal status, and their perceived popularity, on symptoms of social anxiety and depression in adolescents were studied. All analyses were also performed for absolute pubertal maturation. Participants were 397 young adolescents (Mage = 13.06, SD = 0.36, 49.9% girls) at timepoint 1, and 307 (Mage = 14.08, SD = 0.36, 50.5% girls) at timepoint 2. A significant positive relationship was found between relative pubertal timing and symptoms of depression for girls but not boys. Social anxiety symptoms were not significantly related to relative pubertal timing in either sex. Relative pubertal maturation had no effect on change in or persistence of depressive and social anxiety symptoms one year later. The effects of the comparison with the immediate peer environment, did not seem to explain more variance in internalizing symptoms than the effects of early maturation.
Assuntos
Desenvolvimento do Adolescente , Depressão , Feminino , Humanos , Adolescente , Masculino , Grupo Associado , Estudantes , AnsiedadeRESUMO
Adolescents need to develop adequate perspective-taking skills to successfully navigate their increasingly complex social environments. This study investigated adolescents' development of the cognitive processes of egocentric and altercentric interference that influence perspective-taking abilities. Using the Dot Perspective Task, participants' (N = 803; 50.9% female) egocentric and altercentric interference was measured during 3 consecutive years from 12 to 14 years of age. Linear mixed model analyses showed that whereas overall task performance improved over time, egocentric and altercentric interference increased over time. These results suggest that perspective taking develops at slower rates when there are conflicting perspectives than in situations with no conflict. Moreover, we found that girls showed less egocentric interference than boys. This result provides task-based evidence that supports previous findings of higher self-reported perspective taking in adolescent girls than in adolescent boys.
Assuntos
Desenvolvimento do Adolescente , Masculino , Humanos , Adolescente , Feminino , Estudos Longitudinais , Fatores SexuaisRESUMO
Interpersonal connection is a fundamental human motivation, and the extent to which it is fulfilled is a strong predictor of symptoms of internalizing disorders such as social anxiety and depression, perhaps especially during the "social reorienting" period of adolescence. However, little is known about the contribution to this effect of the individual's social motivations, which are intensified during adolescence. Furthermore, social goal orientation - an individual's priorities and intentions in social interactions - is an important predictor of vulnerability to internalizing symptoms. Adolescents spend most of their waking lives in classrooms, bounded social networks with a limited pool of candidates for befriending. This study investigated whether friendships within one's class protects against internalizing symptoms in part by reducing the desire for more classmate friendships, which may tend to promote maladaptive social goals. Participants were 423 young adolescents (M age = 13.2, sd = 0.52 years; 49.4% girls). As predicted, adolescents' number of reciprocated classroom friendships had a protective effect on internalizing symptoms which was serially mediated by desire for more such friendships, and social goal orientation. However, only demonstration-avoidance goals significantly predicted internalizing symptoms. Unreciprocated friendship nominations were unexpectedly associated with stronger desire and more social anxiety symptoms. The results suggest that the effect of number of friends is mediated by the individual's thoughts and feelings about their number of friendships, such that a strong desire for more friendships promotes maladaptive goals, oriented toward social status and consequently less oriented toward the cultivation of interpersonal intimacy with the friends they already have.
Assuntos
Amigos , Relações Interpessoais , Feminino , Humanos , Adolescente , Masculino , Motivação , Grupo Associado , ObjetivosRESUMO
Our social interactions take place within numerous social networks, in which our relationships with others define our position within these networks. In this study, we examined how the centrality of positions within social networks was associated with trust behavior and neural activity in 49 adolescents (Mage = 12.8 years, SDage = 0.4 years). The participants played a trust game with a cartoon animation as a partner, which showed adaptive behavior in response to the participant and was generally untrustworthy. Social network positions were obtained in secondary school classrooms where the participants and their classmates reported on who their friends were. Using social network analysis, a score was calculated that indicated the centrality of everyone's position within the friendship network. The results showed that more central social network positions were associated with higher levels of initial trust behavior, although no evidence was found for a relationship between network position and the adaptation of trust behavior. The results of the functional MRI analyses showed that the centrality of the network positions was positively associated with caudate activity when making trust decisions. Furthermore, the adolescents with more central network positions also showed stronger increases of caudate activity when the partner's return was processed compared to the adolescents with less central network positions. The current study provides initial evidence that social network positions in friendship networks relate to socio-cognitive behavior and neural activity in adolescents.
Assuntos
Comportamento do Adolescente , Confiança , Humanos , Adolescente , Criança , Lactente , Amigos/psicologia , Comportamento do Adolescente/psicologia , Instituições Acadêmicas , Rede Social , Comportamento SocialRESUMO
Sensitivity for rewarding cues and distress signals from children is fundamental to human caregiving and modulated by the neuropeptide oxytocin. In a functional magnetic resonance imaging study, we investigated whether oxytocin regulates neural responses to reward or distress cues form children. In a placebo-controlled, within-subject design, we measured neural responses to positive, negative, and neutral cues from children in 22 healthy female subjects who received oxytocin (24 IU) versus placebo. Further, based on current literature, we hypothesized that oxytocin effects are modulated by experiences of childhood trauma. The task elicited valence-specific effects-positive images activated the ventromedial prefrontal cortex, left anterior cingulate cortex, and right putamen, and images of children in distress activated the bilateral amygdala, hippocampus, and right medial superior frontal cortex. The effects of oxytocin depended on subjective reports of childhood emotional neglect. Self-reported neglect interacted with oxytocin administration in the amygdala, hippocampus, and prefrontal areas. In individuals with higher scores of emotional neglect, oxytocin increased neural reactivity of limbic structures to positive and neutral images. Our findings need replication in larger samples and can therefore be considered preliminary but are in line with the recent literature on the modulating effect of childhood adversity on the sensitivity to oxytocin administration.
Assuntos
Emoções , Ocitocina , Criança , Feminino , Humanos , Encéfalo , Método Duplo-Cego , Emoções/fisiologia , Imageamento por Ressonância Magnética , Ocitocina/farmacologia , Córtex Pré-Frontal/diagnóstico por imagem , Dados PreliminaresRESUMO
During adolescence, major changes in brain mechanisms take place and differentiated representations of both the self and of others are developed. Although studies have investigated the neural mechanisms of self- and other-referential processing in adolescents, the development of these mechanisms remain largely unaddressed. Here, we report a three-year longitudinal study with annual measurements, and investigate the developmental trajectories of activity and connectivity underlying self- and other-referential processes in 34 participants from early to mid-adolescence (mean age timepoints 1, 2, 3 = 12.9, 13.9, 15.0 years). Moreover, we probe whether these correlates continue to develop from mid-adolescence to young adulthood by comparing neural correlates of the adolescents at the last measurement to an independent group of 42 young adults (mean age 22 years). Participants underwent functional MRI while performing a trait judgement task in which they indicated whether an adjective described themselves, a similar or a dissimilar peer. Brain activity within the dorsal medial prefrontal cortex (dMPFC) and right temporal parietal junction (TPJ) showed a quadratic change from early to mid-adolescence, with a peak in activity at the second measurement when evaluating the self, the similar and dissimilar peer. No differential activity was observed when comparing the adolescents to young adults. Functional connectivity did not change from early to mid-adolescence, however, connectivity of the dMPFC with a posterior midline region during self- and other-referential processing relative to the control condition reduced from mid-adolescence to young adulthood. Together, these findings provide insight in the developmental trajectories of brain activity and connectivity underlying the development of the self-concept and representations of peers in adolescence.
Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Humanos , Estudos Longitudinais , Córtex Pré-Frontal , Autoimagem , Adulto JovemRESUMO
OBJECTIVE: Recent findings suggest that diminished processing of positive contextual information about others during interactions may contribute to social impairment in the schizophrenia spectrum. This could be due to general social context processing deficits or specific biases against positive information. We studied the impact of positive and negative social contextual information during social interactions using functional neuroimaging and probed whether these neural mechanisms were associated with real-life social functioning in schizophrenia spectrum disorders. METHODS: Patients with a schizophrenia spectrum disorder (N = 23) and controls disorder (N = 25) played three multi-round trust games during functional magnetic resonance imaging scanning, with no, positive and negative information about the counterpart's trustworthiness, while all counterparts were programmed to behave trustworthy. The main outcome variable was the height of the shared amount in the trust game, i.e. investment, representing an indication of trust. The first investment in the game was considered to be basic trust, since no behavioural feedback was given yet. We performed region-of-interest analyses and examined the association with real-life social functioning using the experience sampling method. RESULTS: Social contextual information had no effect on patients' first investments, whereas controls made the lowest investment after negative and the highest investments after positive contextual information was provided. Over trials, patients decreased investments, suggesting reduced social reward learning, whereas controls increased investments in response to behavioural feedback in the negative context. Patients engaged the dorsolateral prefrontal cortex less than controls during context presentation and showed reduced activity within the caudate during repayments. In patients, lower investments were associated with more time spent alone and social exclusion and lower caudate activation was marginally significantly associated with higher perceived social exclusion. CONCLUSION: The failure to adapt trust to positive and negative social contexts suggests that patients have a general insensitivity to prior social information, indicating top-down processing impairments. In addition, patients show reduced sensitivity to social reward, i.e. bottom-up processing deficits. Moreover, lower trust and lower neural activation were related to lower real-life social functioning. Together, these findings indicate that improving trust and social interactions in schizophrenia spectrum needs a multi-faceted approach that targets both mechanisms.
Assuntos
Esquizofrenia , Córtex Pré-Frontal Dorsolateral , Humanos , Relações Interpessoais , Imageamento por Ressonância Magnética , Recompensa , Esquizofrenia/diagnóstico por imagem , Meio SocialRESUMO
Children's learning capabilities change while growing up. One framework that describes the cognitive and neural development of children's growing learning abilities is the two-component model. It distinguishes processes that integrate separate features into a coherent memory representation (associative component) and executive abilities, such as elaboration, evaluation, and monitoring, that support memory processing (strategic component). In an fMRI study using an object-location association paradigm, we investigated how the two components influence memory performance across development. We tested children (10-12 years, n = 31), late adolescents (18 years, n = 29), and adults (25+ years, n = 30). For studying the associative component, we also probed how the utilisation of prior knowledge (schemas) facilitates memory across age groups. Children had overall lower retrieval performance, while adolescents and adults did not differ from each other. All groups benefitted from schemas, but this effect did not differ between groups. Performance differences between groups were associated with deactivation of the dorsal medial prefrontal cortex (dmPFC), which in turn was linked to executive functioning. These patterns were stronger in adolescents and adults and seemed absent in children. Thus, the children's executive system, the strategic component, is not as mature and thus cannot facilitate memory performance in the same way as in adolescents/adults. In contrast, we did not find age-related differences in the associative component; with activity in the angular gyrus predicting memory performance systematically across groups. Overall, our results suggest that differences of executive rather than associative abilities explain memory differences between children, adolescents, and adults.
Assuntos
Aprendizagem por Associação/fisiologia , Mapeamento Encefálico , Função Executiva/fisiologia , Desenvolvimento Humano/fisiologia , Memória/fisiologia , Córtex Pré-Frontal/fisiologia , Adolescente , Adulto , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Adulto JovemRESUMO
Mentalizing is an important aspect of social cognition and people vary in their ability to mentalize. Despite initial evidence that mentalizing continues to develop throughout adolescence, it is unclear which neural mechanisms underlie individual variability in mentalizing ability in adolescents. Interactions within and between the default-mode network (DMN), frontoparietal network (FPN) and cingulo-opercular/salience network (CO/SN) have been related to inter-individual differences in cognitive processes in both adults and adolescents. Here, we investigated whether intrinsic connectivity within and between these brain networks explained inter-individual differences in affective mentalizing ability in adolescents. Resting-state brain activity was measured using functional MRI and affective mentalizing ability was defined as correct performance on the Reading the Mind in the Eyes test performed outside the scanner. We identified the DMN, FPN and CO/SN, and within and between network connectivity values were submitted to a bootstrapping enhanced penalized multiple regression analysis to predict mentalizing in 66 young adolescents (11-14 years). We showed that stronger connectivity between the DMN and the FPN, together with lower within-network connectivity of the FPN and the CO/SN predicted better mentalizing performance. These novel findings provide insight into the normative developmental trajectory of the neural mechanisms underlying affective mentalizing in early adolescence.
Assuntos
Individualidade , Mentalização , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagemRESUMO
During adolescence, self-concept develops profoundly, accompanied by major changes in hormone levels. Self-evaluations become more complex, and peers and their opinions increasingly salient. Neuroimaging studies have investigated self- and other-related processing in adolescents, however, the influence of similarity of peers on these processes is still unclear, as well as functional connectivity underlying such processes. We investigated the effect of peer similarity on neural activity and connectivity underlying self- and other-referential processing, by distinguishing between a similar and dissimilar peer when making other-evaluations. Moreover, we explored the association between testosterone and brain activity during self-evaluations. Sixty-six young adolescents underwent functional MRI while performing a trait judgement task in which they indicated whether an adjective described themselves, a similar or a dissimilar classmate. The ventral medial prefrontal cortex (MPFC) showed increased engagement in self-referential processing, and the posterior cingulate cortex and right temporal parietal junction during other-evaluations. However, activity did not differ between the similar and dissimilar other conditions. Functional connectivity of the ventral MPFC included the striatum when evaluating the similar peer and frontoparietal regions when evaluating the dissimilar peer. Furthermore, inter-individual differences in testosterone levels were positively associated with dorsal MPFC activity in males. This study provides insight into the influence of peer similarity on activity and connectivity underlying other-referential processing in young adolescents, and suggests that testosterone affects neural correlates of self-referential processing.
Assuntos
Encéfalo/diagnóstico por imagem , Julgamento/fisiologia , Grupo Associado , Autoimagem , Percepção Social , Testosterona/análise , Adolescente , Mapeamento Encefálico , Criança , Emoções/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Saliva/químicaRESUMO
Autism spectrum conditions (ASC) and schizophrenia spectrum conditions (SSC) are both characterized by changes in social-cognitive functioning. Less is known about the overlap and the differences in social-cognitive functioning when comparing individuals with subclinical levels of ASC and SSC, while studies in non-clinical samples have the benefit of avoiding confounds that are present in clinical groups. Therefore, we first examined how autistic-like experiences, positive psychotic-like experiences and the co-occurrence of both correlated with the performance on an extensive battery of social cognition tasks in young adolescents. Second, we examined the effect of autistic-like experiences, psychotic-like experiences and their co-occurrence on friendships in daily life. A total of 305 adolescents (Mage = 12.6, sd = 0.4, 147 boys) participated in the current study. A battery of social cognition tasks, comprising the Reading the Mind in the Eyes task, Dot perspective task and trust game were individually administered in a classroom setting, along with a friendship peer nomination questionnaire. Results indicated no evidence for a relationship between the performance on the social cognition battery and subclinical experiences of autism and/or psychosis. However, results did show that the amount of autistic-like experiences of adolescents were associated with being less often selected as a friend by their peers. By contrast, no relationship between self-reported friendships and autistic-like experiences was found. Neither a relationship between friendships and psychotic-like experiences was reported. This study provides initial evidence that information provided by peers may shed light on (altered) social behavior associated with autistic-like experiences that is not apparent on performance measures, as well as elucidate possible differences between autistic- and psychotic-like experiences.
RESUMO
Memory formation transforms experiences into durable engrams. The stabilization critically depends on processes during and after learning, and involves hippocampal-medial prefrontal interactions that appear to be mediated by the nucleus reuniens of the thalamus in rodents, which corresponds to the human medioventral thalamus. How this region contributes to durable memory formation in humans is, however, unclear. Furthermore, the anterior-, lateral dorsal-, and mediodorsal nuclei appear to promote mnemonic function as well. We hypothesized that durable memory formation is associated with increases in thalamo-cortical interactions during encoding and consolidation. Thirty-three human subjects underwent fMRI while studying picture-location associations. To assess consolidation, resting-state brain activity was measured after study and was compared to a pre-study baseline. Memory was tested on the same day and 48â¯h later. While "weak" memories could only be remembered at the immediate test, "durable" memories persisted also after the delay. We found increased coupling of the medioventral-, adjacent anterior-, lateral dorsal-, and mediodorsal thalamus with the hippocampus and surrounding medial temporal lobe, as well as with anterior and posterior midline regions related to durable memory encoding. The medioventral and lateral dorsal thalamus showed increased connectivity with posterior medial and parietal cortex from baseline to post-encoding rest, positively scaling with the proportion of durable memories formed across subjects. Additionally, the lateral dorsal thalamus revealed consolidation-related coupling with the inferior temporal, retrosplenial, and medial prefrontal cortex. We suggest that thalamo-cortical cross-talk strengthens mnemonic representations at initial encoding, and that cortical coupling of specific thalamic subregions supports consolidation thereafter.
Assuntos
Córtex Cerebral/fisiologia , Consolidação da Memória/fisiologia , Tálamo/fisiologia , Adolescente , Adulto , Mapeamento Encefálico , Feminino , Hipocampo/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiologia , Percepção Visual/fisiologia , Adulto JovemRESUMO
Intrinsic network interactions may underlie individual differences in the ability to remember. The default mode network (DMN) comprises subnetworks implicated in memory, and interactions between the DMN and frontoparietal network (FPN) were shown to support mnemonic processing. However, it is unclear if such interactions during resting-state predict episodic memory ability. We investigated whether intrinsic network interactions within and between the DMN and FPN are related to individual differences in memory performance. Resting-state activity was measured using functional MRI in healthy young adults followed by a memory test for object-location associations that were studied 3 d earlier. We identified two subnetworks within the DMN, the main-DMN and the medial temporal lobe, retrosplenial cortex (MTL_RSC)-DMN. Further, we found regions forming the FPN. Memory performance was associated with lower connectivity within the MTL_RSC-DMN, and stronger connectivity between the main-DMN and FPN. Exploratory whole-brain analysis revealed stronger MTL connectivity with the left posterior parietal cortex that was related to better memory performance. Furthermore, we found increased task-evoked activation during successful retrieval within the main-DMN and FPN, but not within the MTL_RSC-DMN. In sum, lower intrinsic connectivity within the MTL_RSC-DMN, combined with stronger connectivity between the main-DMN and FPN, explain individual differences in memory ability.
Assuntos
Encéfalo/fisiologia , Memória/fisiologia , Rede Nervosa/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Neuroimagem Funcional , Humanos , Individualidade , Imageamento por Ressonância Magnética , Masculino , Lobo Parietal/fisiologia , Lobo Temporal/fisiologia , Adulto JovemRESUMO
RATIONALE: Synaptic memory consolidation is thought to rely on catecholaminergic signaling. Eventually, it is followed by systems consolidation, which embeds memories in a neocortical network. Although this sequence was demonstrated in rodents, it is unclear how catecholamines affect memory consolidation in humans. OBJECTIVES: Here, we tested the effects of catecholaminergic modulation on synaptic and subsequent systems consolidation. We expected enhanced memory performance and increased neocortical engagement during delayed retrieval. Additionally, we tested if this effect was modulated by individual differences in a cognitive proxy measure of baseline catecholamine synthesis capacity. METHODS: Fifty-three healthy males underwent a between-subjects, double-blind, placebo-controlled procedure across 2 days. On day 1, subjects studied and retrieved object-location associations and received 20 mg of methylphenidate or placebo. Drug intake was timed so that methylphenidate was expected to affect early consolidation but not encoding or retrieval. Memory was tested again while subjects were scanned three days later. RESULTS: Methylphenidate did not facilitate memory performance, and there was no significant group difference in activation during delayed retrieval. However, memory representations differed between groups depending on baseline catecholamines. The placebo group showed increased activation in occipito-temporal regions but decreased connectivity with the hippocampus, associated with lower baseline catecholamine synthesis capacity. The methylphenidate group showed stronger activation in the postcentral gyrus, associated with higher baseline catecholamine synthesis capacity. CONCLUSIONS: Altogether, methylphenidate during early consolidation did not foster long-term memory performance, but it affected retrieval-related neural processes depending on individual levels of baseline catecholamines.
Assuntos
Catecolaminas/metabolismo , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Metilfenidato/farmacologia , Lobo Temporal/efeitos dos fármacos , Adolescente , Adulto , Método Duplo-Cego , Hipocampo/diagnóstico por imagem , Hipocampo/metabolismo , Humanos , Imageamento por Ressonância Magnética , Masculino , Memória de Longo Prazo/efeitos dos fármacos , Testes Neuropsicológicos , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/metabolismo , Adulto JovemRESUMO
UNLABELLED: The fate of a memory is partly determined at initial encoding. However, the behavioral consequences of memory formation are often tested only once and shortly after learning, which leaves the neuronal predictors for the formation of durable memories largely unknown. Here, we hypothesized that durable memory formation (as opposed to weak or no memory formation) is reflected through increased activation in the medial temporal lobes and prefrontal cortex, and more consistent processing (i.e., stronger pattern similarity) across encoding material. Thirty-four human subjects studied unique picture-location associations while undergoing fMRI and performed a cued recall test immediately after study as well as 48 h later. Associative memories were defined as "weak" if they were retrieved during the immediate test only. Conversely, "durable" memories persisted also after 48 h. The posterior cingulate cortex showed increased pattern similarity during successful memory formation, independent of the eventual durability. For durable memory encoding, we found increased activation in medial and inferior temporal, prefrontal, and parietal regions. This was accompanied by stronger pattern similarity in lateral prefrontal and parietal regions, as well as in anterior and posterior midline structures that were also engaged during later memory retrieval. Thus, we show that pattern similarity, or consistent processing, in the posterior cingulate cortex predicts associative memory formation at encoding. If this is paralleled by additional activation increases in regions typically related to encoding, and by consistent processing in regions involved in later retrieval, formed memories appear durable for at least 48 h. SIGNIFICANCE STATEMENT: Successful memory formation is typically associated with increased neuronal activation in medial temporal and prefrontal regions at encoding, but memory is often assessed only once and shortly after study. Here, we addressed memory durability, and investigated the neuronal underpinnings of encoding for associations remembered over a longer period of time, less long, or immediately forgotten. We showed that durable memory formation is dependent on increased activation in the hippocampus and neocortical regions related to encoding, and on consistent processing of associative memory traces in midline structures that are involved in later memory retrieval. These findings highlight how durable memories are formed.
Assuntos
Aprendizagem por Associação/fisiologia , Giro do Cíngulo/fisiologia , Memória de Longo Prazo/fisiologia , Memória de Curto Prazo/fisiologia , Rede Nervosa/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Plasticidade Neuronal/fisiologia , Adulto JovemRESUMO
A recent Genome-Wide Association Study showed that the rs2514218 single nucleotide polymorphism (SNP) in close proximity to dopamine receptor D2 is strongly associated with schizophrenia. Further, an in silico experiment showed that rs2514218 has a cis expression quantitative trait locus effect in the basal ganglia. To date, however, the functional consequence of this SNP is unknown. Here, we used functional Magnetic resonance imaging to investigate the impact of this risk allele on striatal activation during proactive and reactive response inhibition in 45 unaffected siblings of schizophrenia patients. We included siblings to circumvent the illness specific confounds affecting striatal functioning independent from gene effects. Behavioral analyses revealed no differences between the carriers (n= 21) and noncarriers (n= 24). Risk allele carriers showed a diminished striatal response to increasing proactive inhibitory control demands, whereas overall level of striatal activation in carriers was elevated compared to noncarriers. Finally, risk allele carriers showed a blunted striatal response during successful reactive inhibition compared to the noncarriers. These data are consistent with earlier reports showing similar deficits in schizophrenia patients, and point to a failure to flexibly engage the striatum in response to contextual cues. This is the first study to demonstrate an association between impaired striatal functioning and the rs2514218 polymorphism. We take our findings to indicate that striatal functioning is impaired in carriers of the DRD2 risk allele, likely due to dopamine dysregulation at the DRD2 location.
Assuntos
Função Executiva/fisiologia , Inibição Psicológica , Neostriado/fisiopatologia , Receptores de Dopamina D2/genética , Esquizofrenia/genética , Esquizofrenia/fisiopatologia , Irmãos , Adulto , Alelos , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , RiscoRESUMO
Mental schemas form associative knowledge structures that can promote the encoding and consolidation of new and related information. Schemas are facilitated by a distributed system that stores components separately, presumably in the form of inter-connected neocortical representations. During retrieval, these components need to be recombined into one representation, but where exactly such recombination takes place is unclear. Thus, we asked where different schema components are neuronally represented and converge during retrieval. Subjects acquired and retrieved two well-controlled, rule-based schema structures during fMRI on consecutive days. Schema retrieval was associated with midline, medial-temporal, and parietal processing. We identified the multi-voxel representations of different schema components, which converged within the angular gyrus during retrieval. Critically, convergence only happened after 24-hour-consolidation and during a transfer test where schema material was applied to novel but related trials. Therefore, the angular gyrus appears to recombine consolidated schema components into one memory representation.
Assuntos
Memória , Lobo Parietal/fisiologia , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Masculino , Radiografia , Adulto JovemRESUMO
Networks of interconnected neocortical representations of prior knowledge, "schemas," facilitate memory for congruent information. This facilitation is thought to be mediated by augmented encoding and accelerated consolidation. However, it is less clear how schema affects retrieval. Rodent and human studies to date suggest that schema-related memories are differently retrieved. However, these studies differ substantially as most human studies implement pre-experimental world-knowledge as schemas and tested item or nonspatial associative memory, whereas animal studies have used intraexperimental schemas based on item-location associations within a complex spatial layout that, in humans, could engage more strategic retrieval processes. Here, we developed a paradigm conceptually linked to rodent studies to examine the effects of an experimentally learned spatial associative schema on learning and retrieval of new object-location associations and to investigate the neural mechanisms underlying schema-related retrieval. Extending previous findings, we show that retrieval of schema-defining associations is related to activity along anterior and posterior midline structures and angular gyrus. The existence of such spatial associative schema resulted in more accurate learning and retrieval of new, related associations, and increased time allocated to retrieve these associations. This retrieval was associated with right dorsolateral prefrontal and lateral parietal activity, as well as interactions between the right dorsolateral prefrontal cortex and medial and lateral parietal regions, and between the medial prefrontal cortex and posterior midline regions, supporting the hypothesis that retrieval of new, schema-related object-location associations in humans also involves augmented monitoring and systematic search processes.