Social network position, trust behavior, and neural activity in young adolescents.

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.

Increased interference from conflicting perspectives and gender differences: A longitudinal study during adolescence.

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.

Preliminary data on oxytocin modulation of neural reactivity in women to emotional stimuli of children depending on childhood emotional neglect.

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.

The Effect of Relative Pubertal Maturation and Perceived Popularity on Symptoms of Depression and Social Anxiety in Adolescent Boys and Girls.

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.

A Few Close Friends? Adolescent Friendships' Effect on Internalizing Symptoms Is Serially Mediated by Desire for More Friends and Social Goal Orientation.

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.

Development of the neural correlates of self- and other-referential processing across adolescence.

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.

Neural, behavioural and real-life correlates of social context sensitivity and social reward learning during interpersonal interactions in the schizophrenia spectrum.

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.

Differences in executive abilities rather than associative processes contribute to memory development.

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.

Neural correlates of self- and other-referential processing in young adolescents and the effects of testosterone and peer similarity.

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.

Functional network interactions at rest underlie individual differences in memory ability.

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.

Thalamo-cortical coupling during encoding and consolidation is linked to durable memory formation.

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 48 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.

Parallel Engagement of Regions Associated with Encoding and Later Retrieval Forms Durable Memories.

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.

Initial investigation of the effects of an experimentally learned schema on spatial associative memory in humans.

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.

Intrinsic network interactions explain individual differences in mentalizing ability in adolescents.

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.

Reduced functional coupling in the default-mode network during self-referential processing.

Activity within the default-mode network (DMN) is thought to be related to self-referential processing, such as thinking about one's preferences or personality traits. Although the DMN is generally considered to function as a network, evidence is starting to accumulate that suggests that areas of the DMN are each specialized for different subfunctions of self-referential processing. Here, we address the issue of functional specialization by investigating changes in coupling between areas of the DMN during self-referential processing. To this aim, brain activity was assessed during a task in which subjects had to indicate whether a trait adjective described their own personality (self-referential, Self condition), that of another person (other-referential, Other condition), or whether the trait was socially desirable (nonreferential, Control condition). To exclude confounding effects of cardiorespiratory processes on activity and functional coupling, we corrected the fMRI signal for these effects. Activity within areas of the DMN was found to be modulated by self-referential processing. More specifically, during the Self condition compared to the Other and Control condition, activity within the dorsal medial prefrontal cortex, ventral medial prefrontal cortex, and posterior cingulate cortex was increased. Moreover, coupling between areas of the DMN was reduced during the Self condition compared to the Other and Control condition, while coupling between regions of the DMN and regions outside the network was increased. As such, these results provide an indication for functional specialization within the DMN and support the notion that each area of the DMN is involved in different subfunctions of self-referential processing.

Social Cognition and Friendships in Adolescents With Autistic-Like Experiences and Psychotic-Like Experiences.

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.

Cardiorespiratory effects on default-mode network activity as measured with fMRI.

The default-mode network (DMN) consists of areas showing more activation during rest than during a task. Several authors propose some form of cognitive processing to underlie BOLD signal changes in the DMN as activity within the network is modulated by the level of effort required by the task and is positively correlated with self-referential processing. Alternatively, BOLD signal changes within the DMN may be caused by cardiorespiratory processes (CR) affecting BOLD signal measurements independent of neuronal activity. The goal of this study is to investigate whether BOLD signal changes within the DMN can be explained by CR effects. To this aim, brain activity, heartbeat, and respiration are measured during resting-state and while subjects perform a cognitive task with a high- and low-demand condition. To correct for CR effects we used RETROICOR (Glover et al., [2000]: Magn Reson Med 44:162-167) in combination with additive linear modeling of changes due to respiration volume, heart rate and heart rate variability. CR effects were present within the frequency-range of the DMN and were located in areas of the DMN, but equally so in other areas. After removal of CR effects, deactivation and resting-state connectivity between the areas of the DMN remained significant. In addition, DMN deactivation was still modulated by task demand. The same CR correction method did remove activation in task-related areas. We take these results to indicate that the BOLD signal within the DMN cannot be explained by CR effects alone and is possibly related to some form of cognitive neuronal processing.

Within-subject variation in BOLD-fMRI signal changes across repeated measurements: quantification and implications for sample size.

Functional magnetic resonance imaging (fMRI) can be used to detect experimental effects on brain activity across measurements. The success of such studies depends on the size of the experimental effect, the reliability of the measurements, and the number of subjects. Here, we report on the stability of fMRI measurements and provide sample size estimations needed for repeated measurement studies. Stability was quantified in terms of the within-subject standard deviation (sigma(w)) of BOLD signal changes across measurements. In contrast to correlation measures of stability, this statistic does not depend on the between-subjects variance in the sampled group. Sample sizes required for repeated measurements of the same subjects were calculated using this sigma(w). Ten healthy subjects performed a motor task on three occasions, separated by one week, while being scanned. In order to exclude training effects on fMRI stability, all subjects were trained extensively on the task. Task performance, spatial activation pattern, and group-wise BOLD signal changes were highly stable over sessions. In contrast, we found substantial fluctuations (up to half the size of the group mean activation level) in individual activation levels, both in ROIs and in voxels. Given this large degree of instability over sessions, and the fact that the amount of within-subject variation plays a crucial role in determining the success of an fMRI study with repeated measurements, improving stability is essential. In order to guide future studies, sample sizes are provided for a range of experimental effects and levels of stability. Obtaining estimates of these latter two variables is essential for selecting an appropriate number of subjects.

Methylphenidate during early consolidation affects long-term associative memory retrieval depending on baseline catecholamines.

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.