Research on language and aging typically shows that language comprehension is preserved across the life span. Recent neuroimaging results suggest that this good performance is underpinned by age-related neural reorganization [e.g., Tyler, L. K., Shafto, M. A., Randall, B., Wright, P., Marslen-Wilson, W. D., & Stamatakis, E. A. Preserving syntactic processing across the adult life span: The modulation of the frontotemporal language system in the context of age-related atrophy. Cerebral Cortex, 20, 352–364, 2010]. The current study examines how age-related reorganization affects the balance between component linguistic processes by manipulating semantic and phonological factors during spoken word recognition in younger and older adults. Participants in an fMRI study performed an auditory lexical decision task where words varied in their phonological and semantic properties as measured by degree of phonological competition and imageability. Older adults had a preserved lexicality effect, but compared with younger people, their behavioral sensitivity to phonological competition was reduced, as was competition-related activity in left inferior frontal gyrus. This was accompanied by increases in behavioral sensitivity to imageability and imageability-related activity in left middle temporal gyrus. These results support previous findings that neural compensation underpins preserved comprehension in aging and demonstrate that neural reorganization can affect the balance between semantic and phonological processing.

Stimulus repetition often leads to facilitated processing, resulting in neural decreases (repetition suppression) and faster RTs (repetition priming). Such repetition-related effects have been attributed to the facilitation of repeated cognitive processes and/or the retrieval of previously encoded stimulus–response (S-R) bindings. Although previous research has dissociated these two forms of learning, their interaction in the brain is not fully understood. Utilizing the spatial and temporal resolutions of fMRI and EEG, respectively, we examined a long-lag classification priming paradigm that required response repetitions or reversals at multiple levels of response representation. We found a repetition effect in occipital/temporal cortex (fMRI) that was time-locked to stimulus onset (EEG) and robust to switches in response, together with a repetition effect in inferior pFC (fMRI) that was time-locked to response onset (EEG) and sensitive to switches in response. The response-sensitive effect occurred even when changing from object names (words) to object pictures between repetitions, suggesting that S-R bindings can code abstract representations of stimuli. Most importantly, we found evidence for interference effects when incongruent S-R bindings were retrieved, with increased neural activity in inferior pFC, demonstrating that retrieval of S-R bindings can result in facilitation or interference, depending on the congruency of response between repetitions.

Categorical perception, an increased sensitivity to between- compared to within-category contrasts, is a stable property of native speech perception that emerges as language matures. While recent research suggests that categorical responses to speech sounds can be found in left prefrontal as well as temporo-parietal areas, it is unclear how the neural system develops heightened sensitivity to between-category contrasts. In the current study, two groups of adult participants were trained to categorize speech sounds taken from a dental-retroflex-velar continuum according to two different boundary locations. Behavioral results suggest that for successful learners, categorization training led to increased behavioral sensitivity for between-category contrasts with no concomitant increase for within-category contrasts. Neural responses to the learned category schemes were measured using a short-interval habituation design during fMRI scanning. While both inferior frontal and temporal regions showed sensitivity to phonetic contrasts sampled from the continuum, only the bilateral middle frontal gyri exhibited a pattern consistent with encoding of the learned category scheme. Taken together, these results support a view in which top-down information about category membership may reshape perceptual sensitivities via attention or executive mechanisms in the frontal lobes.

Stimuli of high emotional significance such as social threat cues are preferentially processed in the human brain. However, there is an ongoing debate, whether or not these stimuli capture attention automatically and weaken the processing of concurrent stimuli in the visual field. This study examined continuous fluctuations of electrocortical facilitation during competition of two spatially separated facial expressions in high and low socially anxious individuals. Two facial expressions were flickered for 3000 ms at different frequencies (14 Hz and 17.5 Hz) to separate the electrocortical signals evoked by the competing stimuli (“frequency-tagging”). Angry faces compared to happy and neutral expressions were associated with greater electrocortical facilitation over visual areas only in the high socially anxious individuals. This finding was independent of the respective competing stimulus. Heightened electrocortical engagement in socially anxious participants was present in the first second of stimulus viewing, and was sustained for the entire presentation period. These results, based on a continuous measure of attentional resource allocation, support the view that stimuli of high personal significance are associated with early and sustained prioritized sensory processing. These cues, however, do not interfere with the electrocortical processing of a spatially separated concurrent face, suggesting that they are effective at capturing attention, but are weak competitors for resources.

The ability to change an established stimulus-behavior association based on feedback is critical for adaptive social behaviors. This ability has been examined in reversal learning tasks, where participants first learn a stimulus-response association (e.g., select a particular object to get a reward), and then need to alter their response when reinforcement contingencies change. While substantial evidence demonstrates that the orbitofrontal cortex (OFC) is a critical region for reversal learning, previous studies have not distinguished reversal learning for emotional associations from neutral associations. The current study examined whether OFC plays similar roles in emotional vs. neutral reversal learning. The OFC showed greater activity during reversals of stimulus-outcome associations for negative outcomes than for neutral outcomes. Similar OFC activity was also observed during reversals involving positive outcomes. Furthermore, OFC activity is more inversely correlated with amygdala activity during negative reversals than during neutral reversals. Overall, our results indicate that the OFC is more activated by emotional than neutral reversal learning and that OFC’s interactions with the amygdala are greater for negative than neutral reversal learning.

The dorsal striatum plays a key role in the learning and expression of instrumental reward associations that are acquired through direct experience. However, not all learning about instrumental actions require direct experience. Instead, humans and other animals are also capable of acquiring instrumental actions by observing the experiences of others. In this study, we investigated the extent to which human dorsal striatum is involved in observational as well as experiential instrumental reward learning. Human participants were scanned with fMRI while they observed a confederate over a live video performing an instrumental conditioning task to obtain liquid juice rewards. Participants also performed a similar instrumental task for their own rewards. Using a computational model-based analysis, we found reward prediction errors in the dorsal striatum not only during the experiential learning condition but also during observational learning. These results suggest a key role for the dorsal striatum in learning instrumental associations, even when those associations are acquired purely by observing others.

Although it is generally assumed that brain damage predominantly affects only the function of the damaged region, here we show that focal damage to critical locations causes disruption of network organization throughout the brain. Using resting state fMRI, we assessed whole-brain network structure in patients with focal brain lesions. Only damage to those brain regions important for communication between subnetworks (e.g., “connectors”)—but not to those brain regions important for communication within sub-networks (e.g., “hubs”)—led to decreases in modularity, a measure of the integrity of network organization. Critically, this network dysfunction extended into the structurally intact hemisphere. Thus, focal brain damage can have a widespread, nonlocal impact on brain network organization when there is damage to regions important for the communication between networks. These findings fundamentally revise our understanding of the remote effects of focal brain damage and may explain numerous puzzling cases of functional deficits that are observed following brain injury.

Electrophysiological and fMRI-based investigations of the ventral temporal cortex of primates provide strong support for regional specialization for the processing of faces. These responses are most frequently found in or near the fusiform gyrus, but there is substantial variability in their anatomical location and response properties. An outstanding question is the extent to which ventral temporal cortex participates in processing dynamic, expressive aspects of faces, a function usually attributed to regions near the superior temporal cortex. Here, we investigated these issues through intracranial recordings from eight human surgical patients. We compared several different aspects of face processing (static and dynamic faces; happy, neutral, and fearful expressions) with power in the high-gamma band (70–150 Hz) from a spectral analysis. Detailed mapping of the response characteristics as a function of anatomical location was conducted in relation to the gyral and sulcal pattern on each patient’s brain. The results document responses with high responsiveness for static or dynamic faces, often showing abrupt changes in response properties between spatially close recording sites and idiosyncratic across different subjects. Notably, strong responses to dynamic facial expressions can be found in the fusiform gyrus, just as can responses to static faces. The findings suggest a more complex, fragmented architecture of ventral temporal cortex around the fusiform gyrus, one that includes focal regions of cortex that appear relatively specialized for either static or dynamic aspects of faces.

Moral sentiment has been hypothesized to reflect evolved adaptations to social living. If so, individual differences in moral values may relate to regional variation in brain structure. We tested this hypothesis in a sample of 70 young, healthy adults examining whether differences on two major dimensions of moral values were significantly associated with regional gray matter volume. The two clusters of moral values assessed were “individualizing” (values of harm/care and fairness), and “binding” (deference to authority, in-group loyalty, and purity/sanctity). Individualizing was positively associated with left dorsomedial prefrontal cortex volume, and negatively associated with bilateral precuneus volume. For binding, a significant positive association was found for bilateral subcallosal gyrus and a trend to significance for the left anterior insula volume. These findings demonstrate that variation in moral sentiment reflects individual differences in brain structure and suggest a biological basis for moral sentiment, distributed across multiple brain regions.

It is widely believed that adults cannot learn a foreign language in the same way that children learn a first language. However, recent evidence suggests that adult learners of a foreign language can come to rely on native-like language brain mechanisms. Here, we show that the type of language training crucially impacts this outcome. We used an artificial language paradigm to examine longitudinally whether explicit training (that approximates traditional grammar-focused classroom settings) and implicit training (that approximates immersion settings) differentially affect neural (electrophysiological) and behavioral (performance) measures of syntactic processing. Results showed that performance of explicitly and implicitly trained groups did not differ at either low or high proficiency. In contrast, electrophysiological (ERP) measures revealed striking differences between the groups’ neural activity at both proficiency levels in response to syntactic violations. Implicit training yielded an N400 at low proficiency, whereas at high proficiency, it elicited a pattern typical of native speakers: an anterior negativity followed by a P600 accompanied by a late anterior negativity. Explicit training, by contrast, yielded no significant effects at low proficiency and only an anterior positivity followed by a P600 at high proficiency. Although the P600 is reminiscent of native-like processing, this response pattern as a whole is not. Thus, only implicit training led to an electrophysiological signature typical of native speakers. Overall, the results suggest that adult foreign language learners can come to rely on native-like language brain mechanisms, but that the conditions under which the language is learned may be crucial in attaining this goal.

Can linguistic semantics affect neural processing in feature-specific visual regions? Specifically, when we hear a sentence describing a situation that includes motion, do we engage neural processes that are part of the visual perception of motion? How about if a motion verb was used figuratively, not literally? We used fMRI to investigate whether semantic content can “penetrate” and modulate neural populations that are selective to specific visual properties during natural language comprehension. Participants were presented audiovisually with three kinds of sentences: motion sentences (“The wild horse crossed the barren field.”), static sentences, (“The black horse stood in the barren field.”), and fictive motion sentences (“The hiking trail crossed the barren field.”). Motion-sensitive visual areas (MT+) were localized individually in each participant as well as face-selective visual regions (fusiform face area; FFA). MT+ was activated significantly more for motion sentences than the other sentence types. Fictive motion sentences also activated MT+ more than the static sentences. Importantly, no modulation of neural responses was found in FFA. Our findings suggest that the neural substrates of linguistic semantics include early visual areas specifically related to the represented semantics and that figurative uses of motion verbs also engage these neural systems, but to a lesser extent. These data are consistent with a view of language comprehension as an embodied process, with neural substrates as far reaching as early sensory brain areas that are specifically related to the represented semantics.

To understand the meanings of words and objects, we need to have knowledge about these items themselves plus executive mechanisms that compute and manipulate semantic information in a task-appropriate way. The neural basis for semantic control remains controversial. Neuroimaging studies have focused on the role of the left inferior frontal gyrus (LIFG), whereas neuropsychological research suggests that damage to a widely distributed network elicits impairments of semantic control. There is also debate about the relationship between semantic and executive control more widely. We used TMS in healthy human volunteers to create “virtual lesions” in structures typically damaged in patients with semantic control deficits: LIFG, left posterior middle temporal gyrus (pMTG), and intraparietal sulcus (IPS). The influence of TMS on tasks varying in semantic and nonsemantic control demands was examined for each region within this hypothesized network to gain insights into (i) their functional specialization (i.e., involvement in semantic representation, controlled retrieval, or selection) and (ii) their domain dependence (i.e., semantic or cognitive control). The results revealed that LIFG and pMTG jointly support both the controlled retrieval and selection of semantic knowledge. IPS specifically participates in semantic selection and responds to manipulations of nonsemantic control demands. These observations are consistent with a large-scale semantic control network, as predicted by lesion data, that draws on semantic-specific (LIFG and pMTG) and domain-independent executive components (IPS).

Context memory retrieval tasks often implicate left ventrolateral prefrontal cortex (LVPFC) during functional imaging. Although this region has been linked to controlled semantic processing of materials, it may also play a more general role in selecting among competing episodic representations during demanding retrieval tasks. Thus the LVPFC response during context memory retrieval may reflect either semantic processing of memoranda or adjudication of interfering episodic memories evoked by memoranda. To distinguish between these hypotheses we contrasted context and item memory retrieval tasks for meaningful and non-meaningful memoranda using functional Magnetic Resonance Imaging (fMRI). Increased LVPFC activation during context compared to item memory only occurred for meaningful memory probes. In contrast, even demanding context retrieval for non-meaningful materials failed to engage LVPFC. These data demonstrate that the activation previously seen during episodic tasks likely reflects semantic processing of the probes during episodic retrieval attempt, not selection among competing elicited episodic representations. Posterior middle temporal gyrus and the body/head of the caudate demonstrated the same selective response as LVPFC, although resting state functional connectivity analyses suggested these two regions likely shared separate functional relationships with the LVPFC.

Although the medial-temporal lobes (MTL), PFC, and parietal cortex are considered primary nodes in the episodic memory network, there is much debate regarding the contributions of MTL, PFC, and parietal subregions to recollection versus familiarity (dual-process theory) and the feasibility of accounts on the basis of a single memory strength process (strength theory). To investigate these issues, the current fMRI study measured activity during retrieval of memories that differed quantitatively in terms of strength (high vs. low-confidence trials) and qualitatively in terms of recollection versus familiarity (source vs. item memory tasks). Support for each theory varied depending on which node of the episodic memory network was considered. Results from MTL best fit a dual-process account, as a dissociation was found between a right hippocampal region showing high-confidence activity during the source memory task and bilateral rhinal regions showing high-confidence activity during the item memory task. Within PFC, several left-lateralized regions showed greater activity for source than item memory, consistent with recollective orienting, whereas a right-lateralized ventrolateral area showed low-confidence activity in both tasks, consistent with monitoring processes. Parietal findings were generally consistent with strength theory, with dorsal areas showing low-confidence activity and ventral areas showing high-confidence activity in both tasks. This dissociation fits with an attentional account of parietal functions during episodic retrieval. The results suggest that both dual-process and strength theories are partly correct, highlighting the need for an integrated model that links to more general cognitive theories to account for observed neural activity during episodic memory retrieval.

Medial temporal lobe (MTL) contributions to the brief maintenance of visual representations were evaluated by studying a group of patients with MTL damage. Eye movements of patients and healthy comparison subjects were tracked while performing a visual search for a target among complex stimuli of varying similarity to that target. Despite the task having no imposed delays, patients were impaired behaviorally, and eye-movement measures showed abnormally rapid degradation of target representations in the patients. Eye-movement data showed a modulation of the duration of fixations as a function of the similarity of fixated array lures to the target, but the effect was attenuated in patients during long fixation paths away from the sample target. This effect manifested despite patients’ shorter searches and more frequent fixations of the sample target. Novel techniques provided unique insight into visual representation without healthy MTL, which may support maintenance of information through hippocampal-dependent relational binding.

The specific role of different parietal regions to episodic retrieval is a topic of intense debate. According to the Attention to Memory (AtoM) model, dorsal parietal cortex (DPC) mediates top–down attention processes guided by retrieval goals, whereas ventral parietal cortex (VPC) mediates bottom–up attention processes captured by the retrieval output or the retrieval cue. This model also hypothesizes that the attentional functions of DPC and VPC are similar for memory and perception. To investigate this last hypothesis, we scanned participants with event-related fMRI whereas they performed memory and perception tasks, each comprising an orienting phase (top–down attention) and a detection phase (bottom–up attention). The study yielded two main findings. First, consistent with the AtoM model, orienting-related activity for memory and perception overlapped in DPC, whereas detection-related activity for memory and perception overlapped in VPC. The DPC overlap was greater in the left intraparietal sulcus, and the VPC overlap in the left TPJ. Around overlapping areas, there were differences in the spatial distribution of memory and perception activations, which were consistent with trends reported in the literature. Second, both DPC and VPC showed stronger connectivity with medial-temporal lobe during the memory task and with visual cortex during the perception task. These findings suggest that, during memory tasks, some parietal regions mediate similar attentional control processes to those involved in perception tasks (orienting in DPC vs. detection in VPC), although on different types of information (mnemonic vs. sensory).

Cognitive flexibility, or the ability to change behavior in response to external cues, is conceptualized as two processes: one for shifting between perceptual features of objects and another for shifting between the abstract rules governing the selection of these objects. Object and rule shifts are believed to engage distinct anatomical structures and functional processes. Dopamine activity has been associated with cognitive flexibility, but patients with dopaminergic deficits are not impaired on all tasks assessing cognitive flexibility, suggesting that dopamine may have different roles in the shifting of objects and rules. The goals of this study were to identify brain regions supporting object and rule shifts and to examine the role of dopamine in modulating these two forms of cognitive flexibility. Sixteen young, healthy subjects underwent functional magnetic resonance imaging while performing a setshift task designed to differentiate shifting between object features from shifting between abstract task rules. Subjects also underwent positron emission tomography with 6-[18F]-fluoro-L-m-tyrosine (FMT), a radiotracer measuring dopamine synthesis capacity. Shifts of abstract rules were not associated with activation in any brain region, and FMT uptake did not correlate with rule shift performance. Shifting between object features deactivated the medial prefrontal cortex and the posterior cingulate and activated the lateral prefrontal cortex, posterior parietal areas, and the striatum. FMT signal in the striatum correlated negatively with object shift performance and deactivation in the medial prefrontal cortex, a component of the default mode network, suggesting that dopamine influences object shifts via modulation of activity in the default mode network.

Most experiments on the “neural correlates of consciousness” employ stimulus reportability as an operational definition of what is consciously perceived. The interpretation of such experiments therefore depends critically on understanding the neural basis of stimulus reportability. Using a high volume of fMRI data, we investigated the neural correlates of stimulus reportability using a partial report object detection paradigm. Subjects were presented with a random array of circularly arranged disc-stimuli and were cued, after variable delays (following stimulus offset), to report the presence or absence of a disc at the cued location, using variable motor actions. By uncoupling stimulus processing, decision, and motor response, we were able to use signal detection theory to deconstruct the neural basis of stimulus reportability. We show that retinotopically specific responses in the early visual cortex correlate with stimulus processing but not decision or report; a network of parietal/temporal regions correlates with decisions but not stimulus presence, whereas classical motor regions correlate with report. These findings provide a basic framework for understanding the neural basis of stimulus reportability without the theoretical burden of presupposing a relationship between reportability and consciousness.

For more than a century, neurologists have hypothesized that the arcuate fasciculus carries signals that are essential for language function; however, the relevance of the pathway for particular behaviors is highly controversial. The primary objective of this study was to use diffusion tensor imaging to examine the relationship between individual variation in the microstructural properties of arcuate fibers and behavioral measures of language and reading skills. A second objective was to use novel fiber-tracking methods to reassess estimates of arcuate lateralization. In a sample of 55 children, we found that measurements of diffusivity in the left arcuate correlate with phonological awareness skills and arcuate volume lateralization correlates with phonological memory and reading skills. Contrary to previous investigations that report the absence of the right arcuate in some subjects, we demonstrate that new techniques can identify the pathway in every individual. Our results provide empirical support for the role of the arcuate fasciculus in the development of reading skills.

Age has a differential effect on cognition, with word retrieval being one of the cognitive domains most affected by aging. This study examined the functional and structural neural correlates of phonological word retrieval in younger and older adults using word and picture rhyme judgment tasks. Although the behavioral performance in the fMRI task was similar for the two age groups, the older adults had increased activation in the right pars triangularis across tasks and in the right pars orbitalis for the word task only. Increased activation together with preserved performance in the older participants would suggest that increased activation was related to compensatory processing. We validated this hypothesis by showing that right pars triangularis activation during correct rhyme judgments was highest in participants who made overall more errors, therefore being most error-prone. Our findings demonstrate that the effect of aging differ in adjacent but distinct right inferior frontal regions. The differential effect of age on word and picture tasks also provides new clues to the level of processing that is most affected by age in speech production tasks. Specifically, we suggest that right inferior frontal activation in older participants is needed to inhibit errors.

Recent studies have shown that selective attention is of considerable importance for encoding task-relevant items into visual short-term memory (VSTM) according to our behavioural goals. However, it is not known whether top-down attentional biases can continue to operate during the maintenance period of VSTM. We used event-related potentials (ERPs) to investigate this question across two experiments. Specifically, we tested whether orienting attention to a given spatial location within a VSTM representation resulted in modulation of the contralateral delay activity (CDA), a lateralized ERP marker of VSTM maintenance generated when participants selectively encode memory items from one hemifield. In both experiments, retrospective cues during the maintenance period could predict a specific item (spatial retro-cue) or multiple items (neutral retro-cue) that would be probed at the end of the memory delay. Our results revealed that VSTM performance is significantly improved by orienting attention to the location of a task-relevant item. The behavioural benefit was accompanied by modulation of neural activity involved in VSTM maintenance. Spatial retro-cues reduced the magnitude of the CDA, consistent with a reduction in memory load. Our results provide direct evidence that top-down control modulates neural activity associated with maintenance in VSTM, biasing competition in favour of the task-relevant information.

Empirical and theoretical studies suggest that human knowledge is partly based on innate concepts that are experience-independent. We can, therefore, consider concepts underlying our knowledge as being broadly divided into inherited and acquired ones. Using fMRI, we studied the brain reaction in 20 subjects to violation of face, space (inherited), and artifact (acquired) concepts by presenting them with deformed faces, impossible figures (i.e., impossible chairs), and deformed planes, respectively, as well as their normal counterparts. Violation of the inherited concepts of face and space led to significant activation in frontoparietal cortex, whereas artifacts did not, thus distinguishing neurologically between the two categories. Participants were further exposed to these deformities daily for 1 month to test the supposition that inherited concepts are not modifiable, hence that prolonged exposure would not change the brain circuits that are engaged when viewing them. Consistent with this supposition, our results showed no significant change in activation for both categories, suggesting that such concepts are stable at the neural level at least within a time frame of 1 month. Finally, we investigated the regions of the brain that are critical for object representation. Our results show distinct and overlapping areas in the ventral visual cortex for all three categories, with faces activating the ventral visual cortex inferiorly, especially centered on right fusiform gyrus, and chairs and planes activating more diffuse regions, overlapping with the superior part of face region and mainly located in middle occipital cortex and parietal areas.

Lexical processing requires both activating stored representations, and selecting among active candidates. The current work uses an eye-tracking paradigm to conduct a detailed temporal investigation of lexical processing. Patients with Broca's and Wernicke's aphasia are studied to shed light on the roles of anterior and posterior brain regions in lexical processing as well as the effects of lexical competition on such processing. Experiment 1 investigates whether objects semantically related to an uttered word are preferentially fixated, e.g., given the auditory target 'hammer', do participants fixate a picture of a nail? Results show that, like normals, both groups of patients are more likely to fixate on an object semantically related to the target than an unrelated object. Experiment 2 explores whether Broca's and Wernicke's aphasics show competition effects when words share onsets with the uttered word, e.g., given the auditory target 'hammer', do participants fixate a picture of a hammock? Experiment 3 investigates whether these patients activate words semantically related to onset competitors of the uttered word, e.g., given the auditory target 'hammock' do participants fixate a nail due to partial activation of the onset competitor hammer? Results of Experiments 2 and 3 show pathological patterns of performance for both Broca's and Wernicke's aphasics under conditions of lexical onset competition. However, the patterns of deficit differed, suggesting different functional and computational roles for anterior and posterior areas in lexical processing. Implications of the findings for the functional architecture of the lexical processing system and its potential neural substrates are considered.

Children's gains in problem-solving skills during the elementary school years are characterized by shifts in the mix of problem-solving approaches, with inefficient procedural strategies being gradually replaced with direct retrieval of domain-relevant facts. We used a well-established procedure for strategy assessment during arithmetic problem solving to investigate the neural basis of this critical transition. We indexed behavioral strategy use by focusing on the retrieval frequency and examined changes in brain activity and connectivity associated with retrieval fluency during arithmetic problem solving in second- and third-grade (7- to 9-year-old) children. Children with higher retrieval fluency showed elevated signal in the right hippocampus, parahippocampal gyrus (PHG), lingual gyrus (LG), fusiform gyrus (FG), left ventrolateral PFC (VLPFC), bilateral dorsolateral PFC (DLPFC), and posterior angular gyrus. Critically, these effects were not confounded by individual differences in problem-solving speed or accuracy. Psychophysiological interaction analysis revealed significant effective connectivity of the right hippocampus with bilateral VLPFC and DLPFC during arithmetic problem solving. Dynamic causal modeling analysis revealed strong bidirectional interactions between the hippocampus and the left VLPFC and DLPFC. Furthermore, causal influences from the left VLPFC to the hippocampus served as the main top–down component, whereas causal influences from the hippocampus to the left DLPFC served as the main bottom–up component of this retrieval network. Our study highlights the contribution of hippocampal–prefrontal circuits to the early development of retrieval fluency in arithmetic problem solving and provides a novel framework for studying dynamic developmental processes that accompany children's development of problem-solving skills.

This study assessed the impact of serotonin transporter genotype (5-HTTLPR) on regional responses to emotional faces in the amygdala and subgenual cingulate cortex (sgACC), while subjects performed a gender discrimination task. Although we found no evidence for greater amygdala reactivity or reduced amygdala–sgACC coupling in short variant 5-HTTLPR homozygotes (s/s), we observed an interaction between genotype and emotion in sgACC. Only long variant homozygotes (la/la) exhibited subgenual deactivation to fearful versus neutral faces, whereas the effect in s/s subjects was in the other direction. This absence of subgenual deactivation in s/s subjects parallels a recent finding in depressed subjects [Grimm, S., Boesiger, P., Beck, J., Schuepbach, D., Bermpohl, F., Walter, M., et al. Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychopharmacology, 34, 932–943, 2009]. Taken together, the findings suggest that subgenual cingulate activity may play an important role in regulating the impact of aversive stimuli, potentially conferring greater resilience to the effects of aversive stimuli in la/la subjects. Using dynamic causal modeling of functional magnetic resonance imaging data, we explored the effects of genotype on effective connectivity and emotion-specific changes in coupling across a network of regions implicated in social processing. Viewing fearful faces enhanced bidirectional excitatory coupling between the amygdala and the fusiform gyrus, and increased the inhibitory influence of the amygdala over the sgACC, although this modulation of coupling did not differ between the genotype groups. The findings are discussed in relation to the role of sgACC and serotonin in moderating responses to aversive stimuli [Dayan, P., & Huys, Q. J., Serotonin, inhibition, and negative mood. PLoS Comput Biol, 4, e4, 2008; Mayberg, H. S., Liotti, M., Brannan, S. K., McGinnis, S., Mahurin, R. K., Jerabek, P. A., et al. Reciprocal limbic–cortical function and negative mood: Converging PET findings in depression and normal sadness. Am J Psychiatry, 156, 675–682, 1999].