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Cortical regions supporting cognitive control and memory judgment are structurally immature in adolescents. Here we studied adolescents (13-15 y.o.) and young adults (20-22 y.o.) using a recognition memory paradigm that modulates cognitive control demands through cues that probabilistically forecast memory probe status. Behaviorally, adolescence was associated with quicker responding in the presence of invalid cues compared to young adulthood. fMRI data demonstrated that while both groups increasingly activated posterior dorsolateral prefrontal (dlPFC), midline, and lateral parietal regions for invalidly compared to validly cued trials, this differential invalid cueing response ended sooner in adolescents, consistent with their quicker responding on invalidly cued trials. Critically, dlPFC also demonstrated reversed brain-behavior associations across the groups. Increased mean dlPFC activation during invalid cueing was linked to improved performance in young adults, whereas increases within adolescents were linked to impaired performance. Resting state connectivity analysis revealed greater connectivity between dlPFC and episodic retrieval linked regions in young adults relative to adolescents. These data demonstrate that the functional interpretation of dlPFC activation hinges on its physical maturation and suggest that the pattern of behavioral and neural response in adolescents reflects different functional integration of cognitive control and memory systems. (Contains 7 figures and 3 tables.)

Individuals with autism spectrum disorder (ASD) often fail to attach context to their memories and are specifically impaired in processing social aspects of contextual information. The aim of the present study was to investigate the modulatory influence of social vs. non-social context on neural mechanisms during encoding in ASD. Using event-related fMRI, 13 boys with ASD and 13 typically developing boys comparable for age and IQ were investigated during encoding of neutral objects presented either with a social (faces) or a non-social (houses) context. A memory paradigm was then applied to identify brain activation patterns associated with encoding of subsequently recollected versus non-recollected objects. On the behavioural level, no significant between-group differences emerged. In particular, no differential effects of context on memory performance were observed. Neurally, however, context-specific group differences were observed in several brain regions. During encoding of subsequently recollected objects presented with a face, ASD subjects (compared to controls) showed reduced neural activation in the bilateral inferior frontal gyrus, bilateral middle frontal gyrus and right inferior parietal lobule. Neural activation in the right inferior frontal gyrus was positively correlated with memory performance in controls, but negatively in ASD individuals. During encoding of subsequently non-recollected objects presented in the non-social context, ASD subjects showed increased activation in the dorsal MPFC. Our findings suggest that in ASD subjects, fronto-parietal brain regions subserving memory formation and the association of contextual information are activated atypically when a social context is presented at encoding. The data add to findings from related research fields indicating that in ASD, socioemotional impairment extends into domains beyond social cognition. Increased activation in the dorsal MPFC in ASD individuals might reflect supervisory cognitive processes related to the suppression of a distracting non-social context. (Contains 2 tables and 4 figures.)

Paired associates learning is impaired in both schizophrenia and amnestic mild cognitive impairment (aMCI), which may reflect hippocampal pathology. In addition, schizophrenia is characterized by the dysfunction of the retino-geniculo-striatal magnocellular (M) visual pathway. The purpose of this study was to investigate the interaction between visual perceptual and memory dysfunctions. We administered a modified version of the CANTAB paired associates learning task to patients with schizophrenia (n = 20), aMCI (n = 20), and two groups of matched healthy controls (n = 20 for each patient group). The stimuli in the paired associates learning task biased information processing toward the M pathways (low contrast, low spatial frequency) and parvocellular (P) pathways (high contrast, high spatial frequency). Results revealed that patients with schizophrenia exhibited a more pronounced learning deficit for M-biased relative to P-biased stimuli. In aMCI, there were similar memory deficits for both types of stimuli. Orientation discrimination for M- and P-biased stimuli was intact in both groups of patients. The number of errors in the M-biased memory condition significantly and inversely correlated with the volume of the right hippocampus in schizophrenia. These results suggest an interaction between M-biased perceptual processing and short-term relational memory in schizophrenia, which may be associated with the structural alteration of the right hippocampus. (Contains 3 tables and 3 figures.)

Children born preterm are at risk for deficits in language and reading. They are also at risk for injury to the white matter of the brain. The goal of this study was to determine whether performance in language and reading skills would be associated with white matter properties in children born preterm and full-term. Children born before 36 weeks gestation (n = 23, mean plus or minus SD age 12.5 plus or minus 2.0 years, gestational age 28.7 plus or minus 2.5 weeks, birth weight 1184 plus or minus 431 g) and controls born after 37 weeks gestation (n = 19, 13.1 plus or minus 2.1 years, 39.3 plus or minus 1.0 weeks, 3178 plus or minus 413 g) underwent a battery of language and reading tests. Diffusion Tensor Imaging (DTI) scans were processed using Tract-Based Spatial Statistics to generate a core white matter skeleton that was anatomically comparable across participants. Fractional anisotropy (FA) was the diffusion property used in analyses. In the full-term group, no regions of the whole FA-skeleton were associated with language and reading. In the preterm group, regions of the FA-skeleton were significantly associated with verbal IQ, linguistic processing speed, syntactic comprehension, and decoding. Combined, the regions formed a composite map of 22 clusters on 15 tracts in both hemispheres and in the ventral and dorsal streams. ROI analyses in the preterm group found that several of these regions also showed positive associations with receptive vocabulary, verbal memory, and reading comprehension. Some of the same regions showed weak negative correlations within the full-term group. Exploratory multiple regression in the preterm group found that specific white matter pathways were related to different aspects of language processing and reading, accounting for 27-44% of the variance. The findings suggest that higher performance in language and reading in a group of preterm but not full-term children is associated with higher fractional anisotropy of a bilateral and distributed white matter network. (Contains 2 tables and 7 figures.)

Functional magnetic resonance imaging (fMRI) was used to compare brain activity during the retrieval of coarse- and fine-grained spatial details and episodic details associated with a familiar environment. Long-time Toronto residents compared pairs of landmarks based on their absolute geographic locations (requiring either coarse or fine discriminations) or based on previous visits to those landmarks (requiring episodic details). An ROI analysis of the hippocampus showed that all three conditions activated the hippocampus bilaterally. Fine-grained spatial judgments recruited an additional region of the right posterior hippocampus, while episodic judgments recruited an additional region of the right anterior hippocampus, and a more extensive region along the length of the left hippocampus. To examine whole-brain patterns of activity, Partial Least Squares (PLS) analysis was used to identify sets of brain regions whose activity covaried with the three conditions. All three comparison judgments recruited the default mode network including the posterior cingulate/retrosplenial cortex, middle frontal gyrus, hippocampus, and precuneus. Fine-grained spatial judgments also recruited additional regions of the precuneus, parahippocampal cortex and the supramarginal gyrus. Episodic judgments recruited the posterior cingulate and medial frontal lobes as well as the angular gyrus. These results are discussed in terms of their implications for theories of hippocampal function and spatial and episodic memory. (Contains 6 tables and 6 figures.)

We begin with a theoretical overview of the concepts of recollection and familiarity, focusing, in the spirit of this special issue, on the important contributions made by Andrew Mayes. In particular, we discuss the issue of when the generation of semantically-related information in response to a retrieval cue might be experienced as recollection rather than familiarity. We then report a series of experiments in which two different types of masked prime, presented immediately prior to the test cue in a recognition memory paradigm, produced opposite effects on Remember vs. Know judgments. More specifically, primes that were conceptually related to the test item increased the incidence of Remember judgments, though only when intermixed with repetition primes (which increased the incidence of Know judgments instead, as in prior studies). One possible explanation--that the fluency of retrieval of item-context associations can be experienced as recollection, even when the source of that fluency is unknown--is counter to conventional views of recollection and familiarity, though it was anticipated by Andrew in his writings nearly two decades ago. (Contains 4 tables, 8 notes, and 7 figures.)

Two experiments explored eye measures (fixations and pupil response patterns) and brain responses (BOLD) accompanying the recognition of visual object stimuli based on familiarity and recollection. In both experiments, the use of a modified remember/know procedure led to high confidence and matched accuracy levels characterising strong familiarity (F3) and recollection (R) responses. In Experiment 1, visual scanning behaviour at retrieval distinguished familiarity-based from recollection-based recognition. Recollection, relative to strength-matched familiarity, involved significantly larger pupil dilations and more dispersed fixation patterns. In Experiment 2, the hippocampus was selectively activated for recollected stimuli, while no evidence of activation was observed in the hippocampus for strong familiarity of matched accuracy. Recollection also activated the parahippocampal cortex (PHC), while the adjacent perirhinal cortex (PRC) was actively engaged in response to strong familiarity (than to recollection). Activity in prefrontal and parietal areas differentiated familiarity and recollection in both the extent and the magnitude of activity they exhibited, while the dorsomedial thalamus showed selective familiarity-related activity, and the ventrolateral and anterior thalamus selective recollection-related activity. These findings are consistent with the view that the hippocampus and PRC play contrasting roles in supporting recollection and familiarity and that these differences are not a result of differences in memory strength. Overall, the combined pupil dilation, eye movement and fMRI data suggest the operation of recognition mechanisms drawing differentially on familiarity and recollection, whose neural bases are distinct within the MTL. (Contains 4 tables and 6 figures.)

The medial temporal lobes (MTL) play an essential role in episodic memory, and accumulating evidence indicates that two MTL subregions--the perirhinal (PRc) and parahippocampal (PHc) cortices--might have different functions. According to the binding of item and context theory ( [16] and [21]), PRc is involved in processing item information, the target of memory encoding, whereas PHc is involved in processing context information, peripheral information that identifies the circumstances of the episode. Here, we used functional magnetic resonance imaging (fMRI) adaptation to test the roles of different MTL subregions in the processing of item and context information. Participants were scanned while viewing a series of objects. Each object was presented with a unique semantic encoding question that elicited a salient cognitive context. The object picture, the encoding question, both, or neither were immediately repeated. We found that PRc activity was sensitive to repetition of the object but not the encoding question whereas PHc activity was sensitive to repetition of the encoding question but not the object. These data are consistent with the idea that the PRc and PHc are differentially involved in the representation of item and context information and additionally suggest that the role of the PHc extends to nonspatial, cognitive context information. (Contains 1 table and 3 figures.)

Multi-voxel pattern analysis (MVPA), or "decoding", of fMRI activity has gained popularity in the neuroimaging community in recent years. MVPA differs from standard fMRI analyses by focusing on whether information relating to specific stimuli is encoded in patterns of activity across multiple voxels. If a stimulus can be predicted, or decoded, solely from the pattern of fMRI activity, it must mean there is information about that stimulus represented in the brain region where the pattern across voxels was identified. This ability to examine the representation of information relating to specific stimuli (e.g., memories) in particular brain areas makes MVPA an especially suitable method for investigating memory representations in brain structures such as the hippocampus. This approach could open up new opportunities to examine hippocampal representations in terms of their content, and how they might change over time, with aging, and pathology. Here we consider published MVPA studies that specifically focused on the hippocampus, and use them to illustrate the kinds of novel questions that can be addressed using MVPA. We then discuss some of the conceptual and methodological challenges that can arise when implementing MVPA in this context. Overall, we hope to highlight the potential utility of MVPA, when appropriately deployed, and provide some initial guidance to those considering MVPA as a means to investigate the hippocampus. (Contains 5 figures.)

Dual-process models of recognition memory distinguish between the retrieval of qualitative information about a prior event (recollection), and judgments of prior occurrence based on an acontextual sense of familiarity. fMRI studies investigating the neural correlates of memory encoding and retrieval conducted within the dual-process framework have frequently reported findings consistent with the view that the hippocampus selectively supports recollection, and has little or no role in familiarity-based recognition. An alternative interpretation of these findings has been proposed, however, in which it is argued that the hippocampus supports the encoding and retrieval of "strong" memories, regardless of whether the memories are recollection- or familiarity-based. Here, we describe the findings of eight fMRI studies from our laboratory: one study of source memory encoding, four studies of the retrieval of contextual information, and three studies of continuous recognition. Together, the findings support the proposal that hippocampal activity co-varies with the amount of contextual information about a study episode that is encoded or retrieved, and not with the strength of an undifferentiated memory signal. (Contains 4 tables and 5 figures.)

The aim of this study was to investigate individual differences in the influence of lexical association on word recognition during auditory sentence processing. Lexical associations among individual words (e.g. salt and pepper) represent one type of semantic information that is available during the processing of words in context. We predicted that individuals would vary in their sensitivity to this type of local context as a function of suppression ability and working-memory capacity. Lexical association was manipulated in auditory sentence contexts, and multiple regression analyses were employed to examine the relation between individuals' brain responses to meaning relations in sentences and measures of working-memory capacity, cognitive control and vocabulary. Lexical association influenced the processing of words that were embedded in sentences and also showed a great deal of individual variability. Specifically, suppression ability emerged as a significant predictor of sensitivity to lexical association, such that individuals who performed poorly on our measure of suppression ability (the Stroop task), compared to those who performed well, showed larger N400 effects of lexical association. (Contains 3 figures and 4 tables.)

Alzheimer's disease (AD) can impair metacognition in addition to more basic cognitive functions like memory. However, while global metacognitive inaccuracies are well documented (i.e., low deficit awareness, or anosognosia), the evidence is mixed regarding the effects of AD on local or task-based metacognitive judgments. Here we investigated local metacognition with respect to the confidence-accuracy relationship in episodic memory (i.e., metamemory). AD and control participants studied pictures of common objects and their verbal labels, and then took forced-choice picture recollection tests using the verbal labels as retrieval cues. We found that item-based confidence judgments discriminated between accurate and inaccurate recollection responses in both groups, implicating relatively spared metamemory in AD. By contrast, there was evidence for global metacognitive deficiencies, as AD participants underestimated the severity of their everyday problems compared to an informant's assessment. Within the AD group, individual differences in global metacognition were related to recollection accuracy, and global metacognition for everyday memory problems was related to task-based metacognitive accuracy. These findings suggest that AD can spare the confidence-accuracy relationship in recollection tasks, and that global and local metacognition measures tap overlapping neuropsychological processes. (Contains 3 figures and 3 tables.)

In general, declarative learning is associated with the activation of the medial temporal lobes (MTL), while the basal ganglia (BG) are considered the substrate for procedural learning. More recently it has been demonstrated the distinction of these systems may not be as absolute as previously thought and that not only the explicit or implicit nature of the memory task alone is important for the distinction of MTL or BG systems. Nevertheless, patients with BG dysfunction--such as patients with Parkinson's disease (PD) or Huntington's disease (HD)--are considered to be impaired at implicit learning. However, a more recent study demonstrated that one implicit learning task, probabilistic classification learning (examples include the weather prediction (WPT) and Mr. Potato Head tasks) is only impaired in PD when it involves learning with corrective feedback (FB) but not when it involves learning in a paired associate (PA) manner, without feedback. Therefore, it has been argued that the presence of feedback rather than the implicit nature of these tasks determines whether or not the BG are recruited. As patients with HD as well as those with PD, have also been shown to be impaired on the standard FB based version of probabilistic classification learning, the question remains as to whether or not there is a similar selective deficit in FB but not PA based probabilistic classification learning in HD. 18 patients with early HD and 18 healthy controls completed FB and PA versions of the WPT task. Relative to controls, HD patients were selectively impaired at WPT learning with feedback. These findings are consistent with previous evidence from studies of probabilistic classification learning in PD. Unlike PD, selective deficits in WPT learning in HD cannot be attributed to the effects of dopaminergic medication and must be directly related to BG dysfunction; for instance even in early HD, only 50% of the neurons in the medial head of caudate remain. We conclude that the striatum is important for WPT learning with feedback. Our findings are consistent with imaging evidence showing recruitment of the caudate during FB based WPT learning, while the MTL is associated with PA based learning. (Contains 3 tables and 4 figures.)

The basic deficits underlying the severe and persistent reading difficulties in dyslexia are still highly debated. One of the major topics of debate is whether these deficits are language specific, or affect both verbal and non-verbal stimuli. Recently, Ahissar and colleagues proposed the "anchoring-deficit hypothesis" (Ahissar, Lubin, Putter-Katz, & Banai, 2006), which suggests that dyslexics have a general difficulty in automatic extraction of stimulus regularities from auditory inputs. This hypothesis explained a broad range of dyslexics' verbal and non-verbal difficulties. However, it was not directly tested in the context of reading and verbal memory, which poses the main stumbling blocks to dyslexics. Here we assessed the abilities of adult dyslexics to efficiently benefit from ("anchor to") regularities embedded in repeated tones, orally presented syllables, and written words. We also compared dyslexics' performance to that of individuals with attention disorder (ADHD), but no reading disability. We found an anchoring effect in all groups: all gained from stimulus repetition. However, in line with the anchoring-deficit hypothesis, controls and ADHD participants showed a significantly larger anchoring effect in all tasks. This study is the first that directly shows that the same domain-general deficit, poor anchoring, characterizes dyslexics' performance in perceptual, working memory and reading tasks. (Contains 2 tables and 4 figures.)

Considering the high risk for individuals with amnestic Mild Cognitive Impairment (A-MCI) to progress towards Alzheimer's disease (AD), we investigated the efficacy of a non-pharmacological intervention, that is, cognitive training that could reduce cognitive difficulties and delay the cognitive decline. For this, we evaluated the efficacy of a 12-week computer-based memory-attention training program based on recognition in subjects with A-MCI and compared their performances with those of A-MCI controls trained in cognitively stimulating activities. The effect of training was assessed by comparing outcome measures in pre- and post-tests 15 days before and after training. To evaluate the duration of training benefits, a follow-up test session was performed 6 months after memory and attention training or cognitively stimulating activities. Outcome measures showed that the trained group, compared to control group, improved episodic recall and recognition. Six months after training, scores remained at the level of the post-test. Since the training program was exclusively based on recognition, our results showed a generalization from recognition to recall processes, which are memory components that represent part of the core cognitive impairments in individuals at risk of converting to AD. Thus, cognitive training based on recognition holds promise as a preventive therapeutic method and could be proposed as a non-pharmacological early-intervention strategy. Future investigations need to focus on methodological constraints and delineating possible neuroplastic mechanisms of action. (Contains 4 tables and 2 figures.)

It is tentatively estimated that 25% of people with early Alzheimer's disease (AD) show impaired awareness of disease-related changes in their own cognition. Research examining both normative self-awareness and altered awareness resulting from brain disease or injury points to the central role of the medial prefrontal cortex (MPFC) in generating accurate self-appraisals. The current project builds on this work--examining changes in MPFC functional connectivity that correspond to impaired self-appraisal accuracy early in the AD time course. Our behavioral focus was self-appraisal accuracy for everyday memory function, and this was measured using the Memory Function Scale of the Memory Awareness Rating Scale--an instrument psychometrically validated for this purpose. Using regression analysis of data from people with healthy memory (n = 12) and people with impaired memory due to amnestic mild cognitive impairment or early AD (n = 12), we tested the hypothesis that altered MPFC functional connectivity--particularly with other cortical midline structures and dorsolateral prefrontal cortex--explains variation in memory self-appraisal accuracy. We spatially constrained (i.e., explicitly masked) our regression analyses to those regions that work in conjunction with the MPFC to evoke self-appraisals in a normative group. This empirically derived explicit mask was generated from the result of a psychophysiological interaction analysis of fMRI self-appraisal task data in a separate, large group of cognitively healthy individuals. Results of our primary analysis (i.e., the regression of memory self-appraisal accuracy on MPFC functional connectivity) were generally consistent with our hypothesis: people who were less accurate in making memory self-appraisals showed attenuated functional connectivity between the MPFC seed region and proximal areas within the MPFC (including subgenual anterior cingulate cortex), bilateral dorsolateral prefrontal cortex, bilateral caudate, and left posterior hippocampus. Contrary to our expectations, MPFC functional connectivity with the posterior cingulate was not significantly related to accuracy of memory self-appraisals. Results reported here corroborate findings of variable memory self-appraisal accuracy during the earliest emergence of AD symptoms and reveal alterations in MPFC functional connectivity that correspond to impaired memory self-appraisal. (Contains 3 figures and 2 tables.)

Most neuropsychological assessments of episodic memory bear little similarity to the events that patients actually experience as memories in daily life. The first aim of this study was to use a virtual environment to characterize episodic memory profiles in an ecological fashion, which includes memory for central and perceptual details, spatiotemporal contextual elements, and binding. This study included subjects from three different populations: healthy older adults, patients with amnestic mild cognitive impairment (aMCI) and patients with early to moderate Alzheimer's disease (AD). Second, we sought to determine whether environmental factors that can affect encoding (active vs. passive exploration) influence memory performance in pathological aging. Third, we benchmarked the results of our virtual reality episodic memory test against a classical memory test and a subjective daily memory complaint scale. Here, the participants were successively immersed in two virtual environments; the first, as the driver of a virtual car (active exploration) and the second, as the passenger of that car (passive exploration). Subjects were instructed to encode all elements of the environment as well as the associated spatiotemporal contexts. Following each immersion, we assessed the patient's recall and recognition of central information (i.e., the elements of the environment), contextual information (i.e., temporal, egocentric and allocentric spatial information) and lastly, the quality of binding. We found that the AD patients' performances were inferior to that of the aMCI and even more to that of the healthy aged groups, in line with the progression of hippocampal atrophy reported in the literature. Spatial allocentric memory assessments were found to be particularly useful for distinguishing aMCI patients from healthy older adults. Active exploration yielded enhanced recall of central and allocentric spatial information, as well as binding in all groups. This led aMCI patients to achieve better performance scores on immediate temporal memory tasks. Finally, the patients' daily memory complaints were more highly correlated with the performances on the virtual test than with their performances on the classical memory test. Taken together, these results highlight specific cognitive differences found between these three populations that may provide additional insight into the early diagnosis and rehabilitation of pathological aging. In particular, neuropsychological studies would benefit to use virtual tests and a multi-component approach to assess episodic memory, and encourage active encoding of information in patients suffering from mild or severe age-related memory impairment. The beneficial effect of active encoding on episodic memory in aMCI and early to moderate AD is discussed in the context of relatively preserved frontal and motor brain functions implicated in self-referential effects and procedural abilities. (Contains 5 figures and 3 tables.)

The role of the anterior temporal lobe (ATL) in semantic memory is now firmly established. There is still controversy, however, regarding the specific role of this region in processing various types of concepts. There have been reports of patients suffering from semantic dementia (SD), a neurodegenerative condition in which the ATL is damaged bilaterally, who present with greater semantic impairment for concrete concepts than for abstract concepts, an effect known as reversal of the concreteness effect. This effect has previously been interpreted as reflecting degraded visual-perceptual features of objects due to damage to the inferior temporal lobes such as is observed in SD. Temporal lobe atrophy in SD, however, is bilateral even if it usually predominates to the left ATL, and it has been found to extend beyond the ATL, throughout the temporal lobes including medial and posterior temporal lobe regions. The question therefore remains whether greater impairment for concrete concepts results from damage to the ATL or from damage to the visual association cortex, and if unilateral damage can produce such a deficit. The aim of the present study was to investigate the processing of concrete and abstract words in rare patients who underwent a selective ATL surgical resection, and to compare their performance with that of patients with selective medial temporal lobe damage sparing the ATL region. Seven patients with a selective unilateral anterior temporal resection (ATL), 15 patients with a selective unilateral amygdalo-hippocampectomy (SeAH), and 15 healthy age- and education-matched controls underwent detailed neuropsychological assessment and carried out a semantic similarity judgment task evaluating their comprehension of concrete and abstract words. Results showed that both ATL and SeAH groups were significantly impaired on the semantic task relative to the control group. Within the patient groups, however, comprehension of concrete words was significantly more impaired than that of abstract words in the ATL group, while comprehension of abstract and concrete words was equally affected in the SeAH group. Results of this study suggest that the ATL region may play a critical role in processing concrete concepts, and that the reversal of the concreteness effect observed in ATL patients may result from damage to a categorical organization underlying the representation of concrete concepts. (Contains 3 figures and 3 tables.)

Memory retrieval can involve activity in the same sensory cortical regions involved in perception of the original event, and this neural "reactivation" has been suggested as an important mechanism of memory retrieval. However, it is still unclear if fragments of experience other than sensory information are retained and later reactivated during retrieval. For example, learning in non-laboratory settings generally involves active exploration of memoranda, thus requiring the generation of action plans for behavior and the use of strategies deployed to improve subsequent memory performance. Is information pertaining to action planning and strategic processing retained and reactivated during retrieval? To address this question, we compared ERP correlates of memory retrieval for objects that had been studied in an active manner involving action planning and strategic processing to those for objects that had been studied passively. Memory performance was superior for actively studied objects, and unique ERP retrieval correlates for these objects were identified when subjects remembered the specific spatial locations at which objects were studied. Early-onset frontal shifts in ERP correlates of retrieval were noted for these objects, which parallel the recruitment of frontal cortex during learning object locations previously identified using fMRI with the same paradigm. Notably, ERPs during recall for items studied with a specific viewing strategy localized to the same supplementary motor cortex region previously identified with fMRI when this strategy was implemented during study, suggesting rapid reactivation of regions directly involved in strategic action planning. Collectively, these results implicate neural populations involved in learning in important retrieval functions, even for those populations involved in strategic control and action planning. Notably, these episodic features are not generally reported during recollective experiences, suggesting that reactivation is a more general property of memory retrieval that extends beyond those fragments of perceptual information that might be needed to re-live the past. (Contains 4 figures and 2 tables.)

Contextual cueing refers to the facilitated ability to locate a particular visual element in a scene due to prior exposure to the same scene. This facilitation is thought to reflect implicit learning, as it typically occurs without the observer's knowledge that scenes repeat. Unlike most other implicit learning effects, contextual cueing can be impaired following damage to the medial temporal lobe. Here we investigated neural correlates of contextual cueing and explicit scene memory in two participant groups. Only one group was explicitly instructed about scene repetition. Participants viewed a sequence of complex scenes that depicted a landscape with five abstract geometric objects. Superimposed on each object was a letter T or L rotated left or right by 90 degrees. Participants responded according to the target letter (T) orientation. Responses were highly accurate for all scenes. Response speeds were faster for repeated versus novel scenes. The magnitude of this contextual cueing did not differ between the two groups. Also, in both groups repeated scenes yielded reduced hemodynamic activation compared with novel scenes in several regions involved in visual perception and attention, and reductions in some of these areas were correlated with response-time facilitation. In the group given instructions about scene repetition, recognition memory for scenes was superior and was accompanied by medial temporal and more anterior activation. Thus, strategic factors can promote explicit memorization of visual scene information, which appears to engage additional neural processing beyond what is required for implicit learning of object configurations and target locations in a scene. (Contains 2 tables and 3 figures.)

The efficiency of prospective memory (PM) typically increases from childhood to young adulthood and then decreases in later adulthood. The current study used event-related brain potentials (ERPs) to examine the development of the neural correlates of processes associated with the detection of a PM cue, switching from the ongoing activity to the prospective task, retrieval of the intention from memory or task set configuration, and strategic monitoring of the environment. The study included 99 participants that were 7.5-83 years of age. Slow wave activity related to strategic monitoring was reliable across the lifespan suggesting that all ages were able to allocate attentional resources to facilitate PM. Additionally, components of the ERPs related to cue detection, switching, and task configuration were reliable across the lifespan, suggesting that similar processes contribute to PM at all ages. In children, PM errors may have resulted from a decoupling of processes supporting cue detection and switching from the ongoing activity to the prospective element of the task. In younger and older adults, PM errors appeared to result from the failure to detect PM cues in the environment. These findings lead to the conclusion that different processes may contribute to variation in PM across the lifespan. (Contains 1 table and 5 figures.)

In the majority of people, functional differences are observed between the two cerebral hemispheres: language production is typically subserved by the left hemisphere and visuospatial skills by the right hemisphere. The development of this division of labour is not well understood and lateralisation of visuospatial function has received little attention in children. In this study we devised a child-friendly version of a paradigm to assess lateralisation of visuospatial memory using functional transcranial Doppler ultrasound (fTCD). In a group of 24 adults we found this child-friendly version gave similar results to the original version of the task. In addition, fourteen children aged 6-8 years successfully completed the child-friendly fTCD task, showing a negative lateralisation index, indicating right hemispheric specialisation at the group level. Additionally, we assessed effects of task accuracy and reaction time on the lateralisation index. No effects were found, at the group level or at the level of single trials, in either the adult or the child group. We conclude that this new task reliably assesses lateralisation of visuospatial memory function in children as young as 6 years of age, using fTCD. As such, it holds promise for investigating development of lateralisation of visuospatial function in typically and atypically developing children. (Contains 2 tables, 3 figures, and 2 footnotes.)

A known contributor to adults' superior memory performance compared to children is their differential reliance on an existing knowledge base. Compared to those of adults, children's semantic networks are less accessible and less established, a difference that is also thought to contribute to children's relative resistance to semantically related false alarms. Using the "congruency effect"--the memory advantage of congruity, we manipulated the encoded stimuli in the present experiment such that the use of the knowledge base at encoding was more--or less--accessible in both children and adults. While being scanned, 15 children (ages 8-11) and 18 young adults saw printed noun/color combinations and were asked to indicate whether each combination existed in nature. A subsequent recognition test was administered outside of the scanner. Behaviorally, although overall memory was higher in the adult group compared to the children, both age groups showed the congruency effect to the same extent. A comparison of the neural substrates supporting the congruency effect between adults and children revealed that whereas adults recruited regions primarily associated with semantic-conceptual processing (e.g., the left PFC and parietal and occipito-temporal cortices), children recruited regions earlier in the processing stream (e.g., the right occipital cortex). This evidence supports the hypothesis that early in development, episodic encoding depends more on perceptual systems, whereas top-down frontal control and parietal structures become more prominent in the encoding process with age. This developmental switch contributes to adults' superior memory performance but may render adults more vulnerable to committing semantically based errors. (Contains 5 figures and 8 tables.)

This study measured episodic memory deficits in individuals with mild cognitive impairment (MCI) as a function of their vascular burden. Vascular burden was determined clinically by computing the number of vascular risk factors and diseases and neuroradiologically by assessing the presence and severity of white matter lesions (WML). Strategic memory processes were measured with free recall and temporal contextual memory tasks requiring self-initiated retrieval. Nonstrategic memory retrieval processes were appraised with a five-choice recognition procedure. Results showed that MCI participants with high vascular burden displayed impairment of strategic memory processes, whereas MCI participants with no vascular burden showed impairment of both strategic and nonstrategic memory processes. A similar pattern was found whether vascular burden was measured using a clinical index of vascular risk profile or whether it was measured neuroradiologically by assessing the extent and severity of subcortical WML. However, the effect of WML on memory differed as function of level of education, used here as a proxy for cognitive reserve. Among participants with MCI, those who had higher education and no WML were the least memory impaired. The study also examined memory as a function of whether patients later progressed to dementia after a three-year follow-up. When examining progressors' performance, strategic and nonstrategic processes were both impaired in progressors with no concomitant vascular conditions, whereas progressors with a high vascular burden showed less impairment of nonstrategic than strategic processes. Overall, results indicate that the presence of vascular burden in MCI is associated with selective impairment of strategic memory processes. (Contains 3 figures and 5 tables.)

Williams syndrome (WS) is a neurogenetic developmental disorder characterized by an increased affinity for music, deficits in verbal memory, and atypical brain development. Music has been shown to improve verbal memory in typical individuals as well as those with learning difficulties, but no studies have examined this relationship in WS. The aim of our two studies was to examine whether music can enhance verbal memory in individuals with WS. In Study 1, we presented a memory task of eight spoken or sung sentences that described an animal and identified its group name to 38 individuals with WS. Study 2, involving another group of individuals with WS (n = 38), included six spoken or sung sentences that identified an animal group name. In both studies, those who had participated in formal music lessons scored significantly better on the verbal memory task when the sentences were sung than when they were spoken. Those who had not taken formal lessons showed no such benefit. We also found that increased enjoyment of music and heightened emotional reactions to music did not impact performance on the memory task. These compelling findings provide the first evidence that musical experience may enhance verbal memory in individuals with WS and shed more light on the complex relationship between aspects of cognition and altered neurodevelopment in this unique disorder. (Contains 7 figures and 6 tables.)

Event-based prospective memory (PM) is a multi-component process that requires remembering the delayed execution of an intended action in response to a pre-specified PM cue, while being actively engaged in an ongoing task. Some neuroimaging studies have suggested that both prefrontal and parietal areas are involved in the maintenance and realization of delayed intentions. In the present study, transcranial magnetic stimulation (TMS) was used to investigate the causal involvement of frontal and parietal areas in different stages of the PM process (in particular, target checking and intention retrieval), and to determine the specific contribution of these regions to PM performance. Our results demonstrate that repetitive TMS (rTMS) interferes with prospective memory performance when applied at 150-350 ms to the right dorsolateral prefrontal cortex (DLPFC), and at 400-600 ms when applied to the left posterior parietal cortex (PPC). The present study provides clear evidence that the right DLPFC plays a crucial role in early components of the PM process (target checking), while the left PPC seems to be mainly involved in later processes, such as the retrieval of the intended action. (Contains 3 figures.)

Among the large variety of attentional tasks that have been used to study sustained attention, the Continuous Performance Task (CPT) is perhaps the most widely used. Despite substantial differences in task characteristics and demands, all CPT paradigms have been referred to as measures of sustained attention. In the present study we introduce a new variant of CPT, which minimizes perceptual and memory components while maximizing the sustained attention components of the task. In addition, we tested the contention that the ability to sustain attention should not be overly dependent on the specific stimuli and task-modality. To this end, we used a new visual Conjunctive CPT (CCPT) developed by Tsal, Shalev, & Mevorach (2005) and its auditory analogue. Using a Multi-Trait-Multi-Method (MTMM) analysis investigating reliability coefficients, convergent validity coefficients and divergent (discriminant) validity coefficients, we established that the new CCPT is a valid measure of sustained attention. In particular, high correlations were obtained between mean RT and SD-RT within each sensory modality. High correlations were also found between performance across sensory modalities (mean convergent validity: 0.71). Finally, low correlations (mean correlation of 0.18) were found between performance in the CCPT tasks and performance in two additional visuospatial attention tasks, which do not rely on sustained attention. These findings suggest that independent of sensory modality, the two CCPT tasks used here tap the same stable construct, namely, sustained attention. We conclude that when a measure of sustained attention is required, researchers should be aware of the caveats of standard CPTs and should be careful in selecting a proper task. Moreover, clinicians should appreciate that some CPT measures may reflect a combination of different cognitive operations rather than pure sustained attention. (Contains 3 figures and 2 tables.)

Previous neuroimaging studies that have examined autobiographical memory specificity have utilized retrieval cues associated with prior searches of the event, potentially changing the retrieval processes being investigated. In the current study, musical cues were used to naturally elicit memories from multiple levels of specificity (i.e., lifetime period, general event, and event-specific). Sixteen young adults participated in a neuroimaging study in which they retrieved autobiographical memories associated with musical cues. These musical cues led to the retrieval of highly emotional memories that had low levels of prior retrieval. Retrieval of all autobiographical memory levels was associated with activity in regions in the autobiographical memory network, specifically the ventromedial prefrontal cortex, posterior cingulate, and right medial temporal lobe. Owing to the use of music, memories from varying levels of specificity were retrieved, allowing for comparison of event memory and abstract personal knowledge, as well as comparison of specific and general event memory. Dorsolateral and dorsomedial prefrontal regions were engaged during event retrieval relative to personal knowledge retrieval, and retrieval of specific event memories was associated with increased activity in the bilateral medial temporal lobe and dorsomedial prefrontal cortex relative to retrieval of general event memories. These results suggest that the initial search processes for memories of different specificity levels preferentially engage different components of the autobiographical memory network. The potential underlying causes of these neural differences are discussed. (Contains 5 figures and 5 tables.)

Compared to adults, relatively little is known about autobiographical memory and the ability to imagine fictitious and future scenarios in school-aged children, despite the importance of these functions for development and subsequent independent living. Even less is understood about the effect of early hippocampal damage on children's memory and imagination abilities. To bridge this gap, we devised a novel naturalistic autobiographical memory task that enabled us to formally assess the memory for recent autobiographical experiences in healthy school-aged children. Contemporaneous with the autobiographical memories being formed, the children also imagined and described fictitious scenarios. Having established the performance of healthy school-aged children on these tasks, we proceeded to make comparisons with children (n = 21) who had experienced neonatal hypoxia/ischaemia, and consequent bilateral hippocampal damage. Our results showed that healthy children could recall autobiographical events, including spatiotemporal information and specific episodic details. By contrast, children who had experienced neonatal hypoxia/ischaemia had impaired recall, with the specific details of episodes being lost. Despite this significant memory deficit they were able to construct fictitious scenarios. This is in clear contrast to adults with hippocampal damage, who typically have impaired autobiographical memory and deficits in the construction of fictitious and future scenarios. We speculate that the paediatric patients' relatively intact semantic memory and/or some functionality in their residual hippocampi may underpin their scene construction ability. (Contains 3 figures and 3 tables.)

The ability to adapt behavior in a changing environment is necessary for humans to achieve their goals and can be measured in the lab with tests of rule-based switching. Disease models, such as cocaine addiction, have revealed that alterations in dopamine interfere with adaptive set switching, culminating in perseveration. We explore perseverative behavior in individuals with cocaine use disorders (CUD) and healthy controls (CON) during performance of the Wisconsin Card Sorting Test (WCST) (N = 107 in each group). By examining perseverative errors within each of the 6 blocks of the WCST, we uniquely test two forms of set switching that are differentiated by either the presence (extradimensional set shifting (EDS)--first 3 blocks) or absence (task-set switching--last 3 blocks) of new contingency learning. We also explore relationships between perseveration and select cognitive and drug use factors including verbal learning and memory, trait inhibitory control, motivational state, and urine status for cocaine (in CUD). Results indicate greater impairment for CUD than CON on the WCST, even in higher performing CUD who completed all 6 blocks of the WCST. Block by block analysis conducted on completers' scores indicate a tendency for greater perseveration in CUD than CON but only during the first task-set switch; no such deficits were observed during EDS. This task-set switching impairment was modestly associated with two indices of immediate recall (r = -0.32, -0.29) and urine status for cocaine [t (134) = 2.3, p less than 0.03]. By distinguishing these two forms of switching on the WCST, the current study reveals a neurocognitive context (i.e. initial stage of task-set switching) implicit in the WCST that possibly relies upon intact dopaminergic function, but that is impaired in CUD, as associated with worse recall and possibly withdrawal from cocaine. Future studies should investigate whether dopaminergically innervated pathways alone, or in combination with other monoamines, underlie this implicit neurocognitive processes in the WCST. (Contains 3 figures and 2 tables.)

Although studies of long-term outcomes of children born preterm consistently show low intelligence quotient (IQ) and visual-motor impairment, studies of their performance in language and reading have found inconsistent results. In this study, we examined which specific language and reading skills were associated with prematurity independent of the effects of gender, socioeconomic status (SES), and IQ. Participants from two study sites (N = 100) included 9-16-year old children born before 36 weeks gestation and weighing less than 2500 grams (preterm group, n = 65) compared to children born at 37 weeks gestation or more (full-term group, n = 35). Children born preterm had significantly lower scores than full-term controls on Performance IQ, Verbal IQ, receptive and expressive language skills, syntactic comprehension, linguistic processing speed, verbal memory, decoding, and reading comprehension but not on receptive vocabulary. Using MANCOVA, we found that SES, IQ, and prematurity all contributed to the variance in scores on a set of six non-overlapping measures of language and reading. Simple regression analyses found that after controlling for SES and Performance IQ, the degree of prematurity as measured by gestational age group was a significant predictor of linguistic processing speed, beta = -0.27, p less than 0.05, R[superscript 2] = 0.07, verbal memory, beta = 0.31, p less than 0.05, R[superscript 2] = 0.09, and reading comprehension, beta = 0.28, p less than 0.05, R[superscript 2] = 0.08, but not of receptive vocabulary, syntactic comprehension, or decoding. The language and reading domains where prematurity had a direct effect can be classified as fluid as opposed to crystallized functions and should be monitored in school-aged children and adolescents born preterm.

Event-related potentials (ERPs) are unique in their ability to provide information about the timing of activity in the neural networks that perform complex cognitive processes. Given the dearth of extant data from normal controls on the question of whether attitude representations are stored in episodic or semantic memory, the goal here was to study the nature of the memory representations used during conscious attitude evaluations. Thus, we recorded ERPs while participants performed three tasks: attitude evaluations (i.e., agree/disagree), autobiographical cued recall (i.e., You/Not You) and semantic evaluations (i.e., active/inactive). The key finding was that the parietal episodic memory (EM) effect, a well-established correlate of episodic recollection, was elicited by both attitude evaluations and autobiographical retrievals. By contrast, semantic evaluations of the same attitude items elicited less parietal activity, like that elicited by Not You cues, which only access semantic memory. In accord with hemodynamic results, attitude evaluations and autobiographical retrievals also produced overlapping patterns of slow potential (SP) activity from 500 to 900 ms preceding the response over left and right inferior frontal, anterior medial frontal and occipital brain areas. Significantly different patterns of SP activity were elicited in these locations for semantic evaluations and Not You cues. Taken together, the results indicate that attitude representations are stored in episodic memory. Retrieval timing varied as a function of task, with earlier retrievals in both evaluation conditions relative to those in the autobiographical condition. The differential roles and timing of memory retrieval in evaluative judgment and memory retrieval tasks are discussed.

Metamemory refers to the ability of individuals to monitor and control their own memory performance. Although little theoretical consideration of the possible differences between the monitoring of episodic and of semantic knowledge has been published, results from patient and drug studies that used the "feeling of knowing" (FOK) paradigm show a selective impairment in the accuracy of episodic monitoring but not in its semantic counterpart. Similarly, neuroimaging studies provide indirect evidence for separate patterns of activation during episodic or semantic FOKs. However, the semantic-episodic distinction hypothesis has not been directly addressed. In the current event-related fMRI study, we used a within-subject, within-experiment comparison of the monitoring of semantic and episodic content. Whereas the common neural correlates of episodic and semantic FOKs observed in this study generally replicate the previous neuroimaging findings, several regions were found to be differentially associated with each task. Activity of the right inferior frontal gyrus was modulated by the semantic-episodic factor only during the negative predictions of retrieval, suggesting that negative predictions are based on partially distinct mechanisms during each task. A posterior midline network, known to be activated during episodic retrieval, was activated during episodic and not semantic monitoring, suggesting that episodic FOKs rely, to some extent, on common episodic retrieval processes. These findings suggest that theoretical accounts of the etiology and function of FOKs may benefit from incorporating the prediction directionality (positive/negative) and the memory domain (semantic/episodic) distinctions.

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with episodic memory encoding and whether these effects would differ depending on the emotional valence of the material. We used a double-blind, within-participants, crossover design in which either glucose (50 g) or a saccharin placebo were administered before scanning, on days approximately 1 week apart. We scanned healthy young male participants with fMRI as they viewed emotionally arousing negative pictures and emotionally neutral pictures, intermixed with baseline fixation. Free recall was tested at 5 min after scanning and again after 1 day. Glucose administration increased activation in brain regions associated with successful episodic memory encoding. Glucose also enhanced activation in regions whose activity was correlated with subsequent successful recall, including the hippocampus, prefrontal cortex, and other regions, and these effects differed for negative vs. neutral stimuli. Finally, glucose substantially increased functional connectivity between the hippocampus and amygdala and a network of regions previously implicated in successful episodic memory encoding. These findings fit with evidence from nonhuman animals indicating glucose modulates memory by selectively enhancing neural activity in brain regions engaged during memory tasks. Our results highlight the modulatory effects of glucose and the importance of examining both regional changes in activity and functional connectivity to fully characterize the effects of glucose on brain function and memory.

The triple-code model, cognitive neuroimaging and developmental behavioral data suggest a specific association between phonological processing and arithmetic fact retrieval. Accordingly, individuals with deficits in phonological processing, such as individuals with developmental dyslexia, are expected to show difficulties in arithmetic fact retrieval. The present study tested this proposal in 25 adults with developmental dyslexia and 25 matched controls by examining strategy use during single-digit multiplication and subtraction and its associations with phonological processing. Findings revealed that individuals with dyslexia retrieved fewer arithmetic facts from memory and were less efficient in doing so. At the same time, they showed deficits in phonological processing. Phonological processing, particularly phonological awareness, was related to arithmetic fact retrieval. This association was especially prominent in multiplication, indicating that fact retrieval in multiplication rather than subtraction is mediated by phonological processes. These data provide ground for future neuroimaging studies, who should examine the neural overlap between phonological processing and multiplication fact retrieval in the same sample of participants. (Contains 5 tables and 3 figures.)

Studies of inhibitory control have focused on inhibition of motor responses. Individuals with ADHD consistently show reductions in inhibitory control and exhibit reduced activity of rLPFC activity compared to controls when performing such tasks. Recently these same brain regions have been implicated in the inhibition of memory retrieval. The degree to which inhibition of motor responses and inhibition of memory retrieval might involve overlapping systems has been relatively unexplored. The current study examined whether inhibitory difficulties in ADHD extend to inhibitory control over memory retrieval. During fMRI 16 individuals with ADHD and 16 controls performed the Think/No-Think (TNT) task. Behaviorally, the Stop Signal Reaction Time task (SSRT) was used to assess inhibitory control over motor responses. To link both of these measures to behavior, the severity of inattentive and hyperactive symptomatology was also assessed. Behaviorally, ADHD individuals had specific difficulty in inhibiting, but not in elaborating/increasing memory retrieval, which was correlated with symptom severity and longer SSRT. Additionally, ADHD individuals showed reduced activity in rLPFC during the TNT, as compared to control individuals. Moreover, unlike controls, in whom the correlation between activity of the rMFG and hippocampus predicts inhibitory success, no such correlation was observed for ADHD individuals. Moreover, decreased activity in rIFG in individuals with ADHD predicted a decrease in the ability to inhibit motor responses. These results suggest that inhibitory functions of rLPFC include control over both memory and motoric processes. They also suggest that inhibitory deficits in individuals with ADHD extend to the memory domain. (Contains 4 figures and 1 table.)

Autism Spectrum Disorders (ASD) are associated with abnormalities in face memory, which evidence suggests has a protracted development through adolescence. The development of face memory in people with and without ASD, from 9 to 29 years old, was examined using the Cambridge Face Memory Test (CFMT). Results indicate that the developmental improvement evident from adolescence to adulthood typically was not apparent in individuals with ASD. While children and adolescents with ASD performed similarly to typically developing individuals comparable in age and IQ, adults with ASD displayed limitations on the CFMT. The pattern of performance was constant across conditions despite differences in the timing of the presentation and delay. This atypical development in ASD is consistent with the view that the processing of complex visual stimuli continues to develop through adolescence, along with the function and structure of the temporal lobes, but that this process is disrupted in ASD. This result underscores the importance of characterizing adolescent development for understanding ASD, and suggests additional opportunities for intervention. (Contains 4 figures and 2 tables.)

The current study compared the neural correlates of associative retrieval of compound (unitized) stimuli and unrelated (non-unitized) stimuli. Although associative recognition was nearly identical for compounds and unrelated pairs, accurate recognition of these different pair types was associated with activation in distinct regions within the medial temporal lobe (MTL). Recognition of previously presented compound words was associated with left perirhinal activity, whereas recognition of unrelated word pairs was associated with activity in left hippocampus. These results provide evidence that perirhinal cortex mediates familiarity-based associative memory of stimuli unitized at encoding, while the hippocampus is required for recollection-based associative memory.

The properties of retrograde amnesia after damage to the hippocampus have been explicated with some success using a rat model of human medial temporal lobe amnesia. We review the results of this experimental work with rats focusing on several areas of consensus in this growing literature. We evaluate the theoretically significant hypothesis that hippocampal retrograde amnesia normally exhibits a temporal gradient, affecting recent, but sparing remote memories. Surprisingly, the evidence does not provide much support for the idea that there is a lengthy process of systems consolidation following a learning episode. Instead, recent and remote memories tend to be equally affected. The extent of damage to the hippocampus is a significant factor in this work since it is likely that spared hippocampal tissue can support at least partial memory retrieval. With extensive hippocampal damage gradients are flat or, in the case of memory tasks with flavour/odour retrieval cues, the retrograde amnesia covers a period of about 1-3 days. There is consistent evidence that at the time of learning the hippocampus interferes with or overshadows memory acquisition by other systems. This contributes to the breadth and severity of retrograde amnesia relative to anterograde amnesia in the rat. The fact that multiple, distributed learning episodes can overcome this overshadowing is consistent with a parallel dual-store theory or a Distributed Reinstatement Theory in which each learning episode triggers a short period of memory replay that provides a brief hippocampal-dependent systems consolidation. (Contains 3 figures and 1 table.)

This study investigated the "latent deficit" hypothesis in two groups of head-injured patients with predominantly frontal lesions, those injured prior to steep morphological and corresponding functional maturational periods for frontal networks (less than or equal to age 25), and those injured greater than 28 years. The latent deficit hypothesis proposes that early injuries produce enduring cognitive deficits manifest later in the lifespan with graver consequences for behavior than adult injuries, particularly after frontal pathology (Eslinger, Grattan, Damasio & Damasio, 1992). Implicit and executive deficits both contribute to behavioral insight after frontal head injury (Barker, Andrade, Romanowski, Morton, & Wasti, 2006). On the basis of morphological and behavioral data, we hypothesized that early injury would confer greater vulnerability to impairment on tasks associated with frontal regions than later injury. Patients completed experimental tasks of implicit cognition, executive function measures and the DEX measure of behavioral insight (Behavioral Assessment of the Dysexecutive Syndrome: Wilson, Alderman, Burgess, Emslie, & Evans, 1996). The Early Injury group were more impaired on implicit cognition tasks compared to controls that Late Injury patients. There were no marked group differences on most executive function measures. Executive ability only contributed to behavioral awareness in the Early Injury Group. Findings showed that age at injury moderates the relationship between executive and implicit cognition and behavioral insight and that early injuries result in long-standing deficits to functions associated with frontal regions partially supporting the latent deficit hypothesis. (Contains 2 figures and 7 tables.)

This review summarizes a series of experiments aimed at answering the question whether the hippocampus in rats can serve as an animal model of amnesia. It is recognized that a comparison of the functions of the rat hippocampus with human hippocampus is difficult, because of differences in methodology, differences in complexity of life experiences, and differences in the degree of hippocampal damage. Notwithstanding, rats and humans with hippocampal damage are similarly impaired on analogous tasks that assess spatial memory, spatial pattern separation, spatial configural and arbitrary associations, temporal order memory, temporal pattern separation, sequential learning, and temporal associations. These data suggest that the rat can serve as a model of memory dysfunction (amnesia) as it relates to spatial and temporal processing of new information. (Contains 2 figures.)

The goal of the present study was to demonstrate that declarative and non-declarative knowledge acquired in an incidental sequence learning task contributes differentially to memory retrieval and leads to dissociable ERP signatures in a recognition memory task. For this purpose, participants performed a sequence learning task and were classified as verbalizers, partial verbalizers, or nonverbalizers according to their ability to verbally report the systematic response sequence. Thereafter, ERPs were recorded in a recognition memory task time-locked to sequence triplets that were either part of the previously learned sequence or not. Although all three groups executed old sequence triplets faster than new triplets in the recognition memory task, qualitatively distinct ERP patterns were found for participants with and without reportable knowledge. Verbalizers and, to a lesser extent, partial verbalizers showed an ERP correlate of recollection for parts of the incidentally learned sequence. In contrast, nonverbalizers showed a different ERP effect with a reverse polarity that might reflect priming. This indicates that an ensemble of qualitatively different processes is at work when declarative and non-declarative sequence knowledge is retrieved. By this, our findings favor a multiple-systems view postulating that explicit and implicit learning are supported by different and functionally independent systems. (Contains 1 table and 8 figures.)

Larger error-related negativities (ERNs) have been consistently found in obsessive-compulsive disorder (OCD) patients, and are thought to reflect the activities of a hyperactive cortico-striatal circuit during action monitoring. We previously observed that obsessive-compulsive (OC) symptomatic students (non-patients) have larger ERNs during errors in a response competition task, yet smaller ERNs in a reinforcement learning task. The finding of a task-specific dissociation suggests that distinct yet partially overlapping medio-frontal systems underlie the ERN in different tasks, and that OC symptoms are associated with functional differences in these systems. Here, we used EEG source localization to identify why OC symptoms are associated with hyperactive ERNs to errors yet hypoactive ERNs when selecting maladaptive actions. At rest, OC symptomatology predicted greater activity in rostral anterior cingulate cortex (rACC) and lower activity in dorsal anterior cingulate cortex (dACC). When compared to a group with low OC symptom scores, the high OC group had greater rACC reactivity during errors in the response competition task and less deactivation of dACC activity during errors in the reinforcement learning task. The degree of activation in these areas correlated with ERN amplitudes during both tasks in the high OC group, but not in the low group. Interactive anterior cingulate cortex (ACC) systems associated avoidance of maladaptive actions were intact in the high OC group, but were related to poorer performance on a third task: probabilistic reversal learning. These novel findings link both tonic and phasic activities in the ACC to action monitoring alterations, including dissociation in performance deficits, in OC symptomatic participants. (Contains 1 table and 6 figures.)

As we learn new information about the social and moral behaviors of other people, we form and update character judgments of them, and this can profoundly influence how we regard and act towards others. In the study reported here, we capitalized on two interesting neurological patient populations where this process of complex "moral updating" may go awry: patients with bilateral damage to ventromedial prefrontal cortex (vmPFC) and patients with bilateral damage to hippocampus (HC). We predicted that vmPFC patients, who have impaired emotion processing, would exhibit "reduced" moral updating, and we also investigated how moral updating might be affected by severe declarative memory impairment in HC patients. The vmPFC, HC, and brain-damaged comparison (BDC) participants made moral judgments about unfamiliar persons before and after exposure to social scenarios depicting the persons engaged in morally good, bad, or neutral behaviors. In line with our prediction, the vmPFC group showed the least amount of change in moral judgments, and interestingly, the HC group showed the most amount of change. These results suggest that the vmPFC and hippocampus play critical but complementary roles in updating moral character judgments about others: the vmPFC may attribute emotional salience to moral information, whereas the hippocampus may provide necessary contextual information from which to make appropriate character judgments. (Contains 4 tables and 7 figures.)

Reliving past events and imagining potential future events engages a well-established "core" network of brain areas. How the brain constructs, or reconstructs, these experiences or scenes has been debated extensively in the literature, but remains poorly understood. Here we designed a novel task to investigate this (re)constructive process by directly exploring how naturalistic scenes are built up from their individual elements. We "slowed-down" the construction process through the use of auditorily presented phrases describing single scene elements in a serial manner. Participants were required to integrate these elements (ranging from three to six in number) together in their imagination to form a naturalistic scene. We identified three distinct sub-networks of brain areas, each with different fMRI BOLD response profiles, favouring specific points in the scene construction process. Areas including the hippocampus and retrosplenial cortex had a biphasic profile, activating when a single scene element was imagined and when 3 elements were combined together; regions including the intra-parietal sulcus and angular gyrus steadily increased activity from 1 to 3 elements; while activity in areas such as lateral prefrontal cortex was observed from the second element onwards. Activity in these sub-networks did not increase further when integrating more than three elements. Participants confirmed that three elements were sufficient to construct a coherent and vivid scene, and once this was achieved, the addition of further elements only involved maintenance or small changes to that established scene. This task offers a potentially useful tool for breaking down scene construction, a process that may be key to a range of cognitive functions such as episodic memory, future thinking and navigation. (Contains 7 tables and 4 figures.)

Recent research has demonstrated that Alzheimer's disease (AD) affects the visual sensory pathways, producing a variety of visual deficits, including the capacity to perceive structure-from-motion (SFM). Because the sensory areas of the adult brain are known to retain a large degree of plasticity, the present study was conducted to explore whether the degradation of a visual function impaired by AD can be reversed or slowed through perceptual learning. Whereas many studies directed at learning in AD examined learning capacities involving the implicit memory system, a largely preserved system in AD, the present study focused on perceptual learning involving visual deficits impaired by AD. Patients with mild or moderately severe AD (N = 8 in each group) were presented with computer displays depicting SFM. Participants completed three sessions a day on three consecutive days with each session comprised of 48 trials. Displays showed eight different geometric solids rendered in three densities of a random dot texture. Participants identified the displayed object by pointing to a corresponding wooden object. Results showed impaired capacity for motion perception and SFM perception in both AD groups. However, performance of patients with mild AD improved over the nine sessions, whereas that of patients with moderate AD remained unchanged. These results suggest that the cortical circuits for SFM are still plastic in the mild AD stage. (Contains 1 table and 7 figures.)

The purpose of this investigation was to test the assumption of asymmetric mapping between words and concepts in bilingual memory as proposed by the Revised Hierarchical Model (RHM, Kroll & Stewart, 1994). Twenty four Spanish-English bilinguals (experiment 1) and twenty English-Spanish bilinguals (experiment 2) were presented with pairs of words, one in English and one in Spanish, and asked to indicate whether or not the words had the same meaning. In half the trials the Spanish word preceded the English, and in the other half the English word preceded the Spanish. In each condition half of the words had the same meaning, and the experiment included both concrete and abstract word trials. Event-related potentials (ERPs) were used to examine lexical-semantic activation during word translation. As predicted, a direction-dependent translation asymmetry was observed in the magnitude of the N400 repetition effect. Specifically, the N400 effect was larger during backward translation (L2-L1) than during forward translation (L1-L2) in both groups of bilinguals. Results are considered in the context of different models of bilingual memory. (Contains 6 tables and 2 figures.)

Understanding the underlying qualitative features of memory deficits in mild cognitive impairment (MCI) can provide critical information for early detection of Alzheimer's disease (AD). This study sought to investigate the utility of both learning and retention measures in (a) the diagnosis of MCI, (b) predicting progression to AD, and (c) examining their underlying brain morphometric correlates. A total of 607 participants were assigned to three MCI groups (high learning-low retention; low learning-high retention; low learning-low retention) and one control group (high learning-high retention) based on scores above or below a 1.5 SD cutoff on learning and retention indices of the Rey Auditory Verbal Learning Test. Our results demonstrated that MCI individuals with predominantly a learning deficit showed a widespread pattern of gray matter loss at baseline, whereas individuals with a retention deficit showed more focal gray matter loss. Moreover, either learning or retention measures provided good predictive value for longitudinal clinical outcome over two years, although impaired learning had modestly better predictive power than impaired retention. As expected, impairments in both measures provided the best predictive power. Thus, the conventional practice of relying solely on the use of delayed recall or retention measures in studies of amnestic MCI misses an important subset of older adults at risk of developing AD. Overall, our results highlight the importance of including learning measures in addition to retention measures when making a diagnosis of MCI and for predicting clinical outcome. (Contains 4 tables and 3 figures.)