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Several recent fMRI studies of episodic and working memory representations converge on the finding that visual information is most strongly represented in occipito-temporal cortex during the encoding phase but in parietal regions during the retrieval phase. It has been suggested that this location shift reflects a change in the content of representations, from predominantly visual during encoding to primarily semantic during retrieval. Yet, direct evidence on the nature of encoding and retrieval representations is lacking. It is also unclear how the representations mediating the encoding-retrieval shift contribute to memory performance. To investigate these two issues, in the current fMRI study, participants encoded pictures (e.g., picture of a cardinal) and later performed a word recognition test (e.g., word "cardinal"). Representational similarity analyses examined how visual (e.g., red color) and semantic representations (e.g., what cardinals eat) support successful encoding and retrieval. These analyses revealed two novel findings. First, successful memory was associated with representational changes in cortical location (from occipito-temporal at encoding to parietal at retrieval) but not with changes in representational content (visual vs. semantic). Thus, the representational encoding-retrieval shift cannot be easily attributed to a change in the nature of representations. Second, in parietal regions, stronger representations predicted encoding failure but retrieval success. This encoding-retrieval "flip" in representations mimics the one previously reported in univariate activation studies. In summary, by answering important questions regarding the content and contributions to the performance of the representations mediating the encoding-retrieval shift, our findings clarify the neural mechanisms of this intriguing phenomenon., (© 2024 Massachusetts Institute of Technology. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)

Functional connectivity is conventionally defined by measuring the similarity between brain signals from two regions. The technique has become widely adopted in the analysis of functional magnetic resonance imaging (fMRI) data, where it has provided cognitive neuroscientists with abundant information on how brain regions interact to support complex cognition. However, in the past decade the notion of "connectivity" has expanded in both the complexity and heterogeneity of its application to cognitive neuroscience, resulting in greater difficulty of interpretation, replication, and cross-study comparisons. In this paper, we begin with the canonical notions of functional connectivity and then introduce recent methodological developments that either estimate some alternative form of connectivity or extend the analytical framework, with the hope of bringing better clarity for cognitive neuroscience researchers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

When we perceive a scene, our brain processes various types of visual information simultaneously, ranging from sensory features, such as line orientations and colors, to categorical features, such as objects and their arrangements. Whereas the role of sensory and categorical visual representations in predicting subsequent memory has been studied using isolated objects, their impact on memory for complex scenes remains largely unknown. To address this gap, we conducted an fMRI study in which female and male participants encoded pictures of familiar scenes (e.g., an airport picture) and later recalled them, while rating the vividness of their visual recall. Outside the scanner, participants had to distinguish each seen scene from three similar lures (e.g., three airport pictures). We modeled the sensory and categorical visual features of multiple scenes using both early and late layers of a deep convolutional neural network. Then, we applied representational similarity analysis to determine which brain regions represented stimuli in accordance with the sensory and categorical models. We found that categorical, but not sensory, representations predicted subsequent memory. In line with the previous result, only for the categorical model, the average recognition performance of each scene exhibited a positive correlation with the average visual dissimilarity between the item in question and its respective lures. These results strongly suggest that even in memory tests that ostensibly rely solely on visual cues (such as forced-choice visual recognition with similar distractors), memory decisions for scenes may be primarily influenced by categorical rather than sensory representations., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Evidence from functional neuroimaging studies of emotional perception shows that when attention is focused on external features of emotional stimuli (external perceptual orienting--EPO), the amygdala is primarily engaged, but when attention is turned inwards towards one's own emotional state (interoceptive self-orienting--ISO), regions of the salience network, such as the anterior insula (AI) and the dorsal anterior cingulate cortex (dACC), also play a major role. Yet, it is unknown if ISO boosts the contributions of AI and dACC not only to emotional 'perception' but also to emotional 'memory'. To investigate this issue, participants were scanned with functional magnetic resonance imaging (fMRI) while viewing emotional and neutral pictures under ISO or EPO, and memory was tested several days later. The study yielded three main findings: (i) emotion boosted perception-related activity in the amygdala during both ISO and EPO and in the right AI exclusively during ISO; (ii) emotion augmented activity predicting subsequent memory in AI and dACC during ISO but not during EPO and (iii) high confidence memory was associated with increased amygdala-dACC connectivity, selectively for ISO encoding. These findings show, for the first time, that ISO promotes emotional memory formation via regions associated with interoceptive awareness of emotional experience, such as AI and dACC., (© The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

The posterior midline region (PMR)-considered a core of the default mode network-is deactivated during successful performance in different cognitive tasks. The extent of PMR-deactivations is correlated with task-demands and associated with successful performance in various cognitive domains. In the domain of episodic memory, functional MRI (fMRI) studies found that PMR-deactivations reliably predict learning (successful encoding). Yet it is unclear what explains this relation. One intriguing possibility is that PMR-deactivations are partially mediated by respiratory artifacts. There is evidence that the fMRI signal in PMR is particularly prone to respiratory artifacts, because of its large surrounding blood vessels. As respiratory fluctuations have been shown to track changes in attention, it is critical for the general interpretation of fMRI results to clarify the relation between respiratory fluctuations, cognitive performance, and fMRI signal. Here, we investigated this issue by measuring respiration during word encoding, together with a breath-holding condition during fMRI-scanning. Stimulus-locked respiratory analyses showed that respiratory fluctuations predicted successful encoding via a respiratory phase-locking mechanism. At the same time, the fMRI analyses showed that PMR-deactivations associated with learning were reduced during breath-holding and correlated with individual differences in the respiratory phase-locking effect during normal breathing. A left frontal region--used as a control region--did not show these effects. These findings indicate that respiration is a critical factor in explaining the link between PMR-deactivation and successful cognitive performance. Further research is necessary to demonstrate whether our findings are restricted to episodic memory encoding, or also extend to other cognitive domains., (Copyright © 2014 Wiley Periodicals, Inc.)

Point Distribution Models (PDM) are some of the most popular shape description techniques in medical imaging. However, to create an accurate shape model it is essential to have a representative sample of the underlying population, which is often challenging. This problem is particularly relevant as the dimensionality of the modeled structures increases, and becomes critical when dealing with complex 3D shapes. In this paper, we introduce a new generalized multiresolution hierarchical PDM (GMRH-PDM) able to efficiently address the high-dimension-low-sample-size challenge when modeling complex structures. Unlike previous approaches, our new and general framework extends hierarchical modeling to any type of structure (multi- and single-object shapes) allowing to describe efficiently the shape variability at different levels of resolution. Importantly, the configuration of the algorithm is automatized thanks to the new agglomerative landmark clustering method presented here. Our new and automatic GMRH-PDM framework performed significantly better than classical approaches, and as well as the state-of-the-art with the best manual configuration. Evaluations have been studied for two different cases, the right kidney, and a multi-object case composed of eight subcortical structures.

Point distribution models (PDM) are one of the most extended methods to characterize the underlying population of set of samples, whose usefulness has been demonstrated in a wide variety of applications, including medical imaging. However, one important issue remains unsolved: the large number of training samples required. This problem becomes critical as the complexity of the problem increases, and the modeling of 3D multiobjects/organs represents one of the most challenging cases. Based on the 3D wavelet transform, this paper introduces a multiresolution hierarchical variant of PDM (MRH-PDM) able to efficiently characterize the different inter-object relationships, as well as the particular locality of each element separately. The significant advantage of this new method over two previous approaches in terms of accuracy has been successfully verified for the particular case of 3D subcortical brain structures.

The accurate segmentation of subcortical brain structures in magnetic resonance (MR) images is of crucial importance in the interdisciplinary field of medical imaging. Although statistical approaches such as active shape models (ASMs) have proven to be particularly useful in the modeling of multiobject shapes, they are inefficient when facing challenging problems. Based on the wavelet transform, the fully generic multiresolution framework presented in this paper allows us to decompose the interobject relationships into different levels of detail. The aim of this hierarchical decomposition is twofold: to efficiently characterize the relationships between objects and their particular localities. Experiments performed on an eight-object structure defined in axial cross sectional MR brain images show that the new hierarchical segmentation significantly improves the accuracy of the segmentation, and while it exhibits a remarkable robustness with respect to the size of the training set.

Abundant research finds that in young adults explicit learning (EL) is more dependent on the medial temporal lobes (MTL) whereas implicit learning (IL) is more dependent on the striatum. Using fMRI, we investigated age differences in each task and whether this differentiation is preserved in older adults. Results indicated that, while young recruited the MTL for EL and striatum for IL, both activations were significantly reduced in older adults. Additionally, results indicated that older adults recruited the MTL for IL, and this activation was significantly greater in older compared with young adults. A significant Task × Age interaction was found in both regions-with young preferentially recruiting the MTL for EL and striatum for IL, and older adults showing no preferential recruit for either task. Finally, young adults demonstrated significant negative correlations between activity in the striatum and MTL during both the EL and IL tasks. These correlations were attenuated in older adults. Taken together results support dedifferentiation in aging across memory systems., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Self-projection, the capacity to re-experience the personal past and to mentally infer another person's perspective, has been linked to medial prefrontal cortex (mPFC). In particular, ventral mPFC is associated with inferences about one's own self, whereas dorsal mPFC is associated with inferences about another individual. In the present fMRI study, we examined self-projection using a novel camera technology, which employs a sensor and timer to automatically take hundreds of photographs when worn, in order to create dynamic visuospatial cues taken from a first-person perspective. This allowed us to ask participants to self-project into the personal past or into the life of another person. We predicted that self-projection to the personal past would elicit greater activity in ventral mPFC, whereas self-projection of another perspective would rely on dorsal mPFC. There were three main findings supporting this prediction. First, we found that self-projection to the personal past recruited greater ventral mPFC, whereas observing another person's perspective recruited dorsal mPFC. Second, activity in ventral versus dorsal mPFC was sensitive to parametric modulation on each trial by the ability to relive the personal past or to understand another's perspective, respectively. Third, task-related functional connectivity analysis revealed that ventral mPFC contributed to the medial temporal lobe network linked to memory processes, whereas dorsal mPFC contributed to the fronto-parietal network linked to controlled processes. In sum, these results suggest that ventral-dorsal subregions of the anterior midline are functionally dissociable and may differentially contribute to self-projection of self versus other.

Emotional events tend to be better remembered than non-emotional events. One goal of cognitive and affective neuroscientists is to understand the neural mechanisms underlying this enhancing effect of emotion on memory. A method that has proven particularly influential in the investigation of the memory-enhancing effect of emotion is the so-called subsequent memory paradigm (SMP). This method was originally used to investigate the neural correlates of non-emotional memories, and more recently we and others also applied it successfully to studies of emotional memory (reviewed in). Here, we describe a protocol that allows investigation of the neural correlates of the memory-enhancing effect of emotion using the SMP in conjunction with event-related functional magnetic resonance imaging (fMRI). An important feature of the SMP is that it allows separation of brain activity specifically associated with memory from more general activity associated with perception. Moreover, in the context of investigating the impact of emotional stimuli, SMP allows identification of brain regions whose activity is susceptible to emotional modulation of both general/perceptual and memory-specific processing. This protocol can be used in healthy subjects, as well as in clinical patients where there are alterations in the neural correlates of emotion perception and biases in remembering emotional events, such as those suffering from depression and post-traumatic stress disorder (PTSD)., (Copyright © 2011 Journal of Visualized Experiments)

Recent functional neuroimaging evidence suggests a bottleneck between learning new information and remembering old information. In two behavioral experiments and one functional MRI (fMRI) experiment, we tested the hypothesis that learning and remembering compete when both processes happen within a brief period of time. In the first behavioral experiment, participants intentionally remembered old words displayed in the foreground, while incidentally learning new scenes displayed in the background. In line with a memory competition, we found that remembering old information was associated with impaired learning of new information. We replicated this finding in a subsequent fMRI experiment, which showed that this behavioral effect was coupled with a suppression of learning-related activity in visual and medial temporal areas. Moreover, the fMRI experiment provided evidence that left mid-ventrolateral prefrontal cortex is involved in resolving the memory competition, possibly by facilitating rapid switching between learning and remembering. Critically, a follow-up behavioral experiment in which the background scenes were replaced with a visual target detection task provided indications that the competition between learning and remembering was not merely due to attention. This study not only provides novel insight into our capacity to learn and remember, but also clarifies the neural mechanisms underlying flexible behavior., Competing Interests: Competing interests. The authors have declared that no competing interests exist.

Aging is associated with preserved enhancement of emotional memory, as well as with age-related reductions in memory for negative stimuli, but the neural networks underlying such alterations are not clear. We used a subsequent-memory paradigm to identify brain activity predicting enhanced emotional memory in young and older adults. Activity in the amygdala predicted enhanced emotional memory, with subsequent-memory activity greater for negative stimuli than for neutral stimuli, across age groups, a finding consistent with an overall enhancement of emotional memory. However, older adults recruited greater activity in anterior regions and less activity in posterior regions in general for negative stimuli that were subsequently remembered. Functional connectivity of the amygdala with the rest of the brain was consistent with age-related reductions in memory for negative stimuli: Older adults showed decreased functional connectivity between the amygdala and the hippocampus, but increased functional connectivity between the amygdala and dorsolateral prefrontal cortices. These findings suggest that age-related differences in the enhancement of emotional memory might reflect decreased connectivity between the amygdala and typical subsequent-memory regions, as well as the engagement of regulatory processes that inhibit emotional responses.

According to the consolidation hypothesis, enhanced memory for emotional information reflects the modulatory effect of the amygdala on the medial temporal lobe (MTL) memory system during consolidation. Although there is evidence that amygdala-MTL connectivity enhances memory for emotional stimuli, it remains unclear whether this enhancement increases over time, as consolidation processes unfold. To investigate this, we used functional magnetic resonance imaging to measure encoding activity predicting memory for emotionally negative and neutral pictures after short (20-min) versus long (1-week) delays. Memory measures distinguished between vivid remembering (recollection) and feelings of knowing (familiarity). Consistent with the consolidation hypothesis, the persistence of recollection over time (long divided by short) was greater for emotional than neutral pictures. Activity in the amygdala predicted subsequent memory to a greater extent for emotional than neutral pictures. Although this advantage did not vary with delay, the contribution of amygdala-MTL connectivity to subsequent memory for emotional items increased over time. Moreover, both this increase in connectivity and amygdala activity itself were correlated with individual differences in recollection persistence for emotional but not neutral pictures. These results suggest that the amygdala and its connectivity with the MTL are critical to sustaining emotional memories over time, consistent with the consolidation hypothesis.

A consistent finding from functional neuroimaging studies of cognitive aging is an age-related reduction in occipital activity coupled with increased frontal activity. This posterior-anterior shift in aging (PASA) has been typically attributed to functional compensation. The present functional magnetic resonance imaging sought to 1) confirm that PASA reflects the effects of aging rather than differences in task difficulty; 2) test the compensation hypothesis; and 3) investigate whether PASA generalizes to deactivations. Young and older participants were scanned during episodic retrieval and visual perceptual tasks, and age-related changes in brain activity common to both tasks were identified. The study yielded 3 main findings. First, inconsistent with a difficulty account, the PASA pattern was found across task and confidence levels when matching performance among groups. Second, supporting the compensatory hypothesis, age-related increases in frontal activity were positively correlated with performance and negatively correlated with the age-related occipital decreases. Age-related increases and correlations with parietal activity were also found. Finally, supporting the generalizability of the PASA pattern to deactivations, aging reduced deactivations in posterior midline cortex but increased deactivations in medial frontal cortex. Taken together, these findings demonstrate the validity, function, and generalizability of PASA, as well as its importance for the cognitive neuroscience of aging.

Compared to young, older adults are more likely to forget events that occurred in the past as well as remember events that never happened. Previous studies examining false memories and aging have shown that these memories are more likely to occur when new items share perceptual or semantic similarities with those presented during encoding. It is theorized that decreased item-specific encoding and increased gist encoding contribute to these age differences in memory performance. The current study used a modified version of the Deese-Roediger-McDermott (DRM) paradigm to investigate the neural correlates of true and false memory encoding. Results indicated that, compared to young, older adults showed reduced activity in medial temporal lobes (MTL), left ventrolateral prefrontal cortex (VLPFC), and visual cortices associated with subsequent true memories. Despite these decreases older adults showed increased activity in right VLPFC and left superior temporal gyrus (STG) for subsequent true memories. Age-related increases in STG were also associated with subsequent false memories. Results support the theory that older adults engage in less item-specific encoding and greater gist encoding, and that these increases in gist encoding support both subsequent true and false memories. Furthermore, results extend findings of reduced frontal asymmetry in aging, often found in block designs, to the subsequent memory paradigm. Results suggest that greater bilateral frontal activity during encoding in aging are not just task-related, but may be associated with subsequent successful memory performance.

The present study aimed to delineate the extent to which unitary executive functions might be shared across the separate domains of episodic and working memory. A mixed blocked/event-related functional magnetic resonance imaging (fMRI) design was employed to assess sustained (tonic control) and transient (phasic control) brain responses arising from incrementing executive demand (source versus item episodic memory - vis-à-vis - two-back versus one-back working memory) using load-dependent activation overlaps as indices of common components. Although an extensive portion of the regional load effects constituted differential control modulations in both sustained and transient responses, commonalities were also found implicating a subset of executive core mechanisms consistent with unitary or domain general control. 'Unitary' control modulations were temporally dissociated into (1) shared tonic components involving medial and lateral prefrontal cortex, striatum, cerebellum and superior parietal cortex, assumed to govern enhanced top-down context processing, monitoring and sustained attention throughout task periods and (2) stimulus-synchronous phasic components encompassing posterior intraparietal sulcus, hypothesized to support dynamic shifting of the 'focus of attention' among internal representations. Taken together, these results converge with theoretical models advocating both unity and diversity among executive control processes.

Regulatory focus theory [Higgins, E. T. Beyond pleasure and pain. American Psychologist, 52, 1280-1300, 1997] postulates two social-cognitive motivational systems, the promotion and prevention systems, for self-regulation of goal pursuit. However, the neural substrates of promotion and prevention goal activation remain unclear. Drawing on several literatures, we hypothesized that priming promotion versus prevention goals would activate areas in the left versus right prefrontal cortex (PFC), respectively, and that activation in these areas would be correlated with individual differences in chronic regulatory focus. Sixteen participants underwent functional magnetic resonance imaging while engaged in a depth-of-processing task, during which they were exposed incidentally to their own promotion and prevention goals. Task-related cortical activation was consistent with previous studies. At the same time, incidental priming of promotion goals was associated with left orbital PFC activation, and activation in this area was stronger for individuals with a chronic promotion focus. Findings regarding prevention goal priming were not consistent with predictions. The data illustrate the centrality of self-regulation and personal goal pursuit within the multilayered process of social cognition.

Functional neuroimaging studies of autobiographical memory have grown dramatically in recent years. These studies are important because they can investigate the neural correlates of processes that are difficult to study using laboratory stimuli, including: (i) complex constructive processes, (ii) recollective qualities of emotion and vividness, and (iii) remote memory retrieval. Constructing autobiographical memories involves search, monitoring and self-referential processes that are associated with activity in separable prefrontal regions. The contributions of emotion and vividness have been linked to the amygdala and visual cortex respectively. Finally, there is evidence that recent and remote autobiographical memories might activate the hippocampus equally, which has implications for memory-consolidation theories. The rapid development of innovative methods for eliciting personal memories in the scanner provides the opportunity to delve into the functional neuroanatomy of our personal past.

We combined measures from event-related functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and cognitive performance (visual search response time) to test the hypotheses that differences between younger and older adults in top-down (goal-directed) attention would be related to cortical activation, and that white matter integrity as measured by DTI (fractional anisotropy, FA) would be a mediator of this age-related effect. Activation in frontal and parietal cortical regions was overall greater for older adults than for younger adults. The relation between activation and search performance supported the hypothesis of age differences in top-down attention. When the task involved top-down control (increased target predictability), performance was associated with frontoparietal activation for older adults, but with occipital (fusiform) activation for younger adults. White matter integrity (FA) exhibited an age-related decline that was more pronounced for anterior brain regions than for posterior regions, but white matter integrity did not specifically mediate the age-related increase in activation of the frontoparietal attentional network.

Using event-related functional magnetic resonance imaging, we identified brain regions involved in successful relational memory (RM) during encoding and retrieval for semantic and perceptual associations or in general, independent of phase and content. Participants were scanned while encoding and later retrieving associations between pairs of words (semantic RM) or associations between words and fonts (perceptual RM). Encoding success activity (ESA) was identified by comparing study-phase activity for items subsequently remembered (hits) versus forgotten (misses) and retrieval success activity (RSA) by comparing test-phase activity for hits versus misses. The study yielded three main sets of findings. First, ESA-RSA differences were found within the medial temporal lobes (MTLs) and within the prefrontal cortex (PFC). Within the left MTL, ESA was greater in the anterior hippocampus, and RSA was greater in the posterior parahippocampal cortex/hippocampus. This finding is consistent with the notion of an encoding-retrieval gradient along the longitudinal MTL axis. Within the left PFC, ESA was greater in ventrolateral PFC, and RSA was greater in dorsolateral and anterior PFC. This is the first evidence of a dissociation in successful encoding and retrieval activity within left PFC. Second, consistent with the transfer-appropriate processing principle, some ESA regions were reactivated during RSA in a content-specific manner. For semantic RM, these regions included the left ventrolateral PFC, whereas for perceptual RM, they included occipitoparietal and right parahippocampal regions. Finally, only one region in the entire brain was associated with RM in general (i.e., for both semantic and perceptual ESA and RSA): the left hippocampus. This finding highlights the fundamental role of the hippocampus in RM.

Prefrontal cortex (PFC) activity associated with emotional evaluation and subsequent memory was investigated with event-related functional MRI (fMRI). Participants were scanned while rating the pleasantness of emotionally positive, negative, and neutral pictures, and memory for the pictures was tested after scanning. Emotional evaluation was measured by comparing activity during the picture rating task relative to baseline, and successful encoding was measured by comparing activity for subsequently remembered versus forgotten pictures (Dm effect). The effect of arousal on these measures was indicated by greater activity for both positive and negative pictures than for neutral ones, and the effect of valence was indicated by differences in activity between positive and negative pictures. The study yielded three main results. First, consistent with the valence hypothesis, specific regions in left dorsolateral PFC were more activated for positive than for negative picture evaluation, whereas regions in right ventrolateral PFC showed the converse pattern. Second, dorsomedial PFC activity was sensitive to emotional arousal, whereas ventromedial PFC activity was sensitive to positive valence, consistent with evidence linking these regions, respectively, to emotional processing and self-awareness or appetitive behavior. Finally, successful encoding (Dm) activity in left ventrolateral and dorsolateral PFC was greater for arousing than for neutral pictures. This finding suggests that the enhancing effect of emotion on memory formation is partly due to an augmentation of PFC-mediated strategic, semantic, and working memory operations. These results underscore the critical role of PFC in emotional evaluation and memory, and disentangle the effects of arousal and valence across PFC regions associated with different cognitive functions.

Whereas some older adults show significant cognitive deficits, others perform as well as young adults. We investigated the neural basis of these different aging patterns using positron emission tomography (PET). In PET and functional MRI (fMRI) studies, prefrontal cortex (PFC) activity tends to be less asymmetric in older than in younger adults (Hemispheric Asymmetry Reduction in Old Adults or HAROLD). This change may help counteract age-related neurocognitive decline (compensation hypothesis) or it may reflect an age-related difficulty in recruiting specialized neural mechanisms (dedifferentiation hypothesis). To compare these two hypotheses, we measured PFC activity in younger adults, low-performing older adults, and high-performing older adults during recall and source memory of recently studied words. Compared to recall, source memory was associated with right PFC activations in younger adults. Low-performing older adults recruited similar right PFC regions as young adults, but high-performing older adults engaged PFC regions bilaterally. Thus, consistent with the compensation hypothesis and inconsistent with the dedifferentiation hypothesis, a hemispheric asymmetry reduction was found in high-performing but not in low-performing older adults. The results suggest that low-performing older adults recruited a similar network as young adults but used it inefficiently, whereas high-performing older adults counteracted age-related neural decline through a plastic reorganization of neurocognitive networks.

By revealing how brain activity during cognitive performance changes as a function of aging, studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are contributing to the development of a new discipline of Cognitive Neuroscience of Aging. This article reviews functional neuroimaging studies of cognitive aging in the domains of visual perception, episodic memory encoding and semantic memory retrieval, episodic memory retrieval, implicit memory, and working memory. The most consistent finding of these studies was that brain activity tends to be less lateralized in older adults than in younger adults. This finding is conceptualized in terms of a model called Hemispheric Asymmetry Reduction in Old Adults (HAROLD). According to a compensation hypothesis, bihemispheric involvement could help counteract age-related neurocognitive decline, whereas, according to a dedifferentiation hypothesis, it reflects a difficulty in recruiting specialized neural mechanisms.

Positron emission tomography and functional magnetic resonance imaging studies have identified brain regions associated with different forms of memory. Working memory has been associated primarily with the bilateral prefrontal and parietal regions; semantic memory with the left prefrontal and temporal regions; episodic memory encoding with the left prefrontal and medial temporal regions; episodic memory retrieval with the right prefrontal, posterior midline and medial temporal regions; and skill learning with the motor, parietal, and subcortical regions. Recent studies have provided higher specificity, by dissociating the neural correlates of different subcomponents of complex memory tasks, and the cognitive roles of different subregions of larger brain areas.

Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have been extensively used to explore the functional neuroanatomy of cognitive functions. Here we review 275 PET and fMRI studies of attention (sustained, selective, Stroop, orientation, divided), perception (object, face, space/motion, smell), imagery (object, space/motion), language (written/spoken word recognition, spoken/no spoken response), working memory (verbal/numeric, object, spatial, problem solving), semantic memory retrieval (categorization, generation), episodic memory encoding (verbal, object, spatial), episodic memory retrieval (verbal, nonverbal, success, effort, mode, context), priming (perceptual, conceptual), and procedural memory (conditioning, motor, and nonmotor skill learning). To identify consistent activation patterns associated with these cognitive operations, data from 412 contrasts were summarized at the level of cortical Brodmann's areas, insula, thalamus, medial-temporal lobe (including hippocampus), basal ganglia, and cerebellum. For perception and imagery, activation patterns included primary and secondary regions in the dorsal and ventral pathways. For attention and working memory, activations were usually found in prefrontal and parietal regions. For language and semantic memory retrieval, typical regions included left prefrontal and temporal regions. For episodic memory encoding, consistently activated regions included left prefrontal and medial temporal regions. For episodic memory retrieval, activation patterns included prefrontal, medial temporal, and posterior midline regions. For priming, deactivations in prefrontal (conceptual) or extrastriate (perceptual) regions were consistently seen. For procedural memory, activations were found in motor as well as in non-motor brain areas. Analysis of regional activations across cognitive domains suggested that several brain regions, including the cerebellum, are engaged by a variety of cognitive challenges. These observations are discussed in relation to functional specialization as well as functional integration.