Neuroanatomical and cognitive mediators of age-related differences in episodic memory

Aging is associated with declines in episodic memory. In this study, the authors used a path analysis framework to explore the mediating role of differences in brain structure, executive functions, and processing speed in age-related differences in episodic memory. Measures of regional brain volume (prefrontal gray and white matter, caudate, hippocampus, visual cortex), executive functions (working memory, inhibitory control, task switching, temporal processing), processing speed, and episodic memory were obtained in a sample of young and older adults. As expected, age was linked to reduction in regional brain volumes and cognitive performance. Moreover, neural and cognitive factors completely mediated age differences in episodic memory. Whereas hippocampal shrinkage directly affected episodic memory, prefrontal volumetric reductions influenced episodic memory via limitations in working memory and inhibitory control. Age-related slowing predicted reduced efficiency in temporal processing, working memory, and inhibitory control. Lastly, poorer temporal processing directly affected episodic memory. No direct effects of age on episodic memory remained once these factors were taken into account. These analyses highlight the value of a multivariate approach with the understanding of complex relationships in cognitive and brain aging.     

Working memory and preparation elicit different patterns of slow wave event-related brain potentials

Some event-related brain potential (ERP) studies of working memory have used delayed match-to-sample designs in which a stimulus (S1) is held in memory for comparison with a subsequent stimulus (S2). During the S1-S2 interval, ERP slow negativities varied with both the type and amount of material held in working memory. One interpretation is that these slow waves index working memory operations. An alternative explanation is that they only reflect general preparatory processing for the response to S2. To decide between these explanations, we used two visual processing tasks that required similar preparation for S2. In one task, visual memory rehearsal operations were required. During the S1-S2 interval, there were clear differences between the amplitudes, topographies, and the effect of information load on the slow waves in the two tasks, thus ruling out preparation only as an explanation.     

Responses of neurons in the inferior temporal cortex in short term and serial recognition memory tasks

Summary Gaffan and Weiskrantz (1980) and Mishkin (1982) have shown that lesions to the inferior temporal visual cortex can impair the performance of serial visual recognition memory tasks. In order to provide evidence on whether the inferior temporal visual cortex contains a mechanism which enables memory to span the intervening items in a serial recognition task, or whether the inferior temporal cortex is merely afferent to such recent memory mechanisms, we analysed the activity of single neurons in the inferior temporal visual cortex and the adjacent cortex in the superior temporal sulcus in both delayed match to sample and serial recognition memory tasks. In the serial recognition task, various numbers of stimuli intervened between the first and second presentations of a stimulus. A considerable proportion (64/264 or 26%) of visually responsive inferotemporal neurons showed a different response to the novel and familiar presentations of a stimulus in the serial recognition memory task, and often a corresponding difference in response between the sample and match presentations of a stimulus in the delayed match to sample task. For the majority of neurons this difference was not sustained across even one intervening stimulus in the serial recognition task, and no neurons bridged more than 2 intervening stimuli. These results show that neurons in the inferior temporal cortex have responses which would be useful for a short term visual memory for stimuli, but would not be useful in recency memory tasks in which more than one stimulus intervenes between the first and second presentations of a stimulus. In this investigation, neurons were recorded both in the cortex on the inferior temporal gyrus (commonly called inferior temporal visual cortex, and consisting of areas TE3,TE2 and TE1 of Seltzer and Pandya 1978), and in the cortex in the adjacent anterior part of the superior temporal sulcus, in which a number of different temporal cortical visual areas have now been described (see Baylis et al. 1986).     

Primate rhinal cortex participates in both visual recognition and working memory tasks: functional mapping with 2-DG

The rhinal cortex in the medial temporal lobe has been implicated in object recognition memory tasks and indeed is considered to be the critical node in a visual memory network. Previous studies using the 2-deoxyglucose method have shown that thalamic and hippocampal structures thought to be involved in visual recognition memory are also engaged by spatial and object working memory tasks in the nonhuman primate. Networks engaged in memory processing can be recognized by analysis of patterns of activation accompanying performance of specifically designed tasks. In the present study, we compared metabolic activation of the entorhinal and perirhinal cortex during the performance of three working memory tasks [delayed response (DR), delayed alternation (DA), and delayed object alternation (DOA)] to that induced by a standard recognition memory task [delayed match-to-sample (DMS)] and a sensorimotor control task in rhesus monkeys. A region-of-interest analysis revealed elevated local cerebral glucose utilization in the perirhinal cortex in animals performing the DA, DOA, and DMS tasks, and animals performing the DMS task were distinct in showing a strong focus of activation in the lateral perirhinal cortex. No significant differences were evident between groups performing memory and control tasks in the entorhinal cortex. These findings suggest that the perirhinal cortex may play a much broader role in memory processing than has been previously thought, encompassing explicit working memory as well as recognition memory.     

Aging effects on selective attention-related electroencephalographic patterns during face encoding

Previous electrophysiological studies revealed that human faces elicit an early visual event-related potential (ERP) within the occipito–temporal cortex, the N170 component. Although face perception has been proposed to rely on automatic processing, the impact of selective attention on N170 remains controversial both in young and elderly individuals. Using early visual ERP and alpha power analysis, we assessed the influence of aging on selective attention to faces during delayed-recognition tasks for face and letter stimuli, examining 36 elderly and 20 young adults with preserved cognition. Face recognition performance worsened with age. Aging induced a latency delay of the N1 component for faces and letters, as well as of the face N170 component. Contrasting with letters, ignored faces elicited larger N1 and N170 components than attended faces in both age groups. This counterintuitive attention effect on face processing persisted when scenes replaced letters. In contrast with young, elderly subjects failed to suppress irrelevant letters when attending faces. Whereas attended stimuli induced a parietal alpha band desynchronization within 300–1000 ms post-stimulus with bilateral-to-right distribution for faces and left lateralization for letters, ignored and passively viewed stimuli elicited a central alpha synchronization larger on the right hemisphere. Aging delayed the latency of this alpha synchronization for both face and letter stimuli, and reduced its amplitude for ignored letters. These results suggest that due to their social relevance, human faces may cause paradoxical attention effects on early visual ERP components, but they still undergo classical top–down control as a function of endogenous selective attention. Aging does not affect the face bottom–up alerting mechanism but reduces the top–down suppression of distracting letters, possibly impinging upon face recognition, and more generally delays the top–down suppression of task-irrelevant information.     

Prefrontal cortex and working memory processes

Working memory is a mechanism for short-term active maintenance of information as well as for processing maintained information. The dorsolateral prefrontal cortex has been known to participate in working memory. The analysis of task-related dorsolateral prefrontal cortex activity while monkeys performed a variety of working memory tasks revealed that delay-period activity is a neural correlate of a mechanism for temporary active maintenance of information, because this activity persisted throughout the delay period, showed selectivity to a particular visual feature, and was related to correct behavioral performances. Information processing can be considered as a change of the information represented by a population of neural activities during the progress of the trial. Using population vectors calculated by a population of task-related dorsolateral prefrontal cortex activities, we demonstrated the temporal change of information represented by a population of dorsolateral prefrontal cortex activities during performances of spatial working memory tasks. Cross-correlation analysis using spike firings of simultaneously isolated pairs of neurons reveals widespread functional interactions among neighboring neurons, especially neurons having delay-period activity, and their dynamic modulation depending on the context of the trial. Functional interactions among neurons and their dynamic modulation could be a mechanism of information processing in the dorsolateral prefrontal cortex.     

Age related changes in emotional memory

Studies have found that emotionally evocative stimuli are better remembered than neutral stimuli, an effect called "emotional enhancement". Researchers have also found that the elderly experience an overall decline in memory relative to the young. We hypothesized that the elderly may experience diminished emotional enhancement, and that this may be one factor contributing to overall memory decline in the elderly. We tested elderly and young subjects on tasks of emotional memory for words and faces. In both the elderly and young, a shift in memory favoring positive stimuli (as opposed to negative and neutral stimuli) was evident, this effect being slightly more marked in the elderly. We suggest that the effects seen in both groups may be due to a shift from the amygdala-hippocampal system to the prefrontal cortex over time. We suggest that the more marked response in the elderly may be due to age-related changes in these brain systems, causing a further shift towards memory for positive material.     

Executive functions and neurocognitive aging: dissociable patterns of brain activity

Studies of neurocognitive aging report altered patterns of brain activity in older versus younger adults performing executive function tasks. We review the extant literature, using activation likelihood estimation meta-analytic methods, to compare age-related differences in the pattern of brain activity across studies examining 2 categories of tasks associated with executive control processing: working memory and inhibition. In a direct contrast of young and older adult activations, older adults engaged bilateral regions of dorsolateral prefrontal cortex as well as supplementary motor cortex and left inferior parietal lobule during working memory. In contrast, age-related changes during inhibitory control were observed in right inferior frontal gyrus and presupplementary motor area. Additionally, when we examined task-related differences within each age group we observed the predicted pattern of differentiated neural response in the younger subjects: lateral prefrontal cortex activity associated with working memory versus right anterior insula/frontal opercular activity associated with inhibition. This separation was largely maintained in older subjects. These data provide the first quantitative meta-analytic evidence that age-related patterns of functional brain change during executive functioning depend on the specific control process being challenged.     

Out of sight but not out of mind: the neurophysiology of iconic memory in the superior temporal sulcus

Iconic memory, the short-lasting visual memory of a briefly flashed stimulus, is an important component of most models of visual perception. Here we investigate what physiological mechanisms underlie this capacity by showing rapid serial visual presentation (RSVP) sequences with and without interstimulus gaps to human observers and macaque monkeys. For gaps of up to 93 ms between consecutive images, human observers and neurones in the temporal cortex of macaque monkeys were found to continue processing a stimulus as if it was still present on the screen. The continued firing of neurones in temporal cortex may therefore underlie iconic memory. Based on these findings, a neurophysiological vision of iconic memory is presented.     

Processing of auditory and visual location information in the monkey prefrontal cortex

Visuospatial working memory mechanisms have been studied extensively at single cell level in the dorsolateral prefrontal cortex (PFCd) in nonhuman primates. Despite the importance of short-term memory of sound location for behavioral orientation, there are only a few studies on auditory spatial working memory. The purpose of this study was to investigate neuronal mechanisms underlying working memory processing of auditory and visual location information at single cell level in the PFCd. Neuronal activity was recorded in monkeys performing a delayed matching-to-sample task (DMTS). The location of a visual or auditory stimulus was used as a memorandum. The majority of the neurons that were activated during presentation of the cue memorandum were selective either for visual or auditory spatial information. A small group of cue related bimodal neurons were sensitive to the location of the cue regardless of whether the stimulus was visual or auditory, suggesting modality independent processing of spatial information at cellular level in the PFCd. Most neurons that were activated during the delay period were modality specific, responding either during visual or auditory trials. All bimodal delay related neurons that responded during both visual and auditory trials were spatially nonselective. The results of the present study suggest that in addition to the modality specific parallel mechanism, working memory of auditory and visual space also involves modality independent processing at cellular level in the PFCd.     

Spatio-temporal Modeling of Evoked Brain Activity During Memory Encoding and Target Comparison in Visual Tasks

In this paper, the temporal pattern of activity and approximate locations of brain areas related to selective attention and visual working memory processes were studied with event related potential (ERP) recordings in healthy humans. Three experimental series included pairs of the following conditions: Face comparison (familiar faces), Pattern comparison (abstract dot patterns), and Passive viewing. Participants compared pairs of consecutive targets presented in composite images on a computer screen. Spatio-temporal multiple dipole models were developed for 128-channel ERPs. Keeping dipole locations and orientations constant, we compared the source activities for ERPs recorded (1) in different tasks for task-specificity of activations, (2) after the first and second stimuli in the pair, i.e. on the encoding and comparison stages of the task, and (3) after the first stimulus in different series to compare encoding in different conditions. Sources located in the inferotemporal brain areas, especially in the left hemisphere, showed increased activity after 200 ms from the first stimulus onset that may indicate encoding into visual working memory. The anterior sources, located near midline and showing activity around or after 300 ms, presumably reflect non-specific memory processes and attentional control. Major task-specific differences were observed in the temporo-parieto-occipital region in 250–500 ms.     

Neural correlates of spatial working memory in humans: a functional magnetic resonance imaging study comparing visual and tactile processes

Recent studies of neural correlates of working memory components have identified both low-level perceptual processes and higher-order supramodal mechanisms through which sensory information can be integrated and manipulated. In addition to the primary sensory cortices, working memory relies on a widely distributed neural system of higher-order association areas that includes posterior parietal and occipital areas, and on prefrontal cortex for maintaining and manipulating information. The present study was designed to determine brain patterns of neural response to the same spatial working memory task presented either visually or in a tactile format, and to evaluate the relationship between spatial processing in the visual and tactile sensory modalities. Brain activity during visual and tactile spatial working memory tasks was measured in six young right-handed healthy male volunteers by using functional magnetic resonance imaging. Results indicated that similar fronto-parietal networks were recruited during spatial information processing across the two sensory modalities-specifically the posterior parietal cortex, the dorsolateral prefrontal cortex and the anterior cingulate cortex. These findings provide a neurobiological support to behavioral observations by indicating that common cerebral regions subserve generation of higher order mental representations involved in working memory independently from a specific sensory modality.     

Spatial reference and working memory across the lifespan of male Fischer 344 rats

Loss of mnemonic function is among the earliest and most disconcerting consequences of the aging process. This study was designed to provide a comprehensive profile of spatial mnemonic abilities in male Fischer 344 (F344) rats across the lifespan. Young, middle-aged, and aged F344 rats were trained in spatial reference and working memory versions of the water maze task. There was a progressive age-related decline in spatial reference memory across the lifespan. Reliable individual differences were observed among aged rats, with some aged rats performing as well as young cohorts and others performing outside this range. An age-related delay-dependent decline was observed on a working memory version of the water maze task although no relationship between performance on reference and working memory tasks was present. Notably, middle-aged rats were impaired relative to young on both tasks. Together these data demonstrate that individual differences in spatial reference memory exist among aged F344 rats and provide novel data demonstrating an unrelated decline in working memory across the lifespan, suggesting that age-related mnemonic dysfunction may occur across multiple brain systems.     

Links between multisensory processing and autism

Autism spectrum disorder is typically associated with social deficits and is often specifically linked to difficulty with processing faces and other socially relevant stimuli. Emerging research has suggested that children with autism might also have deficits in basic perceptual abilities including multisensory processing (e.g., simultaneously processing visual and auditory inputs). The current study examined the relationship between multisensory temporal processing (assessed via a simultaneity judgment task wherein participants were to report whether a visual stimulus and an auditory stimulus occurred at the same time or at different times) and self-reported symptoms of autism (assessed via the Autism Spectrum Quotient questionnaire). Data from over 100 healthy adults revealed a relationship between these two factors as multisensory timing perception correlated with symptoms of autism. Specifically, a stronger bias to perceive auditory stimuli occurring before visual stimuli as simultaneous was associated with greater levels of autistic symptoms. Additional data and analyses confirm that this relationship is specific to multisensory processing and symptoms of autism. These results provide insight into the nature of multisensory processing while also revealing a continuum over which perceptual abilities correlate with symptoms of autism and that this continuum is not just specific to clinical populations but is present within the general population.     

Behind the scenes: How visual memory load biases selective attention during processing of visual streams

We recorded ERPs to investigate whether the visual memory load can bias visual selective attention. Participants memorized one or four letters and then responded to memory‐matching letters presented in a relevant color while ignoring distractor letters or letters in an irrelevant color. Stimuli in the relevant color elicited larger frontal selection positivities (FSP) and occipital selection negativities (OSN) compared to irrelevant color stimuli. Only distractors elicited a larger FSP in the high than in the low memory load task. Memory load prolonged the OSN for all letters. Response mapping complexity was also modulated but did not affect the FSP and OSN. Together, the FSP data suggest that high memory load increased distractability. The OSN data suggest that memory load sustained attention to letters in a relevant color until working memory processing was completed, independently of whether the letters were in working memory or not.     

Priming of two-dimensional visual motion is reduced in older adults

Previously, Y. Jiang, P. Greenwood, and R. Parasuraman (1999) reported that priming of rotating three-dimensional visual objects is age sensitive. The current study investigated whether there is also an age-related difference in priming with simple two-dimensional (2-D) moving stimuli (i.e., whether a prime stimulus moving in a particular direction causes a subsequent ambiguous target stimulus to be seen moving in the same direction as the prime). In 2 experiments, younger and older adults judged the directions of moving sine-wave gratings. Groups differed neither in determining the direction of a single 2-D movement nor in detecting motion reversals in successively moving gratings. However, the older group showed a significant reduction in the extent of 2-D motion priming. The decrement in older adults for visual motion priming may reflect age-related changes in temporal processing in human visual cortex.     

EEG-power and -coherence changes in a unimodal and a crossmodal working memory task with visual and kinesthetic stimuli

We investigated EEG-power and EEG-coherence changes in a unimodal and a crossmodal matching-to-sample working memory task with either visual or kinesthetic stimuli. Angle-shaped trajectories were used as stimuli presented either as a moving dot on a screen or as a passive movement of a haptic device. Effects were evaluated during the different phases of encoding, maintenance, and recognition. Alpha power was modulated during encoding by the stimulus modality, and in crossmodal conditions during encoding and maintenance by the expected modality of the upcoming test stimulus. These power modulations were observed over modality-specific cortex regions. Systematic changes of coherence for crossmodal compared to unimodal tasks were not observed during encoding and maintenance but only during recognition. There, coherence in the theta-band increased between electrode sites over left central and occipital cortex areas in the crossmodal compared to the unimodal conditions. The results underline the importance of modality-specific representations and processes in unimodal and crossmodal working memory tasks. Crossmodal recognition of visually and kinesthetically presented object features seems to be related to a direct interaction of somatosensory/motor and visual cortex regions by means of long-range synchronization in the theta-band and such interactions seem to take place at the beginning of the recognition phase, i.e. when crossmodal transfer is actually necessary.     

Category-specific visual responses of single neurons in the human medial temporal lobe

The hippocampus, amygdala and entorhinal cortex receive convergent input from temporal neocortical regions specialized for processing complex visual stimuli and are important in the representation and recognition of visual images. Recording from 427 single neurons in the human hippocampus, entorhinal cortex and amygdala, we found a remarkable degree of category-specific firing of individual neurons on a trial-by-trial basis. Of the recorded neurons, 14% responded selectively to visual stimuli from different categories, including faces, natural scenes and houses, famous people and animals. Based on the firing rate of individual neurons, stimulus category could be predicted with a mean probability of error of 0.24. In the hippocampus, the proportion of neurons responding to spatial layouts was greater than to other categories. Our data provide direct support for the role of human medial temporal regions in the representation of different categories of visual stimuli.     

The role of ventral and orbital prefrontal cortex in conditional visuomotor learning and strategy use in rhesus monkeys (Macaca mulatta)

Four rhesus monkeys (Macaca mulatta) were trained to learn novel sets of visuomotor associations in 50 trials or less, within single test sessions. After bilateral ablation of the orbital and ventral prefrontal cortex, the monkeys lost the ability to learn these associations within a session, although they could learn them when given several daily sessions. Thus, relatively slow, across-session visuomotor learning depends on neither the ventral nor orbital prefrontal cortex, but rapid, within-session learning does. The ablations also eliminated at least 2 response strategies, repeat-stay and lose-shift, which might account, in part, for the deficit in rapid learning. The deficit is unlikely to result from a failure of visual discriminative ability or working memory: The monkeys could discriminate similar stimulus material within a session, and reducing the working memory load did not improve within-session learning.     

Overlapping functional anatomy for working memory and visual search

Recent behavioural findings using dual-task paradigms demonstrate the importance of both spatial and non-spatial working memory processes in inefficient visual search (Anderson et al. in Exp Psychol 55:301–312, 2008). Here, using functional magnetic resonance imaging (fMRI), we sought to determine whether brain areas recruited during visual search are also involved in working memory. Using visually matched spatial and non-spatial working memory tasks, we confirmed previous behavioural findings that show significant dual-task interference effects occur when inefficient visual search is performed concurrently with either working memory task. Furthermore, we find considerable overlap in the cortical network activated by inefficient search and both working memory tasks. Our findings suggest that the interference effects observed behaviourally may have arisen from competition for cortical processes subserved by these overlapping regions. Drawing on previous findings (Anderson et al. in Exp Brain Res 180:289–302, 2007), we propose that the most likely anatomical locus for these interference effects is the inferior and middle frontal cortex of the right hemisphere. These areas are associated with attentional selection from memory as well as manipulation of information in memory, and we propose that the visual search and working memory tasks used here compete for common processing resources underlying these mechanisms.