Increased Prefrontal Activity with Aging Reflects Nonspecific Neural Responses Rather than Compensation.

Elevated prefrontal cortex activity is often observed in healthy older adults despite declines in their memory and other cognitive functions. According to one view, this activity reflects a compensatory functional posterior-to-anterior shift, which contributes to maintenance of cognitive performance when posterior cortical function is impaired. Alternatively, the increased prefrontal activity may be less efficient or less specific because of structural and neurochemical changes accompanying aging. These accounts are difficult to distinguish on the basis of average activity levels within brain regions. Instead, we used a novel, model-based multivariate analysis technique applied to two independent fMRI datasets from an adult-lifespan human sample (N = 123 and N = 115; approximately half female). Standard analysis replicated the age-related increase in average prefrontal activation, but multivariate tests revealed that this activity did not carry additional information. The results contradict the hypothesis of a compensatory posterior-to-anterior shift. Instead, they suggest that the increased prefrontal activation reflects reduced efficiency or specificity rather than compensation.SIGNIFICANCE STATEMENT Functional brain imaging studies have often shown increased activity in prefrontal brain regions in older adults. This has been proposed to reflect a compensatory shift to greater reliance on prefrontal cortex (PFC), helping to maintain cognitive function. Alternatively, activity may become less specific as people age. This is a key question in the neuroscience of aging. In this study, we used novel tests of how different brain regions contribute to long- and short-term memory. We found increased activity in PFC in older adults, but this activity carried less information about memory outcomes than activity in visual regions. These findings are relevant for understanding why cognitive abilities decline with age, suggesting that optimal function depends on successful brain maintenance rather than compensation.

Age Differentiation within Gray Matter, White Matter, and between Memory and White Matter in an Adult Life Span Cohort.

It is well established that brain structures and cognitive functions change across the life span. A long-standing hypothesis called "age differentiation" additionally posits that the relations between cognitive functions also change with age. To date, however, evidence for age-related differentiation is mixed, and no study has examined differentiation of the relationship between brain and cognition. Here we use multigroup structural equation models (SEMs) and SEM trees to study differences within and between brain and cognition across the adult life span (18-88 years) in a large (N > 646, closely matched across sexes), population-derived sample of healthy human adults from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.org). After factor analyses of gray matter volume (from T1- and T2-weighted MRI) and white matter organization (fractional anisotropy from diffusion-weighted MRI), we found evidence for the differentiation of gray and white matter, such that the covariance between brain factors decreased with age. However, we found no evidence for age differentiation among fluid intelligence, language, and memory, suggesting a relatively stable covariance pattern among cognitive factors. Finally, we observed a specific pattern of age differentiation between brain and cognitive factors, such that a white matter factor, which loaded most strongly on the hippocampal cingulum, became less correlated with memory performance in later life. These patterns are compatible with the reorganization of cognitive functions in the face of neural decline, and/or with the emergence of specific subpopulations in old age.SIGNIFICANCE STATEMENT The theory of age differentiation posits age-related changes in the relationships among cognitive domains, either weakening (differentiation) or strengthening (dedifferentiation), but evidence for this hypothesis is mixed. Using age-varying covariance models in a large cross-sectional adult life span sample, we found age-related reductions in the covariance among both brain measures (neural differentiation), but no covariance change among cognitive factors of fluid intelligence, language, and memory. We also observed evidence of uncoupling (differentiation) between a white matter factor and cognitive factors in older age, most strongly for memory. Together, our findings support age-related differentiation as a complex, multifaceted pattern that differs for brain and cognition, and discuss several mechanisms that might explain the changing relationship between brain and cognition.

Extrinsic and Intrinsic Brain Network Connectivity Maintains Cognition across the Lifespan Despite Accelerated Decay of Regional Brain Activation.

The maintenance of wellbeing across the lifespan depends on the preservation of cognitive function. We propose that successful cognitive aging is determined by interactions both within and between large-scale functional brain networks. Such connectivity can be estimated from task-free functional magnetic resonance imaging (fMRI), also known as resting-state fMRI (rs-fMRI). However, common correlational methods are confounded by age-related changes in the neurovascular signaling. To estimate network interactions at the neuronal rather than vascular level, we used generative models that specified both the neural interactions and a flexible neurovascular forward model. The networks' parameters were optimized to explain the spectral dynamics of rs-fMRI data in 602 healthy human adults from population-based cohorts who were approximately uniformly distributed between 18 and 88 years (www.cam-can.com). We assessed directed connectivity within and between three key large-scale networks: the salience network, dorsal attention network, and default mode network. We found that age influences connectivity both within and between these networks, over and above the effects on neurovascular coupling. Canonical correlation analysis revealed that the relationship between network connectivity and cognitive function was age-dependent: cognitive performance relied on neural dynamics more strongly in older adults. These effects were driven partly by reduced stability of neural activity within all networks, as expressed by an accelerated decay of neural information. Our findings suggest that the balance of excitatory connectivity between networks, and the stability of intrinsic neural representations within networks, changes with age. The cognitive function of older adults becomes increasingly dependent on these factors. SIGNIFICANCE STATEMENT: Maintaining cognitive function is critical to successful aging. To study the neural basis of cognitive function across the lifespan, we studied a large population-based cohort (n = 602, 18-88 years), separating neural connectivity from vascular components of fMRI signals. Cognitive ability was influenced by the strength of connection within and between functional brain networks, and this positive relationship increased with age. In older adults, there was more rapid decay of intrinsic neuronal activity in multiple regions of the brain networks, which related to cognitive performance. Our data demonstrate increased reliance on network flexibility to maintain cognitive function, in the presence of more rapid decay of neural activity. These insights will facilitate the development of new strategies to maintain cognitive ability.

The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults.

In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood-oxygenation level-dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting-state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath-hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age-related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population-based Cambridge Centre for Ageing and Neuroscience cohort (Cam-CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task-based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects of age on task-based activation studies with fMRI do not survive correction for changes in vascular reactivity, and are likely to have been overestimated in previous fMRI studies of ageing. The results from the mediation analysis demonstrate that RSFA is modulated by measures of vascular function and is not driven solely by changes in the variance of neural activity. Based on these findings we propose that the RSFA scaling method is articularly useful in large scale and longitudinal neuroimaging studies of ageing, or with frail participants, where alternative measures of vascular reactivity are impractical.

Neuronal avalanches in the resting MEG of the human brain.

What constitutes normal cortical dynamics in healthy human subjects is a major question in systems neuroscience. Numerous in vitro and in vivo animal studies have shown that ongoing or resting cortical dynamics are characterized by cascades of activity across many spatial scales, termed neuronal avalanches. In experiment and theory, avalanche dynamics are identified by two measures: (1) a power law in the size distribution of activity cascades with an exponent of -3/2 and (2) a branching parameter of the critical value of 1, reflecting balanced propagation of activity at the border of premature termination and potential blowup. Here we analyzed resting-state brain activity recorded using noninvasive magnetoencephalography (MEG) from 124 healthy human subjects and two different MEG facilities using different sensor technologies. We identified large deflections at single MEG sensors and combined them into spatiotemporal cascades on the sensor array using multiple timescales. Cascade size distributions obeyed power laws. For the timescale at which the branching parameter was close to 1, the power law exponent was -3/2. This relationship was robust to scaling and coarse graining of the sensor array. It was absent in phase-shuffled controls with the same power spectrum or empty scanner data. Our results demonstrate that normal cortical activity in healthy human subjects at rest organizes as neuronal avalanches and is well described by a critical branching process. Theory and experiment have shown that such critical, scale-free dynamics optimize information processing. Therefore, our findings imply that the human brain attains an optimal dynamical regime for information processing.

Did I turn off the gas? Reality monitoring of everyday actions.

Failing to remember whether we performed, or merely imagined performing, an everyday action can occasionally be inconvenient, but in some circumstances it can have potentially dangerous consequences. In this fMRI study, we investigated the brain activity patterns, and objective and subjective behavioral measures, associated with recollecting such everyday actions. We used an ecologically valid "reality-monitoring" paradigm in which participants performed, or imagined performing, specified actions with real objects drawn from one of two boxes. Lateral brain areas, including prefrontal cortex, were active when participants recollected both the actions that had been associated with objects and the locations from which they had been drawn, consistent with a general role in source recollection. By contrast, medial prefrontal and motor regions made more specific contributions, with supplementary motor cortex activity being associated with recollection decisions about actions but not locations, and medial prefrontal cortex exhibiting greater activity when remembering performed rather than imagined actions. These results support a theoretical interpretation of reality monitoring that entails the fine-grained discrimination between multiple forms of internally and externally generated information.

Episodic reinstatement in the medial temporal lobe.

The essence of episodic memory is our ability to reexperience past events in great detail, even in the absence of external stimulus cues. Does the phenomenological reinstatement of past experiences go along with reinstating unique neural representations in the brain? And if so, how is this accomplished by the medial temporal lobe (MTL), a brain region intimately linked to episodic memory? Computational models suggest that such reinstatement (also termed "pattern completion") in cortical regions is mediated by the hippocampus, a key region of the MTL. Although recent functional magnetic resonance imaging studies demonstrated reinstatement of coarse item properties like stimulus category or task context across different brain regions, it has not yet been shown whether reinstatement can be observed at the level of individual, discrete events-arguably the defining feature of episodic memory-nor whether MTL structures like the hippocampus support this "true episodic" reinstatement. Here we show that neural activity patterns for unique word-scene combinations encountered during encoding are reinstated in human parahippocampal cortex (PhC) during retrieval. Critically, this reinstatement occurs when word-scene combinations are successfully recollected (even though the original scene is not visually presented) and does not encompass other stimulus domains (such as word-color associations). Finally, the degree of PhC reinstatement across retrieval events correlated with hippocampal activity, consistent with a role of the hippocampus in coordinating pattern completion in cortical regions.

Differential face-network adaptation in children, adolescents and adults.

Faces are complex social stimuli, which can be processed both at the categorical and the individual level. Behavioral studies have shown that children take more than a decade of exposure and training to become proficient at processing faces at the individual level. The neurodevelopmental trajectories for different aspects of face-processing are still poorly understood. In this study, we used an fMR-adaptation design to investigate differential processing of three face aspects (identity, expression and gaze) in children, adolescents and adults. We found that, while all three tasks showed some overlap in activation patterns, there was a significant age effect in the occipital and temporal lobes and the inferior frontal gyrus. More importantly, the degree of adaptation differed across the three age groups in the inferior occipital gyrus, a core face processing area that has been shown in previous studies to be both integral and necessary for individual-level face processing. In the younger children, adaptation in this region seemed to suggest the use of a predominantly featural processing strategy, whereas adaptation effects in the adults exhibited a more strategic pattern that depended on the task. Interestingly, our sample of adolescents did not exhibit any differential adaptation effects; possibly reflecting increased heterogeneity in processing strategies in this age group. Our results support the notion that, in line with improving behavioral face-processing abilities, core face-responsive regions develop throughout the first two decades of life.

Cerebral blood flow predicts multiple demand network activity and fluid intelligence across the adult lifespan.

The preservation of cognitive function in old age is a public health priority. Cerebral hypoperfusion is a hallmark of dementia but its impact on maintaining cognitive ability across the lifespan is less clear. We investigated the relationship between baseline cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) response during a fluid reasoning task in a population-based adult lifespan cohort. As age differences in CBF could lead to non-neuronal contributions to the BOLD signal, we introduced commonality analysis to neuroimaging to dissociate performance-related CBF effects from the physiological confounding effects of CBF on the BOLD response. Accounting for CBF, we confirmed that performance- and age-related differences in BOLD responses in the multiple-demand network were implicated in fluid reasoning. Age differences in CBF explained not only performance-related BOLD responses but also performance-independent BOLD responses. Our results suggest that CBF is important for maintaining cognitive function, while its non-neuronal contributions to BOLD signals reflect an age-related confound. Maintaining perfusion into old age may serve to support brain function and preserve cognitive performance.

Cognitive effort drives workspace configuration of human brain functional networks.

Effortful cognitive performance is theoretically expected to depend on the formation of a global neuronal workspace. We tested specific predictions of workspace theory, using graph theoretical measures of network topology and physical distance of synchronization, in magnetoencephalographic data recorded from healthy adult volunteers (N = 13) during performance of a working memory task at several levels of difficulty. We found that greater cognitive effort caused emergence of a more globally efficient, less clustered, and less modular network configuration, with more long-distance synchronization between brain regions. This pattern of task-related workspace configuration was more salient in the ß-band (16-32 Hz) and γ-band (32-63 Hz) networks, compared with both lower (α-band; 8-16 Hz) and higher (high γ-band; 63-125 Hz) frequency intervals. Workspace configuration of ß-band networks was also greater in faster performing participants (with correct response latency less than the sample median) compared with slower performing participants. Processes of workspace formation and relaxation in relation to time-varying demands for cognitive effort could be visualized occurring in the course of task trials lasting <2 s. These experimental results provide support for workspace theory in terms of complex network metrics and directly demonstrate how cognitive effort breaks modularity to make human brain functional networks transiently adopt a more efficient but less economical configuration.

Adjusting for global effects in voxel-based morphometry: gray matter decline in normal aging.

Results from studies that have examined age-related changes in gray matter based on structural MRI scans have not always been consistent. Reasons for this variability likely include small or unevenly-distributed samples, different methods for tissue class segmentation and spatial normalization, and the use of different statistical models. Particularly relevant to the latter is the method of adjusting for global (total) gray matter when making inferences about regionally-specific changes. In the current study, we use voxel-based morphometry (VBM) to explore the impact of these methodological choices in assessing age-related changes in gray matter volume in a sample of 420 adults evenly distributed between the ages of 18-77 years. At a broad level, we replicate previous findings, showing age-related gray matter decline in nearly all parts of the brain, with particularly rapid decline in inferior regions of frontal cortex (e.g., insula and left inferior frontal gyrus) and the central sulcus. Segmentation was improved by increasing the number of tissue classes and using less age-biased templates, and registration was improved by using a diffeomorphic flow-based algorithm (DARTEL) rather than a "constrained warp" approach. Importantly, different approaches to adjusting for global effects--not adjusting, Local Covariation, Global Scaling, and Local Scaling--significantly affected regionally-specific estimates of age-related decline, as demonstrated by ranking age effects across anatomical ROIs. Split-half cross-validation showed that, on average, Local Covariation explained a greater proportion of age-related variance across these ROIs than did Global Scaling. Nonetheless, the appropriate choice for global adjustment depends on one's assumptions and specific research questions. More generally, these results emphasize the importance of being explicit about the assumptions underlying key methodological choices made in VBM analyses and the inferences that follow.

Autism spectrum traits predict the neural response to eye gaze in typical individuals.

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterised by impaired social interaction and communication, restricted interests and repetitive behaviours. The severity of these characteristics are posited to lie on a continuum extending into the typical population, and typical adults' performance on behavioural tasks that are impaired in ASD is correlated with the extent to which they display autistic traits (as measured by Autism Spectrum Quotient, AQ). Individuals with ASD also show structural and functional differences in brain regions involved in social perception. Here we show that variation in AQ in typically developing individuals is associated with altered brain activity in the neural circuit for social attention perception while viewing others' eye gaze. In an fMRI experiment, participants viewed faces looking at variable or constant directions. In control conditions, only the eye region was presented or the heads were shown with eyes closed but oriented at variable or constant directions. The response to faces with variable vs. constant eye gaze direction was associated with AQ scores in a number of regions (posterior superior temporal sulcus, intraparietal sulcus, temporoparietal junction, amygdala, and MT/V5) of the brain network for social attention perception. No such effect was observed for heads with eyes closed or when only the eyes were presented. The results demonstrate a relationship between neurophysiology and autism spectrum traits in the typical (non-ASD) population and suggest that changes in the functioning of the neural circuit for social attention perception is associated with an extended autism spectrum in the typical population.

The Scale of Functional Specialization within Human Prefrontal Cortex.

At what scale is it possible to observe consistent functional specialization within human prefrontal cortex (PFC), reproducible from one individual to the next? Some studies suggest gross functional divisions between large regions of PFC, but it is not known whether PFC exhibits specialization at the fine-grained scale known to differentiate posterior cortical functions. We used fMRI to confirm a three-way segregation of function between three regions of medial anterior PFC, each centered on coordinates within 15 mm of the other two. Naive participants performed three tasks based on earlier studies, and we investigated activity at regions defined by previous results. In each task, signal was significantly greater at the predicted region than the other two, just millimeters away. These results indicate reproducible functional specialization within PFC, at a much finer scale than previously demonstrated. Furthermore, these findings suggest that divergent results from previous studies may reflect the recruitment of functionally distinct regions and that "reverse inference" should be undertaken with caution.

Perception and conception: temporal lobe activity during complex discriminations of familiar and novel faces and objects.

Recent studies indicate that medial-temporal lobe (MTL) damage, either from focal lesions or neurodegenerative disease (e.g., semantic dementia), impairs perception as well as long-term declarative memory. Notably, however, these two patient groups show different performance for meaningful versus unfamiliar stimuli. In amnesics with nonprogressive MTL lesions, the use of meaningful stimuli, compared with unfamiliar items, boosted discrimination performance. In semantic dementia, a condition characterized by progressive deterioration of conceptual knowledge in the context of anterolateral temporal lobe damage, performance for meaningful stimuli was equivalent to that for unfamiliar items. To further investigate these findings, we scanned healthy volunteers while they performed odd-one-out discriminations involving familiar (i.e., meaningful/famous) and unfamiliar (i.e., novel) objects and faces and a baseline task of size oddity. Outside the scanner, volunteers' recognition memory was assessed. We found above baseline activity in the perirhinal cortex and hippocampus for all object and face discriminations and above baseline activity in the temporal pole for all face discriminations. The comparison of meaningful, relative to novel, faces and objects, revealed increased activity in the perirhinal cortex and hippocampus. In the temporal pole, we also found activity related to meaningfulness for faces but not for objects. Importantly, these meaningfulness effects were evident even for discriminations that were not subsequently well remembered, suggesting that the difference between meaningful and novel stimuli reflects perceptual or conceptual processes rather than solely incidental encoding into long-term memory. The results provide further evidence that the MTL is recruited during complex perceptual discrimination and additionally suggest that these structures are recruited in semantic processing of objects and faces.

Separating vascular and neuronal effects of age on fMRI BOLD signals.

Accurate identification of brain function is necessary to understand the neurobiology of cognitive ageing, and thereby promote well-being across the lifespan. A common tool used to investigate neurocognitive ageing is functional magnetic resonance imaging (fMRI). However, although fMRI data are often interpreted in terms of neuronal activity, the blood oxygenation level-dependent (BOLD) signal measured by fMRI includes contributions of both vascular and neuronal factors, which change differentially with age. While some studies investigate vascular ageing factors, the results of these studies are not well known within the field of neurocognitive ageing and therefore vascular confounds in neurocognitive fMRI studies are common. Despite over 10 000 BOLD-fMRI papers on ageing, fewer than 20 have applied techniques to correct for vascular effects. However, neurovascular ageing is not only a confound in fMRI, but an important feature in its own right, to be assessed alongside measures of neuronal ageing. We review current approaches to dissociate neuronal and vascular components of BOLD-fMRI of regional activity and functional connectivity. We highlight emerging evidence that vascular mechanisms in the brain do not simply control blood flow to support the metabolic needs of neurons, but form complex neurovascular interactions that influence neuronal function in health and disease. This article is part of the theme issue 'Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.

The effects of age on resting-state BOLD signal variability is explained by cardiovascular and cerebrovascular factors.

Accurate identification of brain function is necessary to understand neurocognitive aging, and thereby promote health and well-being. Many studies of neurocognitive aging have investigated brain function with the blood-oxygen level-dependent (BOLD) signal measured by functional magnetic resonance imaging. However, the BOLD signal is a composite of neural and vascular signals, which are differentially affected by aging. It is, therefore, essential to distinguish the age effects on vascular versus neural function. The BOLD signal variability at rest (known as resting state fluctuation amplitude, RSFA), is a safe, scalable, and robust means to calibrate vascular responsivity, as an alternative to breath-holding and hypercapnia. However, the use of RSFA for normalization of BOLD imaging assumes that age differences in RSFA reflecting only vascular factors, rather than age-related differences in neural function (activity) or neuronal loss (atrophy). Previous studies indicate that two vascular factors, cardiovascular health (CVH) and cerebrovascular function, are insufficient when used alone to fully explain age-related differences in RSFA. It remains possible that their joint consideration is required to fully capture age differences in RSFA. We tested the hypothesis that RSFA no longer varies with age after adjusting for a combination of cardiovascular and cerebrovascular measures. We also tested the hypothesis that RSFA variation with age is not associated with atrophy. We used data from the population-based, lifespan Cam-CAN cohort. After controlling for cardiovascular and cerebrovascular estimates alone, the residual variance in RSFA across individuals was significantly associated with age. However, when controlling for both cardiovascular and cerebrovascular estimates, the variance in RSFA was no longer associated with age. Grey matter volumes did not explain age differences in RSFA, after controlling for CVH. The results were consistent between voxel-level analysis and independent component analysis. Our findings indicate that cardiovascular and cerebrovascular signals are together sufficient predictors of age differences in RSFA. We suggest that RSFA can be used to separate vascular from neuronal factors, to characterize neurocognitive aging. We discuss the implications and make recommendations for the use of RSFA in the research of aging.

Task-dependent activation of face-sensitive cortex: an fMRI adaptation study.

Face processing in the human brain recruits a widespread cortical network based mainly in the ventral and lateral temporal and occipital lobes. However, the extent to which activity within this network is driven by different face properties versus being determined by the manner in which faces are processed (as determined by task requirements) remains unclear. We combined a functional magnetic resonance adaptation paradigm with three target detection tasks, where participants had to detect a specific identity, emotional expression, or direction of gaze, while the task-irrelevant face properties varied independently. Our analysis focused on differentiating the influence of task demands and the processing of stimulus changes within the neural network underlying face processing. Results indicated that the fusiform and inferior occipital gyrus do not respond as a function of stimulus change (such as identity), but rather their activity depends on the task demands. Specifically, we hypothesize that, whether the task encourages a configural- or a featural-processing strategy determines activation. Our results for the superior temporal sulcus were even more specific in that we only found greater responses to stimulus changes that may engage featural processing. These results contribute to our understanding of the functional anatomy of face processing and provide insights into possible compensatory mechanisms in face processing.

Medial temporal lobe activity during complex discrimination of faces, objects, and scenes: Effects of viewpoint.

The medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampus and underlying entorhinal, perirhinal and parahippocampal cortex, is traditionally believed to be part of a unitary system dedicated to declarative memory. Recent studies, however, demonstrated perceptual impairments in amnesic individuals with MTL damage, with hippocampal lesions causing scene discrimination deficits, and perirhinal lesions causing object and face discrimination deficits. The degree of impairment on these tasks was influenced by the need to process complex conjunctions of features: discriminations requiring the integration of multiple visual features caused deficits, whereas discriminations that could be solved on the basis of a single feature did not. Here, we address these issues with functional neuroimaging in healthy participants as they performed a version of the oddity discrimination task used previously in patients. Three different types of stimuli (faces, scenes, novel objects) were presented from either identical or different viewpoints. Consistent with studies in patients, we observed increased perirhinal activity when participants distinguished between faces and objects presented from different, compared to identical, viewpoints. The posterior hippocampus, by contrast, showed an effect of viewpoint for both faces and scenes. These findings provide convergent evidence that the MTL is involved in processes beyond long-term declarative memory and suggest a critical role for these structures in integrating complex features of faces, objects, and scenes into view-invariant, abstract representations.

Separate coding of different gaze directions in the superior temporal sulcus and inferior parietal lobule.

Electrophysiological recording in the anterior superior temporal sulcus (STS) of monkeys has demonstrated separate cell populations responsive to direct and averted gaze. Human functional imaging has demonstrated posterior STS activation in gaze processing, particularly in coding the intentions conveyed by gaze, but to date has provided no evidence of dissociable coding of different gaze directions. Because the spatial resolution typical of group-based fMRI studies (approximately 6-10 mm) exceeds the size of cellular patches sensitive to different facial characteristics (1-4 mm in monkeys), a more sensitive technique may be required. We therefore used fMRI adaptation, which is considered to offer superior resolution, to investigate whether the human anterior STS contains representations of different gaze directions, as suggested by non-human primate research. Subjects viewed probe faces gazing left, directly ahead, or right. Adapting to leftward gaze produced a reduction in BOLD response to left relative to right (and direct) gaze probes in the anterior STS and inferior parietal cortex; rightward gaze adaptation produced a corresponding reduction to right gaze probes. Consistent with these findings, averted gaze in the adapted direction was misidentified as direct. Our study provides the first human evidence of dissociable neural systems for left and right gaze.

A unitary signal-detection model of implicit and explicit memory.

Do dissociations imply independent systems? In the memory field, the view that there are independent implicit and explicit memory systems has been predominantly supported by dissociation evidence. Here, we argue that many of these dissociations do not necessarily imply distinct memory systems. We review recent work with a single-system computational model that extends signal-detection theory (SDT) to implicit memory. SDT has had a major influence on research in a variety of domains. The current work shows that it can be broadened even further in its range of application. Indeed, the single-system model that we present does surprisingly well in accounting for some key dissociations that have been taken as evidence for independent implicit and explicit memory systems.