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Degrading face stimuli reduces face discrimination in both young and older adults, but the brain correlates of this decline in performance are not fully understood. We used functional magnetic resonance imaging to examine the effects of degraded face stimuli on face and nonface brain networks and tested whether these changes would predict the linear declines seen in performance. We found decreased activity in the face network (FN) and a decrease in the similarity of functional connectivity (FC) in the FN across conditions as degradation increased but no effect of age. FC in whole-brain networks also changed with increasing degradation, including increasing FC between the visual network and cognitive control networks. Older adults showed reduced modulation of this whole-brain FC pattern. The strongest predictors of within-participant decline in accuracy were changes in whole-brain network FC and FC similarity of the FN. There was no influence of age on these brain-behavior relations. These results suggest that a systems-level approach beyond the FN is required to understand the brain correlates of performance decline when faces are obscured with noise. In addition, the association between brain and behavior changes was maintained into older age, despite the dampened FC response to face degradation seen in older adults., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Evidence suggests that age differences in associative memory are attenuated for associations that are consistent with prior knowledge. Such knowledge structures have traditionally been associated with the default network (DN), which also shows reduced modulation with age. In the present study, we investigated whether DN activity and connectivity patterns could account for this age-related effect. Younger and older adults underwent functional magnetic resonance imaging as they learned realistic and unrealistic prices of common grocery items. Both groups showed greater activity in the DN during the encoding of realistic, relative to unrealistic, prices. Moreover, DN activity at encoding and retrieval and its connectivity with an attention control network at encoding were associated with enhanced memory for realistic prices. Finally, older adults showed overactivation of control regions during retrieval of realistic prices relative to younger adults. Our findings suggest that DN activity and connectivity patterns (traditionally viewed as indicators of cognitive failure with age), and additional recruitment of control regions, might underlie older adults' enhanced memory for meaningful associations., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Moment-to-moment brain signal variability is a ubiquitous neural characteristic, yet remains poorly understood. Evidence indicates that heightened signal variability can index and aid efficient neural function, but it is not known whether signal variability responds to precise levels of environmental demand, or instead whether variability is relatively static. Using multivariate modeling of functional magnetic resonance imaging-based parametric face processing data, we show here that within-person signal variability level responds to incremental adjustments in task difficulty, in a manner entirely distinct from results produced by examining mean brain signals. Using mixed modeling, we also linked parametric modulations in signal variability with modulations in task performance. We found that difficulty-related reductions in signal variability predicted reduced accuracy and longer reaction times within-person; mean signal changes were not predictive. We further probed the various differences between signal variance and signal means by examining all voxels, subjects, and conditions; this analysis of over 2 million data points failed to reveal any notable relations between voxel variances and means. Our results suggest that brain signal variability provides a systematic task-driven signal of interest from which we can understand the dynamic function of the human brain, and in a way that mean signals cannot capture., (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Default-mode network (DMN) connectivity at rest is disrupted in Alzheimer's Disease (AD), but it is unknown whether this abnormality is a static feature, or if it varies across cognitive states. We measured DMN integrity in 16 patients with mild AD and 18 controls during resting state and a simple visual task. Patients showed resting-state deficits in the parahippocampal gyrus and posterior cingulate. No group differences were found during the task. Controls exhibited higher DMN connectivity of multiple regions during rest than task, while the patient group showed no modulation of the DMN between states. However, the relative degree of increased resting- versus task-state co-activation in the posterior cingulate and precuneus was predictive of mini-mental status exam (MMSE) scores in AD patients, while measures at rest or task alone were not associated with MMSE. These findings suggest that a resting state may be more suited to detecting DMN abnormalities in AD than a simple task. However, the degree of state-dependent modulation in the DMN may be a better predictor of the individual cognitive status than a single-state acquisition. This study demonstrates an apparent reduction in the capacity for DMN modulation in individuals with mild AD, the degree of which uniquely predicted cognitive status.

Increasing evidence suggests that brain variability plays a number of important functional roles for neural systems. However, the relationship between brain variability and changing cognitive demands remains understudied. In the current study, we demonstrate experimental condition-based modulation in brain variability using functional magnetic resonance imaging. Within a sample of healthy younger and older adults, we found that blood oxygen level-dependent signal variability was an effective discriminator between fixation and external cognitive demand. Across a number of regions, brain variability increased broadly on task compared with fixation, particularly in younger and faster performing adults. Conversely, older and slower performing adults exhibited fewer changes in brain variability within and across experimental conditions and brain regions, indicating a reduction in variability-based neural specificity. Increases in brain variability on task may represent a more complex neural system capable of greater dynamic range between brain states, as well as an enhanced ability to efficiently process varying and unexpected external stimuli. The current results help establish the developmental and performance correlates of state-to-state brain variability-based transitions and offer a new line of inquiry in the study of rest versus task modes in the human brain.

We explored the effects of aging on 2 large-scale brain networks, the default mode network (DMN) and the task-positive network (TPN). During functional magnetic resonance imaging scanning, young and older participants carried out 4 visual tasks: detection, perceptual matching, attentional cueing, and working memory. Accuracy of performance was roughly matched at 80% across tasks and groups. Modulations of activity across conditions were assessed, as well as functional connectivity of both networks. Younger adults showed a broader engagement of the DMN and older adults a more extensive engagement of the TPN. Functional connectivity in the DMN was reduced in older adults, whereas the main pattern of TPN connectivity was equivalent in the 2 groups. Age-specific connectivity also was seen in TPN regions. Increased activity in TPN areas predicted worse accuracy on the tasks, but greater expression of a connectivity pattern associated with a right dorsolateral prefrontal TPN region, seen only in older adults, predicted better performance. These results provide further evidence for age-related differences in the DMN and new evidence of age differences in the TPN. Increased use of the TPN may reflect greater demand on cognitive control processes in older individuals that may be partially offset by alterations in prefrontal functional connectivity.

We used functional magnetic resonance imaging and a 1-back task to assess working memory (WM) for spatial (sound location) and nonspatial (sound category) auditory information in younger and older adults. A mixed block-event-related design was used to measure sustained activity during each task block and transient activity to targets (repetitions of location or category). In both groups, there was increased sustained activity for category WM in left anterior temporal cortex and inferior prefrontal cortex (PFC) and increased activity for location WM in right inferior parietal cortex and dorsal PFC. There were no reliable age differences in this pattern of activity. Older adults had more sustained activity than younger adults in left PFC during both tasks, suggesting that additional PFC recruitment in older adults reflects nonspecific engagement of frontally mediated task-monitoring processes. Both groups showed lower transient than sustained activity in auditory cortex bilaterally; however, older adults showed smaller target-related reductions of activity during the category task. A greater reduction of activity to category targets in left auditory cortex was associated with better performance on this task in older adults, suggesting that a failure to modulate activity appropriately when a stimulus is repeated, or when a particular feature of the stimulus is repeated, could lead to reduced ability to detect this repetition.

Functional magnetic resonance imaging was used to study brain regions implicated in retrieval of memories that are decades old. To probe autobiographical memory, family photographs were selected by confederates without the participant's involvement, thereby eliminating many of the variables that potentially confounded previous neuroimaging studies. We found that context-rich memories were associated with activity in lingual and precuneus gyri independently of their age. By contrast, retrosplenial cortex was more active for recent events regardless of memory vividness. Hippocampal activation was related to the richness of re-experiencing (vividness) rather than the age of the memory per se. Remote memories were associated with distributed activation along the rostrocaudal axis of the hippocampus whereas activation associated with recent memories was clustered in the anterior portion. This may explain why circumscribed lesions to the hippocampus disproportionately affect recent memories. These findings are incompatible with theories of long-term memory consolidation, and are more easily accommodated by multiple-trace theory, which posits that detailed memories are always dependent on the hippocampus.

To examine functional interactions between prefrontal and medial temporal brain areas during face memory, blood flow was measured in patients with Alzheimer's disease and healthy controls using PET. We hypothesized that controls would show correlated activity between frontal and posterior brain areas, including the medial temporal cortex, whereas patients would not, although frontal activity per se might be spared or even increased compared with controls. We used a delayed match to sample paradigm with delays from 1 to 16 s. There was no change in recognition accuracy with increasing delay in controls, whereas patients showed impaired recognition over all delays that worsened as delay increased. Controls showed increased activity in the bilateral prefrontal and parietal cortex with increasing delay, whereas the patients had increased activity in the right prefrontal, anterior cingulate and left amygdala. Increased activity in the right prefrontal cortex was associated with better memory performance in both groups and activity in the left amygdala was correlated with better performance in the patients. Based on these task and behavioural effects, we examined functional connectivity of the right prefrontal cortex and left amygdala in both groups by determining those areas whose activity was correlated with activity in these regions. In controls, activity in the right prefrontal cortex was positively correlated with blood flow in the left prefrontal cortex, bilateral extrastriate and parietal areas and the right hippocampus. In patients, activity in the right prefrontal cortex was correlated mainly with other prefrontal regions. Areas where activity was correlated with the left amygdala in patients included the bilateral posterior parahippocampal gyri, a number of left prefrontal regions, anterior and posterior cingulate, thalamus, and insula. Controls had a relatively restricted set of regions where activity correlated with the left amygdala, mainly temporal and occipital areas. These results support the idea of a functional disconnection between the prefrontal cortex and the hippocampus in Alzheimer's disease and suggest that memory breakdown in early Alzheimer's disease is related to a reduction in the integrated activity within a distributed network that includes these two areas. The unexpected finding of increased involvement of the amygdala suggests that the patients may have processed the emotional content of the faces to a greater degree than did the controls. Furthermore, the positive association between amygdala activity and memory performance in the patients suggests a possible compensatory role for an emotion-related network of regions.

Young and old adults underwent positron emission tomographic scans while encoding pictures of objects and words using three encoding strategies: deep processing (a semantic living/nonliving judgement), shallow processing (size judgement) and intentional learning. Picture memory exceeded word memory in both young and old groups, and there was an age-related decrement only in word recognition. During the encoding tasks three brain activity patterns were found that differentiated stimulus type and the different encoding strategies. The stimulus-specific pattern was characterized by greater activity in extrastriate and medial temporal cortices during picture encoding, and greater activity in left prefrontal and temporal cortices during encoding of words. The older adults showed this pattern to a significantly lesser degree. A pattern distinguishing deep processing from intentional learning of words and pictures was identified, characterized mainly by differences in prefrontal cortex, and this pattern also was of significantly lesser magnitude in the old group. A final pattern identified areas with increased activity during deep processing and intentional learning of pictures, including left prefrontal and bilateral medial temporal regions. There was no group difference in this pattern. These results indicate age-related dysfunction in several encoding networks, with sparing of one specifically involved in more elaborate encoding of pictures. These age-related changes appear to affect verbal memory more than picture memory.

Regional cerebral blood flow, measured with positron emission tomography, was used to identify brain regions that play a special role(s) in a working memory task for faces. Perceptual matching (no retention interval), short-delay (average = 3.5 s retention interval), intermediate-delay (average = 12.5 s), and long-delay (21 s) tasks were considered. From the idea that brain function is the result of neural interactions, the data were analysed using anatomically based, covariance structural equation modeling. In perceptual matching, the dominant functional interactions were observed among the ventral cortical areas, from extrastriate regions, to the anterior temporal, and into the inferior prefrontal cortex. These interactions decreased with longer delay intervals. In the short-delay functional model, interactions along this ventral stream in the right hemisphere appeared to be rerouted through limbic areas with strong interactions among the hippocampal region, the anterior and posterior cingulate, and the inferior prefrontal cortices. For the intermediate-delay model, the hippocampocingulate interactions continued, but showed a shift to more left hemisphere involvement. In the long-delay network, interactions within the right limbic circuit were reduced in favor of strong bilateral inferior prefrontal and frontocingulate interactions. Effects from the prefrontal cortex, especially from the left hemisphere, to temporal and occipito-temporal cortices were particularly strong in the long-delay model, suggesting recruitment of some of the same circuits primarily involved in face perception. The strong corticolimbic interactions at short and intermediate delays may represent maintenance of an iconic representation of the face during the retention interval. However, at longer delays, where image was more difficult to maintain, a frontocingulate-occipital network was used that could represent an expanded encoding strategy resulting in a more resilient memory.

Cue-directed shifts of spatial attention were examined for a letter-discrimination task in 15 patients with mild to moderate dementia of the Alzheimer type (DAT) and 15 healthy, age-matched controls. Spatial cues were valid, invalid or neutral in indicating probable target location and were presented either centrally at fixation or peripherally 6.7 degrees to the left or right of fixation. Stimulus-onset asynchrony (SOA) between cue and target was varied between 200 ms and 2000 ms. Reaction time (RT) benefits conferred by valid cues did not differ between the DAT group and the controls. However, RT costs incurred by invalid cues were significantly greater in the DAT group than in the control group. Group differences in RT costs plus benefits occurred at short SOAs (less than 500 ms) for peripheral cues and at long SOAs (greater than 500 ms) for central cues. Reaction time costs plus benefits were correlated with right-left asymmetry in resting levels of cerebral glucose metabolism in the superior parietal lobe for DAT patients but not for controls. The results indicate that focusing of attention to spatial location is intact in early DAT, whereas the disengagement of visuospatial attention is impaired. Automatic attention shifts elicited by peripheral cues reveal abnormalities earlier than attention shifts initiated 'effortfully' by central cues. Intact focusing and impaired disengagement of visuospatial attention may be linked to dysfunction in early DAT of cortico-cortical networks linking the posterior parietal and frontal lobes.