The Interactive Role of Sleep and Circadian Rhythms in Episodic Memory in Older Adults.

Adequate sleep is essential for healthy physical, emotional, and cognitive functioning, including memory. However, sleep ability worsens with increasing age. Older adults on average have shorter sleep durations and more disrupted sleep compared with younger adults. Age-related sleep changes are thought to contribute to age-related deficits in episodic memory. Nonetheless, the nature of the relationship between sleep and episodic memory deficits in older adults is still unclear. Further complicating this relationship are age-related changes in circadian rhythms such as the shift in chronotype toward morningness and decreased circadian stability, which may influence memory abilities as well. Most sleep and cognitive aging studies do not account for circadian factors, making it unclear whether age-related and sleep-related episodic memory deficits are partly driven by interactions with circadian rhythms. This review will focus on age-related changes in sleep and circadian rhythms and evidence that these factors interact to affect episodic memory, specifically encoding and retrieval. Open questions, methodological considerations, and clinical implications for diagnosis and monitoring of age-related memory impairments are discussed.

Computational and neural signatures of pre and post-sensory expectation bias in inferior temporal cortex.

As we gather noisy sensory information from the environment, prior knowledge about the likely cause(s) of sensory input can be leveraged to facilitate perceptual judgments. Here, we investigated the computational and neural manifestation of cued expectations in human subjects as they performed a probabilistic face/house discrimination task in which face and house stimuli were preceded by informative or neutral cues. Drift-diffusion modeling of behavioral data showed that cued expectations biased both the baseline (pre-sensory) and drift-rate (post-sensory) of evidence accumulation. By employing a catch-trial functional MRI design we were able to isolate neural signatures of expectation during pre- and post-sensory stages of decision processing in face- and house-selective areas of inferior temporal cortex (ITC). Cue-evoked timecourses were modulated by cues in a manner consistent with a pre-sensory prediction signal that scaled with probability. Sensory-evoked timecourses resembled a prediction-error signal, greater in magnitude for surprising than expected stimuli. Individual differences in baseline and drift-rate biases showed a clear mapping onto pre- and post-sensory fMRI activity in ITC. These findings highlight the specificity of perceptual expectations and provide new insight into the convergence of top-down and bottom-up signals in ITC and their distinct interactions prior to and during sensory processing.

Physical Activity and Cognition: A Mediating Role of Efficient Sleep.

OBJECTIVE: Physical activity benefits executive control, but the mechanism through which this benefit occurs is unclear. Sleep is a candidate mechanism given that it improves with exercise and has restorative effects on the prefrontal cortex. The present cross-sectional study examined the mediating role of sleep in the relationship between physical activity and executive control in young and older adults. PARTICIPANTS: Young (n = 59) and older (n = 53) community-dwelling adults ages 21-30 and 55-80. METHODS: Participants wore an accelerometer for one week to assess sleep efficiency, total sleep time, and physical activity, operationalized as metabolic equivalent of task (METs) during time spent awake. Cognition was assessed in the laboratory across multiple measures of executive control, memory recall, and processing speed. Mediation analyses tested the role of sleep efficiency in the cross-sectional relationship between METs and cognitive performance accounting for age, sex, and education. RESULTS: METs were significantly associated with performance before, but not after accounting for covariates. METs were associated with sleep efficiency but not total sleep time. Sleep efficiency, but not total sleep time, mediated the relationship between METs and working memory, switching, verbal ability and fluency, and recall. Age group did not moderate the mediating role of sleep efficiency in the relationship between METs and performance. CONCLUSION: Sleep efficiency is one pathway by which physical activity may be associated with executive control across young and older adults.

Cortical Networks Involved in Memory for Temporal Order.

We examined the neurobiological basis of temporal resetting, an aspect of temporal order memory, using a version of the delayed-match-to-multiple-sample task. While in an fMRI scanner, participants evaluated whether an item was novel or whether it had appeared before or after a reset event that signified the start of a new block of trials. Participants responded "old" to items that were repeated within the current block and "new" to both novel items and items that had last appeared before the reset event (pseudonew items). Medial-temporal, prefrontal, and occipital regions responded to absolute novelty of the stimulus-they differentiated between novel items and previously seen items, but not between old and pseudonew items. Activation for pseudonew items in the frontopolar and parietal regions, in contrast, was intermediate between old and new items. The posterior cingulate cortex extending to precuneus was the only region that showed complete temporal resetting, and its activation reflected whether an item was new or old according to the task instructions regardless of its familiarity. There was also a significant Condition (old/pseudonew) × Familiarity (second/third presentations) interaction effect on behavioral and neural measures. For pseudonew items, greater familiarity decreased response accuracy, increased RTs, increased ACC activation, and increased functional connectivity between ACC and the left frontal pole. The reverse was observed for old items. On the basis of these results, we propose a theoretical framework in which temporal resetting relies on an episodic retrieval network that is modulated by cognitive control and conflict resolution.

Neural signatures of experience-based improvements in deterministic decision-making.

Feedback about our choices is a crucial part of how we gather information and learn from our environment. It provides key information about decision experiences that can be used to optimize future choices. However, our understanding of the processes through which feedback translates into improved decision-making is lacking. Using neuroimaging (fMRI) and cognitive models of decision-making and learning, we examined the influence of feedback on multiple aspects of decision processes across learning. Subjects learned correct choices to a set of 50 word pairs across eight repetitions of a concurrent discrimination task. Behavioral measures were then analyzed with both a drift-diffusion model and a reinforcement learning model. Parameter values from each were then used as fMRI regressors to identify regions whose activity fluctuates with specific cognitive processes described by the models. The patterns of intersecting neural effects across models support two main inferences about the influence of feedback on decision-making. First, frontal, anterior insular, fusiform, and caudate nucleus regions behave like performance monitors, reflecting errors in performance predictions that signal the need for changes in control over decision-making. Second, temporoparietal, supplementary motor, and putamen regions behave like mnemonic storage sites, reflecting differences in learned item values that inform optimal decision choices. As information about optimal choices is accrued, these neural systems dynamically adjust, likely shifting the burden of decision processing from controlled performance monitoring to bottom-up, stimulus-driven choice selection. Collectively, the results provide a detailed perspective on the fundamental ability to use past experiences to improve future decisions.

Content-specific evidence accumulation in inferior temporal cortex during perceptual decision-making.

During a perceptual decision, neuronal activity can change as a function of time-integrated evidence. Such neurons may serve as decision variables, signaling a choice when activity reaches a boundary. Because the signals occur on a millisecond timescale, translating to human decision-making using functional neuroimaging has been challenging. Previous neuroimaging work in humans has identified patterns of neural activity consistent with an accumulation account. However, the degree to which the accumulating neuroimaging signals reflect specific sources of perceptual evidence is unknown. Using an extended face/house discrimination task in conjunction with cognitive modeling, we tested whether accumulation signals, as measured using functional magnetic resonance imaging (fMRI), are stimulus-specific. Accumulation signals were defined as a change in the slope of the rising edge of activation corresponding with response time (RT), with higher slopes associated with faster RTs. Consistent with an accumulation account, fMRI activity in face- and house-selective regions in the inferior temporal cortex increased at a rate proportional to decision time in favor of the preferred stimulus. This finding indicates that stimulus-specific regions perform an evidence integrative function during goal-directed behavior and that different sources of evidence accumulate separately. We also assessed the decision-related function of other regions throughout the brain and found that several regions were consistent with classifications from prior work, suggesting a degree of domain generality in decision processing. Taken together, these results provide support for an integration-to-boundary decision mechanism and highlight possible roles of both domain-specific and domain-general regions in decision evidence evaluation.

The strength of gradually accruing probabilistic evidence modulates brain activity during a categorical decision.

The evolution of neural activity during a perceptual decision is well characterized by the evidence parameter in sequential sampling models. However, it is not known whether accumulating signals in human neuroimaging are related to the integration of evidence. Our aim was to determine whether activity accumulates in a nonperceptual task by identifying brain regions tracking the strength of probabilistic evidence. fMRI was used to measure whole-brain activity as choices were informed by integrating a series of learned prior probabilities. Participants first learned the predictive relationship between a set of shape stimuli and one of two choices. During scanned testing, they made binary choices informed by the sum of the predictive strengths of individual shapes. Sequences of shapes adhered to three distinct rates of evidence (RoEs): rapid, gradual, and switch. We predicted that activity in regions informing the decision would modulate as a function of RoE prior to the choice. Activity in some regions, including premotor areas, changed as a function of RoE and response hand, indicating a role in forming an intention to respond. Regions in occipital, temporal, and parietal lobes modulated as a function of RoE only, suggesting a preresponse stage of evidence processing. In all of these regions, activity was greatest on rapid trials and least on switch trials, which is consistent with an accumulation-to-boundary account. In contrast, activity in a set of frontal and parietal regions was greatest on switch and least on rapid trials, which is consistent with an effort or time-on-task account.

Role of sleep continuity and total sleep time in executive function across the adult lifespan.

The importance of sleep for cognition in young adults is well established, but the role of habitual sleep behavior in cognition across the adult life span remains unknown. We examined the relationship between sleep continuity and total sleep time as assessed with a sleep-detection device, and cognitive performance using a battery of tasks in young (n = 59, mean age = 23.05) and older (n = 53, mean age = 62.68) adults. Across age groups, higher sleep continuity was associated with better cognitive performance. In the younger group, higher sleep continuity was associated with better working memory and inhibitory control. In the older group, higher sleep continuity was associated with better inhibitory control, memory recall, and verbal fluency. Very short and very long total sleep time was associated with poorer working memory and verbal fluency, specifically in the younger group. Total sleep time was not associated with cognitive performance in any domains for the older group. These findings reveal that sleep continuity is important for executive function in both young and older adults, but total sleep time may be more important for cognition in young adults.

Prior probability and feature predictability interactively bias perceptual decisions.

Anticipating a forthcoming sensory experience facilitates perception for expected stimuli but also hinders perception for less likely alternatives. Recent neuroimaging studies suggest that expectation biases arise from feature-level predictions that enhance early sensory representations and facilitate evidence accumulation for contextually probable stimuli while suppressing alternatives. Reasonably then, the extent to which prior knowledge biases subsequent sensory processing should depend on the precision of expectations at the feature level as well as the degree to which expected features match those of an observed stimulus. In the present study we investigated how these two sources of uncertainty modulated pre- and post-stimulus bias mechanisms in the drift-diffusion model during a probabilistic face/house discrimination task. We tested several plausible models of choice bias, concluding that predictive cues led to a bias in both the starting-point and rate of evidence accumulation favoring the more probable stimulus category. We further tested the hypotheses that prior bias in the starting-point was conditional on the feature-level uncertainty of category expectations and that dynamic bias in the drift-rate was modulated by the match between expected and observed stimulus features. Starting-point estimates suggested that subjects formed a constant prior bias in favor of the face category, which exhibits less feature-level variability, that was strengthened or weakened by trial-wise predictive cues. Furthermore, we found that the gain on face/house evidence was increased for stimuli with less ambiguous features and that this relationship was enhanced by valid category expectations. These findings offer new evidence that bridges psychological models of decision-making with recent predictive coding theories of perception.

Sleep continuity and total sleep time are associated with task-switching and preparation in young and older adults.

Ageing is associated with changes in sleep and decline executive functions, such as task-switching and task preparation. Given that sleep affects executive function, age-related changes in executive function may be attributable to changes in sleep. The present study used a sleep detection device to examine whether or not wake time after sleep onset and total sleep time moderated age differences in task-switching performance and participants' ability to reduce switch costs when given time to prepare. Participants were cognitively healthy [Mini Mental State Examination > 26] younger (n = 54; mean age = 22.9; 67.8% female) and older (n = 45; mean age 62.8; 71.1% female) adults. Using a task-switching paradigm, which manipulated preparation time, we found that smaller global switch costs were associated with lower wake time after sleep onset and longer total sleep time. Greater preparation effects on local switch costs and adoption of a task-set were associated with lower wake time after sleep onset, although this effect was significant only in older adults when stratified by age group. This association was independent of inhibition and working memory abilities. The lack of interactions between sleep and age group indicated that age differences in switch costs were not moderated by better sleep. Our results suggest that young and older adults may benefit similarly from lower wake time after sleep onset and longer total sleep time in overall performance, and individuals with less wake time after sleep onset are more likely to engage preparatory strategies to reduce switch costs and boost task-switching performance.

Repetition related changes in activation and functional connectivity in hippocampus predict subsequent memory.

Using fMRI, this study examined the relationship between repetition-related changes in the medial temporal lobe (MTL) activation during encoding and subsequent memory for similarity of repetitions. During scanning, subjects classified pictures of objects as natural or man-made. Each object-type was judged twice with presentations of either identical pictures or pictures of different exemplars of the same object. After scanning, a surprise recognition test required subjects to decide whether a probe word corresponded to pictures judged previously. When a subject judged the word as "old," a second judgment was made concerning the physical similarity of the two pictures. Repetition related changes in MTL activation varied depending on whether or not subjects could correctly state that pictures were different. Moreover, psychophysiological interactions analyses showed that accuracy in recalling whether the two pictures were different was predicted by repetition-related changes in the functional connectivity of MTL with frontal regions. Specifically, correct recollection was predicted by increased connectivity between the left posterior hippocampus and the right inferior frontal gyrus, and also by decreased connectivity between the left posterior hippocampus and the left precentral gyrus on the second stimulus presentation. The opposite pattern was found for trials that were incorrectly judged on the nature of the repetition. These results suggest that successful encoding is predicted by a combination of increases and decreases in both the MTL activation and functional connectivity, and not merely by increases in activation and connectivity as suggested previously.

A differentiation account of recognition memory: evidence from fMRI.

Differentiation models of recognition memory predict a strength-based mirror effect in the distributions of subjective memory strength. Subjective memory strength should increase for targets and simultaneously decrease for foils following a strongly encoded list compared with a weakly encoded list. An alternative explanation for the strength-based mirror effect is that participants adopt a stricter criterion following a strong list than a weak list. Behavioral experiments support the differentiation account. The purpose of this study was to identify the neural bases for these differences. Encoding strength was manipulated (strong, weak) in a rapid event-related fMRI paradigm. To investigate the effect of retrieval context on foils, foils were presented in test blocks containing strong or weak targets. Imaging analyses identified regions in which activity increased faster for foils tested after a strong list than a weak list. The results are interpreted in support of a differentiation account of memory and are suggestive that the angular gyrus plays a role in evaluating evidence related to the memory decision, even for new items.

Age-related decline in controlled retrieval: the role of the PFC and sleep.

Age-related cognitive impairments often include difficulty retrieving memories, particularly those that rely on executive control. In this paper we discuss the influence of the prefrontal cortex on memory retrieval, and the specific memory processes associated with the prefrontal cortex that decline in late adulthood. We conclude that preretrieval processes associated with preparation to make a memory judgment are impaired, leading to greater reliance on postretrieval processes. This is consistent with the view that impairments in executive control significantly contribute to deficits in controlled retrieval. Finally, we discuss age-related changes in sleep as a potential mechanism that contributes to deficiencies in executive control that are important for efficient retrieval. The sleep literature points to the importance of slow-wave sleep in restoration of prefrontal cortex function. Given that slow-wave sleep significantly declines with age, we hypothesize that age-related changes in slow-wave sleep could mediate age-related decline in executive control, manifesting a robust deficit in controlled memory retrieval processes. Interventions, like physical activity, that improve sleep could be effective methods to enhance controlled memory processes in late life.

The emergence of frequency effects in eye movements.

A visual search experiment employed strings of Landolt Cs to examine how the gap size of and frequency of exposure to distractor strings affected eye movements. Increases in gap size were associated with shorter first-fixation durations, gaze durations, and total times, as well as fewer fixations. Importantly, both the number and duration of fixations decreased with repeated exposures. The findings provide evidence for the role of cognition in guiding eye-movements, and a potential explanation for word-frequency effects observed in reading.

High quality but limited quantity perceptual evidence produces neural accumulation in frontal and parietal cortex.

Goal-directed perceptual decisions involve the analysis of sensory inputs, the extraction and accumulation of evidence, and the commitment to a choice. Previous neuroimaging studies of perceptual decision making have identified activity related to accumulation in parietal, inferior temporal, and frontal regions. However, such effects may be related to factors other than the integration of evidence over time, such as changes in the quantity of stimulus input and in attentional demands leading up to a decision. The current study tested an accumulation account using 2 manipulations. First, to test whether patterns of accumulation can be explained by changes in the quantity of sensory information, objects were revealed with a high quality but consistent quantity of evidence throughout the trial. Imaging analysis revealed patterns of accumulation in frontal and parietal regions but not in inferior temporal regions. This result supports a framework in which evidence is processed in sensory cortex and integrated over time in higher order cortical areas. Second, to test whether accumulation signals are driven by attentional demands, task difficulty was increased on some trials. This manipulation did not affect the nature of accumulating functional magnetic resonance imaging signals, indicating that accumulating signals are not necessarily driven by changes in attentional demand.

Effects of task-set adoption on ERP correlates of controlled and automatic recognition memory.

Successful memory retrieval depends not only on memory fidelity but also on the mental preparedness on the part of the subject. ERP studies of recognition memory have identified two topographically distinct ERP components, the FN400 old/new effect and the late posterior component (LPC) old/new effect, commonly associated with familiarity and recollection, respectively. Here we used a task-switching paradigm to examine the extent to which adoption of a retrieval task-set influences FN400 and LPC old/new effects, in light of the presumption that recollection, as a control process, relies on the adoption of a retrieval task-set, but that familiarity-based retrieval does not. Behavioral accuracy indicated that source memory (experiment 2), but not item recognition (experiment 1), improved with task-set adoption. ERP data demonstrated a larger LPC on stay trials when a task-set had been adopted even with a simple recognition memory judgment. We conclude that adopting a retrieval task-set impacts recollection memory but not familiarity. These data indicate that attentional state immediately prior to retrieval can influence objective measures of recollection memory.

Opposing patterns of neural priming in same-exemplar vs. different-exemplar repetition predict subsequent memory.

The present neuroimaging study examines how repetition-related neural attenuation effects differ as a function of the perceptual similarity of the repetition and subsequent memory. One previous study (Turk-Browne et al., 2006) reported greater attenuation effects for subsequent hits than for misses. Another study (Wagner et al., 2000) found that neural attenuation is negatively correlated with subsequent memory. These opposing results suggest that repetition-related neural attenuation for subsequent hits and misses may be driven by different factors. In order to investigate the factors that affect the degree of neural attenuation, we varied perceptual similarity between repetitions in a scanned encoding phase that was followed by a subsequent memory test outside the scanner. We demonstrated that the degree of neural attenuation in the object processing regions depends on the interaction between perceptual similarity across repeated presentations and the quality their encodings. Specifically, the same areas that decreased neural signal for repetitions of same exemplars that were subsequently recognized with confidence that the repetitions were identical showed a decrease in neural signal for different-exemplar misses but not for the corresponding subsequently recognized hits. Our results imply that repetition-related neural attenuation should be related to the more efficient processing of perceptual properties of the stimuli only if subjects are able to subsequently remember the stimuli. Otherwise, the cause of attenuation may be in the failure to encode the stimuli on the second presentation as shown by the pattern of neural attenuation for the different-exemplar misses.

A parcellation scheme for human left lateral parietal cortex.

The parietal lobe has long been viewed as a collection of architectonic and functional subdivisions. Though much parietal research has focused on mechanisms of visuospatial attention and control-related processes, more recent functional neuroimaging studies of memory retrieval have reported greater activity in left lateral parietal cortex (LLPC) when items are correctly identified as previously studied ("old") versus unstudied ("new"). These studies have suggested functional divisions within LLPC that may provide distinct contributions toward recognition memory judgments. Here, we define regions within LLPC by developing a parcellation scheme that integrates data from resting-state functional connectivity MRI and functional MRI. This combined approach results in a 6-fold parcellation of LLPC based on the presence (or absence) of memory-retrieval-related activity, dissociations in the profile of task-evoked time courses, and membership in large-scale brain networks. This parcellation should serve as a roadmap for future investigations aimed at understanding LLPC function.

Role of the anterior insula in task-level control and focal attention.

In humans, the anterior insula (aI) has been the topic of considerable research and ascribed a vast number of functional properties by way of neuroimaging and lesion studies. Here, we argue that the aI, at least in part, plays a role in domain-general attentional control and highlight studies (Dosenbach et al. 2006; Dosenbach et al. 2007) supporting this view. Additionally, we discuss a study (Ploran et al. 2007) that implicates aI in processes related to the capture of focal attention. Task-level control and focal attention may or may not reflect information processing supported by a single functional area (within the aI). Therefore, we apply a novel technique (Cohen et al. 2008) that utilizes resting state functional connectivity MRI (rs-fcMRI) to determine whether separable regions exist within the aI. rs-fcMRI mapping suggests that the ventral portion of the aI is distinguishable from more dorsal/anterior regions, which are themselves distinct from more posterior parts of the aI. When these regions are applied to functional MRI (fMRI) data, the ventral and dorsal/anterior regions support processes potentially related to both task-level control and focal attention, whereas the more posterior aI regions did not. These findings suggest that there exists some functional heterogeneity within aI that may subserve related but distinct types of higher-order cognitive processing.

Remember the source: dissociating frontal and parietal contributions to episodic memory.

Event-related fMRI studies reveal that episodic memory retrieval modulates lateral and medial parietal cortices, dorsal middle frontal gyrus (MFG), and anterior PFC. These regions respond more for recognized old than correctly rejected new words, suggesting a neural correlate of retrieval success. Despite significant efforts examining retrieval success regions, their role in retrieval remains largely unknown. Here we asked the question, to what degree are the regions performing memory-specific operations? And if so, are they all equally sensitive to successful retrieval, or are other factors such as error detection also implicated? We investigated this question by testing whether activity in retrieval success regions was associated with task-specific contingencies (i.e., perceived targetness) or mnemonic relevance (e.g., retrieval of source context). To do this, we used a source memory task that required discrimination between remembered targets and remembered nontargets. For a given region, the modulation of neural activity by a situational factor such as target status would suggest a more domain-general role; similarly, modulations of activity linked to error detection would suggest a role in monitoring and control rather than the accumulation of evidence from memory per se. We found that parietal retrieval success regions exhibited greater activity for items receiving correct than incorrect source responses, whereas frontal retrieval success regions were most active on error trials, suggesting that posterior regions signal successful retrieval whereas frontal regions monitor retrieval outcome. In addition, perceived targetness failed to modulate fMRI activity in any retrieval success region, suggesting that these regions are retrieval specific. We discuss the different functions that these regions may support and propose an accumulator model that captures the different pattern of responses seen in frontal and parietal retrieval success regions.