Detecting and discriminating novel objects: The impact of perirhinal cortex disconnection on hippocampal activity patterns

Perirhinal cortex provides object‐based information and novelty/familiarity information for the hippocampus. The necessity of these inputs was tested by comparing hippocampal c‐fos expression in rats with or without perirhinal lesions. These rats either discriminated novel from familiar objects (Novel‐Familiar) or explored pairs of novel objects (Novel‐Novel). Despite impairing Novel‐Familiar discriminations, the perirhinal lesions did not affect novelty detection, as measured by overall object exploration levels (Novel‐Novel condition). The perirhinal lesions also largely spared a characteristic network of linked c‐fos expression associated with novel stimuli (entorhinal cortex→CA3→distal CA1→proximal subiculum). The findings show: I) that perirhinal lesions preserve behavioral sensitivity to novelty, whilst still impairing the spontaneous ability to discriminate novel from familiar objects, II) that the distinctive patterns of hippocampal c‐fos activity promoted by novel stimuli do not require perirhinal inputs, III) that entorhinal Fos counts (layers II and III) increase for novelty discriminations, IV) that hippocampal c‐fos networks reflect proximal‐distal connectivity differences, and V) that discriminating novelty creates different pathway interactions from merely detecting novelty, pointing to top‐down effects that help guide object selection. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.     

Effects of acute psychosocial stress on working memory related brain activity in men

Acute psychosocial stress in humans triggers the release of glucocorticoids (GCs) and influences performance in declarative and working memory (WM) tasks. These memory systems rely on the hippocampus and prefrontal cortex (PFC), where GC‐binding receptors are present. Previous studies revealed contradictory results regarding effects of acute stress on WM‐related brain activity. We combined functional magnetic resonance imaging with a standardized psychosocial stress protocol to investigate the effects of acute mental stress on brain activity during encoding, maintenance, and retrieval of WM. Participants (41 healthy young men) underwent either a stress or a control procedure before performing a WM task. Stress increased salivary cortisol levels and tended to increase WM accuracy. Neurally, stress‐induced increases in cortical activity were evident in PFC and posterior parietal cortex (PPC) during WM maintenance. Furthermore, hippocampal activity was modulated by stress during encoding and retrieval with increases in the right anterior hippocampus during WM encoding and decreases in the left posterior hippocampus during retrieval. Our study demonstrates that stress increases activity in PFC and PPC specifically during maintenance of items in WM, whereas effects on hippocampal activity are restricted to encoding and retrieval. The finding that psychosocial stress can increase and decrease activity in two different hippocampal areas may be relevant for understanding the often‐reported phase‐dependent opposing behavioral effects of stress on long‐term memory. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Neural correlates of confidence during item recognition and source memory retrieval: evidence for both dual-process and strength memory theories

Although the medial-temporal lobes (MTL), PFC, and parietal cortex are considered primary nodes in the episodic memory network, there is much debate regarding the contributions of MTL, PFC, and parietal subregions to recollection versus familiarity (dual-process theory) and the feasibility of accounts on the basis of a single memory strength process (strength theory). To investigate these issues, the current fMRI study measured activity during retrieval of memories that differed quantitatively in terms of strength (high vs. low-confidence trials) and qualitatively in terms of recollection versus familiarity (source vs. item memory tasks). Support for each theory varied depending on which node of the episodic memory network was considered. Results from MTL best fit a dual-process account, as a dissociation was found between a right hippocampal region showing high-confidence activity during the source memory task and bilateral rhinal regions showing high-confidence activity during the item memory task. Within PFC, several left-lateralized regions showed greater activity for source than item memory, consistent with recollective orienting, whereas a right-lateralized ventrolateral area showed low-confidence activity in both tasks, consistent with monitoring processes. Parietal findings were generally consistent with strength theory, with dorsal areas showing low-confidence activity and ventral areas showing high-confidence activity in both tasks. This dissociation fits with an attentional account of parietal functions during episodic retrieval. The results suggest that both dual-process and strength theories are partly correct, highlighting the need for an integrated model that links to more general cognitive theories to account for observed neural activity during episodic memory retrieval.     

Mapping parahippocampal systems for recognition and recency memory in the absence of the rat hippocampus

The present study examined immediate‐early gene expression in the perirhinal cortex of rats with hippocampal lesions. The goal was to test those models of recognition memory which assume that the perirhinal cortex can function independently of the hippocampus. The c‐fos gene was targeted, as its expression in the perirhinal cortex is strongly associated with recognition memory. Four groups of rats were examined. Rats with hippocampal lesions and their surgical controls were given either a recognition memory task (novel vs. familiar objects) or a relative recency task (objects with differing degrees of familiarity). Perirhinal Fos expression in the hippocampal‐lesioned groups correlated with both recognition and recency performance. The hippocampal lesions, however, had no apparent effect on overall levels of perirhinal or entorhinal cortex c‐fos expression in response to novel objects, with only restricted effects being seen in the recency condition. Network analyses showed that whereas the patterns of parahippocampal interactions were differentially affected by novel or familiar objects, these correlated networks were not altered by hippocampal lesions. Additional analyses in control rats revealed two modes of correlated medial temporal activation. Novel stimuli recruited the pathway from the lateral entorhinal cortex (cortical layer II or III) to hippocampal field CA3, and thence to CA1. Familiar stimuli recruited the direct pathway from the lateral entorhinal cortex (principally layer III) to CA1. The present findings not only reveal the independence from the hippocampus of some perirhinal systems associated with recognition memory, but also show how novel stimuli engage hippocampal subfields in qualitatively different ways from familiar stimuli.     

Failure of repetition suppression and memory encoding in aging and Alzheimer��s disease

The suppression of neural activity in the medial temporal lobe (MTL) has been suggested as a marker of successful recognition of familiarity in healthy subjects, but to be impaired in patients with Alzheimer’s disease (AD). In this study, we investigated whether the ability to suppress MTL activity during repeated exposure to face-name pairs was related to the ability to successfully encode novel associations in 90 individuals ranging from healthy young and older subjects to mildly impaired elderly and AD patients. Activity in the anterior MTL during Repeated stimuli was inversely related to performance in post-scan associative recognition for the Novel face-name pairs. In a subset (n = 60) of subjects undergoing more detailed neuropsychological testing, greater MTL Repeated activity was correlated with worse word-list delayed recall performance. Failure of response suppression to familiar information may be a sensitive marker of MTL dysfunction and memory impairment in aging and prodromal AD.     

Working memory and amnesia: the role of stimulus novelty

Despite the traditional view that damage to the hippocampus and/or surrounding areas of the medial temporal lobe (MTL) does not impair short-term or working memory (WM), recent research has shown MTL amnesics to be impaired on WM tasks that require maintaining a small amount of information over brief retention intervals (e.g., maintenance of a single face for one second). However, the types of tasks that have demonstrated WM impairments in amnesia tend to have involved novel stimuli. We hypothesized that WM may be impaired in amnesia for tasks that require maintaining novel information, but may be preserved for more familiar material, particularly if the material can be easily rehearsed. To test this hypothesis, patient HC, a 22-year-old developmental amnesic with relatively preserved semantic memory and 20 age and education matched controls performed a delayed match-to-sample task that required maintaining a single famous or non-famous face for 1-8s, digit span and reading span tasks, and a modified Brown-Peterson task that required maintaining a single high- or low-frequency word or a non-word for 4-8s. HC's performance was impaired for non-famous faces but preserved for famous faces, impaired for the reading span task but preserved for digit span, and it was impaired for non-words and unfamiliar low-frequency words but preserved for familiar words. These results support the hypothesis that an intact hippocampus is necessary for maintaining a single novel stimulus in WM. However, stimulus familiarity and rehearsal support WM via cortical regions independent of the MTL.     

Striatal and midbrain connectivity with the hippocampus selectively boosts memory for contextual novelty

The role of contextual expectation in processing familiar and novel stimuli was investigated in a series of experiments combining eye tracking, functional magnetic resonance imaging, and behavioral methods. An experimental paradigm emphasizing either familiarity or novelty detection at retrieval was used. The detection of unexpected familiar and novel stimuli, which were characterized by lower probability, engaged activity in midbrain and striatal structures. Specifically, detecting unexpected novel stimuli, relative to expected novel stimuli, produced greater activity in the substantia nigra/ventral tegmental area (SN/VTA), whereas the detection of unexpected familiar, relative to expected, familiar stimuli, elicited activity in the striatum/globus pallidus (GP). An effective connectivity analysis showed greater functional coupling between these two seed areas (GP and SN/VTA) and the hippocampus, for unexpected than for expected stimuli. Within this network of midbrain/striatal–hippocampal interactions two pathways are apparent; the direct SN–hippocampal pathway sensitive to unexpected novelty and the perirhinal–GP–hippocampal pathway sensitive to unexpected familiarity. In addition, increased eye fixations and pupil dilations also accompanied the detection of unexpected relative to expected familiar and novel stimuli, reflecting autonomic activity triggered by the functioning of these two pathways. Finally, subsequent memory for unexpected, relative to expected, familiar, and novel stimuli was characterized by enhanced recollection, but not familiarity, accuracy. Taken together, these findings suggest that a hippocampal–midbrain network, characterized by two distinct pathways, mediates encoding facilitation and most critically, that this facilitation is driven by contextual novelty, rather than by the absolute novelty of a stimulus. This contextually sensitive neural mechanism appears to elicit increased exploratory behavior, leading subsequently to greater recollection of the unexpected stimulus. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc.     

Neural mechanisms underlying the reward‐related enhancement of motivation when remembering episodic memories with high difficulty

The motivation to receive rewards enhances episodic memories, and the motivation is modulated by task difficulty. In episodic retrieval, however, functional neuroimaging evidence regarding the motivation that mediates interactions between reward and task difficulty is scarce. The present fMRI study investigated this issue. During encoding performed without fMRI, participants encoded Japanese words using either deep or shallow strategies, which led to variation in difficulty level during subsequent retrieval. During retrieval with fMRI, participants recognized the target words in either high or low monetary reward conditions. In the behavioral results, a reward‐related enhancement of memory was found only when the memory retrieval was difficult, and the rewarding effect on subjective motivation was greater in the retrieval of memories with high difficulty than those with low difficulty. The fMRI data showed that reward‐related increases in the activation of the substantia nigra/ventral tegmental area (SN/VTA), medial temporal lobe (MTL), dorsomedial prefrontal cortex (dmPFC), and dorsolateral prefrontal cortex (dlPFC) were greater during the retrieval of memories with high difficulty than those with low difficulty. Furthermore, reward‐related enhancement of functional connectivity between the SN/VTA and MTL and between the SN/VTA and dmPFC during the retrieval of memories with high difficulty was significantly correlated with reward‐related increases of retrieval accuracy and subjective motivation. The reward‐related enhancement of episodic retrieval and retrieval‐related motivation could be most effective when the level of retrieval difficulty is optimized. Such reward‐related enhancement of memory and motivation could be modulated by a network including the reward‐related SN/VTA, motivation‐related dmPFC, and memory‐related MTL. Hum Brain Mapp 38:3428–3443, 2017. © 2017 Wiley Periodicals, Inc.     

The influence of working-memory demand and subject performance on prefrontal cortical activity

Brain imaging and behavioral studies of working memory (WM) converge to suggest that the ventrolateral prefrontal cortex (PFC) mediates a capacity-limited storage buffer and that the dorsolateral PFC mediates memory organization processes that support supracapacity memory storage. Previous research from our laboratory has shown that the extent to which such memory organization processes are required depends on both task factors (i.e., memory load) and subject factors (i.e., response speed). Task factors exert their effects mainly during WM encoding while subject factors exert their effects mainly during WM retrieval. In this study, we sought to test the generalizability of these phenomena under more difficult memory-demand conditions than have been used previously. During scanning, subjects performed a WM task in which they were required to maintain between 1 and 8 letters over a brief delay. Neural activity was measured during encoding, maintenance, and retrieval task periods using event-related functional magnetic resonance imaging. With increasing memory load, there were reaction time increases and accuracy rate decreases, ventrolateral PFC activation decreases during encoding, and dorsolateral PFC activation increases during maintenance and retrieval. These results suggest that the ventrolateral PFC mediates WM storage and that the dorsolateral PFC mediates strategic memory organization processes that facilitate supracapacity WM storage. Additionally, high-performing subjects showed overall less activation than low-performing subjects, but activation increases with increasing memory load in the lateral PFC during maintenance and retrieval. Low-performing subjects showed overall more activation than high-performing subjects, but minimal activation increases in the dorsolateral PFC with increasing memory load. These results suggest that individual differences in both neural efficiency and cognitive strategy underlie individual differences in the quality of subjects' WM performance.     

Encoding and retrieval in human medial temporal lobes: an empirical investigation using functional magnetic resonance imaging (fMRI)

The precise functional role of the hippocampus in human episodic memory is an unresolved question though it has recently been suggested that distinct medial temporal lobe (MTL) regions are involved in encoding and retrieval operations respectively. For example, a recent meta-analysis of positron emission tomography (PET) literature has suggested a rostral-caudal functional division in the medial temporal lobes (MTL), with rostral MTL mediating encoding and caudal MTL retrieval operations. However, a review of the combined PET and fMRI literature, reported in the present issue, while noting systematic discrepancies between PET and fMRI, reaches a conclusion that posterior MTL is involved in encoding. Here we present fMRI data, from a modified artificial grammar learning paradigm, that examines two questions concerning the functional role of the hippocampus, and related MTL structures in episodic memory. Firstly, we test a hypothesis that anterior hippocampus is activated during encoding and that this response is greater for novel items. Secondly, we test whether increasing familiarity with stimulus material is associated with a posterior MTL neural response. Our empirical findings support both hypotheses in that we demonstrate a left anterior hippocampal response sensitive to encoding demands and a posterior parahippocampal response sensitive to retrieval demands. Furthermore, we show that both anterior and posterior hippocampal responses are modulated to the degree to which stimuli can be assimilated into a meaningful rule-based framework.     

A Meta‐analysis on the neural basis of planning: Activation likelihood estimation of functional brain imaging results in the Tower of London task

The ability to mentally design and evaluate series of future actions has often been studied in terms of planning abilities, commonly using well‐structured laboratory tasks like the Tower of London (ToL). Despite a wealth of studies, findings on the specific localization of planning processes within prefrontal cortex (PFC) and on the hemispheric lateralization are equivocal. Here, we address this issue by integrating evidence from two different sources of data: First, we provide a systematic overview of the existing lesion data on planning in the ToL (10 studies, 211 patients) which does not indicate any evidence for a general lateralization of planning processes in (pre)frontal cortex. Second, we report a quantitative meta‐analysis with activation likelihood estimation based on 31 functional neuroimaging datasets on the ToL. Separate meta‐analyses of the activation patterns reported for Overall Planning (537 participants) and for Planning Complexity (182 participants) congruently show bilateral contributions of mid‐dorsolateral PFC, frontal eye fields, supplementary motor area, precuneus, caudate, anterior insula, and inferior parietal cortex in addition to a left‐lateralized involvement of rostrolateral PFC. In contrast to previous attributions of planning‐related brain activity to the entire dorsolateral prefrontal cortex (dlPFC) and either its left or right homolog derived from single studies on the ToL, the present meta‐analyses stress the pivotal role specifically of the mid‐dorsolateral part of PFC (mid‐dlPFC), presumably corresponding to Brodmann Areas 46 and 9/46, and strongly argue for a bilateral rather than lateralized involvement of the dlPFC in planning in the ToL. Hum Brain Mapp 38:396–413, 2017. © 2016 Wiley Periodicals, Inc.     

Contributions of the hippocampal subfields and entorhinal cortex to disambiguation during working memory

The hippocampus and medial temporal lobes (MTL) support the successful formation of new memories without succumbing to interference from related, older memories. Computational models and animal findings have implicated the dentate gyrus (DG), CA3, CA1, and entorhinal cortex (EC) in the disambiguation and encoding of well‐established, episodic events that share common elements. However, it is unknown if these hippocampal subfields and MTL (entorhinal, perirhinal, parahippocampal) cortices also contribute during working memory when overlapping stimuli that share related features are rapidly encoded and subsequently maintained over a brief temporal delay. We hypothesized that activity in CA3/DG hippocampal subfields would be greater for the rapid encoding of stimuli with overlapping features than for the rapid encoding of stimuli with distinct features. In addition, we predicted that CA1 and EC, regions that are associated with creating long‐term episodic representations, would show greater sustained activity across both encoding and delay periods for representations of stimuli with overlapping features than for those with distinct features. We used high‐resolution fMRI during a delayed matching‐to‐sample (DMS) task using face pairs that either shared (overlapping condition, OL) or did not share (non‐overlapping condition, NOL) common elements. We contrasted the OL condition with the NOL condition separately at sample (encoding) and during a brief delay (maintenance). At sample, we observed activity localized to CA3/DG, the subiculum, and CA1. At delay, we observed activity localized to the subiculum and CA1 and activity within the entorhinal, perirhinal, and parahippocampal cortices. Our findings are consistent with our hypotheses and suggest that CA3/DG, CA1 and the subiculum support the disambiguation and encoding of overlapping representations while CA1, subiculum and entorhinal cortex maintain these overlapping representations during working memory. © 2013 Wiley Periodicals, Inc.     

Interference of working memory load with long-term memory formation

Traditionally, it has been assumed that the medial temporal lobe (MTL) is indispensable for long-term memory (LTM) encoding, but only plays a minor role for working memory (WM) maintenance. Recently, however, an increasing number of studies questioned this seemingly clear distinction by showing that the MTL does participate in some WM processes, especially if multiple items are being maintained. This would predict that WM maintenance of multiple items interferes with simultaneous LTM encoding. Here, we tested this idea in a functional magnetic resonance imaging paradigm that required subjects to encode stimuli into LTM during simultaneous WM maintenance of either single or multiple items. Indeed, we found that maintenance of multiple items deteriorates simultaneous LTM encoding as compared with maintenance of single items. WM-related activation of the hippocampus was more pronounced in the condition with high WM load; in contrast, hippocampal activation related to LTM encoding was stronger in the low WM load condition. Successful LTM encoding was associated with a high level of activity in the adjacent parahippocampal cortex (PHC), leading to pronounced parahippocampal subsequent memory effects in the high load condition. This suggests that the PHC is a locus of WM–LTM interaction. Functional connectivity analysis with a seed in the PHC confirmed this result by revealing strong connectivity with the medial frontal cortex, which was only active in the high WM load condition. Taken together, these findings suggest that high WM demands interfere with LTM encoding and thus support the idea that WM and LTM processes interact in the MTL.     

The medial temporal lobes distinguish between within‐item and item‐context relations during autobiographical memory retrieval

During autobiographical memory retrieval, the medial temporal lobes (MTL) relate together multiple event elements, including object (within‐item relations) and context (item‐context relations) information, to create a cohesive memory. There is consistent support for a functional specialization within the MTL according to these relational processes, much of which comes from recognition memory experiments. In this study, we compared brain activation patterns associated with retrieving within‐item relations (i.e., associating conceptual and sensory‐perceptual object features) and item‐context relations (i.e., spatial relations among objects) with respect to naturalistic autobiographical retrieval. We developed a novel paradigm that cued participants to retrieve information about past autobiographical events, non‐episodic within‐item relations, and non‐episodic item‐context relations with the perceptuomotor aspects of retrieval equated across these conditions. We used multivariate analysis techniques to extract common and distinct patterns of activity among these conditions within the MTL and across the whole brain, both in terms of spatial and temporal patterns of activity. The anterior MTL (perirhinal cortex and anterior hippocampus) was preferentially recruited for generating within‐item relations later in retrieval whereas the posterior MTL (posterior parahippocampal cortex and posterior hippocampus) was preferentially recruited for generating item‐context relations across the retrieval phase. These findings provide novel evidence for functional specialization within the MTL with respect to naturalistic memory retrieval. © 2015 Wiley Periodicals, Inc.     

Finding and Not Finding Rat Perirhinal Neuronal Responses to Novelty

There is much evidence that the perirhinal cortex of both rats and monkeys is important for judging the relative familiarity of visual stimuli. In monkeys many studies have found that a proportion of perirhinal neurons respond more to novel than familiar stimuli. There are fewer studies of perirhinal neuronal responses in rats, and those studies based on exploration of objects, have raised into question the encoding of stimulus familiarity by rat perirhinal neurons. For this reason, recordings of single neuronal activity were made from the perirhinal cortex of rats so as to compare responsiveness to novel and familiar stimuli in two different behavioral situations. The first situation was based upon that used in “paired viewing” experiments that have established rat perirhinal differences in immediate early gene expression for novel and familiar visual stimuli displayed on computer monitors. The second situation was similar to that used in the spontaneous object recognition test that has been widely used to establish the involvement of rat perirhinal cortex in familiarity discrimination. In the first condition 30 (25%) of 120 perirhinal neurons were visually responsive; of these responsive neurons 19 (63%) responded significantly differently to novel and familiar stimuli. In the second condition eight (53%) of 15 perirhinal neurons changed activity significantly in the vicinity of objects (had “object fields”); however, for none (0%) of these was there a significant activity change related to the familiarity of an object, an incidence significantly lower than for the first condition. Possible reasons for the difference are discussed. It is argued that the failure to find recognition‐related neuronal responses while exploring objects is related to its detectability by the measures used, rather than the absence of all such signals in perirhinal cortex. Indeed, as shown by the results, such signals are found when a different methodology is used. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.     

Abnormal medial temporal activity for bound information during working memory maintenance in patients with schizophrenia

Alterations of binding in long‐term memory in schizophrenia are well established and occur as a result of aberrant activity in the medial temporal lobe (MTL). In working memory (WM), such a deficit is less clear and the pathophysiological bases remain unstudied. Seventeen patients with schizophrenia and 17 matched healthy controls performed a WM binding task while undergoing functional magnetic resonance imaging. Binding was assessed by contrasting two conditions comprising an equal amount of verbal and spatial information (i.e., three letters and three spatial locations), but differing in the absence or presence of a link between them. In healthy controls, MTL activation was observed for encoding and maintenance of bound information but not for its retrieval. Between‐group comparisons revealed that patients with schizophrenia showed MTL hypoactivation during the maintenance phase only. In addition, BOLD signals correlated with behavioral performance in controls but not in patients with schizophrenia. Our results confirm the major role that the MTL plays in the pathophysiology of schizophrenia. Short‐term and long‐term relational memory deficits in schizophrenia may share common cognitive and functional pathological bases. Our results provide additional information about the episodic buffer that represents an integrative interface between WM and long‐term memory. © 2009 Wiley‐Liss, Inc.     

Electrophysiological signature of working and long‐term memory interaction in the human hippocampus

Recent findings indicate that the hippocampus is not only crucial for long‐term memory (LTM) encoding, but plays a role for working memory (WM) as well. In particular, it has been shown that the hippocampus is important for WM maintenance of multiple items or associations between item features. Previous studies using intracranial electroencephalography recordings from the hippocampus of patients with epilepsy revealed slow positive potentials during maintenance of a single item and during LTM encoding, but slow negative potentials during maintenance of multiple items. These findings predict that WM maintenance of multiple items interferes with LTM encoding, because these two processes are associated with slow potentials of opposing polarities in the hippocampus. Here, we tested this idea in a dual‐task paradigm involving a LTM encoding task nested into a WM Sternberg task with either a low (one item) or a high (three items) memory load. In the high WM load condition, LTM encoding was significantly impoverished, and slow hippocampal potentials were more negative than in the low WM load condition. Time‐frequency analysis revealed that a reduction of slow hippocampal activity in the delta frequency range supported LTM formation in the low load condition, but not during high WM load. Together, these findings indicate that multi‐item WM and LTM encoding interfere within the hippocampus.     

A High‐resolution study of hippocampal and medial temporal lobe correlates of spatial context and prospective overlapping route memory

When navigating our world we often first plan or retrieve an ideal route to our goal, avoiding alternative paths that lead to other destinations. The medial temporal lobe (MTL) has been implicated in processing contextual information, sequence memory, and uniquely retrieving routes that overlap or “cross paths.” However, the identity of subregions of the hippocampus and neighboring cortex that support these functions in humans remains unclear. The present study used high‐resolution functional magnetic resonance imaging (hr‐fMRI) in humans to test whether the CA3/DG hippocampal subfield and parahippocampal cortex are important for processing spatial context and route retrieval, and whether the CA1 subfield facilitates prospective planning of mazes that must be distinguished from alternative overlapping routes. During hr‐fMRI scanning, participants navigated virtual mazes that were well‐learned from prior training while also learning new mazes. Some routes learned during scanning shared hallways with those learned during pre‐scan training, requiring participants to select between alternative paths. Critically, each maze began with a distinct spatial contextual Cue period. Our analysis targeted activity from the Cue period, during which participants identified the current navigational episode, facilitating retrieval of upcoming route components and distinguishing mazes that overlap. Results demonstrated that multiple MTL regions were predominantly active for the contextual Cue period of the task, with specific regions of CA3/DG, parahippocampal cortex, and perirhinal cortex being consistently recruited across trials for Cue periods of both novel and familiar mazes. During early trials of the task, both CA3/DG and CA1 were more active for overlapping than non‐overlapping Cue periods. Trial‐by‐trial Cue period responses in CA1 tracked subsequent overlapping maze performance across runs. Together, our findings provide novel insight into the contributions of MTL subfields to processing spatial context and route retrieval, and support a prominent role for CA1 in distinguishing overlapping episodes during navigational “look‐ahead” periods. © 2014 Wiley Periodicals, Inc.     

Process dissociation between contextual retrieval and item recognition

We employed a source memory task in an event related fMRI study to dissociate MTL processes associated with either contextual retrieval or item recognition. To introduce context during study, stimuli (photographs of buildings and natural landscapes) were transformed into one of four single-color-scales: red, blue, yellow, or green. In the subsequent old/new recognition memory test, all stimuli were presented as gray scale photographs, and old-responses were followed by a four-alternative source judgment referring to the color in which the stimulus was presented during study. Our results suggest a clear-cut process dissociation within the human MTL. While an activity increase accompanies successful retrieval of contextual information, an activity decrease provides a familiarity signal that is sufficient for successful item recognition.     

Dissociating age-related changes in cognitive strategy and neural efficiency using event-related fMRI

We used event-related fMRI to measure brain activity while younger and older adults performed an item-recognition task in which the memory-set size varied between 1 and 8 letters. Each trial was composed of a 4-second encoding period in which subjects viewed random letter strings, a 12-second retention period and a 2-second retrieval period in which subjects decided whether a single probe letter was or was not part of the memory set. For both groups, reaction time increased and accuracy decreased with increasing memory set-size. There were minimal age-related differences in activation patterns with increasing memory set-size in prefrontal cortex (PFC). Regression analyses of individual subjects' performance and cortical activity indicated that speed and accuracy accounted for considerable variance in dorsal and ventral PFC activity during encoding and retrieval. These results suggest that younger and older adults utilize similar working memory (WM) strategies to accommodate increasing memory demand. They support a model of cognitive slowing in which processing rate is related to neural efficiency.