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There has been a long tradition in memory research of adopting the view of a vital role of the medial temporal lobe and especially the hippocampus in declarative memory. Despite the broad support for this notion, there is an ongoing debate about what computations are performed by the different substructures. The present chapter summarizes several accounts of hippocampal functions in terms of the cognitive processes subserved by these structures, the information processed, and the underlying neural operations. Firstly, the value of the distinction between recollection and familiarity for the understanding of the role the hippocampus plays in memory is discussed. Then multiple lines of evidence for the role of the hippocampus in memory are considered. Cumulating evidence suggests that the hippocampus fosters the binding of disparate cortical representations of items and their spatiotemporal context into a coherent representation by means of a sparse conjunctive neural coding. This association of item and context will then lead to the phenomenological experience of recollection. In contrast, surrounding cortical areas have broader neural coding that provide a scalar signal of the similarity between two inputs (e.g. between the encoding and the retrieval). By this they form the basis of a feeling of familiarity, but also might encode the commonalities between these different inputs. However, a more complete picture of the importance of the hippocampus for declarative memories can only be drawn when the interactions of the medial temporal lobe with other brain areas are also taken into account. © 2014 S. Karger AG, Basel.
Memory Function and the Hippocampus
Bertram Opitz
Department of Psychology, University of Surrey, UK
Short Title: Hippocampus and Memory
There has been a long tradition in memory research adopting the view of a vital role of the medial
temporal lobe and especially the hippocampus in declarative memory. Despite the broad support for
this notion, there is an on-going debate about what computations are performed by the different
substructures. The present chapter summarises several accounts of hippocampal functions in terms
of the cognitive processes subserved by these structures, the information processed and the
underlying neural operations. Firstly, the value of the distinction between recollection and familiarity
for the understanding of the role the hippocampus plays in memory is discussed. Then multiple lines
of evidence for the role of the hippocampus in memory are considered. Cumulating evidence
suggests that the hippocampus fosters the binding of disparate cortical representations of items and
their spatio-temporal context into a coherent representation by means of a sparse conjunctive
neural coding. This association of item and context will then lead to the phenomenological
experience of recollection. In contrast, surrounding cortical areas have broader neural coding that
provide a scalar signal of the similarity between two inputs (e.g., between the encoding and the
retrieval). By this they form the basis of a feeling of familiarity but also might encode the
commonalities between these different inputs. However, a more complete picture of the
importance of the hippocampus for declarative memories could only be drawn when the
interactions of the medial temporal lobe with other brain areas are also taken into account.
Bertram Opitz
Department of Psychology
University of Surrey
phone: +44 1483 689449
fax: +44 1483 689553
Ever since the first report of profound amnesia following medial-temporal lobe (MTL) resection in
patient H.M. [1], there has been a large amount of research aiming at the functional role of the MTL
sub regions, especially of the hippocampus, in memory. This research includes all currently available
methods, including neuroimaging studies and electrophysiological recordings in humans, single cell
recordings in animals and neuropsychological studies of patients with brain injuries or of animals
with experimental lesions. Despite that any research method has its own strength and limitations
they all converge on the view that the hippocampus operates in the service of declarative memory.
One cognitive account assumes that the MTL is involved in the recognition of a previously
encountered event [24]. Despite the broad support for this notion, there is an on-going debate
about what computations are performed by different sub regions within the MTL. One prominent
view capitalizing on bidirectional interconnections between the hippocampus and the surrounding
medial-temporal lobe cortex (MTLC) proposes that the hippocampus is important for all forms of
declarative memory, including recognition memory [2]. A contrasting view emphasizes the
differences between the same structures within the MTL suggesting that the hippocampus and the
MTLC support different aspects of recognition memory[3; 5; 6]. In particular, the hippocampus and
the parahippocampal cortex were assumed to support recollection, i.e. recognition of an item on the
basis of the retrieval of specific contextual details of the previous learning experience, whereas the
perirhinal cortex subserves familiarity, i.e. item recognition on the basis of a scalar memory strength
but without retrieval of any specific detail about the study episode. These models, however, are
hard to reconcile with the notion of a highly integrated network connecting all MTLC structures with
each other and, most importantly, with the hippocampus [7]. Thus, more recent modifications
sought to overcome the explanatory limitations of models associating MTLC and hippocampal
functions in terms of the purely cognitive dichotomy between familiarity and recollection,
respectively, by focussing on the kind of information, i.e. item-specific and contextual information,
stored by the different substructures of the MTL [3; 8; 9]. Other models emphasize the putative
operational characteristics of specific brain regions to describe the role of these regions in memory
[7; 10]. The present chapter reviews evidence from animal research, neuropsychological studies with
patients suffering from amnesia and the growing body of neuroimaging studies that form the basis
of each of the different accounts of the role of the hippocampus in memory.
Cognitive Processes Accounts
Following a widely acknowledged cognitive view it has been argued that the hippocampus is vital for
recognition based on recollection but not for recognition based on familiarity (Figure 1A). These
models usually further argue that MTLC regions (especially the perirhinal cortex but not the
parahippocampal cortex) are essential for familiarity based recognition, and that this function is
independent of the hippocampus [3; 11]. Consistent with this view, patients with severe hypoxic
damage to the hippocampus exhibit disproportional large deficits in associative recognition (thought
to rely on recollection) as compared to simple item memory (relying on familiarity, e.g. [12]). An
almost identical pattern of impaired recollection and preserved familiarity has also been observed in
a patient with selective hippocampal atrophy caused by meningitis [13]. Most striking evidence in
favour of dual process models comes from a double dissociation between deficits in recollection or
associative memory following hippocampal damage compared to deficits in familiarity or item
memory following damage to the perirhinal cortex [14]. These observations are paralleled by several
animal studies demonstrating that rats, initially trained to recognize associations between an odour
(e.g. , cumin, lemon, thyme) and one of several digging media (e.g. , sand, wood chips, etc.) and then
retested after selective damage to the hippocampus, exhibited impaired recollection of the
associations while memory for the odours alone was spared indicating intact familiarity [15]. In the
same vein, neuroimaging studies in healthy participants employing associative recognition memory
task demonstrated greater hippocampal activity for successful as compared to failed source
recollection [16]. In this experiment participants studied a word list while alternating between a
pleasant/unpleasant decision and a concrete/abstract decision. At test, they were required to
discriminate between two simultaneously presented test words by selecting the member of the pair
previously associated with a particular encoding task. Successful source retrieval was associated with
increased activity in the left hippocampus.
Another method capitalizes on Receiver-Operating-Characteristics (ROC) assuming that recollection
is a threshold process whereas familiarity varies in a continuous manner with response confidence
[17]. A number of studies have, therefore, used linear and curvi-linear approximations of confidence
ratings (representing recollection and familiarity, respectively) to identify regions where
hemodynamic activity systematically varies with recognition confidence [1820]. Such parametric
analyses consistently showed that hippocampal activity was related to recollection. While some
studies found increasing activity in the perirhinal cortex as perceived strength of familiarity
increased [18], others reported monotonic decreases in activity with increasing memory strength
not only in the perirhinal cortex but also in the anterior hippocampus [19]. Yet another result was
reported in a recent study [20] observing both decreasing and increasing activity as a function of
increasing familiarity in the anterior and posterior perirhinal cortex, respectively. This latter finding
emphasizes the contradictory results with respect to the role the MTLC plays in recognition memory.
A prominent alternative view explains the functional distinction between the hippocampus and the
adjacent MTLC structures described above with a single cognitive process in which differences in
memory strength account for the differential involvement of the hippocampus and the perirhinal
and parahippocampal cortices [2; 4]. While a weak memory trace seems sufficient to engage the
MTLC, strong memories are required to engage the more powerful computational properties of the
hippocampus. Evidence for this view is for example provided by studies demonstrating that amnesic
patients are similarly impaired in all kinds of declarative memory [21]. However, single process
models cannot account for the double dissociations in amnesia and neuroimaging studies cited
above, nor can single process theories account for the double dissociations between the role of the
hippocampus and the surrounding MTLC in recollection and familiarity in recent animal studies.
Information Based Accounts
More recent models move beyond the simple and rather phenomenological dichotomy between
recollection and familiarity towards an understanding of MTL functions in terms of the information
they store. As depicted in Figure 1B these models propose that the perirhinal and the
parahippocampal cortex support the encoding and retrieval of item-specific and contextual
information, respectively whereas the hippocampus stores representations of itemcontext
associations [3; 8; 9]. This view is based on increased hippocampal activity in tasks emphasizing such
conjunctive memory representations such as memorizing paired associates [22], source memory
tasks [23] and tasks requiring also the spatial location of a previously presented item to be
remembered [24]. Conversely, in many of those studies activity in the perirhinal cortex correlates
with item rather than conjunctive memory performance [22; 24]. Together these studies
demonstrated that an increase of activity of the hippocampus is essential for the process of relating
an item to contextual information during retrieval. This notion has gained further support from
neuropsychological studies in amnesic patients [25; 26]. For instance, it was demonstrated that
amnesic patients could well discriminate between old and new visual scenes but were unable to
distinguish between intact old scenes and manipulated old scenes (e.g. by left right shifting of
particular elements within the scene) [26] indicating a deficit in processing the relations of items
within a specific context rather than a deficit in recollection, per se.
Parallel evidence has also been obtained from animal studies showing that hippocampal neurons
develop representations of the specific combination of stimulus elements (odours A and B) and the
context (room X and Y) in which they occur [27]. In the beginning of their training the rats’
hippocampal neurons responded selectively to a specific location in environment occupied by the
animals (so-called place cells”). However, after several exposures to the same contextual
discrimination problem, i.e. odour A is only rewarded in room X, when the animals acquired the
item-context associations, some neurons began to fire selectively during the sampling of a specific
item in a particular context and these cells continued to exhibit item-context specificity after
learning. Similar firing patters for the combination of specific stimuli with a location or behavioural
context in which they occurred was also demonstrated for monkeys [28] and humans [29]. These
results indicate that hippocampal firing patterns reflect unique conjunctions of stimuli with the
places and contexts in which the stimuli occur. Extending this view it was proposed that also
associations of multiple items that share their cortical representations due to a substantial feature
overlap (within the same domain, e.g. two faces or two words) can be stored by the perirhinal cortex
and recognized based on their familiarity [30]. Evidence for this assumption comes from several
neuropsychological patients with selective hippocampal damage demonstrating severe impairments
in the recognition of e.g. objectlocation and facevoice associations, while they were relatively
unimpaired at recognizing pairs of words, non-words, unknown and famous faces after one or
several study trials [31].
Common to all the examples described above and more general to typical episodic memory tasks,
the item presented at the time of learning has to be associated with its specific study context. Later
during recognition this association must be retrieved. As argued above the hippocampus enables the
retrieval of the association of an item with its study context and, consequently, will lead to the
phenomenological experience of recollection. In contrast, the proposed role of perirhinal cortex in
retrieving item information alone is consistent view the dual process view of familiarity based
recognition. Thus, recollection and familiarity can be regarded as rather epiphenomenal to the
information processed within the hippocampus and the MTLC, respectively.
Neural Process Based Accounts
In a similar vein, others have proposed that functional differences between MTL sub-regions are
based on their key computational role in memory [7; 10; 32]. Despite their differences these views
about MTL functions converge on the opinion that the distinct properties of hippocampal neurons
and neurons in the surrounding MTLC subserve different memory processes (Figure 1C). It was
suggested that sparse neural coding within the hippocampus will (a) foster the convergence of
disparate cortical representations of items, actions, etc. and their spatiotemporal context that
compose a unique input into a bound representation of that input and will (b) reduce the probability
that the same neurons within the hippocampus are activated by two different inputs, thereby
leading to distinct (pattern-separated) representations [10; 32]. The process of binding mentioned in
(a) can be specified in terms of relational operations (e.g. identity, greater than or earlier than) that
link together and organize the individual elements of an experience. For example, during paired
associate learning two items provide relational information about their identity with respect to their
spatio-temporal context that is processed by the hippocampus. It is capable to organize any arbitrary
relations and by this very effortful but highly flexible. Consequently, it allows for the rearrangement
of the elements of individual experiences to deal with novel situations. Crucially, the hippocampal
circuitry possesses anatomical and computational characteristics to support these properties of
separated relational bindings (see [3], for a detailed discussion). Due to this separation of different
inputs mentioned in (b) the hippocampus is able to entirely reconstruct each single input (pattern
completion), e.g. an item bound to its study context. It thereby enables the retrieval of contextual
information. Thus, the process of relational binding will lead to recognition based on recollection.
This close connection between relational binding and recollection was corroborated by animal
studies and neuroimaging studies (extensively reviewed by [3; 9]).
In contrast, the neural activity of separate inputs to the MTLC is highly overlapping and therefore
allows processing the shared structure of these separate inputs (representational bindings). For
example, the first presentation of an item in a particular context, e.g. during encoding, weakly
activates a large number of MTLC neurons, whereas repeated and thus familiar stimuli although in a
different context, e.g. during a recognition test, activate only a subset of these neurons representing
the familiar stimuli but every neuron is activated to a stronger degree [32]. Thus, during recognition
the presentation of a studied item initiates a set of processes that may be described in a more
cognitive framework as a comparison between the neural activity associated with the short-lived
representation of the actual stimulus and the confined activity in the MTLC of the previous
encounter of that stimulus. As a result, a scalar familiarity signal is provided that tracks the global
similarity between the test probe and the studied items [33]. It should be noted that similar to the
information based accounts it is assumed that, due to the divergent neural connections of the MTLC
sub regions to neocortical areas, different structures within the MTLC bind different features of the
entire input [7, 34]. While the perirhinal cortex encodes information about objects, the
parahippocampal cortex represents the respective context of that input (Figure 1C).
As a consequence of this representational binding the MTLC is capable extracting the general
regularities inherent in the input over repeated exposures to that input. These regularities mainly
comprise frequency of co-occurrence but may also include transition probabilities or temporal
contingencies (e.g. red and green in a traffic light, or item positions in a list learning paradigm).
However, there are limitations to the ability of the MTLC to abstract the regularities inherent in the
recent input. As the MTLC receives the majority of its inputs from unimodal and polymodal
association areas [34], representational bindings within the MTLC are necessarily based on
superficial perceptual features. Consequently, the MTLC is hardly capable to create abstract
representations that are essential for goal-directed behaviour. However, the prefrontal cortex (PFC)
seems ideally suited for the abstraction of such behaviour-guiding representations [35]. Thus, while
the MTLC mainly binds the representation of the actual item/context to the representation of a
previous occurrence of that same item/context, the PFC mediates the binding of the actual event to
a more abstract or prototypical representation of invariant and non-accidental features of that
This binding view is supported by recent studies demonstrating an impairment of patients with
anterior MTL lesions, including the perirhinal cortex, in perceptual discrimination of complex objects
with a large number of overlapping features [36]. More importantly, this impairment was largest for
objects with pre-existing semantic representations, e.g. beasts as compared to novel objects such as
bar codes. This is consistent with the present view, that representational bindings supported by the
perirhinal cortex link the actual appearance of a particular object to the mental representation of
previous experiences with that same object. In a similar vein, the parahippocampal cortex mediates
representational bindings of contextual features. For instance, it was demonstrated that the
parahippocampal cortex is more active for objects that are strongly associated with a specific
context (e.g. roulette wheel) than for objects that are very weakly associated with many possible
contexts (e.g. cherry) [37]. These examples underscore the important role of both cortices for
representational binding by demonstrating that readdressing object and/or contextual features of
object occurrence during the repeated processing of a particular event require the integrity/activity
of perirhinal and parahippocampal cortex, respectively.
The present chapter summarized part of the recent evidence for the role of the hippocampus and
the surrounding MTLC in memory. Several accounts described hippocampal function in terms of the
cognitive processes subserved by different substructures within the MTL others have focused more
on the different information processed by these structures or on the underlying neural operations.
Although accounts based on the dichotomy between recollection and familiarity have a long
standing tradition in memory research, it is still an open question whether the brain actually
operates on this dichotomy. The two other accounts are more directly related to the different
structures and the respective neural processes. Despite the exact relation of the neural processes to
the assumed cognitive processes remains to be clarified it seems that the neural processes account
cuts across the boundaries inherent in the cognitive processes.
The list of accounts on hippocampal memory function is far from being complete. Other accounts
implicate the hippocampus in recent but not in remote memories. These are special cases of the
overarching issue of memory consolidation assuming that under certain circumstances memories
can become independent of the hippocampus. Although these circumstances are subject to current
debate they are of high importance for amnesia research. Yet others emphasize the role of the
hippocampus in spatial memory. This will be covered in the next chapter. More general, these highly
different views are suggestive of a more general role of MTL substructures in memory than
discussed in the present chapter.
It should be also noted that the hippocampus and the perirhinal and parahippocampal cortices are
interconnected with multiple brain areas in the parietal and frontal lobes. As the focus of this
chapter was on the role of the hippocampus in memory the important contribution of these other
brain structures was not covered. However, only when their role was taken into account a more
complete picture of the importance of the medial temporal lobe for the formation of declarative
memories can be drawn.
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Figure 1. Schematic illustrations of the core assumptions of (A) Cognitive Processes Accounts, (B)
Information Based Accounts (cf. [3]) and (C) Neural Processes Based Accounts (cf. [10])
about the role of different substructures within the medial temporal lobes in memory.
PRC perirhinal cortex, PHC parahippocampal cortex, PFC prefrontal cortex
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... One study has found that both normal old individuals' and aMCI patients' memory can be consolidated due to the significant elevation of endogenous norepinephrine induced by a 6-min aerobic stationary bicycle exercise at 70% VO 2 max (57). Alternatively, it is well-known that the hippocampus is also involved in memory consolidation (58,59). Some researchers have suggested that even mild physical exercise can facilitate the functional connection between the dentate gyrus/CA3 of the hippocampus and cortical regions (e.g., parahippocampal), which may contribute to memory improvement (60). ...
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Introduction Patients with amnestic mild cognitive impairment (aMCI) are more likely to develop dementia compared to patients with non-aMCI (naMCI). Among the mixed samples of aMCI and naMCI, exercise interventions are effective for patients with MCI to improve cognitive functions. However, the influence of exercise interventions on patients with aMCI is still unclear. Objective The objective of this systematic review and meta-analysis is to evaluate the influence of exercise interventions on cognitive functions in patients with aMCI. Methods Four literature databases (PubMed, Web of Science, EBSCO, and Cochrane Library) and three Chinese databases (China National Knowledge Infrastructure, Wanfang, and China Science and Technology Journal Database) were searched from their inception to August 31, 2022. Based on the preliminary search of seven databases and their cited references, a total of 2,290 records were identified. Finally, 10 studies with a total of 28 data points involving 575 participants with aMCI were included in this meta-analysis. If the measurements of outcomes were different among studies, the effect size was synthesized using the standardized mean difference (SMD) with a 95% confidence interval (CI). If the measurements were the same, the weight mean difference (WMD) with a 95% CI was used to integrate the effect size. Data synthesis The results showed that exercise interventions had no significant effects on improving several specific domains of cognitive functions including working memory (WMD = −0.05; 95% CI = −0.74 to 0.63; p = 0.88; I ² = 78%) and attention (SMD = 0.20; 95% CI = −0.31 to 0.72; p = 0.44; I ² = 60%). Additionally, exercise interventions had a significant effect on global cognitive function (SMD = 0.70; 95% CI = 0.50–0.90; p < 0.00001; I ² = 29%) and some specific cognitive domains including immediate recall (SMD = 0.55; 95% CI = 0.28–0.81; p < 0.0001; I ² = 0%), delayed recall (SMD = 0.66; 95% CI = 0.45–0.87; p < 0.00001; I ² = 37%), and executive function (SMD = 0.38; 95% CI = 0.16–0.60; p = 0.0006; I ² = 4%). Furthermore, subgroup analysis based on the intervention forms indicated that multi-component interventions (SMD = 0.44; 95% CI = 0.11–0.77; p = 0.009; I ² = 0%) appeared to be less effective than the single-component intervention (SMD = 0.85; 95% CI = 0.60–1.10; p < 0.00001; I ² = 10%) in terms of boosting global cognitive function. Conclusion This meta-analysis suggests that the exercise can help patients with aMCI improve global cognitive function. And exercise interventions have positive influence on enhancing several specific cognitive domains such as immediate recall, delayed recall, and executive function. Systematic review registration: , identifier: CRD42022354235.
... However, recent research suggests that formation of and navigation on cognitive maps are not limited to physical space, but extend to more abstract conceptual, visual or even social spaces [2][3][4]. A simplified processing framework for the complex can be described as following: highly processed information from our sensory organs are fed into the hippocampal complex where the perceived information is put into context, i.e. associated with past experiences [5]. Grid [6] and place [7] cells enable map like codes, and research suggests that they form cognitive maps [8] [9], thereby contributing to process memories, emotions and navigation [10](cf. ...
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The hippocampal-entorhinal complex plays a major role in the organization of memory and thought. The formation of and navigation in cognitive maps of arbitrary mental spaces via place and grid cells can serve as a representation of memories and experiences and their relations to each other. The multi-scale successor representation is proposed to be the mathematical principle underlying place and grid cell computations. Here, we present a neural network, which learns a cognitive map of a semantic space based on 32 different animal species encoded as feature vectors. The neural network successfully learns the similarities between different animal species, and constructs a cognitive map of 'animal space' based on the principle of successor representations with an accuracy of around 30% which is near to the theoretical maximum regarding the fact that all animal species have more than one possible successor, i.e. nearest neighbor in feature space. Furthermore, a hierarchical structure, i.e. different scales of cognitive maps, can be modeled based on multi-scale successor representations. We find that, in fine-grained cognitive maps, the animal vectors are evenly distributed in feature space. In contrast, in coarse-grained maps, animal vectors are highly clustered according to their biological class, i.e. amphibians, mammals and insects. This could be a possible mechanism explaining the emergence of new abstract semantic concepts. Finally, even completely new or incomplete input can be represented by interpolation of the representations from the cognitive map with remarkable high accuracy of up to 95%. We conclude that the successor representation can serve as a weighted pointer to past memories and experiences, and may therefore be a crucial building block for future machine learning to include prior knowledge, and to derive context knowledge from novel input.
... W trakcie procesu ontogenezy śródmózgowie rozwija się w konary mózgu, nakrywę śródmózgowia i pokrywę śródmózgowia. Z tyłomózgowia wtórnego tworzą się most i móżdżek, natomiast z rdzeniomózgowia wykształca się rdzeń przedłużony (7,33,49). Z wymienionych struktur najważniejszą w aspekcie szeroko pojętego procesu "nauki" jest układ limbiczny, a w zasadzie należący do niego hipokamp (50). ...
The study aimed to summarize the knowledge about selected biochemical processes involved in the process of learning and memorizing in particular brain structures. The brain of mammals is composed of many structures and each of them is involved in the creation of memory processes to a different degree. The relevant element is the hippocampus, which is responsible for transferring information from short-term memory to long-term memory. Learning and memory are also greatly influenced by compounds called neurosteroids, which work by stimulating or inhibiting synaptic transmission. De novo synthesized neurosteroids in most areas of the brain are endogenous modulators of learning and memory formation in the hippocampus. © 2021 Polskie Towarzystwo Nauk Weterynaryjnych. All rights reserved.
A major concern for cardiac arrest (CA) survivors is the manifestation of long-term cognitive impairments. Physical exercise (PE) is a well-established approach to improve cognitive functions under certain pathological conditions. We previously showed that PE post-CA mitigates cognitive deficits, but the underlying mechanisms remain unknown. To define neuroprotective mechanisms, we analyzed whether PE post-CA protects neurons involved in memory. We first performed a contextual fear conditioning (CFC) test to confirm that PE post-CA preserves memory in rats. We then conducted a cell-count analysis and determined the number of live cells in the hippocampus, and septal and thalamic nuclei, all areas involved in cognitive functions. Lastly, we performed RNA-seq to determine PE post-CA effect on gene expression. Following CA, exercised rats had preserved CFC memory than sham PE animals. Despite this outcome, PE post-CA did not protect hippocampal cells from dying. However, PE ameliorated cell death in septal and thalamic nuclei compared to sham PE animals, suggesting that these nuclei are crucial in mitigating cognitive decline post-CA. Interestingly, PE affected regulation of genes related to neuroinflammation, plasticity, and cell death. These findings reveal potential mechanisms whereby PE post-CA preserves cognitive functions by protecting septal and thalamic cells via gene regulation.
Background: American Indians have high prevalence of risk factors for Alzheimer's disease and related dementias (ADRD) compared to the general population, yet dementia onset and frequency in this population are understudied. Intraindividual cognitive variability (IICV), a measure of variability in neuropsychological test performance within a person at a single timepoint, may be a novel, noninvasive biomarker of neurodegeneration and early dementia. Objective: To characterize the cross-sectional associations between IICV and hippocampal, total brain volume, and white matter disease measured by magnetic resonance imaging (MRI) among older American Indians. Methods: IICV measures for memory, executive function, and processing speed, and multidomain cognition were calculated for 746 American Indians (aged 64-95) who underwent MRI. Regression models were used to examine the associations of IICV score with hippocampal volume, total brain volume, and graded white matter disease, adjusting for age, sex, education, body mass index, intracranial volume, diabetes, stroke, hypertension, hypercholesterolemia, alcohol use, and smoking. Results: Higher memory IICV measure was associated with lower hippocampal volume (Beta = -0.076; 95% CI -0.499, -0.023; p = 0.031). After adjustment for Bonferroni or IICV mean scores in the same tests, the associations were no longer significant. No IICV measures were associated with white matter disease or total brain volume. Conclusion: These findings suggest that the IICV measures used in this research cannot be robustly associated with cross-sectional neuroimaging features; nonetheless, the results encourage future studies investigating the associations between IICV and other brain regions, as well as its utility in the prediction of neurodegeneration and dementia in American Indians.
The P2X7 receptor (P2X7R) is a key neuroinflammation target in a variety of neurodegenerative diseases. Improved radiosynthesis was developed according to the previously reported P2X7R antagonist GSK1482160. Biodistribution, radiometabolite, and dynamic positron emission tomography/computed tomography-magnetic resonance imaging (PET/CT-MRI) of the lipopolysaccharide (LPS) rat model and the transgenic mouse model of Alzheimer's disease (AD) revealed a stable, low uptake of [18F]4A in the brain of healthy rats but a higher standardized uptake value ratio (SUVR) in LPS-treated rats (1.316 ± 0.062, n = 3) than in sham (1.093 ± 0.029, n = 3). There were higher area under curves (AUCs) in the neocortex (25.12 ± 1.11 vs 18.94 ± 1.47), hippocampus (22.50 ± 3.41 vs 15.90 ± 1.59), and basal ganglia (22.26 ± 0.81 vs 15.32 ± 1.76) of AD mice (n = 3) than the controls (n = 3) (p < 0.05). Furthermore, 50 min dynamic PET in healthy nonhuman primates (NHPs) indicated [18F]4A could penetrate the blood-brain barrier (BBB). In conclusion, [18F]4A from this study is a potent P2X7R PET tracer that warrants further neuroinflammation quantification in human studies.
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Binding mechanisms are considered as basic cognitive operations, performing different functions in learning and memory. This review will cover two of these binding mechanisms: relational binding of information about stimuli and actions with their spatio-temporal context into a circumscribed cognitive event and representational binding of feature representations common to a number of such events, thereby integrating these representations with existing knowledge and, thus, leading to decontextualized knowledge about the world. I will survey evidence from recent neuropsychological, electrophysiological and neuroimaging studies, including my own work, demonstrating that relational binding operations are performed within the hippocampal system, whereas representational binding is subserved by the surrounding medial-temporal lobe cortex and prefrontal brain areas. I then present examples of conditions that differentially implement both binding mechanisms. Lastly, summarizing the extant literature on binding mechanisms I speculate on whether these binding mechanism operate in a similar way across different cognitive domains or whether they are domain-specific.
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In the test-pair similarity effect, forced-choice recognition is more accurate for similar test pairs, such as leopard-cheetah, than it is for unrelated test pairs, such as leopard-turnip. According to global matching models, this occurs because the retrieved familiarities of similar items are correlated. In the Minerva 2 model, global matching underlies frequency judgments as well as recognition memory. One implication of this model is that judged frequencies of similar items should be correlated. Another implication is that judgments of summed frequency for pairs of words (how many presentations were there of word1 and word2 combined?) should have higher variance when word1 and word2 are similar than when they are unrelated. These predictions were tested and confirmed in two experiments. A review of these and other results suggests that theories of recognition memory should also be applicable to frequency-judgment tasks.
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To account for dissociations observed in recognition memory tests, several dual-process models have been proposed that assume that recognition judgments can be based on the recollection of details about previous events or on the assessment of stimulus familiarity. In the current article, these models are examined, along with the methods that have been developed to measure recollection and familiarity. The relevant empirical literature from behavioral, neuropsychological, and neuroimaging studies is then reviewed in order to assess model predictions. Results from a variety of measurement methods, including task-dissociation and process-estimation methods, are found to lead to remarkably consistent conclusions about the nature of recollection and familiarity, particularly when ceiling effects are avoided. For example, recollection is found to be more sensitive than familiarity to response speeding, division of attention, generation, semantic encoding, the effects of aging, and the amnestic effects of benzodiazepines, but it is less sensitive than familiarity to shifts in response criterion, fluency manipulations, forgetting over short retention intervals, and some perceptual manipulations. Moreover, neuropsychological and neuroimaging results indicate that the two processes rely on partially distinct neural substrates and provide support for models that assume that recollection relies on the hippocampus and prefrontal cortex, whereas familiarity relies on regions surrounding the hippocampus. Double dissociations produced by experimental manipulations at time of test indicate that the two processes are independent at retrieval, and single dissociations produced by study manipulations indicate that they are partially independent during encoding. Recollection is similar but not identical to free recall, whereas familiarity is similar to conceptual implicit memory, but is dissociable from perceptual implicit memory. Finally, the results indicate that recollection reflects a thresholdlike retrieval process that supports novel learning, whereas familiarity reflects a signal-detection process that can support novel learning only under certain conditions. The results verify a number of model predictions and prove useful in resolving several theoretical disagreements.
A review of medial temporal lobe connections reveals three distinct groupings of hippocampal efferents. These efferent systems and their putative memory functions are: (1) The 'extended-hippocampal system' for episodic memory, which involves the anterior thalamic nuclei, mammillary bodies and retrosplenial cortex, originates in the subicular cortices, and has a largely laminar organisation; (2) The 'rostral hippocampal system' for affective and social learning, which involves prefrontal cortex, amygdala and nucleus accumbens, has a columnar organisation, and originates from rostral CA1 and subiculum; (3) The 'reciprocal hippocampal-parahippocampal system' for sensory processing and integration, which originates from the length of CA1 and the subiculum, and is characterised by columnar, connections with reciprocal topographies. A fourth system, the 'parahippocampal-prefrontal system' that supports familiarity signalling and retrieval processing, has more widespread prefrontal connections than those of the hippocampus, along with different thalamic inputs. Despite many interactions between these four systems, they may retain different roles in memory which when combined explain the importance of the medial temporal lobe for the formation of declarative memories.
Neuroimaging and lesion studies have seemed to converge on the idea that the hippocampus selectively supports recollection. However, these studies usually involve a comparison between strong recollection-based memories and weak familiarity-based memories. Studies that avoid confounding memory strength with recollection and familiarity almost always find that the hippocampus supports both recollection and familiarity. We argue that the functional organization of the medial temporal lobe (MTL) is unlikely to be illuminated by the psychological distinction between recollection and familiarity and will be better informed by findings from neuroanatomy and neurophysiology. These findings indicate that the different structures of the MTL process different attributes of experience. By representing the widest array of attributes, the hippocampus supports recollection-based and familiarity-based memory of multiattribute stimuli.
Previous research indicates a critical role of the hippocampus in memory for events in the context in which they occur. However, studies to date have not provided compelling evidence that hippocampal neurons encode event-context conjunctions directly associated with this kind of learning. Here we report that, as animals learn different meanings for items in distinct contexts, individual hippocampal neurons develop responses to specific stimuli in the places where they have differential significance. Furthermore, this conjunctive coding evolves in the form of enhanced item-specific responses within a subset of the preexisting spatial representation. These findings support the view that conjunctive representations in the hippocampus underlie the acquisition of context-specific memories.
Eye movements were monitored to assess memory for scenes indirectly (implicitly). Two eye movement-based memory phenomena were observed: (a) the repetition effect, a decrease in sampling of previously viewed scenes compared with new scenes, reflecting memory for those scenes, and (b) the relational manipulation effect, an increase in viewing of the regions where manipulations of relations among scene elements had occurred. In normal control subjects, the relational manipulation effect was expressed only in the absence of explicit awareness of the scene manipulations. Thus, memory representations of scenes contain information about relations among elements of the scenes, at least some of which is not accessible to verbal report. But amnesic patients with severe memory impairment failed to show the relational manipulation effect. Their failure to show any demonstrable memory for relations among the constituent elements of scenes suggests that amnesia involves a fundamental deficit in relational (declarative) memory processing.
The hallmark of medial temporal lobe amnesia is a loss of episodic memory such that patients fail to remember new events that are set in an autobiographical context (an episode). A further symptom is a loss of recognition memory. The relationship between these two features has recently become contentious. Here, we focus on the central issue in this dispute--the relative contributions of the hippocampus and the perirhinal cortex to recognition memory. A resolution is vital not only for uncovering the neural substrates of these key aspects of memory, but also for understanding the processes disrupted in medial temporal lobe amnesia and the validity of animal models of this syndrome.