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Effect of aging differs for memory of object identity and object position within a spatial context

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There has been considerable focus on investigating age-related memory changes in cognitively healthy older adults, in the absence of neurodegenerative disorders. Previous studies have reported age-related domain-specific changes in older adults, showing increased difficulty encoding and processing object information but minimal to no impairment in processing spatial information compared with younger adults. However, few of these studies have examined age-related changes in the encoding of concurrently presented object and spatial stimuli, specifically the integration of both spatial and nonspatial (object) information. To more closely resemble real-life memory encoding and the integration of both spatial and nonspatial information, the current study developed a new experimental paradigm with novel environments that allowed for the placement of different objects in different positions within the environment. The results show that older adults have decreased performance in recognizing changes of the object position within the spatial context but no significant differences in recognizing changes in the identity of the object within the spatial context compared with younger adults. These findings suggest there may be potential age-related differences in the mechanisms underlying the representations of complex environments and furthermore, the integration of spatial and nonspatial information may be differentially processed relative to independent and isolated representations of object and spatial information.
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Effect of aging differs for memory of object identity
and object position within a spatial context
Tammy Tran,
1
Kaitlyn E. Tobin,
2
Sophia H. Block,
1
Vyash Puliyadi,
1
Michela Gallagher,
1
and Arnold Bakker
2
1
Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, Maryland 21218, USA;
2
Department of
Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA
There has been considerable focus on investigating age-related memory changes in cognitively healthy older adults, in the
absence of neurodegenerative disorders. Previous studies have reported age-related domain-specific changes in older adults,
showing increased difficulty encoding and processing object information but minimal to no impairment in processing
spatial information compared with younger adults. However, few of these studies have examined age-related changes in
the encoding of concurrently presented object and spatial stimuli, specifically the integration of both spatial and nonspatial
(object) information. To more closely resemble real-life memory encoding and the integration of both spatial and nonspa-
tial information, the current study developed a new experimental paradigm with novel environments that allowed for the
placement of different objects in different positions within the environment. The results show that older adults have de-
creased performance in recognizing changes of the object position within the spatial context but no significant differences
in recognizing changes in the identity of the object within the spatial context compared with younger adults. These findings
suggest there may be potential age-related differences in the mechanisms underlying the representations of complex envi-
ronments and furthermore, the integration of spatial and nonspatial information may be differentially processed relative to
independent and isolated representations of object and spatial information.
Advancing age is associated with changes in a number of cognitive
domains (Erickson and Barnes 2003; Salthouse 2004; Craik and
Bialystok 2006). Particularly age-related changes in episodic mem-
ory function have been frequently reported (Grady and Craik 2000;
Craik and Bialystok 2006). In addition to a general decline in long-
term retention, older adults show a reduced ability to differentiate
between highly similar object representations (Yassa et al. 2011;
Stark et al. 2013, 2015; Reagh et al. 2016; Berron et al. 2018) and
object features (Yeung et al. 2017) compared with young adults.
In contrast, spatial representations appear to be relatively spared
(Fidalgo et al. 2016; Stark and Stark 2017) with older adults show-
ing performance similar to young adults recognizing subtle chang-
es in a spatial environment (Berron et al. 2018) and changes in the
location of an object when presented on a blank screen (Reagh
et al. 2016, 2018).
The dissociation and integration of object and spatial infor-
mation has been a key question in memory research. Older adults
show signicant impairments in memory binding and maintain-
ing associations despite having intact memory for the individual
items (Chalfonte and Johnson 1996; Naveh-Benjamin 2000; Old
and Naveh-Benjamin 2008). This is also observed in object-
location binding with impairments in recalling the specic loca-
tion of objects (Kessels et al. 2007; Berger-Mandelbaum and
Magen 2019; Muffato et al. 2019) as well as recalling the identity
of an object within an environment (Schiavetto et al. 2002;
Kessels et al. 2007; Mazurek et al. 2015). The binding of object-
location information has been hypothesized to involve the medial
temporal lobes, including the hippocampus (Postma et al. 2008),
although age-related changes in the prefrontal cortex, posterior
neocortex and other regions have also been implicated in object lo-
cation and object identity tasks (Schiavetto et al. 2002;
Meulenbroek et al. 2010). In the medial temporal lobes, the inte-
gration of object and spatial information is thought to arise from
two parallel information processing streams (Eichenbaum 1999;
Eichenbaum et al. 1999; Davachi 2006; Ranganath and Ritchey
2012; Knierim et al. 2013). One pathway, commonly referred to
as the whatpathway involves the perirhinal cortex and the later-
al entorhinal cortex, and is thought to predominately process
information about objects, items and events, while the where
pathway involving the parahippocampal cortex and the medial en-
torhinal cortex is thought to process contextual and spatial infor-
mation. Information from both pathways is projected to the
hippocampus, which is then thought to integrate the spatial and
nonspatial information into a cohesive memory spacethrough
a mechanism that is common to both object or episodic and spatial
information (Eichenbaum et al. 1999).
However, emerging evidence suggests the processing of object
and spatial information may be more integrated than previously
thought with the lateral entorhinal cortex processing multimodal
information, receiving both object and spatial information (Witter
et al. 2017; Doan et al. 2019; Nilssen et al. 2019). In rodent studies,
the lateral entorhinal cortex has been reported to be involved in
the encoding of features from both the object and the environ-
ment (Deshmukh and Knierim 2011; Yoganarasimha et al. 2011;
Deshmukh et al. 2012; Knierim et al. 2013). Rodent studies using
single cell recordings in the lateral entorhinal cortex show that
neurons in this region encode object-related information as well
as spatial information about the object (e.g., position in relation-
ship to the environment). These studies also show cells in the
Corresponding author: abakker@jhu.edu
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239 Learning & Memory
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lateral entorhinal cortex that track the position of an object in the
environment and do not re when that object is no longer present
(Deshmukh and Knierim 2011). A different subset of cells (object
trace cells) have been reported to re in previously experienced
positions of an object within an environment (Deshmukh and
Knierim 2011; Tsao et al. 2013). Lateral entorhinal cortex lesioned
rodents show no impairment in performing an object-recognition
task, but are impaired at recognizing spatial changes and object
changes within a set of objects in an environment including posi-
tion changes of the objects (Van Cauter et al. 2013) and previously
learned object-place and object-context associations (Wilson et al.
2013a; Chao et al. 2016). Together, these ndings suggest that, be-
yond encoding information about objects, the lateral entorhinal
cortex encodes contextual information and may be binding non-
spatial and spatial information, specically encoding information
about objects and certain spatial properties, including information
about the objects position within environment.
Few studies have examined the role of the lateral entorhinal
cortex in encoding object identity, object position or changes to
the spatial context in humans. Reagh and Yassa (2014) report
that subtle perceptual differences between similar objects (e.g.,
two slightly different apples) elicits activity observed with func-
tional magnetic resonance imaging (fMRI) in both the lateral ento-
rhinal cortex and perirhinal cortex, while changes to an objects
position on a blank screen elicited activity in both the parahippo-
campal cortex and medial entorhinal cortex. Subsequent studies in
older adults show impaired performance recalling the identity of
object (Reagh and Yassa 2014; Stark and Stark 2017; Yeung et al.
2017; Berron et al. 2018; Reagh et al. 2018) but similar performance
recalling position of the object on a screen compared with young
adults (Reagh et al. 2016, 2018). However, these studies examined
memory for object identity and object position on a blank screen,
devoid of any spatial or contextual information. Given the nd-
ings from rodent studies, it appears that object identity and object
position information are represented in relationship to the spatial
environment in which they occur.
To examine the integration of nonspatial and spatial informa-
tion, novel stimuli were developed to mimic real-life environments
where objects could occur within the environment, more closely
resembling animal studies in which rodents experience objects
within an environment. A series of scenes were designed to have
the same perspective, spatial dimensions and outdoor scenery
(Fig. 1A). Scenes were classied into ve general categories: living
room, dining room, kitchen, bedroom, and ofce rooms to allow
for the placement of categorically congruent furniture (Fig. 1B).
Critically, within each scene, two to ve different positions were
dened that an object could logically occupy (Fig. 1C). The scene
stimuli were rst validated using mnemonic ratings and subse-
quently used in a novel object-in-context task to assess memory
for object identity and object position in context and examine
age-related changes in performance on this task in cognitively nor-
mal older adults compared with young adults.
Results
Stimulus validation
Results
To examine the mnemonic attributes of the indoor scenes, a stim-
ulus validation study was conducted in which participants were
asked to judge whether each scene was either newor old.A
scene was correctly judged newif it was seen for the rst time
in the context of the task, and oldif the exact scene was repeated
once or twice (Fig. 2A). Participants correctly identied 67.9% of
new trials as new,76.1% of trials repeated once as old, and
85.7% of trials presented twice as old.To compare the accuracy
between scenes, the average accuracy for each scene was computed
by collapsing the correct trial type responses across participants for
each scene. This resulted in an average accuracy for each scene for
trials presented once, trials repeated once, and trials repeated twice
(Fig. 2B).
Of particular interest were the scenes judged old,as this
would be most representative of how reliably identiable and
memorable each of the scenes were. Average accuracy for trials re-
peated once and correctly called oldwas used to compare the
memorability of individual scenes. Scenes with accuracy scores be-
tween 60%90% were selected for use in subsequent experiments,
resulting in a total of 509 scenes.
Object-in-context experiment
In the Object Familiarization phase of the experiment, participants
viewed images of everyday objects and were asked to rate the ob-
jects as either belonging indooror outdoorto familiarize
themselves with all objects (Fig. 3A). For the Object-in-Context
phase of the experiment scenes were randomly selected from the
B
A
C
Figure 1. Task stimuli. (A) Scenes were designed to have identical di-
mensions and a similar perspective. (B) Scenes were designed to have
two to ve different positions where an object could be reasonably
placed. Across all scenes, the same general positions were available for
object placement. (C) Example of a scene with an object as seen by
the participant. No object was present in the scenes for the stimulus
validation study.
Memory for object position in context
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scenes validated in the stimulus validation study and an object
from the Object Familiarization phase was presented within the
scene (Fig. 3B). Trials consisted of Newtrials with new object
and scene pairings that were presented once; Repeattrials with
object and scene pairings that were presented and subsequently re-
peated once; Identity Changetrials with object and scene pair-
ings that were presented once and the object was changed to a
nonsimilar different but categorically congruent object (i.e., differ-
ent kitchen item in the kitchen environment) on the subsequent
trial using the same scene; and Position Changetrials with object
and scene pairings that were presented once and the position of the
object was changed in a subsequent trial using the same scene (Fig.
3C). Participants were asked to rate a scene and object pairing as
Newwhen they were not seen before in the context of the
task, Oldif the pairing was previously seen in the context of
the task, or Changefor a previously seen pairing where either
the object or the location of the object was changed.
Demographic data and neuropsychological test performance
is included in Table 1. Older adults were by criteria signicantly
older than young adults (t
(45)
= 47.54, P< 0.0001) and completed
signicantly more years of education (t
(45)
= 6.84, P< 0.001).
During the experimental task, young adults correctly identied
82.71% (SD = 13.07%) of New trials while older adults correctly
identied 62.83% (SD = 12.37%) of New trials (new object and
scene pairing). For Repeat trials, where the same object and scene
pairing are repeated, young adults correctly identied 82.40%
(SD = 10.65%) of trials while older adults correctly identied
76.46% (SD = 15.34%) of all trials. For Identity Change trials,
with a new object and scene pairing, young adults correctly identi-
ed 66.56% (SD = 16.55%) of trials while older adults correctly
identied 74.24% (SD = 16.07%) of trials. For Position Change tri-
als, where the position of the object is changed, young adults cor-
rectly identied 80.36% (SD = 13.11%) of trials while older adults
identied 65.02% of trials (SD = 13.04%).
Task performance in older adults showed a signicant effect of
task condition (F
(3,18)
= 4.87, P= 0.01) with signicantly higher per-
formance on Repeat trials compared with New trials (t
(18)
= 2.94, P<
0.01) and Position Change trials (t
(18)
= 3.36, P< 0.001), signi-
cantly lower performance on New trials compared with Identity
Change trials (t
(18)
= 2.08, P= 0.03), and signicantly lower perfor-
mance on Position Change trials compared with Identity Change
trials (t
(18)
= 2.80, P< 0.01). Young adults also showed a signicant
effect of task condition (F
(3,27)
= 9.52, P< 0.001) with signicantly
lower performance on Identity Change trials compared with New
trials (t
(27)
= 3.40, P< 0.01), Repeat trials (t
(27)
= 4.31, P< 0.001),
and Position Change trials (t
(27)
= 3.28, P< 0.01).
Older adults showed signicantly poorer performance identi-
fying new object-in-context trials (New trials: t
(45)
= 5.23, P< 0.001)
and trials in which the position of the object in the context was
changed (Position Change trials: t
(45)
= 3.95, P< 0.001) when com-
pared with young adults. No signicant differences were observed
between young and older adults for trials in which the same object
in context was repeated (Repeat trials: t
(45)
= 1.57, P= 0.12) or in
which the object in the context was changed (Identity Change tri-
als: t
(45)
= 1.58, P= 0.12) (Fig. 4).
A key goal of the current study was to examine the potential
dissociation and age-related changes in memory for object position
changes compared with object changes when presented in the
context of a scene. A two-way analysis of variance comparing the
Identity Change and Position Change trials between young and
older adults showed no main effect of age (F
(1,45)
= 0.63, P= 0.43)
or condition (F
(1,45)
= 1.324, P= 0.26). However, the analysis
showed a signicant interaction between age and condition
(F
(1,45)
= 15.86, P< 0.001), illustrating that older signicantly less
often correctly identied Position Change trials compared with
young adults (Fig. 5A). A subsequent analysis of variance was con-
ducted to examine the response rates of each response option
(new, old, or change) for the Position Change and Identity
Change conditions respectively. For the Identity Change trials,
there was no signicant interaction between young adults and
old adults for the response type (F
(1,45)
= 0.49, P= 0.49) (Fig. 5B).
In contrast, for the Position Change trials, there was a signicant
interaction between young adults and older adults for the response
type (F
(1,45)
= 19.20, P< 0.001), showing that older adults signi-
cantly more often incorrectly identied Position change trials as
Oldand less often correctly identied those trials as New
when compared with younger adults (Fig. 5C). As scenes were de-
signed to have different positions where an object could reason-
ably be placed, each position change trial varied in the relative
spatial distance of the change. To examine the potential effect of
spatial distance in the Position Change trials, a two-away analysis
of variance was used examining performance between young
adults and older adults in the Position Change condition, contrast-
ing trials with low spatial distance and high spatial distance. The
spatial distance between object positions was calculated as the dis-
tance (in pixels) between all potential positions. Distances be-
tween the rst position of an object and the changed position of
the object in the second presentation ranged from 323 pixels to
1506 pixels. The spatial distance between the rst and second pre-
sentation of the object was used to divide Position Change trials
into low and high distance trials, roughly corresponding to posi-
tion changes that were halfway across the spatial context and
B
A
Figure 2. Stimulus validation. (A) Participants were presented with the
scenes and asked to judge whether each scene was New(seen for the
rst time) or Old(a repeated scene). (B) Proportion of correct old re-
sponses to repeated scenes for each scene ranked from least to most
often accurately recalled. Highlighted portion (60%90% accuracy) of
scenes was used in the subsequent experiment.
Memory for object position in context
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across the entirety of the room. This analysis showed no main
effect of distance in behavioral performance (F
(1,116)
= 1.47,
P= 0.23) and no interaction between age and distance (F
(1,116)
=
0.04, P= 0.84).
Discussion
The goal of the current study was to assess age-related changes in
memory for objects and their position in a scene. Using a novel
task for viewing different environments (living rooms, bedrooms,
kitchens, dining rooms, and ofce rooms), younger and older
adults were asked to identify a change in the identity of objects,
as well as the position of the objects. Older adults correctly identi-
ed a similar number of object changes in the scenes but identied
signicantly fewer object position changes compared with young
adults. These ndings expand upon previous studies examining
age-related differences reporting that older adults have difculty
recognizing changes in object identity (Yassa et al. 2011; Stark
et al. 2013, 2015; Reagh et al. 2016; Olsen et al. 2017) and object
features (Yeung et al. 2017) but not in recalling changes in the po-
sitions of an object when items were presented on a blank screen
(Reagh et al. 2016, 2018). Studies examining age-related differenc-
es in memory for spatial information in scenes have reported
mixed results with some reporting minimal age-related impair-
ments in scene recognition (Fidalgo et al. 2016; Stark and Stark
2017) while others have reported no age-related differences
(Berron et al. 2018, 2019). The majority of these studies examined
object identity, scenes or an objects position independently, with-
out assessing the conjunctive encoding of an object and its posi-
tion within a scene. However, mounting evidence suggests that
object and position information, is encoded in relationship to
the environmental context (Van Cauter et al. 2013; Wilson et al.
2013b; Chao et al. 2016).
C
AB
Figure 3. Object-in-Context task. (A) Participants were rst presented with pictures of objects and asked to judge for each item if the object belongs
indooror outdoorto become familiar with the objects. (B) Participants were subsequently presented with the scene and object pairing and asked
to judge for each if the scene was New(never seen before), Old(previously seen), or Change(resembled a previously shown scene and object
pair). (C) Examples of repeat, position change, identity change, and foil stimuli.
Memory for object position in context
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As noted in the background for the current investigation, in
foraging rodents, cells in the lateral entorhinal cortex track the po-
sition of an object in the environment (Deshmukh and Knierim
2011) or the previous positions of an object within the environ-
ment (Tsao et al. 2013). Furthermore, a population-level analysis
of neurons in the lateral entorhinal cortex shows that cells in
this area encode for object, object position and context, and appear
sensitive to encoding contextual information about the environ-
ment (Keene et al. 2016). These ndings suggest that the represen-
tation of complex environments composed of the integration of
spatial and nonspatial may be differentially processed relative to
independent and isolated representations of objects and spatial in-
formation providing a potential explanation for the mixed results
previously reported.
The task used in this study was designed to provide consistent
spatial dimensions and perspective with objects congruent with
the scene placed in plausible locations in the space. The scenes
were equated for memorability based on ratings from a separate
stimulus validation study in an effort to minimize the effects of
novelty, perspective, congruence, and distance on recognition of
object identity and object position. This task is similar to the ap-
proach used in a study by Yeung et al. (2019) showing that patients
with cognitive decline are impaired in recognizing a change in the
position of an object within a scene relative to cognitively normal
older adults as measured by the proportion of eye xations on a
critical object in the environment. In Yeung et al. (2019) the au-
thors manipulated the position of an object in the environment,
and showed that the volume of the lateral entorhinal cortex was as-
sociated with memory for object identity but not for the object lo-
cation within the environment in community dwelling older
adults. As in the current study, the integration of object informa-
tion in a spatial context used by Yeung et al. (2019) required an ini-
tial study phase in which participants familiarized themselves with
the objects used in the task.
In contrast, the task used by Reagh et al. (2018) featured an ob-
ject mnemonic discrimination task without a study phase, requir-
ing discrimination between highly similar and overlapping
representations of either object identity or an object position on
a blank screen without integration of spatial and nonspatial infor-
mation. Berron et al. (2018) similarly used an object mnemonic
discrimination task without a study phase using highly similar
and overlapping representations of object identity, but examined
memory for spatial information using scenes in which an element
of the space itself was manipulated. Whereas the studies by Reagh
et al. (2018) and Berron et al. (2018) reported no age-related differ-
ences in memory for spatial information, the Yeung et al. (2019)
study reported impaired recognition of the position of an object
in a scene consistent with the ndings reported here. Additional
studies are needed to determine whether age-related changes in
memory for object position emerge in particular when an object
is embedded in a scene or whether the processing of complex
scenes itself is associated with age-related changes.
Despite the differences in the tasks used, the studies by Berron
et al. (2018), Reagh et al. (2018), and Yeung et al. (2019) have ob-
served selective engagement of the entorhinal cortex consistent
with the ndings from recording studies in animals. Changes to
object identity have been associated with activation of the lateral
entorhinal cortex (Berron et al. 2018; Reagh et al. 2016, 2018)
while changes to the position of the object (Reagh et al. 2016,
2018) and context (Berron et al. 2018) have been shown to elicit
activation in the medial entorhinal cortex. Additional studies us-
ing neuroimaging approaches in humans are needed to determine
the mechanisms underlying the representations of complex envi-
ronments and whether the integration of spatial and nonspatial in-
formation also engages the lateral or medial entorhinal cortex or
may be differentially processed relative to independent and isolat-
ed representations of objects and spatial information.
Older adults showed signicantly higher performance on the
repeat trials compared with new and position change trials in the
task consistent with a bias toward generalization observed in older
adults (Stark et al. 2013) while young adults showed signicantly
lower performance on the Identity Change trials compared with
Table 1. Demographics and clinical characterization of study
participants
Young adults Older adults
Mean SD Mean SD
Demographics
Subjects 28 19
Sex (M/F) 18/11 8/11
Age (years) 19.26 0.94 65.11 5.00
Education (years) 13.89 1.1 17.11 2.11
Clinical dementia rating scale 0.0
Clinical dementia sum of boxes 0.00 0.00
General cognition
Clock drawing 23.05 2.12
MMSE 29.16 1.07
Memory
Benton visual retention 7.11 1.20
BSRT immediate recall 52.8 7.89
BSRT delayed recall 9.11 2.00
LM immediate recall 51.05 7.29
LM delayed recall 32.58 6.56
Rey-O CFT immediate copy 32.84 2.55
Rey-O CFT delayed recall 18.74 4.45
Working memory
Letter number sequencing 12.63 2.28
Executive functioning
Stroop color wordword 96.32 16.20
Stroop color wordcolor 66.79 13.22
Stroop color wordcolor/word 40.33 8.35
Speed of processing
Symbol-digit modalities test 48.68 9.18
Verbal uency
Verbal uency (FAS) 47.37 15.45
(MMSE) Mini-mental status exam, (BSRT) Buschke selective reminding test,
(LM) Wechsler logical memory test, (Rey-O CFT) Rey-Osterrieth complex
gure test. All values are reported as standard raw scores and fall within the
normal range based on population norms.
Figure 4. Behavioral performance in young and older adults. Older
adults show impaired performance on Position Change trials and New
trials relative to young adults. Bars represent mean ± SEM. (*) P< 0.05.
Memory for object position in context
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New, Repeat, and Position Change trials.In addition to identifying
signicantly fewer position change trials compared with young
adults, older adults also identied signicantly fewer new scene
and object pairings. This nding is consistent with reports of in-
creased false recognition in older adults showing that older adults
are more likely to falsely recall seeing words and pictures (Koutstaal
and Schacter 1997; Norman and Schacter 1997; Dennis and Turney
2018) than younger adults (Devitt and Schacter 2016). Although
increased false recognition in older adults has been well estab-
lished, the mechanisms behind this phenomenon are not well un-
derstood and attributed to a general decline in prefrontal cortex
integrity and connectivity between the prefrontal cortex and the
medial temporal lobe (Devitt and Schacter 2016). In the data ob-
served in this study, the observed difference in recognition memo-
ry between young and older adults does not appear to contribute to
recognition memory for item level changes as age-related decline is
only observed in the position change trials while performance on
the identity change trials remains similar to young adults.
Within the medial temporal lobe (MTL), there has been an in-
creased focus on the lateral entorhinal cortex in recent years due to
the vulnerability of this region in both aging and Alzheimers dis-
ease (AD). The lateral entorhinal cortex is one of the rst regions
where tau neurobrillary tangles, an established classic biomarker
of AD, accumulates (Braak and Braak 1991; Lace et al. 2009; Jack
et al. 2010), and subsequent neuronal degeneration and synaptic
loss occurs (Hoesen et al. 1991; Gómez-Isla et al. 1996; Kordower
et al. 2001; Selkoe 2002). In cognitively normal older adults, the
lateral entorhinal cortex also shows considerable neurobrillary
tangle deposits compared with young adults (Braak and Braak
1991), suggesting that even in healthy aging, the structure and
function of this region may be altered. Indeed, reduced volume
of the lateral entorhinal cortex has been observed in older adults
who perform lower on a test of general cognition and are at high
risk for developing AD (Olsen et al. 2017; Yeung et al. 2017).
Furthermore, hypoactivity of the lateral entorhinal cortex associat-
ed with poor object recognition has been observed in both older
adults (Berron et al. 2018; Reagh et al. 2018) and in patients with
amnestic mild cognitive impairment, a transitional stage between
healthy aging and AD dementia (TT Tran, CL Speck, M Gallagher,
et al., in prep.). Using novel stimuli consisting of objects posi-
tioned within a scene, the current study shows there may be poten-
tial age-related differences in the mechanisms underlying the
representations of complex environments. Furthermore, the inte-
gration of spatial and nonspatial information may be differentially
processed relative to independent and isolated representations of
objects and spatial information. It is possible that the integration
of spatial and nonspatial information depends on the lateral ento-
rhinal cortex and age-related changes are driven by the accumula-
tion of pathology in this region in aging and AD. Further studies
examining age-related changes and domain-specic processing
are needed to determine the neural basis of information processing
of these components in the medial temporal lobe.
Materials and Methods
Stimulus validation
Participants
A total of 181 Johns Hopkins undergraduate students (108 females;
73 males) contributed to the validation of the stimuli used in this
study in exchange for course credit. Data from seventeen partici-
pants were removed from analysis due to inability or failure to
complete the stimulus ratings while data from three participants
were removed for a nonresponse rate >20% and data from four par-
ticipants were removed for below chance accuracy. Complete data
from 157 (90 females; 67 males, aged 1822 yr old) participants
were included in the nal analysis of the scene ratings.
Materials and procedures
A total of 549 indoor scenes were created using the Sims 4 comput-
er game (EA Games). All scenes were designed to have the same per-
spective, spatial dimensions and outdoor scenery. Scenes featured
different types of windows, wallpaper, and ooring and included
sparse furniture, including chairs, tables, sofas, and beds. Scenes
were classied into ve general categories: living room, dining
room, kitchen, bedroom, and ofce rooms to allow for the place-
ment of categorically congruent furniture. Critically, within each
scene, two to ve different positions were dened that an object
could logically occupy. These general positions for object place-
ment were consistent across scenes.
Participants were asked to judge whether each scene was ei-
ther newor old.A scene was correctly judged newif it was
seen for the rst time in the context of the task, and oldif the ex-
act scene was repeated once or twice. A total of 182 scenes were pre-
sented once, 245 scenes were presented twice, and 122 scenes were
presented three times in random order, with participants complet-
ing a total of 549 scenes. The scenes were rearranged between par-
ticipants such that across all participants each scene was tested in
each of the rst presentation, rst repeat and second repeat
conditions.
AB C
Figure 5. Older adults show impaired performance on Position Change but not Identity Change trials. (A) Older adults showed a signicant impairment
on Position trials relative to young adults but no signicant difference on Identity Change trials. (B) Identity Change trials showed no signicant difference
in performance between older adults and young adults. (C) For Position Change trials, older adults more often incorrectly identied position change trials
as old,instead of changecompared with young adults. Bars represent mean ± SEM. (*) P< 0.05.
Memory for object position in context
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Repeated stimuli were spaced apart a minimum of 15 trials
and maximum of 40 trials between rst, second and third presen-
tations. Scenes were presented for 2500 msec with a 500 msec in-
terstimulus interval. Stimuli were presented using Psychtoolbox
3 (Brainard 1997; Pelli 1997; Kleiner et al. 2007) using MATLAB
(The Mathworks) on a Macintosh computer.
Object-in-Context experiment
Participants
Thirty-four young adults and 31 cognitively normal older adults
were enrolled in the Object-in-Context experiment. Young adults
were recruited from the undergraduate population at Johns
Hopkins University and received course credit for their participa-
tion. Data from six young adult participants were excluded from
analysis due to below change performance (n= 4) and incomplete
data collection (n= 2). Older adults were recruited from the com-
munity through yers and online advertisements and were paid
for their participation. Data from 12 older adult participants were
excluded from analysis due to below chance performance (n= 11)
or incomplete data collection (n= 1). This resulted in the analysis
of data from a total of 28 young adults and 19 cognitively normal
older adults in the Object-in-Context experiment (Table 1).
All older adult participants underwent medical, psychiatric,
neurological, and neuropsychological evaluations and completed
the Clinical Dementia Rating Scale (CDR; Morris 1993).
Neuropsychological evaluation included the mini mental status
exam (Folstein et al. 1975), the Buschke selective reminding test
(Buschke and Fuld 1974), the logical memory subtest of the
Wechsler memory scale (Wechsler 1987), the clock drawing test
(Sunderland et al. 1989), the Rey-Osterrieth complex gure test
(Rey 1941; Osterrieth 1944), and the Benton visual retention test
(Benton 1974). Participants were excluded from further participa-
tion if they reported current neurological or psychiatric disorders,
history of major head trauma, history of substance abuse or depen-
dencies, or scored 2.5 standard deviations below published norms
on one or more neuropsychological tests. All older adult partici-
pants had a global CDR and CDR-sum of noxes score of 0.
Materials and procedures
Stimuli consisted of 160 scene stimuli and 200 images of everyday
objects. These scenes were randomly selected from the scenes val-
idated in the stimulus validation study. Scenes were divided into
ve general categories: living room, dining room, kitchen, bed-
room, or ofce rooms to allow for the placement of categorically
relevant objects. All objects and scenes were categorically matched
to allow congruency in the stimuli presentation (e.g., pencils in the
ofce, apple in the kitchen).
Object familiarization phase
In the Object Familiarization phase of the experiment, participants
viewed the 200 images of everyday objects and were asked to rate
the objects as either belonging Indooror Outdoorto familiar-
ize themselves with all objects. Each object was presented on a
blank screen for 2.5 sec with an interstimulus interval of 0.5 sec.
ObjectinContext phase
In the Object-in-Context phase of the experiment, participants
completed 280 trials where an object from the Object
Familiarization phase was presented within a scene. For each
object-in-context trial, a scene was presented with a categorically
appropriate object (e.g., blankets in a bedroom scene) for 3.5 sec
with an interstimulus interval of 0.5 sec. Trials consisted of 40
Newtrials with new object and scene pairings that were present-
ed once, 80 Repeattrials with 40 object and scene pairings that
were presented and subsequently repeated once, 80 Identity
Changetrials with 40 object and scene pairings that were present-
ed once and the object was changed to a nonsimilar different but
categorically congruent object (i.e., different kitchen item in the
kitchen environment) on the subsequent trial using the same
scene, and 80 Position Changetrials with 40 object and scene
pairings that were presented once and the position of the object
was changed in a subsequent trial using the same scene.
Participants were asked to rate a scene and object pairing as
Newwhen they were not seen before in the context of the
task, Oldif the pairing was previously seen in the context of
the task, or Changefor a previously seen pairing where either
the object or the location of the object was changed. Repeated,
Identity Change, and Position Change trials were spaced apart a
minimum of three trials and a maximum of 12 trials with an aver-
age of eight trials between the rst and second presentation.
Trials were presented in six different runs consisting of 70 tri-
als per run. Runs were blocked so the rst three runs would contain
New,”“Repeat,and Identity Changetrials while the last three
runs would contain New,”“Repeat,and Position Change
trials. This order was counterbalanced between participants.
Participants were cued to the trial type at the beginning of each
run. Previous versions of the task using no cues or a random order
of trial types resulted in chance performance in older adults.
Stimuli were presented using Psychtoolbox 3 (Brainard 1997;
Pelli 1997; Kleiner et al. 2007) using Matlab (The Mathworks) on a
Macintosh computer.
Competing interests statement
M.G. is the founder of AgeneBio. M.G. and A.B. are inventors on
Johns Hopkins University intellectual property with patents pend-
ing and licensed to AgeneBio. M.G. consults for the company and
owns company stock, which is subject to certain restrictions under
University policy. A.B. is a consultant for Acadia Pharmaceuticals,
Inc. M.G. and A.Bs role in the current study was in compliance
with the conict of interest policies of the Johns Hopkins School
of Medicine.
Acknowledgments
We thank the staff of the F.M. Kirby Center for Functional Brain
Imaging for their assistance with data collection. This work was
supported by National Institutes of Health grants RC2AG036419,
P50AG05146, and R01AG048349. T.T. was supported by a
National Institute on Aging T32 training grant and a National
Defense Science and Engineering Graduate Fellowship (NDSEG)
grant awarded by Department of Defense, Air Force Ofce of
Scientic Research, NDSEG Fellowship 32 CFR 168a.
References
Benton AL. 1974. Visual retention test. The Psychological Corporation,
New York, NY.
Berger-Mandelbaum A, Magen H. 2019. Self-initiated object-location
memory in young and older adults. Aging Neuropsychol Cogn B Aging
Neuropsychol Cogn 26: 5885. doi:10.1080/13825585.2017.1399981
Berron D, Neumann K, Maass A, Schütze H, Fliessbach K, Kiven V, Jessen F,
Sauvage M, Kumaran D, Düzel E. 2018. Age-related functional changes
in domain-specic medial temporal lobe pathways. Neurobiol Aging 65:
8697. doi:10.1016/j.neurobiolaging.2017.12.030
Berron D, Cardenas-Blanco A, Bittner D, Metzger CD, Spottke A, Heneka MT,
Fliessbach K, Schneider A, Teipel SJ, Wagner M, et al. 2019. Higher CSF
tau levels are related to hippocampal hyperactivity and object
mnemonic discrimination in older adults. J Neurosci 39: 87888797.
doi:10.1523/JNEUROSCI.1279-19.2019
Braak H, Braak E. 1991. Neuropathological stageing of Alzheimer-related
changes. Acta Neuropathol 82: 239259. doi:10.1007/BF00308809
Brainard DH. 1997. The psychophysics toolbox. Spat Vis 10: 433436.
Buschke H, Fuld PA. 1974. Evaluating storage, retention, and retrieval in
disordered memory and learning. Neurology 24: 10191025.
Chalfonte BL, Johnson MK. 1996. Feature memory and binding in young
and older adults. Memory Cognit 24: 403416. doi:10.3758/BF03200930
Chao OY, Huston JP, Li J-S, Wang A-L, de Souza Silva MA. 2016. The medial
prefrontal cortex-lateral entorhinal cortex circuit is essential for
episodic-like memory and associative object-recognition: MPFC-lec is
key for episodic-like and associative memory. Hippocampus 26: 633645.
doi:10.1002/hipo.22547
Craik FIM, Bialystok E. 2006. Cognition through the lifespan: mechanisms
of change. Trends Cogn Sci 10: 131138. doi:10.1016/j.tics.2006.01.007
Memory for object position in context
www.learnmem.org 245 Learning & Memory
Cold Spring Harbor Laboratory Press on March 16, 2023 - Published by learnmem.cshlp.orgDownloaded from
Davachi L. 2006. Item, context and relational episodic encoding in humans.
Curr Opin Neurobiol 16: 693700. doi:10.1016/j.conb.2006.10.012
Dennis NA, Turney IC. 2018. The inuence of perceptual similarity and
individual differences on false memories in aging. Neurobiol Aging 62:
221230. doi:10.1016/j.neurobiolaging.2017.10.020
Deshmukh SS, Knierim JJ. 2011. Representation of non-spatial and spatial
information in the lateral entorhinal cortex. Front Behav Neurosci 5: 69.
doi:10.3389/fnbeh.2011.00069
Deshmukh SS, Johnson JL, Knierim JJ. 2012. Perirhinal cortex represents
nonspatial, but not spatial, information in rats foraging in the presence
of objects: comparison with lateral entorhinal cortex. Hippocampus 22:
20452058. doi:10.1002/hipo.22046
Devitt AL, Schacter DL. 2016. False memories with age: neural and cognitive
underpinnings. Neuropsychologia 91: 346359. doi:10.1016/j
.neuropsychologia.2016.08.030
Doan TP, Lagartos-Donate MJ, Nilssen ES, Ohara S, Witter MP. 2019.
Convergent projections from perirhinal and postrhinal cortices suggest
a multisensory nature of lateral, but not medial, entorhinal cortex. Cell
Rep 29: 617627.e7. doi:10.1016/j.celrep.2019.09.005
Eichenbaum H. 1999. The hippocampus and mechanisms of declarative
memory. Behav Brain Res 103: 123133. doi:10.1016/S0166-4328(99)
00044-3
Eichenbaum H, Dudchenko P, Wood E, Shapiro M, Tanila H. 1999. The
hippocampus, memory, and place cells: is it spatial memory or a
memory space? Neuron 23: 209226. doi:10.1016/S0896-6273(00)
80773-4
Erickson CA, Barnes CA. 2003. The neurobiology of memory changes in
normal aging. Exp Gerontol 38: 6169. doi:10.1016/S0531-5565(02)
00160-2
Fidalgo CO, Changoor AT, Page-Gould E, Lee ACH, Barense MD. 2016. Early
cognitive decline in older adults better predicts object than scene
recognition performance: early cognitive decline in older adults.
Hippocampus 26: 15791592. doi:10.1002/hipo.22658
Folstein MF, Folstein SE, McHugh PR. 1975. Mini-mental state.A practical
method for grading the cognitive state of patients for the clinician. J
Psychiatr Res 12: 189198.
Gómez-Isla T, Price JL Jr, McKeel DW, Morris JC, Growdon JH, Hyman BT.
1996. Profound loss of layer II entorhinal cortex neurons occurs in very
mild Alzheimers disease. J Neurosci 16: 44914500. doi:10.1523/
JNEUROSCI.16-14-04491.1996
Grady CL, Craik FIM. 2000. Changes in memory processing with age. Curr
Opin Neurobiol 10: 224231. doi:10.1016/s0959-4388(00)00073-8
Hoesen GWV, Hyman BT, Damasio AR. 1991. Entorhinal cortex pathology
in Alzheimers disease. Hippocampus 1: 18. doi:10.1002/hipo
.450010102
Jack CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW,
Petersen RC, Trojanowski JQ. 2010. Hypothetical model of dynamic
biomarkers of the Alzheimers pathological cascade. Lancet Neurol 9:
119128. doi:10.1016/S1474-4422(09)70299-6
Keene CS, Bladon J, McKenzie S, Liu CD, OKeefe J, Eichenbaum H. 2016.
Complementary functional organization of neuronal activity patterns
in the perirhinal, lateral entorhinal, and medial entorhinal cortices. J
Neurosci 36: 36603675. doi:10.1523/JNEUROSCI.4368-15.2016
Kessels RPC, Hobbel D, Postma A. 2007. Aging, context memory and
binding: a comparison of what, where and whenin young and older
adults. Int J Neurosci 117: 795810. doi:10.1080/00207450600910218
Kleiner M, Brainard D, Pelli D. 2007. Whats new in Psychtoolbox-3?
Perception 36: 116. doi:10.1068/v070821
Knierim JJ, Neunuebel JP, Deshmukh SS. 2013. Functional correlates of the
lateral and medial entorhinal cortex: objects, path integration and
local-global reference frames. Philos Trans R Soc B Biol Sci 369: 20130369.
doi:10.1098/rstb.2013.0369
Kordower JH, Chu Y, Stebbins GT, DeKosky ST, Cochran EJ, Bennett D,
Mufson EJ. 2001. Loss and atrophy of layer II entorhinal cortex neurons
in elderly people with mild cognitive impairment. Ann Neurol 49:
202213. doi:10.1002/1531-8249(20010201)49:2&lt;202::
AID-ANA40>3.0.CO;2-3
Koutstaal W, Schacter DL. 1997. Gist-based false recognition of pictures in
older and younger adults. J Mem Lang 37: 555583. doi:10.1006/jmla
.1997.2529
Lace G, Savva GM, Forster G, de Silva R, Brayne C, Matthews FE, Barclay JJ,
Dakin L, Ince PG, Wharton SB. 2009. Hippocampal tau pathology is
related to neuroanatomical connections: an ageing population-based
study. Brain 132: 13241334. doi:10.1093/brain/awp059
Mazurek A, Bhoopathy RM, Read JCA, Gallagher P, Smulders TV. 2015.
Effects of age on a real-world whatwherewhen memory task. Front
Aging Neurosci 7: 74. doi:10.3389/fnagi.2015.00074
Meulenbroek O, Kessels RPC, de Rover M, Petersson KM, Olde Rikkert MGM,
Rijpkema M, Fernandez G. 2010. Age-effects on associative object-
location memory. Brain Res 1315: 100110. doi:10.1016/j.brainres.2009
.12.011
Morris JC. 1993. The Clinical Dementia Rating (CDR): current version and
scoring rules. Neurology 43: 24122414. doi:10.1212/wnl.43.11.2412-a
Muffato V, Hilton C, Meneghetti C, Beni RD, Wiener JM. 2019. Evidence for
age-related decits in object-location binding during place recognition.
Hippocampus 29: 971979. doi:10.1002/hipo.23099
Naveh-Benjamin M. 2000. Adult age differences in memory performance:
tests of an associative decit hypothesis. J Exp Psychol Learn Mem Cogn
26: 11701187. doi:10.1037/0278-7393.26.5.1170
Nilssen ES, Doan TP, Nigro MJ, Ohara S, Witter MP. 2019. Neurons and
networks in the entorhinal cortex: a reappraisal of the lateral and medial
entorhinal subdivisions mediating parallel cortical pathways.
Hippocampus 29: 12381254. doi:10.1002/hipo.23145
Norman KA, Schacter DL. 1997. False recognition in younger and older
adults: exploring the characteristics of illusory memories. Mem Cogn 25:
838848. doi:10.3758/BF03211328
Old SR, Naveh-Benjamin M. 2008. Differential effects of age on item and
associative measures of memory: a meta-analysis. Psychol Aging 23: 104
118. doi:10.1037/0882-7974.23.1.104
Olsen RK, Yeung L-K, Noly-Gandon A, DAngelo MC, Kacollja A, Smith VM,
Ryan JD, Barense MD. 2017. Human anterolateral entorhinal cortex
volumes are associated with cognitive decline in aging prior to clinical
diagnosis. Neurobiol Aging 57: 195205. doi:10.1016/j.neurobiolaging
.2017.04.025
Osterrieth PA. 1944. The test of copying a complex gure: a contribution to
the study of perception and memory. Arch Psychol 30: 206356.
Pelli DG. 1997. The VideoToolbox software for visual psychophysics:
transforming numbers into movies. Spat Vis 10: 437442.
Postma A, Kessels RPC, van Asselen M. 2008. How the brain remembers and
forgets where things are: the neurocognition of objectlocation
memory. Neurosci Biobehav Rev 32: 13391345. doi:10.1016/j.neubiorev
.2008.05.001
Ranganath C, Ritchey M. 2012. Two cortical systems for memory-guided
behaviour. Nat Rev Neurosci 13: 713726. doi:10.1038/nrn3338
Reagh ZM, Yassa MA. 2014. Object and spatial mnemonic interference
differentially engage lateral and medial entorhinal cortex in humans.
Proc Natl Acad Sci 111: E4264E4273. doi:10.1073/pnas.1411250111
Reagh ZM, Ho HD, Leal SL, Noche JA, Chun A, Murray EA, Yassa MA. 2016.
Greater loss of object than spatial mnemonic discrimination in aged
adults: selective object memory decits in aging. Hippocampus 26: 417
422. doi:10.1002/hipo.22562
Reagh ZM, Noche JA, Tustison NJ, Delisle D, Murray EA, Yassa MA. 2018.
Functional imbalance of anterolateral entorhinal cortex and
hippocampal dentate/CA3 underlies age-related object pattern
separation decits. Neuron 97: 11871198.e4. doi:10.1016/j.neuron
.2018.01.039
Rey A. 1941. Lexamen psychologique dans les cas dencéphalopathie
traumatique.(Les problems.). Arch Psychol 28: 215286.
Salthouse TA. 2004. What and when of cognitive aging. Curr Dir Psychol Sci
13: 140144. doi:10.1111/j.0963-7214.2004.00293.x
Schiavetto A, Köhler S, Grady CL, Winocur G, Moscovitch M. 2002. Neural
correlates of memory for object identity and object location: effects of
aging. Neuropsychologia 40: 14281442. doi:10.1016/S0028-3932(01)
00206-8
Selkoe DJ. 2002. Alzheimers disease is a synaptic failure. Science 298: 789
791. doi:10.1126/science.1074069
Stark SM, Stark CEL. 2017. Age-related decits in the mnemonic similarity
task for objects and scenes. Behav Brain Res 333: 109117. doi:10.1016/j
.bbr.2017.06.049
Stark SM, Yassa MA, Lacy JW, Stark CEL. 2013. A task to assess behavioral
pattern separation (BPS) in humans: data from healthy aging and mild
cognitive impairment. Neuropsychologia 51: 24422449. doi:10.1016/j
.neuropsychologia.2012.12.014
Stark SM, Stevenson R, Wu C, Rutledge S, Stark CEL. 2015. Stability of
age-related decits in the mnemonic similarity task across task
variations. Behav Neurosci 129: 257268. doi:10.1037/bne0000055
Sunderland T, Hill JL, Mellow AM, Lawlor BA, Gundersheimer J,
Newhouse PA, Grafman JH. 1989. Clock drawing in Alzheimers disease.
J Am Geriatr Soc 37: 725729. doi:10.1111/j.1532-5415.1989.tb02233.x
Tsao A, Moser M-B, Moser EI. 2013. Traces of experience in the
lateral entorhinal cortex. Curr Biol 23: 399405. doi:10.1016/j.cub.2013
.01.036
Van Cauter T, Camon J, Alvernhe A, Elduayen C, Sargolini F, Save E. 2013.
Distinct roles of medial and lateral entorhinal cortex in spatial
cognition. Cereb Cortex 23: 451459. doi:10.1093/cercor/bhs033
Wechsler D. 1987. Weschler memory scale-Revised. The Psychological
Corporation, San Antonio.
Wilson DIG, Langston RF, Schlesiger MI, Wagner M, Watanabe S, Ainge JA.
2013a. Lateral entorhinal cortex is critical for novel object-context
recognition. Hippocampus 23: 352366. doi:10.1002/hipo.22095
Wilson DIG, Watanabe S, Milner H, Ainge JA. 2013b. Lateral entorhinal
cortex is necessary for associative but not nonassociative recognition
Memory for object position in context
www.learnmem.org 246 Learning & Memory
Cold Spring Harbor Laboratory Press on March 16, 2023 - Published by learnmem.cshlp.orgDownloaded from
memory: lec and associative recognition memory. Hippocampus 23:
12801290. doi:10.1002/hipo.22165
Witter MP, Doan TP, Jacobsen B, Nilssen ES, Ohara S. 2017. Architecture of
the entorhinal cortex a review of entorhinal anatomy in rodents with
some comparative notes. Front Syst Neurosci 11: 46. doi:10.3389/fnsys
.2017.00046
Yassa MA, Mattfeld AT, Stark SM, Stark CEL. 2011. Age-related memory
decits linked to circuit-specic disruptions in the hippocampus. Proc
Natl Acad Sci 108: 88738878. doi:10.1073/pnas.1101567108
Yeung L-K, Olsen RK, Bild-Enkin HEP, DAngelo MC, Kacollja A,
McQuiggan DA, Keshabyan A, Ryan JD, Barense MD. 2017. Anterolateral
entorhinal cortex volume predicted by altered intra-item congural
processing. J Neurosci 37: 55275538. doi:10.1523/JNEUROSCI.3664-16
.2017
Yeung L-K, Olsen RK, Hong B, Mihajlovic V, DAngelo MC, Kacollja A,
Ryan JD, Barense MD. 2019. Object-in-place memory predicted by
anterolateral entorhinal cortex and parahippocampal cortex volume in
older adults. J Cogn Neurosci 31: 711729. doi:10.1162/jocn_a_01385
Yoganarasimha D, Rao G, Knierim JJ. 2011. Lateral entorhinal neurons are
not spatially selective in cue-rich environments. Hippocampus 21: 1363
1374. doi:10.1002/hipo.20839
Received November 2, 2020; accepted in revised form May 14, 2021.
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28:2021, Learn. Mem.
Tammy Tran, Kaitlyn E. Tobin, Sophia H. Block, et al.
position within a spatial context
Effect of aging differs for memory of object identity and object
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Introduction The accumulation of neurofibrillary tau tangles, a neuropathological hallmark of Alzheimer’s disease (AD), occurs in medial temporal lobe (MTL) regions early in the disease process, with some of the earliest deposits localized to subregions of the entorhinal cortex. Although functional specialization of entorhinal cortex subregions has been reported, few studies have considered functional associations with localized tau accumulation. Methods In this study, stepwise linear regressions were used to examine the contributions of regional tau burden in specific MTL subregions, as measured by ¹⁸ F-MK6240 PET, to individual variability in cognition. Dependent measures of interest included the Clinical Dementia Rating Sum of Boxes (CDR-SB), Mini Mental State Examination (MMSE), and composite scores of delayed episodic memory and language. Other model variables included age, sex, education, APOE4 status, and global amyloid burden, indexed by ¹¹ C-PiB. Results Tau burden in right Brodmann area 35 (BA35), left and right Brodmann area 36 (BA36), and age each uniquely contributed to the proportion of explained variance in CDR-SB scores, while right BA36 and age were also significant predictors of MMSE scores, and right BA36 was significantly associated with delayed episodic memory performance. Tau burden in both left and right BA36, along with education, uniquely contributed to the proportion of explained variance in language composite scores. Importantly, the addition of more inclusive ROIs, encompassing less granular segmentation of the entorhinal cortex, did not significantly contribute to explained variance in cognition across any of the models. Discussion These findings suggest that the ability to quantify tau burden in more refined MTL subregions may better account for individual differences in cognition, which may improve the identification of non-demented older adults who are on a trajectory of decline due to AD.
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There is now converging evidence from studies in animals and humans that the medial temporal lobes (MTLs) harbor anatomically distinct processing pathways for object and scene information. Recent functional magnetic resonance imaging studies in humans suggest that this domain-specific organization may be associated with a functional preference of the anterior-lateral part of the entorhinal cortex (alErC) for objects and the posterior-medial entorhinal cortex (pmErC) for scenes. As MTL subregions are differentially affected by aging and neurodegenerative diseases, the question was raised whether aging may affect the 2 pathways differentially. To address this possibility, we developed a paradigm that allows the investigation of object memory and scene memory in a mnemonic discrimination task. A group of young (n = 43) and healthy older subjects (n = 44) underwent functional magnetic resonance imaging recordings during this novel task, while they were asked to discriminate exact repetitions of object and scene stimuli from novel stimuli that were similar but modified versions of the original stimuli ("lures"). We used structural magnetic resonance images to manually segment anatomical components of the MTL including alErC and pmErC and used these segmented regions to analyze domain specificity of functional activity. Across the entire sample, object processing was associated with activation of the perirhinal cortex (PrC) and alErC, whereas for scene processing, activation was more predominant in the parahippocampal cortex and pmErC. Functional activity related to mnemonic discrimination of object and scene lures from exact repetitions was found to overlap between processing pathways and suggests that while the PrC-alErC pathway was more involved in object discrimination, both pathways were involved in the discrimination of similar scenes. Older adults were behaviorally less accurate than young adults in discriminating similar lures from exact repetitions, but this reduction was equivalent in both domains. However, this was accompanied by significantly reduced domain-specific activity in PrC in older adults compared to what was observed in the young. Furthermore, this reduced domain-specific activity was associated to worse performance in object mnemonic discrimination in older adults. Taken together, we show the fine-grained functional organization of the MTL into domain-specific pathways for objects and scenes and their mnemonic discrimination and further provide evidence that aging might affect these pathways in a differential fashion. Future experiments will elucidate whether the 2 pathways are differentially affected in early stages of Alzheimer's disease in relation to amyloid or tau pathology.
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The entorhinal cortex (EC) is among the earliest brain areas to deteriorate in Alzheimer's disease (AD). However, the extent to which functional properties of the EC are altered in the aging brain, even in the absence of clinical symptoms, is not understood. Recent human fMRI studies have identified a functional dissociation within the EC, similar to what is found in rodents. Here, we used high-resolution fMRI to identify a specific hypoactivity in the anterolateral EC (alEC) commensurate with major behavioral deficits on an object pattern separation task in asymptomatic older adults. Only subtle deficits were found in a comparable spatial condition, with no associated differences in posteromedial EC between young and older adults. We additionally linked this condition to dentate/CA3 hyperactivity, and the ratio of activity between the regions was associated with object mnemonic discrimination impairment. These results provide novel evidence of alEC-dentate/CA3 circuit dysfunction in cognitively normal aged humans.
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The present study explored self-initiated object-location memory in ecological contexts, as aspect of memory that is largely absent from the research literature. Young and older adults memorized objects-location associations they selected themselves or object-location associations provided to them, and elaborated on the strategy they used when selecting the locations themselves. Retrieval took place 30 min and 1 month after encoding. The results showed an age-related decline in self-initiated and provided object-location memory. Older adults benefited from self-initiation more than young adults when tested after 30 min, while the benefit was equal when tested after 1 month. Furthermore, elaboration enhanced memory only in older adults, and only after 30 min. Both age groups used deep encoding strategies on the majority of the trials, but their percentage was lower in older adults. Overall, the study demonstrated the processes involved in self-initiated object-location memory, which is an essential part of everyday functioning.
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