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![Fig. 2. Schematic of B&W Visual Paired Comparison (VPC) Task. In [A], a...](publication/320747025/figure/fig2/AS:864805862785026@1583197193542/Schematic-of-B-W-Visual-Paired-Comparison-VPC-Task-In-A-a-representative-trial-of_Q320.jpg)
The perirhinal cortex is known to support high-level perceptual abilities as well as familiarity judgments that may affect recognition memory. We tested whether poor perceptual abilities or a loss of familiarity judgment contributed to the recognition memory impairments reported earlier in monkeys with PRh lesions received in infancy (Neo-PRh) (Wei...
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Context 1
... determine if the size of the lesion could have impacted performance on the B&W VPC, additional bivariate Pearson correlations were performed between extent of PRh damage, or unintended damage of the adjacent entorhinal cortex (ERh), and novelty preference at each delay. Table 2 summarizes the average familiarization times for the two groups at each of the three delays tested. ...Context 2
... average total looking times are reported in Table 2 In [A], a representative trial of the VPC task that consisted of a cumulative familiarization phase of 30 s followed by delays from 10, 60 and 120s, after which two Retention tests of 5 s each were given separated by a 5 s delay. In the Retention tests, the now familiar stimulus was paired with a novel, but similar, stimulus. ...Context 3
... average novelty preferences of Neo-PRh and Neo-C groups are illustrated for each of the 3 delays in Fig. 3B, and reported in Table 2 ...Citations
... This task is an S+/S− discrimination task in which the discriminative cue is the repetition of S− stimuli across testing days. It has been interpreted as a familiarity discrimination and is left spared by the type of prefrontal-temporal disconnection that impairs more complex memory for lists of items 30 but is impaired by neonatal perirhinal cortex lesions 31 . Interestingly, Patient NB also shows an impairment in cumulative lifetime familiarity 32 and the build-up of item experience across days in the Constant Negative task might test familiarity in a similar way. ...
... ROC curves have been well established as providing consistent evidence between humans and nonhumans 28 and have provided good evidence of the dual-processes of recollection and familiarity in monkeys 26 . The Constant Negative test of familiarity discrimination has also been used with monkeys from different independent laboratories 30,31 and been shown to be sensitive to neonatal perirhinal cortex damage 31 , which is consistent with the perirhinal hypothesis of familiarity. Each of these tasks has its respective weakness, but those weaknesses are not overlapping. ...
Dual-process accounts of item recognition posit two memory processes: slow but detailed recollection, and quick but vague familiarity. It has been proposed, based on prior rodent work, that the amygdala is critical for the familiarity aspect of item recognition. Here, we evaluated this proposal in male rhesus monkeys (Macaca mulatta) with selective bilateral excitotoxic amygdala damage. We used four established visual memory tests designed to assess different aspects of familiarity, all administered on touchscreen computers. Specifically, we assessed monkeys’ tendencies to make low-latency false alarms, to make false alarms to recently seen lures, to produce curvilinear ROC curves, and to discriminate stimuli based on repetition across days. Three of the four tests showed no familiarity impairment and the fourth was explained by a deficit in reward processing. Consistent with this, amygdala damage did produce an anticipated deficit in reward processing in a three-arm-bandit gambling task, verifying the effectiveness of the lesions. Together, these results contradict prior rodent work and suggest that the amygdala is not critical for the familiarity aspect of item recognition.
... Figure 1 shows pre-surgical and post-surgical MR images of a representative case (Neo-PRh-6). Images from additional cases have been previously published (Zeamer et al., 2015;Weiss et al., , 2017Ahlgrim et al., 2017). ...
... Prior to participating in this study, all subjects had experience with cognitive tests including concurrent discrimination learning, reinforcer devaluation, object reversal learning, safety signal learning, and emotional regulation (Ahlgrim et al., 2017). The Neo-PRh, Neo-C and Neo-UC monkeys had additional experience with tests of object recognition (Zeamer et al., 2015;, WM , perceptual discrimination and familiarity judgments (Weiss et al., 2017). ...
... Arrows point to the rhinal sulcus (left column) and to areas of hypersignal (right column). SeeZeamer et al. (2015),,Weiss et al. ( , 2017, andAhlgrim et al. (2017) for illustration of lesion extent for additional Neo-PRh cases. ...
Previous research indicated that monkeys with neonatal perirhinal lesions (Neo-PRh) were impaired on working memory (WM) tasks that generated proactive interference, but performed normally on WM tasks devoid of interference (Weiss et al., 2016). This finding suggested that the early lesions disrupted cognitive processes important for resolving proactive interference, such as behavioral inhibition and cognitive flexibility. To distinguish between these possibilities, the same Neo-PRh monkeys and their controls were tested using the Intradimensional/Extradimensional attentional set-shifting task (Roberts et al., 1988; Dias et al., 1997). Neo-PRh monkeys completed the Simple and Compound Discrimination stages, the Intradimensional Shift stage, and all Reversal stages comparably to controls, but made significantly more errors on the Extradimensional Shift stage of the task. These data indicate that impaired cognitive flexibility was the likely source of increased perseverative errors made by Neo-PRh monkeys when performing WM tasks, rather than impaired behavioral inhibition, and imply that the perirhinal cortex and its interactions with the PFC may play a unique and critical role in the development of attentional set shifting abilities.
... This was further supported in a later study, in which non-human primates encoding for dissimilar object stimuli preferentially relied on recruitment of the perirhinal cortex during a VPC task (Zeamer, Richardson, Weiss, & Bachevalier, 2015), suggesting that, for object-type stimuli that is dissimilar, non-hippocampal structures may be capable of supporting incidental item recognition. Weiss et al. (2017) also found that non-human primates with perirhinal cortex lesions performed worse than controls during a VPC task involving object-type stimuli, but did not find a significant relationship between the extent of the lesions and novelty preference. It seems likely, however, that this was due to a small sample size and a lack of within-group variability rather than the lack of a true effect. ...
My thesis investigated whether performance on complex scene and object
perceptual and memory tasks would be influenced by possession of different variants of
the APOE gene. A particular focus was on the effect of the APOE-e4 allele on scene
processing. APOE-e4 is known to increase risk for Alzheimer's disease (AD) in later life
and is associated with structural and functional changes in the medial temporal lobe
(MTL) and posteromedial cortex, regions known to be affected early in AD. Previous
studies have shown sensitivity to spatial processing in AD, including difficulties in
differentiating scene, but not object, stimuli (Lee et al., 2006), impairments remembering
scenes over a delay (Bird et al., 2010), and deficits in navigation around spatial
environments (Pengas et al., 2010). These findings suggest that difficulties with complex
spatial processing may be a hallmark of AD, and that investigation of scene processing
in individuals at greater risk of developing AD later in life may be of interest in
understanding the genesis of these later life cognitive impairments.
In Chapter 1, I provide an overview of relevant literature on the APOE gene and
its relationship to AD, and discuss experiments which have demonstrated brain and
behaviour differences between APOE-e4 carriers and non-carriers. I interpret these
findings in the context of recent models of memory which focus on representational
networks, and where distinctions between scene and object processing are a key feature
(Bussey & Saksida, 2007; Graham, Barense, & Lee, 2010; Murray, Wise, & Graham, 2017).
The subsequent chapters describe experiments which aimed to extend the research
described in Chapter 1 by investigating scene perception and memory in carriers of
different APOE alleles in early- and mid-adulthood. In Chapter 2, I describe findings
from applying a novel conjunctive learning task, in which participants were required to
discriminate between objects and scenes. In Chapter 3, I report results from applying a
new visual paired-comparison task in the same group of participants. Chapter 4 extends
the approach outlined in Chapter 3, using the visual paired-comparison task in middle-
aged participants, again focusing on the comparison of performance in groups with
different APOE genotypes. Finally, in Chapter 5, I assess how performance in the tasks
used in Chapters 2-4 are related to the volumes of brain regions (in the MTL and
extrastriate cortex). As these have been strongly linked to object and scene perception
and memory, I was interested in whether volume would be associated with performance
on my new tasks. The final chapter summarises the experimental findings from Chapters
2-5 and explains how these build upon our current body of knowledge about how the
APOE gene affects cognition in both early- and mid-adulthood.
The hippocampus and perirhinal cortex are both broadly implicated in memory; nevertheless, their relative contributions to visual item recognition and location memory remain disputed. Neuropsychological studies in nonhuman primates that examine memory function after selective damage to medial temporal lobe structures report various levels of memory impairment-ranging from minor deficits to profound amnesia. The discrepancies in published findings have complicated efforts to determine the exact magnitude of visual item recognition and location memory impairments following damage to the hippocampus and/or perirhinal cortex. To provide the most accurate estimate to date of the overall effect size, we use meta-analytic techniques on data aggregated from 26 publications that assessed visual item recognition and/or location memory in nonhuman primates with and without selective neurotoxic lesions of the hippocampus or perirhinal cortex. We estimated the overall effect size, evaluated the relation between lesion extent and effect size, and investigated factors that may account for between-study variation. Grouping studies by lesion target and testing method, separate meta-analyses were conducted. One meta-analysis indicated that impairments on tests of visual item recognition were larger after lesions of perirhinal cortex than after lesions of the hippocampus. A separate meta-analysis showed that performance on tests of location memory was severely impaired by lesions of the hippocampus. For the most part, meta-regressions indicated that greater impairment corresponds with greater lesion extent; paradoxically, however, more extensive hippocampal lesions predicted smaller impairments on tests of visual item recognition. We conclude the perirhinal cortex makes a larger contribution than the hippocampus to visual item recognition, and the hippocampus predominately contributes to spatial navigation.
To probe how non-human primates (NHPs) decode temporal dynamic stimuli, we used a two-alternative forced choice task (2AFC), where the cue was dynamic: a movie snippet drawn from an animation that transforms one image into another. When the cue was drawn from either the beginning or end of the animation, thus heavily weighted towards one (the target) of both images (the choice pair), then primates performed at high levels of accuracy. For a subset of trials, however, the cue was ambiguous, drawn from the middle of the animation, containing information that could be associated to either image. Those trials, rewarded randomly and independent of choice, offered an opportunity to study the strategy the animals used trying to decode the cue. Despite being ambiguous, the primates exhibited a clear strategy, suggesting they were not aware that reward was given non-differentially. More specifically, they relied more on information provided at the end than at the beginning of those cues, consistent with the recency effect reported by numerous serial position studies. Interestingly and counterintuitively, this effect became stronger for sessions where the primates were already familiar with the stimuli. In other words, despite having rehearsed with the same stimuli in a previous session, the animals relied even more on a decision strategy that did not yield any benefits during a previous session. In the discussion section we speculate on what might cause this behavioral shift towards stronger bias, as well as why this behavior shows similarities with a repetition bias in humans known as the illusory truth effect.
The medial temporal lobe (MTL) is a collection of brain regions best known for their role in perception, memory, and emotional behavior. Within the MTL, the perirhinal cortex (PRh) plays a critical role in perceptual representation and recognition memory, although its contribution to emotional regulation is still debated. Here, rhesus monkeys with neonatal perirhinal lesions (Neo-PRh) and controls (Neo-C) were tested on the Human Intruder (HI) task at 2 months, 4.5 months, and 5 years of age to assess the role of the PRh in the development of emotional behaviors. The HI task presents a tiered social threat to which typically developing animals modulate their emotional responses according to the level of threat. Unlike animals with neonatal amygdala or hippocampal lesions, Neo-PRh animals were not broadly hyper- or hyporesponsive to the threat presented by the HI task as compared with controls. Instead, Neo-PRh animals displayed an impaired ability to modulate their freezing and anxiety-like behavioral responses according to the varying levels of threat. Impaired transmission of perceptual representation generated by the PRh to the amygdala and hippocampus may explain the animals' inability to appropriately assess and react to complex social stimuli. Neo-PRh animals also displayed fewer hostile behaviors in infancy and more coo vocalizations in adulthood. Neither stress-reactive nor basal cortisol levels were affected by the Neo-PRh lesions. Overall, these results suggest that the PRh is indirectly involved in the expression of emotional behavior and that effects of Neo-PRh lesions are dissociable from neonatal lesions to other temporal lobe structures.
