Elsevier

Consciousness and Cognition

Volume 19, Issue 3, September 2010, Pages 816-828
Consciousness and Cognition

ROC in animals: Uncovering the neural substrates of recollection and familiarity in episodic recognition memory

https://doi.org/10.1016/j.concog.2010.06.023Get rights and content

Abstract

It is a consensus that familiarity and recollection contribute to episodic recognition memory. However, it remains controversial whether familiarity and recollection are qualitatively distinct processes supported by different brain regions, or whether they reflect different strengths of the same process and share the same support. In this review, I discuss how adapting standard human recognition memory paradigms to rats, performing circumscribed brain lesions and using receiver operating characteristic (ROC) methods contributed to solve this controversy. First, I describe the validation of the animal ROC paradigms and report evidence that familiarity and recollection are distinct processes in intact rats. Second, I report results from rats with hippocampal dysfunction which confirm this finding and lead to the conclusion that the hippocampus supports recollection but not familiarity. Finally, I describe a recent study focusing on the medial entorhinal cortex (MEC) that investigates the contribution of areas upstream of the hippocampus to recollection and familiarity.

Introduction

The contribution of two memory types to recognition memory function has been discussed since the time of Aristotle. One of these processes is described as a vague feeling of familiarity or ‘reminiscence’; for example when you recognize somebody, but cannot identify this person by name. The second, the recollection process, involves additional dimensions of memory; for example the spatial or temporal context in which this person was encountered (for a review see Yonelinas (2002)). Interestingly, the recollection and the familiarity processes are differentially affected in aging and in patients with amnesia. Indeed, the recollection process is strongly impaired in aging and amnesia, while the familiarity process is relatively spared (Barbeau et al., 2005, Brandt et al., 2008, Daselaar et al., 2006, Duverne et al., 2008, Düzel et al., 2001, Howard et al., 2006, Peters and Daum, 2008, Prull et al., 2006, Quamme et al., 2004, Turriziani et al., 2008, Vann et al., 2009, Yonelinas et al., 1998; but see Knowlton and Squire, 1995, Schacter et al., 1997). Hence, uncovering the neural substrates of the recollection and the familiarity processes could contribute to the characterization of new targets to rescue at least part of these deficits. A standard method to analyze human recognition memory performance is to use receiver operating characteristic (ROC) functions (for a review see Yonelinas and Parks (2007)). In humans, episodic recognition memory is usually assessed by presenting a study list of items to a subject (for example a list of words appearing on a screen one at a time), and after a delay, presenting a longer list of items composed of the same items intermixed with an equal number of new items, also appearing one at a time. The probability of correct recognition of a study list item (p‘hit’) is plotted as a function of the probability of incorrect recognition of a ‘new’ item (p‘false alarm’) across confidence or bias levels, and the best fitting curve is defined to generate an ROC function (Yonelinas, 1999; see Fig. 1A and C for idealized human ROC curves for item and associative recognition memory, respectively).

Multiple models of recognition memory are based on the contribution of the familiarity and the recollection processes to recognition memory function (for a review see Yonelinas (2002)). Among them, two have been used extensively to study episodic recognition memory in humans: the dual-process model and the one-process model (for reviews see Wixted, 2007, Yonelinas and Parks, 2007 respectively). The dual-process model describes familiarity and recollection processes as qualitatively distinct processes. In light of this model, the familiarity process is described as a rapid and continuous signal detection process sensitive to perceptual manipulations, while the recollection process is described as a slower and conceptually driven threshold process (Atkinson and Juola, 1973, Atkinson and Juola, 1974, Mandler, 1980; see for a review Yonelinas (2002)). Studies using the dual-process model of recognition memory also report that familiarity and recollection have different neural substrates: the hippocampus for recollection, the parahippocampal region for familiarity (Aggleton et al., 2005, Bowles et al., 2007, Yonelinas et al., 2002, Yonelinas et al., 2007; see for reviews Diana et al., 2007, Eichenbaum et al., 2007). According to this model, two distinct indices can be generated from the analysis of ROC functions. The recollection index (R), y-intercept of the ROC function, which reflects the contribution of the recollection process to recognition memory performance, and the familiarity index (F), reflected by the degree of curvilinearity of the function, which reveals the contribution of familiarity to recognition memory performance (see Yonelinas, 1994, Yonelinas and Parks, 2007 for calculation of the indices). Hence, within the frame of the dual-process model, ROC functions are asymmetrical and curvilinear when familiarity and recollection contribute to recognition memory performance (Fig. 1A), asymmetrical and linear when the recollection process is primarily involved (Fig. 1C), or symmetrical and curvilinear when recognition memory is essentially based on the familiarity process (Fig. 5; Aged group).

A major alternative to this model is the one-process theory that describes familiarity and recollection as qualitatively similar processes differing only in the strength of memory they reflect (see for a review Wixted (2007)). Familiarity would reflect weak memory, while recollection would reflect stronger memory or memory involving more information. As a consequence, recollection and familiarity would have a unique neural substrate, the hippocampus and could not vary independently (Manns et al., 2003, Stark and Squire, 2000, Wais et al., 2006; see for a review Squire, Stark, and Clark (2004)). According to this view, the degree of curvilinearity of the ROC function reflects the sum of the strengths of memory components, and its asymmetry reflects greater variability in strength for the ‘old’ than for ‘new’ items.

Among human ROC studies, some report that damage restricted to the hippocampus impairs specifically the recollection process (Aggleton et al., 2005, Quamme et al., 2004, Yonelinas et al., 2002), while others report that both processes are affected in patients with damage thought to be circumscribed to the hippocampus (Manns et al., 2003, Reed and Squire, 1997, Stark and Squire, 2000, Wais et al., 2006). This discrepancy resides mainly in the fact that the hippocampus and the parahippocampal region are adjacent brain structures. Indeed, identifying the precise extent of brain damage in patients with amnesia, or the precise source of brain activity within adjacent brain regions is beyond the spatial and neuropsychological resolution of standard techniques used currently in humans (e.g. functional and structural MRI imaging, and psychological tests). Thus, it has been suggested that the familiarity impairments accompanying the recollection deficits reported in some studies in patients with damage to the hippocampus resulted from additional damage to areas adjacent to the hippocampus (e.g. the parahippocampal region), rather than from damage to the hippocampus per se.

Given the medial temporal lobe is exceptionally conserved across species (Manns & Eichenbaum, 2006), one way to clearly define whether the hippocampus supports familiarity as well as recollection is to perform lesion restricted to the hippocampus in animals, and assess the effect of this circumscribed lesion with behavioral paradigms that allow for the generation of distinct recollection and familiarity indices. We discuss this approach in the present review.

A second major issue in human recognition memory is whether the parahippocampal region is functionally segregated in terms of its contribution to the recollection and the familiarity processes. Indeed, recent human and animal studies suggest that specific areas of the parahippocampal region, which are adjacent and strongly interconnected, contribute to different aspects of memory function (see Eichenbaum et al. (2007) for a review). The perirhinal cortex (PRc) and the lateral entorhinal cortex (LEC) would process information about the familiarity of individual items. In contrast, the postrhinal cortex (POR; parahippocampal cortex in humans) and the medial entorhinal cortex (MEC) would support recollection by representing the spatial and temporal context (whether the items are new or old) in which items have been experienced. However, this hypothesis could not be thoroughly tested in humans principally because of two reasons. One: it is not possible to determine the precise source of brain activity during recognition memory tasks in humans when areas are adjacent. Two: because cases showing restricted lesions to a single area of the parahippocampal region are extremely rare.

In this review I will show how we addressed these two controversial issues by developing behavioral animal ROC paradigms that allow for recognition memory performance to be evaluated in a similar manner to the way that it is in humans (e.g. translational paradigms). Moreover, given these tasks are performed with animals, they present a key advantage over human ROC studies in that they can be combined with stereotactic surgery, which allows for brain areas to be damaged in a very restricted manner, while preventing additional damage to the adjacent brain structures.

Using this approach, we first aimed at investigating the contribution of the hippocampus to recollection and familiarity by performing lesions circumscribed to the hippocampus, and defined whether the hippocampus supports recollection and familiarity, or recollection only. Second, we investigated the contribution of areas upstream of the hippocampus, more specifically the contribution of the MEC, to recollection and familiarity by performing lesion circumscribed to the MEC.

In the first part of this review, I will discuss how animal ROC paradigms contributed to bridging human and animal recognition memory, and brought evidence that recollection and familiarity are qualitatively distinct processes using intact rats. In a second part, I will show that this finding was confirmed in rats with impaired hippocampal function, and will show that animal ROC paradigms brought compelling evidence that the hippocampus supports recollection but not familiarity. In the last part of the review, I will report the first step of a series of studies investigating the functional segregation of the parahippocampal region, which focuses on the characterization of the contribution of the MEC to recollection and familiarity.

Section snippets

A translational model of episodic recognition memory

A prerequisite for animal ROC paradigms to be appropriate translational models is to yield results comparable to those observed in humans, e.g. the contribution of familiarity and recollection to recognition memory performance in rats would be expected to be comparable to that of humans under the same experimental conditions.

Within the frame of the dual-process model, a typical standard human ROC function for single item recognition memory reflects the contribution of the recollection and the

Are recollection and familiarity distinct processes? evidence from intact rats

The first controversial issue that we addressed using animal ROC paradigms was whether recollection and familiarity were qualitatively distinct processes, or whether they reflected different strengths of the same process. Compelling evidence that these processes are distinct would be that one process could support recognition memory performance without a significant contribution of the other. To test this hypothesis, we investigated recognition memory performance of intact rats under memory

Does the hippocampus support the recollection and the familiarity processes? evidence from rats with hippocampal dysfunction

A major controversy in recognition memory is whether the hippocampus supports the recollection process only or whether it also supports the familiarity process. Previous studies report a predominant role for the hippocampus in the recollection process while the parahippocampal region is suggested to primarily contribute to the familiarity process (Brown and Aggleton, 2001, Eichenbaum et al., 1994). However, conflicting results emerged from the ROC literature in humans. Evidence from studies on

Acknowledgments

We thank Jarret Frank for his help in Graphic designs and Zachery Beer for proof-reading. These experiments were Funded by MH71702, MH51520, MH52090 and AG09973.

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