Método de Diseño de Mezcla del Comité 211 del ACI

A problem with the current recognition memory research with respect to this question is the discord between how recognition memory is conceptualised and approached and what the available data is saying. As discussed throughout this first chapter, both in the methodology used to study it and in the theoretical assumptions made, the field of recognition memory sees novelty as an absence, or low level of, a memory strength signal. High novelty is then synonymous to low/no familiarity. In

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this respect the words “novelty” and “familiarity” ascribe to different ends of the same, single, recognition memory process.

This suggestion is appealing as it is adheres to the principles of plurality and parsimony. Assuming a single process can explain all familiarity and novelty assessment behaviour, a second would be unnecessary and redundant. This single process could be coded for at a neural level as a signal that increases or decreases with increased familiarity, the level of the signal would then indicate the level of novelty/familiarity. As described in Section 1.4.2 of this thesis, such a signal has been observed in perirhinal cortex neurons: these show high firing rates for novel (i.e. low familiarity) items which decreases as the animal’s exposure to this item (in duration and/or number of occurrences) increases (Brown & Aggleton, 2001; Kumaran & Maguire, 2007; Xiang & Brown, 1998; Zhu & Brown, 1995).

Despite its intuitive attraction, and although it has pervaded recognition memory research for decades, this conceptualisation of novelty and familiarity and its neural processing requires questioning in light of a body of evidence that hints at a

differentiation between novelty and familiarity processing. For instance, using single unit records in macaques, Xiang and Brown (1998) characterise both novelty and familiarity neurons in the perirhinal cortex. The novelty neurons showed significantly higher firing rates for the first occurrence of novel stimuli (that had not been seen in the previous 2 months) than familiar stimuli (that were seen daily). On the other hand the familiarity neurons had relatively low responses to familiar items (seen daily) but higher rates of firing to novel items (that had not been seen in the previous 2 months) both during their first and second presentation of the day. This differentiation may be better captured by the terms ‘novelty neurons’ and ‘relative- familiarity neurons’ as the information gained from the familiarity neurons is the relative novelty or familiarity of items within a given set (regardless of the number of times these are presented). Similarly, this could be thought of as relative familiarity within a timeframe: the information gained from the familiarity neurons indicates whether the stimuli are novel or familiar across days of experimental testing sessions

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rather than across trials within a single day’s testing session. Regardless of how this is seen, these results add noise to the clear picture that familiarity is supported by response suppression neural activity in perirhinal cortex.

Furthermore, differentiation between novelty and familiarity is also seen in human neuroimaging research. Using fMRI Daselaar, Flek and Cabeza (2006) identify both linear increases (in parahippocampal cortex) and decreases (in perirhinal cortex) in BOLD response with recognition confidence. As participants rate item familiarity with greater confidence (presumably having a stronger feeling of familiarity), the BOLD response in perirhinal cortex decreases linearly, neatly paralleling the animal single unit data. The authors term this a “novelty” response – greater BOLD response for items that are considered novel, with reduced response as items are considered more familiar. On the other hand, as participants rate item familiarity with greater confidence, the BOLD response in parahippocampal cortex increases linearly. The authors term this a “familiarity” response – greater BOLD responses for items judged to be more familiar. While neurological regions don’t work independently, it is unlikely that the BOLD responses seen in the perirhinal and parahippocampal cortecies reflect an inhibitory functional connectivity between these two regions (Lauritzen, 2005; Lee et al., 2010), with local field potentials obtained from inhibitory post-synaptic potentials often thought to result in negative BOLD responses

(Lauritzen, 2005; Lee et al., 2010). This double dissociation, from another

experimental field using different methods also adds further reason to question the understanding that novelty and familiarity are inverses of each other.

Finally recent research has identified that while some individual brain areas’ neural activation (as measured by the protein marker Fos) does not differ between rats exploring novel and familiar objects, how they operate within a neural network is affected by the memory status of the objects the rat is exploring (Albasser et al., 2010). No differences in c-fos expression levels were seen in dentate gyrus (DG), lateral entorhinal cortex (LEnt), or many subregions of CA1 and CA3. Yet structural equation modelling suggests the integration of these is qualitatively different when

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rats are presented with old and new objects. Rats having been presented with novel objects in a Bow-tie maze variant of the SOR (see Figure 1.2) showed

parahippocampal to hippocampal connectivity mediated by the perforant pathway (i.e. Te2<->PRh -> LEnt -> DG -> CA3 -> CA1) while those presented with familiar objects in the same task showed parahippocampal to hippocampal connectivity mediated by the temporo-ammonic pathway (i.e. Te2<->PRh -> LEnt -> CA1). This falls in line with the novelty-encoding hypothesis, where novel items lead further encoding/processing into the hippocampus (Fernández & Tendolkar, 2006). While these results don’t preclude that novelty/familiarity identification is based on a single neural process (indeed c-fos expression levels in caudal perirhinal cortex showed differentiation between the novel and familiar groups), they do highlight that novelty and familiarity processing differs at a network level. With respect to the question of whether novelty and familiarity are a single process, it becomes

apparent that the concept of a “process” can be considered at various levels:

identification of novelty/familiarity? How novelty/familiarity are treated by the MTL? The metacognition of novelty/familiarity? If anything, these results remind us that looking at individual neural areas in isolation is rather simplistic and that higher levels of analysis, such as a network approach, need to be considered given that they offer insight from differing angles.

Figure 1.2: Bow-Tie Maze – a variant of the spontaneous object recognition (SOR) task.

In summary, the question of whether novelty and familiarity are words referring to the inverse of the same process can be addressed at differing levels of analysis, potentially with different outcomes. However, given the data currently available, this

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question is still up for debate at most (if not all) of these levels. Given the

importance and breadth of novelty (as outlines in Section 1.1), the relevance of this question to the assumption of the recognition memory field, and the suggestion that this assumption may be flawed, further consideration and exploration of

novelty/familiarity processing is of significant importance.