La triple hélice

Due to the variety of information that projects to the perirhinal cortex from unimodal cortical areas within the ventral visual, or ‘what’, processing stream, it is ideally suited for forming complex multi-sensory representations of objects (see Section 1.2.1 and Fig. 1.3). Evidence from electrophysiology has highlighted the stimulus-specific nature of perirhinal cortex cells, which selectively respond to the presentation of single objects (Zhu, Brown & Aggleton, 1995). Moreover, perirhinal cortex firing rates also provide information about the familiarity of objects (Brown & Xiang, 1998;

Ringo, 1996). Unlike the perirhinal cortex, cells within the hippocampus are not sensitive to presentations of single items (Zhu et al., 1995), or repetitions of items (Otto & Eichenbaum, 1992b). It is possible that, as focal damage to the entorhinal cortex only causes mild impairments on DNMS (see earlier, Meunier et al., 1993), object based information from the perirhinal and entorhinal cortices is not passed on to the hippocampus, despite the numerous interconnections between these structures (Aggleton & Brown, 1999).

As previously discussed, focal lesions to the hippocampus are rarely associated with impairments on delayed-non-matching to sample (DNMS) tasks for objects (Mishkin, 1978; Mumby et al., 1992; Murray & Mishkin, 1998), whereas damage to the

perirhinal cortex is sufficient to cause impairments on object-based DNMS. There is evidence, however, that lesions to the hippocampal system in monkeys (Buckley, Charles, Browning, & Gaffan, 2004; Hampton, Hampstead, & Murray, 2004) and rats (Aggleton, Hunt, & Rawlins, 1986; Morris, Garrud, Rawlins, & O'Keefe, 1982) do result in selective impairments on tasks that are spatially demanding.

There is also a wealth of electrophysiological data from animals that neural activity within the hippocampus is sensitive to changes in spatial environment, alterations to the spatial arrays of items, and associations between items and their locations (Eichenbaum, 2004; O'Keefe, 1976; O'Keefe, Burgess, Donnett, Jeffrey, & Maguire, 1998; O'Keefe & Dostrovsky, 1971; O'Keefe & Nadel, 1978). These cells have been labelled ‘place cells’, which selectively fire when an animal is placed in a particular location in an environment, or ‘place field’ (O’Keefe & Nadel, 1978). In turn these

‘place cells’ form a context-dependent map (O’Keefe & Nadel, 1978), which can remain stable for several weeks and can support long-term memory of ‘place fields’

(Lever, Wills, Cacucci, Burgess, & O'Keefe, 2002). These maps are also flexible, as place cells can rapidly remap to form representations of novel environments (Muller

& Kubie, 1987). ‘Place cells’ are yet to be identified in the perirhinal cortex and lesions to the perirhinal cortex do not impact significantly upon spatial memory (for a review see Aggleton, Kyda, & Bilkey, 2004).

The evidence described above suggests a fractionation between the perirhinal cortex and hippocampus for visuo-object and visuo-spatial processing. Recently, Winters, Forwood, Cowell, Saksida and Bussey (2004) assessed the performance of rats with perirhinal cortex or hippocampal lesions on tasks of object and spatial memory. The object recognition memory task was designed to minimise spatial and contextual confounds (Fig 1.21). While rats with perirhinal cortex lesions were severely impaired on the object task, rats with hippocampal lesions did not differ from controls, even after retention delays of up to 48 hours (Forwood, Winters, & Bussey, 2005). By contrast, only the hippocampal rats were impaired on the spatial memory task (see also Buckley et al., 2004; Gaffan, 1994, for similar effects following damage to the fornix). These data, therefore, provide compelling double dissociations between the perirhinal cortex and hippocampal contributions to object and spatial memory.

-45-Sample phase Choice phase

Retention

Object recognition Radial maze

Figure 1.21: (A) An illustration o f the spontaneous object recognition task from Winters et al. (2004), which was carried out in a m odified apparatus to m inim ise the potentially confounding influence o f spatial or locom otive factors. (B) The double dissociation between im pairments in object based and spatial m em ory follow ing perirhinal cortex an d hippocam pal damage, respectively. Figures from

Winters et al. (2004).

Despite the empirical success of lesion research, one limitation is that it can overlook the functional significance of brain regions that are associated with, but not critical for, a particular cognitive function. For example, damage to the perirhinal cortex may fail to have an effect on spatial memory due to the compensatory action o f parallel processing routes to the hippocampus (Aggleton & Brown, 2005). As a result, the functional properties of brain regions such as the perirhinal cortex and hippocampus have also been assessed using immediate early gene (IEG) c-fos imaging (for reviews see Brown & Aggleton, 2001; Aggleton & Brown, 2005). This method involves measuring the expression of IEG c-fos, which occurs when neurons are active. In turn, fo s proteins can be visualised and used to quantify neural responses within different brain regions to certain experimental manipulations. An additional benefit o f c-fos imaging over lesion research is that it permits the functional comparison of different regions in the same animals.

Paralleling findings from electrophysiology and lesion research, significant increases in fo s levels have been identified in the perirhinal cortex and area TE, but not in the hippocampus or entorhinal cortex, for the presentation of novel compared to familiar objects (Zhu, McCabe, Aggleton, & Brown, 1997). Moreover, when novel and familiar objects are presented in different visual fields, there are hemispheric differences in c-fos activity in the perirhinal cortex and area TE, whereas no differences occur in the hippocampus or entorhinal cortex (Wan, Aggleton, & Brown,

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-1999; Zhu, McCabe, Aggleton, & Brown, 1996). Increased c-fos activity has been observed in the hippocampus and parahippocampal cortex, but not perirhinal cortex, during spatial memory tasks (Vann, Brown, Erichsen, & Aggleton, 2000), exposure to novel-spatial environments (Vann et al., 2000) and presentation of novel arrangements of familiar objects (Jenkins, Amin, Pearce, Brown, & Aggleton, 2004).

When considered alongside the anatomy of the MTL, the animal research discussed above also indicates that the perirhinal cortex and hippocampus do not contribute equivalently to object versus spatial processing. The perirhinal cortex is highly specialised for processing object based information, selectively responds to the presentation of objects and, when damaged, causes significant impairments on object based DNMS (Meunier et al., 1993; Winters et al., 2004; Zhu et al., 1995; Zhu et al., 1996, 1997). Cells within the hippocampus appear to be sensitive to spatial information, and lesions to this area cause impairments on spatially demanding tasks (Aggleton et al., 1986; Bird & Burgess, 2008; Eichenbaum, 2004; Forwood et al., 2005; Morris et al., 1982; O'Keefe, 1976; O'Keefe et al., 1998; O'Keefe &

Dostrovsky, 1971; O'Keefe & Nadel, 1978; Vann et al., 2000; Winters et al., 2004).

1.6.1.2. Evidence from amnesia

To date, few experiments have directly assessed the memory performance of amnesic populations for different stimuli. In a recent study, the performance of two patient groups, individuals with focal hippocampal atrophy and individuals with wider MTL damage, was compared to matched controls on a forced-choice recognition memory task where the stimuli comprised faces and scenes (Taylor, Henson, & Graham, 2007). Patients with focal hippocampal lesions showed intact recognition memory for faces, but not scenes, whereas patients with damage to the hippocampus and perirhinal cortex were impaired on both face and scene recognition memory.

Likewise, it has been demonstrated that semantic dementia, which is generally associated with disproportionate cell loss in the perirhinal cortex (Barense, Rogers, Bussey, Saksida, & Graham, 2010; Davies, Graham, Xuereb, Williams, & Hodges, 2004; Lee, Levi, Rhys Davies, Hodges, & Graham, 2007), can cause profound impairments in memory for unfamiliar faces while memory for scenes or landscapes remains intact (Cipolotti & Maguire, 2003).

-47-As faces can be processed Shallice, & Cipolotti, 2007; developmental amnesic Jon: Bird, Vargha-Khadem, &

Burgess, 2008; although see data for patient JC, Bird et al., 2007). The ROC data, however, indicate that, if interpreted under the assumptions of DPSD, recollection for faces was intact in these patients (Fig. 1.22). In a similar vein, equivalent performance on item and associative memory for faces, but impairments on both measures for buildings and landscapes, has been identified in a patient with hippocampal pathology (Carlesimo, Fadda, Turriziani, Tomaiuolo, & Caltagirone, 2001).

The key implication of these findings is that MTL contributions to visual recognition memory may not be uniform and cannot be easily explained by a classic distinction between item versus associative memory (Carlesimo et al., 2001), or recollection versus familiarity (Bird et al., 2007; Bird et al., 2008; Cipolotti et al., 2006). These data points are, however, consistent the findings in the animal literature that indicates

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-that the perirhinal cortex and the hippocampus selectively support memory for objects (including faces) and scenes.