Neural correlates of recollection and familiarity: A review of neuroimaging and patient data

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1 Neuropsychologia 45 (2007) Reviews and perspectives Neural correlates of recollection and familiarity: A review of neuroimaging and patient data Erin I. Skinner, Myra A. Fernandes Department of Psychology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada Received 18 September 2006; received in revised form 28 February 2007; accepted 1 March 2007 Available online 12 March 2007 Abstract Dual-process models of recognition memory suggest that two processes contribute to performance: recollection and familiarity. Recent work suggests that the two processes are dissociable at the level of the brain. Here we review 12 studies that used event-related functional magnetic resonance imaging (fmri), and 21 studies of patients with damage to various brain regions, which examined recollection and familiarity using the Remember Know (R/K), process dissociation procedure (PDP), or receiver operator characteristic (ROC) memory paradigms, for insights into the neural basis of each process. Results show that recollection and familiarity are characterized by different patterns of brain activity in frontal, parietal, sensory, and medial temporal cortices. Results suggest that recollection and familiarity cannot be dissociated based on confidence levels alone, and that the two processes are not exclusive. Based on these results, we propose a model in which recollection and familiarity can be dissociated in two ways: recruitment of additional brain regions in frontal, medial temporal, and content-specific cortices during recollection, and in variations in coherence of brain networks activated during recollective- or familiarity-based processing Elsevier Ltd. All rights reserved. Keywords: Memory; Recollection; Familiarity; Neuropsychology; fmri Contents 1. Introduction Method Inclusion criteria Organization of peak activation data in the tables and figures Imaging analyses Analysis of patient data Results Imaging data analysis Recollection Familiarity Comparison of percent signal change in the hippocampus Lesion data analyses Discussion Do recollection and familiarity require different neural structures? Both recollection- and familiarity-based responses are associated with right dorsolateral prefrontal cortex activity, but recollection involves additional prefrontal activity Both recollection and familiarity activate precuneus regions of the parietal lobe (BA 7), but recollection also activates the inferior parietal lobe (BAs 40 and 39) Corresponding author. Tel.: x37776; fax: address: eiskinne@watarts.uwaterloo.ca (E.I. Skinner) /$ see front matter 2007 Elsevier Ltd. All rights reserved. doi: /j.neuropsychologia

2 2164 E.I. Skinner, M.A. Fernandes / Neuropsychologia 45 (2007) The recapitulation of sensory areas occur only during recollection Recollection and familiarity are related to activation in different regions of the MTL Are recollection and familiarity-based recognition responses confounded by confidence levels guiding recognition judgments? What is the relationship between recollective- and familiarity-based recognition judgments? Can a neurocognitive model of recollection and familiarity be formed? Conclusions Acknowledgement References Introduction Dual-process models of recognition postulate two ways in which information can be recognized, referred to as recollection and familiarity (Gardiner, 1988; Jacoby, 1991; Mandler, 1980). Recollection is defined as the mental reinstatement of previous events. During recollection, unique details of a memory are recalled, which may include additional sensory information such as the sounds paired with an event, or the emotions experienced during the initial encoding of the item, scene, or event. The second type of recognition process, referred to as familiarity, is a mental awareness that an event has been experienced in the past, but the memory is lacking the unique details or mental reinstatement of the event that accompanies recollection. The difference between these two processes is easily demonstrated in everyday life by the example of meeting a person you recognize on the street. Sometimes we can specifically place where, or when in the past, we had met the person. This is a recollective process. In contrast, we sometimes gain a strong sense that we have met the person before, but cannot identify where or when we originally encountered the individual. The person is familiar to us, despite the fact that we cannot recollect unique details of the initial meeting event. This is a familiarity process. Three main paradigms are often used to examine the relative contribution of recollection and familiarity to recognition memory. The first is the Remember Know (R/K) paradigm (Tulving, 1985). During a recognition memory test, participants are asked to state whether an item is either Remembered (they can recollect specific information about the item from the study phase), Known (the item is familiar in the absence of a specific recollection), or New (the item was not previously encountered). In general, Remember responses are believed to reflect recollective memory processes, whereas Know responses align more with familiarity-based recognition decisions (Henson, Rugg, Shallice, Jospehs, & Dolan, 1999a; Yonelinas, 2001; Yonelinas & Jacoby, 1995). The second is the process dissociation procedure (PDP) (Jacoby, 1991). In this paradigm, participants are asked to study a list of items in two different contexts, and are subsequently given two recognition tests. In the inclusion test, participants are asked to identify an item as old if they previously encountered the item, regardless of the context in which it was presented. In the exclusion test, participants are asked to identify an item as old only if it was presented in one of the two study contexts. Thus, while correct responses in the inclusion test may be based on both recollective and familiarity processes, correct responses in the exclusion test must be based on recollective, or sourcebased, memory. Using an assumption that the two processes are independent, one can then calculate recollection and familiarity estimates. The third is the Receiving Operator Characteristics (ROC) method (Yonelinas, 2001). Here, participants are required to rate the confidence of their recognition memory responses, and a curve is formed by plotting hits and false alarms against one another as a function of confidence. Familiarity and recollection estimates are then derived using mathematical algorithms that assume recollection is a threshold process, whereas familiarity reflects a signal-detection process. Past cognitive and neuropsychological research suggests recollection and familiarity are functionally distinct processes, with different experimental manipulations producing different effects on recollection and familiarity (for reviews see Diana, Reder, Arndt, & Park, 2006; Gardiner, Ramponi, & Richardson-Klavehn, 2002; Rotello, Macmillan, & Reeder, 2004; Yonelinas, 2002). For example, levels of processing manipulations (Gregg & Gardiner, 1994; Rajaram, 1993), division of attention (Gardiner & Parkin, 1990; Yonelinas, 2001), and benzodiazepine administration (Curran, Gardiner, Java, & Allen, 1993; Hirshman, Fisher, Henthorn, Arndt, & Passannate, 2002) during study, affect recollection estimates more so than familiarity. In contrast, speeded responding experiments suggest that familiarity processes are present earlier than recollection processes (Yonelinas & Jacoby, 1994, 1995). Additionally, changing the perceptual characteristics of word stimuli at test decreases familiarity-based processing while leaving recollection unaffected (Rajaram, 1993; Rajaram & Geraci, 2001). Neuropsychological evidence suggests that recollection and familiarity processes are also dissociable at the level of the brain. There is some evidence that recollection is affected to a greater extent in some special populations, such as amnesic patients with temporal lobe damage (Blaxton & Theodore, 1997; Holdstock, Mayes, Gong, Roberts, & Kapur, 2005; Schacter, Verfaellie, & Anes, 1997; Yonelinas et al., 2002), and older adults (Healy, Light, & Chung, 2005; Norman & Schacter, 1997; Parkin & Walter, 1992). Delineating the set of neural structures that support the recollective and familiarity memory process during memory retrieval is an on-going research question, with implications for current models of recognition memory. For example, there is an on-going debate as to whether the hippocampus and the perirhinal and parahippocampal cortices play different roles in recollection and familiarity (see Aggleton & Brown, 1999; Squrie, Stark, & Clark, 2004 for opposing views), and whether

3 E.I. Skinner, M.A. Fernandes / Neuropsychologia 45 (2007) additional neural structures, such as the prefrontal cortex (PFC), contribute differently to recollective and familiarity memory processes has been more recently examined (Alexander, Stuss, & Fansabedian, 2003; Duarte, Ranganath, & Knight, 2005). In recent years, neuroimaging techniques such as eventrelated potentials (ERP), positron emission tomography (PET), and functional magnetic resonance imaging (fmri) have been used in an attempt to establish the neural patterns that underlie the two memory processes. Using such techniques allows researchers to investigate recollection and familiarity in nonbrain damaged participants. In this review we consider both neuroimaging and patient data in an attempt to delineate common brain structure associated with the two memory processes. We review the findings of 12 studies that used event-related functional magnetic resonance imaging (fmri), and 21 studies of patients with damage to various brain regions. All of these studies examined recollection and familiarity using R/K, PDP, or ROC memory paradigms, in order to pinpoint the key brain regions associated with recollection and familiarity processes during retrieval. By analyzing imaging and lesion data together, we are able to combine the strengths of each methodology. In doing so we hope to address four key questions regarding recollection and familiarity: 1. Do recollection (R) and familiarity (F) processes rely on different neural structures at retrieval? If so, we should be able to identify patterns of brain activity or lesion sites that are common across studies. 2. Are recollection- and familiarity-based recognition responses confounded by confidence levels guiding recognition judgments? Whereas F responses are associated with a range of confidence ratings in one s memory judgment, R responses are almost always associated with high confidence levels (Yonelinas, 2001). Thus, any differences between R and F responses may not be due to recollective and familiarity memory processes per se, but rather to differences in recognition confidence levels. By comparing activation patterns associated with recognition judgments attributed to familiarity, in which the subject is highly confident, with those associated with judgments attributed to recollection (assumed to be high confidence), we can determine whether, at the neural level, recollection is simply a form of recognition memory in which the subject is highly confident of the occurrence of the item or event. In addition, we can dissociate recollection and familiarity from response confidence by determining whether patients who have deficits in recollection, but not familiarity, have a similar distribution in response confidence as controls. 3. What is the relationship between recollective and familiaritybased recognition judgments? An on-going consideration in the dual-process literature concerns the exact nature of the relationship between these processes (Knowlton & Squire, 1995; Yonelinas, Dobbins, Syzmanski, Dhaliwal, & King, 1996). We review three models that describe the relationship: exclusivity, redundancy, and independence, and consider whether the neuroimaging and patient literature can be used to support any of these accounts. 4. Can a neurocognitive model of recollection and familiarity be formed? Here, we address whether a neurocognitive model of recognition memory can be developed based on the results of our review. We begin with a brief explanation of the inclusion criteria that we adopted for this review. We then explain the methods used to create the tables and figures, and describe how the imaging and lesion data were analyzed. This is followed by the results of our analysis. Lastly, we discuss our findings in the context of the four questions outlined above. 2. Method 2.1. Inclusion criteria A summary of the event-related fmri studies included in our review can be found in Table 1, organized in columns by stimulus type (word or pictures), R and F behavioural estimates observed, as well as fmri contrasts performed for each study. We summarized peak activations (in Tables 3 and 4) found in studies that met the following criteria: 1. They used the R/K, PDP, or ROC method to examine recollection and familiarity processes. 2. We limit our analysis to activations found during test (retrieval). 3. We examine both subtraction and parametric contrasts. A list of the contrasts can be found in Tables 3 and 4. Only contrasts that specifically examined recollection or familiarity processes were included (i.e., contrasts that examined general recognition memory were not included). The reader is encouraged to refer to the original article to obtain specific details regarding the contrasts. 4. Only data from healthy younger adults were used. 5. Because retrieval of emotional material may be supported by additional brain regions (Kensinger & Corkin, 2004; Smith, Henson, Dolan, & Rugg, 2004), we report only peak activations relating to neutral stimuli in those studies that examined both neutral and emotional stimuli (Dolcos, LaBar, & Cabeza, 2005; Fenker, Schott, Richardson-Klavehn, Heinze, & Duzel, 2005; Sharot, Delgado & Phelps, 2004). 6. Effects that were specific to the type of material used at test (Woodruff, Johnson, Uncapher, & Rugg, 2005) were not reported Organization of peak activation data in the tables and figures fmri contrasts were classified into two different tables, depending on whether the contrast examined recollection (Table 3) or familiarity (Table 4). Rows of the table denote the study, and columns specify the type of contrast used in that study, as well as Brodmann Area (BA) of activation (increase or decrease), grouped by lobe. In order to directly compare regions showing brain activation across studies, we transformed all studies using MNI coordinates to Taliarch and Tournoux (1988) coordinates using a non-linear transformation matlab function authored by M. Brett (available at For studies that did not report the approximate BA relating to individual coordinates, we used the Taliarch and Tournoux (1988) atlas to determine the BA. If the coordinate was further than 3 mm 3 away from a specific BA, we report the activation in the two closest BAs, using a different symbol. Since Montaldi, Spencer, Roberts, and Mayes (2006) used two different parametric contrasts to estimate familiarity (one that included new responses, and one that did not), we chose to report the coordinates of the parametric contrasts that excluded new responses. For the purpose of the review, we define the medial temporal lobe (MTL) as a collection of brain regions, including the hippocampus proper, the parahippocampus, and the perirhinal and rhinal cortex. Whenever possible, we will note the precise sub-region of MTL being considered. The coordinates from all studies were then over-laid onto a common brain image to allow better visualization of the fmri data (Fig. 1). In cases where the study reported the BA, but not the exact coordinate of peak acti-

4 2166 E.I. Skinner, M.A. Fernandes / Neuropsychologia 45 (2007) Table 1 Summary of fmri studies examining brain activity associated with recollection and familiarity Study Method Stimuli R estimate K estimate Contrasts Encoding Retrieval Henson, Rugg, et al. (1999) R/K Word Word Remember New; Know New; Remember Know; Know Remember Henson, Shallice, et al. (1999) PDP Word Word Exclusion Control; Exclusion Inclusion Eldridge et al. (2000) R/K Word Word Remember Know; Know Remember; Know New a Rugg, Henson, and Robb (2003) PDP Word Word Correct Exclusion Incorrect Inclusion b (Exclusion New) (Inclusion New) b Wheeler and Buckner (2004) R/K Word picture Word Remember Know c ; Know Remember Word sound Word Remember New a ; Know New a Yonelinas et al. (2005) ROC Word Word Remember > High Know; Know: 4>3>2>1;Know:1>2>3>4 Sharot et al. (2004) R/K Image Image Remember Know; Know Remember; Remember New; New Remember Dolcos et al. (2005) R/K Image Image Remember Know a,c Fenker et al. (2005) R/K Word face Word Remember Know; Know Remember Woodruff et al. (2005) R/K Word and picture Word Remember New, Remember Know a Daselaar et al. (2006) ROC Word Word x 2 increase (3>2=1);3>2>1;1>2>3 Montaldi et al. (2006) ROC Scene Scene Remember 3; 3 Remember; 1>2>3; 3>2>1 Note: R = recollection; F = familiarity; 4>3>2>1=increasing confidence; 1>2>3>4=decreasing confidence; x 2 = exponential increase. a Denotes analysis was performed only on selected brain regions. b Denotes analyses performed only on prefrontal cortex. c Denotes contrasts for which activation coordinates were not specified. vation (Dolcos et al., 2005; Wheeler & Buckner, 2004), the activation is not included on the image, but is reported in the tables. The standardized brain was acquired from AFNI (available at and is based on the anatomical dataset (N27) obtained from the Montreal Neurological Institute ( and University of California at Los Angeles ( The coordinates were compiled into a 3D imaging dataset using the AFNI program 3dUndump. This program develops a 3D dataset from an ASCII list of coordinates, with each coordinate having a specified radius and value. Because not all studies report volumetric data, all coordinates were given an equal size of 3 mm 3. The images of the MTL activations (shown in Fig. 2) were developed using the AFNI render plug-in function, which allows viewing of 3D imaging datasets. All other surface brain images were developed Fig. 1. Surface brain image renderings showing activation peaks associated with recollective-based responding (blue activation) and familiarity-based responding (red activation), and response confidence. Peaks in yellow depict regions found to increase with increasing response confidence and regions in orange were found to increase with decreasing response confidence. Activation is depicted in (A) the left hemisphere, in (B) the right hemisphere, in (C) the frontal lobes, and in (D) the parietal and occipital lobes.

5 E.I. Skinner, M.A. Fernandes / Neuropsychologia 45 (2007) Fig. 2. Activation in the right (panel A) and left (panel B) medial temporal lobe relating to recollective-based responding (shown in blue), familiarity-based responding (shown in red), and response confidence (regions found to increase with decreasing response confidence are in orange). in SUMA, a program developed to display 3D cortical surface models (Fig. 1). Activation peaks in blue represent those found for R-based contrasts and activations in red represent F-based contrasts (see Section 3 for a description). We also included those activations found to increase with increasing confidence (shown in yellow) and those found to increase with decreasing confidence (shown in orange) Imaging analyses In order to identify the brain regions associated with R and F processes that were commonly activated across studies, we calculated the percentage agreement in activation for each BA. This measure was calculated by dividing the number of studies that found R- or F-based activation in a given BA, by the number of studies in which activity in that area was possible, given the method of fmri data collection (and multiplying this quotient by 100). That is, not all studies performed whole brain analysis; thus, for some BAs it was not possible to observe any activation. In those cases, the study was not included in the denominator of the percentage agreement calculation. Each study was included only once in the numerator and denominator of the percentage agreement calculation, even if multiple activations were found in a given Brodmann Area in that study, or if more than one contrast was performed in that study (for example, Remember Know and Remember New responses). If the activation was bordering two BAs, the activation was multiplied by 0.5 for each BA. For R-based responding, we included Remember Know, Remember New, Exclusion Recognition, Exclusion Inclusion, Exclusion New, and exponentially modeled contrasts. The percentage agreement can be found, for each region, at the bottom of Table 3. For F-based responses, we included Know Remember and Know New contrasts (see bottom of Table 4). For those paradigms that used confidence measures, activity associated with the highest confidence rating was taken to reflect R-based responding, whereas activity associated with increasing or decreasing confidence was used to reflect F-based responding, as defined by the original experiments. Any percentage that was 50 percent or greater was considered to be a high level of agreement, percentages between 30 and 49 percent were considered to be of intermediate agreement, and any percentage lower than 30 percent was considered to be of low agreement. In Section 3, we highlight only those areas that received high or intermediate percentage agreements, although all peak activations are included in Tables 3 and 4. We additionally calculated percentage agreement for each specific contrast type (i.e., individual percentage scores for Remember Know, Remember New, etc.), but this did not significantly change the findings, and so it is not reported. Lastly, we created separate percentage agreement values for contrasts that examined increasing activation with increasing, and decreasing, response confidence. The imaging studies reviewed here used different thresholds and baselines in order to identify the brain regions related to recollection and familiarity processing. Our determination of percentage agreement may thus provide an underestimation of that region s participation in the said process. Nevertheless, this method provides a way of examining the frequency with which each area has been reported to be significantly active during each process, across several studies Analysis of patient data Table 2 contains a summary of the patient studies included in the review, with stimulus type, as well as recollection and familiarity estimates observed in both the patient and corresponding control group in each study, noted in columns. The hemisphere and lesion location is also noted for each study. All studies that examined the effect of lesions on recollection and familiarity estimates using R/K, PDP, and ROC paradigms were included. The estimates of recollection and familiarity reported for patient and control recognition memory performance were taken directly from the original study, but for those studies in which additional variables, such as frequency or repetition priming were examined, recollection and familiarity estimates were averaged across these additional variables. In addition, we wished to use the review of the lesion data to specifically investigate the role of the MTL in recollective- and familiarity-based memory processes. Past patient work suggests that the MTL may play a crucial role in recollective memory processes (Blaxton & Theodore, 1997; Holdstock et al., 2005; Moscovitch & McAndrews, 2002; Schacter et al., 1997; Yonelinas et al., 2002). Whether damage to this region of the brain also affects familiarity processes, however, and whether recollective processes are more greatly affected by MTL damage than familiarity, is less well known. We also wished to examine whether specific damage to MTL structures, rather than damage to simply any brain structure, has a selective effect on recollective and/or familiarity memory processes. We performed a 3 (Group: MTL lesion, non-mtl lesion, or control) 2 (Memory process: recollection or familiarity) ANOVA on the data, with patient type being a between-subjects, and memory process a within-subject manipulation. 1 Lastly, in order to address whether recollection- and familiarity-based recognition responses are confounded by confidence levels, we performed a further analysis on the Aggleton et al. (2005) study. In this paper, the responses of a participant with a lesion confined to the hippocampus, and those of the control participants, are reported on a response confidence scale of 1 6, with a value of 1 corresponding to a low confident response and a value of 6 corresponding to a high confident response. Aggleton et al. used these estimates to create ROC curves that showed that although that patient had deficits in recollective-based responding, his familiarity-based responses were unaffected. We wished to examine whether this patient would produce a similar distribution of responses across levels of response confidence as controls. If recollection simply reflects high confidence memory responses, the patient should show fewer high confidence responses than controls. We determined the percentage of responses of each confidence level (i.e., the number of responses given for that confidence level, divided by all of the responses, multiplied by 100), separately for items classified as old and new. We then determined whether the percentage of responses at each confidence level, for the patient, was within two units of standard deviation from that of the control group. 1 The Verfaellie and Treadwell (1993) study was not included in either analysis since the specific lesion sites were not reported. Nonetheless we report recollection and familiarity estimates from this study for the reader.

6 2168 E.I. Skinner, M.A. Fernandes / Neuropsychologia 45 (2007) Table 2 Summary of studies examining recollection and familiarity in brain lesioned patients, and the reported estimates for patients and controls from each study Study Method Stimuli Hemisphere Lesion location(s) Recollection Familiarity Patient Control Patient Control Duarte et al. (2005) R/K Pictures R or L FL Levine et al. (1998) R/K Words R Inferior FL Levine et al. (1999) R/K Name face pairs R Inferior FL Blaxton and Theodore R/K Visuospatial designs L or R TL (1997), Exp 1A Blaxton and Theodore R/K Visuospatial designs L or R TL (1997), Exp 2 Moscovitch and McAndrews R/K Faces, words L or R TL (2002) Cipolotti et al. (2006) ROC Words, faces, buildings, scenes B Hp Hirano, Noguchi, Hosokawa, R/K Events B Hp and Takayama (2002) Manns, Hopkins, Reed, R/K Faces, pictures, words B Hp Kitchener, and Squire (2003) Yonelinas et al. (2002) R/K Words B Hp ROC B Hp Wais, Wixted, Hopkins, and ROC Words B Hp Squire (2006) Yonelinas, Kroll, Dobbins, ROC Words L Hp Lazzara, and Knight (1998) Aggleton et al. (2005) R/K Words B Hp, Am, En ROC Yonelinas et al. (2002) R/K B Hp, Ph ROC B Hp, Ph Knowlton and Squire (1995) R/K Words B Hp or Di Schacter, Verfaellie, and R/K Words MTL and/or Di Pradere (1996) Schacter et al. (1997) R/K Words MTL and/or Di Edelstyne, Hunter, and Ellis R/K Names B Th (2006) Hanley et al. (2001) R/K Words L Cd, Fx, Th Kishiyama et al. (2005) R/K Words, pictures B Th ROC Words, faces Verfaellie and Treadwell (1993) PDP Words Amnesics Note: Am = amygdala; B = bilateral; Cd = caudate; Di = diencephalon, En = entorhinal cortex; FL = frontal lobe; Fx = fornix; Hp = hippocampus; L = left hemisphere; MTL = medial temporal lobes; Ph = parahippocampus; R = right hemisphere; TL = temporal lobe; R/K = Remember Know procedure; PDP = process dissociation procedure; ROC = receiver operator characteristics; Th = thalamus. 3. Results 3.1. Imaging data analysis Recollection Peak activations associated with R-based processing, from each study, are reported in Table 3 and are displayed in blue in Figs. 1 and 2. 2 Within the frontal lobe, activation associated with R-based responses was widely dispersed, with little overlap across studies (see Fig. 1, panel C). BAs 10 and 8 both showed 2 We would like to remind the reader that in cases where the study reported the BA, but not the exact coordinate of peak activation, the activation could not be included on the image, but is reported in the tables. high agreement in activation across studies in the left lobe (59 and 50 percent, respectively), and intermediate levels of agreement in the right lobe: 41 percent in BA 6 and 36 percent in BA 46. Within the parietal lobe, we found intermediate agreement in activation in left BAs 31 and 7 (both 40 percent), and high levels in left BA 39 (50 percent). Agreement was also high (60 percent) in BA 40 in the left hemisphere and had intermediate agreement (40 percent) in the right hemisphere (see Fig. 1, panel D). The left anterior cingulate (BA 24) showed an intermediate level of agreement in activation across studies, of 35 percent. The only occipital region found to have intermediate levels of agreement was bilateral BA 19 (40 percent for the left and 30 percent for the right hemisphere). No sub-cortical regions were found to have notable activation levels.

7 Table 3 Activation peaks for recollective-based responses classified according to Brodmann Area Note: BA = Brodmann Area; bg = basal ganglia; cb = cerebellum; Exc = exclusion; ExcNon = Correctly Excluded Non-targets; H = hemisphere; Inc = inclusion; Ins = insula; K = know; mt = medial temporal cortex; N = new; R = remember; th = thalamus; x 2 = exponential increase; = an increase in activation in the left hemisphere; = an increase in activation in the right hemisphere; = an increase in the left hemisphere for which the coordinate lies between two BAs; = an increase in the right hemisphere for which the coordinate lies between two BAs; superscript values represent how many times activation was found in that BA for that study. E.I. Skinner, M.A. Fernandes / Neuropsychologia 45 (2007)

8 2170 E.I. Skinner, M.A. Fernandes / Neuropsychologia 45 (2007) Within the temporal lobe, intermediate levels of agreement were found for the left insula, left BA 22, and bilateral BA 21 (see Table 3). In addition, we found high agreement in MTL activation across studies. Of the 11 studies that examined activity in the MTL, 9 found greater activity for R than F- based responses in the left and/or right hippocampus (Daselaar, Fleck, Dobbins, Madden, & Cabeza, 2006; Dolcos et al., 2005; Eldridge, Knowlton, Furmanski, Bookheimer, & Engel, 2000; Fenker et al., 2005; Montaldi et al., 2006; Sharot et al., 2004; Wheeler & Buckner, 2004; Woodruff et al., 2005; Yonelinas, Otten, Shaw, & Rugg, 2005) (see blue activations, Fig. 2). Of the remaining studies, Henson, Rugg, et al. (1999) found greater activity in the hippocampus for Remember as compared to New responses, but Henson, Shallice, and Dolan (1999), who used the PDP procedure, did not find greater hippocampal activity during exclusion, as compared to inclusion, responses. In addition, 6 of the 10 studies found greater parahippocampal activity for R-based, as compared to F-based, responses (Dolcos et al., 2005; Eldridge et al., 2000; Fenker et al., 2005; Sharot et al., 2004; Woodruff et al., 2005; Yonelinas et al., 2005) Familiarity Peak activations associated with F-based processing, for each study, are reported in Table 4 and are displayed in red in Figs. 1 and 2 (shown in red). In those studies that used familiarity-based subtraction contrasts (for example, Know Remember or Know New responses), as opposed to parametric analyses, the only brain region shown to have a high concordance of activation across studies was left BA 19 (50 percent agreement). Intermediate agreement was found for right BA 9 of the frontal lobe and left precuneus (BA 7) of the parietal lobe (both 33 percent). Within the MTL, only one of six studies found greater parahippocampal activity during F, as compared to N, responses (Eldridge et al., 2000). An analysis of the studies that used parametric contrasts found that in the frontal lobe, both BAs 45 and 6 of the left hemisphere showed high agreement in the tendency to increase activation with increasing confidence (50 percent each). In the inferior parietal lobe, left BA 39 was found to increase with increasing confidence (with 83 percent agreement across studies) (see Fig. 1, yellow points, panel D). Daselaar et al. (2006) also found increasing activation with increasing confidence in the retrosplenial cortex. We also examined regions that were found to increase in activation with decreasing confidence (see Figs. 1 and 2, orange activations). In the frontal lobe, right BAs 44 and 45 were active in 50 and 83 percent of the studies, respectively. Right anterior cingulate also showed relatively high agreement (67 percent). Within the temporal lobe, left insular (100 percent), and bilateral BA 36/37 fusiform (50 percent in each lobe) showed high levels of agreement in activation across studies. In addition, 100 percent of studies found that MTL activation increased with decreasing confidence, specifically in the hippocampus (Yonelinas et al., 2005), perirhinal cortex (Montaldi et al., 2006), and rhinal cortex (Daselaar et al., 2006). Fig. 3. Average percentage signal change in the right and left hippocampus (Hp) according to response type. Bars represent standard error of the mean Comparison of percent signal change in the hippocampus The above analysis showed that R-based responses, more so than F-based responses, were associated with hippocampal activation. In order to examine this finding further, we performed an ANOVA using data from all of the fmri studies that reported percent signal change for Recollection-, Familiarity-, and Newbased responses in the hippocampus, using percent signal change (reported in each study) as the dependent variable, and Response type (R, F, or New) as a within-subject (i.e., within-study) variable. The first ANOVA considered activations in the left, and the second ANOVA, activations in the right hippocampus. For the left hippocampus, five studies reported percent signal change: Daselaar et al. (2006), Eldridge et al. (2000), Fenker et al. (2005), Montaldi et al. (2006), and Yonelinas et al. (2005). We found a significant effect of Response type, F(2, 8) = 21.49, MSE =.06, p <.005, and simple effects analysis showed that while R responses had significantly greater percent signal change than F responses, F(1, 4) = 56.95, MSE =.07, p <.005, and New responses, F(1, 4) = 16.48, MSE =.20, p <.05, there was no difference between F and New responses, F(1, 4) = 0.69, p >.05 (see Fig. 3). Five studies also examined percent signal change in the right hippocampus: Eldridge et al. (2000), Fenker et al. (2005), Montaldi et al. (2006), Woodruff et al. (2005), and Yonelinas et al. (2005). We found similar results in the right hippocampus. There was a significant effect of Response type, F(2, 8) = 17.33, MSE =.03, p <.005, and simple effects analysis again showed that R responses had significantly greater percent signal change than F responses, F(1, 4) = 21.62, MSE =.09, p <.05, and New responses, F(1, 4) = , MSE =.01, p <.001. Unlike the left hemisphere, the right hippocampus also showed that F and New responses differed marginally, F(1, 4) = 4.87, MSE =.074, p >.10, with F responses showing lower percent signal change than New responses (see Fig. 3) Lesion data analyses Data for the lesion analyses are presented in Table 2. In order to investigate the role of the MTL in recollection and familiarity, we examined how lesion location (MTL or non-mtl) affected

9 Table 4 Activation peaks for familiarity-based responses classified according to Brodmann Area BA = Brodmann Area; bg = basal ganglia; cb = cerebellum; Exc = exclusion; ExcNon = Correctly Excluded Non-targets; Inc = inclusion; Ins = insula; K = know; mt = medial temporal cortex; N = new; R = remember; th = thalamus; x 2 = exponential increase; (4>)3>2>1=increasing confidence; 1>2>3(>4) = decreasing confidence; = an increase in activation in the left hemisphere; = an increase in activation in the right hemisphere; = an increase in activation with decreasing confidence in the left hemisphere; = an increase in activation with decreasing confidence in the right hemisphere; =an increase in the left hemisphere for which the coordinate lies between two BAs; = an increase in the right hemisphere for which the coordinate lies between two BAs; = an increase in the left hemisphere with increasing confidence for which the coordinate lied between two BAs; = an increase in the right hemisphere with decreasing confidence for which the coordinate lied between two BAs; superscript values represent how many times activation was found in that BA for that study. E.I. Skinner, M.A. Fernandes / Neuropsychologia 45 (2007)

10 2172 E.I. Skinner, M.A. Fernandes / Neuropsychologia 45 (2007) of responses that were given low confidence ratings (i.e., of value 1), and a greater percentage that were given moderate to high confidence ratings (i.e., of levels 3, 5, and 6). Thus, we found that the patient gave a greater percentage of highly confident new responses than controls. If recollection and familiarity can be differentiated solely on the basis of response confidence, this patient should have produced fewer, rather than a greater number of high confidence ratings. Thus, the finding is in the wrong direction to suggest that deficits in recollection are equivalent to deficits in high response confidence. Fig. 4. Average recollection and familiarity estimates for control participants and patients with lesions in either the medial temporal lobe (MTL) or non-mtl structures. Bars represent standard error of the mean. recollection and familiarity estimates compared to non-lesioned control participants. We conducted a 3 (Group: MTL lesion, non- MTL lesion, or control) 2 (Memory process: recollection or familiarity) ANOVA using recollection and familiarity estimates from control and patient populations as the dependent variable. Ten of the studies contained data from non-mtl lesioned patients, and 11 contained data from MTL lesioned patients, and in 3 studies of the later set, the authors used two different methods to estimate recollection and familiarity; thus, 10, 14, and 24 sets of R and F estimates were included in the non-mtl lesioned, MTL lesioned, and control groups, respectively. We found a significant effect of Group F(2, 45) = 13.61, MSE =.03, p <.001. Inspection of the means shows that both patient groups had lower memory process estimates than controls (see Fig. 4). The main effect of Memory process approached significance, F(1, 45) = 3.17, p =.08. Importantly, there was a significant Group Memory process interaction, F(2, 45) = 4.08, MSE =.02, p <.05. Tukey tests showed that both the non-mtl and MTL lesion groups had lower recollection estimates than controls, t(32) = 2.27 and t(36) = 6.91, respectively; only the MTL lesioned group showed significantly lower familiarity estimates than controls, t(36) = 2.52, p <.05, though the difference between the non-mtl and control group approached significance t(32) = 1.94, p =.062. Of note, the estimate of recollection was significantly lower in the MTL compared to non-mtl group, t(22) = 2.16, p <.05, though the estimate of familiarity-based responses did not differ, t(22) = 0.13, p >.05 (see Fig. 4). We then determined whether the percentage of old and new responses at each confidence level, for a patient shown to have recollective, but not familiarity, deficits, was within two units of standard deviation from that of the control group (see Aggleton et al., 2005 for a table of patient and control data). For responses deemed old, the percentage of responses, at each of the six confidence levels, was within two standard deviations of the average of the control participants at each level except for those at the moderate confidence level (i.e., 3 and 4); at those levels, the patient made a greater percentage of responses than did controls. Importantly, however, the patient showed a similar percentage of responses in the high confidence range as did controls. For responses deemed new, the patient had a lower percentage 4. Discussion Dual-process models of memory suggest there are two processes that can contribute to performance on a recognition test: recollection and familiarity. In the present study we sought to examine commonalities and differences across fmri and patient studies, in terms of the pattern of neural structures characterizing each process. In doing so we hope to answer the four key questions posed in Section 1 regarding these processes, and the relationship between them. Each is discussed in turn Do recollection and familiarity require different neural structures? Our analysis of the imaging and patient data relating to R- and F-based processing can be characterized by four patterns Both recollection- and familiarity-based responses are associated with right dorsolateral prefrontal cortex activity, but recollection involves additional prefrontal activity In the imaging analyses, both R and F responding were found to increase right dosolateral PFC (BA 9/46) activity. Right PFC activity has been found in several other studies of memory retrieval (Nyberg, Cabeza, & Tulving, 1996), and has been linked to post-retrieval processing (Rugg, Fletcher, Firth, Frackowiak, & Dolan, 1996), retrieval mode (Lepage, Ghaffar, Nyber, & Tulving, 2000; Tulving, Kapur, Craik, Moscovitch, & Houle, 1994), and monitoring and verification processes (Cabeza, Lacantore, & Anderson, 2003b; Henson, Shallice, et al., 1999). Henson, Rugg, et al. (1999) found that Know responses had greater right dorsolateral activity than Remember responses, and suggested that the increase was related to additional checking and verification behaviour (Henson, Rugg, Shallice, & Dolan, 2000). As an alternative explanation, Wheeler and Buckner (2004) suggested that the increase in right dorsolateral activity may arise as participants engage in a more exhaustive search for details to accompany their feelings of familiarity with an item. In our review, R and F were both found to activate right dorsolateral regions to some degree. This suggests that while activation in this region may be related to the search and monitoring of contextual information, this process is not related to familiarity per se. The imaging analysis also showed that R, but not F, was related to additional activity in bilateral anterior frontal (BA 10), and bilateral superior frontal (BAs 6 and 8) regions. Anterior

11 E.I. Skinner, M.A. Fernandes / Neuropsychologia 45 (2007) PFC activity has been related to the retrieval of source information (Cansino, Maquet, Dolan, & Rugg, 2002; Dobbins & Wagner, 2005; Kahn, Davachi, & Wagner, 2004; Rugg, Fletcher, Chua, & Dolan, 1999), and Konishi, Chikazoe, Jimura, Asari, and Miyashita (2005) found that the left anterior PFC was specifically involved in retrieval success. Because R responding also involves retrieval of the context in which an item was initially experienced, we would expect to see such overlap in the brain regions recruited during R responding and those observed during retrieval of source information. In addition, superior PFC activity has been related to the use of attentional processes (Cabeza et al., 2003; Nagahama et al., 1998) and top-down attentional control mechanisms (Hopfinger, Buonocore, & Mangun, 2000) during memory retrieval. The results suggest that the additional activity during R responses in the PFC may be related to the successful retrieval of contextual details, and may also reflect attentional shifts, such as a change from search to postretrieval monitoring of contextual details, that may occur during the retrieval of recollective-based information. Lesion data also suggest that additional sub-regions of the frontal lobe selectively support recollection: Levine et al. (1998) and Levine, Freedman, Dawson, Black, and Stuss (1999) showed that damage to the right inferior PFC results in lower recollection estimates relative to controls. Future work is needed to determine how sub-regions within the frontal lobes each contribute to different control processes used during R- and F-based responding. Given that most studies have found increased left PFC activity during source memory retrieval tasks, especially in BAs 47, 44, and 45 (Dobbins & Wagner, 2005; Dobbins, Foley, Schacter, & Wagner, 2002; Kahn et al., 2004; Lundstrom et al., 2003; Lundstrom, Ingvar, & Peterson, 2005; Rugg et al., 1999; Slotnick, Moo, Segal, & Hart, 2003; Takahashi, Ohki, & Miyashita, 2002), we were somewhat surprised that we did not find increased activity during R responding in these regions. However, recent studies that manipulated the effort required to retrieve an item from memory have suggested that BAs 47, 44, and 45 may be involved in controlled processing functions, or when the level of difficulty of the memory task increases (Achim & Lepage, 2005; Badre, Poldrack, Paré-Blagoev, Insler, & Wagner, 2005; Lepage, 2004; Moss et al., 2005; Velanova et al., 2003; Wheeler & Buckner, 2003). This suggested to us that perhaps these regions are not selectively involved in the recovery of source information per se, but instead are found during source, as compared to item, retrieval paradigms because participants need to engage in more effortful or controlled processing. Since the search for source information is encouraged regardless of the end response in studies that use R/K and ROC designs, this may be why we did not find selective activation in this region only during R-, but not F-based, responding. What is more, Duarte et al. (2005) found that although patients with left PFC lesions showed source memory deficits, they did not show significantly impaired recollective processing, measured by the R/K procedure. This suggests that when the level of control, or effort, needed to perform a memory task increases, additional left PFC-mediated processes may be required, but that retrieval of contextual details that can be used to determine source relies on similar regions as observed during R responding Both recollection and familiarity activate precuneus regions of the parietal lobe (BA 7), but recollection also activates the inferior parietal lobe (BAs 40 and 39) Based on our review, the left precuneus was found to be active during both R and F, whereas inferior parietal lobe activations were observed only for R (see Fig. 1 and Tables 1 and 2). Multiple studies have found that the parietal lobe shows greater activation for hit than correct rejection responses (Kahn et al., 2004; Konishi, Wheeler, Donaldson, & Buckner, 2000; Wheeler & Buckner, 2003), and activity in this regions has been shown to increase during successful memory retrieval, regardless of whether memory retrieval involves recall or recognition (Roland & Guylas, 1995), different motor responses or material (Shannon & Buckner, 2004), or manipulations of retrieval effort (Achim & Lepage, 2005; Sohn, Goode, Stenger, Carter, & Anderson, 2003). These findings suggest that the parietal lobe may be involved in memory storage (Roland & Guylas, 1995). Although both R and F were found to activate precuneus regions, only R showed high agreement across studies in activity of the inferior parietal lobe (see Tables 3 and 4), suggesting a specific role for R in this region (Wheeler & Buckner, 2004). Since the parietal lobe may be involved in the storage of memories, one possibility is that parietal lobe activity, in general, is related to the amount of information being extracted; more information about contextual details may be available during R than F responses, accounting for the selective increase. Such an hypothesis is supported by source memory studies which have found greater activity in left lateral parietal cortex during source, as compared to item, memory retrieval (Cansino et al., 2002). An alternative interpretation is that R responses reflect stronger memory traces: Shannon and Buckner (2004) found that activity in parietal cortex was greater following deep, compared to shallow, encoding, and suggested that the level of activity may depend on the strength of the memory trace. Lastly, posterior parietal regions show greater activation during true, as compared to false, recognition (Cabeza, Rao, Wanger, Mayer, & Schacter, 2001; Slotnick & Schacter, 2004), indicating that this region may play a selective role in the accurate recovery of information (Buckner, Raichle, Miezin, & Petersen, 1996). Such hypotheses will need to be tested in future research. Specifically, future studies will need to determine whether the additional parietal activation during R responses represents the amount of information extracted, the strength of the memory trace, or processes relating to retrieval success The recapitulation of sensory areas occur only during recollection Memory retrieval is believed to be accompanied by similar sensory-specific cortical activation as that produced during the initial encoding of an item or event (Norman & O Reilly, 2003; Rubin & Greenberg, 1998; Woodruff et al., 2005). Studies in which participants associate words with pictures, sounds, or faces during encoding and are subsequently asked to retrieve only the word stimulus, have found that secondary visual, secondary auditory, and face processing regions of the brain are activated during word retrieval, depending on which stimulus was associated with the word during encoding (Khander, Burke,

12 2174 E.I. Skinner, M.A. Fernandes / Neuropsychologia 45 (2007) Bien, Ranganath, & Rösler, 2005; Nyberg, Habib, McIntosh, & Tulving, 2000; Vaidya, Zhao, Desmond, & Gabrieli, 2002; Wheeler, Peterson, & Buckner, 2000). Only three of the studies in our review can be compared to these studies. First, Wheeler and Buckner (2004) paired word stimuli with pictures during study, and tested whether a left fusiform region (BA 20) that had previously been found to reactivate during the retrieval of associated word stimuli (Köhler, Moscovitch, Winocur, Houle, & McIntosh, 1998; Wheeler & Buckner, 2003), would be activated during Remember, Know, or both response types. They found content-specific activation only for Remember responses (see Table 2). Second, in the Fenker et al. (2005) study, word stimuli were paired with faces during encoding. Similarly, they found activation in fusiform regions, though in different BAs (BAs 19 and 36/37), and only during Remember responses (see Table 2). Lastly, Woodruff et al. (2005) had participants study either words or pictures, and at test participants were shown either studied words, words of studied pictures, or new words. They found that recollected test words that were studied as pictures elicited greater activity in an anterior fusiform region related to picture processing, and conversely, that recollected words studied as words elicited greater activity in a lateral fusiform area related to visual word form processing. Wheeler and Buckner (2004) and Woodruff et al. (2005) suggested that it is the re-activation of these content-specific regions that determines whether a memory will be consciously recollected or simply familiar. Thus, only Remember responses, or memories that are rich in detail, should activate these sensory-specific cortical areas; this hypothesis was supported in the studies we reviewed. Future neuroimaging studies could examine whether sensory-specific activation occurs reliably, only for R, and not F-based, responses, across multiple sensory domains and experimental paradigms Recollection and familiarity are related to activation in different regions of the MTL Much interest has revolved around the role of the MTL in recollection and familiarity (Aggleton & Brown, 1999; Squrie et al., 2004). Looking first at the imaging data, we found that both left and right hippocampal activity increased to a greater degree during R- than F-based responses (see Figs. 2 and 3). In addition, we found that in 6 of the 11 studies to examine MTL activation, R was associated with greater parahippocampal activation than F, whereas only one study (Eldridge et al., 2000) found greater activation in the parahippocampus for F, as compared to New, responses. These findings indicate that both the hippocampus and parahippocampus are more involved during recollective-, than familiarity-based processing. However, an examination of the parametric contrasts suggests there may be a selective change in MTL activity during F-based retrieval. All studies using parametric analysis found that activation in MTL regions, specifically the hippocampus (Yonelinas et al., 2005), perirhinal cortex (Montaldi et al., 2005), and rhinal cortex (Daselaar et al., 2006) decreased with increasing response confidence. We also found that there was a decrease in right hippocampus activity during F-based responses compared to New responses (see Fig. 3). Together, these results suggest that familiarity-based responding is associated with a decrease in activity in some parts of the MTL. These findings are consistent with a recent review of four imaging studies, in which Henson, Cansino, Herron, Robb, and Rugg (2003) found that old items elicited less activity than new items within a region of the perirhinal cortex, and suggested that this deactivation may represent a familiarity signal in the MTL. An examination of the lesion data may provide key insights into the role of the MTL in mediating R and F memory processes. Although the above analysis suggests that the MTL are involved in both familiarity and recollection, imaging data is necessarily correlational. By examining how R and F are affected by lesions in this region, we are able to make more causal inferences about the contribution of the MTL to R and F responding. Our review of lesion data indicates that both the non-mtl and MTL lesioned groups had lower recollection estimates than controls, whereas only the MTL lesioned group had lower familiarity estimates than controls, although this effect approached significance for the non-mtl group. These results suggest that the MTL plays a specific role in development of a familiarity signal. Importantly, however, the estimate of recollection was significantly lower in the MTL compared to non-mtl patient group, though the estimate of familiarity-based responses did not differ across patient groups, suggesting that the MTL also plays a specific role in recollective processes. One must be careful when using lesion data to investigate the neural structures that support recollection and familiarity at retrieval, however, since deficits in these processes in patients, may be due to impaired encoding of source and item information, rather than an inability to recover that information at retrieval. However, taken together, the lesion data supplement the imaging data in that they suggest that both R- and F-based responses rely on the MTL, although recollection may have a greater reliance on this region than familiarity. These conclusions are supported by a recent study by Gilboa et al. (2006). They examined memory, in two patients with MTL damage, for events acquired before the brain lesion, eliminating the encoding confound. They compared memory for episodic and semantic details of past personal events in patient A.D., who has bilateral fornix and septal damage (effectively severing the connection between the hippocampus to the diencephalon and other cortical regions), to patient K.C., who has extensive bilateral MTL damage. A.D. showed normal memory for semantic details of past events, which was attributed to an intact familiarity process. His memory for episodic details, however, was severely impaired, indicating a disruption in the recollective process required to re-experience the unique details of episodic events. In contrast, K.C. had problems recollecting both semantic and episodic details of past events, signifying a deficit in both familiarity and recollection processes. The authors suggested that the hippocampus proper is required to retrieve the associative elements of episodic memories during recollection, whereas extra-hippocampal structures in the MTL are used to support familiarity processes. We now turn our focus to what neuroimaging techniques may be able to tell us about dual-process models of memory. We first ask whether it is necessary to assume that there are in fact two different memory processes supporting recognition memory or if

13 the experimental findings can be accounted for by differences in response confidence. We then use these neuroimaging findings to explore the nature of the relationship between the two memory processes Are recollection and familiarity-based recognition responses confounded by confidence levels guiding recognition judgments? E.I. Skinner, M.A. Fernandes / Neuropsychologia 45 (2007) To answer this question we can compare the brain regions with high percentage agreement for R responses to those with a high percentage agreement for increasing response confidence. Only BA 39 of the left parietal lobe was identified in both analyses. Thus, we can conclude that brain regions sub-serving recollection are not simply those mediating highly confident memory decisions. Importantly, within the frontal lobes there was no overlap in those Brodmann areas with high agreement during R responses and those active for increasing response confidence. It had been suggested that increased activity in left PFC during R may be due to differences in confidence levels guiding the two response types (Henson, Rugg, et al., 1999). As shown in Fig. 1, panel C, however, the regions of the left PFC activated during increasing confidence for familiaritybased responses differ from those for recollection. This suggests that the increased PFC activation during R responses is uniquely associated with recollection, rather than confidence level, in responses. In addition, we examined whether a patient shown to have recollective deficits would produce a similar distribution of responses across levels of response confidence as controls. If recollection simply reflects high confidence memory responses, the patient should show fewer high confidence responses than controls. Instead we found that the patient had a similar distribution of high response confidence for items deemed to be old, and a greater number of high confidence responses than controls for items deemed to be new. Thus, imaging and lesion data support dual-process models of recognition memory which suggest recollection and familiarity cannot be explained solely in terms of differences in response confidence. In the next section we discuss the contribution of the reviewed studies to current models of recognition memory processes What is the relationship between recollective- and familiarity-based recognition judgments? We review three models that describe the possible relationship between recollective- and familiarity-based memory processes (see Fig. 5 for visual depiction of each). The first is that of exclusivity. Here an item may be recollected or it may be familiar, but no one item can be both recollected and familiar at the same time (see Jones, 1987; Nelson, Schreiber, & McEnvoy, 1992). This model suggests that recollection and familiarity have different neural origins, and suggests no overlap in activation between R and F responses. The second relationship is that of redundancy, which states that all items that are successfully recognized are familiar, and that a subset of these can also be recollected (Joordens & Merikle, 1993). We interpret this Fig. 5. Visual depiction of three models of the relationship between recollection and familiarity. R = recollection; F = familiarity. model as predicting that brain regions active during F responses will completely overlap with those active during R responses (i.e., there should be no region showing unique F activation during F R contrasts), and that R responses will produce neural activation additional to that of F responses. The final relationship is that of independence (Jacoby, Toth, & Yonelinas, 1993). Here, an item may be either recollected or familiar, and only a subset are both recollected and familiar at the same time. This model suggests to us several possible patterns of brain activation: (a) there will be distinct regions of activation for R responses, (b) there will be distinct regions of activation for F responses, and (c) there can be overlap in brain regions showing activation during R and F responses. With respect to the models presented above, the data do not support an exclusivity relationship. Several studies have shown similar areas of activation during R and F responses, which discounts the hypothesis that recollection and familiarity have different origins, and neural signatures. We also found that many studies showed numerous brain regions were unique to R, and some unique to F (Eldridge et al., 2000; Henson, Rugg, et al., 1999; Montaldi et al., 2006; Wheeler & Buckner, 2004). Specifically, the studies reviewed have found additional activation for F, as compared to R responses, in multiple cortical regions, including medial temporal, temporal, cingulate, and frontal regions of the brain. While the redundancy model predicts that R and F responses will activate common brain regions, F responses should not produce activation separate from R responses. Thus, we believe that the current set of neuroimaging studies is more in line with an independence model. Although the above interpretation was intended to separate the models using neuroimaging data, we acknowledge that these cognitive models were developed to depict processes involved solely in the memory representation, whereas neuroimaging data show brain regions involved in both memory representation and the processes involved in controlling the search, selection, monitoring, and verification of the memory. Consequently, even if we are able to show that R and F responses involve both shared and unique areas of activation, we cannot definitively distinguish between redundant and independent relationships, since any unique activation may result from differences in control