Neuropsychologia 50 (2012) 3588–3599

Contents lists available at SciVerse ScienceDirect

Neuropsychologia

journal homepage: www.elsevier.com/locate/neuropsychologia

The face-sensitive N170 component in developmental prosopagnosia

John Towler a, Angela Gosling a, Bradley Duchaine b, Martin Eimer a,n a Department of Psychological Sciences, Birkbeck College, University of London, UK b Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA article info abstract

Article history: Individuals with developmental prosopagnosia (DP) show severe face recognition deficits in the Received 18 June 2012 absence of any history of neurological damage. To examine the time-course of face processing in DP, Received in revised form we measured the face-sensitive N170 component of the event-related brain potential (ERP) in a group 17 September 2012 of 16 participants with DP and 16 age-matched control participants. Reliable enhancements of N170 Accepted 14 October 2012 amplitudes in response to upright faces relative to houses were found for the DP group. This effect was Available online 22 October 2012 equivalent in size to the effect observed for controls, demonstrating normal face-sensitivity of the N170 Keywords: component in DP. Face inversion enhanced N170 amplitudes in the control group, but not for DPs, Face processing suggesting that many DPs do not differentiate between upright and inverted faces in the typical Face recognition manner. These N170 face inversion effects were present for younger but not older controls, while they Face perception were absent for both younger and older DPs. Results suggest that the early face-sensitivity of visual Prosopagnosia Event-related brain potentials processing is preserved in most individuals with DP, but that the face processing system in many DPs is Visual cognition not selectively tuned to the canonical upright orientation of faces. & 2012 Elsevier Ltd. All rights reserved.

1. Introduction impairments of early perceptual stages of face processing (apper- ceptive prosopagnosia; De Renzi, Faglioni, Grossi, & Nichelli, 1991), People with prosopagnosia are unable to recognize and iden- and face-selective deficits at later post-perceptual stages, which tify the faces of familiar individuals, despite normal low-level could include impairments of long-term face memory, or discon- vision and intellect (Bodamer, 1947). Until recently, prosopagno- nections of face perception and face memory (associative proso- sia was thought to result solely from acquired lesions to face- pagnosia; De Renzi et al., 1991). An analogous distinction might sensitive regions in occipito-temporal visual cortex, such as the also apply to individuals with DP. middle and posterior fusiform gyri (e.g., Barton, 2008). However, To identify which stages in the face processing hierarchy are the existence of a different form of prosopagnosia that occurs impaired in prosopagnosia, event-related brain potential (ERP) without history of neurological damage has now been established measures are particularly useful tools. ERPs provide online (e.g., Behrmann & Avidan, 2005; Duchaine & Nakayama, 2006b). measures of neural activity and thus are able to track neural In contrast to acquired prosopagnosia (AP), individuals with correlates of face perception and face recognition on a millisecond- developmental prosopagnosia (DP) typically show severe impair- by-millisecond basis. The earliest ERP markers of face recognition ments of face recognition that emerge in early childhood and are have been found at post-stimulus latencies of 200 ms and beyond assumed to result from a failure to develop normally functioning (e.g., Schweinberger, Pfutze,¨ and Sommer (1995), Begleiter, Porjesz, face processing mechanisms (see Duchaine (2011), for a review). and Wang (1995), Bentin and Deouell (2000), Eimer (2000a), The perception and recognition of faces is a complex achieve- Schweinberger, Pickering, Jentzsch, Burton, and Kaufmann ment that is based on a number of functionally and anatomically (2002)). For example, an occipito-temporal N250 component is distinct processing stages (Bruce & Young, 1986; Haxby & Gobbini, triggered when famous faces are explicitly recognized, but not 2011). Problems at any of these stages could be responsible for the when these faces merely seem familiar (Gosling & Eimer, 2011). face recognition deficits in individuals with AP or DP. The question The N250 has been linked to an early stage of face recognition which face processing mechanisms are impaired in prosopagnosia where incoming visual–perceptual information about a seen face is has not yet been answered conclusively. In AP, two general sources matched with stored representations of familiar faces in visual of face recognition deficits have been distinguished—selective memory. We have recently employed this N250 component to trace the locus of face recognition deficits in DP (Eimer, Gosling, & Duchaine, 2012). Six of the twelve DPs tested showed an N250 n Corresponding author. Tel.: þ44 20 7631 6538; fax: þ44 20 7631 6312. component in response to famous faces on trials where they did E-mail address: [email protected] (M. Eimer). not explicitly recognize these faces. This covert recognition effect

0028-3932/$ - see front matter & 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neuropsychologia.2012.10.017 J. Towler et al. / Neuropsychologia 50 (2012) 3588–3599 3589 indicates that visual memory for famous faces was intact in these the structural and functional integrity of posterior face processing DPs, and suggests that their face recognition deficits may be the areas, in particular the middle fusiform and inferior occipital result of disconnections between a visual store of familiar faces and face areas. semantic memory. Interestingly, the other six DPs tested in this The question whether the face-sensitive N170 component is study did not show such covert recognition effects for the N250 present or absent in individuals with developmental prosopagno- component, which indicates that the locus of face processing sia has been investigated in several studies, but no clear pattern deficits differs across individuals with DP. has emerged so far. There is some evidence that the N170 can be While the N250 component is linked to visual face memory strongly attenuated or entirely abolished in DP. Bentin, Deouell, and face recognition, the well-known face-sensitive N170 com- and Soroker (1999) tested one participant with DP and found that ponent reflects an earlier stage of face processing. The N170 is an N170 amplitude differences in response to faces versus non-face enlarged negativity in response to faces as compared to non-face objects were reduced relative to 12 control participants. Along stimuli that is elicited between 150 and 200 ms after stimulus similar lines, Kress and Daum (2003) found no statistically onset over lateral occipito-temporal areas, (e.g., Bentin, Allison, reliable N170 amplitude differences between faces and houses Puce, Perez, and McCarthy (1996), Eimer, Kiss, and Nicholas for two participants with DP, whereas such differences were (2010), Eimer (2011), Rossion and Jacques (2011)). N170 compo- consistently present in eight control subjects. Bentin, De Gutis, nents are typically accompanied by an enhanced positivity to D’Esposito, and Robertson (2007) reported the absence of a faces at vertex electrode Cz (Botzel¨ & Grusser,¨ 1989; Jeffreys, differential N170 response to faces as compared to non-face 1989). Because the vertex positive potential (VPP) and the N170 control objects (watches) in one DP, whereas this effect was component are usually closely associated, they are assumed to reliably present in a group of 24 control subjects. However, reflect the same underlying face-sensitive brain processes (e.g., results from other studies demonstrate that the N170 is not Joyce and Rossion (2005)). Importantly, the N170 component is always abolished in DP. Harris, Duchaine, and Nakayama (2005) not affected by emotional facial expression (Eimer & Holmes, measured MEPs or ERPs in response to faces and houses in a 2002, 2007) or by face familiarity (e.g., Bentin and Deouell (2000), group of DPs. Of the five DPs tested with MEG, three showed a Eimer (2000a)). This insensitivity to familiarity and emotional face-sensitive M170 component, while two did not. Two DPs were expression suggests that the N170 is linked to the perceptual tested with EEG, and one of them showed a face-sensitive N170. structural encoding of facial features and configurations that Righart and De Gelder (2007) observed enhanced N170 ampli- occurs independently and in parallel with the analysis of emo- tudes for faces relative to non-face control objects (shoes) for two tional expression, and precedes the recognition and identification DPs, whereas no such effect was present for two other DPs. of individual faces (Bruce & Young, 1986). Minnebusch, Suchan, Ramon, and Daum (2007) tested four DPs Because the N170 component is a well-studied electrophysio- and found reliable N170 amplitude differences between faces and logical marker of face perception, finding out whether this houses for three of them. In a recent MEG study, Rivolta, Palermo, component is preserved or abolished in AP or DP is important Schmalzl, and Williams (2012) reported enhanced M170 compo- for our understanding of the nature of prosopagnosia. Given the nents to images of faces versus places for a group of six DPs, and firm links between the N170 and the perceptual structural this enhancement was similar in magnitude to the effect observed encoding of faces, its absence in individuals with prosopagnosia for a group of 11 control participants. Finally, in an experiment would point to an early ‘‘apperceptive’’ locus of their face designed to study the impact of perceptual training on face processing deficits. In contrast, if the N170 component was recognition (De Gutis, Bentin, Robertson, & D’Esposito, 2007), an uniformly preserved in prosopagnosia, this would provide strong individual with DP who had no differential N170 response to evidence of a post-perceptual ‘‘associative’’ locus of face recogni- faces versus watches prior to training showed an enhanced N170 tion impairments. to faces after training. Overall, the main conclusion to be drawn The existing evidence with respect to the properties of the from existing studies of the N170 component in DP is that results N170 component in prosopagnosia is inconclusive. Only very few are highly variable across individuals. One main aim of this study studies have measured ERP markers of face processing in brain- was to investigate the presence or absence of the N170 across a damaged patients with AP. One study found no differential ERP much larger sample of sixteen participants with DP. modulations to faces versus houses in the N170 time range for In addition to its generic face-sensitivity, the N170 component patient PHD who has diffuse cortical damage including a focal left is also highly sensitive to face inversion. Numerous behavioural temporo-parietal lesion (Eimer & McCarthy, 1999), suggesting studies have indicated that upright faces are processed in a more that AP can be due to a disruption of early face-selective perceptual configural or holistic manner than inverted faces or objects (e.g., processing stages. Longer-latency ERP markers of identity-sensitive Tanaka and Sengco (1997), Young, Hellawell, and Hay (1987), Van face processing were also absent for the same patient (Eimer, Belle, de Graef, Verfaillie, Rossion, and Lefevre (2010)), and that 2000a). This was expected, as severe impairments in structural stimulus inversion has much stronger effects on the recognition encoding should have knock-on effects on later face recognition of faces than on object recognition (Yin, 1969). These observations processes. In contrast, another single-case study found a preserved suggest that inversion-induced impairments of face recognition face-selective N170 in prosopagnosic patient FD who had extensive may be linked to disruptions of configural face processing, which lesions to ventral occipito-temporal cortex (Bobes et al., 2004). may be tailored for specifically upright faces. In line with this More recently, Dalrymple et al. (2011) recorded ERPs from five view, a recent study that employed single-unit recording in the patients with AP, and found that the presence of a face-sensitive macaque middle face patch provided strong evidence that faces N170 depended upon the integrity of at least two of the three core are represented by an upright template, regardless of the orienta- face-sensitive regions (fusiform and occipital face areas, posterior tion of an observed face (Freiwald, Tsao, & Livingstone, 2009). superior temporal sulcus). Alonso-Prieto, Caharel, Henson, and Many ERP experiments have demonstrated that the N170 in Rossion (2011) reported a face-selective N170 component over response to inverted faces is enhanced and delayed relative to the the right but not left hemisphere for prosopagnosic patient PS, N170 that is triggered by upright faces (e.g., Bentin et al., 1996; whose lesions include the left fusiform and right occipital face Eimer, 2000b; Rossion et al., 2000; Itier, Alain, Sedore, & areas. In summary, these studies demonstrate that the face- McIntosh, 2007). Two types of explanation have been proposed sensitive N170 component is often absent in patients with AP, for the presence of inversion-induced enhancements of N170 and that the presence of this component appears to be linked to amplitudes (Sadeh & Yovel, 2010). Quantitative accounts assume 3590 J. Towler et al. / Neuropsychologia 50 (2012) 3588–3599 that upright and inverted faces activate the same face-specific Giraud (2006)).Forexample,onlythreeof15DPstestedinarecent mechanisms, and that the enhancement of the N170 component fMRI study did not show face-selectivity in the fusiform gyrus (Furl to inverted faces reflects the increased effort required to process et al., 2011). Because all or nearly all individuals with normal face these faces (Rossion et al., 1999; Marzi & Viggiano, 2007), possibly processing exhibit a face-sensitive N170 and an N170 face inversion due to inversion-induced disruptions of configural processing effect, a failure to exhibit either of these effects may be indicative of (e.g., Sagiv & Bentin, 2001; see also Eimer, Gosling, Nicholas, & impaired early face processing in individual DPs. The observation Kiss, 2011, for further evidence for links between the N170 and that N170 face inversion effects appear to be age-dependent even in configural face processing from rapid neural adaptation). Alter- individuals without face recognition impairments (Gao et al., 2009) native qualitative accounts explain inversion-induced N170 further underlines the importance of assessing ERP markers of face enhancements by proposing that inverted faces activate addi- processing in DP not just at the group level, but also for each tional neural populations (such as neurons sensitive to non-face individual participant. objects) which are not activated by upright faces (e.g., Rossion We measured N170 components to upright and inverted faces et al., 2000). Consistent with this possibility, object-selective and to non-face stimuli for 16 individuals with DP. All of them brain areas respond more strongly to inverted faces than upright reported severe and consistent difficulties in recognizing familiar faces (Haxby et al., 1999; Yovel & Kanwisher, 2005), and TMS to faces since childhood. These reports were verified with standar- the object-sensitive lateral occipital area disrupts the processing dized tests of face processing (see Table 1). Stimuli and proce- of inverted, but not upright faces (Pitcher, Duchaine, Walsh, dures were identical to those used in a previous study (Eimer & Yovel, and Kanwisher 2011). Along similar lines, it has also been Holmes, 2002). Photographic images from five categories (upright suggested that inverted but not upright faces may selectively neutral faces, inverted neutral faces, upright fearful faces, activate eye-specific neurons (Itier et al., 2007). Quantitative and inverted fearful faces, or upright houses) were sequentially qualitative accounts of N170 face inversion effects are not presented at fixation. Participants had to detect and respond to mutually exclusive. For example, Rosburg et al. (2010) measured the immediate repetition of an image that was shown on the ERPs to upright and inverted faces both from the scalp and preceding trial (one-back task). For the participants with intact intracranially, and found inversion-induced activity modulations face processing abilities tested previously (Eimer & Holmes, during the N170 time range in both face-selective and house- 2002), upright faces triggered enhanced N170 amplitudes relative selective cortical areas, consistent with a hybrid account of N170 to upright houses, in line with the face-sensitivity of this compo- face inversion effects. nent. In addition, the N170 was enhanced and delayed for While reliable face inversion effects on N170 amplitudes have inverted as compared to upright faces, thus confirming the been repeatedly observed in studies with young adult partici- presence of typical N170 face inversion effects. Emotional expres- pants, there is now evidence that this effect may not be found in sion had no effect on N170 amplitude or latency, in line with the older individuals. Gao et al. (2009) reported that inversion- assumption that the face-sensitive brain processes that give rise induced N170 amplitude enhancements which were reliably to this component are not involved in the analysis of emotional observed for a group of young participants (aged 23–35 years) facial expression. To confirm these findings, and contrast them were absent for a group of older participants whose age ranged with the effects observed for the group of DPs, a new group of between 61 and 85 years. This dissociation suggests that there sixteen age-matched control participants with intact face proces- may be important changes in the operation of perceptual face sing capabilities was included in the present study. processing stages in older individuals (see also Daniel & Bentin, Two main analyses were conducted to investigate the presence 2012, for similar results). Given the prominence of N170 face and the properties of the face-sensitive N170 component in inversion effects in current discussions about face perception and individuals with DP. The first set of analyses compared ERPs to its neural basis, it is clearly important to find out whether such upright neutral faces and non-face control stimuli (upright effects are also present in individuals with DP. If they are, this would indicate that DPs differentiate between upright and inverted faces in the typical manner during the structural encod- Table 1 Details of the 16 DPs who participated in this experiment and their performance ing of faces. In contrast, atypical N170 face inversion effects on different behavioural tests of face processing. For the Famous Face Test (FFT), would point to differences between DPs and control participants the percentage of correctly recognized faces is listed (recognition rate for at early stages of face perception. To date, few studies have unimpaired participants is above 90%; Garrido et al., 2008). For the Cambridge investigated N170 face inversion effects in DP, and results have Face Memory Test (CMFT), the Cambridge Face Perception Test (CFPT) with upright and inverted faces (upr/inv), and for the Old–New Test (ONT), z-scores been inconclusive. In an MEG study, Dobel, Putsche, Zwitserlood, of each individual’s performance are listed (see text for details). and Junghofer¨ (2008) found normal effects of face inversion on M170 amplitude across a group of seven DPs. In contrast, De Participant Age Sex FFT CFMT CFPTupr CFPTinv ONT Gelder and Stekelenburg (2005) tested a single participant with DP and found no inversion-induced N170 amplitude enhance- (%) zz z z ment. Righart and De Gelder (2007) tested four participants with MC 41 M 24.6 1.38 1.54 1.62 2.46 DP and found that typical N170 face inversion effects were absent EW 32 F 13.3 2.64 .92 .2 3.43 for three of them. The second main aim of the present study was CM 29 M 20.7 4.29 3.1 2.89 14.34 to systematically evaluate the sensitivity of the N170 component NE 31 F 33.3 2.77 1.06 1.62 4.17 JA 46 F 43.6 2.64 .92 .49 3.35 to face inversion in DP, for a large group of sixteen participants. AH 48 F 60.0 1.76 1.06 .63 2.04 In addition to demonstrating the presence or absence of a face- AM 28 F 46.4 2.64 1.74 .49 2.88 sensitive N170 component or of N170 face inversion effects at the SW 28 F 22.0 2.64 1.74 1.05 2.95 group level, these ERP modulations may also be effective neural KS 29 F 15.1 2.9 .92 1.05 9.03 markers of prosopagnosia in individual DPs. Even though group SC 22 F 44.7 2.64 .51 .08 4.15 JL 67 F 40.0 1.76 2.29 .49 6.27 fMRI studies have found weaker face-selectivity and smaller face- SN 54 F 52.5 2.26 2.15 .36 .42 selective areas in DP (Furl,Garrido,Dolan,Driver,&Duchaine,2011), MZ 48 F 53.6 2.52 1.33 .22 6.47 individual DPs often fall within the normal range on these measures CP 39 F 34.7 2.64 .92 1.21 1.11 (Behrmann, Avidan, Marotta, & Kimchi, 2005; Furl et al., 2011; RL 49 M 19.6 3.65 1.88 .77 5.87 MP 49 M 36.8 2.9 1.33 .64 4.42 but see also Bentin et al. (2007), Von Kriegstein, Kleinschmidt, & J. Towler et al. / Neuropsychologia 50 (2012) 3588–3599 3591 houses), in order to test the generic face-sensitivity of the N170 in years), and the age range of the eight older controls was 38–65 years (mean age: DP. At the group level, the question was whether upright faces 50.2 years). would trigger reliably enhanced N170 amplitudes relative to houses across all 16 DPs tested, and whether any such effect 2.2. Stimuli and procedure would be similar in size or smaller than the effect observed for Participants sat in a dimly lit sound attenuated cabin. Photographs of faces or the group of 16 age-matched control participants. At the level of houses were presented on a CRT monitor at a viewing distance of 100 cm, using individual DPs, the presence or absence of a face-sensitive N170 E-Prime software (Psychology Software Tools, Pittsburgh, PA). Stimuli were iden- component was assessed with a non-parametric bootstrap pro- tical to those employed in a previous study (Eimer & Holmes, 2002). They included cedure (Di Nocera & Ferlazzo, 2000). In a second set of analyses, faces of 10 different individuals and 10 different houses. Faces were either fearful or inversion-induced effects on N170 amplitudes and latencies were neutral, and were presented either upright or upside-down, resulting in a total of 40 different face images. Houses were always presented upright. All stimuli were investigated, both at the group level and at the level of individual presented at fixation, with eye gaze straight ahead, against a grey background DPs. At the group level, the question was whether typical (17.6 cd/m2). They subtended a visual angle of 5.51 7.51, and their average inversion-induced N170 modulations (enhanced and/or delayed luminance was 21.9 cd/m2. N170 components for inverted relative to upright faces) would be The experiment consisted of four experimental blocks with 115 trials per block. Participants performed a one-back task where they had to respond with a observed across all DPs tested, and whether these face inversion right-hand button press to the immediate repetition of an image that was effects would be equal or reliably different from the effects presented on the preceding trial. Each block included 15 target trials where such observed for participants with normal face processing abilities. immediate repetitions of an identical image occurred. In the remaining 100 trials Again, bootstrap procedures were used to establish the presence per block, non-repeated upright or inverted neutral or fearful faces, or upright of face inversion effects on N170 amplitudes and latencies for houses were presented in random order and with equal probability. Stimuli were presented for 300 ms, and were separated by an intertrial interval of 1000 ms. individual DPs. To assess the possible impact of participants’ age on the N170 and its sensitivity to face inversion in DPs and 2.3. EEG recording and data analysis controls, additional analyses were conducted for sub-groups of younger and older participants. EEG was DC-recorded with a BrainAmps DC amplifier (upper cut-off frequency 40 Hz, 500 Hz sampling rate) and Ag-AgCl electrodes mounted on an elastic cap from 23 scalp sites (Fpz, F7, F3, Fz, F4, F8, FC5, FC6, T7, C3, Cz, C4, T8, CP5, CP6, P7, 2. Methods P3, Pz, P4, P8, PO7, PO8, and Oz, according to the extended international 10–20 system). Horizontal electrooculogram (HEOG) was recorded bipolarly from the outer canthi of both eyes. During online recording, EEG was referenced to an 2.1. Participants electrode placed on the left earlobe, and was re-referenced off-line to the average of the left and right earlobe. Impedances of all electrodes were kept below 5 kO. Sixteen participants with DP (12 females) were tested. Their age ranged No off-line filters were applied. EEG was epoched off-line from 100 ms before to between 22 and 67 years (mean age: 40 years). All reported severe difficulties 300 ms after stimulus onset. Epochs with activity exceeding 730 mV in the HEOG with face recognition since childhood. They were recruited after contacting us on channel (reflecting horizontal eye movements) or 760 mV at Fpz (indicating eye our research website /http://www.faceblind.orgS. To assess and verify their blinks or vertical eye movements) were excluded from analysis, as were epochs reported face recognition problems, behavioural tests were conducted in two with voltages exceeding 780 mV at any other electrode. sessions on separate days, prior to the EEG recording session. Impairments in the Following artefact rejection, averages were computed for non-target trials (i.e., recognition of famous faces were measured in the Famous Face Test (FFT) for trials where no immediate stimulus repetition occurred and no manual response images of 60 celebrities from entertainment, politics, or sports (see Duchaine & was recorded), separately for upright neutral faces, inverted neutral faces, upright Nakayama (2005), for details). Table 1 shows recognition percentage for famous fearful faces, inverted fearful faces, and upright houses. All ERPs were computed faces in the FFT, separately for each of the sixteen DPs tested. As expected, DPs relative to a 100 ms pre-stimulus baseline. N170 mean amplitudes were com- generally performed poorly in this test, with an average face recognition rate of puted at lateral posterior electrodes P7 and P8 for the 150–190 ms interval after 33.5% (ranging between 13.3% and 60% for individual DPs). For participants with stimulus onset. N170 latencies were quantified as the latency of the most negative unimpaired face recognition abilities, the average recognition rate is 84.6% peak voltage measured during the 130–190 ms post-stimulus interval. (SD¼11.2%) for the same set of famous faces (Garrido, Duchaine, & Nakayama, To investigate the face-sensitivity of the N170 component in the DP group and 2008). To rule out deficits in basic visual functioning as cause of their face compare it to the control group, N170 mean amplitudes in response to upright recognition deficits, the DPs also completed the low-level visual–perceptual tests neutral faces and upright houses were compared. To measure and contrast N170 face of the Birmingham Object Recognition Battery (Riddoch & Humphreys, 1993). Test inversion effects in both groups N170 mean amplitudes and peak latencies were performance was within the normal range for all DPs tested. compared for upright and inverted faces. Preliminary analyses demonstrated that Table 1 shows z-scores of the performance of all 16 DPs in other behavioural N170 amplitudes and face inversion effects on N170 amplitude and latency were face processing tests. In the Cambridge Face Memory Test (CFMT), faces of six unaffected by the emotional expression of faces. This was the case for the DP group target individuals shown in different views are memorized, and then have to be and for participants without DP, confirming previous observations (Eimer & Holmes, distinguished from two simultaneously presented distractor faces (see Duchaine 2002). Therefore, analyses of N170 face inversion effects were based on ERPs to and Nakayama (2006a), for a full description). In the Old–New Face Recognition upright and inverted faces that were averaged across neutral and fearful faces. To test (ONT; Duchaine & Nakayama, 2005), ten target faces (young women photo- identify differences in the face-sensitivity of the N170 and in inversion-induced graphed under similar conditions and from the same angle) are memorized. In the modulations of N170 amplitudes or latencies between participants with and without test phase, target faces and 30 new faces are presented in random order, and an DP, further analyses were conducted across DPs and control participants, with group old/new discrimination is required for each face. In the Cambridge Face Perception as between-subject factor. In additional analyses of the impact of participants’ age, Test (CFPT; Duchaine, Yovel, & Nakayama, 2007), one target face in three-quarter the between-subject factor age (younger versus older) was also included. view is shown above six frontal-view morphed test faces that contain a different We also assessed the presence of statistically reliable N170 effects at the level proportion of the target face and have to be sorted according to their similarity to of individual DPs. For that purpose, a non-parametric bootstrap procedure (Efron the target face. Faces are presented either upright or inverted (shown separately in & Tibshirani, 1993; Di Nocera & Ferlazzo, 2000) was employed. This method Table 1). As can be seen from the z-scores in Table 1, all DPs were impaired in the establishes the reliability of ERP amplitude or peak latency differences between CFMT, and all except one in the ONT. There was also some evidence for face two experimental conditions by resampling two sets of trials that are drawn perception deficits in the CFPT, and these appeared more pronounced for upright randomly (with replacement) from the combined dataset, and then computing faces than for inverted faces. amplitude or latency differences between the two resulting ERPs for a pre-defined Sixteen participants without DP (seven females) were also tested with EEG, time window and electrode. This procedure is repeated a large number of times using identical procedures to those used for the DP group. Each control participant (10,000 iterations in the current study). The resulting distribution of difference was individually age-matched (within a range of74 years) with a participant with values has a mean value of zero, because both sample pairs are drawn from the DP. The age of control participants ranged between 22 and 65 years. The mean age same dataset. Based on this distribution, the reliability of an observed ERP of this control group (40 years) was identical to the mean age of the DP group. To difference between conditions can be assessed for individual participants. If the assess the age-dependence of N170 effects, the DP group and the control group probability of obtaining the observed difference by chance is below 5%, it can be were each subdivided into a younger and an older sub-group, with eight accepted as statistically significant (see also Dalrymple et al. (2011), Eimer et al. participants in these sub-groups. Younger DPs were aged 22–39 years (mean (2012), Oruc- et al. (2011)). This bootstrap method was used to test the reliability age: 29.7 years), and younger controls were aged 22–37 years (mean age: 29.2 of N170 differences between faces and houses, and of inversion-induced N170 years). The age range of the eight older DPs was 41–67 years (mean age: 50.2 amplitude and latency modulations for individual participants. 3592 J. Towler et al. / Neuropsychologia 50 (2012) 3588–3599

3. Results control participants (bottom panel). Fig. 1 also includes topo- graphic maps of N170 difference amplitudes for both groups. 3.1. Behaviour These maps were generated by subtracting ERP mean amplitudes measured in the 150–190 ms post-stimulus time window in Participants with DP were less accurate than control partici- response to houses from mean amplitudes to upright neutral pants in detecting immediate stimulus repetitions (78.7% versus faces. Enhanced N170 components to faces as compared to houses 91.4%), and this difference was significant (t(30)¼2.77; po.01). were observed at P7/8 in both groups. Importantly, this amplitude There was also a trend for DPs to be slower than controls in difference was similar in size for participants with and without correctly detecting image repetitions (625 ms for DPs, 568 ms for DP. These observations were substantiated by statistical analyses control participants), although this difference failed to reach of N170 mean amplitudes obtained at P7/8. For control partici- significance (t(30)¼1.7; p¼.085). Both DPs and control partici- pants, there was a main effect of stimulus category (faces versus pants were more accurate in detecting immediate repetitions of houses: F(1,15)¼7.66; po.02), reflecting larger N170 compo- upright faces than repetitions of inverted faces (control partici- nents to faces as compared to houses. Although this effect tended pants: 95% versus 87%; t(15)¼3.21; p¼.006; DPs: 78% versus 72%; to be larger over the right hemisphere, the stimulus categor- t(15)¼2.4; p¼.03). The size of this face inversion effect on target y recording hemisphere interaction was not significant. Very detection accuracy did not differ between the two groups (Fo1). similar results were obtained for the group of DPs. There was also False alarms to non-repeated images occurred on 1.9% and 1.6% of an effect of stimulus category, F(1,15)¼25.3; po.001, demon- all non-target trials in the DP and control groups, respectively. strating the face-sensitivity of the N170 component in this group. This effect also tended to be more pronounced at P8, but there 3.2. The face-sensitivity of the N170: upright neutral faces versus was no reliable interaction with recording hemisphere. The upright houses similarity of the face-sensitive N170 for participants with and without DP was further assessed in an analysis of N170 mean Fig. 1 shows grand-averaged ERP waveforms obtained at amplitudes across both groups, with group (DPs versus Controls) vertex electrode Cz and at lateral posterior electrodes P7 and P8 as additional factor. There was a main effect of stimulus category in response to upright neutral faces and upright houses. ERPs are (F(2,30)¼30.1; po.001) again confirming the presence of larger shown separately for the DP group (top panel) and the group of N170 amplitudes to faces versus houses. But critically, there was

DP Group Difference Maps Faces - Houses

-9µV N170

300ms

Cz

P8 +14µV P7 150ms - 190ms

-4µV +3µV Upright Faces Houses

Control Group

-9µV N170 300ms

Cz

P8 +14µV P7 150ms - 190ms

-4µV +3µV

Fig. 1. Grand-averaged ERPs elicited by upright neutral faces and upright houses at vertex electrode Cz, and at lateral temporo-occipital electrodes P7 and P8 in the 300 ms interval after stimulus onset, for the group of sixteen DPs (top panel), and for the group of sixteen age-matched control participants without DP (bottom panel). Topographic maps on the right shows the scalp distribution of ERP difference amplitudes (upright neutral faces versus upright houses) in the N170 time window (150– 190 ms post-stimulus), for the DPs (top) and control participants (bottom). J. Towler et al. / Neuropsychologia 50 (2012) 3588–3599 3593 no indication of any interaction between stimulus category and in the N170 time window (150–190 ms post-stimulus) at midline group, or between stimulus category, recording hemisphere, and electrodes Cz and Fz, for the factors stimulus category (face versus group (both F(2,30)o1), which further underlines that the face- house) and electrode (Fz versus Cz). The VPP was present in the sensitivity of the N170 component was very similar for the DP control group (F(1,15)¼5.64; po.05), but not in the DP group group and for participants without DP. Participants’ age had no (F(1,15)o1). However, there was no reliable stimulus categor- effect on this face-sensitivity of the N170 in the control group y group interaction (Fo1). Fig. 2 shows ERPs recorded at right (stimulus category age: Fo1). In the DP group, N170 enhance- occipito-temporal electrode P8 in response to upright neutral ments to faces versus houses were larger for younger than for faces and houses, separately for each of the 16 DPs tested. Face- older participants (stimulus category age: (2,15)¼12.7; po.01), sensitive N170 components (i.e., enhanced N170 amplitudes to but follow-up analyses confirmed that N170 face-sensitivity was faces relative to houses) were present for most but not all DPs. To reliableinbothagegroups. study the presence and reliability of the N170 for individual DPs, As can be seen from the topographic map in Fig. 1 (bottom non-parametric bootstrap analyses were conducted separately for panel), control participants showed the typical N170 scalp dis- each DP on N170 mean amplitude differences between upright tribution: An occipito-temporal N170 component was accompa- faces and houses at P8. Reliably enhanced N170 components in nied by a component of opposite polarity (Vertex Positive response to faces were confirmed for twelve of the 16 DPs tested Potential; VPP) at midline frontocentral electrodes. The activation (as indicated by the symbol ‘^’ in Fig. 2). For two others (AH and pattern observed for the group of DPs in the same time window MP), N170 amplitude differences were in the expected direction, was qualitatively similar, although the frontocentral VPP compo- but did not reach significance in the bootstrap analyses. Only two nent was less pronounced. The reliability of the VPP in both participants with DP (MZ and RL) showed no evidence for an groups was evaluated in analyses of mean amplitudes measured N170 amplitude enhancement to face stimuli, but if anything

-8µV -10µV ^ -22µV ^ -8µV EW ^ CM NE AM ^

+12µV +12µV +16µV +15µV

^ µ µ -8µV ^ -10µV -8 V -20 V ^ SC CP KS ^ SW

µ µ +15µV +12µV +16 V +16 V

-8µV ^ -8µV -12µV -8µV JA MC ^ JL ^ SN ^

µ µ µ +12 V +12 V +15µV +12 V

-8µV -8µV -8µV -8µV MZ AH RL MP

+15µV +12µV +12µV +12µV

Upright Faces Houses

Fig. 2. ERPs elicited for each of the sixteen DPs tested at right occipito-temporal electrode P8 to upright neutral faces (solid lines) and upright houses (dashed lines). Bootstrap analyses confirmed that twelve of the sixteen DPs showed reliably enhanced N170 amplitudes to faces versus houses, as indicated by the symbol ‘^’. Note that different voltage scales were used for individual DPs. 3594 J. Towler et al. / Neuropsychologia 50 (2012) 3588–3599 a tendency in the opposite direction. Analogous bootstrap ana- was not significant (F(1,15)¼2.84; p¼.11). In marked contrast, lyses were conducted for each of the 16 control participants. Nine face orientation had no effect on N170 mean amplitudes in the DP of them showed reliably larger N170 amplitudes to faces versus group (F(1,15)o1). This difference between the two groups was houses. For the other seven, N170 components were numerically further confirmed in an additional analysis of N170 mean ampli- larger to faces than to houses, but this difference remained below tudes across groups. There was a significant interaction between the significance threshold in the bootstrap analyses. face orientation and group (F(2,30)¼6.29; po.02), demonstrating that inversion-induced N170 amplitude enhancements differed reliably between participants with and without DP. 3.3. Effects of face inversion on the N170 component To assess the impact of participants’ age on face inversion effects on N170 amplitudes, separate analyses were conducted for Fig. 3 shows grand-averaged ERP waveforms obtained at younger and older participants. Fig. 3 (bottom panel) shows ERPs lateral posterior electrodes P7 and P8 in response to upright and obtained at right posterior electrode P8 for younger and older DPs inverted faces (collapsed across neutral and fearful faces), for the and control participants, and demonstrates that age had a strong DP group (top) and the group of control participants (bottom). effect in the control group, but not for participants with DP. N170 For the control group, the typical effects of face inversion on the amplitude enhancements to inverted faces were absent not just N170 were observed: Relative to upright faces, inverted faces for older DPs, but also in the younger sub-group. For younger elicited enhanced and delayed N170 components. Remarkably, no control participants, the typical pattern of larger N170 compo- inversion-induced N170 amplitude enhancements were observed nents to inverted faces was observed. In contrast, this effect was for the DP group. If anything, the N170 to upright faces tended to absent in older controls. This pattern was confirmed by analyses be larger than the N170 to inverted faces for participants with DP. of N170 mean amplitudes at P8 for both groups with age (younger These observations were confirmed by statistical analyses of versus older sub-group) as additional factor. For DPs, there was no N170 mean amplitudes. For the control group, there was a main main effect of face orientation and no interaction between face effect of face orientation (upright versus inverted: F(1,15)¼6.73; orientation and age (both F(1,15)o1.6). For control participants, a po.05) on N170 mean amplitudes, reflecting larger N170 significant face orientation age interaction was present components to inverted as compared to upright faces. This effect (F(1,15)¼9.81; po.01), and this was due to the fact that a tended to be larger over the right hemisphere, although the significant face inversion effect was present in the younger sub- interaction between face orientation and recording hemisphere group (F(1,7)¼24.26; po.005), but not in the older sub-group (Fo1). When analyses were conducted separately for younger DP Group

µ -7µV N170 -7 V Younger DPs Younger Controls (22-39 years) (22-37 years) -9µV

300ms

300ms

P7 P8 +10µV

+15µV Upright Faces Inverted Faces Upright Faces Inverted Faces Control Group Older Controls -7µV Older DPs (41-67 years) (38-65 years) N170

P7 P8 +10µV

Fig. 3. Grand-averaged ERPs elicited by upright and inverted faces (collapsed Fig. 4. Grand-averaged ERPs elicited by upright and inverted faces (collapsed across neutral and fearful faces) at lateral temporo-occipital electrodes P7 and P8 across neutral and fearful faces) at right temporo-occipital electrode P8 in the in the 300 ms interval after stimulus onset, for the group of sixteen DPs (top 300 ms interval after stimulus onset, for the sub-groups of younger DPs and panel), and for the group of sixteen age-matched control participants without DP controls (top panel), and for the sub-groups of older DPs and controls (bottom (bottom panel). panel). J. Towler et al. / Neuropsychologia 50 (2012) 3588–3599 3595

Younger DPs

-8µV -12µV ^ -24µV -8µV EW CM NE AM

+12µV +12µV +15µV +15µV ^ -8µV -12µV -8µV -20µV SC CP KS SW

+15µV +12µV +12µV +15µV

Older DPs

-10µV -8µV -12µV -8µV JA MC JL SN

+12µV +12µV +15µV +12µV

-8µV -8µV -8µV -8µV MZ AH RL MP

^

+12µV +12µV +12µV +12µV

Upright Faces Inverted Faces

Fig. 5. ERPs elicited for each of the sixteen DPs tested at right occipito-temporal electrode P8 in response to upright and inverted faces (collapsed across neutral and fearful faces). Bootstrap analyses showed that only three of the sixteen DPs showed reliably enhanced N170 amplitudes to inverted faces, as indicated by the symbol ‘^’. Note that different voltage scales were used for individual DPs. and older participants, with group now included as between- (Fo1). Participants’ age had no effect on inversion-induced N170 subject factor, a significant face orientation group interaction latencies in either group (both Fo1). for younger participants (F(2,15)¼12.43; po.005) reflected the The absence of consistent face inversion effects on N170 presence of N170 face inversion effects for controls and the amplitude across participants with DP is illustrated in Fig. 5, absence of such effects for DPs. In contrast, no face orienta- which shows ERPs recorded at right occipito-temporal electrode tion group interaction was present for older participants P8 in response to upright and inverted faces (collapsed across (F(2,15)o1). neutral and fearful faces), separately for the eight younger DPs Analyses of N170 peak latencies in the control group revealed (top) and the eight older DPs (bottom). Typical face inversion the typical effect of face orientation (F(1,15)¼6.36 po.03), as the effects on N170 amplitudes (i.e., reliably enhanced N170 compo- N170 component was delayed for inverted as compared to nents for inverted relative to upright faces, as revealed by boot- upright faces (168 ms versus 163 ms; see Fig. 2). There was an strap analyses) were only found for three DPs, but were absent for interaction between orientation and recording hemisphere the remaining 13 DPs tested. Fig. 6 shows individual face inver- (F(1,15)¼5.98 po.03), as this effect was more pronounced over sion effects on N170 mean amplitudes, obtained by subtracting the right hemisphere. In the DP group, there was only a 2 ms ERPs to inverted faces from ERPs to upright faces. Results are latency difference for the N170 to inverted and upright faces plotted separately for younger and older participants, both for (163 ms versus 161 ms), which was not significant (Fo1). How- DPs (dark bars) and controls (light bars), and sorted by the ever, there was no significant face orientation group interaction absolute size and polarity of these effects. Larger N170 components 3596 J. Towler et al. / Neuropsychologia 50 (2012) 3588–3599

Younger Participants upright as compared to inverted faces, whereas this unusual pattern was observed for three of the older DPs (see Fig. 6). 6 * 3.4. Correlations between behavioural performance and N170 face 4 inversion effects V) µ ( * 2 * * There were no statistically significant correlations between the performance of individual participants with DP in behavioural C01 C02 C11 C04 C09 C13 CM CP C03 EW SC C06 face processing tests (FFT, CFMT, CFPT, ONT) and individual N170 0 KS AM NE SW face inversion effects (i.e., mean amplitude differences between upright and inverted faces in the N170 time window). However, a -2 * reliable correlation was found for the DP group between the effect * * * * of face inversion on target detection accuracy in the main N170 Inversion effect N170 Inversion -4 * experimental task (the percentage of correctly detected immedi- * * ate repetitions of upright versus inverted faces) and the N170 face inversion effects observed in this task (r(15)¼.601, p¼.014): DPs -6 who tended to show the typical pattern of larger N170 compo- * nents to inverted versus upright faces showed a larger advantage Older Participants in detecting repetitions of upright versus inverted faces, while atypical N170 face inversion effects in the DP group were linked 4 * * to smaller performance differences in response to upright versus inverted target faces. Across the 16 control participants, there was no such link between N170 face inversion effects and the effects * of face inversion on target detection in the one-back task. V) 2 µ (

* 4. Discussion

C10 MZ C07 C15 C05 RL C16 C08 0 JA AH MP C14 SN MC C12 JL We measured the face-sensitive N170 component in a group of 16 individuals with developmental prosopagnosia and in 16 age- matched control participants to find out whether the N170 is present or absent in DP, and to investigate how face inversion -2 affects this component in participants with DP. Results demon- N170 Inversion effect N170 Inversion strated that the face-sensitivity of the N170 component in DPs * * and in control participants is very similar. N170 amplitude -4 enhancements in response to inverted faces are largely absent in individuals with DP, regardless of their age. A different pattern Fig. 6. Face inversion effects on N170 amplitudes for individual DPs (dark bars) was observed for controls, where this effect was present but was and control participants (light bars), sorted according to the size and polarity of strongly age-dependent. As discussed below, these observations this effect. Amplitude values were obtained by subtracting N170 mean amplitudes to inverted faces from N170 mean amplitudes to upright faces, with negative are important for understanding which face processing mechan- values (on the left) reflecting typical N170 face inversion effects, and positive isms are disrupted in DP. values larger N170 amplitudes to upright faces. Significant differences, as revealed by bootstrap analyses, are indicated by asterisks. Results are shown separately for 4.1. N170 shows normal face-sensitivity in most DPs younger and older participants.

The comparison of ERPs to upright neutral faces and upright houses demonstrated that the face-sensitivity of the N170 com- to inverted faces are reflected by negative values and are plotted on ponent is largely preserved in DP. Fig. 1 shows grand-averaged the left, and larger N170 amplitudes to upright faces (reflected by ERP waveforms across all sixteen DPs (top panel), and across all positive values) are plotted on the right. Significant amplitude 16 age-matched control participants (bottom panel), and demon- differences, as demonstrated by single-subject bootstrap analyses, strates that enhanced N170 amplitudes to upright faces as are indicated by asterisks. A clear dissociation between controls compared to houses were triggered in a similar fashion in both and DPs is apparent for younger participants (Fig. 6, top panel): groups. The absence of any interaction between stimulus category seven of the eight younger controls tested showed reliably and group provides strong evidence that the face-sensitive N170 enhanced N170 amplitudes to inverted as compared to upright component is triggered in a very similar fashion in participants faces. In contrast, this typical N170 face inversion was observed for with and without DP. This conclusion is further supported by only two of the younger DPs, whereas as four others even showed a Fig. 2, which shows ERPs triggered in response to upright faces reversal of this effect, with significantly enhanced N170 amplitudes and houses at right temporo-occipital electrode P8 for individual to upright faces. As expected on the basis of the group level DPs. Twelve of the 16 DPs tested had reliably larger N170 analyses, no such clear dissociation between controls and DPs amplitudes to faces relative to houses, and two others showed was evident for older participants. At the individual level, bootstrap the same, albeit non-significant, N170 difference. analysis revealed that only one older DP and one older control These observations are based on a large sample of participants participant showed a significantly enlarged N170 to inverted faces. with DP, and therefore allow more general conclusions than Three other older controls showed N170 amplitude differences in previous studies where single cases or a much smaller number the same direction, which did not pass the conservative significance of participants were tested. In these earlier studies, the face- threshold of the single-case bootstrap analysis. Only one older sensitivity of the N170 was found to be preserved in some control participant showed reliably enhanced N170 amplitudes to individuals with DP, and abolished in others (Bentin et al., 1999, J. Towler et al. / Neuropsychologia 50 (2012) 3588–3599 3597

2007; Harris et al., 2005; Kress & Daum, 2003; Righart & De group differences for older participants. In other words, the Gelder, 2007; Minnebusch et al., 2007; Rivolta et al., 2012). The interaction between face orientation and group that was found results from the present study strongly suggest that the presence across all participants was primarily driven by the younger sub- of a normal face-sensitive N170 component is the rule rather than group. The ERP waveforms for individual participants with DP the exception in developmental prosopagnosia. In this respect, shown in Fig. 5 underline the fact that face inversion effects on DPs might differ from patients with AP, where a disruption of N170 were largely absent for DPs, irrespective of their age. N170 face-sensitivity is more common (e.g., Alonso-Prieto et al. (2011), Dalrymple et al. (2011), Eimer and McCarthy (1999)). The finding that most DPs have a face-sensitive N170 component is 4.3. Conclusions consistent with observations from fMRI studies that many DPs show enhanced activation to faces versus non-face objects in The generic face-sensitivity of the N170 component is very face-selective posterior brain areas (Furl et al., 2011), and extends similar in DPs and control participants, whereas N170 face these results by demonstrating face-sensitivity at relatively early inversion effects are reliably different between these two groups. perceptual stages of visual processing. These observations indi- What do these similarities and differences imply with respect to cate that at least some aspects of the structural encoding of facial the locus of face processing deficits in DP? The absence of face features and configurations remain intact in most individuals inversion effects on N170 amplitudes in most DPs suggest that with DP. It is also important to note that even though N170 they tend to process upright and inverted faces in a similar enhancements for faces versus houses were larger for younger fashion, perhaps because they are less efficient than controls in than for older DPs, these effects remained reliably present for utilizing the prototypical spatial-configural information provided older DPs and also for older controls (see also Daniel and Bentin by upright faces. In fact, the performance observed for the DP (2012), for additional evidence that the face-sensitivity of the group in the Cambridge Face Perception Test (CFPT) suggests that N170 is not age-dependent, for a group of much older participants they were relatively less affected by the disruption of this with a mean age of 77 years). information through face inversion. Their CFPT performance was less impaired for inverted faces than for upright faces (Inverted 4.2. N170 face inversion effects are absent in most DPs z¼.52; Upright: z¼1.35), and this difference was statistically reliable (t(15)¼3.36; po.004). In contrast to the face-sensitivity of the N170, there were It is interesting to note that the presence of atypical N170 face reliable differences between the DP and control groups in the inversion effects has also been observed for other types of effects of face inversion on N170 amplitudes. In the control group, developmental disorders, such as in individuals with autism N170 components were delayed and enhanced for inverted as spectrum disorder (ASD; Webb et al., 2012) or Williams Syn- compared to upright faces (Fig. 3, bottom panel), in line with drome (WS; Grice et al., 2001). The similarity of these findings many previous reports (e.g., Bentin et al. (1996), Eimer (2000b), and the current observations for individuals with DP suggest Itier et al. (2007); Rossion et al. (2000)). In contrast, face inversion common underlying deficits in global aspects of face perception effects on N170 amplitudes were absent for the DP group (Fig. 3, that may be specifically tuned to the processing of upright faces. top panel), and this difference was substantiated by a reliable Age is clearly another important factor for the presence versus interaction between face orientation and group. However, these absence of N170 face inversion effects. Taylor, Batty, and Itier observations at the group level do not provide a full account of (2004) found that inversion-induced N170 amplitude enhance- the pattern of N170 face inversion effects, which turned out to be ments typically found with younger adults only emerged around strongly age-dependent in the control group, but not in the group the age of 11–12 years. For younger children, this effect was of DPs. As shown in Fig. 4, large inversion-induced N170 ampli- inversed, with larger N170 components for upright relative to tude modulations were found for the eight younger control inverted faces. Elderly participants also show no enhancement of participants, but not for the older controls. This difference is the N170 for inverted faces (Daniel & Bentin, 2012; Gao et al., reminiscent of previous observations by Gao et al. (2009) and 2009), and the current results suggest that this deviation from the Daniel and Bentin (2012), who found that N170 amplitude pattern commonly observed with young adult participants may enhancements to inverted as compared to upright faces were already emerge in middle age. present in young but absent in elderly participants. A notable Is there a common factor that might link the different difference is that the mean age of the older participants in these populations that show atypical N170 face inversion effects (young two earlier studies was above 70 years, while the older controls in children, older adults, individuals with DP or with other devel- the current experiments were considerably younger (38–65 opmental disorders)? One candidate factor is the degree of years). This age range is rarely studied in N170 research, where selective functional specialization within ventral visual areas for claims about ‘‘typical’’ N170 effects are usually based on samples upright faces. The observation that upright faces trigger equally of participants in their twenties (but see Wolff, Wiese, and large or even larger N170 components than inverted faces could Schweinberger (in press), for a recent exception). The fact that reflect a tendency for upright faces to activate object-sensitive atypical N170 face inversion effects were obtained in the current areas that would otherwise only be activated by non-face objects study for middle-aged control participants suggests that such or inverted faces due to a general reduction in cortical face- generalizations of findings from young adult participants to older specificity. The level of face-selectivity in visual processing does age groups may not always be warranted. They also suggest that indeed change considerably in the course of development: Acti- important qualitative differences in the way that face perception vation in face-selective regions becomes progressively more operates may not only emerge in the elderly, but already in specialized through childhood into adulthood (Golarai et al. middle age. 2007; Joseph et al., 2011), and the same face-selective regions These observations for control participants are also important appear to become less differentiated and specialized with age to qualify the absence of N170 face inversion effects for DPs. As is (Park et al., 2004). Individuals with ASD show reduced or atypical evident in Fig. 4, these effects differed markedly between younger neural specialization for faces (e.g. Pierce, Muller, Ambrose, Allen, DPs and younger controls. Young controls showed larger N170 and Courchesne (2001)), and a reduction in the face-selectivity of amplitudes for inverted versus upright faces, whereas age- the FFA has been demonstrated for DPs (Furl et al., 2011). matched young DPs did not. In contrast, there were no significant Individuals with WS were found to have much larger FFAs than 3598 J. Towler et al. / Neuropsychologia 50 (2012) 3588–3599 matched controls, again demonstrating an atypical neural specia- a general reduction in the early selectivity of visual processes lization for faces (Golarai et al., 2010). tuned specifically to upright faces as one source for the face Some authors have recently challenged the claim that cortical recognition deficits in developmental prosopagnosia. regions increase in their face-selectivity during development, and have argued that face perceptual expertise is mature during early childhood (McKone, Crookes, Jeffery, & Dilks, 2012). Although this Acknowledgements claim is in line with developmental ERP studies which have found no systematic changes in the face-sensitivity of the N170 from This research was supported by a grant from the Economic and 4 years onwards (Kuefner, de Heering, Jacques, Palmero-Soler, & Social Sciences Research Council (ESRC), UK. Thanks to Joanna Rossion, 2010), it is inconsistent with ERP and fMRI studies of face Parketny for technical assistance and to all prosopagnosic parti- inversion, which demonstrate that the neural systems involved in cipants for taking part in the research. expert adult face perception have a protracted developmental trajectory, and only become fully tuned to upright faces in early References adulthood (Taylor et al., 2004; Passarotti, Smith, DeLano, & Huang, 2007). Alonso-Prieto, E., Caharel, S., Henson, R. N., & Rossion, B. (2011). Early (N170/ The suggestion that the absence of reliable N170 face inversion M170) face-sensitivity despite right lateral occipital brain damage in acquired prosopagnosia. Frontiers in Human Neuroscience, 5, 138. effects observed for DPs in the current study is linked to a general Barton, J. J. S. (2008). Structure and function in acquired prosopagnosia: Lessons reduction in the upright face-selectivity of visual processing that from a series of 10 patients with brain damage. Journal of Neuropsychology, is not exclusive to DP, but is also found in younger children, older 2, 197–225. Begleiter, H., Porjesz, B., & Wang, W. Y. (1995). Event-related brain potentials adults, and individuals with other developmental disorders raises differentiate priming and recognition to familiar and unfamiliar faces. Electro- the obvious question how this reduction is linked to the face encephalography and Clinical Neurophysiology, 94, 41–49. recognition impairments that are the defining feature of DP. In Behrmann, M., & Avidan, G. (2005). Congenital prosopagnosia: Face-blind from birth. Trends in Cognitive Sciences, 9, 180–187. our study, older control participants and older DPs did not differ Behrmann, M., Avidan, G., Marotta, J. J., & Kimchi, R. (2005). Detailed exploration of with respect to their N170 face inversion effects (Fig. 4), yet the face-related processing in congenital prosopagnosia: 1. Behavioral findings. older controls (and older individuals in general) are clearly not Journal of Cognitive Neuroscience, 17, 1130–1149. prosopagnosic. Robust differences in the effects of face inversion Bentin, S., Allison, T., Puce, A., Perez, E., & McCarthy, G. (1996). Electrophysiological studies of face perception in humans. Journal of Cognitive Neuroscience, on N170 amplitudes were found between younger controls and 8, 551–565. younger DPs, and it is possible that these differences mark a Bentin, S., De Gutis, J. M., D’Esposito, M., & Robertson, L. C. (2007). Too many trees critical distinction between DPs and individuals with intact face to see the forest: Performance, ERP and fMRI manifestations of integrative congenital prosopagnosia. Journal of Cognitive Neuroscience, 19, 132–146. processing abilities: DPs have poor face recognition because they Bentin, S., & Deouell, L. Y. (2000). Structural encoding and identification in face never achieve the degree of upright face-specific functional processing: ERP evidence for separate mechanisms. Cognitive Neuropsychology, specialization in visual processing that is characteristic for typi- 17, 35–54. Bentin, S., Deouell, L. Y., & Soroker, N. (1999). Selective visual streaming in face cally developing adults, who may use compensatory strategies to recognition: Evidence from developmental prosopagnosia. Neuroreport, cope with the age-related general decline in functional specializa- 10, 823–827. tion when processing faces. Such strategies may not be available Bobes, M., Lopera, F., Dias Comas, L., Galan, L., Carbonell, F., Bringas, M. L., et al. (2004). Brain potentials reflect residual face processing in a case of prosopag- to individuals with DP who have never developed a typically nosia. Cognitive Neuropsychology, 21, 691–718. specialized face processing system. Bodamer, J. (1947). Die Prosop-Agnosie. (Die Agnosie des Physiognomieerken- How can the hypothesis that DPs show a reduced level of nens). Archiv fur¨ Psychiatrie und Nervenkrankheiten, 179, 6–53. Botzel,¨ K., & Grusser,¨ O. J. (1989). Electric brain potentials evoked by pictures of functional specialization for faces be reconciled with the observa- faces and non-faces: a search for face-specific EEG-Potentials. Experimental tion that the generic face-sensitivity of the N170 component in Brain Research, 77, 349–360. response to upright faces as compared to houses was essentially Bruce, V., & Young, A. (1986). Understanding face recognition. British Journal of normal for the DP group? It is important to note that the N170 is Psychology, 77, 305–327. Dalrymple, K., Oruc-, I., Duchaine, B., Fox, C. J., Iaria, G., Handy, T. C., et al. (2011). not a monolithic component that is tightly linked to one specific The neuroanatomic basis of the face-selective N170 in acquired prosopagno- face processing mechanism, but instead reflects multiple neural sia, a combined ERP/fMRI study. Neuropsychologia, 49, 2553–2563. sources that are associated with different sub-processes involved Daniel, S., & Bentin, S. (2012). Age-related changes in processing faces from detection to identification: ERP evidence. Neurobiology of Aging, 33, 206.e1 in face perception (e.g., Eimer et al. (2010), Rossion and Jacques 206.e28. (2008, 2011), Sadeh, Podlipsky, Zadanov, and Yovel (2010)). While De Gelder, B., & Stekelenburg, J. J. (2005). Naso-temporal asymmetry of the N170 there is clear evidence that the N170 component is associated for processing faces in normal viewers but not in developmental prosopagno- sia. Neuroscience Letters, 376, 40–45. with configural/holistic face processing (Eimer et al., 2011; Sagiv De Gutis, J. M., Bentin, S., Robertson, L. C., & D’Esposito, M. (2007). Functional & Bentin, 2001), it has also been demonstrated that N170 plasticity in ventral temporal cortex following cognitive rehabilitation of a amplitudes are sensitive to isolated face parts, such as the eyes congenital prosopagnosic. Journal of Cognitive Neuroscience, 19, 1790–1802. De Renzi, E., Faglioni, P., Grossi, D., & Nichelli, P. (1991). Apperceptive and (Bentin et al., 1996; Itier et al., 2007). The preserved face- associative forms of prosopagnosia. Cortex, 27, 213–222. sensitivity of the N170 in most DPs tested in this study may Di Nocera, F., & Ferlazzo, F. (2000). Resampling approach to statisitical inference: reflect the normal operation of one aspect of face processing (e.g., Bootstrapping from event-related potentials data. Behavior Research Methods, Instruments, & Computers, 32, 111–119. the detection and encoding of face parts), whereas the absence of Dobel, C., Putsche, C., Zwitserlood, P., & Junghofer,¨ M. (2008). Early left-hemi- N170 face inversion effects in DP could indicate an impairment of spheric dysfunction of face processing in congenital prosopagnosia: An MEG another aspect (e.g., configural face processing), which may be Study. PLoS ONE, 3, 6.e2326. associated with a reduced or atypical degree of functional Duchaine, B. (2011). Developmental prosopagnosia: Cognitive, neural, and devel- opmental investigations. In: A. J. Calder (Ed.), The Oxford handbook of face specialization of the face processing system. perception (pp. 821–838). Oxford: University Press. In summary, the present study has provided new insights into Duchaine, B., & Nakayama, K. (2005). Dissociations of face and object recognition the properties of the N170 component in developmental proso- in developmental prosopagnosia. Journal of Cognitive Neuroscience, 17, 249–261. pagnosia, and into the nature of face processing deficits in DP. The Duchaine, B., & Nakayama, K. (2006a). The Cambridge face memory test: results generic face-sensitivity of the N170 tends to be present in for neurologically intact individuals and investigation of its validity using individuals with DP, indicating that some basic aspects of face inverted face stimuli and prosopagnosic individuals. Neuropsychologia, 44, 576–585. perception are operational. The fact that inversion-induced N170 Duchaine, B., & Nakayama, K. (2006b). Developmental prosopagnosia: a window to modulations are abolished or even reversed in most DPs points to content-specific processing. Current Opinion in Neurobiology, 16, 166–173. J. Towler et al. / Neuropsychologia 50 (2012) 3588–3599 3599

Duchaine, B., Yovel, G., & Nakayama, K. (2007). No global processing deficit in the Minnebusch, D. A., Suchan, B., Ramon, M., & Daum, I. (2007). Event-related Navon task in 14 developmental prosopagnosics. Social, Cognitive, & Affective potentials reflect heterogeneity of developmental prosopagnosia. European Neuroscience, 2, 104–113. Journal of Neuroscience, 25, 2234–2247. Efron, B., & Tibshirani, R. J. (1993). An introduction to the bootstrap. New York: Oruc-, I., Krigolson, O., Dalrymple, K. A., Nagamatsu, L., Handy, T., & Barton, J. Chapman Hall. (2011). Bootstrap analysis of the single subject with event related potentials. Eimer, M. (2000a). Event-related brain potentials distinguish processing stages Cognitive Neuropsychology, 28, 322–337. involved in face perception and recognition. Clinical Neurophysiology, 111, Park, D. C., Polk, T. A., Park, R., Minear, M., Savage, A., & Smith, M. R. (2004). Aging 694–705. reduces neural specialization in ventral visual cortex. Proceedings of the Eimer, M. (2000b). Effects of face inversion on the structural encoding and National Academy of Sciences, 101, 13091–13095. recognition of faces—evidence from event-related brain potentials. Cognitive Passarotti, A. M., Smith, J., DeLano, M., & Huang, J. (2007). Developmental Brain Research, 10, 145–158. differences in the neural bases of the face inversion effect show progressive Eimer, M. (2011). The face-sensitive N170 component of the event-related brain tuning of face-selective regions to the upright orientation. NeuroImage, 34, potential. In: A. J. Calder (Ed.), The Oxford handbook of face perception (pp. 329– 1708–1722. 344). Oxford: University Press. Pierce, K., Muller, R. A., Ambrose, J., Allen, G., & Courchesne, E. (2001). Face Eimer, M., Gosling, A., & Duchaine, B. (2012). Electrophysiological markers of processing occurs outside the fusiform ‘face area’ in autism: Evidence from covert face recognition in developmental prosopagnosia. Brain, 135, 542–554. functional MRI. Brain, 124, 2059–2073. Eimer, M., Gosling, A., Nicholas, S., & Kiss, M. (2011). The N170 component and its Pitcher, D., Duchaine, B., Walsh, V., Yovel, G., & Kanwisher, N. (2011). The role of links to configural face processing: A rapid neural adaptation study. Brain the lateral occipital face and object areas in the face inversion effect. Research, 1376, 76–87. Neuropsychologia, 49, 3448–3453. Eimer, M., & Holmes, A. (2002). An ERP study on the time course of emotional face Riddoch, M. J., & Humphreys, G. W. (1993). BORB: Birmingham object recognition processing. Neuroreport, 13, 427–431. battery. Hove UK: Lawrence Erlbaum Associates Ltd. Eimer, M., & Holmes, A. (2007). Event-related brain potential correlates of Righart, R., & De Gelder, B. (2007). Impaired face and body perception in emotional face processing. Neuropsychologia, 45, 15–31. developmental prosopagnosia. Proceedings of the National Academy of Sciences, Eimer, M., Kiss, M., & Nicholas, S. (2010). Response profile of the face-sensitive 104, 17234–17238. N170 component: A rapid adaptation study. Cerebral Cortex, 20, 2442–2452. Rivolta, D., Palermo, R., Schmalzl, L., & Williams, M. A. (2012). Investigating the Eimer, M., & McCarthy, R. (1999). Prosopagnosia and structural encoding of faces: features of the M170 in congenital prosopagnosia. Frontiers in Human Neu- Evidence from event-related potentials. Neuroreport, 10, 255–259. roscience, 6, 45. Freiwald, W. A., Tsao, D. Y., & Livingstone, M. S. (2009). A face feature space in the Rosburg, T., Ludowig, E., Dumpelmann,¨ M., Alba-Ferrara, L., Urbach, H., & Elge, C. E. macaque temporal lobe. Nature Neuroscience, 12, 1187–1196. (2010). The effects of face inversion on intracranial and scalp recordings of Furl, N., Garrido, L., Dolan, R. J., Driver, J., & Duchaine, B. (2011). Fusiform gyrus event-related potentials. Psychophysiology, 47, 147–157. face selectivity relates to individual differences in facial recognition ability. Rossion, B., Delvenne, J. F., Debatisse, D., Goffaux, V., Bruyer, R., Crommelinck, M., Journal of Cognitive Neuroscience, 23, 1723–1740. et al. (1999). Spatio-temporal localization of the face inversion effect: An Gao, L., Xu, J., Zhang, B. W., Zhao, L., Harel, A., & Bentin, S. (2009). Aging effects on event-related potentials study. Biological Psychology, 50, 173–189. early-stage face perception: An ERP study. Psychophysiology, 46, 970–983. Rossion, B., Gauthier, I., Tarr, M. J., Despland, P., Bruyer, R., Linotte, S., et al. (2000). Garrido, L., Duchaine, B., & Nakayama, K. (2008). Face detection in normal and The N170 occipito-temporal component is delayed and enhanced to inverted faces but not to inverted objects: An electrophysiological account of face- prosopagnosic individuals. Journal of Neuropsychology, 2, 219–240. specific processes in the human brain. Neuroreport, 11, 69–74. Golarai, G., Ghahremani, D. G., Whitfield-Gabrieli, W., Reiss, A., Eberhardt, J. L., Rossion, B., & Jacques, C. (2008). Does physical interstimulus variance account for Gabrieli, J. D. E., et al. (2007). Differential development of high-level visual early electrophysiological face sensitive responses in the human brain? Ten cortex correlates with category-specific recognition memory. Nature Neu- lessons on the N170. Neuroimage, 39, 1959–1979. roscience, 10, 512–522. Rossion, B., & Jacques, C. (2011). The N170: Understanding the time-course of face Golarai, G., Hong, S., Haas, B. W., Galaburda, A. M., Mills, D. L., Bellugi, U., et al. perception in the human brain. In: S. Luck, & E. Kappenman (Eds.), The Oxford (2010). The fusiform face area is enlarged in Williams syndrome. Journal of Handbook of ERP components (pp. 115–142). Oxford: University Press. Neuroscience, 30, 6700–6712. Sadeh, B., Podlipsky, I., Zadanov, A., & Yovel, G. (2010). Face-selective fMRI and Gosling, A., & Eimer, M. (2011). An event-related brain potential study of explicit event-related potential responses are highly correlated: Evidence from simul- face recognition. Neuropsychologia, 49, 2736–2745. taneous ERP-fMRI investigation. Human Brain Mapping, 31, 1490–1501. Grice, S., Spratling, M. W., Karmiloff-Smith, A., Halit, H., Csibra, G., de Haan, M., Sadeh, B., & Yovel, G. (2010). Why is the N170 enhanced for inverted faces? An ERP et al. (2001). Disordered visual processing and oscillatory brain activity in competition experiment. Neuroimage, 53, 782–789. autism and Williams syndrome. Neuroreport, 12, 2697–2700. Sagiv, N., & Bentin, S. (2001). Structural encoding of human and schematic faces: Harris, A., Duchaine, B., & Nakayama, K. (2005). Normal and abnormal face holistic and part-based processes. Journal of Cognitive Neuroscience, 13, selectivity of the M170 response in developmental prosopagnosics. Neuropsy- 937–951. chologia, 43, 2125–2136. Schweinberger, S. R., Pfutze,¨ E. M., & Sommer, W. (1995). Repetition priming and Haxby, J. V., & Gobbini, M. I. (2011). Distributed neural systems for face perception. associative priming of face recognition: Evidence from event-related poten- In: A. J. Calder (Ed.), The Oxford handbook of face perception (pp. 93–110). tials. Journal of Experimental Psychology: Learning, Memory, & Cognition, 21, Oxford: University Press. 722–736. Haxby, J. V., Ungerleider, L. G., Clark, V. P., Schouten, J. L., Hoffman, E. A., & Martin, Schweinberger, S. R., Pickering, E. C., Jentzsch, I., Burton, A. M., & Kaufmann, J. M. A. (1999). The effect of face inversion on activity in human neural systems for (2002). Event-related brain potential evidence for a response of inferior face and object perception. Neuron, 22, 189–199. temporal cortex to familiar face repetitions. Cognitive Brain Research, 14, Itier, R. J., Alain, C., Sedore, K., & McIntosh, A. R. (2007). Early face processing 398–409. specificity: It’s in the eyes! Journal of Cognitive Neuroscience, 19, 1815–1826. Tanaka, J. W., & Sengco, J. (1997). Features and their configuration in face Jeffreys, D. A. (1989). A face-responsive potential recorded from the human scalp. recognition. Memory and Cognition, 25, 583–592. Experimental Brain Research, 78, 193–202. Taylor, M. J., Batty, M., & Itier, R. J. (2004). The faces of development: a review of Joseph, J. E., Gathers, A. D., & Bhatt, R. S. (2011). Progressive and regressive early face processing over childhood. Journal of Cognitive Neuroscience, 16, developmental changes in neural substrates for face processing: Testing 1426–1442. specific predictions of the interactive specialization account. Developmental Van Belle, G., de Graef, P., Verfaillie, K., Rossion, B., & Lefevre, P. (2010). Face Science, 14, 227–241. inversion impairs holistic perception: Evidence from gaze-contingent stimula- Joyce, C., & Rossion, B. (2005). The face-sensitive N170 and VPP components tion. Journal of Vision, 1, 10. manifest the same brain processes: The effect of reference electrode site. Von Kriegstein, K., Kleinschmidt, A., & Giraud, A. L. (2006). Voice recognition and Clinical Neurophysiology, 116, 2613–2631. cross-modal responses to familiar speakers’ voices in prosopagnosia. Cerebral Kress, T., & Daum, I. (2003). Event-related potentials reflect impaired face Cortex, 16, 1314–1322. recognition in patients with congenital prosopagnosia. Neuroscience Letters, Webb, S. J., Merkle, K., Murias, M., Richards, T., Aylward, E., & Dawson, G. (2012). 352, 133–136. ERP responses differentiate inverted but not upright face processing in adults Kuefner, D., de Heering, A., Jacques, C., Palmero-Soler, E., & Rossion, B. (2010). Early with ASD. Social, Cognitive & Affective Neuroscience, 7, 578–787. visually evoked electrophysiological responses over the human brain (P1, Wolff, N., Wiese, H., & Schweinberger, S. R. Face recognition memory across the N170) show stable patterns of face-sensitivity from 4 years to adulthood. adult life span: Event-related potentiale vidence from the own-age bias. Frontiers in Human Neuroscience, 3, 67. Psychology and Aging, http://dx.doi.org/10.1037/a0029112, in press. Marzi, T., & Viggiano, M. P. (2007). Interplay between familiarity and orientation in Yin, R. K. (1969). Looking at upside-down faces. Journal of Experimental Psychology, face processing: an ERP study. International Journal of Psychophysiology, 65, 81, 141–145. 182–192. Young, A., Hellawell, D., & Hay, D. C. (1987). Configural information in face McKone, E., Crookes, K., Jeffery, L., & Dilks, D. D. (2012). A critical review of perception. Perception, 10, 747–759. the development of face recognition: Experience is less important than Yovel, G., & Kanwisher, N. (2005). The neural basis of the behavioural face- previously believed. Cognitive Neuropsychology, 29, 174–212. inversion effect. Current Biology, 15, 2256–2262.