اساس آناتومیک سمت راست صورت گزینشی N170 در پروزوپاگنوزیا اکتسابی :مطالعه ترکیب A ERP / MRI

Abstract The N170 waveform is larger over posterior temporal cortex when healthy subjects view faces than when they view other objects. Source analyses have produced mixed results regarding whether this effect originates in the fusiform face area (FFA), lateral occipital cortex, or superior temporal sulcus (STS), components of the core face network. In a complementary approach, we assessed the face-selectivity of the right N170 in five patients with acquired prosopagnosia, who also underwent structural and functional magnetic resonance imaging. We used a non-parametric bootstrap procedure to perform single-subject analyses, which reliably confirmed N170 face-selectivity in each of 10 control subjects. Anterior temporal lesions that spared the core face network did not affect the face-selectivity of the N170. A face-selective N170 was also present in another subject who had lost only the right FFA. However, face-selectivity was absent in two patients with lesions that eliminated the occipital face area (OFA) and FFA, sparing only the STS. Thus while the right FFA is not necessary for the face-selectivity of the N170, neither is the STS sufficient. We conclude that the face-selective N170 in prosopagnosia requires residual function of at least two components of the core face-processing network.

1. Introduction Face perception is a computationally demanding high-level object recognition task that may involve highly specialized and possibly even face-dedicated cognitive processes. The temporal profile of the neural processing involved in face perception has been measured using event-related potentials (ERP). These show that between 140 and 200 ms after the appearance of a face there is a negative deflection that is larger in amplitude for faces than for non-face objects (Bentin et al., 1996, Botzel et al., 1995 and Jeffreys, 1989). Based on the timing of its emergence and the stimuli that elicit it, it has been proposed that this “face-selective N170” may be associated with encoding of face structure (Eimer, 2000 and Taylor et al., 1999) and/or the detection of faces (Bentin et al., 1996 and Zion-Golumbic and Bentin, 2007). A consistent finding across all studies is that the face-selective N170 is largest in the posterior temporal regions, and larger on the right compared to the left hemispheres (Bentin et al., 1996, Eimer, 1998, Jacques et al., 2007, Rossion et al., 2003 and Webb et al., 2010). In parallel, studies using functional magnetic resonance imaging (fMRI) have revealed a face-processing network in the human ventral occipitotemporal stream, which is also more prominent in the right hemisphere (Fox et al., 2009, Kanwisher et al., 1997 and Sergent et al., 1992). It consists of a core system in the occipitotemporal visual extrastriate cortex, as well as an extended system in more distant cortical regions (Haxby, Hoffman, & Gobbini, 2000). The core system is made up of three areas: the occipital face area (OFA) in the inferior occipital gyrus (Gauthier et al., 2000 and Haxby et al., 2000), the fusiform face area (FFA) in the middle lateral fusiform gyrus (Grill-Spector, Knouf, & Kanwisher, 2004), and the superior temporal sulcus (STS) in the lateral temporal cortex (Hasselmo et al., 1989 and Haxby et al., 2000). The extended system includes regions connected to the core system that perform face-related, though not necessarily face-specific, functions. These areas, which include the anterior temporal lobe, amygdala, auditory cortex, intraparietal sulcus, and insula, are involved in tasks such as accessing semantic information related to identity, evoking an emotional response to a face, and pre-lexical speech perception, like lip reading (Haxby et al., 2000). Which components of this face-processing network play critical roles in the generation of the face-selective N170 continues to be a subject of debate. Based on the fact that the N170 is strongest at electrode sites T5 and T6 – P7 and P8 in new ERP terminology (Rossion & Jacques, 2008) – some propose that the N170 is generated in occipitotemporal regions (Bentin et al., 1996). Alternatively, it has been suggested that the N170 is generated in the STS, given that the N170 amplitude is greater to eyes than to faces and that the STS is activated by moving eyes (Puce, Allison, Bentin, Gore, & McCarthy, 1998). Source analyses have produced mixed results, with some suggesting localization of the face-selective N170 in fusiform gyri (Itier and Taylor, 2002, Rossion et al., 2003 and Schweinberger et al., 2002) as well as the equivalent M170 on magnetoencephalography (Deffke et al., 2007), but others locating it in lateral temporal cortex (Shibata et al., 2002 and Watanabe et al., 2003), more specifically in the STS region (Itier & Taylor, 2004). More recently, inter-subject correlations of fMRI and ERP measures of face-selectivity showed high correlations between the face-selective N170 and face activation in both the FFA and the STS, but not in the OFA (Sadeh, Podlipsky, Zhdanov, & Yovel, 2010). Dual contibutions from FFA and STS are also consistent with another observation that added incremental noise to face images and found that intra-subject changes in the N170 correlated with changes in the bilateral fusiform and superior temporal gyri (Horovitz, Rossion, Skudlarski, & Gore, 2004). Part of the difficulty with N170 localization is that though ERP is a particularly precise measure of the temporal properties of brain function, it provides only a coarse measure of spatial location. An alternate, more direct, approach to the localization of ERP phenomena is to examine their status in human subjects with lesions to various components of the face-processing network. Recent refinements to face-localizer paradigms have made it possible to identify the components of the core system reliably in single subjects (Fox et al., 2009), and therefore to make definitive conclusions about the absence or presence of these components in patients with focal brain damage. Particularly informative may be studies of patients with acquired prosopagnosia, who have lost the ability to recognize the identity of faces following a cerebral insult (Bodamer, 1947). The anatomic locus of their brain damage is quite variable in both its lateralization and anterior-posterior extent (Barton, 2008a and Barton, 2008b). Most common are bilateral or right-sided lesions, with left hemispheric damage alone being quite rare (Barton, 2008a and Barton, 2008b). Lesions commonly affect the medial occipitotemporal lobe, with a possibility of affecting parts of the core network, but can also affect mainly anterior temporal structures (Barton, 2008a, Barton, 2008b and Evans et al., 1995). Our goal was to investigate the anatomic basis of the face-selective N170 by recording ERPs in five patients with acquired prosopagnosia. We first used fMRI to determine the status of the components of the core face-processing network in each individual. We then recorded ERPs while patients viewed pictures of novel faces and objects and used a single-subject analytic method to determine which patients had a preserved face-selective N170 component. By relating the post-lesional status of the core network to the status of the face-selective N170 we sought to determine which areas are necessary and/or sufficient for this face-processing ERP component.

3. Results The fMRI data showed significant variability between our five prosopagnosic subjects in terms of the impact of their brain damage on the different components of the core face network (Fig. 2). In B-AT1 and R-AT2, whose damage was mainly anterior, fMRI revealed that all components in both hemispheres were still detectable by our dynamic face localizer protocol. In R-IOT1 and B-OT/AT1, the extensive medial occipitotemporal damage was associated with loss of the right OFA and FFA, but activation of the right STS could still be detected, as was activity in all three core areas in the left hemisphere. In R-IOT4, there was loss of the right FFA only. Functional neuroimaging of the five prosopagnosic patients. Left column shows a ... Fig. 2. Functional neuroimaging of the five prosopagnosic patients. Left column shows a representative axial T1-weighted structural image of the main lesion in each patient. Next three columns show coronal images of the subtraction of the BOLD signal during viewing of objects from that during viewing of faces, at the level of the STS, FFA and OFA, particularly for the right hemisphere. Figure options For the ERP part of our study, our first step was to determine if the bootstrap analysis of our data showed a significant difference in the N170 amplitude between viewing anonymous faces and viewing objects in our control participants. The results confirmed that all 10 subjects showed a statistically reliable face-selectivity in the 40 ms period surrounding the N170 peak (Fig. 3). This supports our protocol and analytic method as a reliable indicator of any residual N170 face-selectivity in our prosopagnosic cohort. ERP waveforms for the five prosopagnosic patients (left column) and 10 healthy ... Fig. 3. ERP waveforms for the five prosopagnosic patients (left column) and 10 healthy controls (two right columns). Initials in the top left hand corner of each figure denote the identity of the subject. For patients, status of the core face-processing network in the right hemisphere is indicated by the box symbols in the inset (green = intact, grey = damaged). The time of the peak amplitude of the N170 is indicated for both faces and objects (in ms). Dotted lines represent the time window from which the bootstrapping values were sampled – i.e. form 20 ms before to 20 ms after the peak N170 value for each viewing condition. Asterisks show significantly different values for objects versus faces, with p values indicated. Plotting convention is for negative values upwards and positive values downwards. Figure options Subjects B-AT1 and R-AT2, whose anterior temporal lesions had spared all components of the core-face network, showed significant face-selectivity of the N170 (Fig. 3). This confirms suggestions that the face-selective N170 depends on integrity of occipitotemporal structures, and shows that interactions with anterior temporal structures are not required for this face-selectivity. Subject R-IOT4, who lacked only the right FFA, also showed significant residual face-selectivity in the N170, suggesting that the FFA is not necessary for generation of a face-selective N170. In contrast, subjects R-IOT1 and B-OT/AT1, with loss of the FFA and OFA, showed no evidence of greater amplitude of the N170 when viewing faces than when viewing objects, suggesting that the STS alone is insufficient to support face-selectivity of the N170. Regarding the peak latencies of object and face N170s, at a group level the ANOVA showed no significant main effects or interaction. At an individual level, none of the face or object peak latencies of any prosopagnosic subject differed from the mean peak latencies for controls (all ps > 0.05).