illustrates the group-averaged scene-selective activity from the main group of human subjects (n=10, ), using faces as control images, in the folded (), inflated () and flattened () cortical surfaces. Consistent with previous studies (Epstein et al., 2007
; Park and Chun, 2009
), we found significantly higher responses to scenes in three main regions, bilaterally, in the vicinity of: 1) the parahippocampal gyrus (‘PPA’), 2) the transverse occipital sulcus (‘TOS’), and 3) the retrosplenial cortex (‘RSC’).
Figure 1 Overall view of scene-selective regions in human and monkey visual cortex. Both species fixated the center of a screen during block-designed presentation of identical scene vs. face localizing stimuli. In the human data (panels A–E), relatively (more ...)
For comparison, shows a fMRI map from an awake fixating macaque monkey, in response to the same stimuli, displayed in the same cortical surface format. As in humans, multiple scene-biased regions were evident in the macaque. Regions that appear to correspond in the two species (presumptive homologues) are named accordingly in white (cf. ). Below, this putative map correspondence was tested in detail.
For simplicity and historical continuity, we used the original names for the human scene-selective regions PPA, TOS and RSC (Epstein et al., 1999
; Grill-Spector, 2003
; and Maguire, 2001
, respectively). We also extended the original naming scheme to indicate presumptive monkey homologues of these areas, by adding ‘m’ (i.e. mPPA, mTOS, mRSC). However because the present evidence revealed inaccuracies in all these names, a new set of names is proposed in the discussion section, which remain correct across both human and macaque cortex.
Human fusiform anatomy
To clarify the functional
maps of PPA, it is helpful to first document a detail in the anatomical
maps. Generally, the fusiform gyrus is described as a single uninterrupted gyrus (e.g. Polyak, 1957
; Duvornoy, 1999
). However one group (Chao et al., 1999
; Haxby et al., 1999
) distinguished fMRI activity on the ‘medial fusiform’ gyrus, from that on the ‘lateral fusiform’ gyrus. Here we found that this functional subdivision has a rough anatomical correlate: the central portion of the fusiform gyrus is usually split along its length by a shallow sulcus. We named this the ‘middle fusiform sulcus’, separating the ‘medial fusiform’ gyrus from the ‘lateral fusiform’ gyrus.
shows this anatomical feature in the averaged MRI-based cortical surfaces from two independent subject pools: 1) the current group average (n = 10; ) and 2) the averaged surfaces from the standard FreeSurfer average brain (n = 40; ). This cortical surface analysis averages the cortical folding pattern (i.e. the gyri and sulci) without conventional volumentric (3D) blurring. However, note that the cortical folds in each individual surface are best fit to the group-averaged folding pattern, so the individual maps are subject to minor 2D misalignment relative to the group map (Fischl et al., 1999
Figure 2 Evidence for a middle fusiform sulcus in the averaged human cortical surface maps. Panel A shows the averaged surface from the present data (n = 10), and panel B shows the magnified inset from the same data. Panel C shows the averaged map from an independent (more ...)
The middle fusiform sulcus (white arrow) is apparent in both group-averaged cortical surfaces (). In the n = 40 surface, the middle fusiform sulcus is only 2.5 mm deep, thus ~ 5 mm across the cortical surface. By contrast, the two sulci defining the external border of the fusiform gyrus (i.e. collateral and temporal occipital sulci) are much deeper, with maximum depth of ~10 and 6 mm, respectively. In our n=17 subject pool, the group values were similar: the depth and length of the middle fusiform gyrus in those individual surfaces ranged from 2–5 mm and 8–54 mm, respectively.
To confirm the presence of this sulcus in actual brains, we examined ex vivo brains from human autopsy. A middle fusiform sulcus was present in 20 of 24 hemispheres examined (83%). Examples are shown in .
Figure 3 Confirmation of a middle fusiform sulcus in individual ex vivo human brains. Panels A C show ventral views of the temporal lobe in three right hemispheres (anterior = rightmost; lateral = uppermost). Sulci and gyri are indicated as in . In all (more ...)
shows the location of scene-selective activity in this region (‘PPA’), from the main human dataset (n=10), based on group-averaged maps of the anatomy and function from a common set of subjects. Also shown is the center of fMRI activity (the voxel showing the highest statistical bias for scenes) in the group average () and in the individual data comprising our group map (). Counter to expectations, we found that this ventral scene-selective region (the ‘parahippocampal place area’) was not centered on the parahippocampal gyrus. Instead, it was consistently centered near the lateral lip of the collateral sulcus, where it meets the medial fusiform gyrus, in both our group-averaged and the individual maps, in both hemispheres. Of course, a lower-amplitude activity bias could extend onto the parahippocampal gyrus, depending on the statistical threshold chosen, the levels of signal averaging and spatial filtering, and variations between individuals.
Figure 4 Scene-selective activity from the present experiment was consistently centered on the lip of the medial fusiform gyrus and collateral sulcus. The right hemisphere is illustrated; data was similar in the left hemisphere. Panel A: group-averaged activity (more ...)
Role of stimulus variations
There is no single, quantifiable stimulus comparison for localizing PPA. Instead, different studies have localized this region based on correspondingly different scenes or houses, contrasted with various sets of faces, objects, body parts, and/or scrambled scenes. Thus it could be argued that the location of ‘PPA’ varies with the stimuli used to localize it. This could occur if the optimal stimuli vary continuously (instead of area-wise) across the cortical sheet (e.g. Wang et al., 1996
; but see Tootell et al., 2008
). Alternatively, it could occur in some models of a distributed representation (e.g. Ishai et al., 2000a
). Conceivably, either of these hypotheses could explain the presence here of a scene-selective patch of activity located lateral to
, instead of on
the parahippocampal gyrus.
To address this, we directly tested whether the location and topography of ‘PPA’ varies due to corresponding stimulus variations. shows the results produced by four different sets of scenes vs. natural and computer-generated faces, objects, or scrambled scenes (see Methods). Despite these wide stimulus variations, the topography of ‘PPA’ remained remarkably constant in comparisons within a common subject pool.
Figure 5 The topographical shape and center of PPA remains essentially constant, even when produced by different stimuli. All panels show group-averaged scene-selective activity (red/yellow) in medial views of the right hemispheres, equivalent to the views in (more ...)
Thus the unexpected localization of the scene-selective region here (away from the crown of the parahippocampal gyrus) cannot be attributed to stimulus differences between the current vs. past studies. Instead, these results in ‘PPA’ are fully consistent with results in classic lower-level visual areas, such as V1, V2, MT: none of these areas change shape or move across the cortical map, dependent on object stimulus variations.
How does the unexpected PPA localization here compare with analogous localizations in the literature? To clarify this, the following meta-analysis was conducted. The centers of previously published scene-biased activity in this region were translated onto a common, standardized cortical surface (using FreeSurfer and its averaged human brain) based on Talairach coordinates (Talairach and Tournoux, 1988
) reported in previous studies (). Coordinates were found in 12 neuroimaging comparisons of scenes or buildings, relative to faces, objects, or scrambled scenes. Each study was assigned a character, and that distribution is shown in . Eleven studies were based on fMRI; one was based on PET.
References for mata-analysis
Figure 6 A meta-analysis of the previous literature localizes ‘PPA’ to the lip of the collateral sulcus/medial fusiform gyrus, consistent with the current data ( and ). Data are rendered on a standardized cortical surface (more ...)
The averaged center of PPA in the current data (asterisk, from ) lies squarely in the middle of these previously published sites; thus our data were representative. Among the previously published sites, five were located on the crown of the medial fusiform gyrus, but none was on the crown of the parahippocampal gyrus. This and prior descriptions (Haxby et al., 1999
; Levy et al., 2004
) suggest that the ‘parahippocampal place area’ is not centered on the parahippocampal gyrus (see Discussion); instead it is located lateral to that gyrus. However as noted above, sub-maximal activity beyond the center can extend onto adjacent regions of the cortical surface (including the parahippocampal gyrus), depending on thresholding and related factors.
All but one of the remaining sites were located along the lip of the collateral sulcus, which divides the medial fusiform gyrus from the parahippocampal gyrus. The confluence of published centers along the lip (but not within the depth) of the collateral sulcus may reflect signal contributions from the large vein that overlies the collateral sulcus (e.g. Menon et al., 1993
; Kim et al., 1994
), in addition to signal contributions arising from the gray matter itself.
The macaque homologue of human FFA
Human PPA is located immediately adjacent to FFA in the cortical sheet, on the medial side, on the side closest to the splenium of the corpus callosum. Thus any candidate homologue of PPA in the monkey (‘mPPA’) should also lie immediately adjacent to monkey FFA (mFFA), on the side closest to the splenium.
To test that prediction, it was necessary to first localize mFFA as a reference landmark. Previously (Tsao et al., 2003
; Rajimehr et al., 2009
), the location of mFFA was defined based on quantitative transformation of cortical areas in the human and macaque maps, using fMRI and equivalent stimuli, based on maps from individual monkeys. In both reports, mFFA is the large, high-amplitude face-selective patch located ~mid-posteriorly along the length of the superior temporal sulcus, extending from the ventral bank onto the lip of the middle temporal gyrus (e.g. black asterisk in ).
However, additional face-responsive patches have also been reported in this cortical region, which might confuse the accurate localization of mFFA. In the simplest account, both monkeys and humans have two main face patches in corresponding cortical regions of each hemisphere, with the more posterior patch comprising (m)FFA (Hadj-Bouziane et al., 2008
; Rajimehr et al., 2009
; Bell et al., 2009
; Pinsk et al., 2005
). Another account is more complex: the monkey has either three (Tsao et al., 2003
) or six (Tsao et al., 2008a
) face patches in each hemisphere, whereas humans have three (Tsao et al., 2008a
) in this occipito-temporal region.
It is possible that this discrepancy arises in part from variation in the individual maps chosen for illustration. To date, group-averaged maps have not been calculated for the monkey face patches, which would reduce or eliminate such individual variations. To remedy this, group-averaged maps were first calculated from the fMRI data from three monkeys () used throughout this study, based on the same localizing stimuli used in human subjects (faces vs. scenes). In the monkey experiments, we used an exogenous contrast agent (MION; see methods) which increased the spatial specificity of the MRI signal compared to the more conventional BOLD signal used in human studies (Mandeville et al., 1999
; Vanduffel et al., 2001
; Leite et al., 2002
). These averaged data showed two main face patches in each hemisphere (), consistent with those described earlier (Hadj-Bouziane et al., 2008
; Rajimehr et al., 2009
; Bell et al., 2009
; Pinsk et al., 2005
; see also ).
Figure 7 Group-averaged cortical surface maps showing a macaque homologue of human PPA. The data show the averaged fMRI activity (n = 3) from fixating monkeys presented with localizing stimuli identical to those used in the human maps (scene set #2 vs. face set (more ...)
To confirm this finding, we calculated a second group-averaged map based on an additional and independent set (n=4) of monkeys. This second set of activity maps was generated in a different laboratory (NIMH), using a different scanner, based on stimuli that were familiar to the monkeys (i.e. faces of conspecifics, scenes and objects from the laboratory) – as opposed to stimuli that were matched to the human localization studies, as tested first. Despite these technical differences, again the group averages showed two main face patches (black asterisks and arrowheads, ), as expected from previous reports (ibid.).
Figure 8 Group-averaged map of mPPA and mFFA from an independent set of experiments. This group average (n = 4) was based on fMRI acquired at NIMH, based on an independent set of stimuli (monkey faces, and scenes and objects from the housing and training environment (more ...)
At lower thresholds, additional, smaller face-biased patches were sometimes found within a given monkey, as described elsewhere (Tsao et al., 2008
; Ku et al., 2011
). However the presence and location of such additional patches varied across animals, dependent on threshold level and other factors. Accordingly, those patches did not survive group averaging. Note also that face-selective activity in mFFA sometimes extended farther posteriorly (in or near V4d) as in the human maps (e.g. ). However, in both species, retinotopic maps from the same subjects suggest that this variable posterior activity reflects a difference in stimulus size/position, not necessarily face selectivity per se
Based on the cortical maps, a candidate mPPA should lie adjacent to this main face patch (mFFA) in the monkey cortical map, analogous to the relationship of FFA to PPA in the human map. Thus, in macaques, mPPA should lie on the crown of the middle temporal gyrus, slightly anterior and ventral to the posterior middle temporal sulcus.
Such a result has been shown in individual maps from two monkeys (Rajimehr et al., 2011
). Here, that initial finding was confirmed in both sets of group-averaged data ( and ). In one hemisphere, scattered regions of scene-biased activity also extended into the region of occipitotemporal sulcus (). However the latter activity was inconsistent in location, relative to the consistent peak of scene-selective activity in mPPA, in all four averaged hemispheres ( and ).
Figure 9 In human cortex, the scene-selective region ‘TOS’ is centered on the lateral occipital gyrus. All panels show the right hemisphere from a posterior-lateral viewpoint, as in . Panels A–C are cortical surface maps (more ...)
In the original report, the dorsal patch of scene-selective activity was localized on the transverse occipital sulcus; thus it was named ‘TOS’. However prior to that time, a classic retinotopically-defined area (‘V3A’) was also localized on the transverse occipital sulcus (Tootell et al., 1997
). Thus, either: 1) the transverse occipital sulcus spans both activity-defined areas (i.e., V3A plus TOS); 2) the TOS region coincides with (or includes) V3A; or 3) the original localization of TOS is incorrect.
Our evidence supports the third hypothesis. When averaged across subjects and hemispheres, this scene-selective patch (‘TOS’) was centered on the crown of the lateral occipital gyrus (), anterior and ventral to the transverse occipital sulcus. As in PPA, the centers of highest activity occurred on the edges of this gyrus, consistent with a contribution from the large veins overlying the adjacent sulci.
Human area V3A is easily defined based on retinotopic mapping stimuli, because it has a distinctive map of the complete contralateral visual field (Tootell et al., 1997
). In , we localized the scene-selective TOS region relative to retinotopically-defined area V3A, within all hemispheres in which V3A was unambiguously defined, based on two retinotopic criteria: 1) upper vs. lower field subdivisions, and 2) horizontal vs. vertical meridians (see Methods).
Figure 10 In humans, scene-selective ‘TOS’ is consistently located immediately anterior and ventral to retinotopically defined V3A. Panels A–D show data from the flattened right hemisphere of a single subject. Panel A is a summary map of (more ...)
These data confirmed that TOS is consistently located immediately anterior and ventral to V3A, and dorsal to the confluent foveal representations in V1 through V3 (). Thus TOS lies within explicitly retinotopic cortex – extending from V7 (Tootell et al., 1998
) through V3B (Press et al., 2001
) and LO-1 (Larsson and Heeger, 2003).
Next we tested whether a TOS homologue (‘mTOS’) exists in macaque visual cortex. When translated from the human maps to the macaque maps, a homologue for human TOS should lie immediately anterior to macaque V3A (Gattas et al., 1988), in macaque ‘V4d’, and/or the newly described retinotopic representations CIP-1, CIP-2 (Arcaro et al., 2011) and perhaps also the dorsal prelunate (DP) gyrus (Andersen et al., 1990
; Heider et al., 2005
However this specific human-to-monkey prediction is complicated by the existing maps of macaque V3A, which are not perfectly clear. The original single unit maps of V3A frequently showed a representation of the contralateral 180° on the anterior bank of the lunate sulcus, posterior to the prelunate gyrus (Van Essen and Zeki 1978
; Gattass et al., 1988). However in some animals, the anterior (upper field) representation in V3A was less certain (Gattass et al., 1988). A similar uncertainty can be seen in fMRI maps of V3A in some macaques (e.g. the upper field representation in ). When defined by variations in polar angle, the fMRI maps of V3A in macaque consistently extend over the prelunate gyrus (Arcaro et al., 2011; see also ).
Figure 11 Within-hemisphere comparisons of retinotopy and scene-selective activity in macaque TOS. The format is similar to that in . Panels A–C are taken from a single hemisphere, analogous to panels B – D in . Panel A is a retinotopic (more ...)
In all three animals in which the MR slice prescription included this region (MGH), we found patches of scene-selective activity in this general location, extending variably across both sides of the prelunate gyrus (e.g. , and , black arrows). In two monkeys, we were also able to map the retinotopy (). Direct comparison between the scene-biased and retinotopic maps showed that mTOS included area V4d, which is roughly the topographic equivalent of human areas V7, V3B and LO-1 (). However in macaques, this scene-selective activity also extended into area V3A, with some variability. In one hemisphere, mTOS was mainly in area V3A without any clear activity in area V4d (). Thus, ‘mTOS’ activity included V3A (as defined by the polar angle), plus areas more anterior to V3A (as in human TOS). Given the uncertainty in the definition of macaque V3A, it seems likely that the macaque TOS is homologous with human TOS.
In our human maps, scene-selective RSC was consistently located in the fundus of the parieto-occipital sulcus, bilaterally (). Extrapolating from many early architectonic studies, the scene-selective RSC region thus lies near the peripheral retinotopic representations of primary and secondary visual cortex, V1 and V2. To localize these regions in more detail, we first compared functional and anatomical maps based on group-averaged data (). Scene-selective RSC was localized using our main group-averaged data based on faces vs. scenes, as described above. V1 was localized anatomically, based on increased myelination in the stria of Gennari (Hinds et al., 2008
), as translated to the current brain surface using spherical coordinates (Fischl et al., 1999
). The topography of V2 was based on two kinds of data: 1) previous fMRI studies of the retinotopy in human V2 (Sereno et al., 1995
; Engel et al., 1997
; DeYoe et al., 1996
; Pitzalis et al., 2006
) up to 60° eccentricity, and 2) flattened human cortical tissue stained for cytochrome oxidase (Tootell and Taylor 1995
; Horton and Hocking, 1998
) including the far peripheral representation, which reveals thin stripes that are known to span the width of V2 (Tootell et al., 1983
; Horton, 1984
Figure 12 The human scene-selective region ‘RSC’ is located adjacent to peripheral V1. All panels show a medial view of the inflated cortical surface. Panels A and B show the right and left hemispheres (respectively), illustrating the group-averaged (more ...)
These maps also revealed a partially mirror-symmetrical topography in scene-selective regions PPA and RSC (). Although PPA lies farther away from the border with V1, both RSC and PPA lie adjacent to the peripheral representation of V2: PPA is located adjacent to the representation of the upper visual field, while RSC lies adjacent to the representation of lower visual field.
Given these unexpected results in the group-averaged data, we conducted more detailed tests to confirm these conclusions within an individual subject. shows those results, based on patterns of fMRI activity produced by: 1) scenes vs. faces (set #2; to label RSC and PPA); 2) vertical vs. horizontal meridians in the central 20° (retinotopic set #1); 3) monocular activation of the visible limit of the ipsilateral far periphery (the monocular crescent) of the visual field, vs. the (invisible) farther periphery (see Methods). As a reference, we also included the group-averaged border of V1 based on the stria of Gennari.
Overall, we found a good match between the group-averaged data and the individual data. The retinotopically-defined border of V1/V2 (the vertical meridian representation) in the individual subject corresponded well with myelination boundaries in the group-averaged map (), within the central ~ half of V1, where both measures were available. In addition, the peripheral extent of checkerboard-driven activation in the individual map coincided with the peripheral border of V1 in the myelination map (). The peripheral extent of the checkerboard-driven activity spread slightly into adjacent areas, including presumptive V2 and the posterior portion of PPA. This spread of the checkerboard-driven activation was expected; previous studies have demonstrated that both V2 (e.g. Sereno et al., 1995
; DeYoe et al., 1996
; Engel et al., 1997
) and PPA (Rajimehr et al., 2011
) are strongly activated by flickering checkerboards.
As in the group map, RSC in this individual map was located immediately adjacent to the dorsal border of peripheral V1, thus occupying what would otherwise be the peripheral representation of V2. Also consistent with the group comparison, PPA was located adjacent to peripheral V2, at an eccentricity similar (or even more peripheral) to that of RSC.
Based on the translation of cortical maps across species, a presumptive macaque homologue of RSC should be located on the medial bank, in or adjacent to the parietal occipital (medial) sulcus (POm; Pitzagalis et al 2006
). In at least one of the monkeys, we confirmed the presence of that scene-biased patch, bilaterally (). As in human RSC, this presumptive macaque homologue of RSC (‘mRSC’) was small in size and low in amplitude, in response to the localizer used here. This small size and amplitude of RSC may explain why mRSC did not reach threshold in the n=3 group map ().
Figure 13 Evidence for RSC in one macaque monkey. A patch of scene-biased activity was present bilaterally, in a location consistent with the location of RSC in humans (i.e. in POm) (minimum = p < 10 ^ -5; maximum = p < 10 ^ -10). Panels A and B (more ...)