Behavioral Deficits and Cortical Damage Loci in Cerebral Achromatopsia

Full text

Behavioral Deficits and Cortical Damage
Loci in Cerebral Achromatopsia
Seth E. Bouvier
1
and Stephen A. Engel
2
1
Interdepartmental Program in Neuroscience, University of
California at Los Angeles, Los Angeles, CA 90095, USA and
2
Department of Psychology, 1285 Franz Hall Box 951563,
University of California at Los Angeles, Los Angeles,
CA 90095, USA
Lesions to ventral occipital cortex can produce severe deficits in
color vision, a syndrome known as cerebral achromatopsia.
Because most studies examine relatively few cases, however,
uncertainty remains about precisely which cortical loci, when
damaged, produce the syndrome. In addition, the extents of the
associated perceptual deficits remain unclear. To address these
issues, we performed a meta-analysis of 92 case reports from the
literature. The severity of color vision deficits of the cases varied
greatly, although nearly all showed some deficit in color discrim-
ination. Almost all cases tested also showed some loss of spatial
vision. Lesion overlap analyses revealed a relatively small region of
high overlap in ventral occipital cortex. The region of high overlap
was located near areas identified by neuroimaging studies as
important for color perception. For comparison, we performed
a similar analysis of prosopagnosia, a disorder of face perception,
and found several regions of high lesion overlap adjacent to the
region associated with achromatopsia. Because the behavioral
deficits in achromatopsia are often incomplete and never restricted
to color vision, the region of high lesion overlap may be one critical
stage within a stream of many visual areas that participate
nonexclusively in color perception.
Keywords: color, dyschromatopsia, lesions, prosopagnosia, vision
Introduction
Whether the primate brain contains a small region of extras-
triate cortex specialized for color processing has remained
controversial (Lueck et al., 1989; Schiller and Lee, 1991; Zeki
et al., 1991; Heywood et al., 1992; Walsh et al., 1993; Tootell and
Hadjikhani, 2001). Studies of human patients have provided
perhaps the strongest evidence for such a color center. After an
historical controversy (for a review, see Zeki, 1990), cases in
which cortical damage can lead to disturbed color vision,
a disorder termed achromatopsia, have come to be widely
accepted. To date, however, analysis of achromatopsia rests
mostly on single case reports, often with extensive cortical
damage. The few reviews of more than a handful of cases have
not conducted any quantitative analyses (Meadows, 1974; Zeki,
1990). Because of these limitations, the achromatopsia litera-
ture remains difficult to interpret. To examine more thoroughly
the nature of achromatopsia, we cataloged the behavioral
deficits and lesion anatomies of a large number of cases. For
comparison, we collected cases with damage leading to
a different disorder, prosopagnosia.
Materials and Methods
Identification and Selection of Cases
To identify cases of achromatopsia, we first performed literature
searches in the PubMed database using as keywords all combinations
of one term from the group {‘central’, ‘cerebral’, ‘cortical’} and one
from the group {‘achromatopsia’, ‘dyschromatopsia’, ‘color blindness’}.
The search term used to collect prosopagnosia cases was ‘prosopag-
nosia’. The case reports were then screened to remove cases with
developmental or pre-cortical defects. The reference lists of relevant
reviews and case reports were thoroughly examined to identify further
articles. Abstracts from conference proceedings were not collected, as
they were not likely to contain detailed case descriptions. Reports
prior to 1970 and some unobtainable non-English reports were also
excluded.
Tabulation of Behavioral Measurements
Results of behavioral tests were tabulated and categorized by hand.
Behavioral abilities were never categorized as either present or absent
unless a test was explicitly mentioned. For example, some reports of
achromatopsia made no mention of face recognition. Such cases may
have had intact face recognition, but for lack of certainty their abilities
were categorized as ‘unknown’. The full tabulation of test results used in
our analyses is provided as Supplementary Table 1.
Lesion Overlap Analysis
Cases were included in the lesion overlap analysis that had: (i) CT,
MRI or hand-drawn images in horizontal sections; (ii) clearly visible
lesions; and (iii) identifiable brain landmarks. These criteria ex-
cluded some early cases whose CT or MRI images were noisy or
showed only coronal slices. Note that the behavioral results of the
excluded cases were nevertheless included in the tabulation de-
scribed above.
We collected images of cases satisfying these criteria from published
reports, and scanned them into a computer at high resolution. Lesions
were then hand-traced onto a digital brain atlas (Woods et al., 1999) that
was rendered at multiple orientations allowing tracing to occur at the
orientation shown in the case report. The traced slices were rotated to
a common orientation using the AIR software (Woods et al., 1998) and
were projected to a single horizontal plane. We then calculated the
number of cases with a lesion directly above or below each location in
the projection plane. These numbers were rendered as an image
superimposed on the atlas image at the average horizontal location of
all lesions included in the analysis.
To compare lesion overlap results with the results of functional
imaging studies, the coordinates of reported functional activation peaks
were linearly transformed from Talaraich space to the digital brain atlas
space. The locations of the functional activations were then plotted on
the overlap image.
We measured the focality of the lesion overlap by calculating the
size of the overlap regions that were covered by a given percentage
of the total number of lesions (e.g., the number of pixels that were
in at least 50% of the lesions that produced achromatopsia). We
then graphed the size of these overlap regions as a function of the
number of lesions in the overlap. To generate error bars on these
plots, subsets of the achromatopsia patient population were
randomly resampled. Subsets of eight subjects were randomly
selected without replacement, and the size of the overlap region
was computed for each subset. The error bars represent the 5th and
95th percentiles of the distribution of overlap region sizes for each
overlap percentage.
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Cerebral Cortex February 2006;16:183--191
doi:10.1093/cercor/bhi096
Advance Access publication April 27, 2005

Results
Identification of Cases
The searches of achromatopsia terms yielded 722 hits. After
screening for developmental and pre-cortical deficits, 42
articles remained. Of these, two were excluded because the
disorder was of color constancy (Clarke et al., 1998; Ruttiger
et al., 1999). Three were excluded as unobtainable foreign
language papers; two were excluded as unobtainable papers
more than 25 years old. The remaining 35 papers contained
reports of 38 unique cases of achromatopsia. Of the 38 cases, 17
were diagnosed with prosopagnosia.
The PubMed search of keyword ‘prosopagnosia’ returned 347
articles. After screening for developmental and pre-cortical
deficits, 136 articles remained. Of these, 44 were excluded as
unobtainable foreign language papers; 46 were excluded as
unobtainable papers more than 25 years old. The remaining 46
papers contained reports of 73 cases of prosopagnosia. Of the
73 cases, 38 were diagnosed with achromatopsia.
Taken together, the searches produced 76 cases of achroma-
topsia and 90 cases of prosopagnosia. We next reviewed all
papers in the reference lists of the included papers. This review
identified an additional 15 papers containing 16 cases of
achromatopsia and 10 cases of prosopagnosia. This increase
was likely due to the choice of keywords of some papers not
including diagnostic descriptions (e.g. Clarke et al., 1997). In
total, we identified 92 cases of achromatopsia and 100 cases of
prosopagnosia, which are listed in Appendix I and tallied in
Supplementary Table 1. Note that these are not, 192 separate
cases, as many patients have both disorders.
Color Vision Deficits
Most of our collected cases of achromatopsia were given one or
more of three types of color vision tests: color naming, the
Ishihara isochromatic plates, or the Farnsworth--Munsell 15- or
100-hue test. Overall, achromatopsics’ deficits in color vision
span a broad range of severity.
Color naming is the most commonly reported test of color
vision, with 51% of cases tested (47 of 92 cases tested, hereafter
denoted n
tested
=47 and n
total
=92). Typically, subjects are asked
to name the color of paper patches or pieces of string.
Remarkably, 49% of cases tested for color naming were able
to perform normally (n
tested
=47). This percentage should be
treated cautiously, however, because in some reports, naming
tests were conducted informally, were not described or in-
volved naming the colors of common objects which could be
performed from memory rather than perception (e.g. Green and
Lessell, 1977; Adachi-Usami et al., 1995).
The Ishihara plates were also commonly used to test
achromatopsics (48% of achromatopsics, n
total
=92). The
test is most often used to screen for red--green colorblindness
of peripheral origin in non-injured subjects. To pass the test,
subjects must segregate isoluminant colored circles to iden-
tify the letter they form. Of the cases tested with Ishihara
plates, 29% read them normally [three or fewer errors (Birch,
1997), n
teste d
=44].
The Farnsworth--Munsell 100-hue test, and its 15-hue variant,
have been administered to achromatopsics about as often as the
other tests (50%, n
total
=92). Subjects arrange colored disks to
continuously vary in hue. The tests detect deficits in color
discrimination generally, and also identify common peripheral
defects. The worst performing 5% of the normal population
scores between 80 and 195 depending upon age (Kinnear et al.,
2002). Achromatopsics’ scores ranged from 106 to 1245, with
a mean of 582, and none showed patterns typical of dichromatic
or color anomalous observers. Very few of the achromatopsic
patients performed at chance, however, which corresponds to
a score of ~1200 (Victor, 1988). Thus, achromatopsics show
a wide variety of performance in color discrimination, from near
normal to total impairment.
The Nagel anomaloscope, which provides another method
for evaluating color deficits, has been used to evaluate only
a handful of cases (n
tested
=8). In this test, subjects manipulate
the red--green content of a test field to match a given yellow
field. Normal subjects select a unique red--green combination,
while subjects with impaired red--green color vision accept
many different red--green combinations as providing an ade-
quate match. Of the tested cases, three performed normally and
five performed abnormally. Two of the cases with abnormal
performance were consistent with the performance of individ-
uals with peripheral defects in color vision (Young and Fishman,
1980; Rizzo et al., 1993).
Spatial Vision Deficits
The spatial vision of achromatopsic patients has only rarely been
subject to thorough testing. Only 32% (n
total
=92) of cases
report any test of spatial vision at all, and in most of these (67%,
n
tested
=29) acuity is the only measure reported. The mean
acuity of the cases tested was 0.85, roughly equivalent to 20/24
vision. Some isolated tests of spatial vision were also given, such
as figure--ground segregation (Whiteley and Warrington, 1977),
stereo fusion (Pearlman et al., 1978), visual evoked potentials
while viewing gratings (Bartolomeo et al., 1997), dot counting
(Orrell et al., 1995) or reading (Pearlman et al., 1978).
Performance in all of these cases was described as normal.
Also, many cases were given object recognition tests, likely to
rule out object agnosia, and this type of test can also be a crude
measure of spatial vision. Most subjects showed little deficit in
object recognition (see Other Visual Disorders, below).
Of the few pap ers reporting thorough psychoph ysical testing
of spatial vision, most found spatial deficits. One case was
impaired at discrimin ation of illusory bor ders and Glass patter ns
(Gallant et al., 2000). Another case was impaired at object
naming and luminance contrast sensitivity (Merigan et al.,
1997), and another was impaired at texture discrimination
(Mendola and Corkin, 1999). One well-studied case that
showed normal acuity (Mollon et al., 1980) nevertheless
showed abnormal luminance contrast sensitivity (Heywood
et al., 1991; Kentridge et al., 2004). However, one case
exhibited normal contrast sensitivity, at least when tested at
mid- to low-spatial frequencies (Rizzo et al., 1992).
Other Visual Disorders
Several other visual disorders frequently co-occur with achro-
matopsia. Prosopagnosia co-occurs very often; fully 72% of
cases with achromatopsia also have prosopagnosia (n
total
=92).
Co-occurrence with other visual disorders, while less frequent,
is still common: alexia co-occurs at a rate of 13%, spatial or
topographical agnosia at 12%, and object agnosia at 8%.
Topography of Color Loss
Partial field color loss is relatively common; in our sample of
cases, seven had a hemifield color loss (Albert et al., 1975;
184 Achromatopsia Meta-analysis dBouvier and Engel

Damasio et al., 1980; Freedman and Costa, 1992; Paulson et al.,
1994; Silverman and Galetta, 1995; Short and Graff-Radford,
2001) and six had a quarter-field color loss (Kolmel, 1988;
Merigan et al., 1997; Gallant et al., 2000; Uttner et al., 2002;
Mesad et al., 2003). Three cases of quarter-field color loss had
the extent of their color vision rigorously mapped, and each had
clear perceptual boundaries at the vertical and horizontal
midlines (Kolmel, 1988; Merigan et al., 1997). Of the six total
cases of quarter-field color loss, four were localized to the
superior left quadrant, one to the superior right quadrant and
one to the inferior left quadrant (although the presence of an
upper left visual field scotoma in this one case of left inferior
quadrant color loss is also consistent with hemifield color loss).
All of the partial-field color losses with known lesion locations
arose from unilateral lesions (n
tested
=12). In one case of
hemifield color loss, whether the lesion was lateralized was
unknown (Freedman and Costa, 1992). In only one case did
a unilateral lesion lead to a full-field color impairment (Setala
and Vesti, 1994). Of the remaining cases, 10 had unilateral
lesions and unknown extents of color loss, and 51 had bilateral
lesions, and most likely full-field color losses, though the spatial
extent of the loss is seldom mentioned (Bartolomeo et al., 1997;
Beauchamp et al., 2000). There were 17 cases with unknown
lesion laterality and unknown extents of color loss.
Scotomas and Lesion Location
Cases of achromatopsia are commonly accompanied by scoto-
mas—severe vision loss in part of the visual field. Figure 1
summarizes the locations of the scotomas reported in our
sample of patients. For comparison, the figure also shows the
scotomas of our identified cases of prosopagnosia (identified in
a separate literature search—see Materials and Methods). The
vast majority of the entire set of cases with either disorder
(72%; n
tested
=98) had an upper visual field loss. The visual field
losses of the achromatopsic and prosopagnosic populations
were similar in most respects, except the scotomas in proso-
pagnosia were more likely to be located in the left visual field.
Most of the cases with either disorder had bilateral lesions,
but of those with unilateral lesions the majority were in the
right hemisphere. Of achromatopsia cases with reported lesion
laterality, 70% were caused by bilateral lesions, 20% were
caused by a unilateral right lesion and 10% were caused by
a unilateral left lesion (n
tested
=70). The distribution of lesions
leading to prosopagnosia was similar, but perhaps more
lateralized, with 65% bilateral, 32% unilateral right and 3%
unilateral left lesions (n
tested
=48).
Lesion Overlap Analyses
Figure 2A shows the anatomical overlap of all patients with
achromatopsia (n
tested
=46) and of all patients with prosopag-
nosia (n
tested
=52). Both images contain a well-defined,
common region of high overlap in occipitotemporal cortex.
This result was expected, since the most patients in our sample
have both disorders. The common region of high overlap may
very well contain separable sub-regions when damaged lead to
each syndrome alone. Alternatively, since some vascular loca-
tions are more likely to be damaged (Osborne, 1991), the
common region may simply represent a cortical location near
a susceptible vascular location.
To test for the existence of sub-regions associated solely with
achromatopsia, we analyzed the much smaller population of
Figure 1. Scotoma locations. Scotomas are common in cases of achromatopsia and
prosopagnosia. Shown are the percent of cases of achromatopsia and prosopagnosia
with scotomas in the shaded location. The empty circle indicates cases with no
scotomas, and the circle with the question mark indicates cases with scotomas that
did not fit this categorization.
Figure 2. (A) Lesion overlap of all achromatopsia and prosopagnosia cases. The
achromatopsia lesion overlap (left) contains lesions from all cases with achromatopsia
regardless of prosopagnosia diagnosis (n546). The prosopagnosia lesion overlap
(right) contains lesions from all cases with prosopagnosia regardless of achromatopsia
diagnosis (n552). The inserts show the atlas anatomy (see Materials and Methods)
and Talairach Z-coordinate at the average axial slice location for each group of cases.
The lesion overlaps in Figure 4 are on the same anatomical slices. (B) Lesion overlap of
achromatopsia and prosopagnosia cases with single disorder. The achromatopsia
lesion overlap (left) contains lesions from only cases of achromatopsia and intact face
processing (n511). The prosopagnosia lesion overlap (right) contains lesions from
cases of prosopagnosia and intact color processing (n58). The scale bar indicates
1 cm.
Cerebral Cortex February 2006, V 16 N 2 185

patients who were clearly identified as having a deficit in color
vision but intact face recognition. The overlap of cases with
achromatopsia but not prosopagnosia is shown in Figure 2B
(left). The large region of maximum overlap is in the right
hemisphere, where 7 of 11 achromatopsia cases had lesions,
with a center of mass at [30 --73 --2]. Within this region, there are
two small locations where 8 of the 11 achromatopsia cases had
lesions (Talairach coordinates [22 --74 36] and [28 --68 36]).
Only 3 of 8 cases with prosopagnosia and intact color
perception had lesions at the first location and 4 of 8 cases at
the second location.
The three cases that fail to overlap with the rest of the
achromatopsics are all cases with unilateral left hemisphere
lesions. Mirroring the unilateral left hemisphere lesions to the
right hemisphere increased the amount of overlap; one of the
three lesions fell partially within the region of maximum
overlap. Of the two cases that failed to overlap after mirroring
their unilateral left hemisphere lesion into the right hemi-
sphere, both were relatively close to the maximal region: one
lesion was 2 mm and the other was 34 mm from its boundary.
The overlap analysis of cases with prosopagnosia but not
achromatopsia is shown in Figure 2B(right). There are two
regions of maximum overlap in the right hemisphere, where 6 of
8 prosopagnosia cases have lesions. The larger of the two is
located slightly lateral and posterior to the area of maxi-
mum achromatopsia lesion overlap, with a center of mass at
[33 --84 2]. The smaller of the two is located slightly medial and
posterior to the area of maximum achromatopsia overlap, with
a center of mass at [18 --81 2]. Achromatopsia cases had lesions
at the center of mass of the lateral site in 3 of 11 cases and of the
medial site in 4 of 11 cases. As in the achromatopsia analysis, one
of the cases that failed to overlap was the result of a unilateral
left hemisphere lesion. Mirroring the one unilateral left hemi-
sphere lesion to the right hemisphere increased the amount of
overlap; all of the eight subjects’ lesions overlap with either the
medial region or the lateral region.
Overlap of Achromatopsia Lesions is More Focused
Figure 3 shows a comparison of the size of overlap regions for
prosopagnosia and achromatopsia as a function of the number of
cases overlapping. The y-axis indicates the size of the overlap
region, given a criterion amount of overlap. The x-axis indicates
this criterion amount of overlap, measured as a percentage of the
total cases included in the analysis. For example, the size of the
region of overlap that contains 50% of the cases of achromatopsia
is 634 mm
2
. At overlap percentages of 50 and 62.5%, the overlap
of lesions that cause achromatopsia is reliably smaller than the
overlap of lesions causing prosopagnosia. We computed error
bars for the sizes of the achromatopsia overlap regions using
a resampling procedure (see Materials and Methods).
Comparison to Imaging Results
Figure 4 superimposes on the lesion analyses peak activations
from imaging experiments that have attempted to isolate color-
or face-related activity. The left panel shows the peak activations
from studies of color vision superimposed on the achro-
matopsia lesion overlap (McKeefry and Zeki, 1997; Hadjikhani
et al., 1998; Beauchamp et al., 1999; Bartels and Zeki, 2000).
In cases where multiple activations are reported, the anterior
location of the activation is plotted in red, and the posterior
location is plotted in black. In all cases, the peak activations
fall reasonably close [within 64 mm (mean =18.4 mm)] to
the region of maximum lesion overlap.
Figure 4 also plots locations of peak activations from neuro-
imaging studies of face processing superimposed on the
prosopagnosia lesion overlap. Activations are plotted for three
important face-processing areas: the fusiform face area (FFA) in
black; the occipital face area (OFA) in red; and the superior
temporal sulcus (STS) in purple (Haxby et al., 1994; Kanwisher
et al., 1997; Halgren et al., 1999; Puce et al., 1999; Rossion et al.,
2003a,b). Peaks reported in the OFA fall closer to regions of
maximum lesion overlap than peaks in the FFA or the STS.
Figure 3. Achromatopsia and prosopagnosia lesion overlap sizes. Lesion overlaps
from cases with achromatopsia and intact face processing were compared to lesion
overlaps from cases of prosopagnosia and intact color processing at several different
criterion levels. Error bars on achromatopsia lesion sizes were estimated by resampling
the achromatopsia cases in groups of eight, to match the number of prosopagnosia
cases. At criteria of 50 and 62.5% overlap, the overlap of lesions causing
achromatopsia is smaller than the overlap of lesions causing prosopagnosia.
Figure 4. Lesion overlaps with neuroimaging results. Achromatopsia and prosopag-
nosia lesion overlaps are shown with representative neuroimaging peak activations
superimposed. On achromatopsia lesion overlap (left), black symbols indicate posterior
color-sensitive findings and red symbols indicate anterior color-sensitive findings in
studies reporting multiple responses. On prosopagnosia overlap (right), black symbols
indicate responses near the face-sensitive area FFA, red symbols indicate responses
near the face-sensitive area OFA, and the purple symbol indicates a response near the
face-sensitive area STS. Achromatopsia references: circle, Beauchamp et al. (1999);
3, Hadjikhani et al. (1988); triangle, Bartels and Zeki (2000); square, McKeefry and
Zeki (1997). Prosopagnosia references: þ, Haxby et al. (1994); circle, Halgren et al.
(1999); diamond, Kanwisher et al. (1997); 3, Rossion et al. (2003b); square, Rossion
et al. (2003a); star, Puce et al. (1999).
186 Achromatopsia Meta-analysis dBouvier and Engel

Discussion
A Region of High Lesion Overlap in Achromatopsia
Our analysis shows that a relatively small, critical region in
cortex is damaged in almost every known case of achromatop-
sia. The size of this region is reliably smaller than a comparable
region associated with prosopagnosia. The simplest explanation
of our results is that color perception depends upon the intact
function of a small region of cortex. Our lesion data are not
precise enough, and the functional imaging results not well
enough agreed upon, to determine whether the critical region
intersects only a single visual area; it appears close to the
reported locations of putative areas V4v, V8 and V4a(see
below). Our results agree with those from previous studies that
have compared the locations of multiple cases of achromatopsia
(Short and Graff-Radford, 2001; Tanaka et al., 2002), though no
other studies have included formal analysis of lesion overlap
with large numbers of cases.
The localization of the scotomas associated with the cases of
achromatopsia is consistent with the ventral location of the
critical region. Upper field scotomas are by far the most
common type, as has been noted here and by others (e.g.
Meadows, 1974). These scotomas are most likely the result of
injury that extends into V1 or the optic radiations, as both
of these structures represent the upper visual field on their
ventral surface.
Correspondence with Visual Areas
The location of the critical region of lesion overlap aligns well
with areas identified in functional imaging studies. Initial studies
(Lueck et al., 1989; Zeki et al., 1991) reported an area located
on the ventral surface of the occipital cortex specialized for
color vision. Many other neuroimaging experiments that
attempted to localize color-selective responses report peak
activations in this same general region (McKeefry and Zeki,
1997; Zeki and Marini, 1998; Beauchamp et al., 1999; Bartels and
Zeki, 2000). One experiment that simultaneously localized
color- and face-selective responses (Clark et al., 1997) reported
activations consistent with the critical regions identified here:
performance on a color task was associated with a location near
the critical region of lesion overlap in achromatopsia, and
performance on the face task was associated with a more
variable region lateral to the color responsive region.
Measurements of retinotopic organization showed that the
color selective area represents a visual hemifield (McKeefry and
Zeki, 1997; Hadjikhani et al., 1998; Wade et al., 2002). Recently,
a debate has developed regarding whether an additional
quarter-field representation exists between it and ventral area
V3 (also called VP) (Hadjikhani et al., 1998; Bartels and Zeki,
2000; Wade et al., 2002). Our region of maximum overlap in
achromatopsia falls close to the reported locations of both the
original color area and the proposed quarter-field area.
The visual field topography of color vision deficits also
constrains the identity of the damaged visual areas. The part
of space represented is almost certainly restricted to one half of
the visual field, since almost all cases of achromatopsia from
unilateral lesions had spared color vision in at least the
contralateral hemifield [there is one reported case of full-field
color loss from a unilateral lesion (Setala and Vesti, 1994)]. The
presence of crisp quarter-field color impairments further
suggests that in some cases the damaged area or areas may
represent only that portion of visual space. While partial damage
to a hemifield representation could in principle produce
something like a quarter-field deficit, the likelihood of it
producing color loss that completely and exclusively fills
a quarter of the visual field is vanishingly small. Thus, there
are likely to be visual areas with both quarter- and hemifield
representations within the regions of maximum overlap.
Specialization for Color Vision
Overall, there is little doubt that the region that is damaged in
cases of achromatopsia is important for color vision. Many of the
cases in our sample were impaired at color naming and at
recognizing the Ishihara plates. Nearly all of the cases showed
some degree of deficit when tested with the Farnsworth--
Munsell 100-hue test or its 15-hue variant. Of the two cases
approaching normal scores on this test, one recovered within
one month (Nakadomari et al., 1999) and the other recovered
within two years (Beauchamp et al., 1999). In all, the mean error
score for this group was 582, well outside the range of normal
performance (Kinnear and Sahraie, 2002).
Frequently, the loss of color vision is far from complete. Many
of the cases can perform at normal levels on some tasks: 49% can
adequately name or match colors, while 29% have enough
residual chromatic vision to read the Ishihara plates within the
normal limits. One case was able to read the plates when they
are displayed at a greater distance (2 m), but not at reading
distance (Mollon et al., 1980). This may be an example of
residual chromatic processing when the task takes on a figure--
ground aspect at greater viewing distances. Performance on the
Farnsworth--Munsell 100-hue test is also better than chance
(Victor, 1988) for most cases tested. Partially spared color vision
in many of these cases is in agreement with reports of lesion
studies in monkeys, where ablations in the inferior occipito-
temporal lobe, near the visual areas collectively known as IT,
cause deficits similar to human achromatopsia (Heywood et al.,
1988, 1995; Huxlin et al., 2000). Damage to macaque IT cortex
can result in chromatic deficiencies that are either mild (Huxlin
et al., 2000) or profound (Heywood et al., 1995).
There is little evidence, apart from broad measures of acuity,
that the region damaged in achromatopsia is exclusively de-
voted to color vision. When spatial vision was tested in more
detail, substantial deficits were consistently found. Lesions in
non-human primates have produced similar deficits; monkeys
with bilateral IT lesions are at least mildly impaired at spatial
tasks, including, for example, illusory contour detection (Huxlin
et al., 2000), shape matching (Merigan and Saunders, 2004) and
achromatic discrimination (Heywood et al., 1995). For reasons
that remain unclear, however, spatial deficits are smaller or non-
existent in animals with unilateral IT lesions (Merigan and
Saunders, 2004).
Some caution is warranted in interpreting our results. First,
interpretation of the behavioral data is difficult because negative
results of tests are likely underreported, hindering inferences
about general rates of behavioral deficits. Even when tests are
reported, they are often not well described, making detailed
evaluation of behavioral deficits impossible except in a handful
of cases. Second, the lesion overlap analysis was very limited in
its scope. We used only axial images of brain anatomy, which
narrowed the sample size and caused a loss of information about
overlap in the z-dimension. The analysis also used only the
anatomical slices shown in the case reports. These probably
Cerebral Cortex February 2006, V 16 N 2 187

gave a biased sense of lesion location; for example, few cases
show axial images lesions along the ventral surface of occipito-
temporal cortex, for the understandable reason that such
images have few identifiable landmarks and are difficult to
interpret. Finally, and probably most critically, our sample of
cases was biased in that it only included patients diagnosed with
prosopagnosia or achromatopsia. Our review points to the need
for a large prospective study of patients with occiptio-temporal
lesions, where cases are selected based upon lesion location
alone, and the accompanying behavioral deficits are tabulated.
Prosopagnosia
Unlike the results from the analysis of the achromatopsia cases,
the anatomical analysis of prosopagnosia cases did not yield
a single, contiguous region of maximum overlap. Instead, there
were several non-contiguous regions that were lesioned in
many cases. This result agrees well with other evidence for
distributed face processing in cortex (Farah and Aguirre, 1999;
Haxby et al., 2001). There are several candidate face processing
areas: the fusiform face area (FFA) (Kanwisher et al., 1997), the
superior temporal sulcus (STS) (Puce et al., 1998) and the
occipital face area (OFA) (Rossion et al., 2003a). The cases
reported here have lesions most often in the vicinity of the OFA.
The relative infrequency of STS lesions producing prosopagno-
sia is not surprising, since this area responds to changes in facial
expression or viewing angle (Haxby et al., 2000). Deficits in
processing such information might not be diagnosed as proso-
pagnosia. The lack of lesions near the FFA is more surprising,
since other evidence indicates this area is important for face
recognition (Haxby et al., 1994; Kanwisher et al., 1997; Halgren
et al., 1999; Rossion et al., 2003a,b). However, there was
a region of high lesion overlap located relatively close, though
medial to the site of FFA activations (Fig. 4). The misregistration
between the anterior overlap regions and the FFA might result
from a bias in our sample of images. As mentioned above, the
slices chosen for lesion illustration tend to avoid the ventral
surface of the brain, where the FFA is located. The images used
in our study were superior to the FFA, where cortex has curved
around medially and the FFA’s location contains white matter.
Thus, lesions that contained the FFA as well as other more
superior cortex would likely appear more medial in our analysis.
Conclusions: A Color Center?
Our results provide good evidence for a common region
damaged in achromatopsia that is important for color vision.
For there to be a single true color ‘center’, the damaged
region should show three additional properties, however: (i)
It should contain a single visual area; (ii) color vision should
be the only perceptual ability it supports and (iii) color vision
should not be critically dependent upon other late visual
areas. Our results provide at least some reason to doubt
whether each of these properties hold in cases of achroma-
topsia. First, the region of common overlap likely contains
two retinotopically defined visual areas, one containing
a quarter-field representation and one containing a hemifield
representation. Second, the common region is also likely also
important for spatial vision, since spatial deficits almost always
co-occur with achromatopsia. Third, other late visual areas
may play a significant role in color perception, since there is
frequently substantial residual color vision even when the
common region is damaged.
Our results agree with a less centralized view, in which color
perception arises from a stream of processing that flows
through multiple multipurpose visual areas. The many cases of
partially spared color vision suggest that some visual areas
outside the ones commonly damaged in achromatopsia partic-
ipate in the color-processing stream. The frequency of deficits
in spatial vision in cases of achromatopsia likely indicates that
more than one type of information is processed in the damaged
areas. Achromatopsia likely results from the lesion of one
critical step in the many stages of processing that support color
perception.
Notes
Address correspondence to Stephen A. Engel, Department of Psychol-
ogy, 1285 Franz Hall Box 951563, University of California at Los Angeles,
Los Angeles, CA 90095, USA. Email: engel@psych.ucla.edu.
Appendix 1
Case Achromatopsia
diagnosis
Prosopagnosia
diagnosis
Anatomy
available
Reference
Case 1 Present Present Yes Adachi-Usami et al. (1995)
Case 1 Present Unknown No Albert et al. (1975)
Case 1 Unknown Present No Aptman et al. (1977)
Madame D Present Present Yes Bartolomeo et al. (1997)
KG Present Absent Yes Beauchamp et al. (2000)
Case 1 Present Present Yes Brazis et al. (1981)
Mr W Present Present Yes Bruyer et al. (1983)
WM Present Present Yes Cavanagh et al. (1998)
JPC Present Present No Cavanagh et al. (1998)
JPN Present Present No Cavanagh et al. (1998)
Case 1 Present Present Yes Clarke et al. (1997)
Case 2 Absent Present No Clarke et al. (1997)
LM Present Present No Cowey and Vaina (2000)
CM Present Absent Yes Damasio et al. (1980)
EH Present Absent Yes Damasio et al. (1980)
Case 1 Present Present Yes Damasio et al. (1 982)
Case 2 Present Present Yes Damasio et al. (1 982)
Case 3 Unknown Present Yes Damasio et al. (1982)
Case 1 Unknown Present Yes De Renzi (1986)
Case 2 Unknown Present Yes De Renzi (1986)
PA Unknown Present Yes De Renzi et al. (1994)
OR Absent Present Yes De Renzi et al. (1994)
LM Unknown Present Yes De Renzi et al. (1994)
Anna Unknown Present Yes De Renzi and di Pellegrino (1998)
CF Present Present Yes Dumont et al. (1981)
Case 1 Present Absent Yes Duvelleroy-Hommet et al. (1997)
Case 1 Present Present Yes Ettlin et al. (1992)
VH Unknown Present No Evans et al. (1995)
Case 1 Present Present No Freedman and Costa (1992)
CO Absent Present No Gainotti et al. (2003)
AR Present Absent Yes Gallant et al. (2000)
Case 1 Present Present No Goldenberg et al. (1985)
Case 1 Present Present Yes Gomori and Hawryluk (1984)
Case 1 Present Unknown Yes Green and Lessell (1977)
Case 2 Present Present No Green and Lessell (1977)
Case 3 Present Present No Green and Lessell (1977)
Case 4 Present Present No Green and Lessell (1977)
Case 5 Present Absent No Green and Lessell (1977)
Case 1 Absent Present Yes Habib (1986)
Case 1 Present Present No Hoksbergen et al. (1996)
Case 1 Present Unknown No Jaeger et al. (1989)
Case 1 Absent Present Yes Kawahata and Nagata (1989)
Case 1 Present Present No Kay and Levin (1982)
Case 2 Present Present No Kay and Levin (1982)
Case 3 Present Present No Kay and Levin (1982)
BL Present Present No Kennard et al. (1995)
Case 1 Present Absent Yes Kolmel (1988)
Case 2 Present Absent Yes Kolmel (1988)
Case 1 Unknown Present No Kubo et al. (1978)
Case 1 Unknown Present Yes Landis et al. (1986)
Case 2 Unknown Present Yes Landis et al. (1986)
Case 3 Present Present Yes Landis et al. (1986)
Case 4 Absent Present No Landis et al. (1986)
continued
188 Achromatopsia Meta-analysis dBouvier and Engel

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