Psychiatry Research: Philip Brittain, Dominic H. Ffytche, Allison Mckendrick, Simon Surguladze
Psychiatry Research: Philip Brittain, Dominic H. Ffytche, Allison Mckendrick, Simon Surguladze
Psychiatry Research: Philip Brittain, Dominic H. Ffytche, Allison Mckendrick, Simon Surguladze
Psychiatry Research
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p s yc h r e s
Affective Neuroscience Group, Section of Cognitive Neuropsychiatry, King's College London, Institute of Psychiatry, 16 De Crespigny Park, London SE5 8AF, UK
Section of Old Age Psychiatry and Centre for Neuroimaging Sciences, King's College London, Institute of Psychiatry, 16 De Crespigny Park, London SE5 8AF, UK
Department of Optometry & Vision Sciences, The University of Melbourne, Parkville, 3010, Australia
a r t i c l e
i n f o
Article history:
Received 16 July 2009
Received in revised form 8 September 2009
Accepted 22 September 2009
Keywords:
Contrast sensitivity
Visual masking
Global motion
Biological motion
Social perception
Functional status
a b s t r a c t
Visual processing decits are well recognised in schizophrenia and have potentially important clinical
implications. First, the pattern of decits for different visual tasks may help understand the underlying
pathophysiology of the visual dysfunction. Second, several studies report decits correlating with functional
outcomes, suggesting that outcome improvement is possible through visual remediation strategies. We
investigated these issues in a group of 64 schizophrenia patients and matched controls with a battery of
visual tasks targeting different points along the visual pathways and by examining direct and indirect
relationships (via a potential mediator) of such decits to functional outcome. The schizophrenia group was
signicantly worse on the visual tasks overall, with the decit constant for low- and high-level processing.
Zero-order correlations suggested minimal association between vision and outcome, however, correlations
between three visual tasks and social perceptual ability were found which in turn correlated with functional
outcome; path analysis conrmed a signicant but small and indirect effect of biological motion processing
ability on functional outcome mediated by social perception. In conclusion, the pathophysiology of visual
dysfunction affects low- and high-level visual areas similarly and the relationship between decits and
outcome is small and indirect.
2009 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
A large body of research indicates that individuals with schizophrenia experience visual decits (see Butler et al., 2005). The decits
are found in relation to a variety of tasks, particularly those related to
the magnocellular/dorsal stream, a pathway from retina to visual
cortex and beyond linked to visual motion processing and conveying
signals related to low-spatial frequencies (large scale visual detail),
low contrast, and high temporal frequencies. The parvocellular/ventral system, which conveys color and high spatial frequency information, appears relatively spared. The decits are of potential clinical
interest as they may provide clues as to the underlying pathophysiology of the visual dysfunction; different visual perceptual abilities
are resolved at varying points along the visual pathways so that the
overall pattern of decits may point to particular cortical locations
and processes. Most previous studies have focussed on low-level
processing, i.e., those resolved early-on in the visual pathways,
although higher-level visual decits have also been reported,
revealing problems in cortical-level visual processing. Thus, decits
have been found for abilities such as luminance-icker sensitivity
(Slaghuis and Bishop, 2001) static contrast sensitivity (Keri et al.,
2002) and visual masking (Rassovsky et al., 2005) that involve early,
271
85 Hz). The CS task was run from a Mac Tower. The GM and BM tasks were run from a
Centrex PC through a VSG 2/5 graphics card. The MASK and HP tasks were run from a
Dell laptop. Subjects gave their responses by speaking aloud and the test administrator
entered responses on the computer. All tasks were viewed binocularly and were
presented in a random order with the exception of the contrast sensitivity task which
was performed during an initial visual acuity screening session. Viewing distance for
the MASK, GM, BM and HP tasks was 100 cm, and for the visual tasks was kept constant
with a chin rest. The CS task viewing distance was 200 cm and no chin rest was used. All
tasks were forced choice procedures and were preceded by a practise period.
2.2.1. Visual tasks
We focussed on tasks with sensitivity to magnocellular/dorsal stream function,
given the previous evidence of this channels dysfunction in schizophrenia (Butler and
Javitt, 2005). Each section below initially details the aspect of the magnocellular/dorsal
stream targeted by the visual task. Tests of low-level visual processing included contrast detection and visual masking. Intermediate-level visual processing was examined
using a test of global motion perception. The highest level of visual processing was
assessed using a test of biological motion perception.
2.2.1.1. Contrast sensitivity (CS). Magnocellular neurons have lower contrast thresholds
(Livingstone and Hubel, 1988) and preferentially activate to low-spatial frequency
stimuli below about 1.5 cycles/ (Legge, 1978). The Freiburg Contrast Test version 5.6.1
(Bach, 2007) was used to assess contrast detection thresholds. A Landolt C optotype is
used where the gap of the C can have one of four orientations (Fig. 1). Subjects were
required to name the orientation (up, down, left, right). The gure subtended 5.7 of
visual angle and the gap had an equivalent spatial frequency of 0.5 cycles/. Threshold is
estimated with a Best PEST (parameter estimation by sequential testing) algorithm
and an adaptive-staircase procedure. The contrast sensitivity result is the logarithmized inverse of the threshold contrast, dened with the Michelson contrast (Lmax
Lmin)/(Lmax + Lmin). There were 28 trials. Higher values indicated better sensitivity
to contrast.
2.2.1.2. Visual masking (MASK). Magnocellular neurons are sensitive to transient stimuli
(Breitmeyer and Julesz, 1975) and have short latencies (Breitmeyer, 1975). Furthermore, the location masking task used here is thought to further increase magnocellular
involvement (Cadenhead et al., 1998). The masking procedures and stimuli (Fig. 2)
were those used by Green et al. (2002). The target was a square with a small gap in one
of its sides (the gap was irrelevant for the version of the task used here). The square
could appear in any one of four locations on the screen (upper left, upper right, lower
left, lower right). For each trial, the subjects were asked to state the location of the
target. Each target subtended 0.27 of visual angle and was located 1.03 of visual angle
from the xation cross, which was presented 400 ms before each target presentation
for 300 ms. The target's contrast was set for each subject with a thresholding procedure.
This produces a grey scale value called the critical stimulus intensity at which all
subjects can see the unmasked target on approximately 84% of trials. The mask
consisted of a 4 4 array of adjacent boxes (a 2 2 array in each quadrant) that
appeared together in the same spatial locations as the target could appear, i.e., target
and mask were superimposed in one of the quadrants. The duration of the target was
12.5 ms and the duration of the mask was 25 ms. The stimulus onset asynchrony
(SOA) is the time between the onset of the stimulus and the onset of the mask. Twelve
SOAs ranging from 75 (forward masking) to 75 ms (backward masking) were
presented in randomized fashion, 12 trials were presented for each SOA and the four
possible locations of the target were counterbalanced (an SOA of 0 where mask and
target are displayed simultaneously was also presented but was not used in the
analysis). Percentage correct rates for each of the six backward and six forward making
SOAs were averaged and used as the masking performance score, as analysis revealed
there was no differential performance between groups on the forward versus backward
trials. Higher values indicated better performance. A no-mask condition was randomly
interspersed within the masking trials and the observed equal performance between
groups suggested that attentional problems in the patient group would not account for
any decit on this task.
2.2.1.3. Global motion (GM). Global motion is determined in cortical area V5/MT
(Newsome and Par, 1988), a dorsal stream area (Ungerleider and Haxby, 1994). The
stimulus was a 10 of visual angle circular area containing 100 moving dots. Each dot
was 8.5 min arc in diameter. A percentage of the dots moved upwards or downwards
(signal dots) at 2.86/s, whilst the remaining dots (noise dots) moved in random
272
Fig. 2. Illustration of the visual masking task with xation cross in the centre. Three
different screen shots are shown from left to right. The target (far left) is a square with
a small gap in one of the sides. The mask (middle) is four composite squares made of
four smaller squares. The two appear separately, although so close together in time that
the presence of the mask disrupts the perception of the target, usually resulting in a
fused image (far right).
directions (Fig. 3). For each trial, the direction of the signal dots (up or down) was
chosen at random. The duration of each trial was 400 ms. Subjects were required to
name the direction of the signal dots. The ratio of signal dots began at 100% and used a
3-down, 1-up staircase procedure which terminated after four reversals. Two staircases
were interleaved and ran simultaneously. Correct identication by the subject resulted
in the signal strength being degraded by replacing signal dots with noise dots. An
incorrect response increased the number of signal dots. Different dots are chosen to be
signal or noise on each frame in order to limit the availability of local motion cues.
Hence, the observer needs to integrate the motion cues across the movie sequence to
determine the signal direction of motion and cannot determine it by tracking individual
dots. The initial step-size was 8% which halved after the rst two reversals. The mean
percentage of signal dots at the last four reversals (two from each staircase) was taken
as the global motion perception threshold. This was transformed into a sensitivity
measure with the formula: 1/threshold, so that like the other visual tasks, higher values
indicated better performance.
2.2.1.4. Biological motion (BM). Biological motion perception is dependent on downstream areas of the dorsal stream, but may also be subserved by ventral stream
components (Vaina et al., 2001). An array of randomly moving dots appeared within a
10 of visual angle square area. Each dot was 6.8 min arc in diameter. The initial number
of dots was 50. Each presentation lasted 3500 ms. After 2000 ms, 12 signal dots moved
in such a way as to represent a human body (Fig. 4) walking, either to the left or to the
right. The gure moved at a velocity of 4.5/s. A 1-down, 1-up staircase procedure was
used and continued for 42 trials. The design was a three-alternative procedure whereby
the subject responded that the gure moved to the left, to the right, or that the subject
had not seen the gure. If the subject responded correctly, the number of randomly
moving noise dots in the next trial increased by 20, reducing to 10 after the rst
reversal. If the response was incorrect or didn't see the number of noise dots in the
next trial decreased by 10. There was no signicant difference in the number of didn't
see responses in the patient and control groups (P > 0.05). The mean number of dots in
trials 3242 was used as the biological motion perception threshold. Pilot work
indicated that this was a sufcient number of trials to reach a performance plateau.
Higher values indicated better biological motion perception.
2.2.2. Social cognitionsocial perception (HP)
The Half-Prole of Nonverbal Sensitivity (Ambady et al., 1995), which consists of
the rst 110 scenes of the Prole of Nonverbal Sensitivity (Rosenthal et al., 1979) was
used to assess social perception, a type of social cognition (Green et al., 2005a). The
Half-PONS consists of a series of 2-s video clips containing the facial expressions, voice
intonations and/or bodily gestures of a Caucasian female acting a variety of social
situations. Each scene contains either one, two or three of these social cues. Before each
clip the subject was presented with a card detailing two possible answers (e.g.,
ordering food in a restaurant or threatening someone), one of which was correct.
Immediately afterwards the subject was required to choose which description best
described the presented clip. Higher scores indicated better social perception.
Fig. 3. Schematic illustration of the global motion dot stimuli. Dots (shown as arrows
indicating their direction of movement) either move in a common direction (signal
direction down or up, down in this example) or move randomly. Three different levels
of signal-to-noise ratio are shown here; 100% coherence (left), 75% coherence (middle),
50% coherence (right).
Fig. 4. Schematic illustration of a point-light walker. Lines joining dots are for
illustration only. When the gure dots move the percept of a human walking is
apparent. Increasing numbers of moving distracter dots (middle and right) eventually
make the human gure imperceptible.
Table 1
Mean and standard deviation subject characteristics for the patient and control groups.
Age
Gender
Education in years
Visual acuitya
WASI IQ scoreb
Handedness (L/R/Ambi)
PANSSc Positive
PANSS Negative
CPZ equivalentd
Illness duration in years
Role Functioning Scale subscales and total
Working productivity
Independent living, self care
Immediate social network relationships
Extended social network relationships
Global functioning index (GFI)
a
Patient group
(N = 64)
Control group
(N = 65)
41.89 (11.05)
M = 34
14.20 (3.18)
1.31 (0.22)
101.91 (15.24)
(0/60/4)
13.52 (4.51)
14.36 (5.26)
461.95 (381.61)
18.41 (10.79)
41.29 (9.57)
M = 35
14.90 (3.14)
1.33 (0.22)
107.37 (13.49)
(0/62/3)
3.14 (1.76)
4.8 (1.95)
5.11 (1.24)
4.66 (1.36)
17.70 (5.18)
273
Table 2
Data from the four visual tasks (CS, MASK, GM, BM; putatively ordered from low-level to high-level visual processing) and the social perception task, the half-PONS (HP).
Task
P values
2.24
53.32
0.068
211.95
84.57
2.20
48.04
0.059
186.25
79.74
0.31
0.37
0.32
0.41
0.97
0.086
0.048
0.076
0.020
<0.000
(0.13)
(14.27)
(0.029)
(62.98)
(4.68)
(0.14)
(15.78)
(0.028)
(60.56)
(7.55)
(1.10)
(1.11)
(0.97)
(0.96)
(1.42)
Mean and standard deviation raw scores for the control group and patient group. z-scores are for the patient group only. A negative z-score of 1 indicates a decrease in performance
of one standard deviation of the mean control group scores on that task. P-values are equivalent for raw scores and z-scores.
3. Results
Subject characteristics and the functional outcome measurements
are reported in Table 1. The patient group had a signicantly lower
mean IQ than the control group.
3.1. Task differences between groups
The mean raw scores for each task are presented in Table 2
together with the z-transformed data. The schizophrenia group performed worse on the visual tasks but impairments were greatest on
the social perception task.
To further examine the visual decits in schizophrenia we performed
a mixed model ANOVA with a two-level between group factor (patient
or control) and a four-level within group factor (visual task; CS, MASK,
GM, BM). The main between-group was signicant (F (1,127) = 11.239,
P = 0.001, partial eta2 = 0.081), indicating an overall worse performance by the patient group on the visual tasks. This difference remained
signicant after co-varying for IQ. The task by group interaction was not
signicant, suggesting the decit did not vary across the visual hierarchy
(GreenhouseGeisser corrected F (3,381) = 0.071, P = 0.968, partial
eta2 = 0.001); the interaction effect being equivalent to the main
within-subjects effect of task type due to the control z-scores being
based on their own means and standard deviations. We then compared
the patients z-scores on the CS task and the BM task (the tasks
producing the least and the greatest decit) using a paired t-test. This
was not signicant (t = 0.476, df = 63, P = 0.636) indicating that,
although the z-scores and post hoc t-tests (Table 2) suggest a greater
decit at the highest compared to the lowest levels of the visual system,
the increase in decit is not statistically signicant. These results suggest
the visual decit in schizophrenia is constant across the visual
processing hierarchy for the tests used here.
3.2. Visual performance, social perception and functional outcome
Table 3 shows the zero-order correlation matrix for the visual
tasks, social perception and functional outcome measures in the
Table 3
Pearson correlation coefcients between visual tasks, social perception and functional outcome measures for the schizophrenia group P < 0.05, P < 0.01.
Visual tasks
1. Contrast sensitivity (CS)
2. Masking (MASK)
3. Global motion (GM)
4. Biological motion (BM)
Social perception
5. Half-PONS (HP)
Role Functioning Scale (RFS)
6. Working productivity
7. Independent living, self care
8. Immediate social relationships
9. Extended social relationships
10. Global functioning index (GFI)
0.09
0.08
0.21
0.32
0.42
0.47
0.10
0.36
0.36
0.08
0.09
0.24
0.04
0.11
0.11
0.11
0.36
0.11
0.19
0.06
0.01
0.04
0.07
0.05
0.20
0.31
0.32
0.32
0.34
0.58
0.49
0.52
0.81
0.54
0.61
0.86
0.62
0.77
0.82
0.44
0.12
0.13
0.03
0.02
0.09
274
Fig. 5. Path model showing signicant direct (solid lines) and indirect (dashed lines)
paths between visual processing, social perception and functional status in schizophrenia. Standardised path coefcients (beta) are noted above each path. The
coefcient for the indirect path refers to both segments, i.e., visionsocial perception
and social perception to function. P < 0.05, P < 0.01.
visual areas with the faulty signal propagating from one level of the
visual hierarchy to the next, a slight but non-signicant accumulation or amplication occurring between the lowest and highest
levels. In fact, performance was worse on the masking task than on
the global motion task even though the former is most often
described as being an early-visual task (Sergi and Green, 2003)
whereas the latter is thought to be resolved cortically in area V5/MT
(Newsome and Par, 1988). However, recent neuroimaging data
(Green et al., 2005b) suggests that masking may recruit subcortical
thalamic regions and several down-stream cortical visual areas
including the lateral occipital area. As such, masking may recruit a
broader array of processing capacities and be more sensitive to any
underlying decit.
Regarding the relationship between the visual processing measures and the functional outcome measure, the strength of the zeroorder correlations was weak in this patient group. With the exception
of 1 association from 20, they did not replicate the levels of correlation
seen in some earlier studies (Butler et al., 2005; Kim et al., 2005). A
subsequent path analysis revealed that the ability of patients on one of
the visual tasks, biological motion perception, had a signicant and
positive but indirect effect, via social perceptual ability, on a
functional outcome composite measure (better visual performance
associated with better functional outcome).
Our study design allowed us to consider two possible mechanisms
which might underlie the differences found in previous studies
reporting zero-order visual processing and functional outcome
associations. The rst of these was the impact of the visual processing
level studied. The zero-order correlations between vision and
outcome here, whilst mostly non-signicant, did not suggest an
increase in the strength of association for higher- compared to lowerlevels of the visual hierarchy. However, the path analysis suggests that
an increase in association strength for higher levels of the hierarchy
might be found within the indirect pathway. The fact that the highlevel BM task was retained in the path model, whilst the lower-level
MASK and GM tasks were removed, suggests that any signicant
indirect path from vision to outcome runs from the highest level of
visual processing. Also, when the model was re-run with only either
the MASK or GM tasks, indirect path beta weights were 0.13
compared to 0.16 for the BM task. Effectively, the MASK and GM
tasks add no increased predictive ability over the BM task. This was
also reected in the greater association between the BM and HP tasks
than between the CS and HP tasks. For indirect paths, it appears the
level of processing may inuence the strength of association between
vision and outcome and it is possible that this effect contributes to the
variation in reported zero-order correlations found in previous
studies.
The second mechanism was the role of a potential mediating
variable; social cognition. In our study this was assessed with a social
perception task. We postulated that some high-level visual tasks,
such as the biological motion task used by Kim et al. (2005), may tap
in to social cognitive processes and thus inate the apparent
association between vision and functional outcome through the
association between social cognition and the latter. Our study
supports this. The Kim et al. (2005) study, which found a very strong
association between vision and function (r = 0.71), used a biological
motion task which involved potentially socially relevant motor acts
such as kicking, throwing and climbing. Our version of this task
involved just a walking gure. The indirect path revealed in our
analysis suggests that biological motion perception is signicantly
associated with functional outcome via social cognition but that the
zero-order correlation between a more pure measure of biological
motion perception and outcome is non-signicant. These facts suggest
that future studies investigating these associations should ensure any
biological motion measures have as little socially relevant content as
possible to avoid the association with outcome conating with social
cognitive processes.
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