Teufel
Teufel
Teufel
Edited by Thomas D. Albright, The Salk Institute for Biological Studies, La Jolla, CA, and approved May 28, 2015 (received for review February 26, 2015)
Many neuropsychiatric illnesses are associated with psychosis, i.e., Psychosis—a loss of contact with external reality—is charac-
hallucinations (perceptions in the absence of causative stimuli) and terized by delusions (irrational, often bizarre beliefs) and hal-
delusions (irrational, often bizarre beliefs). Current models of brain lucinations (perceptions in the absence of causative stimuli).
function view perception as a combination of two distinct sources Conceptual and computational models of psychosis have hy-
of information: bottom-up sensory input and top-down influences pothesized that an imbalance in the combination of bottom-up
from prior knowledge. This framework may explain hallucinations sensory evidence and top-down prior knowledge is at the core of
this altered state of mind (8–12). According to such models, at
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and delusions. Here, we characterized the balance between visual
bottom-up and top-down processing in people with early psychosis
the perceptual level, an undue reliance on prior knowledge in
perception may lead to the emergence of aberrant perceptions
(study 1) and in psychosis-prone, healthy individuals (study 2) to
such as hallucinations. The current study tests this hypothesis in
elucidate the mechanisms that might contribute to the emergence of the visual domain by characterizing the impact of prior knowl-
psychotic experiences. Through a specialized mental-health service, edge on the perception of ambiguous stimuli in two groups of
we identified unmedicated individuals who experience early psy- people: a clinical group with early psychotic experiences (study
chotic symptoms but fall below the threshold for a categorical diagnosis. 1) and healthy volunteers showing differing levels of proneness
We observed that, in early psychosis, there was a shift in information to such experiences (study 2). Although the conventional view
processing favoring prior knowledge over incoming sensory evidence. focuses preferentially on auditory hallucinations in psychosis,
In the complementary study, we capitalized on subtle variations in epidemiological evidence indicates that hallucinations in the vi-
perception and belief in the general population that exhibit graded sual domain are very common in, for example, schizophrenia
similarity with psychotic experiences (schizotypy). We observed (13). In fact, vision seems to play a prominent role in the de-
that the degree of psychosis proneness in healthy individuals, and, velopment of psychosis given that basic visual symptoms identi-
specifically, the presence of subtle perceptual alterations, is also fied before illness onset are one of the most powerful predictors
associated with stronger reliance on prior knowledge. Although, in of the emergence of later psychotic disorders (14).
the current experimental studies, this shift conferred a performance To determine mechanisms for the emergence of perceptual psy-
benefit, under most natural viewing situations, it may provoke chotic symptoms as purely as possible, we conducted two comple-
anomalous perceptual experiences. Overall, we show that early mentary studies. First, using a case-control study design, we
psychosis and psychosis proneness both entail a basic shift in visual
characterized the balance between visual bottom-up and top-down
information processing, favoring prior knowledge over incoming
sensory evidence. The studies provide complementary insights to a Significance
mechanism by which psychotic symptoms may emerge.
Perceiving things that are not there and holding unfounded,
visual perception | psychosis | top-down processing | predictive coding | bizarre beliefs (hallucinations and delusions, respectively) are
schizophrenia psychotic symptoms that occur in particular syndromes including
affective psychoses, paranoid states, and schizophrenia. We
studied the emergence of this loss of contact with reality based
T o interact successfully with our physical and social environ-
ment, we need appropriate information about relevant states
of the world, such as the size, location, or distance of an object.
on current models of normal brain function. Working with
clinical individuals experiencing early psychosis and nonclinical
individuals with high levels of psychosis proneness, we show
However, there is no direct access to this information, only to
that their visual perception is characterized by a shift that favors
sensory stimulation caused by the environment. This sensory in-
prior knowledge over incoming sensory evidence. Given that
formation is inherently ambiguous and, on its own, rarely suffices
these alterations in information processing are evident early on
to uniquely specify our surroundings (1). The human visual system
in psychosis and even in association with subtle perceptual
overcomes this challenge by combining ambiguous sensory in-
changes indicating psychosis proneness, they may be important
formation with prior knowledge of the environment to generate a
factors contributing to the emergence of severe mental illnesses.
robust and unambiguous representation of the world around us (1–
7). This insight has been formalized under the tenets of Bayesian Author contributions: C.T. conceived of the study; C.T. and P.C.F. designed research; C.T.,
decision theory and is typically modeled within a predictive coding N.S., V.D., J.F., and P.R.M. performed research; C.T. and P.C.F. analyzed data; C.T., N.S., V.D.,
framework. Here, the notion is that expectations based on prior J.P., J.F., I.M.G., and P.C.F. wrote the paper; and J.P. and I.M.G. managed patient pool.
knowledge are fed back from higher to lower levels of information The authors declare no conflict of interest.
processing, thereby shaping the way incoming signals are treated This article is a PNAS Direct Submission.
by lower-level mechanisms. This influence is labeled top-down Freely available online through the PNAS open access option.
processing. The present study tests the hypothesis that psychotic 1
To whom correspondence should be addressed. Email: teufelc@cardiff.ac.uk.
experiences arise from an increased use of prior knowledge in This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.
constructing meaningful percepts from ambiguous sensory inputs. 1073/pnas.1503916112/-/DCSupplemental.
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the Cardiff Anomalous Perception Scale (CAPS) (16) and the
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experimental design thus provides an ideal index of the impact
of knowledge on perception. This notion is supported by pre- Peters Delusion Inventory (PDI) (17). Note that, although other
vious psychophysical and neuroimaging literature, which indi- schizotypy scales such as Oxford-Liverpool Inventory of Feel-
cates that disambiguation of two-tone images is due to top-down ings and Experiences (O-LIFE) (27) and Schizotypal Personality
influences from high-level processes onto low-level visual func- Questionnaire (SPQ) (28) characterize a number of schizotypal
tion (3, 23–26). In particular, two-tone image perception recruits features, CAPS and PDI are specific to clinical features relating
memory processes and object knowledge associated with cortical to hallucinations and delusions respectively. In study 2, we thus
areas such as precuneus and dorsolateral prefrontal cortex; these recruited a larger sample of individuals from the general population
processes activate stored, high-level visual representations of the and related their tendency to rely on prior knowledge in visual
template images and feed back information to lower-level areas perception to their schizotypy scores. The task was identical to that
to shape perceptual processing, even as early as the primary visual used in the previous experiment except for two aspects: Given that
cortex V1. study 2 involved healthy observers only, we extended testing to 16
In study 1, observers performed a yes/no discrimination task, rather than 12 sessions to obtain a more precise estimate of every
in which they viewed briefly presented two-tone images of people observer’s d′; second, an improved stimulus set was used that con-
and similar-looking control images without an embedded object tained two image categories (people and animals) rather than one
(Fig. 1A). Within each session, these images were presented (people) as in study 1.
before and after the observer received prior knowledge by The results of study 2 are plotted in Fig. 3A. As expected, prior
viewing template images (Figs. 1B and 2). On every trial ob- knowledge resulted in a significant improvement in the ability to
servers were required to indicate whether a given image con- distinguish between test and control images (Fig. 3A left plot; paired
tained a person or not (Fig. 1C and SI Materials and Methods). t test, df = 39, t = 7.08, P < 0.001). Similar to the previous experi-
Based on signal detection theory, we derived two measures from ment, we also observed a criterion shift (Fig. 3A, Right; paired t test,
the observers’ performance: (i) d′, a pure index of an observer’s df = 39, t = 4.11, P < 0.001). Due to the differences in experimental
perceptual mechanisms independent of response bias; and (ii) design, we cannot directly compare performance across experiments.
criterion, which captures the general bias of observers to report Nevertheless, as expected, it is evident that inclusion of a second
the presence of an object. As an objective performance measure image category in study 2 made the task more difficult, explaining
of the influence of knowledge on perception, we were primarily the performance differences between the two experiments in healthy
interested in the change in d′ after having been exposed to rel- observers. Importantly and in line with the results of study 1, Fig. 3B
evant image information. indicates that the performance benefit due to prior knowledge was
The results support our hypothesis (Fig. 1D). As expected, a related to both the extent to which an observer experienced
mixed 2 × 2 ANOVA with the between-subjects factor group and anomalous perceptual phenomena similar to those of psychotic
the within-subjects factor block found an overall increased ability
patients as measured by CAPS (Fig. 3B, Left; product-moment,
to distinguish between test and control images measured in terms
r = 0.42, df = 38, t = 2.98, P < 0.01) and the extent to which they
of d′ after having viewed template images in comparison with
before having seen them [F(1,32) = 29.27, P < 0.001]. Critically, showed a delusion-like style of thinking as measured by PDI
this main effect was qualified by an interaction between group (Fig. 3B, Right; r = 0.33, df = 38, t = 2.14, P < 0.05). As was
and block, indicating that the improvement in performance dif- expected, however, the schizotypy scales for perception and belief
fered between the groups [F(1,32) = 5.02, P < 0.05]. As can be were positively correlated (r = 0.40, df = 38, t = 2.67, P < 0.05),
seen in the left plot in Fig. 1D and supported by post hoc tests, and we therefore conducted a first-order partial correlation
both groups showed an improvement in performance (paired analyses to determine the amount of variability in performance
t test, controls: df = 15, t = 2.17, P < 0.05; clinical group: df = 17, that can be explained by schizotypal features related to perception
t = 5.60, P < 0.001), but this was on average more than twice as or belief alone. This analysis indicated a very specific effect. The
large in the clinical group (mean ± SE: 0.35 ± 0.06) compared relation between a delusion-like style of thinking and performance
with controls (0.14 ± 0.07). It is noteworthy that the increased benefit due to prior knowledge disappeared once an observer’s
benefit in the clinical group was observed in the absence of an anomalous perceptual experiences were taken into account (first-
overall difference between groups [F(1,32) < 1, not significant] order partial correlation, r = 0.19, df = 37, t = 1.17, not signifi-
and was not due to a difference in baseline performance in the cant). By contrast, a significant relation between CAPS and
Before block (Welch’s two-sample t test, before clinical vs. be- performance benefit remained even when PDI was controlled for
fore controls: df = 31.16, t = 0.19, not significant). (r = 0.35, df = 37, t = 2.28, P < 0.05).
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and down the hierarchy and affects the whole system (8, 30), a system, rather than by influences on visual function from higher-
notion that might ultimately account for atypicalities in both lower- level knowledge areas outside the visual system. Our findings are
level perceptual processing and higher-level belief formation in se- therefore not at odds with decreased susceptibility to some visual
vere mental illnesses and psychosis proneness (30). illusions in schizophrenic patients (37, 38, 40, 41). In fact, we argue
As previously discussed, our aim in conducting these studies was that our findings dovetail with and complement these previous re-
specifically to try to understand the processes that contribute to sults in a surprising way: independently of the underlying mecha-
the emergence of psychotic symptoms rather than to examine a nisms, atypicalities within the visual system result in the outputs of
particular categorical diagnosis within which psychosis may occur. the perceptual analysis being less well structured and less adaptive.
This approach is part of a more general move in translational This could lead to an increased reliance on sources of information
research aimed at developing our understanding of the mecha- from outside the visual system to structure visual percepts and
nisms by which symptoms arise (22); this is seen as a necessary might make psychotic patients “hungry” for prior object knowledge.
prelude to a successful classificatory system in psychiatry. We do It is this latter effect that was demonstrated in the current study.
not advocate that we can do without diagnostic systems in psy- We should add that an explanation of these findings in terms
chiatry but rather selected our approach to fit the specific question of better memory for the information provided by the templates
we aimed to address. Ultimately, it will be extremely interesting to is implausible in both studies. Existing evidence suggests that
determine whether the shift in the bottom-up/top-down balance both early psychosis and high schizotypal characteristics may be
identified here is a transdiagnostic effect, occurring generally in associated with poorer working memory (44, 45).
early psychosis and psychosis proneness, or whether it is specific to Although performance improvements due to prior knowledge
a particular diagnostic category such as schizophrenia. This future were increased in the clinical group in study 1, these individuals
work will be important and we suggest that having identified such were no worse (than controls) in their ability to discriminate am-
a cognitive biomarker will prove very useful in examining, and biguous two-tone images without prior knowledge. This finding is
validating or challenging existing taxonomies of mental illness. not directly relevant to the main question addressed in this study
Computational explanations of the balance between sensory but it is interesting because it contrasts with previous studies in
evidence and prior knowledge as highlighted by our study are patients with established schizophrenia who show reduced ability
typically cast in terms of Bayesian models of perception and for- to spontaneously disambiguate two-tone images of faces without
malized within a predictive coding framework (5, 31, 32). In this prior knowledge (46, 47). This previous effect is most likely related
setting, the integration of bottom-up and top-down signals is me- to well-established schizophrenic deficits in early and midlevel vi-
diated by the relative amount of information each of these com- sion that affect perceptual organization, context processing and
ponents provides: the stronger the sensory evidence is relative to integration (37, 38, 48–53) rather than to top-down influences from
prior knowledge, the more it will impact on the final processing high-level visual cognition as in the current study. We did not di-
output; conversely, if prior knowledge provides a relatively greater rectly probe early and midlevel visual function in our participants,
amount of information it will be weighted more strongly. Our but it seems most likely that the absence of impairments in spon-
findings fit comfortably with such a computational account: a taneous disambiguation of two-tone images in the clinical group
stronger reliance on top-down processing in psychosis-prone in- might be due to the specific nature of our stimulus material, which
dividuals as identified in both of our experiments suggests that was extensively piloted to be difficult to disambiguate without prior
prior knowledge provides a large amount of information relative to knowledge (for details, see SI Materials and Methods).
the amount of sensory evidence. Importantly, this could either be To conclude, if we are to make progress in understanding the
due to atypically strong knowledge representations or, alterna- nature of psychotic experiences and how they relate to cognitive
tively, to an unusually noisy sensory system. Given well-established and neural markers, we have to identify candidate mechanisms for
psychotic deficits in early visual processing as discussed below, the how they may arise based on a growing understanding of the
latter explanation might be more likely. However, the findings relevant perceptual and cognitive systems. Here, we identified a
cannot distinguish between these hypotheses. In this context, it is shift in visual information-processing in early psychosis and in
interesting to note that the same theme of an imbalance between psychosis-prone healthy individuals. In both cases, top-down prior
bottom-up and top-down processing figures prominently in current knowledge was favored over bottom-up sensory evidence. These
debates about autism (33, 34). This similarity highlights the notion alterations directly relate to visual function in healthy individuals
that predictive coding might provide a common framework within and our findings support the notion of a continuum between
which to understand mental illness more generally. An important normality and psychotic experiences. The changes in information
task for the future will be to explain the specificities of the different processing we report here might be among the influences that, in
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