International Journal of Psychophysiology 83 (2012) 240–247

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International Journal of Psychophysiology

journal homepage: www.elsevier.com/locate/ijpsycho

Review

A challenging, unpredictable world for people with Autism Spectrum Disorder

Marie Gomot a,⁎, Bruno Wicker b
a
UMR-S ‘Imaging and Brain’, INSERM U930, CNRS ERL3106, Université François-Rabelais de Tours, France
b
Institut de Neurosciences Cognitives de la Méditerranée, CNRS UMR 6193, Aix-Marseille University, Marseille, France

a r t i c l e i n f o a b s t r a c t

Article history: Autism is a pervasive neurodevelopmental disorder characterized by impairment of communication and social
Received 6 May 2011 interaction, as well as by high levels of repetitive and ritualistic behaviours. This last dimension results in
Received in revised form 12 September 2011 major difficulties in daily life: clinical reports of individuals with Autism Spectrum Disorder (ASD) show that
Accepted 16 September 2011
they present tantrums as a response to change, or restricted interests and repetitive behaviours in order to pre-
Available online 1 October 2011
vent or minimize change. Such a crucial need to maintain sameness suggests substantial differences in how the
Keywords:
ASD brain predicts the environment, and this might have a fundamental role in the deficit revealed in the highly
Autism Spectrum Disorder (ASD) unpredictable social world. Several lines of evidence indicating difficulties in generating or using predictions in
ERPs ASD due to atypical information processing will be presented in this review. For instance, several studies have
fMRI revealed that people with ASD demonstrate a unique profile of cognitive abilities, with strategies that depend
Mismatch negativity to an abnormally large extent on sensory systems, at the expense of more integrative processing requiring an
P3 awareness of contextual subtleties necessary for prediction. At a more elementary level, patients with autism
Context manifest unusual processing of unpredictable events, which might be rooted in a basic difference in how the
Prediction
brain orients to changing, novel sensory stimuli. This review presents results from ERPs and fMRI studies illus-
trating the psychophysiological mechanisms and neural bases underlying such phenomena in ASD. We propose
that such dysfunction in the ability to build flexible prediction in ASD may originate from impaired top–down
influence over a variety of sensory and higher level information processing, a physiopathological hypothesis
which dovetails with the cortical under connectivity current theory.
© 2011 Elsevier B.V. All rights reserved.

1. Introduction recognition using fMRI (Bar, 2004; Bar et al., 2006). The findings have
revealed that low-level visual perception in occipito-temporal areas is
Interacting with the environment is a particularly demanding activ- not the result of pure bottom–up processes but is guided by information
ity. The brain has quickly and simultaneously to process very complex from high-level cognitive frontal areas. In this regard predictions are in-
multi-sensory information. This seems to require attentional prepara- timately associated to attentional processes as they enable the brain to
tion in order to ignore irrelevant information and privilege the proces- allocate its resources of information processing to selected sensory in-
sing of the most relevant information for appropriate adaptation of puts for reducing its computational load. Although the ‘proactive
future behaviour. Part of the adaptation thus consists of generating brain’ model has been developed in the domain of visual recognition,
mental simulations or previews of future events, which are then used the general principles could also be applied to auditory perception
as a basis for forecasts or predictions about an event's likely conse- where rapid coarse information processing also occurs from subcortical
quences. In this respect a recent model proposes that in complex cir- nuclei through extra-lemniscal projections to the prefrontal regions
cumstances such as social interactions the brain builds predictions by (Kraus et al., 1994; Martinez-Moreno et al., 1987). Prefrontal activity
combining multiple analogies (Bar, 2004). Such predictions do not in return participates in guiding auditory perception performed at the
need to be created afresh in new situations, but rely instead on existing level of the auditory associative cortex in the superior temporal gyrus
scripts, which are the result of real as well as expected experiences. Our and superior temporal sulcus (Garrido et al., 2009). Given the omni-
perception of the environment thus relies on existing knowledge as presence of predictions, it is likely that their influence pervades far
much as it does on incoming sensory information. This ‘proactive more than just sensory object perception and also affects emotion pro-
brain’ model has been mainly studied in the domain of visual perceptual cessing (Kveraga et al., 2007). Prediction processes may thus be critical
to adaptive cognitive, behavioural, and social function.
Neurodevelopmental disorders offer an opportunity for identifying
⁎ Corresponding author at: INSERM U930, Team ‘Autism’, Centre de Pédopsychiatrie,
CHRU Bretonneau, 2 Bd Tonnellé, 37044 TOURS Cedex 9, France. Tel.: + 33 2 47 47 86
cognitive and brain mechanisms underlying altered trajectories of devel-
64; fax: + 33 2 47 47 38 46. opment of adaptive behaviour. Autism Spectrum Disorder (ASD) is a per-
E-mail address: [email protected] (M. Gomot). vasive neurodevelopmental disorder marked by social deficits and verbal

0167-8760/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.ijpsycho.2011.09.017
 M. Gomot, B. Wicker / International Journal of Psychophysiology 83 (2012) 240–247 241

and non-verbal communication deficiencies together with stereotyped and Winkler, 1999; Winkler et al., 1996). This has been supported by
behaviour and limited activities and interests, also characterized by Escera et al.(2003) who supplied evidence for the involvement of the
strong resistance to changes in the surrounding environment (APA, prefrontal cortex in providing top–down modulation of the deviance de-
2000). Most researchers now agree on the biological origin of this disor- tection system in the temporal cortices. This notion of top–down guiding
der and although the cause is still largely unknown, it has been suggested of auditory change detection has been further developed by Garrido et al.
that genetic and environmental factors could be involved alone or in com- (2008; 2009), in the framework of the predictive coding model (Friston,
bination as possible causal or predisposing elements to developing ASD. 2005), a view highly consistent with the model of a visual proactive brain
Several psychological and theoretical theories have been proposed to presented by Bar (2004).
account for the behavioural and cognitive difficulties that characterize
ASD. The present review is framed in relation to the ‘proactive brain’ cog- 3.1.1. MMN to tones and speech stimuli
nitive neuroscience theoretical account, with the aim of explaining a va- Contrary to most auditory ERPs, the MMN matures very early and its
riety of symptoms in ASD, ranging from resistance to change to deficit in underlying mechanisms are assumed to be similar across the lifespan
planning and social interaction. Our intention here is not to perform an (Cheour et al., 2000; Gomot et al., 2000). As MMN recording does not re-
exhaustive literature review, but rather to assemble results from exper- quire the subject's participation, it is very appropriate to study the dy-
iments suggesting a dysfunction in the ability to build flexible prediction namics of the central auditory processes involved in change detection
in ASD, that may originate from impaired top–down influence over a va- in clinical populations.
riety of sensory and higher level information processing. Findings from MMN has long been considered as useful in the study of speech
electrophysiological and neuroimaging studies exploring the neural sounds discrimination and has thus been investigated in clinical popu-
bases of both basic perceptual and more complex cognitive information lations with communication disorders, including individuals with ASD.
processing will be presented. Most studies have reported either normal or reduced MMN amplitudes
in response to vowel change in these patients (Kemner et al., 1995; Kuhl
2. Clinical observations et al., 2005; Lepisto et al., 2008; Lepisto et al., 2006). However studies of
auditory deviance detection using elementary stimuli had previously
Clinical observations have demonstrated that people with ASD show provided information on the ability of the neural system to predict
unusual reactivity to sensory stimuli. Self reports commonly mention and react to changing events. MMN studies involving more basic audi-
atypical sensory responses (Bogdashina, 2003; Williams, 1992), espe- tory stimuli such as tones have been performed in people with ASD,
cially during childhood, and a systematic review of the literature indi- but the findings reported have been rather inconsistent. Some studies
cates that rates of sensory processing dysfunction may be as high as have indicated that MMN amplitude for pitch deviants in individuals
90% in individuals with ASD (Baker et al., 2008; Baranek et al., 2006; with ASD is in the normal range (Ceponiene et al., 2003) whereas others
Leekam et al., 2007; Tomchek and Dunn, 2007). These specific sensory have shown a reduced response (Dunn et al., 2008; Lepisto et al., 2006).
particularities affect all modalities and mainly include enhanced per- Shorter (Gomot et al., 2002; Kujala et al., 2007), normal and longer la-
ceptual function such as visual hyperacuity (Ashwin et al., 2009), hyper- tencies (Jansson-Verkasalo et al., 2003; Oram Cardy et al., 2005; Seri
acusis (Khalfa et al., 2004) and acute tactile sensitivity (Blakemore et al., et al., 1999) have also been reported in this population. These findings
2006). However, hypo-reactivity to sensory stimuli has also been exten- support the notion that there are differences, but not necessarily im-
sively reported in all sensory modes (Ben-Sasson et al., 2009; Reynolds pairments, in the speed and robustness of the early stage of auditory
and Lane, 2008). These paradoxical responses to sensory stimuli often change detection in ASD.
observed in the same individual with ASD, lead to a lack of consensus In our previous work involving children with ASD, we have inves-
on the exact nature of the underlying sensory dysfunction, but could ex- tigated the processes involved in the automatic detection of minor
plain many of the characteristic autistic behaviours, such as stereotyped frequency changes, using a similar oddball paradigm in electrophysi-
behaviour and quest for sameness (see Gerrard and Rugg (2009) for a ological (Gomot et al., 2002) and fMRI studies (Gomot et al., 2006).
comprehensive review). Sensitivity to any change occurring in the envi- The electrophysiological results showed abnormal MMN topography
ronment is also a fundamental feature of ASD that appears to be a dura- over the frontal regions in children with ASD compared to controls.
ble treatment-resistant symptom, which prevents the individual from fMRI confirmed the hypothesis of atypical frontal change processing
adapting. For instance, enhanced detection of specific features in the au- in ASD as it demonstrated smaller activity in the anterior cingulate
ditory modality suggest an exaggerated perception of even slight (a region mainly involved in the distribution of attentional resources)
changes in the environment and a feeling of stimulus overload, trigger- in children with ASD than in controls in response to deviant events.
ing distressful reactions to specific sounds (O'Riordan and Passetti, These studies using different brain investigation techniques provided
2006). This oversensitivity to changes may lead to an inability to antic- evidence of normal auditory temporal activity but atypical function-
ipate and adapt to new sensory inputs, in both the visual (Loth et al., ing of the left prefrontal cortex, during the automatic detection of
2008) and the auditory (Gomot et al., 2010) modalities. acoustic changes in children with autism.
In this respect the processes involved in pre-attentional detection of However, the involvement of these neurophysiological particularities
changes in stimulus features based on prediction regarding regularity of in the behavioural need to preserve sameness in ASD remained to be
sensory input, as well as attentional processes involved in novelty and clarified. We therefore examined further the relationships between elec-
target detection, have been extensively investigated in ASD. trophysiological responses to a passive auditory oddball paradigm and
clinical assessments focusing on intolerance of change in order to pro-
3. Violation of prediction: deviance and novelty processing vide evidence of possible brain-behaviour relationships (Gomot et al.,
2010). Subjects with ASD displayed significantly shorter MMN latency
3.1. Mismatch negativity than controls, indicating atypical sensory expectation. Indeed basic re-
search on MMN has shown that shorter MMN latencies were recorded
In the auditory modality, representations of regularity are involved for greater intensity deviation (Schroger and Winkler, 1995) and for
in the deviance detection process reflected by mismatch negativity larger frequency deviation (Naatanen et al., 1982; Tiitinen et al.,
(MMN), an event-related potential (ERP) that reflects a marker of 1994). Children with ASD would thus process slightly deviant events
error detection caused by a deviation from a learned regularity. It results as if they were presented with large deviants, either because of an atyp-
from comparison between the auditory input and a memory trace of ical formation of the standard sensory memory trace or due to dysfunc-
previous sounds embodied in top–down predictions, thus reflecting an tion in the mismatch process itself. Bioclinical relationships indicated
on-line updating of the model for predicting auditory inputs (Naatanen that these electrophysiological particularities were significantly more
242 M. Gomot, B. Wicker / International Journal of Psychophysiology 83 (2012) 240–247

marked in children who displayed greater difficulties in tolerating and young adults with ASD (Courchesne et al., 1984; Courchesne et al.,
change, suggesting that the atypical neurophysiological mechanism of 1985; Ferri et al., 2003; Kemner et al., 1995; Townsend et al., 2001),
change perception identified might be associated with one of the hall- but might be enhanced in children (Ferri et al., 2003; Gomot et al.,
mark behavioural manifestations of ASD. 2002). Furthermore, the amplitude of the P3a was found to be correlated
with behavioural measurements of intolerance to change in children
3.1.2. MMN to prosody with ASD, suggesting that greater difficulties in dealing with unexpected
The voice is a key vector of social information and it has an impor- events might be due to greater brain activity in response to attention-
tant adaptive role very early in human development. Auditory change catching rare stimuli (Gomot et al., 2010). Differences in findings in chil-
detection in control populations, as reflected by MMN, is enhanced dren and in adults with ASD raise the question of the development of
for rare stimuli spoken with emotion as compared to neutral prosody compensatory mechanisms and highlight the need of carrying out stud-
(De Baene et al., 2004; Schirmer et al., 2005). MMN might thus consti- ies using the same paradigm at all ages in order to distinguish between
tute a suitable electrophysiological index of automatic change detec- age-related and stimulus feature-related effects.
tion embedded in an emotional context. Delayed P3a latency has been repetitively found in ASD (Townsend
Disorder of emotional prosody has been frequently identified as a core et al., 2001). In a three stimulus oddball paradigm, Sokhadze et al.
feature of the syndrome in individuals with ASD who develop language (2009) showed that ASD subjects displayed delayed P3a response to vi-
(Paul et al., 2005b). Clinical observations report monotonic or machine- sual novel stimuli, especially in the right hemisphere, suggesting that
like intonation, deficits in the use of pitch and control of volume, and individuals with ASD require more time to process information needed
use of aberrant stress patterns. When these differences are present they for the successful differentiation of target and novel stimuli. These find-
are persistent and show little change over time, even when other aspects ings indicating differences in amplitudes and longer latencies of the
of language improve. Compared to the extensive studies reporting atypi- electrophysiological index of attention-dependent novelty-processing
cal expressive prosody, few studies have focused on receptive prosody. suggest unusual violation of sensory expectancy in ASD, possibly due
Nevertheless, behavioural experiments have provided evidence that re- to difficulties in building flexible predictions about the upcoming event.
ceptive prosody scores in ASD correlated with expressive prosody perfor-
mance (Paul et al., 2005a; Peppe et al., 2007). Only two studies have 3.3. P3b
investigated MMN in response to changes in emotional prosody of a
two syllable word in ASD (Korpilahti et al., 2007; Kujala et al., 2005), Predictions related to contextual processing has been linked to the
and both reported smaller activity in the right hemisphere compared to P300 component of the ERP (Donchin and Coles, 1988; Polich and
controls. However, as mentioned above, previous findings by our team Criado, 2006). A quite extensive literature supports the notion that hy-
and others using tone pitch variations to examine MMN in ASD support potheses about the environment are continuously generated as a func-
the possibility that deficits in the detection of changes in basic auditory tion of incoming information (Donchin and Coles, 1988), and that the
features may be underlain mostly by particularities in prefrontal activity target P300 component (P3b) provides a measure of the evaluation of
(Gomot et al., 2008; Gomot et al., 2006; Gomot et al., 2002). Such findings environmental signals as a function of context (Squires et al., 1976;
support the hypothesis of particular top–down processes involved in the Fogelson et al., 2010). Such processing has been shown to rely on the
automatic detection of auditory irregularity in ASD, which might contrib- prefrontal cortex activity (Barcelo and Knight, 2007).
ute to abnormal prosody perception in this population. ERP studies on target detection and attention to novelty have dem-
onstrated clear deficits in individuals with ASD. While P3b latency re-
3.1.3. Visual MMN mains fairly unchanged (Courchesne et al., 1989; Lincoln et al., 1993;
Recent studies have provided convincing evidence for a visual equiv- Oades et al., 1988), several studies have reported that the P3b ampli-
alent of MMN (vMMN) in response to deviancy based on various stimu- tude to targets in ASD subjects was smaller than in controls in the audi-
lus features such as colour (Czigler et al., 2002), form (Berti and Schroger, tory (Dawson et al., 1988; Kemner et al., 1995; Lincoln et al., 1993;
2004); (Stagg et al., 2004), motion (Kremlacek et al., 2006; Pazo-Alvarez Townsend et al., 2001), visual (Kemner et al., 1999) or both modalities
et al., 2004), spatial frequency (Kimura et al., 2006; Maekawa et al., (Ciesielski et al., 1990; Courchesne et al., 1985; Courchesne et al., 1989;
2005), and orientation (Astikainen et al., 2008; Czigler and Csibra, Hoeksma et al., 2004; Novick et al., 1980) despite normal performance
1992). A number of studies in adults have identified vMMN as a nega- on the task. This reduced P3b amplitude has been interpreted as reflect-
tive detection peaking 100–250 ms post stimulus change onset (see ing dysfunctions in context updating and in the ability to sustain atten-
Pazo-Alvarez et al., 2003 for a review). Similar to the auditory MMN, tion to target stimuli, again suggesting that individuals with ASD
the vMMN is thought to reflect the memory-based detection of deviants process novelty differently and display unusual cognitive expectancy.
as demonstrated by equiprobability paradigms that make it possible to Overall, these ERP findings suggest that the neural circuits necessary
control the effects of global presentation (Czigler et al., 2002). for the processing of irregularities in the sensory stream, such as auto-
In contrast to the increasing literature on vMMN in adults, no studies matic discrimination of stimulus features, pre-attentive novelty detec-
have been published on its maturation. Nevertheless automatic devian- tion, or target detection may be aberrant in ASD (see Jeste and Nelson
cy detection has recently been investigated in the visual modality in 11- (2009) for an exhaustive review), and might be considered in relation
year-old children with ASD. These children showed an earlier visual to the difficulty that ASD individuals have in properly allocating attention
mismatch response with atypical morphology: they displayed positive and modifying their expectancy of contextually-relevant sequences of
occipito-parietal activity spreading over the central region whereas the sensory information. Interestingly, low-frequency rTMS has been applied
control group showed a negative response localized over the bilateral over the dorsolateral prefrontal cortex of ASD patients during an oddball
occipito-parieto-temporal sites. These findings suggest that unusual re- task, to increase the inhibitory circuitry in this area known to be involved
actions to change are underlain by atypical general change processing in- in attentional executive processes. rTMS resulted in a short-term func-
dependent of the sensory modality (Cléry et al., in revision). tional reorganization of cortical activity leading to modifications of
ERPs (Sokhadze et al., 2010): the amplitude of the P3a component to
3.2. P3a rare novel stimuli normalizing in ASD subjects, and the P3b showing in-
creased reactivity to targets and decreased reactivity to frequent stan-
The P3a response has been used to assess how individuals with ASD dards. The authors concluded that low-frequency rTMS minimized
involuntarily orient to unattended changes in their environment. cortical responses to irrelevant stimuli and increased responses to rele-
When elicited by attention-catching novel sounds or deviants, the P3a vant stimuli and might represent a remarkable lead for future treatment
response was generally found to be smaller in amplitude in adolescents development.
 M. Gomot, B. Wicker / International Journal of Psychophysiology 83 (2012) 240–247 243

4. Context processing and change blindness found to be hyper-activated during the active run (Gomot et al., 2006)
(Fig. 1). The IPL is assumed to be involved in the pre-attentive gating
Contextual processing is essential for the performance of cognitive mechanism that determines the extent to which unattended novel stim-
functions (Braver and Barch, 2002; Braver et al., 2005) and enables ex- uli enter awareness (Jaaskelainen et al., 2004), such pre-attentive mech-
traction of relevant environmental information to guide our behaviour anisms being influenced by frontal top–down processes (Cycowicz and
in facilitating the selection of an appropriate task-specific response Friedman, 1998). Therefore, depending on the context (instruction), in-
(Fogelson et al., 2010). Proper use of contextual information requires dividuals with ASD may have an abnormally narrow or an abnormally
the ability to move from a local to a global level of processing. As such, broad focus of attention toward changing events. Similar attention im-
it entails the capacity to combine information in order to construct pairments were demonstrated in the spatial domain in a task that re-
higher-level meanings in context that contributes to predicting incom- quired stimulus discrimination following a spatial cue that preceded
ing events. Evidence from neuropsychological, event-related potential the target presentation with either a long (voluntary spatial attention)
and neuroimaging studies supports a key role of the prefrontal cortex or a short (automatic attention) inter-stimulus interval (Haist et al.,
in contextual processing (Barcelo and Knight, 2007; Huettel et al., 2005). The pattern of fMRI findings suggest that ASD is associated with
2005; MacDonald et al., 2000). a deficit in automatic spatial attention and with atypical voluntary spatial
People with ASD demonstrate a unique profile of perceptual and cog- attention skills.
nitive abilities, characterised by overly focusing on the local level at the In the same trend, several reports suggested that individuals with
expense of the global view. This pattern has been evidenced during visu- ASD focus their attention on less contextually relevant aspects of the vi-
al processing (Jolliffe and Baron-Cohen, 1997), as well as in the context of sual scene, show superior perceptual discrimination, and notice details
a conceptual deficit as originally demonstrated in homograph reading which are often ignored by typical observers. The ability to detect
tasks (Snowling et al., 1986). Similarly, people with ASD are not fooled changes in a visual scene has therefore been investigated in ASD using
by visual illusions such as Tichener Circles which depend on whether the change blindness paradigm that makes it possible to assess the in-
the context is taken into account or not (Happe, 1999). Moreover, it fluence of context on automatic attention. However, analysis of the
has been shown that subjects with ASD are not affected by interfering vi- few studies in this domain reveals inconsistent findings. Of the five
sual (Jolliffe and Baron-Cohen, 1997) or auditory (Foxton et al., 2003) studies performed, one showed superior levels of task performance in
‘gestalts’. This lack of interference as well as the weaker tendency to in- ASD (Smith and Milne, 2009) and another reported a similar error de-
tegrate separate events has been interpreted as reflecting a deficit in tection rate (Fletcher-Watson et al., 2008). The other three reported de-
the ‘coherent whole’ representation (Happe and Frith, 2006). Rather creased levels of performance, one showing a lack of attentional bias
than a dysfunction of global processing, it was then proposed, mostly toward faces (Kikuchi et al., 2009) and the other two a default in con-
on the basis of study of auditory attention processes that revealed en- text facilitation effect (Fletcher-Watson et al., 2006; Loth et al., 2008).
hanced pitch processing (Bonnel et al., 2003; Heaton et al., 2008), that For instance, the ASD participants did not show the usual top–down fa-
low-level information processing systems for sensory stimuli might be cilitator effect of scene-schema expectations on scene-unrelated substi-
over-developed in ASD (Mottron et al., 2000 ; Plaisted et al., 2003). tutions and were thus significantly slower and less accurate than the
This hypothesis has been further conceptualised within the Enhanced control group in detecting scene-unrelated objects (Loth et al., 2008).
Perceptual Functioning Model (EPF) (Mottron et al., 2006). EPF notably These findings suggest a weaker influence of schematic expectations
proposes that the automatic progression from local to global visual pro- on spontaneous attention in individuals with ASD.
cessing that normally occurs in vision is compromised and that, as a con- To summarise, the reduction in the normal tendency to process in-
sequence, individuals with ASD retain access to local structures. formation within its context may be a consequence of a processing
Following this line, Bertone et al. (2003) proposed that people with bias for featural and local information, and a relative failure to extract
ASD encounter specific difficulties with the processing of complex infor- the general picture. This lack of building and/or using context can be
mation involving not only primary but also associative brain areas. interpreted in the framework of the proactive brain, with the hypothe-
Few brain imaging studies have investigated the neural correlates of sis that the core difficulty in processing socially-relevant information in
context processing in ASD. In a study employing fMRI while subjects per- ASD might be based on a more general deficit of prediction. The social
formed Embedded Figures Tasks, Ring et al. (1999) tested local/global environment is permanently and rapidly moving and changing, and so-
processing during visual search for a simple shape in a complex figure. cial situations are those where predictions are the most important and
Whereas prefrontal areas were preferentially activated in typical subjects, the most solicited. In this context, building predictions would act as
individuals with ASD demonstrated greater activation of ventral occipito- an attentional filter, allowing minimizing processing of incoming stim-
temporal regions, associated with superior task performance. The authors uli and allocating mental resources to more relevant contextual infor-
concluded that the ASD group strategy depends to an abnormal extent on mation. Interestingly, this propensity to invest in the predictable is
visual systems for analysis of object features, at the expense of more inte- thought to be primarily a top–down, internally driven process, sup-
grative processing. Such hypo-activation of prefrontal areas during visuo- ported by long-range connectivity between prefrontal and posterior as-
spatial context processing has subsequently been confirmed by other sociative brain areas (Bar, 2007).
groups (Lee et al., 2007; Manjaly et al., 2007). Another study addressed
brain activity associated with global information processing, in which
context was provided by gaze direction (Pelphrey et al., 2002). The find-
ings suggested that gaze processing deficits in ASD subjects is not due to
weak gaze discrimination per se, but rather linked to an inability to use in-
formation from gaze direction to anticipate and to solve social situations
that demand awareness of contextual subtleties.
At a more elementary perceptual level, it is admitted that the context
in which sensory stimuli occur does pervade their subsequent proces-
sing. During an active auditory oddball task, Gomot et al. (2008) showed
enhanced activation of the inferior parietal and prefrontal regions in ASD
subjects in response to novel targets. Interestingly, using the same audi-
tory oddball sequence but presented in passive conditions, they found Fig. 1. Atypical left Inferior Parietal Lobule (IPL) activity associated with novelty detec-
that the inferior parietal lobule (IPL) was hypo-activated in children tion in children with ASD depends on the instruction. Novel vs. Standard: Unattended
with ASD in response to novel stimuli, whereas this same region was condition, Ctrl N ASD (yellow); Attended condition, ASD N Ctrl (green).
244 M. Gomot, B. Wicker / International Journal of Psychophysiology 83 (2012) 240–247

5. Planning and flexibility extensive coordinated functioning of remote processing centres. The
ASD brain might thus not develop from a local to a distributed organiza-
Executive functions refer to a range of abilities, including behavioural tions as currently observed during normal maturation (Fair et al., 2009).
control, planning, working memory, and set shifting (Baddeley, 1986; Taken together, results from functional connectivity analysis during
Robbins, 1996; Shallice, 1982), allowing to adapt flexibly to changing en- executive functioning tasks provide converging evidence in line with
vironmental contingencies. Among these adaptive skills, planning neces- the (long-range) under-connectivity hypothesis proposed by Just et al.
sitates building prediction about our own actions and their consequences, (2004), which might constitute the neural basis of a fault in automatic
and set-shifting requires flexible adaptation to changes in ongoing rule or anticipation of ongoing information. A recent study directly investigat-
stream of events that fail to match with our expectation. In this regard ed the influence of global processing on lower-level visual perception in
these executive processes closely rely on predictive abilities. Executive ASD using a paradigm in which local and global processes were
dysfunction in ASD has been a particularly active topic of investigation requested at the same time (Liu et al., 2011). In such a task, the automat-
since the pioneer studies (Ozonoff et al., 1991; Rumsey, 1985; Russell ic global processing of the background information usually interferes
et al., 1999) to such an extent that an Executive Dysfunction model with the concurrent local processing, causing additional cognitive re-
has been proposed (Hill, 2004; Hill and Bird, 2006) and is still being de- sources to be recruited to deal with the interference. Thus, greater activa-
veloped (Corbett et al., 2009; Happe et al., 2006; Ozonoff et al., 2004). tion in the frontal brain regions and increased functional connectivity
Some authors argue that executive dysfunction can explain the main between these executive regions and the visuospatial regions was
symptoms of ASD (Hill, 2004). For instance, problems with social inter- found in controls. Conversely the participants with ASD did not show in-
action might be due to a lack of flexibility leading to difficulties in taking creased activation in the superior frontal and medial frontal brain re-
another individual's perspective, whereas repetitive behaviours may gions, nor increased functional connectivity between the medial frontal
stem from a lack of generative ability or difficulty in set shifting to a and posterior regions. This again suggests impairment in top–down reg-
new behaviour (Turner, 1999). Research into executive functioning ulation on perceptive regions necessary to catch the whole picture.
suggests that individuals with ASD generally experience difficulties, es- Anatomically, recent studies of axonal connectivity of area 32 of ante-
pecially in planning (Ozonoff and Jensen, 1999) and cognitive flexibility rior cingulate cortex (ACC) and prefrontal areas revealed an exuberance
(Kaland et al., 2008; Ozonoff and Jensen, 1999). Only a few functional of thin axons that course over short or medium distances in the ASD
magnetic resonance imaging studies have investigated the neural sub- brain, which may lead to occupation of sites normally available to the
strates of these executive cognitive functions in ASD. Just et al. (2007) considerably sparser long-distance pathways (Zikopoulos and Barbas,
used the Tower of London task to explore brain activations associated 2010). The latter are at a competitive disadvantage, not only because
with planning. Behavioural results showed that ASD individuals dis- they develop later, but also because they need additional time to extend
played similar error rates but longer reaction times than controls long axons to form synapses in the prefrontal cortex. Reduction in the
when the number of moves required to perform the task increased. strength of long-distance pathways in ASD may thus be secondary to
During this planning task the same brain areas were activated to similar the excessive short-range connections of ACC. Again, this connectivity
degrees in both groups. However, the degree of functional connectiv- bias may help explain why individuals with ASD do not adequately
ity between frontal and parietal areas was lower in ASD than in con- shift attention when necessary, and engage in repetitive and inflexible
trols. The authors concluded that the neural basis of impaired behaviour.
planning in ASD entails a lower degree of integration of information
across certain cortical areas resulting from reduced intracortical 7. Link with other theories of ASD suggesting impairment in
connectivity (Just et al., 2007). Functional connectivity analysis per- predictions
formed during a cognitive control task (while subjects were preparing
to overcome a prepotent response) also revealed lower levels of function- Finally, particular features in predicting forecoming events have
al connectivity and less network integration between frontal, parietal, previously been mentioned, although not necessarily further devel-
and occipital regions in the ASD group, associated with higher error oped, in neuropsychological models of ASD.
rate in response to the most difficult trials that need greater involvement Among these models, the psychological ‘extreme male brain theory’
of cognitive control process (Solomon et al., 2009). Altogether these find- stipulates that individuals with ASD preferentially develop a systemising
ings showed roughly similar performance in control and ASD groups but style (typical male functioning) at the expense of empathising skills
differences in the temporal connectivity of the different brain areas en- (Baron-Cohen, 2002). According to this assumption, people prone to
gaged by the cognitive task. This supports the hypothesis of the devel- the systemizing style are generally good at understanding systems that
opment of alternative strategies in ASD possibly rooted in atypical are highly predictable as they are governed by very clear rules. Systemiz-
fronto-parietal functional connectivity, rather than a cognitive defi- ing is the ability to observe a physical system and make predictions about
cit per se. how it works (Baron-Cohen, 2006). Such cognitive style works well for
phenomena that are lawful and deterministic but it is of almost no use
6. A brain connectivity bias when it comes to predicting moment-by-moment changes in a person's
behaviour. To predict human behaviour, empathising is required. Empa-
Research in ASD over the last ten years has been marked by specific thizing allows to identify another person's emotions and thoughts, and
focus on socio-emotional processing. Brain function in ASD has mainly to respond to these with an appropriate emotion. Baron-Cohen and
been investigated with tasks related to social cognition such as face per- others have shown that individuals with ASD can perform at normal or
ception, emotion recognition, or theory of mind. Particularities have been often superior levels in tasks requiring the systemization of information.
revealed within the socio-emotional brain areas including the medial People with ASD scored higher on the Systemizing Quotient (SQ) ques-
prefrontal cortex, fusiform gyrus, posterior superior temporal sulcus tionnaire (Baron-Cohen et al., 2003), performed better on tests of intui-
and amygdala (Frith, 2001; Gervais et al., 2004; Pierce et al., 2004; Schultz tive physics (Lawson et al., 2004) and can reach extremely high levels
et al., 2003). The under-connectivity theory of autism has further been of achievement in systemizing domains, such as mathematics, physics,
proposed on the basis of neuroimaging evidence of anatomical and func- and computer science (Wheelwright and Baron-Cohen, 2001). Con-
tional connectivity disruption in ASD (Belmonte et al., 2004; Just et al., versely patients with ASD are poor at empathizing, as dealing with infor-
2004; Thai et al., 2009; Wicker et al., 2008). This suggests that the beha- mation that is rather unpredictable and less controllable is particularly
vioural markers of ASD are directly or indirectly caused by limitations in challenging for those people whose flexible prediction abilities are im-
the communication between frontal and posterior brain regions, and pre- paired. Baron-Cohen proposed that although systemising and empathis-
dicts that these limitations will impact on those tasks that require ing are in one way similar as both allow us to make sense of events and
 M. Gomot, B. Wicker / International Journal of Psychophysiology 83 (2012) 240–247 245

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