The Neuroscience of Autism Spectrum Disorders || Attentional Network Deficits in Autism Spectrum Disorders

C H A P T E R

3.3

Attentional Network Deficits in AutismSpectrum Disorders

Jin FanDepartment of Psychology, Queens College, The City University of New York, Flushing; Departments of Psychiatry and

Neuroscience, and Seaver Autism Center for Research and Treatment, Mount Sinai School of Medicine,

New York, NY, USA

T

h

O U T L I N E

Introduction
281
Attention as an Organ System
281
he Neu

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Attentional functions
282 Attentional networks 282
Impairments of Attentional Functions and theirNeural Substrates in Autism
283
Alerting
283
281roscience of Autism Spectrum Disorders.

.doi.org/10.1016/B978-0-12-391924-3.00019-3

Orienting
284 Executive control 284
The Attention Model of Autism
285
Conclusion
286
Acknowledgments
286
INTRODUCTION

Attention refers to the activity of a set of brainnetworks that can influence the priority of the computa-tions of other brain networks for access to conscious-ness. Typical functions of attention involve obtainingand maintaining a state of vigilance or alertness, selec-tion of sensory information, and monitoring andresolving conflict between possible responses. Attentionis involved in all cognitive functions as the gateway tovoluntary control of thoughts, feelings, and actions,and is critical to the establishment of higher-level cogni-tive functions. Autism spectrum disorders (ASD) arecharacterized by deficits of social interaction andcommunication as well as repetitive behaviors andrestricted interest in the environment. While studieshave shown significant cognitive abnormalities inautism (e.g., theory of mind), the relative primacy inthe development of these deficits remains unclear.

Although attentional difficulties (e.g., deficits of joint/shifting attention) are common in children and adults

with ASD, such deficits have not been considered to bea core symptom of ASD. The purpose of this chapter isto provide a neurocognitive framework for the attentiondeficits observed in autism. The reader will notice that asattention is divided into its component subsystems, thelink between specific attention deficits (along with corre-sponding changes in neurocircuitry) and pathologicalfeatures of ASD in cognitive and social developmentwill become clear. The evidence presented in this chapterwill build the argument that attentional deficits in autismmay be part of its primary pathology and show relation-ships to the core symptom domains. In this review, I willexamine behavioral and neuroimaging data that suggestthat such deficits play a much more important role in thepathophysiology of autism than previously thought.

ATTENTION AS AN ORGAN SYSTEM

To facilitate understanding of the neural bases ofattention, it can be treated as an organ system with its

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http://dx.doi.org/10.1016/B978-0-12-391924-3.00019-3

ACC

LPFC

Right frontalarea

FEF

• Alerting network• Orienting network• Executive control network

Pulvinar

Thalamus

Superiorcolliculus

IPC

TPJ

FIGURE 3.3.1 Functional anatomy of the attentional networks.Right frontal and parietal areas, while TPJ is active for tonic andphasic alerting. The pulvinar, superior colliculus, IPC, and FEF areactive for orienting. The ACC and LPFC are important regions forexecutive control. ACC: anterior cingulate cortex; IPC: intraparietalcortex; FEF: frontal eye fields; LPFC: lateral prefrontal cortex; TPJ:temporal parietal junction.

3.3. ATTENTIONAL NETWORK DEFICITS IN AUTISM SPECTRUM DISORDERS282

own anatomy and circuitry. A system is defined asa group of differentiated structures made up of variouscellular components and adapted to the performance ofsome specific function. As such, the attentional systemhas been defined in specific functional and anatomicalterms (Posner and Badgaiyan, 1998; Posner and Fan,2008; Posner and Petersen, 1990).

Attentional functions

Attention comprises three separate functional compo-nents: alerting, orienting, and executive control. Thealerting function is further divided into tonic and phasicalertness. Tonic (or intrinsic) alertness reflects generalwakefulness and arousal, whereas phasic alertnessrefers to changes in response readiness to a target, oftenfollowing an external warning stimulus. The orientingfunction involves the selection of specific informationfrom numerous sensory inputs. Orienting can bereflexive (exogenous), as when a sudden target eventdirects attention to its location, or it can be more volun-tary (endogenous), as when a person searches the visualfield looking for a target. Orienting that involves headand/or eye movements toward the target is called overtorienting, whereas orienting that does not involve headand/or eye movement is referred to as covert orienting.Orienting involves rapid or slow shifting of attentionamong objects within a modality or among varioussensory modalities, and has three elementary opera-tions: disengaging attention from its current focus,moving attention to the new target, and engaging atten-tion on the new target (Posner et al., 1984). The executivecontrol function of attention involves the engagement ofmore complex mental operations during monitoringand resolving conflict between computations orresponses, such as in a color Stroop task (MacLeod,1991) (e.g., the word RED is written in blue color andyour task is to name the ink color of the word), in whichthe competition between the two processes of colornaming (blue) and word meaning (red) has to be solvedbefore one can make a response.

Attentional networks

Each of these three attentional functions is mediatedby anatomically distinct neural networks and neuro-transmitters (Figure 3.3.1 and Table 3.3.1). Alerting hasbeen associated with thalamic, frontal, and parietalregions and is influenced by the cortical distribution ofthe brain’s noradrenergic (NAergic) system,which arisesfrom the locus coeruleus in the midbrain (Coull et al.,1996;Marrocco et al., 1994). Blocking theNAergic systemblocks the normal effect of warning signals (Marrocco etal., 1994). The NAergic system has also been implicatedin maintaining an alert state (Witte and Marrocco, 1997).

3. BRAIN IMAGING AND NEUROPATHOLO

The orienting system for visual events has been asso-ciated with brain areas such as the superior parietallobule, temporal parietal junction (TPJ) and the frontaleye fields (FEF) (Corbetta et al., 2000; Corbetta andShulman, 2002; Posner, 1980; Posner and Cohen, 1984;Posner et al., 1982). It has been shown that bilaterally,the intraparietal cortex (IPC) and the FEF are involvedin orienting, whereas the right TPJ and inferior frontalgyrus are involved in reorienting (Corbetta et al., 2000;Corbetta and Shulman, 2002). Our functional magneticresonance imaging (fMRI) study showed that the TPJis involved in alerting rather than orienting (Fan et al.,2005). This finding has subsequently been confirmedby other groups (Thiel and Fink, 2007). Cholinergicsystems arising in the basal forebrain play an importantrole in modulating orienting. Injections of muscarinicantagonist scopolamine into the lateral intraparietalarea in nonhuman primates have been shown toincrease reaction time and decrease performance accu-racy in a covert orienting task (Davidson and Marrocco,2000), suggesting that this network is related to acetyl-choline (ACh). The site of this effect is not in the basalforebrain, but in the parietal lobe. Damage to the parietallobe is associated with deficits in disengagement ofattention (Posner et al., 1984). Damage to the superiorcolliculus and other midbrain structures is associatedwith a deficit in movement of attention (Posner andPetersen, 1990). Lesions to the pulvinar nucleus of thethalamus are associated with deficits in engagement ofvisual attention (Rafal and Posner, 1987).

GY OF AUTISM SPECTRUM DISORDERS

TABLE 3.3.1 Attentions and Possible Brain Regions and Neurotransmitters Involved

Attentional functions Subcomponents Brain regions involved Neurotransmitters

Alerting Tonic alertingPhasic alerting

Thalamic, frontal, parietal regions, locus ceruleus,cerebellum and brainstem, temporal parietal junction

Noradrenaline

Orienting DisengagingMovingEngaging

Superior parietal lobule, frontal eye field,superior colliculus, midbrain structures, pulvinarnucleus of thalamus

Acetylcholine

Executive control Anterior cingulate cortex, lateral prefrontal cortex Dopamine

IMPAIRMENTS OF ATTENTIONAL FUNCTIONS AND THEIR NEURAL SUBSTRATES IN AUTISM 283

Finally, the executive control of attention involves theanterior cingulate cortex (ACC) and the lateral prefrontalcortex (LPFC) (Matsumoto and Tanaka, 2004) and ismodulated by dopamine (Benes, 2000; Lidow et al.,1991). Other regions, such as the anterior insular cortex,also play a role in executive control (Craig, 2009). Anumber of neuroimaging studies have shown activationof the dorsal ACC in tasks requiring subjects to respondto one dimension of a stimulus rather than a strong con-flicting dimension (Botvinick et al., 2001; Bush et al., 2000;Fan et al., 2003; MacDonald et al., 2000).

IMPAIRMENTS OF ATTENTIONALFUNCTIONS AND THEIR NEURAL

SUBSTRATES IN AUTISM

There is accumulating data to support the presence ofattention impairments in ASD. In a comprehensivereview, Allen and Courchesne (2001) suggested thatimpairments of attention are among the most consis-tently reported cognitive deficits in autism. Thefollowing section describes deficits of attentional func-tions and networks in ASD, based on the view of func-tional separation and specification of attention,providing a framework for a more comprehensive inter-pretation and better understanding of the attentionalimpairments observed in affected individuals.

Alerting

Some studies have shown that children with autismpossess a normal ability to sustain attention (Pascual-vaca et al., 1998), and that their difficulties in sustainingattention may not be a primary impairment but may bedue to a developmental delay and to motivationalcontingencies of a task (Garretson et al., 1990). However,there is evidence that altered arousal mechanisms inASD, such as a chronically high state of arousal (Huttet al., 1964) and aberrant response to novelty, mayunderlie some of the observed behavioral abnormalitiessuch as attention to social and nonsocial stimuli(Dawson and Lewy, 1989). The evidence supporting


the argument of normal ability to sustain attentioncomes from studies that employed the commonly usedContinuous Performance Test (CPT) (Rosvold et al.,1956) to measure sustained attention or vigilance, whichfailed to show any performance deficits in patients withautism (Buchsbaum et al., 1992; Garretson et al., 1990;Pascualvaca et al., 1998; Siegel et al., 1992; 1995).Although the results from the CPT appeared to showno evidence of deficits related to alerting (Casey et al.,1993; Pascualvaca et al., 1998), the two types of alertingfunctions, tonic and phasic alertness, were not consid-ered separately. When past data is reanalyzed exam-ining phasic and tonic alerting separately, autisticchildren benefited less than controls from the presenceof a cue (i.e., deficit of phasic alerting), and autisticsavants had slower response than controls in the no-cue condition (i.e., deficit of tonic alerting).

Morphometric studies have also shown evidence ofanatomical abnormalities in the parietal lobe in ASD(Courchesne et al., 1993), though not in other regionstypically associated with the alerting network (see Table3.3.1). However, numerous studies of individuals withautism provide evidence of anatomical abnormalitiesin the cerebellum (Courchesne et al., 1994; Hashimotoet al., 1995; Murakami et al., 1989), and brainstem(Courchesne et al., 1994; Hashimoto et al., 1995;Murakami et al., 1989). The cerebellum has been hypoth-esized to play a role in anticipatory operation, an ideaconsistent with the concept of phasic alerting (Allenand Courchesne, 2001), while nuclei in the brainstemare known to be related to tonic attention (e.g., locuscoeruleus) (Witte and Marrocco, 1997).

The cerebellum may play an important role in antic-ipating upcoming sensory events and in optimizingneural systems (e.g., brainstem, thalamus, and cerebralcortex) that mediate arousal and are involved in pro-cessing such events (Courchesne et al., 1994). In ASD,the abnormally low density of Purkinje cells in thecerebellar cortex may lead to disinhibition of the cere-bellar deep nuclei and consequent overexcitement ofthe thalamus and cerebral cortex. The cerebellummay also influence higher cognitive function, as ithas widespread connections with numerous non-motorareas, including the reticular activation system,



brainstem, thalamus, and parietal cortex (Itoh and Miz-uno, 1979; Kitano et al., 1976; Moruzzi and Magoun,1949; Nieuwenhuys et al., 1988; Sasaki et al., 1972;Schmahmann and Pandya, 1989; Snider, 1950; Vilenskyand van Hoesen, 1981). The cerebellum has also beenshown to have modulatory effects on sensory respon-siveness (Crispino and Bullock, 1984). Taken together,these findings suggest abnormalities in the alertingfunction of attention and that these functional abnor-malities may be related to structural abnormalitiesthat have frequently been reported in autism.

Orienting

It is a well-documented phenomenon that individualswith ASD do not orient to human faces normally.Although some studies have shown an orienting deficitrelated to social cues (e.g., Dawson et al., 1998), othersprovide evidence of an orienting deficit in autisticpatients that is not due to social information (Landryand Bryson, 2004; Renner et al., 2006; Teder-Salejarvi etal., 2005). Spatial orienting of attention has been studiedextensively in autism using the spatial attentionparadigm (Posner et al., 1984) (e.g., Casey et al., 1993;Townsend et al., 1996a, b). In a study by Casey andcolleagues (1993), patients with ASD showing savantskills provided evidence for abnormalities of both disen-gaging and moving of attention. Wainwright-Sharp andBryson (1993) demonstrated deficits in disengaging andmoving attention and difficulty processing briefly pre-sented cue information within the visual modality.Townsend and colleagues (1996a) separated individualswith ASD into groups with (P+) or without (P�) parietallobe abnormalities as defined by reduced posterior pari-etal cortex volume. The P+ group showed significantlyslower reaction times when detecting a target in anunexpected location relative to in an expected location,emphasizing the important role of the parietal lobes inthe functional deficits of orienting in autism.

An orienting deficit is also evident in tasks that requirerapid shifting of attention between modalities (Courch-esne et al., 1994), between object features (Courchesneet al., 1994; Rinehart et al., 2001), and between spatiallocations (Belmonte, 2000; Harris et al., 1999; Townsendet al., 1996a,b; Wainwright and Bryson, 1996; Wain-wright-Sharp and Bryson, 1993), and in responding toauditory or visual context stimulation when intensivelyfocused on processing a single piece of information (Lov-aas et al., 1971; 1979; TownsendandCourchesne, 1994). Inaddition, orientingdeficits also appearedwhen adjustingand updating the scope and focus of attention (Burack etal., 1997), in engaging visual attention in the presence ofdistractors (Burack, 1994), in disengaging attentionfrom a spatial focus (Wainwright and Bryson, 1996),


and in dividing attention between auditory and visualchannels (Casey et al., 1993). In other words, when thereare multiple parallel inputs from different sensorysystems or within one sensory modality, the ability toprocess the information of the unattended input is signif-icantly reduced in patients with ASD.

It has been observed that both patients with autismand patients with cerebellar damage have impairmentsin shifting attention between sensory modalities. Somehave proposed that such deficits may be a contributorto the development of ASD. Deficits in the ability todisengage and move attention have been reported inautism in relation to abnormal development of the cere-bellum (Akshoomoff et al., 2002). Abnormalities of theparietal lobes (Courchesne et al., 1993) have been relatedto a deficit of the orienting function (Townsend andCourchesne, 1994). In general, evidence suggests thatparietal lobe abnormalities are associated with difficul-ties in disengaging attention from current focus andthat cerebellar abnormalities affect the rapid and accu-rate moving of attention to a new focus in ASD.

Executive control

The over-focused or selective attention found inpatients with ASD (Lovaas et al., 1979; Lovaas andSchreibman, 1971) may reflect abnormal function ofexecutive attention. A dysfunction of executive controlin autism persists throughout development (Luna etal., 2007), and may be attributed to abnormalities offrontal lobes in patients with ASD (Aylward et al.,2002; Carper and Courchesne, 2000; Courchesne et al.,2001; Koshino et al., 2008; Sparks et al., 2002). Earlystudies have shown poor performance in patients withautism on executive tasks requiring a shift of mentalsets (Kanner, 1943; Lovaas et al., 1971; 1979). In a studyby Casey and colleagues (1993), although individualswith ASD with savant skills and normal controlsshowed no significant difference on single visual andsingle auditory CPT, those with savantism showeda significant deficit on dual visual and dual auditoryCPT, indicating a limited capacity in executive controlof attention for task switching. In the non-computerizedversion of the Wisconsin Card Sorting Test (WCST) (Pas-cualvaca et al., 1998), individuals with ASD show highererror rates and fewer categories, suggesting deficits ofexecutive control (i.e., mental flexibility).

One study showed that the most consistent deficit inpatients with ASD was in their performance of complexverbal tasks requiring cognitive switching and initiationof efficient lexical retrieval strategies, whereas cognitiveinhibition was intact (Kleinhans et al., 2005). It wasdemonstrated that decreased accuracy of response shift-ing in patients with autism was associated with


THE ATTENTION MODEL OF AUTISM 285

relatively reduced activation in frontal, striatal, andparietal regions, and that repetitive behavior was nega-tively correlated with cingulate functional activation(Shafritz et al., 2008). In a recent magnetic resonancespectroscopy study of the attentional networks in ASD,lower glutamate plus glutamine concentration in theright ACCwas found (Bernardi et al., 2011), which couldpotentially underlie deficits in executive control in ASD.

Although a behavioral deficit in cognitive control ingeneral has been demonstrated (Solomon et al., 2008),it has been shown that social stimuli can further interferewith cognitive control and activation of structures sub-serving this function, including the ACC (Dichter andBelger, 2007). In terms of neuropathology, Kemper andBauman (1993) have demonstrated that the ACC consis-tently exhibits abnormalities in postmortem studies ofpatients with autism. Frith and colleagues (2001) havefound ASD to be associated with deficits in midlinefrontal areas related to theory of mind, and Chiu andcolleagues (2008) have demonstrated abnormal patternsof cingulate activity during performance of an interper-sonal exchange game, suggesting that cingulate deficitscould underlie the social deficits associated with ASD.

The phenomena of ‘stimulus overselectivity’ (some,usually more relevant, aspects of a stimulus are selectedto the exclusion of other aspects of the stimulus) and‘underselectivity’ suggest that there are deficits in themonitoring function of the executive control network.Lovaas and colleagues (Lovaas and Schreibman, 1971)showed that children with normal developmentresponded equally to a complex stimulus consisting ofvisual, auditory, and tactile elements, whereas childrenwith autism responded primarily to only one element.Burack (1994) showed that the performance of patientswith autism on a forced-choice reaction time task wasimpaired in the presence of distractors, with no benefitfrom the presence of a smaller window to focus atten-tion. Since individuals typically benefit from a smallerwindow to focus attention in the presence of distractors,these findings suggest an impairment best explained byan abnormal interaction between orienting and execu-tive control functions. The impaired ability to filterextraneous information in ASD (related to deficits inexecutive control of attention) has also been suggestedas a primary source of over-arousal (Burack, 1994; Daw-son and Lewy, 1989). Overselectivity and underselectiv-ity correlate with the presence or absence of parietal lobeabnormality in autism (Allen and Courchesne, 2001;Townsend and Courchesne, 1994).

THE ATTENTION MODEL OF AUTISM

An attention model of autism was proposed over 30years ago (e.g., Gold and Gold, 1975). As discussed,


there is evidence to support an atypical pattern of atten-tion in ASD (Goldstein et al., 2001). It has been arguedthat attention may partly underlie the abnormal patternsof subjective experience reported by patients withautism (Murray et al., 2005). Further, abnormal func-tional activation related to impaired attention in ASD‘may be the developmental basis of higher order cogni-tive styles, such as weak central coherence’ (Belmonteand Yurgelun-Todd, 2003). In this context, the deficitsin social and cognitive development in autism may beconceptualized as having an attentional component.For example, amygdala activity, related to emotion pro-cessing, is dynamically modulated by the thalamocorti-cal pathways (Das et al., 2005) related to the alerting andorienting functions. Additionally, orienting and execu-tive control functions of attention are of fundamentalimportance during the normal exchange of information(e.g., joint attention between infants and mothers),which happens frequently, rapidly, often unpredictably,or with conflict between mental processes or responses.

Courchesne and colleagues (1994) have shown thatearly damage in one system alters neural organizationin other interconnected systems. They hypothesizedthat the Purkinje neuron loss seen in ASD would resultin deficits in timely and accurate direction of attentionand the expression of intention. Deficits in direction ofattention would then lead to deficits in infant–motherjoint social and affective interactions and eventuallyto more complex verbal and nonverbal communicationdeficits (Courchesne et al., 1994). In addition to socialcommunication difficulties, deficits in orienting maybe associated with executive control, as appears to bethe case in schizophrenia (Early et al., 1989a, b; Posneret al., 1988). An orienting deficit could arise based inpart on abnormal function of frontal areas that arepart of the executive control network. The linksbetween executive control and self-regulation havebeen established by studies using connectivity analysis(Crottaz-Herbette and Menon, 2006; Etkin et al., 2006)and suggest that deficits in the executive controlnetwork could have widespread consequences forcognition and emotion.

Given the widespread impairment of every aspect ofattention described above, one question that remains ishow an attentional theory of ASD would account forthe uneven developmental profile often observed, aswell as the specific impairment in social communicationthat is characteristic of ASD. While mother–child inter-action affected in ASD can be explained by deficits indirection of attention, it is not obvious why deficits indirection of attention appear to be more severe for socialthan nonsocial stimuli (e.g., Dawson et al., 1998; 2004;Maestro et al., 2002), or why young children with autismpreferentially orient to nonsocial over social stimuli(e.g., Klin et al., 2009; Kuhl et al., 2005). As we defined



attention as functioning to impact the order of thecomputations of other brain networks for access toconsciousness, perhaps the attentional profile in ASDis more related to deficits interacting with the networksrelated to social functioning, such as social communica-tion, which may differentiate autism from other disor-ders such as attention deficit/hyperactivity disorder.Potential interactions with other neural networks (e.g.,social communication network) require furtherinvestigation.

Finally, despite the accumulation of studies support-ing an attentional theory for autism, such studies sofar have only focused on single components of attentionwithout treating attention as an organ system that has itsown functions and networks, as I and my colleagueshave proposed (Posner Fan, 2008). The interactionsamong these attentional functions and networks, andbetween these attentional networks and other domain-specific networks for social function and communica-tion, would provide a useful heuristic to understandthe underlying mechanisms of attentional deficits inASD and their implications.

CONCLUSION

Data suggest that attentional deficits are a consistentfinding in ASD. Viewing such data in the context of anattentional network system (i.e., alerting, orienting, andexecutive functions), may help identify abnormalities ofneurocircuitry in autism that result in attentionaldysfunction. The attentional network framework mayalso allow us to hypothesize about the role of atten-tional difficulties in the primary pathophysiology ofASD.

ACKNOWLEDGMENTS

This work was supported by a NIH grant R21MH083164 to J.F. The author would like to thank Drs EvdokiaAnagnostou, Nicholas T. Van Dam, David Grodberg,Xiaosi Gu, Patrick R. Hof, and Michael I. Posner formaking insightful comments and for helping in editing.

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The Neuroscience of Autism Spectrum Disorders || Attentional Network Deficits in Autism Spectrum Disorders