Neural Connectivity and Activity-Dependent Genes in Autism
Assumptions of the PDPM provide heuristics that bridge theory on the development of joint attention with phenomenon associated with the nature of autism. One of these is that the PDPM links theory and research on early social behavior impairments to neural connectivity models of the etiology of autism.
Over the last 10 years numerous research groups have proposed that problems in functional connectivity between brain regions contribute to the development of autism [e.g., Courchesne & Pierce, 2005; Geschwind & Levitt, 2007; Horwitz et al., 1988; Just et al., 2004; Lewis & Elman, 2008; Wickelgren, 2005]. However, rather than specific to autism, impaired connectivity has been posited to be central to many forms of mental retardation and developmental disorders [Dierson & Ramakers, 2006]. So, how do neurodevelopmental connectivity impairments lead to the specific social symptom impairments of autism, and how are these different from the connectivity impairments that characterize other developmental disorders?
One possibility is that mental retardation may be associated with connectivity impairments within proximal brain networks, but that autism may be characterized by distal connectivity problems [Courchesne & Pierce, 2005; Lewis & Elman, 2008]. Indeed, several studies suggest that distal connectivity problems between frontal and temporal–parietal networks may be especially prominent in autism [Cherkassky, Kana, Keller, & Just, 2006; Courchesne & Pierce, 2005; Wicker et al., 2008]. The PDPM offers a moderately explicit developmental account of how the impairment of distal frontal–parietal pathways may have an early and robust effect specific to a disturbance of joint attention and related social symptom of autism such as lack of spontaneously sharing experiences with other people. The PDPM's focus on the fundamental relations between the joint processing of attention information, learning and symbolic development also provides a means for understanding why variations in the strength of the disturbance of anterior–posterior connectivity could contribute to phenotypic variability in autism such as the co-occurrence of mental retardation and or specific language impairments in some children.
The connectivity assumptions of PDPM also lead to the prediction that differences in the development of joint attention in typical and atypical children should be associated with measures of synchrony or coherence in cortical activity or development. There is some support for this, but currently available data are no more than suggestive in this regard [Mundy et al., 2000; Mundy, Fox, & Card, 2003]. Nevertheless, the PDPM offers a conceptual framework that emphasizes the benefits of a multidisciplinary approach to neurodevelopment, attention, connectionist network models of development and autism [Cohen, 2007; Lewis & Elman, 2008]. This emphasis is in line with the recent call for a multidisciplinary examination of relations between EEG or imagining coherence in developmental as well as intervention studies of autism [Dawson, 2008].
It also may be that autism is associated with postnatal connectivity processes that are more activity dependent than is the case in mental [Morrow et al., 2008]. Morrow et al. observed that the n expressions of three genes associated with the two large deletions specific to families of children with autism (c3orf58, NHE9 and PCDH10) are regulated by neuronal activity. From this observation, Morrow et al.  raise the hypothesis that defects in activity-dependent gene expression may be a cause of cognitive deficits in autism. They note that these genes likely have a defined temporal course of vulnerability to atypical expression depending on the timing and quality of the young child's postnatal activity and experience-dependent processes.
The PDPM proposes that problems with initiating activity, specifically IJA activity, may be especially key to understanding activity-dependent alterations of gene expression associated with autism. Some evidence consistent with this proposition stems from the observation that activity of children with autism may affect and modify the attempts of caregivers to scaffold the development of joint attention in their children [Adamson, McArthur, Markov, Dunbar, & Bakeman, 2001]. Indeed, if the PDPM is correct, it may be important to build an understanding of genetic influences on the typical range of expression of individual differences in IJA in infant development. Little if any information currently exists on this topic. Recent observations, however, have revealed a surprising degree of variability and longitudinal stability among infants on IJA measures from 9 to 18 months of age. This suggests that these infant measures may have sufficient psychometric characteristics to make it possible to bring behavioral or metabolic genetic methods to bear in the study of sources of variance in early joint attention development [Mundy et al., 2007].
The PDPM, Visual Attention Control and Autism
The work of several research groups indicates that basic mechanisms of visual control may play a role in autism [Brenner, Turner, & Muller, 2007; Johnson et al., 2005; Landry & Bryson, 2004]. Brenner et al.  have noted that one of the essential issues for this line of research is to understand precisely, “how an ocular-motor system that is over-specialized for certain tasks and under-specialized for others early in life might affect later development in [social] domains such as joint attention” (p 1302). The PDPM offers a guide in this regard. First, it encourages the research community to recognize the possibility that joint attention may not be a “later” development, but one that begins as part of the development of volitional visual attention control by the fourth month of life. In addition, the PDPM provides one path for understanding how significantly altered early visual preferences could have a cascading effect on the development of intentional joint attention and autism [Mundy, 1995]. Consider two recent studies in this regard.
McCleery, Allman, Carver, and Dobkins  observed that magnocellular visual processing may remain atypically enhanced in a sample of 6-month-old infant siblings of children with autism. Similarly, Karmel, Gardner, Swensen, Lennon, and London  observed visual attention patterns that are consistent with a magnocellular bias in 6-month-olds in neonatal intensive care who later received the diagnosis of autism at 3 years of age. The magnocellular visual system contributes to orienting based on movement and contrast sensitivity related to small achromatic differences in brightness. This system dominates early visual orienting. However, by 2–4 months visually orienting becomes increasingly influenced by the parvocellular system, which contributes to orienting based on high-resolution information about shape or low-resolution information about color and shades of gray. The studies of Karmel et al.  and McCleery et al.  raise the possibility that a delay in the developmental shift from the magnocellular to parvocellular visual systems could alter what children with autism choose or prefer to attend to early in life.
Hypothetically, the maintenance of a magnocellular bias may lead to a relatively long-standing visual preference for objects characterized by movement or achromatic contrasts such as surface edges, power lines, spinning objects, the outlines of faces or mouth movement. Reciprocally, the decreased influence of the parvocellular system could lead to developmental delays in the emergence of a visual attention bias to targets that are socially informative but involve differentiation based on high resolution of shape and color information, such as may be involved in the distal processing of eyes and facial expressions. Thus, the alteration of visual preferences during early critical periods of development could degrade the establishment of the dynamic system of internal information processing about active looking, relative to contingent social feedback, and information about the attention of other people [Mundy, 1995; Mundy & Burnette, 2005]. Moreover, if magnocelluar guidance bias and connectivity impairments are orthogonal processes in the etiology of autism, combinations of varying levels of their effects could present as phenotypic differences in joint attention processing and social symptom expression, such as some children having difficulty in disengaging object attention and others have difficulty flexibly integrating aspects of social attention. Both problems could lead to a significant common pathway of developmental disturbance through disruption of the dynamic development of the joint attention system.
Early Intervention, Learning, Motivation and the PDPM
The PDPM may also help to explain why joint attention is a pivotal skill in early intervention for children with autism [Bruinsma, Koegle, & Koegle, 2004; Charman, 2004; Mundy & Crowson, 1997]. Improvements in pivotal skills, by definition, lead to positive changes in a broad array of other problematic behaviors. This appears to be the case with joint attention. It can be improved with early intervention [e.g., Kasari, Freeman, & Paparella, 2006; Kasari et al., 2007; Pierce & Schreibman, 1995; Rocha, Schriebman, & Stahmer, 2007; Yoder & Stone, 2006]. Equally important, joint attention improvement has collateral benefits on language, cognitive and social development [Jones, Carr, & Feeley, 2006; Kasari et al., 2007; Whalen & Schreibman, 2006]. The level of expression of joint attention behaviors at the beginning of intervention may also mediate responsiveness to early intervention in children with autism [Bono et al., 2004; Yoder & Stone, 2006].
According to the PDPM, joint attention is a pivotal skill in autism because its improvement has multiple effects on social learning. Recall that joint attention facilitates the self-organization of information processing to optimize incidental as well as structured social-learning opportunities [Baldwin, 1995]. Hence, impairment in joint attention may be viewed as part of a broader social constructivist-learning disturbance in autism. By the same token effective intervention likely improves social constructivist learning in autism.
Second, the PDPM proposes that joint attention serves as a foundation for social-cognitive development. Social-cognitive development is defined in terms of advances in the comparative processing of information about self and others, rather than singularly in terms of changes in knowledge about intentionality. Following connectionist cognitive theory [McClelland & Rogers, 2003; Otten, Henson, & Rugg, 2001], an assumption of the PDPM is that whenever semantic information is acquired during social learning, it is also encoded in parallel with the activation of a frontal–temporal–parietal neural joint attention network that maps relations between representations of information about self-directed attention and information about the attention of other people. Thus, every time we process information in social learning we encode it as an activation pattern in a distributed semantic network in conjunction with an activation pattern of the anterior–posterior cortical joint attention network (see Figs. 4 and 5). Recall that deeper information processing and learning occurs best in the context of the simultaneous activation of multiple neural networks during encoding [Otten et al., 2001]. If so, joint attention may lead to deeper processing because it adds activation of the distributed social attention network (a form of episodic encoding) to the network activation associated more directly with semantic information. This conjecture provides one interpretation of the observation that joint attention facilitates depth of processing in 9-month-olds [Striano, Chen et al., 2006; Striano, Reid et al., 2006]. It also suggests that part of the learning disability of autism occurs because children with this disorder do not reap the full benefits of encoding semantic information in conjunction with episodic memory encoded within the integrated processing of self and other attention. This, in turn, may help to explain the attenuation of self-referenced memory effects in autism [Henderson et al., 2009].
Third, a related proposition of the PDPM is that as overt joint attention becomes an increasingly internalized (representational) process it supports the social coordination of covert mental attention to cognitive representations. The coordination of covert attention among people to a specific mental representation (or categorical exemplar) is an essential element of symbolic thought [Tomasello et al., 2005]. The PDPM assumes that months of practice of the social coordination of overt attention (i.e., joint attention) in the first years of life is required before we can internalize and transform this function to the social coordination of covert mental attention to common representations signified by symbols. Thus, symbolic thought processes incorporate, indeed may require the activation of the self–other joint attention system. Joint attention on the other hand does not necessarily involve symbolic process [Mundy, Sigman, Ungerer, & Sherman, 1987]. Consistent with this observation joint attention is a unique predictor of pretend play development in children with autism relative to measures of imitation or executive functions [Rutherford et al., 2008]. Also symbolic play intervention may have a greater impact on joint attention development than joint attention intervention may have on symbolic play development in young children with autism [Kasari et al., 2006].
Fourth, the joint processing of attention information also plays a fundamental role in social cognition defined in terms of the development of knowledge about intentions in self and others [Mundy & Newell, 2007]. The assumption here is that when infants or primates practice monitoring others' attention (RJA), statistical learning ultimately leads to the associative rule “where others' eyes go, their behavior follows” [Jellema et al., 2000]. Similarly, anterior monitoring or self-awareness of control of visual attention likely leads awareness of the self-referenced associative rule that “where my eyes go, my intended behavior follows” [Mundy & Newell, 2007]. An integration of the development of these “concepts” leads to the logical cognitive output “where others eyes gotheir intended behavior follows,” which is a building block of social-cognitive development [Mundy & Newell, 2007]. Social cognition of this kind is thought to enable new and more efficient levels of social or cultural learning, which is atypical in autism.
Finally, the constructivist assumptions of the PDPM stress that motivation factors are part of a crucial fifth path of association between joint attention and social learning. IJA requires “choosing” between behavior goals, such as fixated looking at an event, or alternating looking to the event and another person. Choice among behavior goals is thought to involve frontal and medial cortical processing of the relative reward associated with different goals [e.g., Holroyd & Coles, 2002]. Therefore, IJA impairment in autism may be related to deficits in bio-behavioral processes associated with reward sensitivity and motivation [Dawson, 2008; Kasari et al., 1990; Mundy, 1995]. Alternatively, the less volitional characteristics of the posterior attention system suggest that motivation processes may be less likely to contribute to RJA or gaze following problems in the development of autism [Mundy, 1995].
The motivational tendencies involved in IJA deficits in autism could be expressed in one of three basic patterns. Social stimuli could be aversive for children with autism and, therefore, these children less frequently spontaneously look to others to share interest in objects or events. However, the aversion hypothesis is complicated by observations of behaviors indicative of relatively intact caregiver attachment in many children with autism and a willingness to engage in playful physical interactions with strangers [e.g., Mundy et al., 1986; Sigman & Ungerer, 1984]. On the other hand, social stimuli may not be aversive. Rather, they may simply not be as rewarding as may be the case in typical development leading to a relative attenuation of social orienting and joint attention early in the life of children with autism [Dawson, Meltzoff, Osterling, Rinalidi, & Brown, 1998; Mundy, 1995]. Finally, social stimuli could have a positive valence for children with autism, but be overshadowed by an atypically strong visual preference that makes objects rather than social elements of the world more “interesting” [Karmel et al., 2008; McCleery et al., 2007; Mundy & Crowson, 1997].
The construction of effective empirical approaches to address these alternatives is one of the current outstanding challenges in the science of autism [Dawson, 2008; Koegel et al., 2003]. Research on joint attention in relation to motivation and the perceived valence of objects in adults [Bayliss et al., 2006] offers one potential route for developmental and functional neurocognitive studies on this topic. Bayliss et al.  have shown that looking at pictures with another person lends a more positive perceived valence to the pictures than when looking at pictures in conjunction with directional arrows. First it could be useful to determine if this phenomenon is evident among people with autism or related to symptom presentation. If not present, or if individual differences are related to symptom presentation, it may be possible and useful to examine the cortical and/or striatal systems involved in preference for stimuli viewed in joint attention vs. non-joint attention conditions in people with autism vs. comparison groups. Alternatively, the literature on early intervention may be the best source of information on motivation and its role in joint attention development in autism. Early intervention studies offer some of the most systematic investigations to date of how to structure social engagements with young children with autism to modify and increase their motivation to initiate episodes of shared attention and shared experience with others [e.g., Kasari et al., 2006,2007].
In conclusion, only in its most expansive or grandiose interpretation can the PDPM be viewed as an explanatory model of joint attention, or autism. Nevertheless, the PDPM does serve a purpose. It presents a new perspective on joint attention that suggests its impairment in autism is more than an epiphenomenon associated with other fundamental precursor or successor processes. The alternative perspective of the PDPM can be summed up in terms of several general principles. First, autism is as much about impairments in self-generated constructivist activity as it is about problems in perceiving or responding to the behavior of others. Hence, we need to consider the neurodevelopments involved in initiating behavior and attention control as well as those involved in perceiving and responding to the behaviors of others to understand this disorder [Mundy, 2003]. Second, joint attention and social cognition are forms of information processing that give rise to knowledge, but their development may not be wholly defined in terms of stages of knowledge acquisition. Third, joint attention is a form of parallel processing because it involves the conjoint perception and analysis of information about self-attention and the attention of other people. This conjoint analysis of information involves distributed processing across an anterior cortical system for processing internal information about goal-directed attention, and a posterior cortical system for processing external information about the attention-related behavior of other people. This observation encourages the adoption of a multidisciplinary approach to better link constructivist, connectionist neuroscience with parallel and distributed cognitive-processing models to better understand the specific nature of the social impairments of autism.