ReviewAutism as a neural systems disorder: A theory of frontal-posterior underconnectivity
Highlights
► Our theory attributes autism to impaired frontal-posterior brain connectivity. ► We present functional and structural brain imaging and behavioral evidence. ► We model underconnectivity with frontal-posterior bandwidth constraints. ► We account for language and social deficits and perceptual sparing in autism. ► We account for individual differences in functional connectivity in autism.
Introduction
Although autism has surely been with mankind for millennia, it was systematically identified only recently by Kanner (1943), and Asperger (1944). Both of these papers were psychiatric case studies of children, and their characterizations of the behaviors in autism remain accurate and insightful to this day. Although neither of these seminal papers provided a scientific account of autism at either the behavioral or neuroscientific level, they both suggested a possible biological origin for the disorder. Despite this identification of the disorder in the 1940s, scientific research into autism (and its funding) remained small in scale in the U.S. until the 1990s, when new methods of cognitive and social neuroscience were developed and began to be applied to autism. Methods including genomics, eye-movement tracking, and electrophysiology held the promise of providing an understanding of the psychological and biological mechanisms that underpin the disorder. Our focus here is on the findings from another new method, neuroimaging of brain structure and of brain activity. In this paper, we propose a formal model of autism that integrates some of the recent neuroimaging findings, instantiating a cortical systems underconnectivity theory of autism.
Autism has long been an enigma in at least three ways: one way is that the symptoms (disorder of social and communicative behaviors, and a restricted range of interests) are diverse and seemingly unrelated; another way is that the syndrome does not bear an obvious correspondence to a particular biological function (such as some forms of blindness being related to damage to the visual cortex); and a third way is that occasionally autism is manifested as a perceptual advantage. However, with the rapid development of new scientific understanding of brain function that has occurred in the past two decades, it is now possible to make sense of these three aspects of the enigma: the diversity of the symptoms of autism can now be understood as a manifestation of a neural systems disorder whose impacts are widespread; the link to a biological substrate is being illuminated by functional and anatomical brain imaging as well as by genomic research; and the understanding of the brain and cognition as a complex system illuminates how a perturbation of the system can have both negative and positive impacts on system functioning. The theory we propose here attempts to provide a detailed scientific account of some aspects of the enigma.
Autism has recently been characterized as a disorder of neurological origin with abnormalities found in the coordinated functioning of brain regions. This theoretical view, the cortical underconnectivity theory, first emerged from fMRI (functional magnetic resonance imaging) measurements of cortical activation in several types of thinking tasks. These studies showed that the degree of synchronization of the activation (or functional connectivity) between frontal and posterior brain regions was lower in autism. The observation was first made in a language comprehension task (Just et al., 2004), and undersynchronization of activation during task performance has since been found between the frontal lobe and more posterior regions in a wide variety of other tasks (Damarla et al., 2010, Just et al., 2004, Just et al., 2007, Kana et al., 2006, Kana et al., 2007, Kana et al., 2009, Koshino et al., 2005, Koshino et al., 2008, Mason et al., 2008, Mizuno et al., 2011, Schipul et al., 2011; see Schipul et al., in press for a recent review). We propose that the lower synchronization arises because the communication bandwidth between frontal and posterior cortical areas is lower in autism than in the typical population. We use the term bandwidth to refer to the maximal rate of data transfer supported by a communication channel, taking into account the impact of noise, consistent with Shannon's (1949) usage.
Decreased bandwidth would clearly impact system performance when the interregional communication needs were high enough. Some of the central questions that emerge from examining underconnectivity in autism are: (1) How would a bandwidth constraint in autism affect the communication transfer between frontal and posterior regions? (2) How might a brain with autism adapt to or compensate for such an impairment? (3) Does the physical or anatomical distance between cortical areas play a key role in information transfer in autism? (4) Are there underlying structural and developmental bases for the underconnectivity? and (5) Can computational modeling of fMRI data account for the variation in synchronization (functional connectivity) in terms of variation in several structural and functional attributes of the brain? In this paper, we attempt to address these questions using a formal theory accompanied by a computational model.
This article is organized into several sections below: a brief summary of previous findings, a description of underconnectivity theory and of its implementation as a computational model, and a discussion of the theory and its relation to other theories.
Section snippets
Previous biological findings
Several types of previous background findings concerning brain biology lend plausibility to underconnectivity theory, although they are not a part of the theory proper.
Convergence of the brain imaging evidence implicating disrupted connectivity in autism
Aside from the lower-level biological mechanisms cited above that could underpin cortical connectivity disruption, four recent brain imaging findings more directly implicate aberrant cortical connectivity in autism, and they do so in a tightly convergent way.
First, the synchronization of activation (or functional connectivity) between frontal and posterior regions of the cortex is lower in autism than in control groups during task performance across a number of different domains of thought,
Underconnectivity theory
The cortical underconnectivity theory that we have previously proposed in the context of specific tasks (Just et al., 2004, Just et al., 2007) posits that inter-regional (systems level) connective circuitry in the brain is disrupted in autism, and that patterns of thought that are particularly dependent on integration of frontal and more posterior contributions are disrupted. Furthermore, the theory attributes disruptions in psychological functions such as Theory of Mind and executive
Computational modeling of brain function and cognition
As functional imaging is increasingly providing finer detail about brain activation, computational modeling provides a theory-building workspace where the new pieces of information about underlying mechanisms can be brought together and their co-functioning can be examined (Just and Varma, 2007). In this workspace, the component mechanisms can be specified in detail, and their ability to account for the observed phenomena can be tested, as a few initial attempts have shown (Anderson et al., 2004
The 4CAPS model of frontal-posterior underconnectivity in autism
The new model takes as its point of departure the 4CAPS model of TOL problem-solving in healthy adults (Newman et al., 2003), and modifies it to account for the fMRI findings of lower functional connectivity in autism in this task (Just et al., 2007). The first modification is the enforcement of bandwidth constraints on communication between frontal and posterior centers. The second modification, which is assumed to arise as an adaptation to the bandwidth constraints, is increased autonomy of
Modeling results
The control and autism models were run on several blocks of the stimuli used in the Just et al. (2007) study. The models solved the problems making the same moves as the human participants (using the shortest solution path), generating a predicted fMRI time series for each model center. Correlations between these time series were computed for pairs of model centers in each model, corresponding to the functional connectivity measures of the human data.
Discussion of the model
Formal modeling of a complex process constitutes a theoretical account to provide added value beyond a verbal description of the underlying mechanism. A verbal description of a dynamic process cannot capture the detail of the processing or the unfolding of events over time. Modeling enforces a specific, precise computational implementation of the theory, shedding light on both the sufficiency and necessity of its proposals. The ability of the models to solve TOL problems also demonstrates the
Relation to other theories of autism
The concreteness of the computational model facilitates the comparison between underconnectivity theory and predecessor approaches to autism, such as the theories of weak central coherence (Frith, 1989), impaired complex information processing (Minshew et al., 1997), enhanced perceptual functioning (Mottron et al., 2006), mindblindness (Baron-Cohen, 1995), impaired social processing and motivation (Dawson et al., 2002), and longer-distance cortical communication. All of these theories capture
Questions raised by the theory
Although the underconnectivity perspective provides a useful theoretical framework for investigating autism, the theory does not currently provide the answers to some remaining central questions about autism. We view the current form of the underconnectivity theory as preliminary, and anticipate that future research will result in considerable refinement, expansion, and modification. Below we raise some of the key questions that are currently framed by the theory but which have not yet been
Summary
Underconnectivity theory proposes that autism be characterized as a neural systems disorder marked by frontal-posterior connectivity abnormalities. Because of lowered bandwidth between frontal and posterior brain networks in autism, the flow of information between frontal and posterior areas is impaired, resulting in deficits in tasks that require substantial frontal contribution and in increased reliance on posterior regions. This increased dependence on more posterior regions could become
Acknowledgements
This research was supported by the Autism Centers of Excellence Grant HD055748 from the National Institute of Child Health and Human Development and the Office of Naval Research Grant N00014-07-1-0041.
References (148)
- et al.
The variability of human, BOLD hemodynamic responses
NeuroImage
(1998) - et al.
Diffusion tensor imaging of the corpus callosum in Autism
NeuroImage
(2007) - et al.
Synthetic brain imaging: grasping, mirror neurons and imitation
Neural Networks
(2000) - et al.
Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients
Neuroimage
(2010) - et al.
White matter structure in autism: preliminary evidence from diffusion tensor imaging
Biological Psychiatry
(2004) - et al.
Accelerated maturation of white matter in young children with autism: a high B value DWI study
NeuroImage
(2007) - et al.
Attention does not modulate neural responses to social stimuli in autism spectrum disorders
NeuroImage
(2006) - et al.
A model of attentional impairments in autism: first steps toward a computational theory
Cognitive Systems Research
(2005) - et al.
Localized enlargement of the frontal cortex in early autism
Biological Psychiatry
(2005) - et al.
Cerebral lobes in autism: early hyperplasia and abnormal age effects
NeuroImage
(2002)
Less white matter concentration in autism: 2D voxel-based morphometry
NeuroImage
EEG power and coherence in autistic spectrum disorder
Clininical Neurophysiology
An artificial neural network analogue of learning in autism
Biological Psychiatry
Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection
Current Opinion in Neurobiology
Brain overgrowth in autism during a critical time in development: implications for frontal pyramidal neuron and interneuron development and connectivity
International Journal of Developmental Neuroscience
Children's reading performance is correlated with white matter structure measured by diffusion tensor imaging
Cortex
Dopaminergic and non-dopaminergic value systems in conditioning and outcome-specific revaluation
Brain Research
Microstructural connectivity of the arcuate fasciculus in adolescents with high-functioning autism
NeuroImage
Autism spectrum disorders: developmental disconnection syndromes
Current Opinion in Neurobiology
The link between brain learning, attention, and consciousness
Consciousness and Cognition
Inadequate cortical feature maps: a neural circuit theory of autism
Biological Psychiatry
Rapid conduction and the evolution of giant axons and myelinated fibers
Current Biology
Evidence for executive dysfunction in autism
Neuropsychologia
Morphometric study of human cerebral cortex development
Neuropsychologia
Sources of group differences in functional connectivity: an investigation applied to autism spectrum disorder
NeuroImage
Topographic maps are fundamental to sensory processing
Brain Research Bulletin
Inhibitory control in high-functioning autism: decreased activation and underconnectivity in inhibition networks
Biological Psychiatry
Altering cortical connectivity: remediation-induced changes in the white matter of poor readers
Neuron
The intrinsic functional organization of the brain is altered in autism
NeuroImage
Language laterality in autism spectrum disorder and typical controls: a functional, volumetric, and diffusion tensor MRI study
Brain and Language
Functional connectivity in an fMRI working memory task in high-functioning autism
NeuroImage
Diffusion tensor imaging of white matter in the superior temporal gyrus and temporal stem in autism
Neuroscience Letters
Microglia promote the death of developing Purkinje cells
Neuron
Theory of Mind disruption and recruitment of the right hemisphere during narrative comprehension in autism
Neuropsychologia
An integrated theory of the mind
Psychological Review
A clinicopathological study of autism
Brain
Are autistic children ‘behaviorists’?
Journal of Autism and Developmental Disorders
Mindblindness: An Essay on Autism and Theory of Mind
Histoanatomic observations of the brain in early infantile autism
Neurology
Unfamiliar face recognition in relatively able autistic children
Journal of Child Psychology and Psychiatry and Allied Disciplines
Linear systems analysis of functional magnetic resonance imaging in human V1
The Journal of Neuroscience
The temporal binding deficit hypothesis of autism
Developmental Psychopathology
Hypothesis: Is infantile autism a hypoglutamatergic disorder? Relevance of glutamate–serotonin interactions for pharmacotherapy
Journal of Neural Transmission
Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes
Brain
Selective stabilization of developing synapses as a mechanism for the specification of neuronal networks
Nature
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