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Cited by 563Autism Spectrum Disorder ResearchChild and Animal Learning DevelopmentAction Observation and Synchronization

Autism as a disorder of prediction

Open access
Sinha, Pawan, Kjelgaard, Margaret M., Gandhi, Tapan K., Tsourides, Kleovoulos, Cardinaux, Annie L., Pantazis, Dimitrios, Diamond, Sidney P., Held, Richard M.·2014·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1416797111PMC PMC4210351
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Abstract

Significance: Autism is characterized by diverse behavioral traits. Guided by theoretical considerations and empirical data, this paper develops the hypothesis that many of autism's salient traits may be manifestations of an underlying impairment in predictive abilities. This impairment renders an otherwise orderly world to be experienced as a capriciously “magical” one. The hypothesis elucidates the information-processing roots of autism and, thereby, can aid the identification of neural structures likely to be differentially affected. Behavioral and neural measures of prediction might serve as early assays of predictive abilities in infants, and serve as useful tools in intervention design and in monitoring their effectiveness. The hypothesis also points to avenues for further research to determine molecular and circuit-level causal underpinnings of predictive impairments.

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Registry

Crossref · 10.1073/pnas.1416797111

Cites

119 of 119 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 99 cited sources checked · 0 supported · 0 flagged

  • Premisecitation
    § 1. The Hypothesis of Predictive Impairment in Autism · p. 2

    The core diagnostic domains of autism can be represented as temporally evolving Markov systems whose transitions are probabilistic.

    “The underlying domains all constitute temporally unfolding Markov systems, with progressions from one state to another governed by probabilistic links (Fig. 1 A ).”
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  • Interpretationreasoning
    § 1. The Hypothesis of Predictive Impairment in Autism · p. 2

    Because of that shift, some event relationships obvious to neurotypical people would become imperceptible to autistic people.

    “As a consequence of this shift, several relationships that are evident to a neurotypical individual would become undetectable to a person with autism.”
    Quote in the paperSubstantial claim
  • Premisecitation
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 3

    More than a third of autistic individuals are estimated to show some form of insistence on sameness.

    “It is estimated that more than one-third of all individuals on the autism spectrum display some form of IoS (14).”
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    • cites [14] source

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  • Premisecitation
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 3

    Insistence on sameness is a defining feature of autism.

    “Insistence on sameness (IoS) is a hallmark feature of autism.”
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    • cites [15] source

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  • Premisecitation
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 3

    Being less able to predict events increases anxious responses even when no aversive outcome follows.

    “Predictability is a fundamental modulator of anxiety in that reduction in the ability to predict events, even without any associated aversive consequence, enhances anxious responses (21, 22).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [21] Abbott BB, Badia P (1986) Predictable versus unpredictable shock conditions and physiological measures of stress: A reply to Arthur. Psychol Bull 100:384 -387. source

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    • cites [22] Herry C, et al. (2007) Processing of temporal unpredictability in human and animal amygdala. J Neurosci 27(22):5958 -5966. source

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    Interpretationreasoning
    § Autism as a disorder of prediction · p. 2

    Some prominent features of autism may stem from an underlying deficit in predictive abilities.

    “we describe how theoretical considerations and a review of empirical data lead to the hypothesis that some salient aspects of the autism phenotype may be manifestations of an underlying impairment in predictive abilities.”
    Quote in the paperNot a substantial claim

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    Interpretationnone given
    § 1. The Hypothesis of Predictive Impairment in Autism · p. 2

    Autism may involve inaccurate estimation of the conditional probability of one state given another and elapsed time.

    “The hypothesis of predictive impairment in autism (PIA) posits that autism may be associated with inaccuracies in estimating the P (B j A, Δ t ) conditional probability.”
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    Interpretationreasoning
    § 1. The Hypothesis of Predictive Impairment in Autism · p. 2

    Effective performance in those domains requires estimating the transition-probability matrix of the underlying Markov system.

    “To perform well in these domains, one necessarily needs to estimate the underlying Markov system, i.e., the matrix of interstate transition probabilities.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning
    § 1. The Hypothesis of Predictive Impairment in Autism · p. 2

    A decrease in predictive capacity would appear as an upward-left shift of the association sensitivity function in the strength-versus-temporal-separation space.

    “A reduction in one ' s predictive ability would, in this space, manifest as a shift of the ASF toward the upper left.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning
    § 1. The Hypothesis of Predictive Impairment in Autism · p. 2

    The brain must derive state-to-state conditional probabilities from observed temporal sequences.

    “from an observed temporal sequence, the brain has to estimate the conditional probability P (B j A, Δ t )”
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    Premisecitation
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 3

    Nearly 90% of autistic children are estimated to have sensory abnormalities, often hypersensitivity to stimuli that neurotypical people can ignore.

    “It is estimated that nearly 90% of all children on the autism spectrum suffer from sensory abnormalities, often hypersensitivities, to stimuli that a neurotypical individual could easily ignore (28).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Leekam SR, Nieto C, Libby SJ, Wing L, Gould J (2007) Describing the sensory abnormalities of children and adults with autism. J Autism Dev Disord 37(5):894 -910. source

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    Interpretationreasoning
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 3

    Rituals and insistence on sameness may both result from and help reduce anxiety caused by unpredictability.

    “Taken together, these results suggest that rituals and an insistence on sameness may be a consequence of, and a way to mitigate, anxiety arising out of unpredictability.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 3

    A parsimonious reading is that reliance on rituals and stimming in autism arises from and tries to lessen the effects of unpredictability.

    “a parsimonious interpretation of the reliance on rituals and stimming behaviors observed in autism is that they emerge from, and represent attempts to minimize, the consequences of unpredictability.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 3

    Stimulus predictability is a major determinant of habituation; for typically developing people, greater sequence predictability produces greater habituation.

    “A key determinant of habituation is stimulus predictability. For typically developing subjects, predictability of a sequence is directly proportional to the extent of habituation it induces (22, 34 -36).”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [22] Herry C, et al. (2007) Processing of temporal unpredictability in human and animal amygdala. J Neurosci 27(22):5958 -5966. source

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    • cites [34] Sokolov EN (1960) The Central Nervous System and Behavior III (Macy Foundation, New York).

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    • cites [35] McDaniel JW (1964) The effects of stimulus predictability upon auditory habituation and acquisition. Dissertation (Texas Technical College, Lubbock, TX).

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    • cites [36] Turk-Browne NB, Scholl BJ, Chun MM (2008) Babies and brains: Habituation in infant cognition and functional neuroimaging. Front Hum Neurosci 2:16.

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    Premisecitation
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 4

    Dynamic object tracking systems use predictive methods such as Kalman filtering, and impaired prediction causes errors in online position estimation.

    “Computational systems for dynamic object tracking rely on predictive techniques such as Kalman filtering (46). These systems demonstrate that a key consequence of impaired prediction is errors in online position estimation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Welch G, Bishop G (2001) An introduction to the Kalman Filter. Proc SIGGRAPH 2001 (Association for Computing Machinery, Los Angeles), pp 19 -24.

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    Interpretationreasoning
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 3

    If a person is less able to detect predictive links in a stimulus sequence, they will be less able to predict the next event, which would impair habituation and produce hypersensitivity.

    “Reduction in discerning predictive relationships between events in a stimulus sequence would reduce a person ' s ability to predict the onset of the next event. Such a lack of predictability would compromise habituation and lead to hypersensitivity.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Habituation suppresses sustained stimulation.

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    Premisereasoning
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 4

    Theory of mind involves assigning hidden causes to observations about a person by linking past history to current behavior.

    “Theory of mind requires the ability to ascribe invisible causes to observations about a person by connecting past history with current behavior.”
    Quote in the paperSubstantial claim

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    Interpretationreasoning
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 3

    PIA proposes that an internal prediction deficit makes environmental stimuli seem more chaotic, reducing habituation and increasing stress.

    “the PIA hypothesis suggests that an endogenous predictive impairment causes environmental stimuli to appear more chaotic, leading to reduced habituation and hence greater stress.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Habituation suppresses sustained stimulation.

  • May combine two claims.

    Premisecitation
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 3

    Studies show that unpredictable stressors are central to torture and produce anxiety, fear, and aversion.

    “Several studies have demonstrated that unpredictability of stressors is one of the key aspects of torture and leads to the development of anxiety, fear, and aversion (19, 37).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [19] source

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    • cites [37] Bas ¸o glu M, Mineka S (1992) The role of uncontrollable and unpredictable stress in posttraumatic stress responses in torture survivors. Torture and Its Consequences: Current Treatment Approaches (Cambridge Univ Press, Cambridge, UK), pp 185 -255.

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    Interpretationreasoning
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 5

    If prediction systems are differentially affected in autism, then relatively spared skills should be deterministic and not rely on temporally unfolding conditional probabilities.

    “If the prediction systems of the brain are differentially affected in autism, then one can expect that the skills left largely untouched would be the ones that are deterministic and where good performance does not depend on estimates of temporally unfolding conditional probabilities.”
    Quote in the paperSubstantial claim

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    Interpretationreasoning
    § 3. Predictions Arising from the PIA Hypothesis · p. 5

    Hyperarousal of these structures is expected to cause hypermalleable learning, where current experience outweighs earlier experience, a condition called hyperplasticity.

    “Hyperarousal of these structures would, in turn, be expected to lead to hypermalleability of learning; current exposure would have disproportionate weight and supersede earlier experience, constituting a kind of ' hyperplasticity. '”
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    Interpretationreasoning
    § 2. The PIA Hypothesis as a Partial Account of the Autism Phenotype · p. 5

    Most of these domains are strongly rule-based and reduce outcome uncertainty; except for music, they are static and do not require prediction over time.

    “Most of them, especially mathematics calendar calculations and music, are strongly rule-based, and, thus, minimize uncertainty of outcomes. Furthermore, with the exception of music, they are static, thereby obviating the need for prediction over time.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § 3. Predictions Arising from the PIA Hypothesis · p. 5

    Later studies have also reported these observations.

    “More recent studies (84, 85) have also documented these observations.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [84] Lyons V, Fitzgerald M (2004) Humor in autism and Asperger syndrome. J Autism Dev Disord 34(5):521 -531. source

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    • cites [85] Samson AC, Huber O, Ruch W (2013) Seven decades after Hans Asperger ' s observations: A comprehensive study of humor in individuals with Autism Spectrum Disorders. Humor 26:441 -460. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § 3. Predictions Arising from the PIA Hypothesis · p. 5

    Hans Asperger observed that his patients were humorless and did not understand jokes.

    “In describing his patients, Hans Asperger had noted that ' an essential characteristic of these children is their humorlessness. They do not understand jokes . . . ' (83).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [83] Asperger H (1944) Die ' Autistischen Psychopathen ' im Kindesalter. Eur Arch Psychiatry Clin Neurosci 117:76 -136.

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    Interpretationnone given
    § 4. Conclusion · p. 5

    The idea of core impairments shared by most autism cases appears to conflict with the heterogeneity of the phenotype.

    “However, the notion of core impairments, shared by most cases of autism, seems to be at odds with the heterogeneity of the phenotype.”
    Quote in the paperSubstantial claim

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    Interpretationreasoning
    § 4. Conclusion · p. 5

    We believe that predictive impairment may be an endophenotype shared across individuals with autism.

    “Based on theoretical considerations and a review of past literature, we believe that predictive impairment may constitute an endophenotype shared across individuals.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § 4. Conclusion · p. 5

    Autism can have many causes, but there is some commonality across its manifestations, which is why there is a shared clinical diagnosis.

    “Autism can have many etiologies, and yet, there is some commonality across manifestations, hence a shared clinical diagnosis.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [98] Tager-Flusberg H, Joseph RM (2003) Identifying neurocognitive phenotypes in autism. Philos Trans R Soc Lond B Biol Sci 358(1430):303 -314. source

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    • cites [99] Losh M, Childress D, Lam K, Piven J (2008) Defining key features of the broad autism phenotype: A comparison across parents of multiple- and single-incidence autism families. Am J Med Genet B Neuropsychiatr Genet 147B(4):424 -433. source

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    • cites [100] Jones W, Klin A (2009) Heterogeneity and homogeneity across the autism spectrum: The role of development. J Am Acad Child Adolesc Psychiatry 48(5):471 -473. source

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    Interpretationreasoning
    § 4. Conclusion · p. 5

    Such parametric differences may help explain phenotypic variability and provide a basis for a taxonomy of autism subtypes.

    “Such parametric differences may help account for the phenotypic variability observed across individuals on the autism spectrum and also potentially provide the basis for a principled taxonomy of different autism subtypes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning
    § 4. Conclusion · p. 6

    The PIA hypothesis is appealing because it offers a unifying explanation for several autistic traits.

    “Although it is certainly possible that the different autistic traits have different etiologies, what is appealing about the PIA hypothesis is its parsimony -an account that is able to provide a unifying explanation for not just a single trait, but for several of them.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § 4. Conclusion · p. 6

    Motor difficulties are thought to arise from cerebellar abnormalities.

    “Motor difficulties are believed to arise from abnormalities in the cerebellum (106).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [106] Mostofsky SH, et al. (2009) Decreased connectivity and cerebellar activity in autism during motor task performance. Brain 132(Pt 9):2413 -2425. source

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  • Classified as probably not a substantial claim.

    Premisecitation
    § 4. Conclusion · p. 6

    Explanatory accounts have been proposed for each autistic trait described in Sections 2 and 3.

    “Explanatory accounts have indeed been offered for each of the autistic traits we have described in Sections 2 and 3 .”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [102] Takeuchi M, Harada M, Nishitani H (2002) Deficiency of ' theory of mind ' in autism estimated by fMRI. Int Congr Ser 1232:737 -740. source

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    • cites [103] Gallese V, Goldman A (1998) Mirror neurons and the simulation theory of mindreading. Trends Cogn Sci 2(12):493 -501. source

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    • cites [104] Hadjikhani N (2007) Mirror neuron system and autism Progress in Autism Research , ed Carlisle PC, (Nova Science Publishers, Happauge, NY), pp 151 -166.

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § 4. Conclusion · p. 6

    Theory of Mind difficulties have been suggested to arise from abnormalities in cortical substrates for social cognition or in the mirror neuron system.

    “For instance, difficulties in Theory of Mind have been suggested as arising from abnormalities of the cortical substrates for social cognition (102) or in the mirror neuron system (refs. 103 and 104 but see 105).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [102] Takeuchi M, Harada M, Nishitani H (2002) Deficiency of ' theory of mind ' in autism estimated by fMRI. Int Congr Ser 1232:737 -740. source

      Not checked in the free run.

    • cites [103] Gallese V, Goldman A (1998) Mirror neurons and the simulation theory of mindreading. Trends Cogn Sci 2(12):493 -501. source

      Not checked in the free run.

    • cites [104] Hadjikhani N (2007) Mirror neuron system and autism Progress in Autism Research , ed Carlisle PC, (Nova Science Publishers, Happauge, NY), pp 151 -166.

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27 of 27

  • The paper relies on this without support.

    Autism has multiple causes.

    “Autism likely owes its genesis to a multiplicity of causes.”

  • The paper relies on this without support.

    Habituation suppresses sustained stimulation.

    “A key role in suppressing sustained stimulation is played by our ability to habituate.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • There may be important differences in neurobiological, emotional and cognitive responses to stressors for autistic people, warranting tailored anxiety models, assessments and interventions.

    “There may be important differences in neurobiological, emotional and cognitive responses to stressors for autistic people, which warrant tailored anxiety models, assessments and interventions [24].”

    From Autistic Cognition: Charting Routes to Anxiety (2021) · cites this paper as [24]

    The PIA hypothesis section (p. 3) proposes that impaired prediction can make stimuli seem more chaotic to autistic people, increasing stress and anxiety. The Conclusion (p. 6) discusses behavioral tests, neural markers, and therapeutic interventions for autism. It does not specifically call for tailored anxiety models, assessments, and interventions based on differences across neurobiological, emotional, and cognitive stress responses. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Autism has been cast as a 'disorder of prediction'.

    “with autism even being cast as a 'disorder of prediction' [136].”

    From How Do Expectations Shape Perception? (2018) · cites this paper as [136]

  • In the elaboration of the Bayesian brain hypothesis of ASD and subsequent theoretical papers, results from numerous earlier cognitive and psychophysical studies were re-interpreted post hoc in the novel framework.

    “In the elaboration of the Bayesian brain hypothesis of ASD (2) and subsequent theoretical papers (3, 4, 97–99), results from numerous earlier cognitive and psychophysical studies were re-interpreted post hoc in the novel framework.”

    From Can Bayesian Theories of Autism Spectrum Disorder Help Improve Clinical Practice? (2016) · cites this paper as [99]

  • A rapidly gaining theory of autism spectrum disorder is that individuals with autism spectrum disorder lack a robust historical representation of the world, making it difficult to predict upcoming events.

    “A theory of ASD that is rapidly gaining credibility is the notion that individuals with ASD do not have a robust historical representation of the world. This lack of a probabilistic “map” of the world makes it difficult for those with ASD to predict upcoming events, and this lack of predictive coding thus limits interactions with the external environment (Pellicano and Burr, 2012; Sinha et al., 2”

    From Behavioral, Perceptual, and Neural Alterations in Sensory and Multisensory Function in Autism Spectrum Disorder (2015) · cites this paper as Sinha et al., 2014

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. G Welch G Bishop An introduction to the Kalman Filter. Proc SIGGRAPH 2001 (Association for Computing Machinery Los Angeles) pp 19–24. (2001).

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Related

Authors
Sinha, P., Kjelgaard, M. M., Gandhi, T. K., Tsourides, K., Cardinaux, A. L., Pantazis, D., Diamond, S. P., & Held, R. M.
Affiliations
  • Massachusetts Institute of Technology (US)
  • MGH Institute of Health Professions (US)
  • Defence Institute of Physiology and Allied Sciences (IN)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2014-10-06
Volume
111
Issue
42
Pages
15220-15225
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1416797111
PMC
PMC4210351
OpenAlex
W2088415689
Cited by
563
References
119
Citations by year
2026: 43 · 2025: 47 · 2024: 48 · 2023: 67 · 2022: 47 · 2021: 79 · 2020: 56 · 2019: 41 · 2018: 38 · 2017: 40 · 2016: 36 · 2015: 20
FWCI
17.70
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Social Sciences › Psychology › Developmental and Educational Psychology › Child and Animal Learning Development
  • Social Sciences › Psychology › Social Psychology › Action Observation and Synchronization
Keywords
autism spectrum disorder, prediction, predictive processing, autism phenotype, theory of mind, social cognition, diagnostic biomarkers, autism treatment
MeSH terms
Autistic Disorder, Basal Ganglia, Cerebellum, Cognition, Corpus Striatum, Humans, Infant, Language, Markov Chains, Models, Theoretical, Neuronal Plasticity, Phenotype, Probability, Social Behavior, Time Factors

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