Cited by 394Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology Research

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The intense world syndrome-an alternative hypothesis for autism

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Markram, Henry·2007·Frontiers in Neuroscience

DOI 10.3389/neuro.01.1.1.006.2007PMC PMC2518049

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Abstract

Autism is a devastating neurodevelopmental disorder with a polygenetic predisposition that seems to be triggered by multiple environmental factors during embryonic and/or early postnatal life. While significant advances have been made in identifying the neuronal structures and cells affected, a unifying theory that could explain the manifold autistic symptoms has still not emerged. Based on recent synaptic, cellular, molecular, microcircuit, and behavioral results obtained with the valproic acid (VPA) rat model of autism, we propose here a unifying hypothesis where the core pathology of the autistic brain is hyper-reactivity and hyper-plasticity of local neuronal circuits. Such excessive neuronal processing in circumscribed circuits is suggested to lead to hyper-perception, hyper-attention, and hyper-memory, which may lie at the heart of most autistic symptoms. In this view, the autistic spectrum are disorders of hyper-functionality, which turns debilitating, as opposed to disorders of hypo-functionality, as is often assumed. We discuss how excessive neuronal processing may render the world painfully intense when the neocortex is affected and even aversive when the amygdala is affected, leading to social and environmental withdrawal. Excessive neuronal learning is also hypothesized to rapidly lock down the individual into a small repertoire of secure behavioral routines that are obsessively repeated. We further discuss the key autistic neuropathologies and several of the main theories of autism and re-interpret them in the light of the hypothesized Intense World Syndrome.

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Authors: Markram, H.
Affiliations: École Polytechnique Fédérale de Lausanne (CH)
Corresponding author: Markram, Henry
ORCID: Markram, Henry
Venue: Frontiers in Neuroscience
Publisher: Frontiers Media SA
Published: 2007-11-01
Volume: 1
Issue: 1
Pages: 77-96
ISSN: 1662-453X (ISSN-L)
1662-4548
DOI: 10.3389/neuro.01.1.1.006.2007
PMC: PMC2518049
OpenAlex: W2128332414
Cited by: 394
References: 258
Citations by year: 2026: 7 · 2025: 13 · 2024: 10 · 2023: 21 · 2022: 17 · 2021: 32 · 2020: 19 · 2019: 35 · 2018: 25 · 2017: 37 · 2016: 22 · 2015: 34 · 2014: 28 · 2013: 26 · 2012: 18
FWCI: 4.84
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Neuroscience (publishedVersion, cc-by)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
Funders: European Commission
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: autism spectrum disorder, neural circuits, neocortex, amygdala, social withdrawal, repetitive behavior, autism theory, neuropathology

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