The Intense World Theory – A Unifying Theory of the Neurobiology of Autism

Abstract

Autism covers a wide spectrum of disorders for which there are many views, hypotheses and theories. Here we propose a unifying theory of autism, the Intense World Theory. The proposed neuropathology is hyper-functioning of local neural microcircuits, best characterized by hyper-reactivity and hyper-plasticity. Such hyper-functional microcircuits are speculated to become autonomous and memory trapped leading to the core cognitive consequences of hyper-perception, hyper-attention, hyper-memory and hyper-emotionality. The theory is centered on the neocortex and the amygdala, but could potentially be applied to all brain regions. The severity on each axis depends on the severity of the molecular syndrome expressed in different brain regions, which could uniquely shape the repertoire of symptoms of an autistic child. The progression of the disorder is proposed to be driven by overly strong reactions to experiences that drive the brain to a hyper-preference and overly selective state, which becomes more extreme with each new experience and may be particularly accelerated by emotionally charged experiences and trauma. This may lead to obsessively detailed information processing of fragments of the world and an involuntarily and systematic decoupling of the autist from what becomes a painfully intense world. The autistic is proposed to become trapped in a limited, but highly secure internal world with minimal extremes and surprises. We present the key studies that support this theory of autism, show how this theory can better explain past findings, and how it could resolve apparently conflicting data and interpretations. The theory also makes further predictions from the molecular to the behavioral levels, provides a treatment strategy and presents its own falsifying hypothesis.

Increased power of resting-state gamma oscillations in autism spectrum disorder detected by routine electroencephalography

“…Ongoing neural activity can be assessed noninvasively during a resting-state EEG recording, i.e., in the absence of task performance or sensory stimulation, in which patterns of neural oscillations may be detected [2]. It has been suggested that elevated oscillatory activity in ASD might indicate hyperactivity in cortical circuits, and subsequently may be associated with the ''autistic'' state [3,4], which is in agreement with a recent review summarizing EEG abnormalities during resting-state paradigms in ASD, reporting increased power in low (delta, theta) and high frequencies (beta, gamma) and reduced activity in middlerange frequencies (alpha) [2]. A few experimental studies report altered resting-state gamma activity by EEG or MEG.…”

Abnormal Mechanisms of Plasticity and Metaplasticity in Autism Spectrum Disorders and Fragile X Syndrome

“…These changes at the level of a single neuron or synapse lead to the development and maintenance of neural circuitry. We and others have suggested that abnormalities in regulation of these synaptic changes lead to larger-scale alterations in plasticity and metaplasticity that may account for the neurological and behavioral phenotype of ASD and fragile X syndrome (FXS) (Markram and Markram 2010;Oberman et al 2015).…”

“…ASD is diagnosed by clinical criteria, and the exact brain dysfunction that leads to the behavioral phenotype in nonsyndromic ASD remains unknown. However, altered mechanisms of synaptic, use-dependent plasticity and metaplasticity are likely essential components of the ASD pathophysiology (Dolen and Bear 2009;Markram and Markram 2010;Oberman et al 2010Oberman et al , 2012Oberman 2015).…”

Facilitating Autism Research

“…These include the "Intense World" hypothesis of Markram and Markram (2010), in which stimuli experienced as painfully intense lead to selective attention and avoidance of social input. Similarly, Kinsbourne (2011) suggests that an unstable arousal system leads to avoidance of unpredictable social input, to restricted interests, and to inward focus of attention.…”