Monday, December 12, 2016

Autism brain response theory a dead end

Study: Autism brain response theory a dead end
University of Rochester Medical Center

A new study in the journal Cerebral Cortex challenges the hypothesis that nerve cells in the brains of individuals with autism spectrum disorders do not reliably and consistently respond to external stimuli.

“Our findings show there is no measurable variation in how individuals with autism respond to repeated visual and tactile stimuli,” said John Foxe, PhD, the chair of the University of Rochester Medical Center Department of Neuroscience and senior author of the study. “Consequently, the concept that the symptoms of Autism may arise from unreliable brain activity in response to the senses is in all likelihood a scientific cul–de–sac.”

The neuronal unreliability theory, which has gained traction in recent years in the wake of a study published in 2012, is based on the assumption that the brain’s response to repetitive stimuli – visual, audio, or touch – should be steady and consistent. According to this theory, the brain’s response is not constant in individuals with autism and, consequently, alters their perception of the physical environment and impairs cognitive and social development.

The theory did not ring true with Foxe and his colleagues, based on their decades of studying the brain activity of children with autism spectrum disorders. Furthermore, the original studies that formed the basis for this hypothesis involved functional MRI experiments which measure changes in the blood oxygen levels in the brain. While fluctuations in blood flow are important indicators of brain activity, these measures do not precisely correlate to the more rapid electrical activity that occurs in the brain when nerve cells are stimulated.

The new study involved 20 individuals diagnosed with autism and 20 individuals who served as healthy controls. The participants were fitted with a dense array of electrodes on the surface of their scalp to record brain electrical activity and were then exposed to repeated visual stimuli. No matter how the researchers measured the variability of the responses, brain responses in autism were as stable as those of the controls. To make sure that this wasn’t just the case in the visual system, the team also evaluated tactile inputs – repeated touches to the wrists of participants – and, once again, measures of brainwave responses provided no evidence whatsoever of increased response variability in the individuals with autism.

“The point of this study is not to make the case that there aren’t any differences in the way that people with an autism spectrum disorders process touch, sight or sound; research shows clear differences in some cases,” said Sophie Molholm, PhD, an associate professor of Pediatrics and Neuroscience at the Albert Einstein College of Medicine and co–author of the study. “Rather, it is to say that whatever those differences may be, they likely don’t simply arise because the brain responses in autism are more variable.”

The authors contend that, while the study essentially demonstrates negative findings, it represents an important contribution in the field of autism where much of our understanding of the disease is – to the frustration of patients, families, research, and caregivers alike – long on theory and conjecture but short on solid scientific fact.

Butler JS, Molholm S, Andrade GN, Foxe JJ. An Examination of the Neural
Unreliability Thesis of Autism. Cereb Cortex. 2016 Dec 6. [Epub ahead of print]


An emerging neuropathological theory of Autism, referred to here as "the neural unreliability thesis," proposes greater variability in moment-to-moment cortical representation of environmental events, such that the system shows general instability in its impulse response function. Leading evidence for this thesis derives from functional neuroimaging, a methodology ill-suited for detailed assessment of sensory transmission dynamics occurring at the millisecond scale. Electrophysiological assessments of this thesis, however, are sparse and unconvincing. We conducted detailed examination of visual and somatosensory evoked activity using high-density electrical mapping in individuals with autism (N = 20) and precisely matched neurotypical controls (N = 20), recording large numbers of trials that allowed for exhaustive time-frequency analyses at the single-trial level. Measures of intertrial coherence and event-related spectral perturbation revealed no convincing evidence for an unreliability account of sensory responsivity in autism. Indeed, results point to robust, highly reproducible response functions marked for their exceedingly close correspondence to those in neurotypical controls.


  1. Pantelis PC, Byrge L, Tyszka JM, Adolphs R, Kennedy DP. A specific
    hypoactivation of right temporo-parietal junction/posterior superior temporal sulcus in response to socially awkward situations in autism. Soc Cogn Affect Neurosci. 2015 Oct;10(10):1348-56.

    People with autism spectrum disorder (ASD) often have difficulty comprehending social situations in the complex, dynamic contexts encountered in the real world. To study the social brain under conditions which approximate naturalistic situations, we measured brain activity with FUNCTIONAL MAGNETIC RESONANCE IMAGING: while participants watched a full-length episode of the sitcom The Office. Having quantified the degree of social awkwardness at each moment of the episode, as judged by an independent sample of controls, we found that both individuals with ASD and control participants showed reliable activation of several brain regions commonly associated with social perception and cognition (e.g. those comprising the 'mentalizing network') during the more awkward moments. However, individuals with ASD showed less activity than controls in a region near right temporo-parietal junction (RTPJ) extending into the posterior end of the right superior temporal sulcus (RSTS). Further analyses suggested that, despite the free-form nature of the experimental design, this group difference was specific to this RTPJ/RSTS area of the mentalizing network; other regions of interest showed similar activity across groups with respect to both location and magnitude. These findings add support to a body of evidence suggesting that RTPJ/RSTS plays a special role in social processes across modalities and may function atypically in individuals with ASD navigating the social world.

  2. Shen IH, Lin SC, Wu YY, Chen CL. An Event-Related Potential Study on the Perception and the Recognition of Face, Facial Features, and Objects in Children With Autism Spectrum Disorders. Percept Mot Skills. 2016 Dec 7. pii:0031512516681694. [Epub ahead of print]

    The study investigated whether children with autism spectrum disorders (ASD) showed atypical patterns of brain specialization for face processing, whether the response to familiar and unfamiliar faces, facial features, and objects were different from typically developing children. Event-related potentials were recorded in 5- to 8-year-old children (12 children with ASD, 12 typically developing children) using passive viewing paradigm. The fastest P1 latencies to faces and the largest P1 amplitudes to objects were observed in both participant groups. Both groups exhibited larger N170 response to faces and eyes, F(3, 66) = 46.94, p < .0001). However, earlier P1 and N170 latencies were found on left hemisphere in children with ASD, respectively, F(1, 83) = 4.32, p = .04; F(1, 83) = 6.73, p = .01, indicating an atypical face processing pattern. All children showed a significant effect of familiarity for objects and mouths, F(1, 71) = 33.97, p < .0001; F(1, 71 = 15.94, p = .0002. Children with ASD revealed smaller negative central to faces relative to typically developing children. Face processing abnormalities revealed in children with ASD very likely exist.

  3. Green SA, Hernandez L, Bookheimer SY, Dapretto M. Reduced modulation of thalamocortical connectivity during exposure to sensory stimuli in ASD. Autism Res. 2016 Nov 29. doi: 10.1002/aur.1726. [Epub ahead of print]

    Recent evidence for abnormal thalamic connectivity in autism spectrum disorders (ASD) and sensory processing disorders suggests the thalamus may play a role in sensory over-responsivity (SOR), an extreme negative response to sensory stimuli, which is common in ASD. However, there is yet little understanding of changes in thalamic connectivity during exposure to aversive sensory inputs in individuals with ASD. In particular, the pulvinar nucleus of the thalamus is implicated in atypical sensory processing given its role in selective attention, regulation, and sensory integration. This study aimed to examine the role of pulvinar connectivity in ASD during mildly aversive sensory input. Functional magnetic resonance imaging was used to examine connectivity with the pulvinar during exposure to mildly aversive auditory and tactile stimuli in 38 youth (age 9-17; 19 ASD, 19 IQ-matched typically developing (TD)). Parents rated children's SOR severity on two standard scales. Compared to TD, ASD participants displayed aberrant modulation of connectivity between pulvinar and cortex (including sensory-motor and prefrontal regions) during sensory stimulation. In ASD participants, pulvinar-amygdala connectivity was correlated with severity of SOR symptoms. Deficits in modulation of thalamocortical connectivity in youth with ASD may reflect reduced thalamo-cortical inhibition in response to sensory stimulation, which could lead to difficulty filtering out and/or integrating sensory information. An increase in amygdala connectivity with the pulvinar might be partially responsible for deficits in selective attention as the amygdala signals the brain to attend to distracting sensory stimuli.