Overconnectivity in the brain underlies sensory overresponsivity in autism

June 16, 2015

By Will Boggs MD

NEW YORK (Reuters Health) - Functional overconnectivity between brain regions underlies the sensory overresponsivity (SOR) seen in young people with autism spectrum disorder (ASD), according to results from two research teams.


"Some families may find it helpful to know that their child is avoiding or reacting negatively to sensory stimuli because their brain works a little differently, rather than because they are being 'difficult,'" Dr. Shulamite A. Green from the University of California, Los Angeles, told Reuters Health by email.

"Physicians can let them know that their child's brain is overwhelmed by the stimuli and does not seem able to get used to the stimuli as quickly as happens with others' brains. So while the parent might be distracted by a loud noise for a few seconds and then be able to move on and forget about it, the child with SOR continues to be bothered by the noise, likely making it difficult for that child to attend to other stimuli, such as social cues," Dr. Green continued.


Although as many as 70% of youth with ASD meet criteria for SOR, little is known about its neurobiological basis. Two June 10 online reports in JAMA Psychiatry aim to clarify the neurological underpinnings of SOR.


Dr. Green's team examined functional amygdala-orbitofrontal cortex connectivity during exposure to three stimulus conditions (auditory, tactile, and both) in 19 youths with an ASD and 19 typically developing matched controls.


While functional magnetic resonance imaging (fMRI) findings did not differ between groups in the auditory condition (traffic noise), the tactile condition (rubbing with a scratchy wool fabric) elicited greater activation in the bilateral somatosensory cortex in ASD subjects. When both stimuli were presented concurrently, the ASD group had greater activation in the bilateral somatosensory cortex, left superior temporal gyrus, right orbitofrontal cortex, and left amygdala.


The subgroup of ASD individuals who had SOR showed significant differences in habituation to tactile stimulation: initial activity in the amygdala and somatosensory cortex decreased more slowly or inconsistently in the ASD with SOR subgroup.


Further analyses showed that the ASD without SOR subgroup had the strongest negative amygdala-prefrontal functional connectivity, the ASD with SOR subgroup showed less negative connectivity, and the typically developing subgroup showed slightly positive connectivity between the right amygdala and orbitofrontal cortex.


"Stronger brain connectivity between regions in the brain (i.e., prefrontal cortex) which help regulate and inhibit strong emotional response (in the amygdala) . . . may indicate that these youth have a compensatory mechanism in their brain helping them to regulate their response," Dr. Green said.


"There is some research evidence that treating sensory symptoms can improve quality of life, for example by reducing anxiety, and I think it is likely that early identification and treatment of SOR, as well as early intervention around improving daily living skills and coping strategies can improve outcomes for children with SOR on the autism spectrum," Dr. Green concluded. "However, more research is still needed in this area."


Using a different approach, Dr. Leonardo Cerliani, from the University of Groningen, the Netherlands, and colleagues used independent component analysis on resting-state fMRI to quantify interactions between brain networks in 539 male individuals with a diagnosis of either autism or Asperger syndrome and 573 age-matched controls, all selected from the publicly available Autism Brain Imaging Data Exchange (ABIDE) database.


"I would like to stress that our study used a different strategy with respect to most previous functional connectivity studies, as we analyzed interactions between entire networks, rather than between specific components of each network," Dr. Cerliani told Reuters Health by email.

"As we stated in the introduction and the conclusions of the paper, functional integration in the brain occurs at different level of scale, and it is entirely possible that the functional connectivity phenotype of people with ASD is characterized by different features according to the level of anatomical scale at which they are investigated," he added.


Compared with the typically developing control group, the ASD group showed increased functional connectivity between primary sensory networks and subcortical networks (thalamus and basal ganglia).


Moreover, the strength of these functional connections correlated significantly with the severity of autistic traits in the ASD group.


"Sensory atypicalities, although not specific for autism or solely predictive of any psychiatric condition, are important indicators of the mental state of an individual, and should receive attention as much as the social symptoms, by means of targeted standardized tests and questionnaires: acquiring an extensive behavioral phenotyping is as important as acquiring high-quality neuroimaging data, especially in a population like that of ASD, where the interindividual variability is very high," Dr. Cerliani said.


Coauthor Dr. Marc Thioux, also from University of Groningen, told Reuters Health by email, "There are two ways through which our findings (together with those of other labs) could contribute to the treatment. The first one is already implemented in many good schools, by many teachers, and by many parents at home: create the necessary conditions for the child to be able to focus, trying to understand how it can feel to be overwhelmed by such or such sensation."


"The second way these findings could contribute to the treatment has to do with the excitatory/inhibitory imbalance probably responsible for the sensory abnormalities and insistence on sameness evident in a percentage of children with autism. In the future, it might be possible to treat these symptoms by the use of a drug targeting certain neurotransmitters in newborns showing signs of an imbalance between neuronal excitation and inhibition," Dr. Thioux said.


Dr. Neil D. Woodward and Dr. Carissa J. Cascio, from Vanderbilt University School of Medicine, Nashville, Tennessee, wrote an accompanying editorial. Dr. Cascio told Reuters Health by email, "fMRI isn't typically used clinically for individuals with ASD at this point, but with further study we hope that it one day may give us insights into risk for ASD, help us to differentially diagnose ASD, and give us information about how the brain is responding to treatment."


"At some point, resting-state fMRI might be used to identify subtypes within the autism spectrum, and to make predictions about who is likely to respond best to what treatment options," she said. "However, more research is necessary before these possibilities can be realized."


"Resting state functional connectivity MRI offers some important advantages compared to task-based fMRI, including holistic information about the brain as a network, and feasibility in a broader range of clinical groups and in animal models of disease," Dr. Cascio added. "These features may accelerate the contributions of neuroimaging to our understanding of various psychiatric conditions."


Dr. Teresa Tavassoli from Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, told Reuters Health by email, "The study by Green et al. 2015 is very timely, since the underlying neural mechanisms of sensory hyper-reactivity are poorly understood. Findings of less neural habituation towards tactile stimuli, but not auditory, in children with ASD and sensory hyper-reactivity were particularly interesting."

"Since sensory reactivity symptoms are very common in ASD and are a new criterion in the most recent DSM-5, including sensory reactivity measures in the diagnostic process would help to inform further research and guide treatment," Dr. Tavassoli concluded.


Both studies were supported by several organizations. The authors and commentators reported no disclosures.

SOURCE: http://bit.ly/1KWTOyE and http://bit.ly/1ehvbCE and http://bit.ly/1JQ94A9

JAMA Psychiatry 2015.

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