Brain connectivity analyses have implications for future ASD interventions

Results from two studies using functional MRI to examine brain connectivity among individuals with autism spectrum disorder offer new understandings of sensory processing among these individuals, which may influence future interventions.

“Individuals with autism spectrum disorder (ASD) exhibit severe difficulties in social interaction, motor coordination, behavioral flexibility and atypical sensory processing, with considerable interindividual variability,” study researcher Leonardo Cerliani, PhD, of the University Medical Center in Groningen, Netherlands, and colleagues wrote in JAMA Psychiatry. “This heterogeneous set of symptoms recently led to investigating the presence of abnormalities in the interaction across large-scale brain networks. To date, studies have focused either on constrained sets of brain regions or whole-brain analysis, rather than focusing on the interaction between brain networks.”

Researchers compared the intrinsic functional connectivity between brain networks among 166 males, with a mean age of 17.6 years, diagnosed with autism or Asperger’s syndrome, and 193 typical developing males, with a mean age of 16.9 years) using resting-state functional MRI.

Compared with typical developing males, those with ASD exhibited increased functional connectivity between primary sensory networks and subcortical networks, specifically the thalamus and basal ganglia, (P < .001). The strength of these connections correlated with severity of autistic traits among children with ASD (P < .0067).

As age increased, subcortico-cortical interaction decreased among all study participants (P < .012), but this association was only significant among typical developing males (P < .009).

“We report that hyperconnectivity between subcortical regions and sensory cortices is a central feature in ASD. This hyperconnectivity was related to the degree of autistic traits in the examined sample of individuals with ASD,” Cerliani and colleagues wrote. “We propose that such hyperconnections could relate to abnormal sensory processing in that they represent an alteration of the normal equilibrium between sensory information stemming from the thalamus and top-down influence from higher-order cortices.”

Sensory processing among high-functioning patients with ASD

A second study, conducted by Shulamite A. Green, PhD, of the University of California, Los Angeles, and colleagues, used functional MRI to compare brain responses and habituation to mildly aversive auditory and tactile stimuli among 19 high-functioning individuals with ASD with 19 typical developing age- and IQ-matched controls. Study participants were aged 9 to 17 years.

Researchers found youth with ASD exhibited stronger activation in primary sensory cortices and the amygdala (P < .05) compared with typical developing youths. When controlling for anxiety, this activity was positively associated with symptoms of sensory overresponsivity.

A subgroup of participants with ASD and sensory overresponsivity had decreased neural habituation to stimuli in sensory cortices and the amygdala compared with those without sensory overresponsivity.

Analysis indicated a pattern of amygdala downregulation, with negative connectivity between the amygdala and orbitofrontal cortex among youths with ASD without sensory overresponsivity (P < .05).

Neil D. Woodward

“These findings have implications for intervention,” according to Green and colleagues. “First, the greatest overresponsiveness occurred in response to multiple simultaneous stimuli, suggesting that minimalizing exposure to multiple sensory modalities could help youth with ASDs cope with [sensory overresponsivity]… Second, youth with ASDs without [sensory overresponsivity] appear to have more ability to downregulate their response to sensory stimuli. This finding may indicate that intervention for [sensory overresponsivity] should focus on building coping strategies rather than on normalizing sensory processing.”

In response to these study findings, Neil D. Woodward, PhD, and Carissa J. Cascio, PhD, of Vanderbilt University School of Medicine, conclude that resting-state functional MRI has the potential to advance personalized medicine in psychiatry, but comes with limitations.

Carissa J. Cascio

“Resting-state [functional] MRI is a promising method for uncovering the neural correlates of mental disorders and advancing personalized medicine in psychiatry,” Woodward and Cascio wrote in an accompanying editorial. “A limitation for [resting-state functional] MRI in the effort to identify brain-behavior relationships is that it is a measure of fluctuation in neural activity in the absence of a specific externally prescribed behavior. As such, [resting-state functional] MRI will likely remain a complement to task-based imaging. However, because of its task-free nature, [resting-state functional] MRI can span human clinical populations and animal models to achieve a level of translational continuity that has eluded functional neuroimaging thus far.” – by Amanda Oldt

Disclosure: The researchers report no relevant financial disclosures.

References:

Cerliani L, et al. JAMA Psychiatry. 2015; doi:10.1001/jamapsychiatry.2015.0101.

Green SA, et al. JAMA Psychiatry. 2015; doi:10.1001/jamapsychiatry.2015.0737.

Woodward ND, et al. JAMA Psychiatry. 2015; doi: 10.1001/jamapsychiatry.2015.0484.