Current behavioral interventions for autism focus on increasing quality of life and language development whereas pharmacological interventions are directed at managing the secondary manifestations such as anxiety and repetitive and obsessive behaviors. Pharmacological research directed at the core features of autism is limited. Propranolol, a beta-adrenergic antagonist, has been shown to improve verbal problem solving in typically developing controls as well as people with autism, and research into propranolol’s pharmacotherapeutic effects is warranted.
Current theories suggest that autism may be due to altered network flexibility within cortical regions important for information processing and findings suggest both hypo- and hyper-activation, depending on the network. Functional magnetic resonance imaging, fMRI, allows for the measurement of a correlate of flexibility of access to networks, as assessed by functional connectivity. We therefore wish to determine fcMRI alterations with and without beta-adrenergic agents. We have previously shown the beneficial effects of propranolol during verbal problem solving may be due to increased flexibility of access to cortical networks important for language processing. We wish to extend this line of research to facial and emotional processing and hypothesize that during propranolol administration subjects will show increased connectivity.
Objectives:
Our objective is to examine the mechanism of the beneficial effects of a currently available pharmacotherapeutic agent, propranolol, on the core features of autism by assessing functional connectivity using fMRI during facial and emotional salience processing.
Methods:
We examined a pilot sample of individuals with autism during administration of propranolol, nadolol, and placebo. Nadolol provides a control for general vascular effects on BOLD fcMRI because nadolol is a beta-adrenergic antagonist that does not cross the blood brain barrier. After drug administration, subjects were placed in the 3T magnetic resonance scanner at the University of Missouri Brain Imaging Center and asked to complete a faces-matching task. Stimuli consisted of faces either exhibiting angry, fearful, or neutral expression. A priori regions of interest, ROIs, were used to extract region-specific activation in the frontal cortex, fusiform gyrus, middle temporal gyrus, superior temporal gyrus, posterior parietal cortex, and amygdala. Correlations between pairs of ROIs were calculated and transformed using Fishers z calculation.
Results:
The facial matching task activated our main regions of interest, fusiform and amygdala, allowing for the use of these regions as seeds for functional connectivity analyses. We found a significant effect for drug such that functional connectivity was significantly altered during propranolol trials compared to placebo.
Conclusions:
With this preliminary data, we show that the cognitive benefits of propranolol in autism may extend beyond language processing and may be due to alterations of flexibility of access to networks due to effects on beta-adrenergic receptors. Better understanding of the effects of the beta-adrenergic system on neuronal processing, especially in the autism population, and modulation of the beta-adrenergic system pharamacologically could lead to development of additional treatments for the core features of autism. Additional research is required to fully understand these alterations and determine possible biomarkers, such as genetic status, of who may benefit most from beta-adrenergic intervention.
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