Objectives: Our objective was to examine the potential mechanism of the beneficial effects of a currently available pharmacotherapeutic agent, propranolol, on the core features of autism by assessing functional connectivity using fMRI.
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 since nadolol is a beta-adrenergic antagonist but does not cross the blood brain barrier. After drug administration, subjects were placed in a 3T magnetic resonance scanner at Ohio State University and asked to complete a cognitive flexibility task, the compound remote associates (CRA), and two verbal fluency tasks, one based on letters and the other based on categories. Structural T1-weighted images were acquired using a T1 weighted 3D FFE pulse sequence (TR=25 ms; TE=3.6 ms; 64 axial slices; 2.2 mm thick). BOLD contrast functional scans were acquired using a gradient echo EPI sequence (TR=3 s; TE=35 ms; 35 axial slices, 4mm thick; α = 90°). A priori regions of interest, ROIs, were used to extract region-specific activation in the inferior frontal cortex, fusiform gyrus, middle temporal gyrus, and posterior parietal cortex. Correlations between pairs of ROIs were computed by calculating the correlation coefficient between the time series for each ROI pair and then standardized using Fischer’s Z-transformation.
Results: There was a significant effect of drug such that functional connectivity was significantly higher for propranolol trials compared to nadolol and placebo, which did not appear to significantly differ from each other. These results were most robust for the CRA task.
Conclusions: Although this is preliminary data, we begin to show the cognitive benefits of propranolol in autism may be due to increased network flexibility due to alterations of beta-adrenergic mechanisms. Theses alterations seem to be most beneficial for more difficult compared to easier tasks. Better understanding of the effects of the beta-adrenergic system on language 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.
See more of: Brain Imaging: fMRI-Social Cognition and Emotion Perception
See more of: Brain Structure & Function