International Meeting for Autism Research (May 7 - 9, 2009): Noradrenergic EFFECTS on Functional Connectivity in Autism

Noradrenergic EFFECTS on Functional Connectivity in Autism

Friday, May 8, 2009: 5:40 PM
Northwest Hall Room 1 (Chicago Hilton)
A. Narayanan , Integrated Biomedical Sciences Graduate Program, The Ohio State University, Columbia, MO
C. White , Neurology, The Ohio State University, Columbus, OH
S. Saklayen , Ibgp, The Ohio State University, Columbia, MO
M. Scaduto , College of Medicine, The Ohio State University, Columbus, OH
A. Abduljalil , Radiology, The Ohio State University, Columbus, OH
P. Schmalbrock , Radiology, The Ohio State University, Columbus, OH
D. Q. Beversdorf , Radiology, University of Missouri, Columbia, Columbia, MO
Background: Previous experiments have demonstrated decreased functional connectivity in subjects diagnosed with ASD when compared to controls, during language tasks. Therefore, drugs that affect functional connectivity may be beneficial in ASD. Noradrenergic antagonists have shown benefit for individuals with ASD in a semantic network flexibility task. The noradrenergic system is upregulated in stress, which causes a decrease in the flexibility of access to semantic networks, resulting in decreased performance in individuals without neurodevelopmental diagnoses under stress. This impairment in the network flexibility due to stress is reversed by administration of centrally acting β-adrenergic antagonists. Propranolol (a central and peripheral β-blocker) has also shown benefit for language and social behavior in ASD.

Objectives: We wished to determine whether administration of propranolol would increase functional connectivity observed during language tasks in ASD as compared to nadolol (peripheral-only β-blocker), administered to control for effects on peripheral blood flow.

Methods: Subjects with ASD and age and IQ-matched controls without neurodevepmental diagnoses were scanned using a Philips 3T scanner, while instructed to respond to the pronunciation (phonological) of a word related to a cue word in a block-design task. Data was preprocessed and analyzed using SPM5 and the correlation of time series was calculated and compared between drug conditions.

Results: Administration of propranolol revealed a significant main effect of increased functional connectivity between activated brain regions across all brain region pairs as compared to nadolol. Effects on heart rate and blood pressure were identical between the two drugs.  These results reveal an increase in functional connectivity upon administration of propranolol in ASD that is not attributable to peripheral blood flow effects.

Conclusions: This may suggest an anatomical substrate for the effects of noradrenergic agents on tasks involving a network search within the brain.