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Grants

Career Development Award for Lindsay Oberman, Ph.D.

This grant provided support for Dr. Lindsay Oberman in a translational research project that extended and bridged two independent lines of research, both previously funded by the NLMFF. Specifically, with funding from NLMFF as well as NIH and Harvard Catalyst, Dr. Alvaro Pascual-Leone and Dr. Oberman have developed methods to noninvasively measure experience-dependent cortical plasticity both in healthy controls and patients with idiopathic ASD and Fragile X syndrome. Using noninvasive repetitive transcranial magnetic stimulation (rTMS), Drs. Oberman and Pascual-Leone have shown that patients with idiopathic ASD show an exaggerated LTD-like suppression of cortical excitability following a short train of rTMS while those with Fragile X (without ASD) syndrome show a complete lack of LTD-like suppression in response to the same rTMS protocol.

Under a separate line of research, also previously funded by the NLMFF, Dr. Matthew Anderson developed a mouse model of ASD based on triplication of the UBE3a gene (the genetic mutation that causes idic15 in humans) that reconstitutes correlates of the three core behavioral deficits that define ASD. Furthermore, they developed a model mechanism where they proposed that social deficits in individuals with idic15 may be a consequence of excessive experience-dependent social homeostasis.

Independently, these two lines of research have both contributed to our understanding of the underlying pathophysiology of the behavioral deficits that characterize ASD. A complete understanding, however, requires the direct translation of insights that we gain from basic science to applications that have direct impact for patients with the disorder. With this focus, this project aimed to create a multi-disciplinary collaboration between the Anderson and Pascual-Leone lab with Dr. Oberman as the catalyst of this translational bridge. Thus, the aim was to develop novel assays, based on the previous work in the Anderson and Pascual-Leone lab, to evaluate neurological and behavioral phenotypes in human patients with a specific syndromic form of ASD, idic15.