This, along with comprehensive

pre- and post-testing of behavioral, cognitive, and neurobiological outcomes thought to be associated with the mechanism of motivation, would allow for the between-subjects isolation of the specific role that social motivation may play in producing ARQ197 FDA change among individuals with ASD. Such research would aid in uncovering the possible mechanistic role of social motivation in engendering change in social behavior, and in assessing the centrality of the social motivation hypothesis in explaining deficits in ASD. While this approach may run counter to the belief that whole “treatment packages” are necessary to produce change (and, indeed, this Inhibitors,research,lifescience,medical may be so for macro-level change), it provides a venue in which to carefully specify the processes by which each component of intervention produces specific changes in social-communicative outcomes. Moreover, it is consonant with the emerging framework of lifelong neuroplastic change that may subtend change across domains of human neurocognitive and behavioral functioning.132 Third, Inhibitors,research,lifescience,medical having carefully isolated a potential mechanism and its proximal neurocognitive effects, lab-based efficacy studies of interventions built around these mechanisms should be conducted Inhibitors,research,lifescience,medical using multi-trait, multi-method

assessment and well-defined and -controlled populations. While such studies have been criticized for lacking ecological validity,133 they are nonetheless valuable for addressing important considerations such as dose-response Inhibitors,research,lifescience,medical curves associated with minimal and maximal treatment response, additive 17-AAG versus multiplicative effects of concurrent mechanisms, and

effects on auxiliary outcomes. Related to this, use of more sophisticated methodological approaches, such as dismantling studies, and statistical procedures, such as multilevel modeling,88 will allow us to make direct comparisons of active treatments and understand the timecourse Inhibitors,research,lifescience,medical of change across identified mechanisms and their outcomes. Additionally, these studies could also be applied to TD populations with familial risk of ASD or to those evincing some level of ASD psychopathology (ie, the broader autism phenotype134). Such studies would be useful in identifying the degree to which identified mechanisms of change are somewhat ”unique“ to ASD, or are representative of extreme version of more normative social psychopathological AV-951 processes (ie, transdiagnostic treatment processes). Finally, efficacious interventions based on well-defined mechanisms should be “scaled up” to “real-world” effectiveness studies. These studies should be implemented in community-based clinics recruiting representative samples of clinically referred populations with ASD. Such studies not only provide a test of ecological validity, but also allow for the use of existing practice as a “natural laboratory” to test questions that defy examination in controlled settings.