Abstract
Functional Magnetic Resonance Imaging (fMRI) has consistently highlighted impaired or aberrant functional connectivity across brain regions of autism spectrum disorder (ASD) patients. However, the manifestation and neural substrates of these alterations are highly heterogeneous and often conflicting. Moreover, their neurobiological underpinnings and etiopathological significance remain largely unknown. A deeper understanding of the complex pathophysiological cascade leading to aberrant connectivity in ASD can greatly benefit from the use of model organisms where individual pathophysiological or phenotypic components of ASD can be recreated and investigated via approaches that are either off limits or confounded by clinical heterogeneity. Despite some obvious limitations in reliably modeling the full phenotypic spectrum of a complex developmental disorder like ASD, mouse models have played a central role in advancing our basic mechanistic and molecular understanding of this syndrome. Recent progress in mouse brain connectivity mapping via resting-state fMRI (rsfMRI) offers the opportunity to generate and test mechanistic hypotheses about the elusive origin and significance of connectional aberrations observed in autism. Here we discuss recent progress toward this goal, and illustrate initial examples of how the approach can be employed to establish causal links between ASD-related mutations, developmental processes, and brain connectional architecture. As the spectrum of genetic and pathophysiological components of ASD modeled in the mouse is rapidly expanding, the use of rsfMRI can advance our mechanistic understanding of the origin and significance of the connectional alterations associated with autism, and their heterogeneous expression across patient cohorts.
Highlights
Reviewed by: Jason Lerch, The Hospital for Sick Children, Canada Shruti Gopal, University of Miami, USA
Recent progress in mouse brain connectivity mapping via resting-state Functional Magnetic Resonance Imaging (fMRI) offers the opportunity to generate and test mechanistic hypotheses about the elusive origin and significance of connectional aberrations observed in autism
As the spectrum of genetic and pathophysiological components of autism spectrum disorder (ASD) modeled in the mouse is rapidly expanding, the use of resting-state fMRI (rsfMRI) can advance our mechanistic understanding of the origin and significance of the connectional alterations associated with autism, and their heterogeneous expression across patient cohorts
Summary
Reviewed by: Jason Lerch, The Hospital for Sick Children, Canada Shruti Gopal, University of Miami, USA. Despite some obvious limitations in reliably modeling the full phenotypic spectrum of a complex developmental disorder like ASD, mouse models have played a central role in advancing our basic mechanistic and molecular understanding of this syndrome. Recent progress in mouse brain connectivity mapping via resting-state fMRI (rsfMRI) offers the opportunity to generate and test mechanistic hypotheses about the elusive origin and significance of connectional aberrations observed in autism. As the spectrum of genetic and pathophysiological components of ASD modeled in the mouse is rapidly expanding, the use of rsfMRI can advance our mechanistic understanding of the origin and significance of the connectional alterations associated with autism, and their heterogeneous expression across patient cohorts. Previously identified mutations, genetic syndromes, and de novo copy number variations (CNVs) account for about 10–20% of ASD cases, none of these single known genetic causes accounts for more than
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