Systems Biology of Autism: Translating Recent Developments in Neuro-imaging into the Clinical Realm

One of the most exciting possibilities for autism treatment is to devise means to excite cortical neuronal plasticity by direct sensory, particularly auditory, and electrodermal (scalp) stimulus. To achieve this goal requires knowledge of the temporal dynamics of auditory processing of pure tones (MEG), activity-dependent responses to naturalistic acoustic inputs (fMRI), and overall connectivity patterns across brain regions (resting state networks).

Parents and family members of those with autism have often remarked that minimally verbal individuals on the ASD can sometimes hum or sing religious prayers, show-tunes from musicals, and school fight songs. This seems to suggest that the auditory facility in humans has distinct cortical pathways for activating the vocal system (‘music’ and ‘speech’). Remarkably, this has been borne out in a recent study by Kanwisher and colleagues at M.I.T. (Norman-Haignere et al., Neuron 88, 1281-1296 (2015). It is also the case, based on the elegant work of Roberts and his collaborators at Children’s Hospital of Philadelphia, that auditory information is abnormally encoded in children with autism owing to delayed cortical development (Edgar et al., Molecular Autism 6, 69-83, 2015). These two landmark studies in autism research present a great opportunity for defining imaging-based early biomarkers for delayed language development.

Any discussion of the etiology of autism is inevitably prefaced with a statement about the heterogeneity of this developmental disorder, especially when genes, proteins and circuits are invoked. Yet, many of the observable behaviors, strengths and deficits, are strikingly similar. Recent resting state imaging studies at the Berenson-Allen Centre (BIDMC) involving differently-localized brain lesions, but with similar neurological symptoms, have revealed shared functional connectivity (Boes et al., Brain, 2015 in press). Tal Kenet (Martinos Center, MGH) and associates have demonstrated that resting state circuitry in autism is abnormal and stunted during development (Kitzbichler et al, Brain, 2013). Michael D. Fox and colleagues have suggested that these discoveries will make it possible to guide the application of stimulatory electric currents in distinct spatial and temporal sequence (‘a symphony of pulses’) to bring about therapeutically helpful redirection of brain circuits (Fox et al., PNAS (USA), E4367-E4375, 2014).

Maria Brincker,PhD
Assistant Professor (Philosophy of Mind & Neuroscience)
University of Massachusetts Boston

Using Brain Connectivity to Localize and Treat Neuropsychiatric Symptoms
Michael Fox, MD, PhD 
Assistant Professor of Neurology, Harvard Medical School
Director, Laboratory for Brain Network Imaging and Modulation
Associate Director, Berenson-Allen Center for Noninvasive Brain Stimulation
Associate Director, Deep Brain Stimulation Program
Beth Israel Deaconess Medical Center

The Spectral Signature of Functional Connectivity Abnormalities in ASD
Tal Kenet, PhD 
Assistant Professor of Neurology, Harvard Medical School
Scientific Director, TRANSCEND
Principal Investigator, Department of Neurology
MIT-MGH Martinos Center for Biomedical Imaging
Massachusetts General Hospital

Maria Mody, PhD
Assistant Professor in Radiology, Harvard Medical School
Assistant in Neuroscience, Massachusetts General Hospital

Transcranial Magnetic Stimulation (TMS): A Promising Tool for Translating Pathophysiology to Novel Interventions in ASD
Lindsay Oberman, PhD 
Assistant Professor of Psychiatry and Human Behavior
Brown University
Director of the Neuroplasticity and Autism Spectrum Disorder Program
Bradley Hospital

Prognostic and Stratification Biomarkers: MEG Indices, Supported by dMRI and MRS
Timothy Roberts, PhD 
Vice Chair of Research in Radiology Professor of Radiology
Children’s Hospital of Philadelphia

Linking Autistic Visual Symptoms to Reduced Inhibitory Signaling in the Brain 
Caroline Robertson, PhD 
Postdoctoral Research Fellow
McGovern Institute for Brain Research
MIT
Junior Fellow
Harvard Society of Fellows, Harvard University

Using Big Data and Micro-Movements to Help Advance Detection and Select Treatment Criteria for Neuropsychiatric Disorders
Elizabeth Torres, PhD 
Associate Professor
Cognitive Psychology/Computational Neuroscience
Rutgers University

AMMT – An Intervention to Get Minimally Verbal Children with Autism to Speak
Gottfried Schlaug, MD, PhD 
Director, Music and Neuroimaging Laboratory, Stroke Recovery Laboratory and Division Chief, Cerebrovascular Diseases
Associate Professor of Neurology,
Beth Israel Deaconess Medical Center and Harvard Medical School

2016

The Nancy Lurie Marks Family Foundation, Wellesley, MA