Rose F. Kennedy Intellectual and Developmental Disabilities Research Center - Human Clinical Phenotyping (HCP) Core

Current Projects Aided by the HCP

PI: Sophie Molholm, Ph.D.

Multisensory Processing and Integration in Autism 

 Atypical integration of multisensory inputs has been suggested as a major component of autism, and indeed there is clinical and behavioral support for this view.   Where and when in the neural processing stream sensory integration deficits occur is as yet unknown, and gaining an understanding of this will be essential in defining the neuropathology of autism. In fact, there is precious little understanding of the basic development of healthy sensory integration mechanisms in typically developing children, although recent work in animal models is beginning to shed some light. Under this project, we use established electrophysiological metrics of multisensory integration that we have developed in our laboratory in healthy adults, to test the hypothesis that multisensory integration is impaired in autism.  The high-density electrical recordings of neural activity that we record provide a precise measure of when in the information processing stream sensory integration differs from typically developing matched controls, as well as a good model of the underlying brain processes that are affected.  Specific hypotheses about when and where multisensory processes are affected in autism stem from the thesis that there is impoverished connectivity between distant cortical regions in this population.  The data acquired under this project will provide a strong empirical test of deficits in multisensory integration processes in autism.  Understanding how multisensory integration develops and changes over childhood will significantly inform models of multisensory integration, and provide an initial benchmark against which predictions about possible disordered multisensory integration in a host of developmental disorders can be made.  

Cognitive Neurophysiology Lab website 

Cognitive Neurophysiology Lab Facebook Page  


 

PI: John J. Foxe, Ph.D.

Assistant Professor: Lars Ross, Ph.D

Brain Imaging in Autism Spectrum Disorders 

This study consists of a variety of experiments that use different techniques to investigate the brain mechanisms underlying the behavior of individuals diagnosed with ASD. One prominent idea about the possible causes of ASD behavior is that some of the many different parts of the brain do not communicate with one another as they do in typically developing individuals. This brain abnormality may give rise to the difficulty of individuals with ASD to effectively integrate information from different senses. This important function called "multisensory integration" is essential for interpersonal communication and social behavior both well known to be impaired in ASD. We use advanced technology called Magnetic Resonance Imaging (or MRI) to assess the structure of the brain and how different parts of the brain are connected to one another. We also investigate the activity of the brain when engaged in a task requiring the integration of information from different senses. In an effort to understand the relationship between brain structure/function and behavior we relate our MRI data to those gathered in related experiments and neuropsychological assessments outside the scanner. In these experiments we engage our participants in different multisensory tasks. Finally, we collect genetic information from our participants to investigate a possible connection between genetic makeup, brain structure/function and behavior. Using this variety of technological and experimental approaches will provide a more comprehensive understanding on the brain mechanisms underlying ASD behavior and will therefore allow unique and new insights into the etiology of Autism which are particularly relevant for therapeutic intervention.

Cognitive Neurophysiology Lab website 

Cognitive Neurophysiology Lab Facebook Page  


 

PI: John Foxe, Ph.D. and Alexandra Djuick, Ph.D.

Postdoctoral Fellow: Hans-Peter Frey, Ph.D.

Neurophysiology of Receptive Speech in Rett Syndrome 

Rett Syndrome, a neuro-developmental disorder that affects about 1 in 10,000 females, is characterized by a regressive loss of acquired spoken language and motor capabilities during the first two years of life. In patients who do not produce speech and lack motor abilities to respond to spoken words in a controlled manner, it is all too common to assume a more general lack of speech capabilities. However, recent evidence suggests that this is likely not a valid assumption for patients with Rett syndrome. There are now several anecdotal reports indicating altogether greater receptive language processing skills in RETT children. This project therefore aims at developing widely applicable quantitative tests of the most important aspects of receptive speech processing using objective neurophysiological methods. The goal is to determine just how intact the receptive speech system is in RETT, with important implications for the development of assistive communication devices for these oft-neglected children.


 

PI: John Foxe, Ph.D. and Sophie Molholm, Ph.D.

Electrophysiological Assessment of Sensory Processing and Sensory Integration in Sensory Processing Disorder 

For most individuals sensory processing occurs automatically and is not disruptive to ongoing higher-order cognitive processing. For a small but significant subset of the population, however, sensory processing is disordered and obtrusive, disrupting normal cognitive-emotional functioning (e.g., Ben-Sasson, Carter, & Briggs-Gowan, 2009; Shalita, Vatine, & Parush, 2008). This current program of research is designed to test the hypothesis that the brains of children classified with a Sensory Processing Disorder (SPD) process sensory inputs differently. We use high-density electrophysiology to measure whether the SPD brain exhibits greater sensitivity to auditory and somatosensory stimulation, and correlate these brain responses with behavioral measures of sensitivity to auditory and somatosensory stimulation.

Cognitive Neurophysiology Lab website 

Cognitive Neurophysiology Lab Facebook Page  


 

PI: Brett Abrahams, Ph.D.

DNA Variation and Genetic Disorders 

Work in Dr. Brett Abraham's lab employs a blend of molecular genetics and developmental neurobiology to identify novel genes that may influence risk of autism and to understand how those genes function. Although some autism-related genes have already been identified, none show a specific relationship to the clinical diagnosis of autism. Instead, they appear to contribute to a range of related neurodevelopmental disorders, such as: intellectual disability, language impairment, schizophrenia, bipolar disorder and epilepsy. We hope to enroll subjects who are on the autism spectrum and/or have other disorders of cognition, as well as healthy subjects without any cognitive disorders. Characterization of genetic differences between individuals will allow us to uncover factors that may contribute to autism spectrum disorders and related disorders of cognition.

Abrahams Lab webpage  


 

PI: John Greally, Ph.D.

Predoctoral Fellow: Esther Berko, MD/Ph.D. Student

Advanced Parental Age and Autism: The role of aneuploidy and uniparental disomy in ASD pathogenesis 

Numerous studies have demonstrated that rates of autism spectrum disorders (ASDs) rise with older ages of the parents. Researchers are currently investigating the ways an aging paternal germline can contribute to Autism Spectrum Disorders (ASDs), namely through increased rates of mutation of the DNA sequence. Although the effects of paternal age, namely higher rates of mutation and copy number variation in offspring, have indeed been linked to ASDs, no study has determined the potential role of maternal age. We propose that maternal nondisjunction and resulting aneuploidy could cause ASDs and remain undetected. Since most aneuploidies are lethal embryonically, surviving offspring often undergo a "rescue" event that restores normal chromosome number. Depending on when an aneuploidy rescue occurs and which chromosome is lost, offspring exhibit either covert mosaic aneuploidy in sub-populations of cells or heterodisomic uniparental disomy (UPD). These defects have been implicated in other genetic disorders and may contribute to the molecular basis of ASDs, but are, surprisingly, unlikely to have been detected by current approaches that utilize cultured blood, a tissue that demonstrates low or absent levels of aneuploidy in mosaic individuals. In this study, we will perform comprehensive analysis of the genomes of children with ASD born to parents of advanced age, employing DNA isolated from buccal epithelium. By comparing children's genotypes with their parents and applying computational analysis on SNP array signal intensities, this study has the potential to identify the prevalence of covert mosaicism and heterodisomic UPD in children with ASDs.

Greally Lab website 

More information on this project 


 

PI: Pierfilippo De Santis, Ph.D

Aging Study 

A general decline in executive control mechanisms is a common, and to a certain degree, a reluctantly accepted aspect of normal aging. Of course, there is great variance in the extent of this decline, ranging from severe debilitating in some adults, to the more acceptable mild-to-moderate decline that is the hallmark of a much larger cohort. Whereas these more subtle deficits may not be life-threatening, they nonetheless cause real distress and negatively impact general quality-of-life and sense of well-being. Yet, there are also those elderly individuals that we all encounter, who somehow manage to retain and perhaps even improve their mental “sharpness” and flexibility over their later years. What makes these individuals special? Are there fundamental neuroprotective aspects of their biological makeup? Do they by some means escape the structural changes in frontal cortex that seem to be a factor in the decline of executive functioning with? Recent work suggests that this is not the basis for their success; rather, one fundamental way in which these individuals stave off the negative effects of cognitive aging is by recruiting and reconfiguring executive control processes in the frontal lobes. We found clear functional evidence for additional recruitment of frontal circuits and that activity in these regions is often considerably amplified relative to that seen in healthy young adults during standard executive tasks. That there appears to be the possibility for large-scale functional plasticity during later life is surely encouraging. If it were simply the case that these adults were not as susceptible to basic structural changes, then the options for intervention in those who are susceptible might be relatively more limited. However, if cognitive strategies and neural network reconfigurations can compensate for basic structural decline, then the picture becomes more hopeful, for if we can understand these reconfigurations and perhaps the strategies that allow for them, we can potentially teach them to those who have not managed to learn them independently. Our goal is to build basic understanding of the cognitive processes and neural underpinnings that protect these high performing elderly, and also to understand what occurs in the average to low performing elderly who fail to maintain optimal performance.

Cognitive Neurophysiology Lab website 

Cognitive Neurophysiology Lab Facebook Page  

What the RFK-IDDRC Encompasses

  • The IDDRC, one of Einstein’s oldest and most established programs, is one in which basic scientists and clinicians are focused on intellectual and developmental disabilities (IDDs) of children. Its collaborators have a common goal of disease discovery, diagnosis, prevention and treatment. It encompasses:
  • A revitalized administrative program, building new and productive collaborations at Einstein and its affiliated hospitals by uniting basic scientists focused on normal and abnormal brain development and function with clinicians caring for children with IDDs
 

Contact Us

If you would like to participate or enroll your child in research, please call: 718.862.1826 or email: childrensresearchunit@einstein.yu.edu 

If you are seeking clinical services for your child, please call: 718.430.8500  

 
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