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GRANTS FUNDED IN 2011

Beth Israel Deaconess Medical Center, Boston, MA
2011– 2013

Principal Investigator: Gottfried Schlaug, MD, PhD

Using Auditory-Motor Mapping Training to Facilitate Speech Output in Nonverbal Children with Autism: An Intervention and Imaging Study

Language deficits represent the core diagnostic features of Autism Spectrum Disorders (ASD). In some cases, language deficits are observed after an apparently normal onset, while in others, language abilities never develop at all (Tager-Flusberg, 2003). Up to 25% of individuals with ASD lack the ability to communicate with others using speech sounds. Despite their verbal communication deficits, children with ASD often display enhanced music and auditory-perception abilities (Bonnel et al., 2003; Heaton, 2003). In addition, they enjoy auditory-motor activities such as making music, through singing or playing an instrument (Trevarthen et al., 1996). Such positive responses to music suggest that an intonation- or singing-based intervention may have significant therapeutic potential. Dr. Schlaug’s laboratory has successfully used an intervention known as Melodic Intonation Therapy (MIT) to facilitate speech output in stroke patients with Broca’s aphasia, who initially struggled to speak. Recently, they have also developed a similar therapy that is adapted for children with ASD. At present, there are no established techniques that reliably improve speech in nonverbal children with ASD (Francis, 2005). Two published case studies (Miller & Toca, 1979; Hoelzley, 1993) as well as Dr. Schlaug’s preliminary data from a number of nonverbal children with ASD have shown that an intonation-based technique has great potential. This research examines the potential utility of a novel intervention termed auditory-motor mapping training (AMMT), in assisting nonverbal children with ASD to develop speech. This intervention has significant therapeutic potential for at least three reasons. First, it capitalizes on the inherent musical strengths of children with ASD, and offers activities that they intrinsically enjoy. Second, it engages and potentially modifies a network of brain regions that may be dysfunctional in ASD (Lahav et al., 2007; Wan, Demaine, Zipse et al., 2010; Wan & Schlaug, 2010). Finally, AMMT is an adaptation of MIT that has been successful in facilitating speech output in stroke patients who previously struggled to speak. In addition, secondary to determining the efficacy of AMMT as an intervention for nonverbal children with ASD, the investigators also aim to examine whether the severe language deficits in these nonverbal children are due to abnormalities in certain language pathways of the brain. They will be using structural brain imaging techniques such as diffusion tensor imaging to answer this question.

Gottfried Schlaug



The Children's Hospital of Philadelphia, Philadelphia, PA
2011-2013

Principal Investigator: Timothy Roberts, Ph.D.

Longitudinal MEG of Auditory Processing in ASD

The project will be supported by the resources of the Children's Hospital of Philadelphia (CHOP). This will allow for the utilization of the extensive expertise of the scientific staff (physicists, neuropsychologists, neuroscientists, bioengineers, radiologists) as well as the support staff (research assistants, MR technologists, etc.). CHOP has extensive non-invasive imaging resources including whole-cortex magnetoencephalography (MEG), 3T MRI with 32-channel head coil and very large autism and control populations. The project builds upon extensive structural and functional studies of the auditory system in autism that Dr. Roberts’ group has conducted over the last five years, funded in part by the NLMFF. Given the strong evidence for an abnormal trajectory of brain development in autism spectrum disorders (ASD), set in the context of inter-subject heterogeneity, this study adopts an intra-subject longitudinal design in a well-characterized cohort, with advanced functional, structural imaging (including imaging of white matter, recording of brain waves, and measurement of brain chemistry) and neuropsychological assessment follow-up of this cohort at 2+ years of their original exam.

Click here to read the NLMFF Interview with Dr. Roberts

Children's Hospital of Philadelphia



Houston Methodist Hospital, Houston, TX
2011-2012

Principal Investigator:Gustavo C. Román, MD, Houston Methodist Neurological Institute

Autism:  Predictive effect of low-thyroid function during the first trimester of gestation

The increasing incidence of Autism Spectrum Disorders (ASD) in the USA and Europe suggests a causal environmental factor.  Neuropathological brain changes in autism are consistent with an alteration of neuronal cortical migration occurring early in gestation (gestational age, GA 8-12 weeks).  Maternal thyroid hormones are critical for neuronal migration.  Thyroid function depends on appropriate iodine content in the diet; also, numerous environmental factors affect thyroid function.  A large number of anti-thyroid compounds are present in many natural and man-made products.  Based on clinical and experimental evidence, Román postulated that maternal hypothyroxinemia (low T4) during the first trimester (GA 8-12 weeks) may adversely affect neuronal migration leading to abnormal cortical formation of brain and cerebellum, resulting in autism.

This research project aims to test the hypothesis that abnormal function tests during pregnancy predict autism by performing appropriate statistical analyses using de-identified data contained in the database from a cohort of mothers and their children [The Generation R Study] in Rotterdam, The Netherlands. It is expected that the incidence of ASD will be significantly higher in the group of cases with early maternal hypothyroxinemia compared to normal controls. 



Lurie Family Autism Center / Massachusetts General Hospital
2011


Principal Investigator: Andrew W. Zimmerman, M.D.

A Trial of Sulforaphane in Autism

Despite intensive research efforts, neither prevention nor treatment of underlying mechanisms in autism is currently possible. In a recently published study, Dr. Zimmerman and colleagues confirmed anecdotal observations that behavioral symptoms in autistic children improve during episodes of fever. The cellular mechanisms underlying the effects of fever in autism remain to be clarified, however it is likely that heat shock proteins are involved. Dr. Zimmerman and his group hypothesize that in autism, enhancement of under-expressed genes and induction of the cellular stress response proteome, including heat shock proteins, will occur in response to treatment with sulforaphane. Mounting evidence shows that sulforaphane, a derivative of cruciferous vegetables (and therefore of low toxicity), defends cells against stresses by upregulating a network of cytoprotective genes that defend against oxidation, inflammation and mitochondrial dysfunction. All of these processes have been described in autism, in which multiple genes appear to be involved, with mutations that are not lethal but cause marked dysfunction, especially in the central nervous system. To date, specific gene mutations account for only 10-15% of patients with autism. Positive effects of fever occur in from 38 to 83% of patients with autism. Sulforaphane, as both oral and topical broccoli sprout extracts, penetrates the CNS and is well tolerated. It has been shown to be bioavailable to nerve cells and accumulates in the brain with various routes of administration. Dr. Zimmerman and his group propose a Phase I/II study of sulforaphane in 45 young adult males with autism, 13-30 years of age. They will measure a core feature of autistic spectrum disorders: social communication deficits. Cellular effects of sulforaphane will be measured in lymphocytes during treatment. The trial’s primary objectives are to answer whether treatment administered within a specified dose range is safe, treatment administered within a specified dose range is well tolerated by young autistic males, there is evidence of a measurable effect on behavioral symptoms, there is evidence that treatment within the specified range has observable activity affecting social communication, and key cellular biomarkers support the hypothesized mechanism.


Massachusetts Advocates for Children, Boston, MA
2002, 2003, 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011

Establishment and Support of the Autism Special Education Legal Support Center


The goal of this project is to provide training, technical assistance, and advocacy services necessary to ensure that children with autism receive equal educational opportunities. Goals include: Providing parents with information about state-of-the-art services and programs available to meet individual needs of students with disabilities; Insuring that children with autism receive special education services necessary to reach their potential in areas impacted by their disability; Increasing public awareness and understanding of the potential and competency of individuals with autism, targeting policy makers, media, educators, service providers, as well as the general public. The Autism Special Education Legal Support Center will accomplish these goals by: providing community-based workshops for parents, educators, and medical professionals regarding legal rights and range of service options available for children with autism; providing a hotline to give legal and technical assistance to families of children with autism; training attorneys to increase representation of low-income students with autism to ensure that children receive legally mandated special education services; and providing information to the media, the legislature, and other policy makers regarding changes necessary to ensure children with autism receive services that reflect their potential.

Click here to read the NLMFF Interview with Massachusetts Advocates for Children

Massachusetts Advocates for Children




Massachusetts General Hospital

2011

Principal Investigators: Sarabeth Broder-Fingert, MD and Kimberly Kopecky

Hospital Admissions Plans for Patients with Autism at Massachusetts General Hospital

The primary research objective is to expand and study the outcome of a quality improvement project known as "Autism Care Plans (ACPs).” The investigators hypothesize that the use of ACPs will improve the in-hospital experience for patients with autism and their families. On paper, the ACP is a template for caregivers of patients with autism to fill out prior to hospital admission. The ACP documents the patient's primary modes of expressive and receptive communication, social and pragmatic considerations when preparing for patient hospitalization, and relevant sensory/perceptual issues. The investigators will be evaluating pre and post-hospitalization caregiver satisfaction after these templates have been utilized in the inpatient setting.

The ACP for patients with autism strives to ensure 1) appropriate and efficient patient care, 2) patient and family satisfaction with hospital performance and services, 3) reduced adverse outcomes in the inpatient setting and 4) cost effectiveness. The ACP attempts to achieve the above goals using a three-pronged approach. The first element of the ACP is to enhance communication between patient and doctor. The second element of the ACP attempts to make autistic patients as comfortable as possible within the unfamiliar and often unpredictable hospital environment. The third element of the ACP involves extensive provider education and outcome analysis.


Massachusetts General Hospital


 
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