Timothy Roberts and his colleagues at the Children’s Hospital of Philadelphia are studying the responsiveness of neural oscillatory measures to acute administration of STX209 (arbaclofen), a GABAB agonist and a candidate therapeutic for autism spectrum disorder (ASD).
Whole-exome sequencing studies of sporadic autism cases have identified SCN2A, which encodes the neuronal voltage-gated sodium channel NaV1.2, as one of the most commonly mutated genes associated with autism. How dysfunctional NaV1.2 affects neurons and consequent circuit function to produce behaviors associated with autism is not well understood.
Fei Xu and her colleagues conduct research on early cognitive and language development in typically developing infants and children. Using a novel approach of conceptualizing autism as a learning disorder, the researchers aim to investigate the capacity of children with autism in making inductive generalizations.
Anatomical and electrophysiological studies have made it clear that dysfunction in the cerebellum, and in Purkinje cells specifically, is linked to behavioral abnormalities in autism. This correlation is compelling, but it has been difficult to make a causative link between the anatomical and physiological defects and the associated behaviors.
Although autism is characterized primarily by impairments in social skills and communication, as well as restricted interests and repetitive behaviors, it has become evident that attention abnormalities may play a critical role in the symptom presentation of the disorder. Attention refers to the activity of a set of alerting, orienting and executive-control brain networks. Flexibility in these networks allocates mental resources to influence the priority of domain-specific information processing. By using the Attention Network Test (ANT), Jin Fan and his colleagues at theQueens College/CUNY previously showed lower efficiency of the visual alerting and executive control networks in autism, when compared with controls.
To understand the neurobiology behind autism, we need data at the cellular level. This is difficult to come by in humans, as the data are typically limited to analyses of postmortem tissue, or data from animal models. However, there is an opportunity to obtain physiological data directly from neurons in the human brain in a clinical setting — through depth electrode and surface grid monitoring in neurosurgical patients for the treatment of medically refractory epilepsy. This project involves several hospitals where such data can be recorded.
Understanding the emotional state of a person one is communicating with stands at the center of meaningful and successful human interaction, and speech serves as a conduit for conveying critical emotional information in everyday communication. Social communication deficits constitute a core characteristic of children with autism. Research has identified a specific impairment in interpreting the emotional content of speech, known as affective prosody, in individuals with autism. Little is known about the biological basis for affective prosody difficulties in children with autism.
The proposed research takes advantage of the resources available at the University of Oxford in the U.K. to validate a new noninvasive magnetic resonance imaging (MRI) biomarker of autism using postmortem imaging. This has enormous potential for subsequent development as a tool for early detection, diagnosis, monitoring and assessment of individuals with autism. Steven Chance and his colleagues seek to better understand the cause of autism by investigating the neuroanatomical basis of the condition. Accurate diagnosis in life is difficult because the detailed changes in the cerebral cortex cannot be seen in brain imaging of living people.
A core symptom of autism involves impaired social relationships. One reason for this may be that individuals with autism do not experience the typical rewarding aspects of social interactions. Specific brain areas are critical for experiencing such social pleasures and specific brain chemicals may be important for promoting social interactions.
Genetics is important in the etiology of autism, with many identified candidate genes linking autism to synaptic pathology. Although understanding autism at the level of genes and synapses is essential, developing novel therapeutics requires an understanding of the dysfunction of neural circuits that control autism-related behavior. This entails knowledge of the affected neuronal subtypes and how their interactions may be disrupted in distinct brain regions and developmental stages.