Most children with tuberous sclerosis complex (TSC) suffer from neurodevelopmental disabilities, including intellectual disability (ID) and autism spectrum disorder (ASD). In a large prospective study that followed infants with TSC in the first 3 years of life, we found that infants with TSC had developmental delays that were specific to non-verbal communication skills as early as age 6 months, skills that are important for the development of social functioning. We also found that by 12 months of age, developmental delays, particularly in non-verbal communication, predicted the development of ASD.
Evidence for these early delays reinforces the tremendous need for early intervention for all infants with TSC, with a focus on improving non-verbal cognition and social communication skills. While there exists tremendous excitement about the effectiveness of MTORC1 inhibitors and preventative anti-epileptics to improve cognition and social behavior in children with TSC, these pharmacologic treatments do not preclude the need for evidence-based behavioral interventions. However, no studies have investigated whether early intervention can improve social communication skills in infants with TSC. As a result, families of infants with TSC struggle to receive adequate interventions targeting these areas of development.
We propose to study an evidence-based behavioral intervention in infants with TSC, combining the efforts of investigators with expertise in autism intervention, infant development, and TSC. The proposed intervention study adapts a parent-mediated treatment called JASPER (Joint Attention, Symbolic Play, Engagement, Regulation) that has successfully improved outcomes in toddlers and young children with ASD. In addition to testing the primary effects of this early intervention on developmental outcomes of infants with TSC, we also will use electrophysiological (EEG; electroencephalogram) methods to examine low level visual processing, face processing, and resting state EEG oscillations prior to and after intervention. These brain markers are sensitive to subtle changes in brain development and may be able to capture responses to treatment prior to clinical or behavioral change. They also can inform the brain basis for the behavioral changes found with intervention. Our primary goal is to determine if social communication function can be improved with a targeted, short-term JASPER intervention, and if specific infant characteristics impact or modify the improvements made with treatment.
Research has shown that early intervention improves cognitive and behavioral outcomes in children with atypical development. From a clinical and health services standpoint, evidence of effectiveness of early intervention will justify its value for all infants with TSC, before clinical diagnoses of ASD or ID are made. The earlier we provide treatment, the more likely we will be able to improve developmental outcomes, decreasing symptoms that lead to the diagnosis of neurodevelopmental disabilities in TSC.