Autism Spectrum Disorder (ASD) is a chronic developmental disorder classified by deficits in social communication and restricted or repetitive patterns of behavior. A highly comorbid disorder with ASD is Attention Deficit Hyperactivity Disorder (ADHD) characterized by inattention, hyperactivity, and impulsivity. Deficits in empathy and facial affect recognition have been observed in children with ASD and ADHD. Through the APEX 5-week intensive Summer Treatment Program (STP), the UW Autism Center integrates naturalistic therapy for children diagnosed with ASD and/or ADHD aged 6 to 12. Within this evidence-based program, children develop social and behavioral skills through structured recreational and learning activities. During the summer of 2019, we collected the Positive and Negative Affect Schedule for Children (PANAS-C) from 120 participants ages 6-12 weekly. The PANAS-C measures youth anxiety and mood by asking participants to rate each emotion, five positive and five negative, on a point scale from 1 (not at all) to 5 (very much). Through multiple regression analyses, we aim to examine child affect through the PANAS-C within the context of variables such as age, gender, and diagnosis. We hypothesize that during participation in the summer treatment program, positive affect ratings will increase as negative affect ratings decrease. We expect that the combination of integrative social skills training, positive reinforcement, and acquisition of behavioral skills, will increase positive affect for children in this setting.

The maternal bond is an intimate attachment between a primary caregiver (PC) and their infant which provides the infant with security, facilitating physical, social, and emotional development. A sensitive and responsive environment, such as the presence of healthy maternal bonds, guides an infant’s neurodevelopment. Changes in mood and emotional state can alter the care a PC provides and cause difficulties in bonding with their infant, impacting the baby’s psychological and physical development. In infants, the mechanisms by which development may be impacted are unknown. Recently, research has shown early atypical attention to visual pop-out in autism spectrum disorders. Attention to visual pop-out describes our cognitive ability to quickly identify differing objects presented among similar looking ones. In this project, we investigated whether PC mental health affects attention to visual pop-out in infants. Participants included 50 infants who were assessed at 6 and 12 months of age. PCs completed the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) at both timepoints. Infants watched a 4-minute visual pop-out paradigm, which included social (face) and non-social (shape) trials. We assessed responses to visual pop-outs and explored whether BDI and BAI scores correlated with visual pop-out performance at 6 and 12 months. We also investigated whether BDI and BAI scores influenced the development of attention to visual pop-out between 6 and 12 months. We hypothesized infants of primary caregivers who report more (a) depressive and (b) anxious symptoms will demonstrate weaker identification of the pop-out during social trials compared to their peers but be unaffected during nonsocial trials. This study will help deepen our understanding of the impact of maternal depression and anxiety on infant development and help health providers identify and support families.

Current estimates by the centers for disease control (CDC) suggests that roughly 1 in 59 children in the US are affected by Autism Spectrum disorder (ASD). Despite its high prevalence, our current understanding on the biological etiology of ASD is limited. However, an ASD associated gene, TAOK2, which encodes a serine/threonine protein kinase, has been found to mediate neurodevelopmental disorders like ASD. Mutations within TAOK2 are associated with atypical neural connectivity in different brain regions, abnormal synapse formation, reduced cortical layering, and increases in brain size. Though TAOK2 plays a crucial role in neuronal development through phosphorylation of its substrate proteins, catalyzing or inhibiting their activity to regulate cellular processes, substrates of TAOK2 have not been fully elucidated and several candidate substrates have yet to be explored. Through my research, I explore TAOK2's interaction with putative substrate HDAC6, a histone deacetylase enzyme that functions to mediate a variety of cellular processes such as protein degradation, transcription, and the ability to regulate α-tubulin to mediate microtubule dependent cell motility. HDAC6 has been identified as a putative substrate of TAOK2 through mass spectrometry. Here, I present my findings regarding TAOK2's regulation of HDAC6 deacetylase activity and the potential it has for expanding our understanding of the molecular mechanisms underlying ASD.

Hoarseness is a common symptom reported to generalist healthcare providers, with approximately 1% of the clinical population being affected by it each year. It can be caused by multiple etiologies, such as hoarseness due to a cold, acid reflux, or laryngeal cancer. Perceptual evaluation of the voice is inaccurate, and it is therefore difficult to differentiate between hoarseness requiring urgent referral for specialty evaluation (i.e. laryngeal cancer) versus a disorder that could be managed without specialty care (i.e. acute laryngitis). The current gold standard of diagnosis for hoarseness is laryngoscopy, an in-clinic endoscopy recording of the larynx performed by an otolaryngologist specialist. Our research team seeks to improve perceptual voice evaluation by developing and testing machine learning algorithms which analyze voice for underlying pathology, beginning with an algorithm which screens voice for laryngeal masses. We hypothesize that our algorithm will have greater than 80% sensitivity and specificity in the classification of voice samples from patients with laryngeal masses. To test this, we are developing a large, prospective database of voice samples from a laryngology clinic using a smartphone application. Subjects are adult patients presenting to the laryngology clinic, with and without voice disorders, who have had a recent laryngoscopy exam and no laryngeal surgery within the past three months. We are collecting patient history which could influence voice quality, such as age, gender, alcohol use, smoking history, and subject-perceived voice disorder impact. After collection of the voice sample and patient history, cases are classified into underlying pathologic categories. We see recruitment of a well-classified and prospective patient population with a range of voice disorders. This work could lead to improved screening of patients with hoarseness in underserved and primary care settings, and more appropriate and timelier specialist referrals and treatment.

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by impairments in social interaction and repetitive behaviors. One of the most common mutations leading to ASD is 15q11-q13 duplication, a CNV mutation where extra copies of a chromosomal region are expressed. The major gene within this region is ube3a. My lab has generated a mice model with increased copies of this gene and demonstrated a novel deficit in phosphorylated-AKT, a key protein in the mTOR/AKT signaling pathway. Other mice models of autism have exhibited deficits in this pathway and have rescued behavioral deficits with a drug, rapamycin. Rapamycin is an inhibitor of a key protein of the mTOR/AKT pathway suggesting a similar behavioral rescue might be observed with ube3a transgenic autism model mice. Behavioral testing of 4 groups of 20 mice, wild type and ube3a transgenic mice treated with and without rapamycin, found that there were no baseline social deficits in ube3a transgenic mice not treated with rapamycin. This is not similar to previously published findings and could be due to a number of reasons. It can be difficult to get consistent results with mice behavioral testing. In order to assess if rapamycin had its intended effect in restoring deficit levels of phospho-AKT, protein levels will be assessed. Brain slices from the hippocampus of behaviorally tested mice will be analyzed by western blot, a method of identifying and measuring specific proteins. Successful rapamycin treatment would be observed as increased levels of phospho-AKT, similar to wild type mice. This would suggest that repeated mice behavioral testing is needed and therapeutic treatment of the mTOR/AKT signaling pathway could be a viable target for patients with 15q11-q13 duplication.

Recent work published by my colleagues and I showed that diagnostic ultrasound, applied directly over the visual cortex of human participants, increased the likelihood that they would observe visual effects while looking at a visual target, with that likelihood increasing over the course of the experiment. However due to a lack of EEG data, it is impossible to know the biophysical mechanisms and neural pathways that generate the observed effects on brain function. To better understand the full effect and mechanism of our initial findings, I helped develop a surgical protocol for a mouse model allowing for the collection of EEG data while exposing the animal to a combination of light and diagnostic ultrasound stimuli. EEG data was collected from 5 mice using a stimulus paradigm that we believed would increase the rodent's susceptibility to light stimulus. I utilized Matlab for processing, visualization, and statistical analysis of the data to determine the effects and hypothesize potential biophysical mechanisms of the stimuli. My analysis focused on determining whether the ultrasound stimulus successfully increased the susceptibility of the visual cortex, and which brain frequency bands were modulated by the stimulation.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by the presence of repetitive patterns of behaviors and deficits in social communication and interaction. Attention to social information is a key component of the development of social communication. Previous studies used eye tracking to examine visual scanning patterns associated with social attention in children with ASD and neurotypical children. Eye tracking is used to both identify the atypical patterns of social attention and to predict clinical outcomes in ASD. Although atypical eye gazing patterns are considered as potential biomarkers, researchers commonly consider data loss in eye tracking as error or noise, and rarely investigate it more thoroughly. In this proposal, we hypothesize that loss of data is a potential signature of core social motivation issue when a social video is playing, and, rather than being a nuisance variable, which reflects the broader continuum of social attentional-motivational challenges faced by individuals with ASD. We used eye tracking to confirm previous findings on atypical attention patterns, and further utilize behavior coding to examine the three types of causes of data loss including blinking, non-compliant behaviors, and technical error. We hypothesize that data loss due to blinking is associated with a lack of social motivation and that data loss due to non-compliant behaviors is associated with executive function. Social motivation and executive function were measured by parent reports. Exploring data loss in eye tracking may help reveal comprehensive and fundamental factors of diminished social motivation and neurocognition in ASD.