Superior spatial abilities in Autism Spectrum Disorder (ASD) are popularly associated with savant behaviors, and have been demonstrated in previous studies including tests of spatial intelligence. Our study examines participant's performance on a classical mental rotation task, which provides an objective measure of spatial ability. We seek to demonstrate how differences in reaction time (RT) and brain responses of adults with ASD differ from controls in this task. Previous research in typical individuals demonstrates that as the degree of rotation increases, participants are slower to make orientation decisions. These RT measures suggest individuals mentally rotate a second image to a reference image in order to make a decision. Our study tested age and IQ matched ASD and typical controls in a task that required a decision about the orientation of images of block alphabet letters. Participants were asked to decide whether the second of two images was identical to or a mirror of the first image. Images were presented at one of four angles. Dense array electroencephalography (EEG) and RT were recorded. Thirty-five male adults (17 in ASD, 18 in control) participated. RT, IQ, angle of images, and accuracy were variables for behavioral analysis. EEG data was analyzed in the time/frequency domain using open source and in-house software. EEG and RT measures from each trial of the task were compared based on subject group, types of images (normal or mirrored), and angle of images. Our analysis extends to include investigating brain activity prior to the pressing of the response key (the time that participants are making a decision). No general advantage in mean RT was seen in ASD group, however, high performance IQ (PIQ) participants in ASD group performed faster over the course of the experiment. This suggests high PIQ autistics may learn faster in this particular task.

Dystonia Chorea is a very rare disease that includes the recurrent, aimless, uncontrollable, and sometimes painful movements of chorea, as well as the characteristics of dystonia, such as twisting, contorted movements or abnormal postures caused by sustained muscle contractions. The objective of the Raskind Lab is to identify the genes that are responsible for rare forms of neurogenetic diseases using exome sequencing and linkage analysis. For the Dystonia Chorea family, chromosome X was selected for initial analysis because the pedigree suggested possible X linkage. Chromosome 4 and 9 held candidate genes with some evidence for linkage. Within these regions, the variants were filtered for sequence-read quality and sharing of variants by affected people. Only variants for which the affected people were heterozygous for the alternate and reference bases were further considered. We did literature searches for protein functions and disease similarities with Dystonia Chorea, however none were identified. We will assess a more complete linkage analysis to identify new regions of interest on other chromosomes for analysis of exome variants.

Experimental studies have suggested that pain and dyspnea (shortness of breath) may involve the same affective experience. This association has not been explored in large community samples. We analyzed data from Cohort 12 of the Medicare Health Outcomes Survey, which measured subjective health status in 275,000 Medicare Managed Care recipients in 2010 and 2012. Dyspnea was defined by aggregating three questions (shortness of breath at rest, while walking one block, and while climbing stairs). Pain was measured by a question about how much pain interfered with normal work inside and outside the home during the last month. Both measures were dichotomized as high and low / none. We produced descriptive statistics to characterize the overlap of pain and dyspnea at baseline. We created regression models to measure the strength of the association of pain with dyspnea, adjusting for age, sex, race, education, and three potential medical causes of dyspnea (CHF, obesity and asthma). We estimated the likelihood of dyspnea and pain co-occurring at the two measurement points two years apart. 22.2% of participants without dyspnea had pain and 69.9% of those with dyspnea had pain. In an adjusted regression model, participants with dyspnea were 8.3 times more likely to have pain than those without dyspnea. Pain was strongly associated with the onset and the persistence of dyspnea. In this large sample of Medicare recipients, pain and dyspnea were very strongly associated, to the degree that they may represent different facets of the same experience. These results confirm experimental studies about the affective experience of both symptoms. These findings might help clinicians to appreciate better how patients experience pain and dyspnea. Additional research is needed to understand the exact mechanisms by which pain and dyspnea co-occur, and other risk factors for them.

Individuals with autism spectrum disorder (ASD) demonstrate impairment in communicating with others and responding to social cues appropriately. These impairments may extend to family members. The Broader Autism Phenotype (BAP) refers to relatives of individuals with ASD who exhibit impairments similar to those with ASD. BAP suggests that some traits of ASD may be inherited separately and exist in individuals without ASD. Social language impairment is consistently observed in individuals with ASD. Twins are useful in studying the genetic components of a disorder, because they share 50% (dizygotic) or 100% (monozygotic) of their genes. This study examined the presence of BAP traits in disconcordant twin pairs (where only one twin has an ASD diagnosis) compared to twin pairs with typical development. twins aged 7 to 30 years completed a 15-20 minute conversation with an experimenter, which was later coded for pragmatic (social) language abilities using the Pragmatic Language Scale (PRS). In the PRS, coders blind to diagnosis, rated individuals on skills such as eye contact, intonation, facial expression and reciprocity of conversation. First, analyses compared pragmatic language in three groups: (1) the twin with ASD, (2) the unaffected twin of the child with ASD, and (3) an age and gender matched typical twin with no family history of ASD. We expected that pragmatic language was most impaired in the ASD group compared to the typical group, with the unaffected twin showing intermediacy performance, suggesting that pragmatics are part of the broader phenotype. Next, we compared the relationship of symptom severity in the twin with ASD and the level of pragmatic language in their unaffected sibling. This study will provide insight as to whether pragmatic language skills are a part of the broader autism phenotype and the degree to which they are related to familial autism symptoms.

Autism Spectrum Disorder (ASD) is characterized by deficits in communication, social skills, and repetitive behaviors. Understanding the risk factors in early childhood that lead to the diagnosis of autism is an important area of research. Specifically, researchers are trying to understand how communication development differs in children who go on to develop autism in comparison to those that do not. Previous research has shown that 18.7% of infants, who have at least one older sibling with ASD, develop autism. In this current study, two groups of infants between the ages of six and twenty-four months were tracked longitudinally: high-risk infants who have an older sibling with ASD and low risk infants who have no family history of ASD. The Communication and Symbolic Behavior Scales (CSBS) protocol was used to identify various communication modes used by each infant at 12 and 18 months of age. The videotaped interactions between the infant, clinician, and parent were coded offline by a group of trained undergraduates. The following communicative acts were defined and coded: (1) behavior regulation: the infant’s attempt to control some behavior of an individual around him/her; (2): social interaction: the infant’s ability to bring attention to him/herself; and (3) joint attention: the infant’s ability to bring attention to an object. Our aim is to explore differences between rates of communicative acts in high risk and low risk infants at 12 months of age. Previous research suggests that children with ASD are less likely to draw the attention of others to objects or events. We hypothesize that high risk infants will display significantly lower rates of communication acts in all three domains when compared to their low risk peers. This study will contribute to a better understanding of possible deficits in early communication in this high-risk population, leading to earlier intervention opportunities.

A critical problem in the treatment of addiction is the tendency of addicted individuals to relapse to drugs-seeking with as many as 90% of addicts relapsing to use within one year. Exposure to stress is an important factor that precipitates relapse, though the exact mechanism is yet unknown. The Lateral Habenula (LHb) and the Rostromedial Tegmental Nucleus (RMTg), nuclei in the dorsal diencephalon, have recently become brain regions of interest in addiction research. Both regions have been shown to be important regulators of the midbrain dopaminergic systems, which are involved in relapse to cocaine seeking. However, very little is known about the precise role of these nuclei in stress-induced cocaine relapse. In our initial experiments, male, Long-Evans rats were handled for 3 days, and then injected with cocaine (10mg/kg) or exposed to intermittent footshock. Preliminary results demonstrate an increase in the expression of cFos, an early-detection transcription factor and marker for neuronal activity, in both the LHb and RMTg upon acute exposure to cocaine or foot shock. Studies are currently underway to determine the role of the LHb, and LHb projections to the RMTg on stress-induced cocaine reinstatement using the DREADD (Designer Receptors Exclusively Activated by Designer Drugs) technology in a rat self-administration reinstatement model.

Autism Spectrum Disorders (ASD) are characterized by atypical social development, decreased verbal and non-verbal communication, and repetitive behaviors. Retrospective studies of children with autism suggest an association between pregnant mothers’ use of certain medications and the occurrence of ASD diagnoses in their children. Other findings have also determined a relationship between an infant’s cognitive development and maternal mental health. In addition to maternal variables influencing development, infants may be at genetic risk based on sibling status: specifically, infants with siblings who have been diagnosed with ASD are at high-risk for also developing ASD. Using data from the Early Connections study – a longitudinal study of high-risk infant siblings compared to low-risk infants, we examined whether maternal variables resulted in added risk for poor child outcomes in the high-risk group. Information about family history of medical and psychiatric diagnoses, mother’s medication use during pregnancy, pregnancy complications, and other details pertaining to the mother’s delivery history were compiled for three groups: infants who develop autism (high risk, n=13, low risk, n=1); high risk infants who do not develop autism (n=32); and low risk infants who do not develop autism (n=42). Data analysis is ongoing. This study will examine the role of prenatal and postnatal effects in infant development in a high-risk sample. It is expected that mothers of high-risk infants will exhibit more medical and psychiatric conditions.The results of this study could aid in medical care for families who have a child with autism and are considering care options during a later pregnancy.

Event related potentials (ERP) are electrophysiological responses of the brain measured during an electroencephalogram (EEG). The Mismatch Negativity (MMN) is an ERP component that occurs as a result of the brain detecting a deviant sound among a sequence of standards. It is represented by a negative peak in the fronto-central region of the scalp with latency 100-250 ms after onset of the abnormal stimulus. Previous studies have shown that the MMN is reduced in children with autism spectrum disorders (ASD) relative to typically developing children. It has been suggested that this indicates atypical automatic auditory processing in ASD. Other research has found abnormal MMN activity in schizophrenia patients as well. These studies have found an association between MMN activity and test measures of social function in individuals with schizophrenia. It has been theorized that impairment in auditory detection present in schizophrenia (as evidenced by a reduced MMN) may have downstream effects on certain facets of social cognition. No known work has yet been done to assess the same association in ASD. This study investigated the relationship of the MMN with social skills in individuals with ASD. In this study, EEG was recorded from children and adolescents with and without autism while they listened to auditory stimuli consisting of a standard sound ("ba") and deviant sounds ("da," "bi") to elicit an MMN. Parents reported on children’s social adaptive behavior in the Vineland assessment. The aims of this study are to (1) replicate previous findings that individuals with ASD have a reduced MMN relative to typically developing individuals, and (2) explore the relationship between the MMN and social behavior in children with ASD and typical development, as measured in the Vineland. A strong association may shed light on the sensory involvement in typical social functioning.

Autism is a disorder characterized by deficits in social and communication skills and repetitive behaviors. Fifty-two percent of the children with autism are treated with medication for some of the common co-morbid behaviors – e.g., anxiety, aggression, and hyperactivity. However, only 49-69% of these children respond positively to the medication, and about 18-26% of these children experience side effects such as insomnia, sedation, and increased appetite. An extensive series of trial-and-error might be needed for a patient, which could be time-consuming and stressful for both the patient and parents. A reliable method is needed to predict the effectiveness of the pharmacological treatment. This study used electroencephalography (EEG) to detect early changes in the brain that we cannot yet observe in behavior. Children who are diagnosed with autism and starting a medication (e.g. stimulant, antidepressant, or atypical antipsychotics) participated in this study. EEG was recorded while the subjects participated in a social processing task, a resting task, and the Go-NoGo inhibition task. The participant’s caregiver completed three questionnaires: Child and Adolescent Symptom Inventory, Aberrant Behavior Checklist, and Social Communication Questionnaire. This project analyzed the subject’s change in EEG and behavioral data over three different time points (T1= before, T2= one week after, T3= one month after the start of medication). Multiple aspects of each individual’s EEG signal were examined by comparing the difference from T1-T2 and T1-T3 against the null hypotheses of no change (or comparing change to 0). The goal of this project is to search changes in the EEG signal that is related to positive (or negative) behavioral changes in this population. This study will provide an important first step for understanding changes in the brain in response to medications, which may provide useful information to professionals during the process of choosing the most effective medication for children with autism.

Autism is a developmental disability characterized by social deficits, communication deficits, and repetitive behaviors. Previous research has shown that having an older sibling with autism is a significant risk marker for a younger infant sibling developing ASD. The Early Connections study investigated the developmental trajectory of infants, looking for early markers that may predict whether or not ASD will be developed later on in toddlerhood. The two subject groups were identified as follows: high-risk (infants with an older sibling with ASD) and low-risk (infants that do not have any family history with ASD). Both groups were tracked longitudinally from 6 to 24 months at 6-month intervals. The Communication and Symbolic Behavior Scales Developmental Profile (CSBS DP), an assessment tool for early communication in infants and toddlers, was administered to both groups at 12 and 18 months. Each infant was videotaped during the CSBS DP administration and those videos were coded offline by trained undergraduate coders. Coding is still in progress. Using the CSBS DP, previous studies have shown that delayed word, sound, and language development are consistent markers for ASD. Therefore, we expect infants from the high-risk group to have lower CSBS DP scores in word and sound acquisition domains when compared to the low risk-group. A better understanding of early deficits in the core elements of language development will provide researchers with clearer insight on early identifiable signs of ASD. Targeted intervention in language acquisition may help children at high risk for ASD overcome potential communication deficits earlier on in development, thereby improving future prognosis.

Serotonin (5-HT) is implicated in numerous emotional behaviors, including depression and anxiety. One form of serotonin receptors is the 5-HT_1B autoreceptor, which is involved in regulating 5-HT transmission and uptake. 5-HT_1B autoreceptors are located on serotonergic neurons and are pharmacologically indistinguishable from 5-HT_1B heteroreceptors located on non-serotonergic neurons. Distinguishing between activation of the two receptor types is important as they have different functions. A novel strategy to accomplish this is to use an engineered receptor to mimic the 5-HT_1B autoreceptor using a modified DREADD receptor (Designer Receptor Exclusively Activated by a Designer Drug). The DREADD-1B receptor will mimic the 5-HT_1B autoreceptor function with pharmacological specificity. The DREADD-1B receptor is G_i/o-coupled G-protein coupled receptor that is activated by the selective ligand clozapine-N-oxide. When G_i/o-coupled GPCRs are activated, decreases in intracellular adenylyl cyclase and, subsequently, cAMP levels are measured. It is expected that when the DREADD-1B receptor is activated, a decrease in cAMP levels will be observed. To verify this, I created a stable DREADD-1B cell line and will use transient transfections of a luciferase plasmid to measure cAMP levels via proportional luminescence using luciferin. Optimizing the conditions for receptor activation and observing sufficient decreases in cAMP levels will confirm the general functionality of the receptor. If there are large variations in the downstream biochemistry between the DREADD-1B receptor and the 5-HT_1B autoreceptor, using the DREADD-1B receptor as a surrogate for the 5-HT_1B autoreceptor could have profound effects on behavioral data obtained in other projects. Creating and characterizing the DREADD-1B receptor in an in vitro setting will provide valuable information and tools for future projects involving the 5-HT_1B autoreceptor and this novel tool.

The primary cilium is a sensory organelle found on most cells. In the brain, most or all neurons contain a single primary cilium, yet its function is not entirely understood. Ciliopathies are defined as a group of disorders physiologically characterized by malformation or dysfunction of primary cilia, which in turn result in a variety of symptoms including cognitive deficits, retinal blindness, situs inversus and polydactyly. The serotonin 6 receptor (5-HT6) is the only 5-HT receptor that localizes to neuronal primary cilia, and previous research has implemented the receptor in learning, memory, and drug addiction. Our experiment will investigate the link between neuronal primary cilia and 5-HT6 in an attempt to better understand the significance of this unique localization. Using an immortalized line of rat adrenal cells (PC12), we will express the 5-HT6 receptor using viral vectors, and then pharmacologically manipulate the activity of the receptors with either an agonist (WAY 399885) or an antagonist (SB 208466). We will first stain the cells using immunohistochemistry, then image using florescence microscopy, and lastly quantify the morphological change in primary cilia length. We expect to see a shortening of primary cilium in response to the introduction of an antagonist, and an increase in length with an agonist. Since the 5-HT6 receptor has been shown to be homologous between rats and humans, a practical application of this research could eventually result in a pharmaceutical solutions to some of the cognitive symptoms associated with ciliopathies like congenital cerebellar ataxia or Joubert syndrome.

Studies using electroencephalography (EEG) have supported the theory that mu rhythms, oscillating bands in the 8-13 Hz range, are related to sensorimotor processing. At rest, EEG mu rhythms are continuous but become suppressed during the observation and execution of biological motion. Individuals with autism spectrum disorder (ASD), a disorder characterized by social and communication impairments, display atypical mu activity. Individuals with ASD exhibit typical mu suppression when executing self-made movements but significantly less suppression when observing the same movements. Individuals with ASD also show consistent impairments in imitative ability. One theory is that dysfunction in the observation/execution system contributes to this impaired imitation ability. To this point, studies have primarily focused on mu attenuation during the observation of hand or body movements, but few have focused on mu in response to facial movement. Since facial processing is integral to social learning, understanding perception deficits for facial movements may be important for understanding social impairment in individuals with ASD. This study will investigate whether sensorimotor processing of faces correlates to imitative ability by analyzing the relationship between mu attenuation of facial movement and facial imitation in children with ASD. For our study EEG was recorded while children and adolescents with and without ASD observed computer generated faces performing biologically possible and impossible movements. Participants then completed a battery of imitation tasks which included imitation of facial gestures using the mouth, eyes, or tongue. We hypothesize that the level of mu attenuation during observation of biologically possible facial movements will correlate with facial imitation ability in children with autism. Furthermore, decreased mu attenuation to biologically possible faces will be related to an increased number of imitation errors. Results of this study may help to improve understanding of social impairments of ASD children as related to deficits in sensorimotor perception of biological motion.

Most of the questionnaires used to assess college students’ thoughts about their drinking are developed by researchers and are passively responded to by participants. Such researcher-generated measures, however, may not accurately reflect college students’ thoughts about their drinking. In contrast, the current study used participants’ own words in response to an open-ended measure to evaluate advantages and disadvantages college students perceive in maintaining their current drinking behaviors. Participants were college students (N=760) at the University of Washington who reported at least one heavy drinking episode in the past thirty days. The Decisional Balance Worksheet (DBW), an open-ended measure of motivation to change, was used to record the pros and cons of current drinking behaviors. Conventional content analysis methods were used to extract common themes. Findings indicated that social, “fun,” and psychological effects of drinking were the most commonly mentioned advantages of drinking, whereas physical side effects, money, and calories/weight gain were the most commonly mentioned disadvantages of drinking. These findings show that college students use alcohol to achieve certain kinds of psychological states, enhance social interactions, and ease day-to-day stress. Further, many college students report experiencing physical side effects of drinking as well as more minor inconveniences, such as concerns about calories. In contrast, previous researcher-generated decisional balance measures have emphasized very different categories for advantages (e.g., coping, social, and excitement) and disadvantages (e.g., health effects, lack of control, and legal problems) (Migneault et al., 1997). Our findings therefore suggest that using open-ended questionnaires may result in a more accurate representation of what college students perceive as advantages and disadvantages to drinking.

Gaze-following allows infants to identify social and cultural information. Ongoing research examines what experiences help infants learn about the gaze of others. This research finds that particular experiences help infants learn about visual perception and affects their gaze-following. 18-month-olds watched an adult’s goal-directed actions while wearing a trick blindfold that looked opaque but was see-through. When infants observed the blindfolded adult successfully perform visually guided behaviors (grabbing a toy), they later gaze-followed as though the adult could see through the blindfold. However, when they watched the blindfolded adult’s unsuccessful behaviors (missing a toy), they treated her as though the blindfold blocked her view. These results show that infants are able to use their observation of others’ motor behaviors to learn about their perceptions. The present research examines whether infants’ gaze patterns during the observational experience affect infant learning about perception. Infants’ looking will be coded during the observational experience to identify the number of gaze shifts from the adult’s action pattern (grabbing or missing) to the adult’s face, called action-to-face looking (A-F looking). We hypothesize that infants who frequently perform A-F looking will be more likely to learn whether or not the blindfolded adult can see through the occluder. We will analyze gaze-following scores as a function of high versus low frequency A-F lookers (median split) and observational experience group. We expect that a 2 (high vs. low A-F looks) x 2 (grab vs. miss) ANOVA will reveal a significant interaction. We expect infants who more frequently shift their gaze during observation will be more likely to learn about perceptual status and thus gaze-follow more frequently. Infants’ gaze-shift patterns have implications for how infants’ attention and looking patterns support their nonverbal learning and development.

This research examines the relationship between an individual’s beliefs about authority and purity when making moral decisions and an individual’s alcohol consumption, specifically whether those who strongly identify with purity or authority consume more or less alcohol than those who do not. This is important to consider because few studies have looked at the relationship between moral considerations and alcohol consumption. We hypothesized that those who place comparatively less emphasis on authority and purity when making decisions about what is morally right would report higher levels of alcohol consumption. Participants (N=860; 41% male, 59% female) completed an online screening as a part of a larger study. Primarily, we focused on the Moral Foundations Questionnaire (Graham et al., 2011), in particular the authority and purity subscales. In addition, we considered the Daily Drinking Questionnaire (Collins, Parks, & Marlatt, 1985), Quantity/Frequency Measure (Marlatt, Baer, & Larimer, 1995), and whether participants met criteria for heavy episodic drinking (NIAAA, 2004). Preliminary analyses indicated that there is statistically significant negative correlation between alcohol consumption and authority as well as purity. These findings may extend our understanding of how treatment and prevention programs can target individuals that place relatively less importance on purity or authority. Future research is necessary to determine how authority and purity considerations with moral decisions can be used to better understand college students’ risky alcohol consumption.

 Among individuals diagnosed with autism spectrum disorder (ASD), a delay or diminishment of the development of language and communication is found to be a core feature of the disorder. Children with ASD are also found to have more difficulty with verbal working memory tasks when compared to typically developing individuals, although findings have been mixed. In other clinical populations in which communication is impaired, one aspect of language that has been found to be related to verbal working memory is narrative ability, though this has not been thoroughly tested among children with ASD. Previous work has shown that verbal working memory relates to communication skills in children with ASD, albeit this study did not investigate narrative ability specifically. The current study had the goal of investigating the relation between verbal working memory and narrative ability in children with ASD. Data was collected from 21 participants. Participants were children from 6 to 11 years of age with autism spectrum disorder and average or above average IQ. Working memory was measured with the Children’s Memory Scale Numbers subtest, and narrative ability was coded from a speech sample obtained during the Autism Diagnostic Observation Schedule. The planned analysis was a partial correlation between verbal working memory and narrative ability controlling for IQ. Our prediction was that better verbal working memory would be a predictor for stronger narrative ability above and beyond IQ.

Autism is a neurodevelopmental disorder, with symptoms related to social communication and repetitive behavior. In addition to these symptoms, a significant number of children with autism exhibit anxiety. One way to understand the biological underpinnings of anxiety is to measure responses of the automonic nervous system. Children with autism spectrum disorders (ASD) have shown hyper sympathetic responses to some tasks, while showing hypo sympathetic responses to others. In this study we examine two questions. The first objective of our study is to compare the behavior and skin conductance of typically developing children and children with ASD during a working memory task. Our second objective is to test whether individual differences in skin conductance within the group with ASD correlate to internalizing behaviors. Twenty-one 6 and 7 year old children with idiopathic ASD and 21 typically developing children participated. There were no group differences in age, IQ, or sex ratio. Continuous recordings of the skin conductance response (SCR) signals were collected during the digit span task for both groups of children. Internalizing behaviors were assessed via the Behavior Assessment System for Children, second edition. We expect to find higher level of SCR for the group of children with ASD, given previous reports of increased SCR among children with ASD in tasks that were cognitively or socially demanding. For the second part of the study we predict that there will be a positive correlation between the level of SCR and internalizing behaviors. Our results may illuminate what biological features correlate with these challenging internalizing behaviors. This could identify a subgroup of children with higher levels of anxiety and increase our understanding and treatment of anxiety in individuals with autism spectrum disorders.