Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by challenges in communication, social interaction, and restricted repetitive behaviors and interests (RRBs). Studies have alluded that a relationship exists between RRBs and difficulties with emotional regulation in ASD individuals. However, a better understanding of this relationship is not only critical for improving therapeutic approaches for individuals with ASD, but also to understand the underlying mechanisms of the disorder. In this study, we aim to explore the relationship between emotional control and compulsive and ritualistic behaviors in youth aged 8–17 years with and without ASD as well as look at sex as a confounder. Emotional control will be assessed using Behavioral Rating Inventory Executive Functioning T-scores, and the presence of Compulsive and Ritualistic Behaviors were assessed from the Repetitive Behavior Scale-Revised subdomains. We will compare emotional control scores between participants with and without these behaviors (based on clinical cutoff). To do so, first, we will conduct an ANOVA to assess the impact of Group (ASD vs TD), Sex (M vs F), and Compulsive behavior (Above/Below Clinical Cutoff) and their interactions on Emotion Control (dependent variable). Second, we will conduct the same analyses with Ritualistic behaviors on Emotion Control.  We hypothesize that youth with compulsive and ritualistic behaviors will demonstrate lower emotional control than those without (main effect of RRBs). We also predict that males will have lower emotional control than females (main effect of sex) and that autistic youth will have lower emotional control than their typically developing peers (main effect of diagnosis). This research has the potential to reveal insights regarding the interaction between emotional regulation and RRBs in youth with ASD, highlighting the importance of interventions targeting emotional control. Such interventions can improve emotional regulation and also address compulsive and ritualistic behaviors.

Autism is a neurodevelopmental condition characterized by social-communication differences and restricted, repetitive behaviors (American Psychological Association, 2013). While racial disparities in autism prevalence have been documented, not much research has examined how these differences appear in autism screening measures. This study investigates racial differences in Autism Spectrum Quotient (AQ) scores among non-autistic Asian and White adults to assess potential biases in autism screening. Using data from three NIH-funded studies (COBRA, BEAM, and The Korean Study), AQ scores from 166 participants (n=102 White, n=64 Asian) will be analyzed through t-tests and Repeated Measures Analysis of Variance (ANOVA) to compare total and subscale scores. Preliminary observation suggests that non-autistic Asian participants may be more likely to score higher on the AQ, raising concerns about false positives in autism screenings. Understanding these differences will help improve diagnostic accuracy, reduce disparities, and promote equitable access to neurodevelopmental resources.

Xylazine is a veterinary sedative that has become a common adulterant in fentanyl products due to its ability to prolong the euphoric effects of fentanyl. Adulterated drug mixtures containing xylazine have been linked to an increased risk for respiratory depression and fatal overdose. Existing treatments for overdose such as naloxone do not work against xylazine and there is currently no FDA approved reversal agent for xylazine toxicity. Monoclonal antibodies (mAbs) are a promising therapeutic option to reverse drug overdose and can be used to target small molecules by sequestering them in the bloodstream and preventing their passage into the brain. Previously, we made a series of xylazine haptens and formulated them into vaccines where they were found to induce strong antibody responses, reduce brain to serum ratio of xylazine, and mitigate respiratory depression in Sprague-Dawley rats. Based on the protective effects of our xylazine conjugate vaccines, we hypothesized that we can create an effective reversal agent by isolating xylazine specific mAbs. In this study, we immunized mice with xylazine conjugate vaccines to generate antibodies specific against xylazine. We then used the secondary lymphoid organs of the vaccinated mice to establish stable mAb producing cell lines using hybridoma technology. Hybridomas were screened with ELISA and lead candidates were selected and sequenced for further characterization. We will conduct in-vitro characterization assays to quantify binding affinity, functional activity, and thermostability of our lead mAbs. Furthermore, in-vivo studies will assess the efficacy of our mAb lead candidates in rodent models.

Overdose deaths in the United States have rapidly increased in the past few years accounting for over 107,000 deaths in 2022 with more than half being attributed to the co-usage of opioids and stimulants. Despite the prevalence of polysubstance use, research has predominantly focused on single substance use, leaving a gap in knowledge regarding its neurological effects. Addiction-associated behaviors such as drug-seeking, drug-taking, and relapse vulnerability has been attributed dysregulation of the striatum. We recently found that polysubstance exposure to methamphetamine and fentanyl leads to behavioral differences in methamphetamine-seeking but not fentanyl-seeking relative to single-substance rats, suggesting that polysubstance use causes distinct changes in striatal circuitry. Our overarching objective is to determine to what extent pursuit of methamphetamine and fentanyl involves shared neural pathways. How do distinct striatal neuron subpopulations responsive to either methamphetamine or fentanyl regulate drug-seeking in animals exposed to both substances? To investigate this, rats are placed into self-administration boxes and undergo two phases of daily intermittent access drug self-administration. In the first phase of self-administration, lasting 10 days, a novel targeted recombination in active population (TRAP) technology and recombinant viral vector is used to target inhibitory designer receptors exclusively activated by designer drugs (DREADDs) to striatal cells that are activated during fentanyl- or methamphetamine-seeking. For the second phase of the experiment, lasting 28 days, rats are then divided into groups for either self-administration of methamphetamine, fentanyl or a polysubstance model. Using chemogenetic manipulations in polysubstance rats, we will test the hypothesis that inhibition of the striatal neuron subpopulations active during fentanyl-seeking will decrease methamphetamine-seeking whereas inhibition of methamphetamine activated neurons will have no impact on fentanyl-seeking. These experiments will provide important insights and lay the groundwork for future studies into how striatal circuits regulate behavior during single and polysubstance use of opioids and stimulants.

Each year, approximately 84,100 adolescents and young adults (AYAs) in the United States are diagnosed with cancer. Beyond the physical challenges that come with cancer, they also face significant psychosocial barriers, including gaps in health literacy, limited access to professional mental health support, and uncertainty about the future. Addressing these unmet needs requires innovative approaches, and social media, particularly Instagram offers a unique opportunity to bridge the gap between traditional healthcare services and the psychosocial needs of AYAs. With 2 billion users, Instagram is widely used for connection and information sharing, making it a valuable platform for health-related support and education. This study qualitatively analyzes Instagram posts under popular pediatric cancer hashtags to: (1) explore how AYAS and caregivers use social media for health information and support, (2) identify barriers they face in healthcare, and (3) examine how social media can enhance health literacy and education. A direct content analysis of 300 posts was conducted using a newly created Instagram account to minimize algorithmic bias. AI tools, including ChatGPT, Perplexity, and Microsoft Copilot, helped identify commonly used hashtags, which were then cross-referenced on Instagram. The most frequently used hashtags include #childhoodcancer, #childhoodcancerawareness, #pediatriccancer, #stupidcancer, #fightlikeakid, and #morethan4. An iterative coding process, using sets of 5–10 posts, was employed to develop and refine a codebook based on existing literature. Posts were categorized by metrics, user profiles, content types, health-related quality of life, and social support. My coding team consisting of myself, and 3 other investigators will code the data using REDCap, with descriptive statistics analyzed in R Studio. Findings from this study will highlight how Instagram can serve as a powerful tool to improve health literacy, education, and mental health support for AYAs with cancer, ultimately bridging critical gaps in healthcare accessibility and education.

Social norms are informal, shared rules that dictate people’s behavior, influenced by social expectations and potential consequences. Teachers' social norms can influence their willingness to adopt evidence-based practices (EBP) in schools. Although previous research has shown that social norms affect teachers’ behavior with decision-making and prioritization of tasks, less is known about how these norms impact successful implementation of EBP. Understanding how social norms affect teachers’ ability to adopt EBP in the classroom is important in understanding the barriers and facilitators in the school environment, which can in turn guide more effective implementation strategies. These strategies are crucial, as these planned approaches help to promote the adoption and integration of EBP into school settings through training, support, and other resources. This study investigates the relationship between teachers’ perceptions of social norms and their fidelity in implementing EBP. Data were drawn from a larger randomized control trial. Perceptions of social norms were collected via self-report surveys from 324 teachers and observed fidelity was collected via trained school personnel from 39 observers across 25 schools. In future analyses, we will examine the relationship between teachers’ perceived social norms and observed fidelity through Pearson’s correlation coefficient using data from timepoint 7, collected two months post-training. Successful EBP implementation can benefit both the teacher and the overall school environment, which in turn may contribute to positive student outcomes. Findings will contribute to the understanding of how social norms influence EBP implementation in school settings.

The fidelity of evidence-based practices (EBPs) for social-emotional learning in education is influenced by the attitudes of teachers. Teachers who believe an EBP is valuable are more likely to follow its guidelines and implement it as intended. However, the impact of years of teaching experience on these attitudes remains unclear. While experienced teachers may resist EBPs in favor of familiar methods, others may be more flexible and willing to use their experience to implement EBPs effectively. Experience may also foster positive attitudes towards EBPs as teachers feel more confident in their ability to implement them. To address the gap in understanding how years of experience influence teacher attitudes and EBP fidelity, this study will explore the role of experience as a moderator. Data were collected from a larger randomized control trial with a sample of 276 K-8 teachers from 46 elementary schools. This study focuses on three timepoints: 4, 7, and 9 months after training on Positive Greetings at the Door (PGD), an EBP designed for all students. At each timepoint, teachers completed online surveys, and their attitudes were measured using the Evidence-Based Practice Attitudes Scale (EBPAS). Fidelity of PGD delivery was assessed through observations of teachers by trained school personnel. Pearson’s correlation will be conducted to examine the relationship between teacher attitudes and PGD fidelity, while multiple regression analyses will assess how years of teaching experience moderates this relationship. The findings will provide insight into factors that may act as facilitators or barriers to EBP delivery, particularly implications for addressing barriers through selection and tailoring strategies used to improve integration of EBPs, as well as developing teacher training to support high EBP fidelity in schools.

Autism is a neurodevelopmental disorder characterized by differences in social-communication and the presence of restricted and repetitive behaviors and interests. Many autistic individuals engage in “camouflaging” to hide or change their behaviors associated with autism to avoid social stigma. This study aims to explore neurophysiological characteristics underlying camouflaging. Electroencephalography (EEG) is a popular psychophysiological tool that measures brain activity through oscillatory patterns, reflecting various cognitive and emotional processes. Specifically, during “resting state” (when the brain is exposed to minimal external stimuli), theta waves have been shown to have increased activity during periods of increased cognitive load, attentional demands, and task difficulty – mental states that all relate to camouflaging based on qualitative research.  Participants included autistic (n=108) as well as non-autistic adults (n=85), between the ages of 15 and 31 years. Participants completed the Camouflaging Autistic Traits Questionnaire (CAT-Q) which measured three domains of camouflaging in autism: compensation, masking, and assimilation. EEG recordings were taken during resting state and oscillatory activity in the theta frequency band (4-8 Hz) will be analyzed. Our hypothesis is that camouflaging traits will be positively correlated with theta wave activity.  Camouflaging can lead to various challenges for autistic individuals, including depression and anxiety. Thus, identifying the proposed analyses could provide valuable insight into the cognitive and emotional processes of camouflaging, ultimately contributing to a better understanding and potential treatment for mental health challenges faced by the autistic community.

Decision During Drinking (D3 study) is currently developing a mobile app aimed at reducing negative alcohol-related outcomes with a focus on young adults. D3 offers modules to educate users on identifying cues that influence their decisions, understanding their values after drinking, and engaging in practices to avoid such experiences. I have aided in the design of the prototype of the D3 program, both creating new features and adapting previously developed features. The current study assesses core aspects of human centered design on two of the D3 study features I helped to create in Figma. The first is an activity that compares participants’ perception on alcohol expectancies to alcohol’s physiological effects. The second is a “roadmap” planning tool that guides users to create action plans to cope with specific drinking cues, linking each plan to personal values. By using an iterative design approach from research participants’ feedback, I refined the user interface (UI) to improve the features. I am adapting measures on usability (i.e. System Usability Scale) to assess the metrics for these features specifically. Data is being collected from online surveys on the usability of these features. I predict that the final usability score would be higher than the industry-standard threshold (e.g. score of ≥ 70), so the features will provide a seamless and intuitive user interface. Based on the improvements, if deemed usable, these feature designs could be applied to other clinical app developments. 

Serotonin serves a vital role in the regulation of stress responses, and variance in the release of serotonin was found to contribute to various mental illnesses such as anxiety and depression. Current mental health treatments heavily rely on Selective Serotonin Reuptake Inhibitors (SSRIs). While these medications are generally effective, there are patient populations for whom SSRIs show limited efficacy. Recent studies found that in response to stress, the expression of the FKBP5 gene also increases and modulates many neuronal pathways including serotonin. This experiment determined whether manipulating FKBP5 gene expression in the dorsal raphe (DRN) directly correlates with serotonin release in the basolateral amygdala (BLA), an established neural circuit for fear. To manipulate FKBP5 gene expression, an adeno-associated FKBP5-Cre virus was injected into the DRN of Pet1-Cre transgenic mice, causing up or downregulation of FKBP5 in the DRN. To gauge the effects of FKBP5, fiber photometry was used to measure the release of serotonin following optogenetic activation of the DRN-BLA pathway using a 5HT GRAB sensor injected into the BLA. We hypothesize that increased FKBP5 expression in the DRN will increase serotonin release to the BLA, and as FKBP5 expression is decreased, the release of serotonin to the BLA will decrease. Success in modulating serotonin release using FKBP5 gene expression will expand therapeutic targets in mental illness research, mitigating the gap in treatment efficacy for patients who have undergone ineffective SSRI therapy.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental conditions that are known to co-occur with decreased sleep quality and quantity. ASD is characterized by social communication differences and restricted, repetitive behaviors and interests.  ADHD is characterized by inattention and/or hyperactivity/impulsivity. Previous research found higher instances of sleep disruptions within adults with ADHD as well as autistic populations compared to neurotypical adults. However, quantitative data around the associations between ASD and sleep disruptions is sparse.  This leads to our research question which is, how does sleep disruption affect autistic, autistic + ADHD adult’s sleep quality and quantity compared to neurotypical adults? We hypothesize that ASD+ADHD and ASD adults have experience higher sleep disruptions (fewer hours of sleep and lower quality) compared to non-autistic adults. Participants included autistic adults (n=66), autistic adults with ADHD (n=39), and non-autistic adults (n=221) enrolled in the NIH-funded COBRA and BEAM studies, which investigated how the brain processes sensory and visual information.  Autism diagnoses were confirmed using standard assessments (such as Autism Diagnostic Observation Schedule, 2nd Edition, Autism Quotient) by clinicians.  Participants self-reported ADHD diagnoses, sleep quantity (hours per night on weekdays, hours per night on weekends), and sleep quality (over the past week on a 4-point Likert scale). An ANOVA will be used to compare sleep quality and quantity between diagnostic groups. Understanding neurodivergent populations’ sleep quality and quantity helps improve public health communication around sleep health, which is particularly important population health issue given the link between sleep, mental and physical health. Finally, identifying populations most in need of sleep interventions helps us address the increased number of adults with sleep disturbance and disorders.

Transgender and nonbinary individuals (TNB) face significant discrimination in healthcare settings, which is strongly associated with disparities in alcohol use and treatment access. These barriers often result in delayed or avoided care, exacerbating both physical and mental health issues. The literature reflects a lack of comprehensive understanding and research regarding the specific systemic barriers contributing to avoidance of alcohol healthcare among TNB individuals. This study aims to assess how healthcare experiences influence decisions to engage with alcohol healthcare within the TNB community and discusses future considerations for improvement. TNB adults (N = 26) completed an individual qualitative interview either in-person or online. As part of a larger semi-structured interview about alcohol use, participants were asked about their experiences discussing alcohol use and/or receiving alcohol interventions from medical providers. Participants identified as 30.8% transfeminine, 26.9% transmasculine, and 57.7% nonbinary and were between the ages of 18 and 57. The interview was audio recorded and transcribed by HIPAA-compliant Zoom and transcripts were then cross-checked and edited to ensure their accuracy. Ongoing qualitative analysis is conducted in Dedoose to identify emerging themes. Interactive coding procedures included two coders completing deductive codes identified with prior literature and two coders independently using inductive coding to identify new themes. Discrepancies are identified and discussions support reaching consensus. Understanding the intersection of healthcare mistreatment and substance use disorders in this demographic will inform future policies and interventions designed to create more inclusive and supportive healthcare environments for TNB individuals.

Previous research has suggested that Dynorphin, the endogenous opioid peptide, signals through KOR (Kappa Opioid Receptor) binding and causes negative affective states like anxiety and stress. Dyn-KOR signal activation has been found to instigate drug reinstatement. Based on previous research, questions about why Dyn-KOR signaling leads to drug reinstatement and what level of Dyn-KOR antagonism will mediate this behavior arose. The current project focused on characterizing Dyn-KOR signaling during Cocaine Self-Administration using in-vivo Fiber Photometry recording. Sprague-Dawley rats underwent cranial surgery where I injected a kLight sensor in the Prelimbic Cortex and the Nucleus Accumbens and implanted a fiber optic into each injection site. Chronic IV (intravenous) catheters were inserted into the right jugular vein and then threaded through the right shoulder into a pedestal implanted between the shoulder blades. Rats were attached to IV lines threaded through an operant chamber that was attached to a syringe of 5mg/mL cocaine. Following training, rats would undergo five days of Short Access in the operant chamber for an hour. Following Short Access, rats would go through two weeks of Long Access where they are run in the operant chambers for six hours each day. Fiber Photometry recordings were taken on the last two days of the Short Access week and Long Access weeks. Animals were put through a thirty-day Incubation period where, once over, were injected with KOR agonist U-50 (10mg/kg) and recorded. The day after were injected with KOR antagonist norBNI (nor-Binaltorphimine dihydrochloride, 15mg/kg) and injected with U-50 thirty minutes following and recorded. I collected brain samples from perfusion and fixed samples in 4% PFA (Paraformaldehyde).

Veterans and civilians in areas of military conflict are often exposed to explosions, resulting in blast injury: a complex polytrauma experience usually characterized by traumatic brain injury. Blast injury is also accompanied by observable changes to gut bacteria populations. These microbiota alterations influence the gut-brain axis, a two-way communication lane between the digestive tract and the central nervous system (CNS). Changes that impact the axis are linked to neuroinflammation, altered behavior, and more, affecting the overall health of the CNS. In fact, blast-induced microbiota changes are correlated with increased anxiety-like behavior as demonstrated recently in the Schindler Lab, the mechanisms of which are not fully elucidated. The current study aims to investigate the pathophysiology of the gut epithelium after blast exposure, an area no known studies have explored, as a potential route by which the microbiota affects behavior. With collected gut tissue from blasted mice, histological analysis will be carried out using hematoxylin & eosin (H&E) staining and Visiopharm software to measure morphological differences in villus length and smooth muscle thickness between blasted mice and a control group. Generally, short villus length and decreased smooth muscle thickness are signs of high intestinal permeability, which may lead to increased systemic inflammation that eventually reaches the CNS. Further studies will include in vivo assays investigating gut permeability, immunofluorescence histopathology, and fecal microbiota transplant studies to establish a potential causal role of the gut microbiota in driving blast injury outcomes. In short, blast injury is a traumatic experience that affects veterans and military violence victims alike, and understanding the mechanisms by which the gut-brain axis aggravates inflammation and behavior potentially provides therapeutic targets for treatment.

Despite widespread drug abuse, treatment options for people in recovery are oftentimes ineffective, as current research fails to cover the full range of the ways in which opioid, stimulant, or other substance contribute to substance use disorders. The goal of our study is to model how polysubstance use disorders operate in the human brain utilizing a translational rat model of addiction. 64 rats were assigned into single or polysubstance cohorts. Each rat was implanted with a jugular catheter, allowing a controlled dose of methamphetamine or fentanyl to be self-administered through a lever press, along with a drug-associated cue light. The cohorts completed a 3 week period of self-administration, followed by extinction, modeling withdrawal and abstinence. After extinction, the animals went through cue-induced reinstatement, a model of relapse. No drugs are dispensed when the lever is pressed, however the light cue continues to be used as a stimulus signal. Within a large dataset following this model, we are looking to uncover patterns related to differences in drug-taking and reinstatement behavior between the different cohorts. Correlations between the rats’ sex, polysubstance use, and other measurements of their behaviors offers a crucial lens of the more nuanced ways in which methamphetamine and fentanyl influence addiction-related behaviors. Methamphetamine and fentanyl function through distinct neural circuits, thus affecting behavior in individual and synergistic manners. To complement the current work, future studies will investigate the neurocircuitry underlying polysubstance use disorders utilizing whole brain imaging. Gaining clarity into how the nervous system responds to the interaction of both drugs present would mean the ability to develop targeted treatments options. Assuming there’s one treatment that works to treat all polysubstance addictions minimizes individual experiences and ignores the reality that we need to better understand the neurobehavioral aspects of addiction so people can get accurate and effective help.

Veterans have high rates of early life adversity and mild traumatic brain injury (mTBI), both of which are risk factors for PTSD. Our laboratory has found that common risk factors for stress and PTSD are exacerbated by increased expression of stress-sensitive gene FKBP5. We are testing whether FKBP5 mediates a synergistic interaction between early life adversity and mTBI to produce symptoms associated with PTSD in veterans. A prior study used illness as early life trauma and concussive blast as adult trauma. In our study, the traumas are better specialized to veterans. I'm exposing C57BL/6 mice to limited bedding and nesting (LBN) adversity pre-weaning and concussive blast trauma post-weaning. Post-natal days two-nine, mice undergo LBN using insufficient bedding, reducing maternal care and increasing stress, simulating housing issues and neglect often endured by veterans in childhood. In week 13, I'm using a blast tube to administer a concussive blast to mice similar to that experienced by veterans from improvised explosive devices, resulting in mTBI. LBN, concussive blast, and sex are the variables. In week 17, I'm conducting Open Field Tests and fear conditioning on subjects to test generalized and novel fear responses and anxiety levels. Mice that endured both traumas should have the most generalized fear. If so, we will have shown that there is a synergistic interaction between early life adversity and mild traumatic brain injury that intensifies PTSD associated symptoms. Mice with both traumas are expected to have the highest FKBP5 RNA levels. We’ll analyze FKBP5 to determine how it participates in serotonin pathways resulting in these symptoms, and whether LBN and mTBI synergize to increase FKBP5 expression. We want to exemplify the role of FKBP5 as it has potential to be used in PTSD and other stress disorder treatments.

Alcohol is known to cause a number of cognitive impairments including reduced memory and attention and increased risk-taking decisions. Individuals with anxiety and depression also often have characterizations of cognitive impairments, as do individuals who have high levels of impulsivity. However, less is known on whether cognitive performance is worse while impaired among those with high levels of impulsivity or symptoms of anxiety or depression. This study examines whether individual differences in impulsivity, and anxiety and depressive symptoms (ranging from none to moderate) are associated with cognitive performance on attention, memory, and decision-making tasks during alcohol intoxication. Participants included 30 young adult (aged 21-24) drinkers with recent alcohol-related consequences. As part of a larger study, participants completed a baseline survey that included measures of impulsivity, anxiety, and depression. Participants completed a series of cognitive assessments to measure performance on sustained attention, working memory, and risk-taking decisions after peak blood alcohol concentration (BAC) of ~0.10. Anxiety and depression are linked to distractibility, cognitive fatigue, and difficulty maintaining focus, and therefore I hypothesize moderate symptoms of anxiety and depression will be associated with poorer performance in sustained attention compared to those with no symptoms. Additionally, I predict that higher impulsivity scores will be associated with greater cognitive impairment across all tasks, particularly in decision-making and working memory, as impulsive individuals may struggle more with inhibiting automatic responses. Regression analyses will be used to examine these hypotheses. Since data collection occurred at a single time point, this study serves as a preliminary investigation, and further research using repeated measures across different BAC levels is needed. Findings from this study could lay the groundwork for identifying key predictors of cognitive impairment while drinking, particularly by examining how different psychological and behavioral traits interact with alcohol's effects on cognitive performance.

The opioid crisis is an escalating public health emergency, with fentanyl posing major challenges due to its potency and addictive properties. Current treatments address withdrawal but fail to target persistent cravings and relapse triggers. Under Dr. Susan Ferguson and Dr. Alex Whitebirch, I investigate the neural mechanisms underlying fentanyl addiction using rodent models. This research focuses on dopamine (DA) dynamics within the prefrontal cortex (PFC), a key brain region implicated in addiction. Our approach employs the conditioned place preference (CPP) paradigm, a behavioral test that measures a rodent's preference for a drug-paired environment. DA activity in the PFC is monitored in real-time during CPP via fiber photometry of the GRABDA2m fluorescent DA sensor, expressed in glutamatergic neurons through an intersectional virus strategy. We aim to determine whether the development of fentanyl CPP is accompanied by altered DA signaling in the PFC. DA input to the PFC originates from neurons in the VTA, while pyramidal tract (PT) neurons in the PFC project to the VTA and are implicated in suppressing drug-seeking behaviors. To investigate how PT neurons regulate DA signaling, we use Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to selectively inhibit them. Investigating the behavioral and neurochemical consequences of PT inhibition will provide insight into whether this pathway enhances or suppresses dopamine release. We hypothesize that our conditioning paradigm will lead to enhanced PFC DA signals associated with entry into a fentanyl-paired environment, and that PT neuron inhibition will further enhance DA signals and fentanyl-associated place preference. My role in this research includes surgical procedures, photometry and chemogenetic experiments, data analysis, and histological processing. By advancing our understanding of fentanyl’s impact on dopamine pathways and the role of the PFC, this project aims to inform the development of more effective therapeutic interventions for opioid use disorder and relapse prevention.

The glymphatic system is a brain-wide network of perivascular spaces that facilitates waste clearance by exchanging cerebrospinal fluid and interstitial fluid, promoting the clearance of solutes like amyloid β and tau from the brain. Impairment of the glymphatic system has been demonstrated in models of traumatic brain injury (TBI), which has emerged as a risk factor for neurodegenerative conditions like Alzheimer’s disease. These findings suggest that glymphatic impairment may contribute to the development of post-traumatic neurodegenerative conditions, highlighting the potential for therapeutic intervention. Post-TBI sleep disruption, headaches, cognitive deficits, and the brain's subsequent vulnerability to downstream neurodegeneration is a particular concern among veteran and athlete populations. Prazosin, an alpha-1 adrenergic receptor antagonist, has been used clinically in these groups to treat trauma-induced nightmares, where it has been shown to alleviate sleep disruption. However, little is known about its impact on the glymphatic system which is most active during sleep. Here, we hypothesized that glymphatic function is enhanced by blockade of central adrenergic tone, and that this modulation would improve deficits observed in mild blast and impact TBI models. To evaluate the effect of prazosin on glymphatic function in a murine model, we assessed glymphatic function in sham, blast TBI, and impact TBI mice following a 28-day treatment with prazosin. Post-injury behavioral tests were conducted to evaluate cognitive impairments across treatment groups. Using an intracisternal co-injection of infrared and conventional fixable fluorescent tracer, CSF distribution was evaluated through a validated in vivo dynamic imaging technique and paired with whole-slice fluorescent imaging. Our findings so far suggest enhancement of glymphatic function in sham-TBI prazosin treated groups compared to the control. Continued study may better elucidate the mechanisms that underlie post-TBI neurodegeneration, and provide insight into potential targets for treating neuropathological conditions linked to glymphatic system impairment.

People experiencing homelessness are disproportionately affected by alcohol-related morbidity and mortality, with a 7 times higher prevalence of alcohol use disorder (AUD) than the general population. Past research shows that in-person harm reduction treatment for alcohol (HaRT-A) within Housing First facilities is preferred because it focuses on client-centered goals and improving quality of life. This study is a pilot study which is part of an ongoing project adapting HaRT-A into a digital platform (eHaRT-A), to assess the feasibility, usability & acceptability of the electronic harm reduction treatment for alcohol (eHaRT-A). Participants were recruited from low-barrier, permanent supportive housing.  Residents (N = 34) were interested in participating in the study. Participants (n=19), who were interested and eligible, first completed a 45-minute assessment questionnaire asking them about their substance use, quality of life, and pain. Then, they completed one eHaRT-A session, followed by a feedback interview. Recruitment and completion rates were used to assess eHaRT-A feasibility (i.e., percentage screened who expressed interest, qualified, and completed eHaRT-A). My teammates and I utilized self-report measures, including the Acceptability of Intervention Measure (AIM) and the System Usability Scale (SUS) to evaluate participants’ perceptions of eHaRT-A. A priori thresholds for high acceptability (AIM≥3/5) and usability (SUS≥ 70/100) were established. Among those eligible, 86.4% completed the full study, demonstrating high feasibility. The data we analyzed showed a mean AIM score of 4.45 and a mean SUS score of 81.2, indicating strong acceptability and usability.  eHaRT-A’s feasibility, acceptability, and usability, demonstrate its potential as a scalable, harm reduction intervention. These findings support the integration of telehealth interventions into supportive house programs, offering a promising approach to addressing health disparities and improving access to care for this vulnerable population.

Alcohol and cannabis are associated with increased rates of sexual risk behaviors, especially unprotected sex, and decreased perception of the risk involved in unprotected sex. However, little research has explored the relationship between the context of substance use (e.g., partner presence, simultaneous alcohol and cannabis use) and sexual risk behaviors. Multilevel models tested if simultaneous alcohol and cannabis use with a romantic partner present was associated with a greater likelihood of sex, sex while intoxicated, or unprotected sex compared to using only alcohol with a romantic partner present. Young adults (n=409, ages 18-25) who reported using alcohol alone at least three times and alcohol and cannabis simultaneously at least once in the last month were recruited from the Seattle area. Participants completed six two-week periods of twice-daily surveys over two years. Items measured alcohol and cannabis use, presence of others during use, whether sexual intercourse occurred, condom use, and intoxication during intercourse. Analyses were conducted on 308 participants who reported the presence of a romantic partner during use at least once. Simultaneous alcohol and cannabis use with a partner present was associated with significantly higher rates of sex while intoxicated compared to days when only alcohol was used with a partner present. No other associations were found. Although there was no increase in the likelihood of sex or unprotected sex on simultaneous use days with a partner present (versus alcohol-only days with a partner present), there was an increased likelihood of sex while intoxicated. The increased likelihood of sex while intoxicated on simultaneous use days with a partner present could lead to issues with consent and harmful emotional/psychological outcomes (e.g., guilt, regret, lowered self-esteem, worse self-image). Future work could expand the definition of sexual risk behaviors to include these outcomes of sexual encounters rather than focusing exclusively on protection.

The cerebellum (Cb) is typically associated with the regulation of motor behavior. However, recent studies have shown that the Cb has connections to other brain regions associated with higher-order cognitive functions, such as the Hippocampus (HPC), suggesting that the Cb is involved in modulating cognitive behavior. The literature also implies that dynamic changes in the levels of the neurotransmitters Dopamine (DA) and Norepinephrine (NE) may underlie the functionality of involved circuits. This project aims to characterize specific cerebellar circuits involved in the modulation of learning and memory. To test this question, I ran a Fear Conditioning (FC) paradigm in which a conditioned stimulus (CS+), a tone, was presented with an aversive unconditioned stimulus (US), a shock. An additional tone, CS-, was presented without shock. A cohort of 7 mice (4 control, 3 experimental) were run through the paradigm and injected with the optogenetic construct ChR2 to stimulate Purkinje Cell (PC) terminals that synapse on the Lateral Cerebellar Nuclei (LCN). Additionally, Fiber Photometry (FP) was used to record changes in DA and NE in the LCN. I used ezTrack’s python packages to analyze freezing % as the measure of learning, and coded python notebooks to process and visualize DA and NE signals. Mice that received ChR2 stimulation on PC terminals displayed better associative learning between CS+ and US compared to mice that did not receive ChR2 stimulation. These mice also extinguished the association of CS+ and US sooner than unstimulated controls. We also expect these mice to display elevated levels of DA and NE that is statistically significant compared to unstimulated controls. These experiments elucidating cerebellar circuitry in cognitive behaviors may serve to expand our understanding of neural substrate alterations in cognitive function. The LCN may also be a novel locus for targeted therapeutics in human affective disorders.

Decision-making is important for quality of life. Adaptive decision-making can improve one’s quality of life, while maladaptive decision-making may be detrimental. Here, we investigate the effect of Cannabidiol (CBD) on neuroeconomic decision-making in rats, specifically cognitive flexibility, and inflexibility. Rats were trained in a concurrent choice task, where a set number of lever presses resulted in a high reward (HR, 4 food pellets) and a low reward (LR, 1 food pellet). The first treatment level consisted of two behavioral treatment groups, where one group had the HR lever alternating between the left and right side of the operant chamber (flexible group), and the other group (inflexible group) had the HR lever stay on the same side for 20 sessions, where each session had forced trials (one lever accessible) and choice trials (both levers accessible). The metric used for assessing flexible and inflexible choice behavior was the number of choice trials needed to reach the criterion, criterion defined as 10 choice trials within a 12-choice trial sliding window being assigned to the HR lever, which is considered significant bias according to the binomial statistics. The next treatment level is the vehicle vs CBD, where the flexible or inflexible groups receive 20 vapes of vehicle or CBD. As a control experiment, we tested for any effect of vehicle (vegetable-glycerin/propylene-glycol, 20/80) between or within flexible and inflexible groups by administering vehicle vape or no vape in the vape chambers. Preliminarily, we found no statistical effect of vehicle exposure to either behavioral group no main effect in a three-way ANOVA (F1, 20 = 1.753, p=0.2005), however more subjects need to be added as there is a small trend towards vehicle affecting the development of inflexibility. After the control experiment, we will compare the effects of CBD in this behavioral paradigm.

Substance use disorders are a devastating global issue and using multiple substances simultaneously has become common among drug users. Polysubstance use has been linked with higher rates of mortality, overdose, and relapse when compared to single substance use. There is currently little research on how using multiple substances simultaneously affects behavior and motivation to take drugs. Our goal is to better understand the motivations of drug seeking and consumption in rats with a history of polysubstance use compared to rats with a history of single substance use. Rats (n=18 male,18 female) were implanted with jugular catheters and trained to press a lever for an infusion of either 0.0015 mg/kg/infusion of fentanyl (fentanyl-only: FENT) or 0.1mg/kg/infusion of methamphetamine (methamphetamine-only: METH), or both (polysubstance: POLY). The rats then underwent a behavioral economics threshold test, in which the concentrations of fentanyl and methamphetamine were decreased over ten days in an attempt to determine the level of effort and motivation for the drug at each dose. The FENT and METH rats only underwent the behavior economics test for one drug and POLY rats were randomly assigned to either fentanyl or methamphetamine. Our preliminary results suggest that polysubstance use increases the motivation for consuming fentanyl but not methamphetamine; however, sample sizes are small right now and further analysis is needed. In future experiments, we will image the brains of these rats using light sheet microscopy to map the neurocircuit activation that may point to differences between polysubstance and single substance use. Understanding the differences between polysubstance and single-substance use is imperative for designing effective treatment plans that address the motivations behind drug use.

The opioid epidemic remains a critical public health crisis, with opioid use disorder (OUD) affecting millions worldwide. Research indicates significant sex differences in addiction patterns, with women exhibiting faster addiction progression, heightened cravings, and increased relapse rates compared to men. However, the biological mechanisms underlying these differences remain poorly understood. This study aims to investigate how chronic heroin use and withdrawal impact gonadal hormone levels in male and female rats, shedding light onto the role of opioid addiction on hormonal regulation. Using a 20-day heroin treatment followed by a 20-day withdrawal period, we examined changes in locomotor response, fluctuations in key gonadal hormones (testosterone, estradiol, and progesterone), and differences in brain activity patterns. Our preliminary data  suggest that females more consistently develop sensitization to heroin and also do so at an earlier time point compared to males. Our ongoing research is working to quantify serum hormone levels across heroin treatment, as well as developing a way to measure neural estradiol activity in real-time during sensitization. Future work will focus on the long-term effects of hormonal disruptions on brain signaling pathways and opioid receptor regulation, with the ultimate goal of informing sex-specific therapeutic interventions for individuals struggling with opioid addiction. Understanding these hormonal changes is crucial for developing more effective, personalized treatment strategies for OUD. By furthering the research on opioid addiction and endocrine function, this research highlights the need to consider sex as a biological variable in addiction studies.

Alcohol consumption is known to influence individuals' perceptions and engagement in various activities, often altering how they experience different social, recreational, and everyday tasks. Understanding the effects of alcohol on enjoyment is crucial for identifying potential risks associated with alcohol use, particularly among college students. This research study aims to explore how college students perceive their enjoyment of activities like household chores, social interactions, and leisure when alcohol is consumed, compared to when alcohol is not consumed. Given the prevalent drinking habits among university students, particularly in social settings, it is important to examine how alcohol may shape their experiences in everyday life. Participants are fraternity and sorority-affiliated college students at a large public university who are enrolled in a larger study focused on increasing the availability of and engagement in substance-free social activities. The study is currently collecting data and anticipates a sample size of N = 300.  Participants will complete an online survey of self-report questionnaires. The Substance-Free Reinforcement Survey (SFRS; Correia et al, 2002) will be used to assess participants’ enjoyment of a variety of activities with and without alcohol use. Participants were asked to rate their enjoyment on a scale from 0 (unpleasant or neutral) to 4 (extremely pleasant). Activities included social and individual activities, such as group gatherings, personal leisure activities, and household chores. We will conduct t-test to evaluate whether there are differences in enjoyment between activities experienced while use alcohol versus activities experienced without alcohol. The study’s results will provide valuable insights into the relationship between alcohol use and student engagement in everyday activities. These findings could ultimately inform interventions aimed at reducing harmful alcohol consumption while promoting healthier and more fulfilling social and recreational behaviors. Understanding these dynamics can lead to more effective strategies for addressing alcohol-related risks on college campuses. 

Autism Spectrum Disorder (ASD) is a developmental disorder characterized by impairments on socialization and communication skills. Research shows that socialization for neurotypical (NT) individuals can be exhausting- depending on personality traits, desire to conform to social settings, and similarly their social skills. When compared to neurotypical individuals, autistic individuals tend to experience socialization withdrawls to a higher degree leading to irritability and lethargy in behavior. This study aims to look at the relationship between socialization, irritability and lethargy. 399 participants (ASD 280) aged 6-11 years from the NIH funded Autism Biomarkers Consortium for Clinical Trials (ABCCT) were included in the analysis. Parents of participants completed questionnaires based on behaviors they observed in their child within the past 6 months using the Social Responsiveness Scale (SRS-2) and Aberrant Behavior Checklist (ABC) measure. Within the SRS-2, the t-scores from the Social Communication, Social Cognition, and Social Motivation scores will be used. We will divide these scores into high and low socialization, cognition, and motivation based on clinical cutoff. Scores on irritability and lethargy will be derived from ABC measure. Analysis of Variance (ANOVAs) will be run to look at the differences in lethargy and irritability scores based on high/low socialization. We expect to see individuals with higher communication, motivation and socialization skills to have lower scores of lethargy and irritability. We also expect to see scores within the SRS-2 and ABC measures to be lower for autistic individuals. This study will help us gain a better understanding of the emotional and autonomic effects socialization can have on autistic individuals. 

As incidences of opioid use disorder (OUD) have surged to an astonishing 2.5 million individuals, trends of concurrent opioid and psychostimulant use have also risen to a dire degree. Despite this growing number of polysubstance related overdose deaths, current research has primarily focused on the effects of single-substance drug exposure–creating a knowledge gap in our understanding of polysubstance use and corresponding treatment modalities. Thus, we aimed to investigate the differential effects of fentanyl and methamphetamine (METH) polysubstance exposure compared to single substance exposure on drug-induced hyperlocomotion and social interaction in male and female Sprague Dawley rats (n=40). We initially hypothesized that polysubstance exposure to fentanyl and METH would generate distinct behavioral effects on locomotor behavior compared to single-substance exposed animals. We found that in polysubstance and METH-only rats, METH-induced locomotion increased over time in males, but not in females. Additionally, we observed that polysubstance exposure exacerbated fentanyl-induced locomotion in males compared to their fentanyl-only counterparts. We further hypothesized that polysubstance exposure would amplify drug-induced social deficits compared to METH-only and fentanyl-only groups. Seeing how recent literature suggests that psychedelic drugs may have substantial therapeutic and prosocial effects, we also hypothesized that the psychedelic compound R-(-)2,5-dimethoxy-4-iodoamphetamine (DOI) would reverse social deficits observed in both single and polysubstance exposure. We found that social deficits emerged in our polysubstance males and females. We additionally observed a social deficit in our METH-only treated females, but not males. We are currently investigating if the effects of DOI may reverse these deficits. Considering these sex-specific findings, it is crucial that we continue investigating the diverging impacts between males and females to develop targeted therapeutic interventions for polysubstance use.

Young adult cannabis use has become increasingly prevalent in the US, particularly among individuals attending four-year colleges. The perceived social acceptability of cannabis use plays a crucial role in shaping attitudes and behaviors towards substance consumption. While societal attitudes towards cannabis have evolved over the last two decades, there is a gap in understanding how these perceptions differ between college students and their non-college peers. My research aims to compare perceptions about the social acceptability of cannabis with the actual frequency of use among young adults who attend four-year colleges, versus same aged individuals that are not attending school. I am using a subsample of young adults using baseline data from a larger longitudinal study on health behaviors, the Washington Young Adult Health Survey (WYAHS), for the analysis. I am conducting the data preparation and analysis using SPSS. I believe that there will be a significant difference in perceived social acceptability of cannabis use between college students and those not attending school, but I also anticipate that actual consumption will not be significantly different. The results of this research could be important for improving substance use education and addressing preconceived notions of cannabis use acceptability among young adults. Previous research on the WYAHS data has shown significant changes in substance use behaviors over the last six years, especially throughout the pandemic. Future research is needed, which focuses on how my findings may change when based on data from before the COVID-19 pandemic.

Heroin, a commonly used opioid, has played a significant role in the escalating opioid crisis, highlighting the urgent need to better understand the neural mechanisms underlying its addictive properties. Despite well-documented sex differences in opioid use disorder (OUD), the majority of preclinical research has been conducted in male animal models, limiting our understanding of how biological sex influences addiction-related behaviors. This study investigates the role of sex differences in heroin-induced locomotor sensitization and hormonal adaptations in a rodent model. Using a rodent model, we administered intravenous heroin and tracked activity to assess sensitization to the effects of heroin on locomotion. Following treatment, the rats underwent 20 days of withdrawal from heroin. Blood samples were collected throughout treatment and withdrawal to track changes in serum hormone levels. Our findings indicate that female rats show locomotor sensitization at an earlier time point and exhibit a greater degree of escalation compared to males. This suggests potential sex-specific mechanisms influencing opioid addiction vulnerability and progression. We aim to continue quantifying gonadal hormone fluctuations throughout heroin exposure and withdrawal with additional cohorts of animals. Future experiments aim to use fiber photometry to image estradiol activity in the brain during sensitization, providing a real-time insight into its role in opioid-induced changes in behaviors.