I am interested in understanding the neural mechanisms that underlie cognitive and social functioning heterogeneity in autism spectrum disorder (ASD). Impairments in social and cognitive functioning in children with ASD are intrinsically related to the changes in information processing. Moreover, social and cognitive functioning are emergent neural processes that can be manipulated by robust molecular neuromodulators. Social behaviors are specifically related to the neuropeptides, oxytocin (OT) and arginine vasopressin (AVP), while both social and cognitive functioning have been related to the endogenous cannabinoid (or endocannabinoid) system. Therefore, my postdoctoral research (funded by a T32 postdoctoral fellowship from the NIMH) investigates the role of neuromodulators (i.e., social neuropeptides and endocannabinoids) in social functioning in autistic children. My PI-lead efforts are include mass spectrometry method development and treatment-related clinical neurophysiological assessment in autistic children. Individually, my research interests are centered on leveraging a translational neuroscience skill set to interrogate information processing in ASD pathophysiology and understand its relationship with (potential dysregulation of) endocannabinoid signaling.
Plasma anandamide concentrations are lower in children with autism spectrum disorder
2018; 9: 18
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted, stereotyped behaviors and impairments in social communication. Although the underlying biological mechanisms of ASD remain poorly understood, recent preclinical research has implicated the endogenous cannabinoid (or endocannabinoid), anandamide, as a significant neuromodulator in rodent models of ASD. Despite this promising preclinical evidence, no clinical studies to date have tested whether endocannabinoids are dysregulated in individuals with ASD. Here, we addressed this critical gap in knowledge by optimizing liquid chromatography-tandem mass spectrometry methodology to quantitatively analyze anandamide concentrations in banked blood samples collected from a cohort of children with and without ASD (N = 112).Anandamide concentrations significantly differentiated ASD cases (N = 59) from controls (N = 53), such that children with lower anandamide concentrations were more likely to have ASD (p = 0.041). In keeping with this notion, anandamide concentrations were also significantly lower in ASD compared to control children (p = 0.034).These findings are the first empirical human data to translate preclinical rodent findings to confirm a link between plasma anandamide concentrations in children with ASD. Although preliminary, these data suggest that impaired anandamide signaling may be involved in the pathophysiology of ASD.
View details for PubMedID 29564080
Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism.
Proceedings of the National Academy of Sciences
2017; 114 (30): 8119-8124
Autism spectrum disorder (ASD) is characterized by core social deficits. Prognosis is poor, in part, because existing medications target only associated ASD features. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may be a blood-based biomarker of social functioning and a possible treatment for ASD. However, prior OXT treatment trials have produced equivocal results, perhaps because of variability in patients' underlying neuropeptide biology, but this hypothesis has not been tested. Using a double-blind, randomized, placebo-controlled, parallel design, we tested the efficacy and tolerability of 4-wk intranasal OXT treatment (24 International Units, twice daily) in 32 children with ASD, aged 6-12 y. When pretreatment neuropeptide measures were included in the statistical model, OXT compared with placebo treatment significantly enhanced social abilities in children with ASD [as measured by the trial's primary outcome measure, the Social Responsiveness Scale (SRS)]. Importantly, pretreatment blood OXT concentrations also predicted treatment response, such that individuals with the lowest pretreatment OXT concentrations showed the greatest social improvement. OXT was well tolerated, and its effects were specific to social functioning, with no observed decrease in repetitive behaviors or anxiety. Finally, as with many trials, some placebo-treated participants showed improvement on the SRS. This enhanced social functioning was mirrored by a posttreatment increase in their blood OXT concentrations, suggesting that increased endogenous OXT secretion may underlie this improvement. These findings indicate that OXT treatment enhances social abilities in children with ASD and that individuals with pretreatment OXT signaling deficits may stand to benefit the most from OXT treatment.
View details for DOI 10.1073/pnas.1705521114
View details for PubMedCentralID PMC5544319
Atypical sensory reactivity influences auditory attentional control in adults with autism spectrum disorders.
2016; 9 (10): 1079-1092
Frequent observations of atypical sensory reactivity in people with autism spectrum disorders (ASD) suggest that the perceptual experience of those on the Spectrum is dissimilar to neurotypicals. Moreover, variable attention abilities in people with ASD, ranging from good control to periods of high distractibility, may be related to atypical sensory reactivity. This study used auditory event-related potential (ERP) measures to evaluate top-down and bottom-up attentional processes as a function of perceptual load, and examined these factors with respect to sensory reactivity. Twenty-five age and IQ-matched participants (ASD: 22.5 year, SD = 4.1 year; Controls: 22.8 year, SD = 5.1 year) completed the Adolescent/Adult Sensory Profile prior to performing a modified 3-stimulus (target, non-target, and distractor) auditory oddball target detection task EEG was recorded during task completion. ERP analysis assessed early sensory processing (P50, ∼50 ms latency; N100, ∼100 ms latency), cognitive control (N200, ∼200 ms latency), and attentional processing (P3a and P3b, ∼300 ms latency). Behavioral data demonstrates participants with ASD and neurotypical performed similarly on auditory target detection, but diverged on sensory profiles. Target ERP measures associated with top-down control (P3b latency) significantly increased under greater load in controls, but not in participants with ASD. Early ERP responses associated with bottom-up attention (P50 amplitude) were positively correlated to increased sensory sensitivity. Findings suggest specific neural mechanisms for increased perceptual capacity and enhanced bottom-up processing of sensory stimuli in people with autism. Results from participants with ASD are consistent with load theory and enhanced perceptual functioning. Autism Res 2016, 9: 1079-1092. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
View details for DOI 10.1002/aur.1593
View details for PubMedID 26778164
Endocannabinoid signaling in social functioning: an RDoC perspective.
2016; 6 (9)
Core deficits in social functioning are associated with various neuropsychiatric and neurodevelopmental disorders, yet biomarker identification and the development of effective pharmacological interventions has been limited. Recent data suggest the intriguing possibility that endogenous cannabinoids, a class of lipid neuromodulators generally implicated in the regulation of neurotransmitter release, may contribute to species-typical social functioning. Systematic study of the endogenous cannabinoid signaling could, therefore, yield novel approaches to understand the neurobiological underpinnings of atypical social functioning. This article provides a critical review of the major components of the endogenous cannabinoid system (for example, primary receptors and effectors-Δ9-tetrahydrocannabinol, cannabidiol, anandamide and 2-arachidonoylglycerol) and the contributions of cannabinoid signaling to social functioning. Data are evaluated in the context of Research Domain Criteria constructs (for example, anxiety, chronic stress, reward learning, motivation, declarative and working memory, affiliation and attachment, and social communication) to enable interrogation of endogenous cannabinoid signaling in social functioning across diagnostic categories. The empirical evidence reviewed strongly supports the role for dysregulated cannabinoid signaling in the pathophysiology of social functioning deficits observed in brain disorders, such as autism spectrum disorder, schizophrenia, major depressive disorder, posttraumatic stress disorder and bipolar disorder. Moreover, these findings indicate that the endogenous cannabinoid system holds exceptional promise as a biological marker of, and potential treatment target for, neuropsychiatric and neurodevelopmental disorders characterized by impairments in social functioning.
View details for DOI 10.1038/tp.2016.169
View details for PubMedID 27676446
View details for PubMedCentralID PMC5048207
The Role of Right Inferior Parietal Cortex in Auditory Spatial Attention: A Repetitive Transcranial Magnetic Stimulation Study.
The Role of Right Inferior Parietal Cortex in Auditory Spatial Attention: A Repetitive Transcranial Magnetic Stimulation Study
2015; 10 (12): e0144221
View details for DOI 10.1371/journal.pone.0144221