My innovative research program studies cognitive and behavioral neuroscience in children and adolescents, with a primary focus on elucidating the neural substrates of salient brain-behavior relationships in children with psychological and psychiatric disorders. The overarching goal of my research is to improve our understanding of the development of different cognitive and behavioral skills in order to design mechanistically driven interventions that will improve precision medicine for mental health. Biologically based diagnosis and treatment are extremely limited for psychological and psychiatric disorders but also critically needed to increase early identification and improve treatment outcomes, especially for neurodevelopmental disorders in which early intervention is the most efficacious. My early career training has fostered unique expertise for studying both the neurobiology of cognitive and behavioral development as well as the treatment of psychological and psychiatric disorders in clinical populations, and my early career research has primarily utilized non-invasive neuroimaging approaches (e.g., MRI & EEG) to study cognitive and behavioral neuroscience and develop biomarkers for clinical research, especially for autism spectrum disorder (ASD).

Administrative Appointments

  • Associate Director for Strategic Program Development, Stanford Center for Precision Mental Health and Wellness (2022 - Present)

Clinical Trials

  • Targeting the Neurobiology of Restricted and Repetitive Behaviors in Children With Autism Using N-acetylcysteine Recruiting

    The goal of this study is to target the neurobiology of restricted and repetitive behaviors in children with autism spectrum disorder using N-acetylcysteine (NAC), a well-tolerated nutritional supplement that has shown promise for reducing symptom severity in recent small-scale trials. The findings from this research will shed light on the mechanisms of action underlying the clinical benefits of NAC.

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Graduate and Fellowship Programs

  • Child Psychiatry (Fellowship Program)

All Publications

  • Genetic and environmental influences on structural brain measures in twins with autism spectrum disorder MOLECULAR PSYCHIATRY Hegarty, J. P., Pegoraro, L. L., Lazzeroni, L. C., Raman, M. M., Hallmayer, J. F., Monterrey, J. C., Cleveland, S. C., Wolke, O. N., Phillips, J. M., Reiss, A. L., Hardan, A. Y. 2020; 25 (10): 2556–66
  • Frequency Drift in MR Spectroscopy at 3T. NeuroImage Hui, S. C., Mikkelsen, M., Zollner, H. J., Ahluwalia, V., Alcauter, S., Baltusis, L., Barany, D. A., Barlow, L. R., Becker, R., Berman, J. I., Berrington, A., Bhattacharyya, P. K., Blicher, J. U., Bogner, W., Brown, M. S., Calhoun, V. D., Castillo, R., Cecil, K. M., Choi, Y. B., Chu, W. C., Clarke, W. T., Craven, A. R., Cuypers, K., Dacko, M., de la Fuente-Sandoval, C., Desmond, P., Domagalik, A., Dumont, J., Duncan, N. W., Dydak, U., Dyke, K., Edmondson, D. A., Ende, G., Ersland, L., Evans, C. J., Fermin, A. S., Ferretti, A., Fillmer, A., Gong, T., Greenhouse, I., Grist, J. T., Gu, M., Harris, A. D., Hat, K., Heba, S., Heckova, E., Hegarty, J. P., Heise, K., Jacobson, A., Jansen, J. F., Jenkins, C. W., Johnston, S. J., Juchem, C., Kangarlu, A., Kerr, A. B., Landheer, K., Lange, T., Lee, P., Levendovszky, S. R., Limperopoulos, C., Liu, F., Lloyd, W., Lythgoe, D. J., Machizawa, M. G., MacMillan, E. L., Maddock, R. J., Manzhurtsev, A. V., Martinez-Gudino, M. L., Miller, J. J., Mirzakhanian, H., Moreno-Ortega, M., Mullins, P. G., Near, J., Noeske, R., Nordhoy, W., Oeltzschner, G., Osorio-Duran, R., Otaduy, M. C., Pasaye, E. H., Peeters, R., Peltier, S. J., Pilatus, U., Polomac, N., Porges, E. C., Pradhan, S., Prisciandaro, J. J., Puts, N. A., Rae, C. D., Reyes-Madrigal, F., Roberts, T. P., Robertson, C. E., Rosenberg, J. T., Rotaru, D., O'Gorman Tuura, R. L., Saleh, M. G., Sandberg, K., Sangill, R., Schembri, K., Schrantee, A., Semenova, N. A., Singel, D., Sitnikov, R., Smith, J., Song, Y., Stark, C., Stoffers, D., Swinnen, S. P., Tain, R., Tanase, C., Tapper, S., Tegenthoff, M., Thiel, T., Thioux, M., Truong, P., van Dijk, P., Vella, N., Vidyasagar, R., Vovk, A., Wang, G., Westlye, L. T., Wilbur, T. K., Willoughby, W. R., Wilson, M., Wittsack, H., Woods, A. J., Wu, Y., Xu, J., Lopez, M. Y., Yeung, D. K., Zhao, Q., Zhou, X., Zupan, G., Edden, R. A. 2021: 118430


    PURPOSE: Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.METHOD: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).RESULTS: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.DISCUSSION: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.

    View details for DOI 10.1016/j.neuroimage.2021.118430

    View details for PubMedID 34314848

  • Effects of stress on functional connectivity during verbal processing. Brain imaging and behavior Nair, N., Hegarty, J. P., Ferguson, B. J., Hooshmand, S. J., Hecht, P. M., Tilley, M., Christ, S. E., Beversdorf, D. Q. 2019


    Effects of stress on functional connectivity (FC) in specific language processing regions of the brain during verbal fluency tasks were explored. Roles of gender and serotonin transporter gene polymorphisms (5-HTTLPR), associated with stress susceptibility, were also examined to understand their effect. Forty-five healthy volunteers (Mean age: 19.6±1.6years; 28 females) participated. Functional magnetic resonance imaging was carried out while participants performed letter and category fluency tasks. These tasks were interposed with the Montreal Imaging Stress Test to induce stress or a no-stress control task. Buccal swabs collected were used to genotype for the presence of polymorphisms on the SLC6A4 gene known to contribute to atypical stress responses. Significant variations in strength of FC were noted between several ROIs, including left inferior frontal gyrus and left middle temporal gyrus. Overall, males showed regional increases in FC strength over long and short distances during task under stress. Additionally, variability in effects of stress on task performance was associated with effects of stress on FC. Results suggest that long distance FC may be strengthened to compensate for additional cognitive load of the stressor but that specific short distance functional connections may be strengthened in a gender specific manner. Additionally, FC may serve as a marker for effects of stress on performance. This is the first study exploring stress effects on language tasks with imaging markers. Future studies will need to explore stress susceptible populations and establish the role of FC as a marker, with implications for targeted therapeutic interventions.

    View details for DOI 10.1007/s11682-019-00221-5

    View details for PubMedID 31833016

  • Beta-adrenergic antagonism alters functional connectivity during associative processing in a preliminary study of individuals with and without autism. Autism : the international journal of research and practice Hegarty, J. P., Zamzow, R. M., Ferguson, B. J., Christ, S. E., Porges, E. C., Johnson, J. D., Beversdorf, D. Q. 2019: 1362361319868633


    Beta-adrenergic antagonism (e.g. propranolol) has been associated with cognitive/behavioral benefits following stress-induced impairments and for some cognitive/behavioral domains in individuals with autism spectrum disorder. In this preliminary investigation, we examined whether the benefits of propranolol are associated with functional properties in the brain. Adolescents/adults (mean age = 22.54 years) with (n = 13) and without autism spectrum disorder (n = 13) attended three sessions in which propranolol, nadolol (beta-adrenergic antagonist that does not cross the blood-brain barrier), or placebo was administered before a semantic fluency task during functional magnetic resonance imaging. Autonomic nervous system measures and functional connectivity between language/associative processing regions and within the fronto-parietal control, dorsal attention, and default mode networks were examined. Propranolol was associated with improved semantic fluency performance, which was correlated with the baseline resting heart rate. Propranolol also altered network efficiency of regions associated with semantic processing and in an exploratory analysis reduced functional differences in the fronto-parietal control network in individuals with autism spectrum disorder. Thus, the cognitive benefits from beta-adrenergic antagonism may be generally associated with improved information processing in the brain in domain-specific networks, but individuals with autism spectrum disorder may also benefit from additional improvements in domain-general networks. The benefits from propranolol may also be able to be predicted from baseline autonomic nervous system measures, which warrants further investigation.

    View details for DOI 10.1177/1362361319868633

    View details for PubMedID 31416333

  • A pilot investigation of neuroimaging predictors for the benefits from pivotal response treatment for children with autism. Journal of psychiatric research Hegarty, J. P., Gengoux, G. W., Berquist, K. L., Millan, M. E., Tamura, S. M., Karve, S., Rosenthal, M. D., Phillips, J. M., Hardan, A. Y. 2019; 111: 140–44


    Children with autism spectrum disorder (ASD) frequently exhibit language delays and functional communication deficits. Pivotal response treatment (PRT) is an effective intervention for targeting these skills; however, similar to other behavioral interventions, response to PRT is variable across individuals. Thus, objective markers capable of predicting treatment response are critically-needed to identify which children are most likely to benefit from this intervention. In this pilot study, we investigated whether structural neuroimaging measures from language regions in the brain are associated with response to PRT. Children with ASD (n = 18) who were receiving PRT to target their language deficits were assessed with MRI at baseline. T1-weighted images were segmented with FreeSurfer and morphometric measures of the primary language regions (inferior frontal (IFG) and superior temporal (STG) gyri) were evaluated. Children with ASD and language deficits did not exhibit the anticipated relationships between baseline structural measures of language regions and baseline language abilities, as assessed by the number of utterances displayed during a structured laboratory observation (SLO). Interestingly, the level of improvement on the SLO was correlated with baseline asymmetry of the IFG, and the size of the left STG at baseline was correlated with the level of improvement on standardized parental questionnaires. Although very preliminary, the observed associations between baseline structural properties of language regions and improvement in language abilities following PRT suggest that neuroimaging measures may be able to help identify which children are most likely to benefit from specific language treatments, which could help improve precision medicine for children with ASD.

    View details for PubMedID 30771619

  • Genetic and environmental influences on cortico-striatal circuits in twins with autism. Genetic and environmental influences on cortico-striatal circuits in twins with autism. Hegarty, J. P., Lazzeroni, L. C., Raman, M. M., Hallmayer, J. C., Cleveland, S. C., Phillips, J. M., Reiss, A. L., Hardan, A. Y. 2019

    View details for DOI 10.1503/jpn.190030

  • Brain connectivity theories of autism Encyclopedia of Autism Spectrum Disorders Hegarty, J. P., Hardan, A. Y., Muller, R. Springer-Verlag. 2019; 2nd
  • Effects of stress on functional connectivity during problem solving. NeuroImage Nair, N. n., Hegarty, J. P., Ferguson, B. J., Hecht, P. M., Tilley, M. n., Christ, S. E., Beversdorf, D. Q. 2019: 116407


    Our purpose was to examine how stress affects functional connectivity (FC) in language processing regions of the brain during a verbal problem solving task associated with creativity. We additionally explored how gender and the presence of the stress-susceptible short allele of the serotonin transporter gene polymorphism influenced this effect.Forty-five healthy participants (Mean age: 19.6 ± 1.6 years; 28 females) were recruited to be a part of this study and genotyped to determine the presence or absence of at least one copy of the short (S) allele of the serotonin transporter gene, which is associated with greater susceptibility to stress. The participants underwent functional magnetic resonance imaging in two separate sessions (stress and no stress control). One session utilized a modified version of the Montreal Imaging Stress Test (MIST) to induce stress while the other session consisted of a no stress control task. The MIST and control tasks were interleaved with task blocks during which the participants performed the compound remote associates task, a convergent task that engages divergent thinking, which is a critical component of creativity. We examined the relationship between stress effects on performance and effects on connectivity of language processing regions activated during this task.There was no main effect of stress on functional connectivity for individual ROI pairs. However, in the examination of whether stress effects on performance related to effects on connectivity, changes in middle temporal gyrus connectivity with stress correlated positively with changes in solution latency for individuals with the S allele, but anti-correlated for those with only the L allele. A trend towards a gene × stress interaction on solution latency was also observed.Results from the study suggest that genetic susceptibility to stress, such as the presence of the S allele, affects neural correlates of performance on tasks related to verbal problem solving, as indicated by connectivity of the middle temporal gyrus. Future work will need to determine whether connectivity of the middle temporal gyrus serves as a marker for the effect of stress susceptibility on cognition, extending into stress susceptible patient populations.

    View details for DOI 10.1016/j.neuroimage.2019.116407

    View details for PubMedID 31809888

  • Genetic and Environmental Influences on Lobar Brain Structures in Twins With Autism. Cerebral cortex (New York, N.Y. : 1991) Hegarty, J. P., Lazzeroni, L. C., Raman, M. M., Pegoraro, L. F., Monterrey, J. C., Cleveland, S. C., Hallmayer, J. F., Wolke, O. N., Phillips, J. M., Reiss, A. L., Hardan, A. Y. 2019


    This investigation examined whether the variation of cerebral structure is associated with genetic or environmental factors in children with autism spectrum disorder (ASD) compared with typically developing (TD) controls. T1-weighted magnetic resonance imaging scans were obtained from twin pairs (aged 6-15 years) in which at least one twin was diagnosed with ASD or both were TD. Good quality data were available from 30 ASD, 18 discordant, and 34 TD pairs (n = 164). Structural measures (volume, cortical thickness, and surface area) were generated with FreeSurfer, and ACE modeling was completed. Lobar structures were primarily genetically mediated in TD twins (a2 = 0.60-0.89), except thickness of the temporal (a2 = 0.33 [0.04, 0.63]) and occipital lobes (c2 = 0.61 [0.45, 0.77]). Lobar structures were also predominantly genetically mediated in twins with ASD (a2 = 0.70-1.00); however, thickness of the frontal (c2 = 0.81 [0.71, 0.92]), temporal (c2 = 0.77 [0.60, 0.93]), and parietal lobes (c2 = 0.87 [0.77, 0.97]), and frontal gray matter (GM) volume (c2 = 0.79 [0.63, 0.95]), were associated with environmental factors. Conversely, occipital thickness (a2 = 0.93 [0.75, 1.11]) did not exhibit the environmental contributions that were found in controls. Differences in GM volume were associated with social communication impairments for the frontal (r = 0.52 [0.18, 0.75]), temporal (r = 0.61 [0.30, 0.80]), and parietal lobes (r = 0.53 [0.19, 0.76]). To our knowledge, this is the first investigation to suggest that environmental factors influence GM to a larger extent in children with ASD, especially in the frontal lobe.

    View details for DOI 10.1093/cercor/bhz215

    View details for PubMedID 31711118

  • Cerebro-Cerebellar Functional Connectivity is Associated with Cerebellar Excitation-Inhibition Balance in Autism Spectrum Disorder JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS Hegarty, J. P., Weber, D. J., Cirstea, C. M., Beversdorf, D. Q. 2018; 48 (10): 3460–73
  • Corpus callosum Encyclopedia of Autism Spectrum Disorders Hegarty, J. P., Hardan, A. Y., Frazier, T. W. Springer-Verlag. 2018; 2nd
  • Corpus callosum abnormalities in autism Encyclopedia of Autism Spectrum Disorders Hegarty, J. P., Hardan, A. Y., Frazier, T. W. Springer-Verlag. 2018; 2nd
  • Agenesis of the corpus callosum Encyclopedia of Autism Spectrum Disorders Hegarty, J. P., Hardan, A. Y., Frazier, T. W. Springer-Verlag. 2018; 2nd
  • A proton MR spectroscopy study of the thalamus in twins with autism spectrum disorder. Progress in neuro-psychopharmacology & biological psychiatry Hegarty, J. P., Gu, M. n., Spielman, D. M., Cleveland, S. C., Hallmayer, J. F., Lazzeroni, L. C., Raman, M. M., Frazier, T. W., Phillips, J. M., Reiss, A. L., Hardan, A. Y. 2017


    Multiple lines of research have reported thalamic abnormalities in individuals with autism spectrum disorder (ASD) that are associated with social communication impairments (SCI), restricted and repetitive behaviors (RRB), or sensory processing abnormalities (SPA). Thus, the thalamus may represent a common neurobiological structure that is shared across symptom domains in ASD. Same-sex monozygotic (MZ) and dizygotic (DZ) twin pairs with and without ASD underwent cognitive/behavioral evaluation and magnetic resonance imaging to assess the thalamus. Neurometabolites were measured with (1)H magnetic resonance spectroscopy (MRS) utilizing a multi-voxel PRESS sequence and were referenced to creatine+phosphocreatine (tCr). N-acetyl aspartate (NAA), a marker of neuronal integrity, was reduced in twins with ASD (n=47) compared to typically-developing (TD) controls (n=33), and this finding was confirmed in a sub-sample of co-twins discordant for ASD (n=11). NAA in the thalamus was correlated to a similar extent with SCI, RRB, and SPA, such that reduced neuronal integrity was associated with greater symptom severity. Glutamate+glutamine (Glx) was also reduced in affected versus unaffected co-twins. Additionally, NAA and Glx appeared to be primarily genetically-mediated, based on comparisons between MZ and DZ twin pairs. Thus, thalamic abnormalities may be influenced by genetic susceptibility for ASD but are likely not domain-specific.

    View details for PubMedID 28941767

  • Beta-adrenergic antagonism modulates functional connectivity in the default mode network of individuals with and without autism spectrum disorder. Brain imaging and behavior Hegarty, J. P., Ferguson, B. J., Zamzow, R. M., Rohowetz, L. J., Johnson, J. D., Christ, S. E., Beversdorf, D. Q. 2016: -?


    The beta-adrenergic antagonist propranolol benefits some social and communication domains affected in autism spectrum disorder (ASD), and these benefits appear to be associated with increased functional connectivity (FC) in the brain during task performance. FC is implicated in ASD, with the majority of studies suggesting long distance hypo-connectivity combined with regionally specific local hyper-connectivity. The objective in the current investigation was to examine the effect of propranolol on FC at rest and determine whether ASD-specific effects exist. Participants with and without ASD attended three sessions in which propranolol, nadolol (a beta-adrenergic antagonist that does not cross the blood-brain barrier), or placebo were administered. Resting-state fMRI data were acquired, and graph theory techniques were utilized to assess additional aspects of FC. Compared to placebo, propranolol administration was associated with decreased FC in the dorsal medial prefrontal cortex subnetwork of the default mode network and increased FC in the medial temporal lobe subnetwork, regardless of diagnosis. These effects were not seen with nadolol suggesting that the alterations in FC following propranolol administration were not exclusively due to peripheral cardiovascular effects. Thus, beta-adrenergic antagonism can up- or down- regulate FC, depending on the network, and alter coordinated functional activation in the brain. These changes in information processing, as demonstrated by FC, may mediate some of the clinical and behavioral effects of beta-adrenergic antagonism previously reported in patients with ASD.

    View details for PubMedID 27714553

  • Morphological differences in the lateral geniculate nucleus associated with dyslexia NEUROIMAGE-CLINICAL Giraldo-Chica, M., Hegarty, J. P., Schneider, K. A. 2015; 7: 830-836


    Developmental dyslexia is a common learning disability characterized by normal intelligence but difficulty in skills associated with reading, writing and spelling. One of the most prominent, albeit controversial, theories of dyslexia is the magnocellular theory, which suggests that malfunction of the magnocellular system in the brain is responsible for the behavioral deficits. We sought to test the basis of this theory by directly measuring the lateral geniculate nucleus (LGN), the only location in the brain where the magnocellular and parvocellular streams are spatially disjoint. Using high-resolution proton-density weighted MRI scans, we precisely measured the anatomical boundaries of the LGN in 13 subjects with dyslexia (five female) and 13 controls (three female), all 22-26 years old. The left LGN was significantly smaller in volume in subjects with dyslexia and also differed in shape; no differences were observed in the right LGN. The functional significance of this asymmetry is unknown, but these results are consistent with the magnocellular theory and support theories of dyslexia that involve differences in the early visual system.

    View details for DOI 10.1016/j.nicl.2015.03.011

    View details for Web of Science ID 000373172600091

    View details for PubMedID 26082892

  • Alexithymia and Impairment of Decoding Positive Affect: An fMRI Study JOURNAL OF COMMUNICATION Hesse, C., Floyd, K., Rauscher, E. A., Frye-Cox, N. E., Hegarty, J. P., Peng, H. 2013; 63 (4): 786-806

    View details for DOI 10.1111/jcom.12039

    View details for Web of Science ID 000322639400011