Master of Arts, San Diego State University (2010)
Doctor of Philosophy, University of Missouri Columbia (2015)
Bachelor of Science, Clemson University (2006)
Antonio Hardan, Postdoctoral Faculty Sponsor
A pilot investigation of neuroimaging predictors for the benefits from pivotal response treatment for children with autism.
Journal of psychiatric research
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 DOI 10.1016/j.jpsychires.2019.02.001
View details for PubMedID 30771619
Genetic and environmental influences on structural brain measures in twins with autism spectrum disorder.
Atypical growth patterns of the brain have been previously reported in autism spectrum disorder (ASD) but these alterations are heterogeneous across individuals, which may be associated with the variable effects of genetic and environmental influences on brain development. Monozygotic (MZ) and dizygotic (DZ) twin pairs with and without ASD (aged 6-15 years) were recruited to participate in this study. T1-weighted MRIs (n=164) were processed with FreeSurfer to evaluate structural brain measures. Intra-class correlations were examined within twin pairs and compared across diagnostic groups. ACE modeling was also completed. Structural brain measures, including cerebral and cerebellar gray matter (GM) and white matter (WM) volume, surface area, and cortical thickness, were primarily influenced by genetic factors in TD twins; however, mean curvature appeared to be primarily influenced by environmental factors. Similarly, genetic factors accounted for the majority of variation in brain size in twins with ASD, potentially to a larger extent regarding curvature and subcortical GM; however, there were also more environmental contributions in twins with ASD on some structural brain measures, such that cortical thickness and cerebellar WM volume were primarily influenced by environmental factors. These findings indicate potential neurobiological outcomes of the genetic and environmental risk factors that have been previously associated with ASD and, although preliminary, may help account for some of the previously outlined neurobiological heterogeneity across affected individuals. This is especially relevant regarding the role of genetic and environmental factors in the development of ASD, in which certain brain structures may be more sensitive to specific influences.
View details for DOI 10.1038/s41380-018-0330-z
View details for PubMedID 30659287
Cerebro-Cerebellar Functional Connectivity is Associated with Cerebellar Excitation-Inhibition Balance in Autism Spectrum Disorder.
Journal of autism and developmental disorders
Atypical functional connectivity (FC) and an imbalance of excitation-to-inhibition (E/I) have been previously reported in cerebro-cerebellar circuits in autism spectrum disorder (ASD). The current investigation used resting state fMRI and proton magnetic resonance spectroscopy (1H-MRS) to examine the relationships between E/I (glutamate+glutamine/GABA) and FC of the dorsolateral prefrontal cortex and posterolateral cerebellar hemisphere from 14 adolescents/adults with ASD and 12 age/sex/IQ-matched controls. In this pilot sample, cerebro-cerebellar FC was positively associated with cerebellar E/I and listening comprehension abilities in individuals with ASD but not controls. Additionally, a subgroup of individuals with ASD and low FC (n=5) exhibited reduced E/I and impaired listening comprehension. Thus, altered functional coherence of cerebro-cerebellar circuits in ASD may be related with a cerebellar E/I imbalance.
View details for DOI 10.1007/s10803-018-3613-y
View details for PubMedID 29796960
A proton MR spectroscopy study of the thalamus in twins with autism spectrum disorder.
Progress in neuro-psychopharmacology & biological psychiatry
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 DOI 10.1016/j.pnpbp.2017.09.016
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
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
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 2013; 63 (4): 786-806