Papers by Leanna Hernandez
Mobile social media often feature the ability to " Like " content posted by others. This study ex... more Mobile social media often feature the ability to " Like " content posted by others. This study examined the effect of Likes on youths' neural and behavioral responses to photographs. High school and college students (N = 61, ages 13–21) viewed theirs and others' Instagram photographs while undergoing functional Magnetic Resonance Imaging (fMRI). Participants more often Liked photographs that appeared to have received many (vs. few) Likes. Popular photographs elicited greater activity in multiple brain regions, including the nucleus accumbens (NAcc), a hub of the brain's reward circuitry. NAcc responsivity increased with age for high school but not college students. When viewing images depicting risk-taking (vs. nonrisky photographs), high school students, but not college students, showed decreased activation of neural regions implicated in cognitive control.
Journal of the American Academy of Child & Adolescent Psychiatry, 2016
Background: A large number of studies – relying on a variety of neuroimaging tools and paradigms ... more Background: A large number of studies – relying on a variety of neuroimaging tools and paradigms – have reported abnormalities in the so-called mirror neuron system (MNS) in individuals with autism. However, a few studies have failed to find significant group differences. These negative findings have been heralded as evidence against the hypothesis that MNS dysfunction may contribute to core deficits in autism. Objectives: The present study had two main aims. First, we aimed to replicate our prior findings of MNS dysfunction in a considerably larger and independent sample of children and adolescents with ASD. Second, we aimed to further examine how responsivity within the MNS might vary as a function of symptom severity in order to assess how relatively minor differences in sample characteristics may affect study results when comparing individuals with ASD to neurotypical controls. Methods: While undergoing two fMRI scans, a total of 40 children and adolescents with ASD and 14 typic...
Background: Multiple genes in the MET receptor tyrosine kinase (MET) signaling pathway have been ... more Background: Multiple genes in the MET receptor tyrosine kinase (MET) signaling pathway have been linked to autism spectrum disorder (ASD) susceptibility (Campbell, 2008); however, the mechanisms by which variation in these genes predispose individuals to ASD remains unclear. We recently found that a common functional variant in MET (rs1858830) is related to reductions in structural and functional connectivity in ASD (Rudie et al, Under Review), in line with previous studies characterizing ASD as a disorder marked by structural and functional underconnectivity (Schipul, 2011). Urokinase plasminogen activator receptor (PLAUR) cleaves hepatocyte growth factor, which binds the MET receptor and activates downstream signaling of multiple processes including axon formation and synaptogenesis. A common functional variant in PLAUR (rs344781) was found to be associated with ASD and there was also evidence of a gene-gene interaction between the MET and PLAUR variants such that individuals with...
Background: A common variant (rs1858830) in the promoter region of MET receptor tyrosine kinase (... more Background: A common variant (rs1858830) in the promoter region of MET receptor tyrosine kinase (MET) has been associated with ASD risk across multiple independent samples (Campbell 2006, Campbell 2008, Jackson 2009). In the primate, MET is enriched in neurons and their axons which project from subcortical limbic forebrain structures -- as well as temporal, parieto-occipital and limited frontal cortices -- to target regions during synaptogenesis (Judson 2010). MET transcript and protein expression in postmortem temporal cortex is reduced in ASD, as well as in neurotypical individuals who carry this common risk variant (Campbell 2007). Interestingly, many regions in which MET is highly expressed are involved in socio-emotional processing and have been found to exhibit abnormal functional activity in ASD (see Di Martino 2009). Objectives: Despite clear evidence that the MET promoter variant disrupts MET expression, which is crucial for typical circuit development, no studies have exam...
Background: A growing body of evidence suggests that autism spectrum disorders (ASDs) are related... more Background: A growing body of evidence suggests that autism spectrum disorders (ASDs) are related to altered communication between brain regions. Specifically, there are reports of reduced long-range connectivity across networks required for complex social behavior (e.g., Just 2004 2007; Koshino et al., 2005;Kleinhans et al., 2008; Kana et al., 2009). In an emotional facial processing task, we have previously found that, compared to typically developing children, children with ASD display increased local connectivity between different frontal regions and reduced long range connectivity between frontal and parietal cortex, as well as between amygdala and visual areas (Rudie et al. under review). Interestingly, recent work has shown that, during the course of typical development, functional brain networks show increases in long-range functional connectivity among nodes within a given network as well as reduced local (i.e., intralobar) connectivity among nodes in different networks (e....
Brain and Behavior, 2015
Background: Neuroimaging studies can shed light on the neurobiological underpinnings of autism sp... more Background: Neuroimaging studies can shed light on the neurobiological underpinnings of autism spectrum disorders (ASD). Studies of the resting brain have shown both altered baseline metabolism from PET/SPECT and altered functional connectivity (FC) of intrinsic brain networks based on resting-state fMRI. To date, however, no study has investigated these two physiological parameters of resting brain function jointly, or explored the relationship between these measures and ASD symptom severity. Methods: Here, we used pseudo-continuous arterial spin labeling with 3D background-suppressed GRASE to assess resting cerebral blood flow (CBF) and FC in 17 youth with ASD and 22 matched typically developing (TD) children. Results: A pattern of altered resting perfusion was found in ASD versus TD children including frontotemporal hyperperfusion and hypoperfusion in the dorsal anterior cingulate cortex. We found increased local FC in the anterior module of the default mode network (DMN) accompanied by decreased CBF in the same area. In our cohort, both alterations were associated with greater social impairments as assessed with the Social Responsiveness Scale (SRS-total T scores). While FC was correlated with CBF in TD children, this association between FC and baseline perfusion was disrupted in children with ASD. Furthermore, there was reduced long-range FC between anterior and posterior modules of the DMN in children with ASD. Conclusion: Taken together, the findings of this studythe first to jointly assess resting CBF and FC in ASDhighlight new avenues for identifying novel imaging markers of ASD symptomatology.
NeuroImage: Clinical, 2013
Structural and functional underconnectivity have been reported for multiple brain regions, functi... more Structural and functional underconnectivity have been reported for multiple brain regions, functional systems, and white matter tracts in individuals with autism spectrum disorders (ASD). Although recent developments in complex network analysis have established that the brain is a modular network exhibiting small-world properties, network level organization has not been carefully examined in ASD. Here we used resting-state functional MRI (n=42 ASD, n=37 typically developing; TD) to show that children and adolescents with ASD display reduced short and long-range connectivity within functional systems (i.e., reduced functional integration) and stronger connectivity between functional systems (i.e., reduced functional segregation), particularly in default and higher-order visual regions. Using graph theoretical methods, we show that pairwise group differences in functional connectivity are reflected in network level reductions in modularity and clustering (local efficiency), but shorter characteristic path lengths (higher global efficiency). Structural networks, generated from diffusion tensor MRI derived fiber tracts (n=51 ASD, n=43 TD), displayed lower levels of white matter integrity yet higher numbers of fibers. TD and ASD individuals exhibited similar levels of correlation between raw measures of structural and functional connectivity (n= 35 ASD, n=35 TD). However, a principal component analysis combining structural and functional network properties revealed that the balance of local and global efficiency between structural and functional networks was reduced in ASD, positively correlated with age, and inversely correlated with ASD symptom severity. Overall, our findings suggest that modeling the brain as a complex network will be highly informative in unraveling the biological basis of ASD and other neuropsychiatric disorders.
Neuron, 2012
As genes that confer increased risk for autism spectrum disorder (ASD) are identified, a crucial ... more As genes that confer increased risk for autism spectrum disorder (ASD) are identified, a crucial next step is to determine how these risk factors impact brain structure and function and contribute to disorder heterogeneity. With three converging lines of evidence, we show that a common, functional ASD risk variant in the Met Receptor Tyrosine Kinase (MET) gene is a potent modulator of key social brain circuitry in children and adolescents with and without ASD. MET risk genotype predicted atypical fMRI activation and deactivation patterns to social stimuli (i.e., emotional faces), as well as reduced functional and structural connectivity in temporo-parietal regions known to have high MET expression, particularly within the default mode network. Notably, these effects were more pronounced in individuals with ASD. These findings highlight how genetic stratification may reduce heterogeneity and help elucidate the biological basis of complex neuropsychiatric disorders such as ASD.
We investigated a unique way in which adolescent peer influence occurs on social media. We develo... more We investigated a unique way in which adolescent peer influence occurs on social media. We developed a novel
functional MRI (fMRI) paradigm to simulate Instagram, a popular social photo-sharing tool, and measured adolescents’
behavioral and neural responses to likes, a quantifiable form of social endorsement and potential source of peer
influence. Adolescents underwent fMRI while viewing photos ostensibly submitted to Instagram. They were more
likely to like photos depicted with many likes than photos with few likes; this finding showed the influence of virtual
peer endorsement and held for both neutral photos and photos of risky behaviors (e.g., drinking, smoking). Viewing
photos with many (compared with few) likes was associated with greater activity in neural regions implicated in
reward processing, social cognition, imitation, and attention. Furthermore, when adolescents viewed risky photos (as
opposed to neutral photos), activation in the cognitive-control network decreased. These findings highlight possible
mechanisms underlying peer influence during adolescence.
Frontiers in Psychology, 2014
Functional magnetic resonance imaging (fMRI) has become a premiere technique for studying the dev... more Functional magnetic resonance imaging (fMRI) has become a premiere technique for studying the development and neural mediation of a wide range of typical and atypical behaviors in children. While the mechanism of the blood oxygen level-dependent (BOLD) fMRI signal has been a focus of investigation in the mature brain, it has been largely unexamined in the developing brain. One critical component of the BOLD signal that has been noted to change with age is cerebral blood flow (CBF). Reports of CBF in children based on clinical radioactive tracing methods have found elevated CBF in childhood relative to adulthood, which could affect the BOLD response. This study used non-invasive arterial spin labeling magnetic resonance imaging to study resting state and activity-driven CBF in conjunction with the functional BOLD response in healthy children 8 and 12 years of age and in adults. Participants performed a finger-tapping task to generate robust activation measured in the motor cortex. Quantification of resting state CBF demonstrated higher CBF in 8 year olds and in 12 year olds relative to adults. The absolute increase in CBF between baseline rest and peak response during the motor task was also higher in both child groups compared to adults. In contrast, the relative increase of CBF above baseline, expressed as percent of CBF change, was comparable across groups. The percent of BOLD signal change was also stable across age groups. This set of findings suggests that along with elevated CBF in childhood, other component processes of the BOLD response are also in an elevated state such that together they yield a net BOLD effect that resembles adults. These findings coincide with our previous examination of hemodynamics in primary sensory cortex. Although the magnitude of the BOLD response appears consistent between childhood and adulthood, the underlying physiology and cerebrovascular dynamics that give rise to the BOLD effect differ between immature and mature neural systems.
Human Brain Mapping, 2013
Our understanding of cerebral blood flow (CBF) in the healthy developing brain has been limited d... more Our understanding of cerebral blood flow (CBF) in the healthy developing brain has been limited due to the invasiveness of methods historically available for CBF measurement. Clinically based studies using radioactive tracers with children have focused on resting state CBF. Yet potential age-related changes in flow during stimulation may affect the blood oxygenation level dependent (BOLD) response used to investigate cognitive neurodevelopment. This study used noninvasive arterial spin labeling magnetic resonance imaging to compare resting state and stimulus-driven CBF between typically developing children 8 years of age, 12 years of age, and adults. Further, we acquired functional CBF and BOLD images simultaneously to examine their relationship during sensory stimulation. Analyses revealed age-related CBF differences during rest; the youngest group showed greater CBF than 12-year-olds or adults. During stimulation of the auditory cortex, younger children also showed a greater absolute increase in CBF than adults. However, the magnitude of CBF response above baseline was comparable between groups. Similarly, the amplitude of the BOLD response was stable across age. The combination of the 8 year olds' elevated CBF, both at rest and in response to stimulation, without elevation in the BOLD response suggests that additional physiological factors that also play a role in the BOLD effect, such as metabolic processes that are also elevated in this period, may offset the increased CBF in these children. Thus, CBF measurements reveal maturational differences in the hemodynamics underlying the BOLD effect in children despite the resemblance of the BOLD response between children and adults.
Cerebral Cortex, 2012
A growing body of evidence suggests that autism spectrum disorders (ASDs) are related to altered ... more A growing body of evidence suggests that autism spectrum disorders (ASDs) are related to altered communication between brain regions. Here, we present findings showing that ASD is characterized by a pattern of reduced functional integration as well as reduced segregation of large-scale brain networks. Twentythree children with ASD and 25 typically developing matched controls underwent functional magnetic resonance imaging while passively viewing emotional face expressions. We examined whole-brain functional connectivity of two brain structures previously implicated in emotional face processing in autism: the amygdala bilaterally and the right pars opercularis of the inferior frontal gyrus (rIFGpo). In the ASD group, we observed reduced functional integration (i.e., less long-range connectivity) between amygdala and secondary visual areas, as well as reduced segregation between amygdala and dorsolateral prefrontal cortex. For the rIFGpo seed, we observed reduced functional integration with parietal cortex and increased integration with right frontal cortex as well as right nucleus accumbens. Finally, we observed reduced segregation between rIFGpo and the ventromedial prefrontal cortex. We propose that a systems-level approach-whereby the integration and segregation of large-scale brain networks in ASD is examined in relation to typical development-may provide a more detailed characterization of the neural basis of ASD.
JAMA Psychiatry, 2015
More than half of youth with autism spectrum disorders (ASDs) have sensory overresponsivity (SOR)... more More than half of youth with autism spectrum disorders (ASDs) have sensory overresponsivity (SOR), an extreme negative reaction to sensory stimuli. However, little is known about the neurobiological basis of SOR, and there are few effective treatments. Understanding whether SOR is due to an initial heightened sensory response or to deficits in regulating emotional reactions to stimuli has important implications for intervention. To determine differences in brain responses, habituation, and connectivity during exposure to mildly aversive sensory stimuli in youth with ASDs and SOR compared with youth with ASDs without SOR and compared with typically developing control subjects. Functional magnetic resonance imaging was used to examine brain responses and habituation to mildly aversive auditory and tactile stimuli in 19 high-functioning youths with ASDs and 19 age- and IQ-matched, typically developing youths (age range, 9-17 years). Brain activity was related to parents' ratings of children's SOR symptoms. Functional connectivity between the amygdala and orbitofrontal cortex was compared between ASDs subgroups with and without SOR and typically developing controls without SOR. The study dates were March 2012 through February 2014. Relative increases in blood oxygen level-dependent signal response across the whole brain and within the amygdala during exposure to sensory stimuli compared with fixation, as well as correlation between blood oxygen level-dependent signal change in the amygdala and orbitofrontal cortex. The mean age in both groups was 14 years and the majority in both groups (16 of 19 each) were male. Compared with neurotypical control participants, participants with ASDs displayed stronger activation in primary sensory cortices and the amygdala (P < .05, corrected). This activity was positively correlated with SOR symptoms after controlling for anxiety. The ASDs with SOR subgroup had decreased neural habituation to stimuli in sensory cortices and the amygdala compared with groups without SOR. Youth with ASDs without SOR showed a pattern of amygdala downregulation, with negative connectivity between the amygdala and orbitofrontal cortex (thresholded at z > 1.70, P < .05). Results demonstrate that youth with ASDs and SOR show sensorilimbic hyperresponsivity to mildly aversive tactile and auditory stimuli, particularly to multiple modalities presented simultaneously, and show that this hyperresponsivity is due to failure to habituate. In addition, findings suggest that a subset of youth with ASDs can regulate their responses through prefrontal downregulation of amygdala activity. Implications for intervention include minimizing exposure to multiple sensory modalities and building coping strategies for regulating emotional response to stimuli.
Neuropsychopharmacology, 2014
Neuroimaging investigations of autism spectrum disorders (ASDs) have advanced our understanding o... more Neuroimaging investigations of autism spectrum disorders (ASDs) have advanced our understanding of atypical brain function and structure, and have recently converged on a model of altered network-level connectivity. Traditional task-based functional magnetic resonance imaging (MRI) and volume-based structural MRI studies have identified widespread atypicalities in brain regions involved in social behavior and other core ASD-related behavioral deficits. More recent advances in MR-neuroimaging methods allow for quantification of brain connectivity using diffusion tensor imaging, functional connectivity, and graph theoretic methods. These newer techniques have moved the field toward a systems-level understanding of ASD etiology, integrating functional and structural measures across distal brain regions. Neuroimaging findings in ASD as a whole have been mixed and at times contradictory, likely due to the vast genetic and phenotypic heterogeneity characteristic of the disorder. Future longitudinal studies of brain development will be crucial to yield insights into mechanisms of disease etiology in ASD sub-populations. Advances in neuroimaging methods and large-scale collaborations will also allow for an integrated approach linking neuroimaging, genetics, and phenotypic data.
Metaphor and Symbol, 2012
Individuals with ASD show consistent impairment in processing pragmatic language when attention t... more Individuals with ASD show consistent impairment in processing pragmatic language when attention to multiple social cues (e.g., facial expression, tone of voice) is often needed to navigate social interactions. Building upon prior fMRI work examining how facial affect and prosodic cues are used to infer a speaker's communicative intent, the authors examined whether children and adolescents with ASD differ from typically developing (TD) controls in their processing of sincere versus ironic remarks. At the behavioral level, children and adolescents with ASD and matched TD controls were able to determine whether a speaker's remark was sincere or ironic equally well, with both groups showing longer response times for ironic remarks. At the neural level, for both sincere and ironic scenarios, an extended cortical network-including canonical language areas in the left hemisphere and their right hemisphere counterparts-was activated in both groups, albeit to a lesser degree in the ASD sample. Despite overall similar patterns of activity observed for the two conditions in both groups, significant modulation of activity was detected when directly comparing sincere and ironic scenarios within and between groups. While both TD and ASD groups showed significantly greater activity in several nodes of this extended network when processing ironic versus sincere remarks, increased activity was largely confined to left language areas in TD controls, whereas the ASD sample showed a more bilateral activation profile which included both language and "theory of mind" areas (i.e., ventromedial prefrontal cortex). These findings suggest that, for high-functioning individuals with ASD, increased activity in right hemisphere homologues of language areas in the left hemisphere, as well as regions involved in social cognition, may reflect compensatory mechanisms supporting normative behavioral task performance.
Journal of the American Academy of Child & Adolescent Psychiatry, 2013
Sensory over-responsivity (SOR), defined as a negative response to or avoidance of sensory stimul... more Sensory over-responsivity (SOR), defined as a negative response to or avoidance of sensory stimuli, is both highly prevalent and extremely impairing in youth with autism spectrum disorders (ASD), yet little is known about the neurological bases of SOR. This study aimed to examine the functional neural correlates of SOR by comparing brain responses to sensory stimuli in youth with and without ASD. A total of 25 high-functioning youth with ASD and 25 age- and IQ-equivalent typically developing (TD) youth were presented with mildly aversive auditory and visual stimuli during a functional magnetic resonance imaging (fMRI) scan. Parents provided ratings of children's SOR and anxiety symptom severity. Compared to TD participants, ASD participants displayed greater activation in primary sensory cortical areas as well as amygdala, hippocampus, and orbital-frontal cortex. In both groups, the level of activity in these areas was positively correlated with level of SOR severity as rated by parents, over and above behavioral ratings of anxiety. This study demonstrates that youth with ASD show neural hyper-responsivity to sensory stimuli, and that behavioral symptoms of SOR may be related to both heightened responsivity in primary sensory regions as well as areas related to emotion processing and regulation.
This fMRI study investigated neural responses while making appraisals of self and other, across t... more This fMRI study investigated neural responses while making appraisals of self and other, across the social and academic domains, in children and adolescents with and without autism spectrum disorders (ASD). Compared to neurotypical youth, those with ASD exhibited hypoactivation of ventromedial prefrontal cortex during self-appraisals. Responses in middle cingulate cortex (MCC) and anterior insula (AI) also distinguished between groups. Stronger activity in MCC and AI during self-appraisals was associated with better social functioning in the ASD group. Although self-appraisals were significantly more positive in the neurotypical group, positivity was unrelated to brain activity in these regions. Together, these results suggest that multiple brain regions support making self-appraisals in neurotypical development, and function atypically in youth with ASD.
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Papers by Leanna Hernandez
functional MRI (fMRI) paradigm to simulate Instagram, a popular social photo-sharing tool, and measured adolescents’
behavioral and neural responses to likes, a quantifiable form of social endorsement and potential source of peer
influence. Adolescents underwent fMRI while viewing photos ostensibly submitted to Instagram. They were more
likely to like photos depicted with many likes than photos with few likes; this finding showed the influence of virtual
peer endorsement and held for both neutral photos and photos of risky behaviors (e.g., drinking, smoking). Viewing
photos with many (compared with few) likes was associated with greater activity in neural regions implicated in
reward processing, social cognition, imitation, and attention. Furthermore, when adolescents viewed risky photos (as
opposed to neutral photos), activation in the cognitive-control network decreased. These findings highlight possible
mechanisms underlying peer influence during adolescence.
functional MRI (fMRI) paradigm to simulate Instagram, a popular social photo-sharing tool, and measured adolescents’
behavioral and neural responses to likes, a quantifiable form of social endorsement and potential source of peer
influence. Adolescents underwent fMRI while viewing photos ostensibly submitted to Instagram. They were more
likely to like photos depicted with many likes than photos with few likes; this finding showed the influence of virtual
peer endorsement and held for both neutral photos and photos of risky behaviors (e.g., drinking, smoking). Viewing
photos with many (compared with few) likes was associated with greater activity in neural regions implicated in
reward processing, social cognition, imitation, and attention. Furthermore, when adolescents viewed risky photos (as
opposed to neutral photos), activation in the cognitive-control network decreased. These findings highlight possible
mechanisms underlying peer influence during adolescence.