FMRI in children is increasingly used in clinical application and in developmental research; however, little is known how pediatric patient and typically developing populations successfully complete studies. We examined pediatric success rates with Epilepsy, Attention Deficit/ Hyperactivity Disorder (ADHD), Autism Spectrum Disorders (ASD), and typically developing children (TYP). We also examined the affect of age, and, for ADHD populations, medication status on success rates. We defined a successful fMRI individual run when the data were interpretable and included in group statistics. For unsuccessful runs, datasets with excessive motion or floor task performance were categorized when possible. All clinical groups scanned less successfully than controls; medication status did not affect ADHD success (Epilepsy: 80%; ADHD (off methylphenidate): 77%; ADHD (on methylphenidate): 81%; ASD: 70%; TYP: 87%). Ten to 18-year-olds had a significantly greater scan success rate than 4-6-year-olds; adolescents (13-18-year-olds) demonstrated greater scan success rates than 7-9-year-olds. Success rate for completing an entire battery of experimental runs (n=2-6), varied between 50-59% for patient populations and 69% for TYP (79% when excluding 4-6-year-olds). Success rate for completing one run from a battery was greater than 90% for all groups, except for ASD (81%). These data suggest 20-30% more children should be recruited in these patient groups, but only 10-20% for TYP for research studies. Studies with 4-6-year-olds may require 20-40% additional participants; studies with 10-18-year-olds may require 10-15% additional participants.Functional magnetic resonance imaging (fMRI) is an established tool in the study of brain function in children with developmental disorders, acquired disorders, and typical development (TYP) and has a clinical application in pre-surgical planning for children with Epilepsy (Medina et al., 2007). Unlike structural MRI where participants are required to lie still (and may do so while sleeping), fMRI requires awake and cooperative participants which precludes the use of sedation. There is a paucity of data examining the success rate of scanning children in fMRI paradigms.Address Correspondence: Benjamin E. Yerys, Children's National Medical Center, Children's Research Institute -Neuroscience, 111 Michigan Ave, NW, Washington, DC 20010, byerys@cnmc.org, Phone: 301-738-8940. NIH Public Access Author ManuscriptHum Brain Mapp. Author manuscript; available in PMC 2010 October 1. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptOne study has examined scan success rate in over 200 TYP children between 5-to 18-years of age (Byars et al., 2002). This study defined scan success as children completing at least one of four fMRI tasks and an anatomical reference scan. Children between the ages of five and six had a success rate of 47%; children between the ages of seven and nine had a success rate of 76%; and children above the age of ten had a success rate of 96%. It is unk...

Functional pathology of the default mode network is posited to be central to social-cognitive impairment in autism spectrum disorders (ASD). Altered functional connectivity of the default mode network's midline core may be a potential endophenotype for social deficits in ASD. Generalizability from prior studies is limited by inclusion of medicated participants and by methods favoring restricted examination of network function. This study measured resting-state functional connectivity in 22 8–13 year-old non-medicated children with ASD and 22 typically developing controls using seed-based and network segregation functional connectivity methods. Relative to controls the ASD group showed both under- and over-functional connectivity within default mode and non-default mode regions, respectively. ASD symptoms correlated negatively with the connection strength of the default mode midline core—medial prefrontal cortex–posterior cingulate cortex. Network segregation analysis with the participation coefficient showed a higher area under the curve for the ASD group. Our findings demonstrate that the default mode network in ASD shows a pattern of poor segregation with both functional connectivity metrics. This study confirms the potential for the functional connection of the midline core as an endophenotype for social deficits. Poor segregation of the default mode network is consistent with an excitation/inhibition imbalance model of ASD.

Social emotions are affective states elicited during social interactions and integral for promoting socially appropriate behaviors and discouraging socially inappropriate ones. Social emotion-processing deficits significantly impair interpersonal relationships, and play distinct roles in the manifestation and maintenance of clinical symptomatology. Elucidating the neural correlates of discrete social emotions can serve as a window to better understanding and treating neuropsychiatric disorders. Moral cognition and social emotion-processing broadly recruit a frontotemporo-subcortical network, supporting empathy, perspective-taking, self-processing, and rewardprocessing. The present review specifically examines the neural correlates of embarrassment, guilt, envy, and schadenfreude. Embarrassment and guilt are selfconscious emotions, evoked during negative evaluation following norm violations and supported by a fronto-temporo-posterior network. Embarrassment is evoked by social transgressions and recruits greater anterior temporal regions, representing conceptual social knowledge. Guilt is evoked by moral transgressions and recruits greater prefrontal regions, representing perspective-taking and behavioral change demands. Envy and schadenfreude are fortune-ofother emotions, evoked during social comparison and supported by a prefronto-striatal network. Envy represents displeasure in others' fortunes, and recruits increased dorsal anterior cingulate cortex, representing cognitive dissonance, and decreased reward-related striatal regions. Schadenfreude represents pleasure in others' misfortunes, and recruits reduced empathy-related insular regions and increased reward-related striatal regions. Implications for psychopathology and treatment design are discussed.

Empathy cultivates deeper interpersonal relationships and is important for socialization. However, frequent exposure to emotionally-demanding situations may put people at risk for burnout. Burnout has become a pervasive problem among medical professionals because occupational burnout may be highly sensitive to empathy levels. To better understand empathy-induced burnout among medical professionals, exploring the relationship between burnout severity and strength of empathy-related brain activity may be key. However, to our knowledge, this relationship has not yet been explored. We studied the relationship between self-reported burnout severity scores and psychological measures of empathic disposition, emotional dissonance and alexithymia in medical professionals to test two contradictory hypotheses: Burnout is explained by (1) ‘compassion fatigue' that is, individuals become emotionally over involved; and (2) ‘emotional dissonance' that is, a gap between felt and expressed emotion, together with reduced emotional regulation. Then, we tested whether increased or decreased empathy-related brain activity measured by fMRI was associated with burnout severity scores and psychological measures. The results showed that burnout severity of medical professionals is explained by ‘reduced' empathy-related brain activity. Moreover, this reduced brain activity is correlated with stronger emotional dissonance and alexithymia scores and also greater empathic disposition. We speculate that reduced emotion recognition (that is, alexithymia) might potentially link with stronger emotional dissonance and greater burnout severity alongside empathy-related brain activity. In this view, greater empathic disposition in individuals with higher burnout levels might be due to greater difficulty identifying their own emotional reactions. Our study sheds new light on the ability to predict empathy-induced burnout.

Though circumscribed interests are pathognomonic with autism, how these interests differ from those expressed during neutotypical (NT) development remains unknown. Using a novel measure, the Interests Scale (IS), this study compares interests between 76 NT individuals and 109 individuals with high-functioning autism spectrum disorder (HF-ASD) matched group-wise on age, IQ and gender ratio. Participants and their parents/caregivers completed diagnostic measures (Autism Diagnostic Interview-Revised [ADI-R], Autism Diagnostic Observation Schedule [ADOS]; HF-ASD only), cognitive tests (Wechsler IQ Scales), and questionnaires (the Repetitive Behavior Scale-Revised [RBS-R], the Behavior Rating Inventory of Executive Function [BRIEF], and the Social Responsiveness Scale [SRS]), in addition to the IS. HF-ASD and NT individuals did not differ in number of interest areas, but the types of interests differed considerably. HF-ASD individuals had significantly more intense and interfering interests than NT individuals. Using only the intensity score, 77.5% of individuals were correctly classified (NT or HF-ASD) in a discriminant function analysis. Among individuals with HF-ASD, IS scores were significantly related to ADOS, BRIEF, RBS-R and SRS scores, but not to ADI-R scores, IQ, gender, age or psychotropic medication use. The type and intensity, but not the number, of interests distinguish high-functioning children with ASD from NT children.

The current fMRI study investigated the neural foundations of evaluating oneself and others during early adolescence and young adulthood. Eighteen early adolescents (ages 11–14, M = 12.6) and 19 young adults (ages 22–31, M = 25.6) evaluated if academic, physical, and social traits described themselves directly (direct self-evaluations), described their best friend directly (direct other-evaluations), described themselves from their best friend’s perspective (reflected self-evaluations), or in general could change over time (control malleability-evaluations). Compared to control evaluations, both adolescents and adults recruited cortical midline structures during direct and reflected self-evaluations, as well as during direct other-evaluations, converging with previous research. However, unique to this study was a significant three-way interaction between age group, evaluative perspective, and domain within bilateral ventral striatum. Region of interest analyses demonstrated a significant evaluative perspective by domain interaction within the adolescent sample only. Adolescents recruited greatest bilateral ventral striatum during reflected social self-evaluations, which was positively correlated with age and pubertal development. These findings suggest that reflected social self-evaluations, made from the inferred perspective of a close peer, may be especially self-relevant, salient, or rewarding to adolescent self-processing – particularly during the progression through adolescence – and this feature persists into adulthood.

Autism spectrum disorder (ASD) is often associated with high levels of inflexible thinking and rigid behavior. The neural correlates of these behaviors have been investigated in adults and older adolescents, but not children. Prior studies utilized set-shifting tasks that engaged multiple levels of shifting, and depended on learning abstract rules and establishing a strong prepotent bias. These additional demands complicate simple interpretations of the results. We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of set-shifting in 20 children (ages 7-14) with ASD and 19 typically developing, matched, control children. Participants completed a set-shifting task that minimized non-shifting task demands through the use of concrete instructions that provide spatial mapping of stimuli-responses. The shift/stay sets were given an equal number of trials to limit the prepotent bias. Both groups showed an equivalent ‘switch cost’, responding less accurately and slower to Switch stimuli than Stay stimuli, although the ASD group was less accurate overall. Both groups showed activation in prefrontal, striatal, parietal, and cerebellum regions known to govern effective set-shifts. Compared to controls, children with ASD demonstrated decreased activation of the right middle temporal gyrus across all trials, but increased activation in the mid-dorsal cingulate cortex/superior frontal gyrus, left middle frontal and right inferior frontal gyri during the Switch vs. Stay contrast. The successful behavioral switching performance of children with ASD comes at the cost of requiring greater engagement of frontal regions, suggesting less efficiency at this lowest level of shifting.

Depression is associated with negative attention and attribution biases and maladaptive emotion responsivity and regulation, which adversely impact self-evaluations and interpersonal relationships. Using functional magnetic resonance imaging, we investigated the neural substrates of these impairments. We compared neural activity recruited by 126 clinically depressed and healthy adolescents (ages 11–17 years) during social exclusion (Exclusion > Inclusion) using Cyberball. Results revealed significant interaction effects within left anterior insula (AI)/inferior frontal gyrus and left middle temporal gyrus. Insula hyperresponsivity was associated with peer exclusion for depressed adolescents but peer inclusion for healthy adolescents. In additional, healthy adolescents recruited greater lateral temporal activity during peer exclusion. Complementary effect size analyses within independent parcellations offered converging evidence, as well as highlighted medium-to-large effects within subgenual/ventral anterior cingulate cortex and lateral prefrontal, lateral temporal and lateral parietal regions implicated in emotion regulation. Depressogenic neural patterns were associated with negative self-perceptions and negative information processing biases. These findings suggest a neural mechanism underlying cognitive biases in depression, as reflected by emotional hyperresponsivity and maladaptive regulation/reappraisal of negative social evaluative information. This study lends further support for salience and central executive network dysfunction underlying social threat processing, and in particular, highlights the anterior insula as a key region of disturbance in adolescent depression.