Behavioral and neurodevelopmental precursors to binge-type eating disorders: support for the role of negative valence systems.

BACKGROUND: Pediatric loss-of-control (LOC) eating is a robust behavioral precursor to binge-type eating disorders. Elucidating precursors to LOC eating and binge-type eating disorders may refine developmental risk models of eating disorders and inform interventions. METHOD: We review evidence within constructs of the Negative Valence Systems (NVS) domain, as specified by the Research Domain Criteria framework. Based on published studies, we propose an integrated NVS model of binge-type eating-disorder risk. RESULTS: Data implicate altered corticolimbic functioning, neuroendocrine dysregulation, and self-reported negative affect as possible risk factors. However, neuroimaging and physiological data in children and adolescents are sparse, and most prospective studies are limited to self-report measures. CONCLUSIONS: We discuss a broad NVS framework for conceptualizing early risk for binge-type eating disorders. Future neural and behavioral research on the developmental trajectory of LOC and binge-type eating disorders is required.

Functional connectivity during facial and vocal emotion recognition: Preliminary evidence for dissociations in developmental change by nonverbal modality.

The developmental trajectory of emotion recognition (ER) skills is thought to vary by nonverbal modality, with vocal ER becoming mature later than facial ER. To investigate potential neural mechanisms contributing to this dissociation at a behavioural level, the current study examined whether youth's neural functional connectivity during vocal and facial ER tasks showed differential developmental change across time. Youth ages 8-19 (n = 41) completed facial and vocal ER tasks while undergoing functional magnetic resonance imaging, at two timepoints (1 year apart; n = 36 for behavioural data, n = 28 for neural data). Partial least squares analyses revealed that functional connectivity during ER is both distinguishable by modality (with different patterns of connectivity for facial vs. vocal ER) and across time-with changes in connectivity being particularly pronounced for vocal ER. ER accuracy was greater for faces than voices, and positively associated with age; although task performance did not change appreciably across a 1-year period, changes in latent functional connectivity patterns across time predicted participants' ER accuracy at Time 2. Taken together, these results suggest that vocal and facial ER are supported by distinguishable neural correlates that may undergo different developmental trajectories. Our findings are also preliminary evidence that changes in network integration may support the development of ER skills in childhood and adolescence.

Functional patterns of neural activation during vocal emotion recognition in youth with and without refractory epilepsy.

Epilepsy has been associated with deficits in the social cognitive ability to decode others' nonverbal cues to infer their emotional intent (emotion recognition). Studies have begun to identify potential neural correlates of these deficits, but have focused primarily on one type of nonverbal cue (facial expressions) to the detriment of other crucial social signals that inform the tenor of social interactions (e.g., tone of voice). Less is known about how individuals with epilepsy process these forms of social stimuli, with a particular gap in knowledge about representation of vocal cues in the developing brain. The current study compared vocal emotion recognition skills and functional patterns of neural activation to emotional voices in youth with and without refractory focal epilepsy. We made novel use of inter-subject pattern analysis to determine brain areas in which activation to emotional voices was predictive of epilepsy status. Results indicated that youth with epilepsy were comparatively less able to infer emotional intent in vocal expressions than their typically developing peers. Activation to vocal emotional expressions in regions of the mentalizing and/or default mode network (e.g., right temporo-parietal junction, right hippocampus, right medial prefrontal cortex, among others) differentiated youth with and without epilepsy. These results are consistent with emerging evidence that pediatric epilepsy is associated with altered function in neural networks subserving social cognitive abilities. Our results contribute to ongoing efforts to understand the neural markers of social cognitive deficits in pediatric epilepsy, in order to better tailor and funnel interventions to this group of youth at risk for poor social outcomes.

Social brain networks: Resting-state and task-based connectivity in youth with and without epilepsy.

Individuals with epilepsy often experience social difficulties and deficits in social cognition. It remains unknown how disruptions to neural networks underlying such skills may contribute to this clinical phenotype. The current study compared the organization of relevant brain circuits-the "mentalizing network" and a salience-related network centered on the amygdala-in youth with and without epilepsy. Functional connectivity between the nodes of these networks was assessed, both at rest and during engagement in a social cognitive task (facial emotion recognition), using functional magnetic resonance imaging. There were no group differences in resting-state connectivity within either neural network. In contrast, youth with epilepsy showed comparatively lower connectivity between the left posterior superior temporal sulcus and the medial prefrontal cortex-but greater connectivity within the left temporal lobe-when viewing faces in the task. These findings suggest that the organization of a mentalizing network underpinning social cognition may be disrupted in youth with epilepsy, though differences in connectivity within this circuit may shift depending on task demands. Our results highlight the importance of considering functional task-based engagement of neural systems in characterizations of network dysfunction in epilepsy.

Children and adolescents' neural response to emotional faces and voices: Age-related changes in common regions of activation.

The perception of facial and vocal emotional expressions engages overlapping regions of the brain. However, at a behavioral level, the ability to recognize the intended emotion in both types of nonverbal cues follows a divergent developmental trajectory throughout childhood and adolescence. The current study a) identified regions of common neural activation to facial and vocal stimuli in 8- to 19-year-old typically-developing adolescents, and b) examined age-related changes in blood-oxygen-level dependent (BOLD) response within these areas. Both modalities elicited activation in an overlapping network of subcortical regions (insula, thalamus, dorsal striatum), visual-motor association areas, prefrontal regions (inferior frontal cortex, dorsomedial prefrontal cortex), and the right superior temporal gyrus. Within these regions, increased age was associated with greater frontal activation to voices, but not faces. Results suggest that processing facial and vocal stimuli elicits activation in common areas of the brain in adolescents, but that age-related changes in response within these regions may vary by modality.

Social anxiety and age are associated with neural response to social evaluation during adolescence.

Adolescence is a sensitive period for the development of adaptive social behaviors and social anxiety, possibly due to aspects of brain development. However, research is needed to examine interactions among age, social anxiety, and social dynamics previously shown to influence neural responding. The current functional magnetic resonance imaging (fMRI) study examines brain function in 8-18 year-olds with varying levels of social anxiety. Interactions are examined among age, social anxiety, and two key task factors: valence and predictability of social interactions. Results demonstrate age, social anxiety severity, and each of the two key task-based factors interact to predict neural response in the caudate, middle and superior temporal gyri. In particular, among adolescents less-than 13 years of age, higher social anxiety predicted greater responding to unpredictable negative evaluations. However, in this same age group, the opposite pattern emerged during receipt of unpredictable positive evaluations, with less neural response in more anxious youth. Adolescents aged 13 and older overall showed less robust effects. We discuss these findings in terms of age- and anxiety-related differences in socioemotional processing.

Brain substrates of infant-mother attachment: contributions of opioids, oxytocin, and norepinephrine.

The aim of this paper is to review recent work concerning the psychobiological substrates of social bonding, focusing on the literature attributed to opioids, oxytocin and norepinephrine in rats. Existing evidence and thinking about the biological foundations of attachment in young mammalian species and the neurobiology of several other affiliative behaviors including maternal behavior, sexual behavior and social memory is reviewed. We postulate the existence of social motivation circuitry which is common to all mammals and consistent across development. Oxytocin, vasopressin, endogenous opioids and catecholamines appear to participate in a wide variety of affiliative behaviors and are likely to be important components in this circuitry. It is proposed that these same neurochemical and neuroanatomical patterns will emerge as key substrates in the neurobiology of infant attachments to their caregivers.

Oxytocin is elevated in plasma of 10-day-old rats following gastric distension.

In adult rats, oxytocin (OT) has been shown to reduce the intake of both food and fluids, and oxytocinergic cells are activated by gastric distension and administration of the intestinal peptide cholecystokinin (CCK-8). These and other findings indicate that OT can play a role in inhibiting ingestion under some conditions. A previous study has shown, however, that oxytocinergic cells are unresponsive to CCK-8 in 2-day-old rats. We report here that OT is elevated in the plasma of 10-day-old rats after induction of gastric distension with both mother's milk and saline. These results indicate that the vagal-hypothalamic axis becomes mature between 2- and 10-days of age in infant rats.

Modulation of emotion by cognition and cognition by emotion.

In this study, we examined the impact of goal-directed processing on the response to emotional pictures and the impact of emotional pictures on goal-directed processing. Subjects (N=22) viewed neutral or emotional pictures in the presence or absence of a demanding cognitive task. Goal-directed processing disrupted the BOLD response to emotional pictures. In particular, the BOLD response within bilateral amygdala and inferior frontal gyrus decreased during concurrent task performance. Moreover, the presence of both positive and negative distractors disrupted task performance, with reaction times increasing for emotional relative to neutral distractors. Moreover, in line with the suggestion of the importance of lateral frontal regions in emotional regulation [Ochsner, K. N., Ray, R. D., Cooper, J. C., Robertson, E. R., Chopra, S., Gabrieli, J. D., et al. (2004). For better or for worse: neural systems supporting the cognitive down-and up-regulation of negative emotion. NeuroImage, 23(2), 483-499], connectivity analysis revealed positive connectivity between lateral superior frontal cortex and regions of middle frontal cortex previously implicated in emotional suppression [Beauregard, M., Levesque, J., and Bourgouin, P. (2001). Neural correlates of conscious self-regulation of emotion. J. Neurosci., 21 (18), RC165.; Levesque, J., Eugene, F., Joanette, Y., Paquette, V., Mensour, B., Beaudoin, G., et al. (2003). Neural circuitry underlying voluntary suppression of sadness. Biol. Psychiatry, 53 (6), 502-510.; Ohira, H., Nomura, M., Ichikawa, N., Isowa, T., Iidaka, T., Sato, A., et al. (2006). Association of neural and physiological responses during voluntary emotion suppression. NeuroImage, 29 (3), 721-733] and negative connectivity with bilateral amygdala. These data suggest that processes involved in emotional regulation are recruited during task performance in the context of emotional distractors.

Internal carotid artery dissection associated with scuba diving.

A 52-year-old man presented to the emergency department with dysphasia and a headache after scuba diving. He was treated initially for decompression sickness. Subsequent workup revealed bilateral internal carotid artery dissection. The risk factors, presenting symptoms, diagnosis, and treatment of internal carotid artery dissection are reviewed. The importance of considering unusual causes of neurologic deficits after scuba diving is emphasized.

Survival of Poria weirii on paired plots in alder and conifer stands.

Cubes of Douglas-fir wood decayed by Poria weirii (Murr.) Murr. were buried for 12 months on paired plots in red alder and in confier soils on the Cascade Head Experimental Forest. Survival of the fungus was not significantly different in the two soils, although pH was significantly lower and nitrate content significantly higher in alder soils. Even though effects on fungus survival were nil, red alder, for other reasons, might still be used to reduce damage caused by P. weirii root not on areas of heavy infestation.

Lepromin-induced suppressor cells in lepromatous leprosy.

The presence or absence of suppressor cells in leprosy patients was investigated by measuring peripheral blood lepromin-induced suppression of the Con A response. Significant suppressor activity was measured in 15 of 15 untreated or recently treated patients with lepromatous leprosy and 3 of 5 patients with borderline lepromatous leprosy. In addition, in patients with lepromatous leprosy, suppressor cell activity was found in 10 of 14 patients that had been under treatment for more than 1 year but in only 2 of 27 patients who had active or thalidomide controlled erythema nodosum leprosum. Suppression was observed in only 5 of 29 tuberculoid leprosy patients, 1 of 6 patient contacts, and 0 of 11 normal controls. The differences between the lepromatous or borderline lepromatous group as compared with the tuberculoid group were statistically significant (P less than 0.001). Our findings confirm the presence of lepromin-triggered suppressor cells in the peripheral blood of patients with lepromatous leprosy. These suppressor cells may contribute to the selective unresponsiveness of lepromatous patients to the antigens of Mycobacterium leprae.

Anthropometric norms for the dialysis population.

Although norms are available for healthy subjects, it is preferable, when interpreting anthropometry in individual dialysis patients, to compare measurements with norms for the stable dialysis population. The purpose of this study was to develop these reference anthropometric norms for dialysis patients. Triceps skinfold (TSF), subscapular skinfold (SSF), and mid-upper arm circumference (MUAC) measurements were made in 925 patients with no major illness, who were being treated by chronic maintenance dialysis in 27 dialysis facilities. Of these, 609 patients treated by hemodialysis (HD) were in subgroups large enough to compare with those from the National Health and Nutrition Examination Survey (NHANES) II. Diabetic patients were significantly different from nondiabetic patients; therefore, the two groups were analyzed separately. Male HD patients (diabetic and nondiabetic) did not differ significantly from the NHANES II data. Diabetic HD females did not differ significantly from the NHANES II data, except for the TSF of black women older than 55 years. Measurements of nondiabetic HD females (black and white) were significantly below the NHANES II data. In 138 continuous ambulatory peritoneal dialysis (CAPD) patients, measurements were similar to those of HD patients.

Genetically restricted suppressor T-cell clones derived from lepromatous leprosy lesions.

Leprosy is a spectral disease in which immune responses to Mycobacterium leprae correlate with the clinical, bacteriological and histopathological manifestations of disease, so study of its pathology provides insights into immunoregulatory mechanisms in man. At the tuberculoid pole, patients have few lesions in the skin which contain rare organisms and are able to mount strong cell-mediated immune responses to M. leprae antigens. In contrast, at the lepromatous pole, patients have disseminated skin lesions containing large numbers of acid-fast bacilli and are selectively unresponsive to antigens of M. leprae. M. leprae-induced suppressor cells derived from peripheral blood have been reported to be active in vitro, yet their in vivo significance has remained unclear. Because the focal point of the immune response to M. leprae is the skin lesion consisting of lymphocytes and macrophages, we have recently developed methods for isolating lymphocytes from skin biopsies of leprosy patients. We report here that two T8 clones derived from lepromatous leprosy skin biopsies, in the presence of lepromin, suppress concanavalin A (Con-A) responses both of peripheral blood mononuclear cells and of T4 clones in an HLA-D (HLA, histocompatibility locus antigen)-restricted manner. Moreover, these T8 clones suppressed responses of HLA-D-matched, but not HLA-D-mismatched antigen-responsive T4 clones to M. leprae antigens, indicating that T-cell suppression is major histocompatibility complex (MHC)-restricted at some level in man.