Faculty Bibliography

A widely held view is that top-down modulation of sensory information relies on an amodal control network that acts through the thalamus to regulate incoming signals. Olfaction lacks a direct thalamic projection, which suggests that it may differ from other modalities in this regard. We investigated the late positive complex (LPC) amplitudes of event-related potentials (ERP) from 28 participants, elicited by intensity-matched olfactory, auditory and visual stimuli, during a condition of focused attention, a neutral condition, and a condition in which stimuli were to be actively ignored. Amplitudes were largest during the attend condition, lowest during the ignore condition, with the neutral condition in between. A Bayesian analysis resulted in strong evidence for similar effects of task across sensory modalities. We conclude that olfaction, despite its unique neural projections, does not differ from audition and vision in terms of task-dependent neural modulation of the LPC.

We argue that subjective emotional experience, the feeling, is the essence of an emotion, and that objective manifestations in behavior and in body or brain physiology are, at best, indirect indicators of these inner experiences. As a result, the most direct way to assess conscious emotional feelings is through verbal self-report. This creates a methodological barrier to studies of conscious feelings in animals. While the behavioral and physiological responses are not "˜emotions,"™ they contribute to emotions indirectly, and sometimes profoundly. Whether non-verbal animals have emotional experiences is a difficult, maybe impossible, question to answer in the positive or negative. But because behavioral and physiological responses are important contributors to emotions, and the circuits underlying these are highly conserved, studies of animals have an important role in understanding how emotions are expressed and regulated in the brain. Conflation of circuits that directly give rise to conscious emotional feelings with circuits that indirectly influences these conscious feelings has hampered progress in efforts to understand emotions, and also to understand and to develop treatments for emotional disorders. Recognition of differences in these circuits will allow research in animals to have a lasting impact on understanding of human emotions as research goes forward.

Infant gross motor development is vital to adaptive function and predictive of both cognitive outcomes and neurodevelopmental disorders. However, little is known about neural systems underlying the emergence of walking and general gross motor abilities. Using resting state fcMRI, we identified functional brain networks associated with walking and gross motor scores in a mixed cross-sectional and longitudinal cohort of infants at high and low risk for autism spectrum disorder, who represent a dimensionally distributed range of motor function. At age 12 months, functional connectivity of motor and default mode networks was correlated with walking, whereas dorsal attention and posterior cingulo-opercular networks were implicated at age 24 months. Analyses of general gross motor function also revealed involvement of motor and default mode networks at 12 and 24 months, with dorsal attention, cingulo-opercular, frontoparietal, and subcortical networks additionally implicated at 24 months. These findings suggest that changes in network-level brain-behavior relationships underlie the emergence and consolidation of walking and gross motor abilities in the toddler period. This initial description of network substrates of early gross motor development may inform hypotheses regarding neural systems contributing to typical and atypical motor outcomes, as well as neurodevelopmental disorders associated with motor dysfunction.

Objectives: Once-daily dosing with dasotraline, a novel dopamine and norepinephrine reuptakeinhibitor, achieves stable plasma concentrationsover 24 hours with once-daily dosing. This studyevaluated dasotraline in children aged 6-12 years(NCT02428088).
METHOD(S): Patients were randomized 1:1:1 to 6 weeks ofonce-daily, fixed-dose dasotraline 2 or 4 mg/day, or placebo.The primary efficacy endpoint was change from baseline(CFB) at Week 6 in ADHD Rating Scale Version IV-HomeVersion (ADHD RS-IV HV) total score, using a mixed modelfor repeated measures (MMRM) in the intent-to-treat (ITT)population. Secondary endpoints included Clinical GlobalImpression-Severity (CGI-S) score and safety endpoints.
RESULT(S): The mean age of 342 randomized patients was9.1 [SD: 1.9] years; 66.7% were male. Overall, 79% ofpatients completed the study. In the ITT population(N = 336), ADHD RS-IV HV total score improvedsignificantly with dasotraline 4 mg/day vs placebo(leastsquares [LS] mean [SE] CFB at Week 6:-17.53 [+/- 1.31]vs-11.36 [+/- 1.29], respectively, p < 0.001; effect size[ES]: 0.48). Inattentiveness and hyperactivity/impulsivity subscale scores significantly improved with 4 mg/dayvs placebo at Week 6 (p = 0.001, p = 0.003, respectively).Improvement in CGI-S score was statistically significantwith dasotraline 4 mg/day vs placebo(LS mean [SE] CFBat Week 6:-1.39 [+/- 0.12] vs-1.04 [+/- 0.12], respectively,p = 0.040; ES: 0.29). No significant improvement wasobserved on the ADHD RS-IV HV total score and theCGI-S score for dasotraline 2 mg/day vs placebo. Themost frequent treatment-emergent AEs (=5% and higherthan placebo) were (2 mg/day; 4 mg/day; placebo):insomnia (15.3%; 21.7%; 4.3%, all terms combined),decreased appetite (12.6%; 21.7%; 5.2%), weight loss(5.4%; 8.7%; 0%), irritability (3.6%; 7.0%; 6.0%),nasopharyngitis (0.9%; 5.2%; 0.9%), and nausea (0%;5.2%; 2.6%).
CONCLUSION(S): Compared with placebo, dasotraline4 mg/day significantly improved ADHD symptoms inchildren, as assessed by ADHD RS-IV HV total score andinattentiveness and hyperactivity/impulsivity subscalescores. Dasotraline was generally well tolerated; mostcommon AEs were insomnia, decreased appetite, weightloss and irritability

This study investigated the clinical utility of the Achenbach System of Empirically Based Assessment (ASEBA) for identifying youth at risk for suicide. Specifically, we investigated how well the Total Problems scores and the sum of two suicide-related items (#18 "Deliberately harms self or attempts suicide" and #91 "Talks about killing self") were able to distinguish youth with a history of suicidal behavior. Youth (N = 1117) aged 5-18 were recruited for two studies of mental illness. History of suicidal behavior was assessed by semi-structured interviews (K-SADS) with youth and caregivers. Youth, caregivers, and a primary teacher each completed the appropriate form (YSR, CBCL, and TRF, respectively) of the ASEBA. Areas under the curve (AUCs) from ROC analyses and diagnostic likelihood ratios (DLRs) were used to measure the ability of both Total Problems T scores, as well as the summed score of two suicide-related items, to identify youth with a history of suicidal behavior. The Suicide Items from the CBCL and YSR performed well (AUCs = 0.85 and 0.70, respectively). The TRF Suicide Items did not perform better than chance, AUC = 0.45. The AUCs for the Total Problems scores were poor-to-fair (0.33-0.65). The CBCL Suicide Items outperformed all other scores (ps = 0.04 to <0.0005). Combining the CBCL and YSR items did not lead to incremental improvement in prediction over the CBCL alone. The sum of two questions from a commonly used assessment tool can offer important information about a youth's risk for suicidal behavior. The low burden of this approach could facilitate wide-spread screening for suicide in an increasingly at-risk population.

OBJECTIVES:We provide an opportunity for implementing preventive interventions to decrease suicide mortality among prior suicide attempters. We aim to identify sex-specific high risk periods and factors for later suicide death among suicide attempters. METHODS:8537 suicide attempters of Korea National Suicide Survey were collected from January 1, 2007 to December 31, 2011 and data on suicide death was obtained as of December 31, 2012. The risk period and risk factors for later suicide death was computed by Kaplan-Meier survival estimates and by plotting the hazard function using the Epanechnikov Kernal smoothing method and cox proportional hazard regression modeling. RESULTS:The hazard for later suicide death was significant up to 10 months for females and 20 months for males. Age 50-69 years (HR, 3.29; [CI: 1.80-6.02] and not being intoxicated with alcohol (HR, 1.94 [1.27-2.97])) in male attempters were significant risk factors for later suicide death. CONCLUSION:Risk for later suicide death was significantly increased during the first full year following index attempts for all with an addition 8 months of risk for males, especially those of advanced age who were sober at the time of attempt.

Classical trigeminal neuralgia (TN) is a specific type of neuropathic orofacial pain of which the plasticity of brain structure and connectivity have remained largely unknown. A total of 62 TN patients were included and referred to MRI scans. Voxel-based morphometry was used to analyze the change of gray matter volume. Resting-state functional imaging was used to analyze the connectivity between brain regions. The results showed gray matter volume reduction in components of the prefrontal cortex, precentral gyrus, cerebellar tonsil, thalamus, hypothalamus, and nucleus accumbens among right TN patient and in the inferior frontal gyrus, precentral gyrus, cerebellum, thalamus, ventral striatum, and putamen among left TN patients. The connections between the right superior frontal gyrus and right middle frontal gyrus were lower in right TN patients. The connection between the left precentral gyrus and the left superior frontal gyrus was lower while the connection between bilateral thalamus was higher in left TN patients. The changes of volume in bilateral thalamus of right TN patients and left ventral striatum of left TN patients, and the connectivity between bilateral thalamus of left TN patients were moderately correlated with pain duration. These findings suggest that brain regions such as the thalamus may not only be involved in processing of pain stimuli but also be important for the development of TN. The left hemisphere may be dominant in processing and modulation of TN pain signal. Chronification of TN induces volume changes in brain regions which are associated with emotional or cognitive modulation of pain. Hum Brain Mapp 39:609-621, 2018. © 2017 Wiley Periodicals, Inc.

OBJECTIVE:Exercise-induced wheeze (EIW) has been found to be associated with asthma-related urgent care in school-aged children. Despite asthma's high prevalence and morbidity among adolescents, this association has not been examined in adolescents. We tested the association of EIW and other asthma symptoms to asthma-related ED visits and hospitalizations in urban adolescents with probable asthma. We hypothesized that EIW would be associated with urgent care. METHODS:In this cross-sectional study 30,467 high school students (mean age = 16.0) from 49 NYC schools completed two brief validated measures, one assessing probable asthma and the other the frequency of six asthma symptoms over the past year. Adolescents also reported if in the past year they had an asthma-related ED visit or hospitalization. Analyses presented here included students with probable asthma (n = 9149). Using logistic regression, we modeled each asthma symptom as a function of ED visits and hospitalizations adjusting for sex, age, race/ethnicity and asthma severity. Multivariable models included all symptoms to account for the potential interaction between symptoms. RESULTS:Among adolescents with probable asthma, EIW was associated with ED visits and hospitalizations. In multivariable models wheeze without a cold, chest tightness, night wakening, but not EIW, were significantly associated with both ED visits and hospitalizations. CONCLUSIONS:Unlike findings with younger children, EIW does not appear to be associated with ED visits and hospitalizations among urban adolescents with probable asthma. Instead, symptoms, such as chest tightness and night wakening, appear to be important at identifying adolescents at risk for asthma-related urgent care.