Faculty Bibliography

Connectomics has enhanced our understanding of neurocognitive development and decline by the integration of network sciences into studies across different stages of the human life span. However, these studies commonly occurred independently, missing the opportunity to test integrated models of the dynamical brain organization across the entire life span. In this review article, we survey empirical findings in life-span connectomics and propose a generative framework for computationally modeling the connectome over the human life span. This framework highlights initial findings that across the life span, the human connectome gradually shifts from an 'anatomically driven' organization to one that is more 'topological'. Finally, we consider recent advances that are promising to provide an integrative and systems perspective of human brain plasticity as well as underscore the pitfalls and challenges.

Research on avoidance conditioning began in the late 1930s as a way to use laboratory experiments to better understand uncontrollable fear and anxiety. Avoidance was initially conceived of as a two-factor learning process in which fear is first acquired through Pavlovian aversive conditioning (so-called fear conditioning), and then behaviors that reduce the fear aroused by the Pavlovian conditioned stimulus are reinforced through instrumental conditioning. Over the years, criticisms of both the avoidance paradigm and the two-factor fear theory arose. By the mid-1980s, avoidance had fallen out of favor as an experimental model relevant to fear and anxiety. However, recent progress in understanding the neural basis of Pavlovian conditioning has stimulated a new wave of research on avoidance. This new work has fostered new insights into contributions of not only Pavlovian and instrumental learning but also habit learning, to avoidance, and has suggested that the reinforcing event underlying the instrumental phase should be conceived in terms of cellular and molecular events in specific circuits rather than in terms of vague notions of fear reduction. In our approach, defensive reactions (freezing), actions (avoidance) and habits (habitual avoidance) are viewed as being controlled by unique circuits that operate nonconsciously in the control of behavior, and that are distinct from the circuits that give rise to conscious feelings of fear and anxiety. These refinements, we suggest, overcome older criticisms, justifying the value of the new wave of research on avoidance, and offering a fresh perspective on the clinical implications of this work.

Left ventricular assist devices (LVADs) have been successfully used in patients with heart failure. However, LVADs may trigger immune activation, leading to higher frequencies of autoantibodies. We describe the clinical, epidemiological, and laboratory characteristics of LVAD recipients with false positive hepatitis C (FPHC) serology among 39 consecutive adult LVAD recipients who bridged to heart transplantation from January 2007 to January 2013 at Montefiore Medical Center. FPHC patients were identified as those with post-LVAD positive hepatitis C ELISA antibody tests and negative confirmatory testing with hepatitis C RNA PCR and/or radioimmunoblot assay. Ten (26%) patients previously seronegative for hepatitis C were found to have FPHC after device placement. Of the 39 patients, 32 had HeartMate II devices. The mean age at LVAD placement was 55 years. FPHC correlated with older age at the time of LVAD implantation and with receipt of packed red blood cell transfusions, but not with gender, fresh frozen plasma transfusions, panel reactive antibodies, globulin fraction, rheumatoid factor, or anticardiolipin antibodies. Clinicians should be aware of this increased risk of FPHC in older LVAD patients and those more heavily transfused in order to avoid unnecessary apprehension and possible delay in transplantation. Further studies should be done to evaluate the possible relationship between transfused blood products and immunomodulation.

This article reviews research on the development of motor behavior from a developmental systems perspective. We focus on infancy when basic action systems are acquired. Posture provides a stable base for locomotion, manual actions, and facial actions. Experience facilitates improvements in motor behavior and infants accumulate immense amounts of experience with all of their basic action systems. At every point in development, perception guides motor behavior by providing feedback about the results of just prior movements and information about what to do next. Reciprocally, the development of motor behavior provides fodder for perception. More generally, motor development brings about new opportunities for acquiring knowledge about the world, and burgeoning motor skills can instigate cascades of developmental changes in perceptual, cognitive, and social domains. WIREs Cogn Sci 2017, 8:e1430. doi: 10.1002/wcs.1430 For further resources related to this article, please visit the WIREs website.

Distinguishing threatening from nonthreatening stimuli is essential for survival and stimulus generalization is a hallmark of anxiety disorders. While auditory threat learning produces long-lasting plasticity in primary auditory cortex (Au1), it is not clear whether such Au1 plasticity regulates memory specificity or generalization. We used muscimol infusions in rats to show that discriminatory threat learning requires Au1 activity specifically during memory acquisition and retrieval, but not during consolidation. Memory specificity was similarly disrupted by infusion of PKMζ inhibitor peptide (ZIP) during memory storage. Our findings show that Au1 is required at critical memory phases and suggest that Au1 plasticity enables stimulus discrimination.

Infection with Zika virus is an emerging public health crisis. We observed prolonged detection of virus RNA in vaginal mucosal swab specimens and whole blood for a US traveler with acute Zika virus infection who had visited Honduras. These findings advance understanding of Zika virus infection and provide data for additional testing strategies.

Androgen loss is an important clinical concern because of its cognitive and behavioral effects. Changes in androgen levels are also suspected to contribute to neurological disease. However, the available data on the effects of androgen deprivation in areas of the brain that are central to cognition, like the hippocampus, are mixed. In this study, morphological analysis of pyramidal cells was used to investigate if structural changes could potentially contribute to the mixed cognitive effects that have been observed after androgen loss in males. Male Sprague-Dawley rats were orchidectomized or sham-operated. Two months later, their brains were Golgi-impregnated for morphological analysis. Morphological endpoints were studied in areas CA3 and CA1, with comparisons to females either intact or 2 months after ovariectomy. CA3 pyramidal neurons of orchidectomized rats exhibited marked increases in apical dendritic arborization. There were increases in mossy fiber afferent density in area CA3, as well as robust enhancements to dendritic structure in area CA3 of orchidectomized males, but not in CA1. Remarkably, apical dendritic length of CA3 pyramidal cells increased, while spine density declined. By contrast, in females overall dendritic structure was minimally affected by ovariectomy, while dendritic spine density was greatly reduced. Sex differences and subfield-specific effects of gonadal hormone deprivation on the hippocampal circuitry may help explain the different behavioral effects reported in males and females after gonadectomy, or other conditions associated with declining gonadal hormone secretion.

OBJECTIVE: Since 1997 pediatric residencies have been required to provide a 4-week block rotation in developmental and behavioral pediatrics (DBP), but it is not known whether this has altered the care and management of children by practicing pediatricians. To compare the self-reported practice patterns of pediatricians who were trained with 4 or more weeks of DBP to the practice patterns of those who were trained for < 4 weeks. METHODS: We used self-reported practices from the American Academy of Pediatrics Periodic Survey #85. Pediatricians were asked whether they never, sometimes or usually inquired about and screened for, and whether they treated/managed/co-managed ADHD, depression, anxiety, behavior problems and learning problems. They were also asked about a series of barriers to care. Analyses were weighted to account for low response rates. RESULTS: Those with more DBP training were significantly more likely to treat/manage/co-manage depression, anxiety, behavior problems and learning problems, but were still doing so less than one third of the time. There were no differences in the care of patients with ADHD or in screening or inquiring about mental health conditions. Those with more training were more likely to perceive somewhat fewer barriers and to report more specific familiarity with some DSM criteria and some treatment modalities. CONCLUSION: Longer training is associated with more treatment, but significant deficits in self-reported practice remain, leaving much room for additional improvement in the training of clinicians in DBP.

While psychiatric comorbidities of attention-deficit/hyperactivity disorder (ADHD) have been extensively explored, less attention has been paid to somatic conditions possibly associated with this disorder. However, mounting evidence in the last decade pointed to a possible significant association between ADHD and certain somatic conditions, including obesity. This papers provides an update of a previous systematic review on the relationship between obesity and ADHD (Cortese and Vincenzi, Curr Top Behav Neurosci 9:199-218, 2012), focusing on pertinent peer-reviewed empirical papers published since 2012. We conducted a systematic search in PubMed, Ovid, and Web of Knowledge databases (search dates: from January 1st, 2012, to July 16th, 2016). We retained a total of 41 studies, providing information on the prevalence of obesity in individuals with ADHD, focusing on the rates of ADHD in individuals with obesity, or reporting data useful to gain insight into possible mechanisms underlying the putative association between ADHD and obesity. Overall, over the past 4 years, an increasing number of studies have assessed the prevalence of obesity in individuals with ADHD or the rates of ADHD in patients with obesity. Although findings are mixed across individual studies, meta-analytic evidence shows a significant association between ADHD and obesity, regardless of possible confounding factors such as psychiatric comorbidities. An increasing number of studies have also addressed possible mechanisms underlying the link between ADHD and obesity, highlighting the role, among others, of abnormal eating patterns, sedentary lifestyle, and possible common genetic alterations. Importantly, recent longitudinal studies support a causal role of ADHD in contributing to weight gain. The next generation of studies in the field should explore if and to which extent the treatment of comorbid ADHD in individuals with obesity may lead to long-term weight loss, ultimately improving their overall well-being and quality of life.