Neocortex is an important part of the mammalian brain that is quite different from its homologue of the dorsal cortex in the reptilian brain. Whereas dorsal cortex is small, thin, and composed of a single layer of neurons, neocortex is thick and has six layers, while being variable across species in size, number of functional areas, and architectonic differentiation. Early mammals had little neocortex, with perhaps 20 areas of poor structural differentiation. Many extant mammals continue to have small brains with little neocortex, but they often have sensory specializations reflected in the organization of sensory areas in neocortex. In primates, neocortex is variously enlarged and characterized by structural and other specializations, including those of cortical networks devoted to vision and visuomotor processing.In humans, neocortex occupies 80% of the volume of the brain, where as many as 200 areas may exist.
primates; reptiles; dorsal cortex; visual cortex; marsupials; monotremes
Research on consumer decision making and aging is especially important for fostering a better understanding of ways to maintain consumer satisfaction and high decision quality across the life span. We provide a review of extant research on the effects of normal aging on cognition and decision processes and how these age-related processes are influenced by task environment, meaningfulness of the task, and consumer expertise. We consider how research centered on these topics generates insights about changes in consumption decisions that occur with aging and identify a number of gaps and directions for future research.
aging; decision making; consumers
The following on esophageal disease in pediatrics contains commentaries on acquisition of neuromuscular maturation; physiology of esophageal peristaltic and sphincteric reflexes; implications for clinical practice; and conditions that predispose to severe gastroesophageal reflux disease (GERD) in children with potential risk for esophageal cancer.
embryology; peristalsis; sphincteric reflexes; fetal swallowing; airway protection; Barrett's esophagus; GERD
Sponsored by the New York Academy of Sciences and with support from the National Institute of Mental Health, the Life Technologies Foundation, and the Josiah Macy Jr. Foundation, “Advancing Drug Discovery for Schizophrenia” was held March 9–11 at the New York Academy of Sciences in New York City. The meeting, comprising individual talks and panel discussions, highlighted basic, clinical, and translational research approaches, all of which contribute to the overarching goal of enhancing the pharmaceutical armamentarium for treating schizophrenia. This report surveys work by the vanguard of schizophrenia research in such topics as genetic and epigenetic approaches; small molecule therapeutics; and the relationships between target genes, neuronal function, and symptoms of schizophrenia.
schizophrenia; genetics; GWAS; neuronal function; small molecules; therapeutics
Sponsored by the New York Academy of Sciences, the Warren Alpert Medical School of Brown University and the University of Massachusetts Boston, “Behavioral Epigenetics” was held on October 29–30, 2010 at the University of Massachusetts Boston Campus Center, Boston, Massachusetts. This meeting featured speakers and panel discussions exploring the emerging field of behavioral epigenetics, from basic biochemical and cellular mechanisms to the epigenetic modulation of normative development, developmental disorders, and psychopathology. This report provides an overview of the research presented by leading scientists and lively discussion about the future of investigation at the behavioral epigenetic level.
behavior; epigenetics; chromosome; gene regulation; transcription; methylation
In this paper, we review the current literature to highlight relations between age-associated declines in dopaminergic and serotonergic neuromodulation and adult age differences in adaptive goal-directed behavior. Specifically, we focus on evidence suggesting that deficits in neuromodulation contribute to older adults’ behavioral disadvantages in learning and decision making. These deficits are particularly pronounced when reward information is uncertain or the task context requires flexible adaptations to changing stimulus–reward contingencies. Moreover, emerging evidence points to age-related differences in the sensitivity to rewarding and aversive outcomes during learning and decision making if the acquisition of behavior critically depends on outcome processing. These age-related asymmetries in outcome valuation may be explained by age differences in the interplay of dopaminergic and serotonergic neuromodulation. This hypothesis is based on recent neurocomputational and psychopharmacological approaches, which suggest that dopamine and serotonin serve opponent roles in regulating the balance between approach behavior and inhibitory control. Studying adaptive regulation of behavior across the adult life span may shed new light on how the aging brain changes functionally in response to its diminishing resources.
aging; neuromodulation; motivation; cognitive control
Mutations in genes encoding the Calcium-Release Activated Calcium (CRAC)
channel abolish calcium influx in cells of the immune system and cause severe
congenital immunodeficiency. Patients with autosomal recessive mutations in the
CRAC channel gene ORAI1, its activator Stromal
Interaction Molecule 1 (STIM1) and mice with
targeted deletion of Orai1, Stim1 and Stim2
genes reveal important roles for CRAC channels in adaptive and innate immune
responses to infection and in autoimmunity. Since CRAC channels have important
functions outside the immune system, ORAI1 and STIM1 deficiency are associated
with a unique clinical phenotype. This review will give an overview of CRAC
channel function in the immune system, examine the consequences of CRAC channel
deficiency for immunity in human patients and mice and discuss genetic defects
in immunoreceptor-associated signaling molecules that compromise calcium influx
and cause immunodeficiency.
Immunodeficiency; T cells; CRAC channels; ORAI1; STIM1
With life expectancy dramatically increasing throughout much of the world, people have to make choices with a longer future in mind than they ever had to before. Yet, many indicators suggest that undersaving for the long term often occurs: in America, for instance, many individuals will not be able to maintain their preretirement standard of living in retirement. Previous research has tried to understand problems with intertemporal choice by focusing on the ways in which people treat present and future rewards. In this paper, the author reviews a burgeoning body of theoretical and empirical work that takes a different viewpoint, one that focuses on how perceptions of the self over time can dramatically affect decision making. Specifically, when the future self shares similarities with the present self, when it is viewed in vivid and realistic terms, and when it is seen in a positive light, people are more willing to make choices today that may benefit them at some point in the years to come.
future self-continuity; behavioral economics; intertemporal choice; temporal discounting; retirement saving
Time and time perceptions are integral to decision making because any meaningful choice is embedded in a temporal context and requires the evaluation of future preferences and outcomes. The present review examines the influence of chronological age on time perceptions and horizons and discusses implications for decision making across the life span. Time influences and interacts with decision making in multiple ways. Specifically, this review examines the following topic areas: (1) processing speed and decision time, (2) internal clocks and time estimation, (3) mental representations of future time and intertemporal choice, and (4) global time horizons. For each aspect, patterns of age differences and implications for decision strategies and quality are discussed. The conclusion proposes frameworks to integrate different lines of research and identifies promising avenues for future inquiry.
We outline a contextual and motivational model of judgment and decision-making (JDM) biases across the life span. Our model focuses on abilities and skills that correspond to deliberative, experiential, and affective decision-making processes. We review research that addresses links between JDM biases and these processes as represented by individual differences in specific abilities and skills (e.g., fluid and crystallized intelligence, executive functioning, emotion regulation, personality traits). We focus on two JDM biases—the sunk-cost fallacy (SCF) and the framing effect. We trace the developmental trajectory of each bias from preschool through middle childhood, adolescence, early adulthood, and later adulthood. We conclude that life-span developmental trajectories differ depending on the bias investigated. Existing research suggests relative stability in the framing effect across the life span and decreases in the SCF with age, including in later life. We highlight directions for future research on JDM biases across the life span, emphasizing the need for process-oriented research and research that increases our understanding of JDM biases in people’s everyday lives.
sunk costs; framing effect; dual processes; heuristics; biases
Everyday problem solving involves examining the solutions that individuals generate when faced with problems that take place in their everyday experiences. Problems can range from medication adherence and meal preparation to disagreeing with a physician over a recommended medical procedure or compromising with extended family members over where to host Thanksgiving dinner. Across the life span, research has demonstrated divergent patterns of change in performance based on the type of everyday problems used as well as based on the way that problem-solving efficacy is operationally defined. Advancing age is associated with worsening performance when tasks involve single-solution or fluency-based definitions of effectiveness. However, when efficacy is defined in terms of the diversity of strategies used, as well as by the social and emotional impact of solution choice on the individual, performance is remarkably stable and sometimes even improves in the latter half of life. This article discusses how both of these approaches to everyday problem solving inform research on the influence that aging has on everyday functioning.
everyday problem solving; aging; coping; practical intelligence; decision making
The orbital frontal cortex (OFC) has been implicated in a number of psychiatric disorders, including depression, anxiety, phobia, and obsessive-compulsive disorder. Thus, a better understanding of its functions will likely provide critical information to understand the specific behavioral and cognitive processes affected in these human disorders. In recent years, a growing number of studies have provided evidence for anatomical and functional differentiation within the OFC. Here we discuss the effects of selective OFC (areas 11/13) lesions on social behavior, emotional regulation, and behavioral adaptation. Damage to these specific OFC subfields in adult monkeys resulted in profound changes in the flexible modulation of responses guided by reward value that could explain the poor fear regulation and disturbed social interactions observed in the same animals. A similar pattern of results was found when the OFC lesions were done in infancy. Thus, in monkeys, self-regulation abilities mediated by OFC areas 11/13 emerge from midinfancy through adolescence.
orbitofrontal cortex; rhesus; behavior; emotion; flexibility
Major well-defined medical problems that are, in part, the unfortunate outcome of a negative social environment may include specific addictive diseases and other mental health disorders, in particular the affective disorders of anxiety, depression, social phobia, and post-traumatic stress syndrome. This overview touches on the topic of extreme marginalization associated with addiction and other mental health disorders, along with arrest, imprisonment, and parole. All of these are characterized by lasting stigma that hauntingly continues to impact upon each person suffering from any of these problems.
addiction; mental health disorders; stigma; imprisonment
Hofbauer cells (HBCs) are placental macrophages that are present in the villus across gestation. Despite their identification more than 100 years ago, their specific role in placental function remains largely unelucidated. We initially review aspects of their history and biology as well as evidence for putative sites of origin. To gain insight into their potential function, we then describe complications of pregnancy including villitis of unknown etiology (VUE) and histological chorioamnionitis (HCA), in which alterations in numbers, gene expression, or other characteristics of HBCs have been documented to occur. We further review methods for isolation of HBCs and in vitro studies that explore their role in relation to other major cell types in the placenta and examine their actions in cytokine-mediated inflammation. We conclude that HBCs play a key role in placental pathophysiology, and future advances in their isolation and culture would enable mechanistic insight into their villus function.
placenta; Hofbauer cells; fetal macrophages; preterm delivery; villitis of unknown etiology; chorioamnionitis
The following series of concise summaries addresses the evolution of infectious agents in relation to sex in animals and humans from the perspective of three specific questions: (1) what have we learned about the likely origin and phylogeny, up to the establishment of the infectious agent in the genital econiche, including the relative frequency of its sexual transmission; (2) what further research is needed to provide additional knowledge on some of these evolutionary aspects; and (3) what evolutionary considerations might aid in providing novel approaches to the more practical clinical and public health issues facing us currently and in the future?
evolution; infectious agents; sexual transmission; econiche
Clinical use of positron emission tomography (PET) is now well established in neurodegenerative disorders, especially in the diagnosis of dementia. Measurement of cerebral glucose metabolism is of significant value, and it facilitates early diagnosis, appropriate differential diagnosis, and the evaluation of drug treatment in patients with dementia. In addition, tracers offer new perspectives for studying the neuropathology of underlying dementia, such as the accumulation of amyloid proteins, tau-proteins, or the presence of neuroinflammation. Finally, PET tracer studies of different neurotransmitter systems in dementia may not only increase the understanding of pathophysiologic mechanisms of the different disorders, but also improve diagnostic accuracy. In conclusion, PET imaging with different tracers offers reliable biomarkers in dementia, which can assist clinicians in the diagnosis of different dementing disorders, especially in the situation of overlapping phenotypes.
PET/CT; dementia; Alzheimer’s disease
Molecular imaging with PET offers a broad variety of tools supporting the diagnosis of movement disorders. The more widely applied PET imaging techniques have focused on the assessment of neurotransmitter systems, predominantly the pre- and postsynaptic dopaminergic system. Additionally, PET imaging with [18F] fluorodeoxyglucose has been extensively used to assess local synaptic activity in the resting state and to highlight local changes in brain metabolism accompanying changes in neural activity in movement disorders. PET imaging has provided us with diagnostic agents as well as tools for evaluation of novel therapeutics, and has served as a powerful means for revealing in vivo changes at different stages of movement disorders and within the course of an individual patient’s illness.
PET/CT; movement disorders; Parkinson’s disease
Individuals weigh information about both rewarding and aversive stimuli in order to make adaptive decisions. Most studies of the orbitofrontal cortex (OFC), an area where appetitive and aversive neural subsystems might interact, have focused only on reward. Using a classical conditioning task where novel stimuli are paired with reward or aversive air-puff, we discovered that two groups of orbitofrontal neurons respond preferentially to conditioned stimuli associated with rewarding and aversive outcomes; however, information about appetitive and aversive stimuli converges on individual neurons from both populations. Therefore, neurons in OFC might participate in appetitive and aversive networks that track the motivational significance of stimuli even when they vary in valence and sensory modality. Further, we show that these networks, which also extend to the amygdala, exhibit different rates of change during reversal learning. Thus, although both networks represent appetitive and aversive associations, their distinct temporal dynamics might indicate different roles in learning processes.
orbitofrontal cortex; reinforcement learning; conditioning; reward; aversive; monkey
Osteoarthritis (OA) is a highly prevalent disease affecting more than 20% of American adults. Predispositions include joint injury, heredity, obesity, and aging. Biomechanical alterations are commonly involved. However, the molecular mechanisms of this disease are complex, and there is currently no effective disease-modifying treatment. The initiation and progression of OA subtypes is a complex process that at the molecular level probably involves many cell types, signaling pathways, and changes in extracellular matrix. Ex vivo studies with tissue derived from OA patients and in vivo studies with mutant mice have suggested that pathways involving receptor ligands such as TGF-β1, WNT3a, and Indian hedgehog; signaling molecules such as Smads, β-catenin, and HIF-2a; and peptidases such as MMP13 and ADAMTS4/5 are probably involved to some degree. This review focuses on molecular mechanisms of OA development related to recent findings.
osteoarthritis; articular cartilage; growth factors; Mmp13; Adamts5
The superior colliculus (SC) is well known for its involvement in the conversion of sensory stimuli into motor commands. This sensorimotor integration is made possible by the collective activity of multiple neuronal connections throughout the SC. Still, the majority of SC research focuses on in vivo extracellular recordings of behaving monkeys or in vitro patch-clamp recordings from lower mammals. Here, we discuss the results of an in vitro voltage imaging technique in which population activity across the rodent SC circuitry was visualized to bridge the gap between single-cell recordings and whole-animal behavior.1 The high temporal and spatial resolution of the voltage imaging technique allowed us to visualize of patterns of activity following stimulation at discrete laminae. Stimulation within either the superficial or intermediate layer showed recruitment of disparate SC circuitry. These results provide insight into the circuit dynamics and neuronal populations that underlie behavior.
circuits; electrical stimulation; sensorimotor; eye movements
The following on endoscopic treatments of Barrett's esophagus includes commentaries on animal experiments on cryotherapy; indications for cryotherapy, choice of dosimetry, number of sessions, and role in Barrett's esophagus and adenocarcinoma; recent technical developments of RFA technology and long-term effects; the comparative effects of diverse ablation procedures and the rate of recurrence following treatment; and the indications for treatment of dysplasia and the role of radiofrequency ablation.
cryosurgery; esophageal neoplasms; Barrett's esophagus; dysplasia; adenocarcinoma; specialized intestinal metaplasia; subsquamous glandular mucosa; buried glands; radiofrequency ablation; argon plasma coagulation; multipolar electrocautery; PDT; Halo90; Halo180; Halo360; balloon sizing; carcinoma; subsquamous glands; proton pump inhibitor therapy; AspECT trial; multifocal disease; neosquamous epithelium
Systems pharmacology approaches can be used to identify and predict drug-induced adverse events. Disease-centered networks within the human interactome allow us to predict which drugs may produce a similar pathophysiology. Such predictions can be tested in animal models.
systems pharmacology; network biology; personalized medicine
Single-molecule fluorescence imaging has provided unprecedented access to the dynamics of ribosome function, revealing transient intermediate states that are critical to ribosome activity. Imaging platforms have now been developed that are capable of probing many hundreds of molecules simultaneously at temporal and spatial resolutions approaching the sub-millisecond time and the sub-nanometer scales. These advances enable both steady- and pre-steady state measurements of individual steps in the translation process as well as processive reactions. The data generated using these methods have yielded new, quantitative structural and kinetic insights into ribosomal activity. They have also shed light on the mechanisms of antibiotics targeting the translation apparatus, revealing features of the structure-function relationship that would be difficult to obtain by other means. This review provides an overview of the types of information that can be obtained using such imaging platforms and a blueprint for using the technique to assess how small-molecule antibiotics alter macromolecular functions.
antibiotics; ribosome; smFRET; translation; tRNA
The following on molecular aspects of esophageal development contains commentaries on esophageal striated myogenesis and transdifferentiation; conversion from columnar into stratified squamous epithelium in the mouse esophagus; the roles for BMP signaling in the developing esophagus and forestomach; and evidence of a direct conversion from columnar to stratified squamous cells in the developing esophagus.
BMP signaling; esophagus; forestomach; stratification; differentiation; myogenesis; transdifferentiation; fate mapping; embryonic esophageal culture model; columnar epithelium; stratified squamous epithelium
Obesity has various deleterious effects on health largely associated with metabolic abnormalities including abnormal glucose and lipid homeostasis that are associated with vascular injury and known cardiac, renal, and cerebrovascular complications. Advanced age is also associated with increased adiposity, decreased lean mass, and increased risk for obesity-related diseases. Although many of these obesity- and age-related disease processes have long been subsumed to be secondary to metabolic or vascular dysfunction, increasing evidence indicates that obesity also modulates nonvascular diseases such as Alzheimer's disease (AD) dementia. The link between peripheral obesity and neurode-generation will be explored, using adipokines and AD as a template. After an introduction to the neuropathology of AD, the relationship between body weight, obesity, and dementia will be reviewed. Then, population-based and experimental studies that address whether leptin modulates brain health and mitigates AD pathways will be explored. These studies will serve as a framework for understanding the role of adipokines in brain health.
adiponectin; Alzheimer; amyloid; leptin