Regional Brain Responses in Nulliparous Women to Emotional Infant Stimuli

Infant cries and facial expressions influence social interactions and elicit caretaking behaviors from adults. Recent neuroimaging studies suggest that neural responses to infant stimuli involve brain regions that process rewards. However, these studies have yet to investigate individual differences in tendencies to engage or withdraw from motivationally relevant stimuli. To investigate this, we used event-related fMRI to scan 17 nulliparous women. Participants were presented with novel infant cries of two distress levels (low and high) and unknown infant faces of varying affect (happy, sad, and neutral) in a randomized, counter-balanced order. Brain activation was subsequently correlated with scores on the Behavioral Inhibition System/Behavioral Activation System scale. Infant cries activated bilateral superior and middle temporal gyri (STG and MTG) and precentral and postcentral gyri. Activation was greater in bilateral temporal cortices for low- relative to high-distress cries. Happy relative to neutral faces activated the ventral striatum, caudate, ventromedial prefrontal, and orbitofrontal cortices. Sad versus neutral faces activated the precuneus, cuneus, and posterior cingulate cortex, and behavioral activation drive correlated with occipital cortical activations in this contrast. Behavioral inhibition correlated with activation in the right STG for high- and low-distress cries relative to pink noise. Behavioral drive correlated inversely with putamen, caudate, and thalamic activations for the comparison of high-distress cries to pink noise. Reward-responsiveness correlated with activation in the left precentral gyrus during the perception of low-distress cries relative to pink noise. Our findings indicate that infant cry stimuli elicit activations in areas implicated in auditory processing and social cognition. Happy infant faces may be encoded as rewarding, whereas sad faces activate regions associated with empathic processing. Differences in motivational tendencies may modulate neural responses to infant cues

Non-Invasive Brain-to-Brain Interface (BBI): Establishing Functional Links between Two Brains

Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer's intention to stimulate a rat's brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer's intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0 +/- 3.0% accuracy, with a time delay of 1.59 +/- 1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications.open12

A simulation study on the effects of neuronal ensemble properties on decoding algorithms for intracortical brain-machine interfaces

Background: Intracortical brain-machine interfaces (BMIs) harness movement information by sensing neuronal activities using chronic microelectrode implants to restore lost functions to patients with paralysis. However, neuronal signals often vary over time, even within a day, forcing one to rebuild a BMI every time they operate it. The term "rebuild" means overall procedures for operating a BMI, such as decoder selection, decoder training, and decoder testing. It gives rise to a practical issue of what decoder should be built for a given neuronal ensemble. This study aims to address it by exploring how decoders' performance varies with the neuronal properties. To extensively explore a range of neuronal properties, we conduct a simulation study. Methods: Focusing on movement direction, we examine several basic neuronal properties, including the signal-to-noise ratio of neurons, the proportion of well-tuned neurons, the uniformity of their preferred directions (PDs), and the non-stationarity of PDs. We investigate the performance of three popular BMI decoders: Kalman filter, optimal linear estimator, and population vector algorithm. Results: Our simulation results showed that decoding performance of all the decoders was affected more by the proportion of well-tuned neurons that their uniformity. Conclusions: Our study suggests a simulated scenario of how to choose a decoder for intracortical BMIs in various neuronal conditions

The effects of exercise on pain, fatigue, insomnia, and health perceptions in patients with operable advanced stage rectal cancer prior to surgery: a pilot trial

Background: Promoting quality of life (QoL) is a key priority in cancer care. We investigated the hypothesis that, in comparison to usual care, exercise post-neoadjuvant chemoradiation therapy/prior to surgical resection will reduce pain, fatigue, and insomnia, and will improve physical and mental health perceptions in patients with locally advanced stage rectal cancer. Methods: In this non-randomized controlled pilot trial, patients in the supervised exercise group (EG; Mage = 64 years; 64% male) and in the control group (CG; Mage = 72 years; 69% male) completed the European Organization for Research and Treatment of Cancer core Quality of Life questionnaire and the RAND 36-Item Health Survey three times: pre-neoadjuvant chemoradiation therapy (Time 1; nEC = 24; nCG = 11), post-neoadjuvant chemoradiation therapy/pre-exercise intervention (Time 2; nEC = 23; nCG = 10), and post-exercise intervention (Time 3; nEC = 22; nCG = 10). The 6-week exercise intervention was delivered in hospital and comprised of interval aerobic training. Patients trained in pairs three times per week for 30 to 40 minutes. Data were analyzed by Mann-Whitney tests and by Wilcoxon matched-pairs signed rank tests. Results: No significant between-group differences in change were found for any of the outcomes. In both groups, fatigue levels decreased and physical health perceptions increased from pre- to post-exercise intervention. Pain levels also decreased from pre- to post-exercise intervention, albeit not significantly. Conclusions: The findings from this study can be used to guide a more definitive trial as they provide preliminary evidence regarding the potential effects of pre-operative exercise on self-reported pain, fatigue, insomnia, and health perceptions in patients with locally advanced rectal cancer. Trial registration: This study has been registered with clinicaltrials.gov (NCT01325909; March 29, 2011)

Response perseveration and ventral prefrontal sensitivity to reward and punishment in male problem gamblers and smokers

Pathological gambling (PG) is associated with maladaptive perseverative behavior, but the underlying mechanism and neural circuitry is not completely clear. Here, the hypothesis was tested that PG is characterized by response perseveration and abnormalities in reward and/or punishment sensitivity in the ventral frontostriatal circuit. Executive functioning was assessed to verify if these effects are independent of the dorsal frontostriatal circuit. A group of smokers was also included to examine whether impairments in PG generalize to substance use disorders. Response perseveration and reward/punishment sensitivity were measured with a probabilistic reversal-learning task, in which subjects could win and lose money. Executive functioning was measured with a planning task, the Tower of London. Performance and fMRI data were acquired in 19 problem gamblers, 19 smokers, and 19 healthy controls. Problem gamblers showed severe response perseveration, associated with reduced activation of right ventrolateral prefrontal cortex in response to both monetary gain and loss. Results did not fully generalize to smokers. Planning performance and related activation of the dorsal frontostriatal circuit were intact in both problem gamblers and smokers. PG is related to response perseveration and diminished reward and punishment sensitivity as indicated by hypoactivation of the ventrolateral prefrontal cortex when money is gained and lost. Moreover, intact planning abilities and normal dorsal frontostriatal responsiveness indicate that this deficit is not due to impaired executive functioning. Response perseveration and ventral prefrontal hyporesponsiveness to monetary loss may be markers for maladaptive behavior seen in chemical and nonchemical addictions. © 2009 Nature Publishing Group All rights reserved

The ECOUTER methodology for stakeholder engagement in translational research.

BACKGROUND: Because no single person or group holds knowledge about all aspects of research, mechanisms are needed to support knowledge exchange and engagement. Expertise in the research setting necessarily includes scientific and methodological expertise, but also expertise gained through the experience of participating in research and/or being a recipient of research outcomes (as a patient or member of the public). Engagement is, by its nature, reciprocal and relational: the process of engaging research participants, patients, citizens and others (the many 'publics' of engagement) brings them closer to the research but also brings the research closer to them. When translating research into practice, engaging the public and other stakeholders is explicitly intended to make the outcomes of translation relevant to its constituency of users. METHODS: In practice, engagement faces numerous challenges and is often time-consuming, expensive and 'thorny' work. We explore the epistemic and ontological considerations and implications of four common critiques of engagement methodologies that contest: representativeness, communication and articulation, impacts and outcome, and democracy. The ECOUTER (Employing COnceptUal schema for policy and Translation Engagement in Research) methodology addresses problems of representation and epistemic foundationalism using a methodology that asks, "How could it be otherwise?" ECOUTER affords the possibility of engagement where spatial and temporal constraints are present, relying on saturation as a method of 'keeping open' the possible considerations that might emerge and including reflexive use of qualitative analytic methods. RESULTS: This paper describes the ECOUTER process, focusing on one worked example and detailing lessons learned from four other pilots. ECOUTER uses mind-mapping techniques to 'open up' engagement, iteratively and organically. ECOUTER aims to balance the breadth, accessibility and user-determination of the scope of engagement. An ECOUTER exercise comprises four stages: (1) engagement and knowledge exchange; (2) analysis of mindmap contributions; (3) development of a conceptual schema (i.e. a map of concepts and their relationship); and (4) feedback, refinement and development of recommendations. CONCLUSION: ECOUTER refuses fixed truths but also refuses a fixed nature. Its promise lies in its flexibility, adaptability and openness. ECOUTER will be formed and re-formed by the needs and creativity of those who use it

Pharmacological differentiation of opioid receptor antagonists by molecular and functional imaging of target occupancy and food reward-related brain activation in humans

Opioid neurotransmission has a key role in mediating reward-related behaviours. Opioid receptor (OR) antagonists, such as naltrexone (NTX), can attenuate the behaviour-reinforcing effects of primary (food) and secondary rewards. GSK1521498 is a novel OR ligand, which behaves as an inverse agonist at the μ-OR sub-type. In a sample of healthy volunteers, we used [11C]-carfentanil positron emission tomography to measure the OR occupancy and functional magnetic resonance imaging (fMRI) to measure activation of brain reward centres by palatable food stimuli before and after single oral doses of GSK1521498 (range, 0.4–100 mg) or NTX (range, 2–50 mg). GSK1521498 had high affinity for human brain ORs (GSK1521498 effective concentration 50=7.10 ng ml−1) and there was a direct relationship between receptor occupancy (RO) and plasma concentrations of GSK1521498. However, for both NTX and its principal active metabolite in humans, 6-β-NTX, this relationship was indirect. GSK1521498, but not NTX, significantly attenuated the fMRI activation of the amygdala by a palatable food stimulus. We thus have shown how the pharmacological properties of OR antagonists can be characterised directly in humans by a novel integration of molecular and functional neuroimaging techniques. GSK1521498 was differentiated from NTX in terms of its pharmacokinetics, target affinity, plasma concentration–RO relationships and pharmacodynamic effects on food reward processing in the brain. Pharmacological differentiation of these molecules suggests that they may have different therapeutic profiles for treatment of overeating and other disorders of compulsive consumption

The power of comparative and developmental studies for mouse models of Down syndrome

Since the genetic basis for Down syndrome (DS) was described, understanding the causative relationship between genes at dosage imbalance and phenotypes associated with DS has been a principal goal of researchers studying trisomy 21 (Ts21). Though inferences to the gene-phenotype relationship in humans have been made, evidence linking a specific gene or region to a particular congenital phenotype has been limited. To further understand the genetic basis for DS phenotypes, mouse models with three copies of human chromosome 21 (Hsa21) orthologs have been developed. Mouse models offer access to every tissue at each stage of development, opportunity to manipulate genetic content, and ability to precisely quantify phenotypes. Numerous approaches to recreate trisomic composition and analyze phenotypes similar to DS have resulted in diverse trisomic mouse models. A murine intraspecies comparative analysis of different genetic models of Ts21 and specific DS phenotypes reveals the complexity of trisomy and important considerations to understand the etiology of and strategies for amelioration or prevention of trisomic phenotypes. By analyzing individual phenotypes in different mouse models throughout development, such as neurologic, craniofacial, and cardiovascular abnormalities, greater insight into the gene-phenotype relationship has been demonstrated. In this review we discuss how phenotype-based comparisons between DS mouse models have been useful in analyzing the relationship of trisomy and DS phenotypes

CXCR2 Inhibition – a novel approach to treating CoronAry heart DiseAse (CICADA): study protocol for a randomised controlled trial

Abstract Background There is emerging evidence of the central role of neutrophils in both atherosclerotic plaque formation and rupture. Patients with lower neutrophil counts following acute coronary syndromes tend to have a greater coronary flow reserve, which is a strong predictor of long-term cardiovascular health. But so far, no data are available regarding the impact of neutrophil inhibition on cardiovascular clinical or surrogate endpoints. Therefore, the aim of this study is to investigate the effects of AZD5069, a cysteine-X-cysteine chemokine receptor 2 (CXCR2) inhibitor, on coronary flow reserve and coronary structure and function in patients with coronary artery disease. Methods/Design Ninety subjects with coronary artery disease undergoing percutaneous coronary intervention will be included in this investigator-driven, randomised, placebo-controlled, double-blind, phase IIa, single-centre study. Participants will be randomised to receive either AZD5069 (40 mg) administered orally twice daily or placebo for 24 weeks. Change in coronary flow reserve as determined by 13N-ammonia positron emission tomography-computed tomography will be the primary outcome. Change in the inflammatory component of coronary plaque structure and the backward expansion wave, an invasive coronary physiological measure of diastolic function, will be assessed as secondary outcomes. Discussion Cardiovascular surrogate parameters, such as coronary flow reserve, may provide insights into the potential mechanisms of the cardiovascular effects of CXCR2 inhibitors. Currently, ongoing trials do not specifically focus on neutrophil function as a target of intervention, and we therefore believe that our study will contribute to a better understanding of the role of neutrophil-mediated inflammation in coronary artery disease. Trial registration EudraCT, 2016-000775-24 . Registered on 22 July 2016. International Standard Randomised Controlled Trial Number, ISRCTN48328178 . Registered on 25 February 2016

Neuromarketing and consumer neuroscience:contributions to neurology

Background: 'Neuromarketing' is a term that has often been used in the media in recent years. These public discussions have generally centered around potential ethical aspects and the public fear of negative consequences for society in general, and consumers in particular. However, positive contributions to the scientific discourse from developing a biological model that tries to explain context-situated human behavior such as consumption have often been neglected. We argue for a differentiated terminology, naming commercial applications of neuroscientific methods 'neuromarketing' and scientific ones 'consumer neuroscience'. While marketing scholars have eagerly integrated neuroscientific evidence into their theoretical framework, neurology has only recently started to draw its attention to the results of consumer neuroscience.Discussion: In this paper we address key research topics of consumer neuroscience that we think are of interest for neurologists; namely the reward system, trust and ethical issues. We argue that there are overlapping research topics in neurology and consumer neuroscience where both sides can profit from collaboration. Further, neurologists joining the public discussion of ethical issues surrounding neuromarketing and consumer neuroscience could contribute standards and experience gained in clinical research.Summary: We identify the following areas where consumer neuroscience could contribute to the field of neurology:. First, studies using game paradigms could help to gain further insights into the underlying pathophysiology of pathological gambling in Parkinson's disease, frontotemporal dementia, epilepsy, and Huntington's disease.Second, we identify compulsive buying as a common interest in neurology and consumer neuroscience. Paradigms commonly used in consumer neuroscience could be applied to patients suffering from Parkinson's disease and frontotemporal dementia to advance knowledge of this important behavioral symptom.Third, trust research in the medical context lacks empirical behavioral and neuroscientific evidence. Neurologists entering this field of research could profit from the extensive knowledge of the biological foundation of trust that scientists in economically-orientated neurosciences have gained.Fourth, neurologists could contribute significantly to the ethical debate about invasive methods in neuromarketing and consumer neuroscience. Further, neurologists should investigate biological and behavioral reactions of neurological patients to marketing and advertising measures, as they could show special consumer vulnerability and be subject to target marketing