Audio-Visual Integration in a Redundant Target Paradigm: A Comparison between Rhesus Macaque and Man.

The mechanisms underlying multi-sensory interactions are still poorly understood despite considerable progress made since the first neurophysiological recordings of multi-sensory neurons. While the majority of single-cell neurophysiology has been performed in anesthetized or passive-awake laboratory animals, the vast majority of behavioral data stems from studies with human subjects. Interpretation of neurophysiological data implicitly assumes that laboratory animals exhibit perceptual phenomena comparable or identical to those observed in human subjects. To explicitly test this underlying assumption, we here characterized how two rhesus macaques and four humans detect changes in intensity of auditory, visual, and audio-visual stimuli. These intensity changes consisted of a gradual envelope modulation for the sound, and a luminance step for the LED. Subjects had to detect any perceived intensity change as fast as possible. By comparing the monkeys' results with those obtained from the human subjects we found that (1) unimodal reaction times differed across modality, acoustic modulation frequency, and species, (2) the largest facilitation of reaction times with the audio-visual stimuli was observed when stimulus onset asynchronies were such that the unimodal reactions would occur at the same time (response, rather than physical synchrony), and (3) the largest audio-visual reaction-time facilitation was observed when unimodal auditory stimuli were difficult to detect, i.e., at slow unimodal reaction times. We conclude that despite marked unimodal heterogeneity, similar multisensory rules applied to both species. Single-cell neurophysiology in the rhesus macaque may therefore yield valuable insights into the mechanisms governing audio-visual integration that may be informative of the processes taking place in the human brain

Defining Medical Futility in Ethics, Law and Clinical Practice: An Exercise in Futility?

The debate as to the meaning of medical futility and what physicians should do in clinical practice dates back to the time of the writings of Hippocrates and Plato where it was said, "To attempt futile treatment is to display an ignorance that is allied to madness". In simpler times assertions regarding the obvious were sufficient to indicate what was thought "fitting" as a medical practitioner. In recent times, however, modern technology, professional values and power, patient autonomy, limited health care resources and societal expectations, make for a much more potent and potentially explosive mixture. In this article we argue that futility is a problem that will not go away, both because of increased health expectations and emerging technologies that keep making possible what was previously impossible. The problem of definition and its ramifications in terms of institutional policies is one in which the legal profession and its process (which often represents and reflects societal values) has a key role to play by way of critical reflection and appraisal

The effect of spatial–temporal audiovisual disparities on saccades in a complex scene

In a previous study we quantified the effect of multisensory integration on the latency and accuracy of saccadic eye movements toward spatially aligned audiovisual (AV) stimuli within a rich AV-background (Corneil et al. in J Neurophysiol 88:438–454, 2002). In those experiments both stimulus modalities belonged to the same object, and subjects were instructed to foveate that source, irrespective of modality. Under natural conditions, however, subjects have no prior knowledge as to whether visual and auditory events originated from the same, or from different objects in space and time. In the present experiments we included these possibilities by introducing various spatial and temporal disparities between the visual and auditory events within the AV-background. Subjects had to orient fast and accurately to the visual target, thereby ignoring the auditory distractor. We show that this task belies a dichotomy, as it was quite difficult to produce fast responses (<250 ms) that were not aurally driven. Subjects therefore made many erroneous saccades. Interestingly, for the spatially aligned events the inability to ignore auditory stimuli produced shorter reaction times, but also more accurate responses than for the unisensory target conditions. These findings, which demonstrate effective multisensory integration, are similar to the previous study, and the same multisensory integration rules are applied (Corneil et al. in J Neurophysiol 88:438–454, 2002). In contrast, with increasing spatial disparity, integration gradually broke down, as the subjects’ responses became bistable: saccades were directed either to the auditory (fast responses), or to the visual stimulus (late responses). Interestingly, also in this case responses were faster and more accurate than to the respective unisensory stimuli

Effect of intranasally administered insulin on cerebral blood flow and perfusion:a randomized experiment in young and older adults

Pathophysiology, epidemiology and therapy of agein

Confined placental mosaicism:Distribution of chromosomally abnormal cells over the term placenta

Objective: Non-invasive prenatal testing (NIPT) investigates placental DNA and may detect confined placental mosaicism (CPM). The aim of this study was to confirm CPM in the term placenta in cases with abnormal NIPT but normal follow-up cytogenetic studies of fetus and mother. Additionally we examined the distribution of abnormal cells over the placenta. Methods: Four chorionic villus (CV) biopsies from four placental quadrants were requested in cases where CPM was assumed. Both cell lineages of the CV, cytotrophoblast (CTB) and mesenchymal core (MC), were analyzed separately with SNP array. Results: The chromosome aberration was confirmed in 67 % of the placentas. Three quarters of the CTB and MC biopsies from these mosaic placentas were uniformly normal (57 %) or abnormal (20 %), and a minority showed mosaicism. Among 16 cases of CPM where first trimester CV were examined as well, 11 had chromosomally normal results during pregnancy. Discussion: Cytogenetic investigations of term placental biopsies suspected to be affected with CPM did not reveal the chromosome aberration in one third of the placentas. This is caused by the patchy pattern in which chromosomally abnormal cells are distributed over the placenta with the majority of the biopsies being uniformly normal. Further CPM research, including its clinical impact, requires the analysis of more than four biopsies to get insight into the extent of the affected part. Moreover, a subset of CPM type 1 and 3 seems to be only detectable with NIPT and not with first trimester CVS.</p

Use of three-dimensional computed tomography overlay for real-time cryoballoon ablation in atrial fibrillation reduces radiation dose and contrast dye

AIMS: Cryoballoon pulmonary vein (PV) isolation in patients with atrial fibrillation has proven to be effective in short-term and long-term follow-up. To visualise the PV anatomy, pre-ablation contrast pulmonary venography is commonly performed. Three-dimensional (3D) computed tomography (CT) overlay is a new technique creating a live 3D image of the left atrium by integrating a previously obtained CT scan during fluoroscopy. To evaluate the benefits of 3D CT overlay during cryoballoon ablation, we studied the use of 3D CT overlay versus contrast pulmonary venography in a randomised fashion in patients with paroxysmal atrial fibrillation undergoing cryoballoon PV isolation. METHODS AND RESULTS: Between October 2012 and June 2013, 30 patients accepted for PV isolation were randomised to cryoballoon PV isolation using either 3D CT overlay or contrast pulmonary venography. All patients underwent a pre-procedural cardiac CT for evaluation of the anatomy of the left atrium (LA) and the PVs. In the 3D CT overlay group, a 3D reconstruction of the LA and PVs was made. An overlay of the CT reconstruction was then projected over live fluoroscopy. Patients in the contrast pulmonary venography group received significantly more contrast agent (77.1 ± 21.2 cc vs 40.1 ± 17.6 cc, p < 0.001) and radiation (43.0 ± 21.9 Gy.cm2 vs 28.41 ± 11.7 Gy.cm2, p = 0.04) than subjects in the 3D CT overlay group. There was no difference in total procedure time, fluoroscopy time and the amount of cryoapplications between the two groups. CONCLUSION: The use of 3D CT overlay decreases radiation and contrast dye exposure and can assist in guiding cryoballoon-based PV isolation

Effects of intranasal insulin application on the hypothalamic BOLD response to glucose ingestion

Abstract The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease. In this study, we assessed whether intranasal insulin can be used to enhance neuronal hypothalamic responses to glucose ingestion. In a randomized, double-blinded, placebo-controlled 4-double cross-over experiment, hypothalamic activation was measured in young non- diabetic subjects by determining blood-oxygen-level dependent MRI signals over 30 minutes before and after ingestion of 75 g glucose dissolved in 300 ml water, under intranasal insulin or placebo condition. Glucose ingestion under placebo condition lead to an average 1.4% hypothalamic BOLD decrease, under insulin condition the average response to glucose was a 2.2% decrease. Administration of water did not affect the hypothalamic BOLD responses. Intranasal insulin did not change circulating glucose and insulin levels. Still, circulating glucose levels showed a significant dampening effect on the BOLD response and insulin levels a significant strengthening effect. Our data provide proof of concept for future experiments testing the potential of intranasal application of insulin to ameliorate defective homeostatic control in patients with type 2 diabetes

Design requirements of upper extremity supports for daily use in Duchenne muscular dystrophy with severe muscle weakness

BackgroundPeople with Duchenne muscular dystrophy (DMD) cope with progressive muscular weakness and consequential upper extremity function loss. They benefit from arm supports, or arm exoskeletons, to assist arm function. Especially for severe muscle weakness (DMD &gt;= Brooke Scale 4), the design of such arm support is challenging. This study aims to structurally develop functional and technical design requirements of arm supports for people with DMD Brooke Scale 4.MethodsAn overview of clinical characteristics and a classification of clinically meaningful activities were derived from data from the Dutch Dystrophinopathy Database and available literature. Based on these, functional and technical design requirements of arm supports were developed and matched to the achievable needs of the user.ResultsFirst, the clinical characteristics of the target population, such as strength, range of motion, and functional ability, are given. Next, clinically relevant activities of daily living are translated to functional requirements categorised in a 'must,' 'should,' and 'could' category. Last, the technical requirements to realise these functional goals are presented.ConclusionsThe recommendations following from the functional user needs, technical requirements, and safety considerations can be used to make the development of assistive arm supports for people with DMD Brooke Scale 4 more user-centred