Explore the vast range of titles available.

An understanding of the relationship between changes in neural activity and the accompanying hemodynamic response is crucial for accurate interpretation of functional brain imaging data and in particular the blood oxygen level-dependent (BOLD) fMRI signal. Much physiological research investigating this topic uses anesthetized animal preparations, and yet, the effects of anesthesia upon the neural and hemodynamic responses measured in such studies are not well understood. In this study, we electrically stimulated the whisker pad of both awake and urethane anesthetized rats at frequencies of 1–40 Hz. Evoked field potential responses were recorded using electrodes implanted into the contralateral barrel cortex. Changes in hemoglobin oxygenation and concentration were measured using optical imaging spectroscopy, and cerebral blood flow changes were measured using laser Doppler flowmetry. A linear neural–hemodynamic coupling relationship was found in the awake but not the anesthetized animal preparation. Over the range of stimulation conditions studied, hemodynamic response magnitude increased monotonically with summed neural activity in awake, but not in anesthetized, animals. Additionally, the temporal structure of the hemodynamic response function was different in awake compared to anesthetized animals. The responses in each case were well approximated by gamma variates, but these were different in terms of mean latency (approximately 2 s awake; 4 s anesthetized) and width (approximately 0.6 s awake; 2.5 s anesthetized). These findings have important implications for research into the intrinsic signals that underpin BOLD fMRI and for biophysical models of cortical hemodynamics and neural–hemodynamic coupling.

ObjectiveTo characterise the self-isolating household units (bubbles) during the COVID-19 Alert Level 4 lockdown in New Zealand.Design, setting and participantsIn this cross-sectional study, an online survey was distributed to a convenience sample via Facebook advertising and the Medical Research Institute of New Zealand’s social media platforms and mailing list. Respondents were able to share a link to the survey via their own social media platforms and by email. Results were collected over 6 days during Alert Level 4 from respondents living in New Zealand, aged 16 years and over.Main outcomes measuresThe primary outcome was the mean size of a self-isolating household unit or bubble. Secondary outcomes included the mean number of households in each bubble, the proportion of bubbles containing essential workers and/or vulnerable people, and the mean number of times the home was left each week.Results14 876 surveys were included in the analysis. The mean (SD) bubble size was 3.58 (4.63) people, with mean (SD) number of households 1.26 (0.77). The proportion of bubbles containing one or more essential workers, or one or more vulnerable persons was 45.3% and 42.1%, respectively. The mean number of times individual bubble members left their home in the previous week was 12.9 (12.4). Bubbles that contained at least one vulnerable individual had fewer outings over the previous week compared with bubbles that did not contain a vulnerable person. The bubble sizes were similar by respondent ethnicity.ConclusionIn this New Zealand convenience sample, bubble sizes were small, mostly limited to one household, and a high proportion contained essential workers and/or vulnerable people. Understanding these characteristics from a country which achieved a low COVID-19 infection rate may help inform public health interventions during this and future pandemics.

Unexpected, biologically salient stimuli elicit a short-latency, phasic response in midbrain dopaminergic (DA) neurons. Although this signal is important for reinforcement learning, the information it conveys to forebrain target structures remains uncertain. One way to decode the phasic DA signal would be to determine the perceptual properties of sensory inputs to DA neurons. After local disinhibition of the superior colliculus in anesthetized rats, DA neurons became visually responsive, whereas disinhibition of the visual cortex was ineffective. As the primary source of visual afferents, the limited processing capacities of the colliculus may constrain the visual information content of phasic DA responses.

The relationship between neural activity and accompanying changes in cerebral blood flow (CBF) and oxygenation must be fully understood before data from brain imaging techniques can be correctly interpreted. Whether signals in fMRI reflect the neural input or output of an activated region is still unclear. Similarly, quantitative relationships between neural activity and changes in CBF are not well understood. The present study addresses these issues by using simultaneous laser Doppler flowmetry (LDF) to measure CBF and multichannel electrophysiology to record neural activity in the form of field potentials and multiunit spiking. We demonstrate that CBF-activation coupling is a nonlinear inverse sigmoid function. Comparing the data with previous work suggests that within a cortical model, CBF shows greatest spatial correlation with a current sink 500 μm below the surface corresponding to sensory input. These results show that care must be exercised when interpreting imaging data elicited by particularly strong or weak stimuli and that hemodynamic changes may better reflect the input to a region rather than its spiking output.

BackgroundIn randomised controlled trials, as-needed inhaled corticosteroid (ICS)-formoterol reliever therapy reduces severe exacerbation risk compared with maintenance ICS plus short-acting beta2-agonist (SABA) reliever in adolescent and adult asthma, but results in slightly worse control of asthma symptoms, as measured by mean Asthma Control Questionnaire-5 (ACQ-5) score.ObjectiveTo assess the levels and changes in asthma control for as-needed budesonide–formoterol versus maintenance budesonide plus SABA in post hoc analyses from the Novel START and PRACTICAL clinical trials.MethodsThe number and proportion of participants at study end in each ACQ-5 category (‘well-controlled’, ‘partly controlled’ or ‘inadequately controlled’ symptoms), and in each responder category based on the minimal clinically important difference for ACQ-5 of 0.5 (improved, no change and worse) with as-needed budesonide–formoterol and maintenance budesonide plus SABA treatment were calculated.ResultsWith last observation carried forwards, 189/214 (88.3%) and 354/434 (81.6%) of patients in the budesonide–formoterol group had ‘well-controlled’ or ‘partly controlled’ symptoms at the end of the study, vs 183/214 (85.5%) and 358/431 (83.1%) in the budesonide maintenance group, for Novel START and PRACTICAL, respectively. The proportion of patients whose symptom control was either improved or unchanged from baseline was 190/214 (88.8%) and 368/434 (84.8%) for budesonide–formoterol, vs 185/214 (86.4%) and 376/431 (87.2%) for maintenance budesonide, in Novel START and PRACTICAL respectively.ConclusionsThere were no clinically important differences in the proportions of patients with ‘well-controlled’ or ‘partly controlled’ asthma symptoms, or proportions who improved or maintained their level of control, with as-needed budesonide–formoterol versus maintenance budesonide plus SABA.

An essential prerequisite for the accurate interpretation of noninvasive functional brain imaging techniques, such as blood oxygen level dependent (BOLD) fMRI, is a thorough understanding of the coupling relationship between neural activity and the haemodynamic response. The current study investigates this relationship using rat barrel cortex as a model. Neural input was measured by applying current source density (CSD) analysis to multi-laminar field potentials to remove ambiguities regarding the origin of the signal inherent in single electrode recordings. Changes in cerebral blood flow (CBF) were recorded with a laser Doppler flowmetry probe. The magnitude of neural and CBF responses were modulated over a large range by altering both the intensity and frequency of electrical whisker pad stimulation. Consistent with previous findings [Devor, A., et al., 2003. Neuron 39, 353–359; Sheth, S.A., et al., 2004. Neuron 42, 347–355] a power law function well described the relationship between neural activity and haemodynamics. Despite the nonlinearity of the coupling over the whole data set, the relationship was very well approximated by a linear function over mid-range stimuli. Altering the frequency of stimulation at 1.2 mA shifted the neural activity and corresponding haemodynamic response along this linear region, reconciling recent reports of a nonlinear relationship [Devor, A., et al., 2003. Neuron 39, 353–359; Jones, M., et al., 2004. NeuroImage 22, 956–965; Sheth, S.A., et al., 2004. Neuron 42, 347–355] with previous work that found a linear coupling relationship when altering stimulation frequency [Martindale, J., et al., 2003. J. Cereb. Blood Flow Metab. 23, 546–555; Ngai, A.C., et al., 1999. Brain Res. 837, 221–228; Sheth, S., et al., 2003. NeuroImage 19, 884–894]. Using stimuli within this linear range in imaging studies would simplify the interpretation of findings.

This article investigates the relation between stimulus-evoked neural activity and cerebral hemodynamics. Specifically, the hypothesis is tested that hemodynamic responses can be modeled as a linear convolution of experimentally obtained measures of neural activity with a suitable hemodynamic impulse response function. To obtain a range of neural and hemodynamic responses, rat whisker pad was stimulated using brief (≤2 seconds) electrical stimuli consisting of single pulses (0.3 millisecond, 1.2 mA) combined both at different frequencies and in a paired-pulse design. Hemodynamic responses were measured using concurrent optical imaging spectroscopy and laser Doppler flowmetry, whereas neural responses were assessed through current source density analysis of multielectrode recordings from a single barrel. General linear modeling was used to deconvolve the hemodynamic impulse response to a single “neural event” from the hemodynamic and neural responses to stimulation. The model provided an excellent fit to the empirical data. The implications of these results for modeling schemes and for physiologic systems coupling neural and hemodynamic activity are discussed.

The temporal relationship between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is important in the biophysical modeling and interpretation of the hemodynamic response to activation, particularly in the context of magnetic resonance imaging and the blood oxygen level–dependent signal. Grubb et al. (1974) measured the steady state relationship between changes in CBV and CBF after hypercapnic challenge. The relationship CBVαCBFΦ has been used extensively in the literature. Two similar models, the Balloon (Buxton et al., 1998) and the Windkessel (Mandeville et al., 1999), have been proposed to describe the temporal dynamics of changes in CBV with respect to changes in CBF. In this study, a dynamic model extending the Windkessel model by incorporating delayed compliance is presented. The extended model is better able to capture the dynamics of CBV changes after changes in CBF, particularly in the return-to-baseline stages of the response.

In adults with mild asthma, a combination of an inhaled corticosteroid with a fast-onset long-acting β-agonist (LABA) used as reliever monotherapy reduces severe exacerbations compared with short-acting β-agonist (SABA) reliever therapy. We investigated the efficacy of combination budesonide–formoterol reliever therapy compared with maintenance budesonide plus as-needed terbutaline. We did a 52-week, open-label, parallel-group, multicentre, superiority, randomised controlled trial at 15 primary care or hospital-based clinical trials units and primary care practices in New Zealand. Participants were adults aged 18–75 years with a self-reported doctor's diagnosis of asthma who were using SABA for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids in the previous 12 weeks. We randomly assigned participants (1:1) to either reliever therapy with budesonide 200 μg–formoterol 6 μg Turbuhaler (one inhalation as needed for relief of symptoms) or maintenance budesonide 200 μg Turbuhaler (one inhalation twice daily) plus terbutaline 250 μg Turbuhaler (two inhalations as needed). Participants and investigators were not masked to group assignment; the statistician was masked for analysis of the primary outcome. Six study visits were scheduled: randomisation, and weeks 4, 16, 28, 40, and 52. The primary outcome was the number of severe exacerbations per patient per year analysed by intention to treat (severe exacerbations defined as use of systemic corticosteroids for at least 3 days because of asthma, or admission to hospital or an emergency department visit because of asthma requiring systemic corticosteroids). Safety analyses included all participants who had received at least one dose of study treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616000377437. Between May 4, 2016, and Dec 22, 2017, we assigned 890 participants to treatment and included 885 eligible participants in the analysis: 437 assigned to budesonide–formoterol as needed and 448 to budesonide maintenance plus terbutaline as needed. Severe exacerbations per patient per year were lower with as-needed budesonide–formoterol than with maintenance budesonide plus terbutaline as needed (absolute rate per patient per year 0·119 vs 0·172; relative rate 0·69, 95% CI 0·48–1·00; p=0·049). Nasopharyngitis was the most common adverse event in both groups, occurring in 154 (35%) of 440 patients receiving as-needed budesonide–formoterol and 144 (32%) of 448 receiving maintenance budesonide plus terbutaline as needed. In adults with mild to moderate asthma, budesonide–formoterol used as needed for symptom relief was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline. The findings support the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid–formoterol reliever therapy is an alternative regimen to daily low-dose inhaled corticosteroid for patients with mild asthma. Health Research Council of New Zealand.

Recent studies have shown that the haemodynamic responses to brief (<2 secs) stimuli can be well characterised as a linear convolution of neural activity with a suitable haemodynamic impulse response. In this paper, we show that the linear convolution model cannot predict measurements of blood flow responses to stimuli of longer duration (>2 secs), regardless of the impulse response function chosen. Modifying the linear convolution scheme to a nonlinear convolution scheme was found to provide a good prediction of the observed data. Whereas several studies have found a nonlinear coupling between stimulus input and blood flow responses, the current modelling scheme uses neural activity as an input, and thus implies nonlinearity in the coupling between neural activity and blood flow responses. Neural activity was assessed by current source density analysis of depth-resolved evoked field potentials, while blood flow responses were measured using laser Doppler flowmetry. All measurements were made in rat whisker barrel cortex after electrical stimulation of the whisker pad for 1 to 16 secs at 5 Hz and 1.2 mA (individual pulse width 0.3 ms).