Frontal Non-Invasive Neurostimulation Modulates Antisaccade Preparation in Non-Human Primates

A combination of oculometric measurements, invasive electrophysiological recordings and microstimulation have proven instrumental to study the role of the Frontal Eye Field (FEF) in saccadic activity. We hereby gauged the ability of a non-invasive neurostimulation technology, Transcranial Magnetic Stimulation (TMS), to causally interfere with frontal activity in two macaque rhesus monkeys trained to perform a saccadic antisaccade task. We show that online single pulse TMS significantly modulated antisaccade latencies. Such effects proved dependent on TMS site (effects on FEF but not on an actively stimulated control site), TMS modality (present under active but not sham TMS on the FEF area), TMS intensity (intensities of at least 40% of the TMS machine maximal output required), TMS timing (more robust for pulses delivered at 150 ms than at 100 post target onset) and visual hemifield (relative latency decreases mainly for ipsilateral AS). Our results demonstrate the feasibility of using TMS to causally modulate antisaccade-associated computations in the non-human primate brain and support the use of this approach in monkeys to study brain function and its non-invasive neuromodulation for exploratory and therapeutic purposes

Multisensory visual–tactile object related network in humans: insights gained using a novel crossmodal adaptation approach

Neuroimaging techniques have provided ample evidence for multisensory integration in humans. However, it is not clear whether this integration occurs at the neuronal level or whether it reflects areal convergence without such integration. To examine this issue as regards visuo-tactile object integration we used the repetition suppression effect, also known as the fMRI-based adaptation paradigm (fMR-A). Under some assumptions, fMR-A can tag specific neuronal populations within an area and investigate their characteristics. This technique has been used extensively in unisensory studies. Here we applied it for the first time to study multisensory integration and identified a network of occipital (LOtv and calcarine sulcus), parietal (aIPS), and prefrontal (precentral sulcus and the insula) areas all showing a clear crossmodal repetition suppression effect. These results provide a crucial first insight into the neuronal basis of visuo-haptic integration of objects in humans and highlight the power of using fMR-A to study multisensory integration using non-invasinve neuroimaging techniques

Visual area V5/hMT+ contributes to perception of tactile motion direction: a TMS study

Human imaging studies have reported activations associated with tactile motion perception in visual motion area V5/hMT+, primary somatosensory cortex (SI) and posterior parietal cortex (PPC; Brodmann areas 7/40). However, such studies cannot establish whether these areas are causally involved in tactile motion perception. We delivered double-pulse transcranial magnetic stimulation (TMS) while moving a single tactile point across the fingertip, and used signal detection theory to quantify perceptual sensitivity to motion direction. TMS over both SI and V5/hMT+, but not the PPC site, significantly reduced tactile direction discrimination. Our results show that V5/hMT+ plays a causal role in tactile direction processing, and strengthen the case for V5/hMT+ serving multimodal motion perception. Further, our findings are consistent with a serial model of cortical tactile processing, in which higher-order perceptual processing depends upon information received from SI. By contrast, our results do not provide clear evidence that the PPC site we targeted (Brodmann areas 7/40) contributes to tactile direction perception

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402