The causal role of left and right superior temporal gyri in speech perception in noise : A Transcranial Magnetic Stimulation Study

Successful perception of speech in everyday listening conditions requires effective listening strategies to overcome common acoustic distortions, such as background noise. Convergent evidence from neuroimaging and clinical studies identify activation within the temporal lobes as key to successful speech perception. However, current neurobiological models disagree on whether the left temporal lobe is sufficient for successful speech perception or whether bilateral processing is required. We addressed this issue using TMS to selectively disrupt processing in either the left or right superior temporal gyrus (STG) of healthy participants to test whether the left temporal lobe is sufficient or whether both left and right STG are essential. Participants repeated keywords from sentences presented in background noise in a speech reception threshold task while receiving online repetitive TMS separately to the left STG, right STG, or vertex or while receiving no TMS. Results show an equal drop in performance following application of TMS to either left or right STG during the task. A separate group of participants performed a visual discrimination threshold task to control for the confounding side effects of TMS. Results show no effect of TMS on the control task, supporting the notion that the results of Experiment 1 can be attributed to modulation of cortical functioning in STG rather than to side effects associated with online TMS. These results indicate that successful speech perception in everyday listening conditions requires both left and right STG and thus have ramifications for our understanding of the neural organization of spoken language processing

Transcranial magnetic stimulation and motor evoked potentials in speech perception research

Transcranial magnetic stimulation (TMS) has been employed to manipulate brain activity and to establish cortical excitability by eliciting motor evoked potentials (MEPs) in speech processing research. We will discuss the history, methodological underpinnings, key contributions, and future directions for studying speech processing using TMS and by eliciting MEPs. Furthermore, we will discuss specific challenges that are encountered when examining speech processing using TMS or by measuring MEPs. We suggest that future research may benefit from using TMS in conjunction with neuroimaging methods such as functional Magnetic Resonance Imaging or electroencephalography, and from the development of new stimulation protocols addressing cortico-cortical inhibition/facilitation and interhemispheric connectivity during speech processing

Modulation of intra- and inter-hemispheric connectivity between primary and premotor cortex during speech perception

Primary motor (M1) areas for speech production activate during speech perception. It has been suggested that such activation may be dependent upon modulatory inputs from premotor cortex (PMv). If and how PMv differentially modulates M1 activity during perception of speech that is easy or challenging to understand, however, is unclear. This study aimed to test the link between PMv and M1 during challenging speech perception in two experiments. The first experiment investigated intra-hemispheric connectivity between left hemisphere PMv and left M1 lip area during comprehension of speech under clear and distorted listening conditions. Continuous theta burst stimulation (cTBS) was applied to left PMv in eighteen participants (aged 18–35). Post-cTBS, participants performed a sentence verification task on distorted (imprecisely articulated), and clear speech, whilst also undergoing stimulation of the lip representation in the left M1 to elicit motor evoked potentials (MEPs). In a second, separate experiment, we investigated the role of inter-hemispheric connectivity between right hemisphere PMv and left hemisphere M1 lip area. Dual-coil transcranial magnetic stimulation was applied to right PMv and left M1 lip in fifteen participants (aged 18–35). Results indicated that disruption of PMv during speech perception affects comprehension of distorted speech specifically. Furthermore, our data suggest that listening to distorted speech modulates the balance of intra- and inter-hemispheric interactions, with a larger sensorimotor network implicated during comprehension of distorted speech than when speech perception is optimal. The present results further understanding of PMv-M1 interactions during auditory-motor integration

On Machine-Learned Classification of Variable Stars with Sparse and Noisy Time-Series Data

With the coming data deluge from synoptic surveys, there is a growing need for frameworks that can quickly and automatically produce calibrated classification probabilities for newly-observed variables based on a small number of time-series measurements. In this paper, we introduce a methodology for variable-star classification, drawing from modern machine-learning techniques. We describe how to homogenize the information gleaned from light curves by selection and computation of real-numbered metrics ("feature"), detail methods to robustly estimate periodic light-curve features, introduce tree-ensemble methods for accurate variable star classification, and show how to rigorously evaluate the classification results using cross validation. On a 25-class data set of 1542 well-studied variable stars, we achieve a 22.8% overall classification error using the random forest classifier; this represents a 24% improvement over the best previous classifier on these data. This methodology is effective for identifying samples of specific science classes: for pulsational variables used in Milky Way tomography we obtain a discovery efficiency of 98.2% and for eclipsing systems we find an efficiency of 99.1%, both at 95% purity. We show that the random forest (RF) classifier is superior to other machine-learned methods in terms of accuracy, speed, and relative immunity to features with no useful class information; the RF classifier can also be used to estimate the importance of each feature in classification. Additionally, we present the first astronomical use of hierarchical classification methods to incorporate a known class taxonomy in the classifier, which further reduces the catastrophic error rate to 7.8%. Excluding low-amplitude sources, our overall error rate improves to 14%, with a catastrophic error rate of 3.5%.Comment: 23 pages, 9 figure

Effects of Deletion of Macrophage ABCA7 on Lipid Metabolism and the Development of Atherosclerosis in the Presence and Absence of ABCA1

ABCA7, a close relative of ABCA1 which facilitates cholesterol efflux to lipid-poor apoproteins, has been implicated in macrophage lipid efflux and clearance of apoptotic cells in in vitro studies. In the current study, we investigated the in vivo effects of macrophage ABCA7 deficiency on lipid metabolism and atherosclerosis. Chimeras with dysfunctional ABCA7 in macrophages and other blood cells were generated by transplantation of bone marrow from ABCA7 knockout (KO) mice into irradiated low-density lipoprotein receptor (LDLr) KO mice. Unexpectedly, macrophage ABCA7 deficiency did not significantly affect atherosclerosis susceptibility of LDLr KO mice after 10 weeks Western-type diet feeding. However, ABCA7 deficiency was associated with 2-fold (p<0.05) higher macrophage ABCA1 mRNA expression levels. Combined disruption of ABCA1 and ABCA7 in bone-marrow-derived cells increased atherosclerotic lesion development (1.5-fold (p>0.05) as compared to wild type transplanted mice. However, single deletion of ABCA1 had a similar effect (1.8-fold, p<0.05). Macrophage foam cell accumulation in the peritoneal cavity was reduced in ABCA1/ABCA7 dKO transplanted animals as compared to single ABCA1 KO transplanted mice, which was associated with increased ABCG1 expression. Interestingly, spleens of ABCA1/ABCA7 double KO transplanted mice were significantly larger as compared to the other 3 groups and showed massive macrophage lipid accumulation, a reduction in CD3+ T-cells, and increased expression of key regulators of erythropoiesis. In conclusion, deletion of ABCA7 in bone marrow-derived cells does not affect atherogenesis in the arterial wall neither in the absence or presence of ABCA1. Interestingly, combined deletion of bone marrow ABCA1 and ABCA7 causes severe splenomegaly associated with cellular lipid accumulation, a reduction in splenic CD3+ T cells, and induced markers of erythropoeisis. Our data indicate that ABCA7 may play a role in T cell proliferation and erythropoeisis in spleen

Which method is best for the induction of labour?: A systematic review, network meta-analysis and cost-effectiveness analysis

Background: More than 150,000 pregnant women in England and Wales have their labour induced each year. Multiple pharmacological, mechanical and complementary methods are available to induce labour. Objective: To assess the relative effectiveness, safety and cost-effectiveness of labour induction methods and, data permitting, effects in different clinical subgroups. Methods: We carried out a systematic review using Cochrane methods. The Cochrane Pregnancy and Childbirth Group’s Trials Register was searched (March 2014). This contains over 22,000 reports of controlled trials (published from 1923 onwards) retrieved from weekly searches of OVID MEDLINE (1966 to current); Cochrane Central Register of Controlled Trials (The Cochrane Library); EMBASE (1982 to current); Cumulative Index to Nursing and Allied Health Literature (1984 to current); ClinicalTrials.gov; the World Health Organization International Clinical Trials Registry Portal; and hand-searching of relevant conference proceedings and journals. We included randomised controlled trials examining interventions to induce labour compared with placebo, no treatment or other interventions in women eligible for third-trimester induction. We included outcomes relating to efficacy, safety and acceptability to women. In addition, for the economic analysis we searched the Database of Abstracts of Reviews of Effects, and Economic Evaluations Databases, NHS Economic Evaluation Database and the Health Technology Assessment database. We carried out a network meta-analysis (NMA) using all of the available evidence, both direct and indirect, to produce estimates of the relative effects of each treatment compared with others in a network. We developed a de novo decision tree model to estimate the cost-effectiveness of various methods. The costs included were the intervention and other hospital costs incurred (price year 2012–13). We reviewed the literature to identify preference-based utilities for the health-related outcomes in the model. We calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit. We represent uncertainty in the optimal intervention using cost-effectiveness acceptability curves. Results: We identified 1190 studies; 611 were eligible for inclusion. The interventions most likely to achieve vaginal delivery (VD) within 24 hours were intravenous oxytocin with amniotomy [posterior rank 2; 95% credible intervals (CrIs) 1 to 9] and higher-dose (≥ 50 μg) vaginal misoprostol (rank 3; 95% CrI 1 to 6). Compared with placebo, several treatments reduced the odds of caesarean section, but we observed considerable uncertainty in treatment rankings. For uterine hyperstimulation, double-balloon catheter had the highest probability of being among the best three treatments, whereas vaginal misoprostol (≥ 50 μg) was most likely to increase the odds of excessive uterine activity. For other safety outcomes there were insufficient data or there was too much uncertainty to identify which treatments performed ‘best’. Few studies collected information on women’s views. Owing to incomplete reporting of the VD within 24 hours outcome, the cost-effectiveness analysis could compare only 20 interventions. The analysis suggested that most interventions have similar utility and differ mainly in cost. With a caveat of considerable uncertainty, titrated (low-dose) misoprostol solution and buccal/sublingual misoprostol had the highest likelihood of being cost-effective. Limitations: There was considerable uncertainty in findings and there were insufficient data for some planned subgroup analyses. Conclusions: Overall, misoprostol and oxytocin with amniotomy (for women with favourable cervix) is more successful than other agents in achieving VD within 24 hours. The ranking according to safety of different methods was less clear. The cost-effectiveness analysis suggested that titrated (low-dose) oral misoprostol solution resulted in the highest utility, whereas buccal/sublingual misoprostol had the lowest cost. There was a high degree of uncertainty as to the most cost-effective intervention

Neural and cognitive mechanisms affecting perceptual adaptation to distorted speech

The majority of everyday communication occurs in the presence of distortions, such as background noise, yet the human ability to understand speech in adverse listening conditions is remarkably robust. Past research has investigated perceptual adaptation to different speech conditions, however, our knowledge of the individual differences and the associated cognitive and neural mechanisms affecting perceptual adaptation is still limited. The work described in this thesis therefore aimed to advance our understanding of this research area, with specific focus first on determining the extent to which adaptation to one distortion generalises to another, second, determining the underlying cognitive mechanisms of this adaptation process and finally determining what role, if any, the left ventral premotor cortex plays in adaptation. This thesis presents results from eight experiments, two behavioural and six using Transcranial Magnetic Stimulation (TMS) as the primary research tool. Results from experiments 1 and 2 (behavioural) show that measures of verbal intelligence, specifically vocabulary knowledge, working memory and general cognitive functioning underpin the perceptual learning process, providing support for statistical learning to occur and assist adaptation to distorted speech. Additionally, the results suggest participants possess a general skill that enables generalisation of learning from one adverse listening condition to another. Experiments 3 to 8 used TMS to modulate perception of speech in noise in a bilateral superior temporal region. However, no effect of using this protocol was found when applied to the left ventral premotor cortex whilst participants adapted to time-compressed speech. The results of the experiments described in this thesis are considered in the context of our current understanding of the cognitive and neural mechanisms associated with perceptual adaptation to distorted speech. It is believed that the results will contribute significantly to existing knowledge due to use of novel research methodologies e.g., use of multiple distortions, multiple speakers and TMS

Neural bases of accented speech perception

The recognition of unfamiliar regional and foreign accents represents a challenging task for the speech perception system (Floccia et al., 2006; Adank et al., 2009). Despite the frequency with which we encounter such accents, the neural mechanisms supporting successful perception of accented speech are poorly understood. Nonetheless, candidate neural substrates involved in processing speech in challenging listening conditions, including accented speech, are beginning to be identified. This review will outline neural bases associated with perception of accented speech in the light of current models of speech perception, and compare these data to brain areas associated with processing other speech distortions. We will subsequently evaluate competing models of speech processing with regards to neural processing of accented speech. See Cristia et al. (2012) for an in-depth overview of behavioral aspects of accent processing

Effects of coil orientation on Motor Evoked Potentials from Orbicularis Oris

This study aimed to characterise effects of coil orientation on the size of Motor Evoked Potentials (MEPs) from both sides of Orbicularis Oris (OO) and both First Dorsal Interosseous (FDI) muscles, following stimulation to left lip and left hand Primary Motor Cortex. Using a 70mm figure-of-eight coil, we collected MEPs from eight different orientations while recording from contralateral and ipsilateral OO and FDI using a monophasic pulse delivered at 120% active motor threshold. MEPs from OO were evoked consistently for six orientations for contralateral and ipsilateral sites. Contralateral orientations 0°, 45°, 90°, and 315° were found to best elicit OO MEPs with a likely cortical origin. The largest FDI MEPs were recorded for contralateral 45°, invoking a posterior–anterior (PA) current flow. Orientations traditionally used for FDI were also found to be suitable for eliciting OO MEPs. Individuals vary more in their optimal orientation for OO than for FDI. It is recommended that researchers iteratively probe several orientations when eliciting MEPs from OO. Several orientations likely induced direct activation of facial muscles