Motor imagery of speech:the involvement of primary motor cortex in manual and articulatory motor imagery

Motor imagery refers to the phenomenon of imagining performing an action without action execution. Motor imagery and motor execution are assumed to share a similar underlying neural system that involves primary motor cortex (M1). Previous studies have focused on motor imagery of manual actions, but articulatory motor imagery has not been investigated. In this study, transcranial magnetic stimulation (TMS) was used to elicit motor-evoked potentials (MEPs) from the articulatory muscles [orbicularis oris (OO)] as well as from hand muscles [first dorsal interosseous (FDI)]. Twenty participants were asked to execute or imagine performing a simple squeezing task involving a pair of tweezers, which was comparable across both effectors. MEPs were elicited at six time points (50, 150, 250, 350, 450, 550 ms post-stimulus) to track the time course of M1 involvement in both lip and hand tasks. The results showed increased MEP amplitudes for action execution compared to rest for both effectors at time points 350, 450 and 550 ms, but we found no evidence of increased cortical activation for motor imagery. The results indicate that motor imagery does not involve M1 for simple tasks for manual or articulatory muscles. The results have implications for models of mental imagery of simple articulatory gestures, in that no evidence is found for somatotopic activation of lip muscles in sub-phonemic contexts during motor imagery of such tasks, suggesting that motor simulation of relatively simple actions does not involve M1

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

A programme for risk assessment and minimisation of progressive multifocal leukoencephalopathy developed for vedolizumab clinical trials

Introduction Over the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment. No single standard for such risk minimisation exists. Vedolizumab is a recently developed monoclonal antibody to α4β7 integrin. Its clinical development necessitated a dedicated PML risk minimisation assessment as part of a global preapproval regulatory requirement. Objective The aim of this study was to describe the multiple risk minimisation elements that were incorporated in vedolizumab clinical trials in inflammatory bowel disease patients as part of the risk assessment and minimisation of PML programme for vedolizumab. Methods A case evaluation algorithm was developed for sequential screening and diagnostic evaluation of subjects who met criteria that indicated a clinical suspicion of PML. An Independent Adjudication Committee provided an independent, unbiased opinion regarding the likelihood of PML. Results Although no cases were detected, all suspected PML events were thoroughly reviewed and successfully adjudicated, making it unlikely that cases were missed. Conclusion We suggest that this programme could serve as a model for pragmatic screening for PML during the clinical development of new drugs

Event-Driven User-Centric Middleware for Energy Efficient Buildings and Public Spaces

In this work, the design of an event-driven user-centric middleware for monitoring and managing energy consumption in public buildings and spaces is presented. The main purpose is to increase the energy efficiency, reducing consumption, in buildings and public spaces. To achieve this, the proposed service-oriented middleware has been designed to be event based, also exploiting the user behaviours patterns of the people who live and work into the building. Furthermore, it allows an easy integration of heterogeneous technologies in order to enable a hardware independent interoperability between them. Moreover, a Heating Ventilation and Air Conditioning (HVAC) control strategy has been developed and the whole infrastructure has been deployed in a real-world case study consisting of a historical building. Finally the results will be presented and discusse

Viability and Application of Mounting Personal PID VOC Sensors to Small Unmanned Aircraft Systems

Using a UAS-mounted sensor to allow for a rapid response to areas that may be difficult to reach or potentially dangerous to human health can increase the situational awareness of first responders of an aircraft crash site through the remote detection, identification, and quantification of airborne hazardous materials. The primary purpose of this research was to evaluate the remote sensing viability and application of integrating existing commercial-off-the-shelf (COTS) sensors with small unmanned aircraft system (UAS) technology to detect potentially hazardous airborne contaminants in emergency leak or spill response situations. By mounting the personal photoionization detector (PID) with volatile organic compound VOC sensor technology on UAS platforms, the needed information may be obtained at an optimum range and resolution without needlessly exposing a human to possible adverse conditions

The role of hearing ability and speech distortion in the facilitation of articulatory motor cortex

Excitability of articulatory motor cortex is facilitated when listening to speech in challenging conditions. Beyond this, however, we have little knowledge of what listener-specific and speech-specific factors engage articulatory facilitation during speech perception. For example, it is unknown whether speech motor activity is independent or dependent on the form of distortion in the speech signal. It is also unknown if speech motor facilitation is moderated by hearing ability. We investigated these questions in two experiments. We applied transcranial magnetic stimulation (TMS) to the lip area of primary motor cortex (M1) in young, normally hearing participants to test if lip M1 is sensitive to the quality (Experiment 1) or quantity (Experiment 2) of distortion in the speech signal, and if lip M1 facilitation relates to the hearing ability of the listener. Experiment 1 found that lip motor evoked potentials (MEPs) were larger during perception of motor-distorted speech that had been produced using a tongue depressor, and during perception of speech presented in background noise, relative to natural speech in quiet. Experiment 2 did not find evidence of motor system facilitation when speech was presented in noise at signal-to-noise ratios where speech intelligibility was at 50% or 75%, which were significantly less severe noise levels than used in Experiment 1. However, there was a significant interaction between noise condition and hearing ability, which indicated that when speech stimuli were correctly classified at 50%, speech motor facilitation was observed in individuals with better hearing, whereas individuals with relatively worse but still normal hearing showed more activation during perception of clear speech. These findings indicate that the motor system may be sensitive to the quantity, but not quality, of degradation in the speech signal. Data support the notion that motor cortex complements auditory cortex during speech perception, and point to a role for the motor cortex in compensating for differences in hearing ability

There is more to accommodation of the eye than simply minimizing retinal blur.

Eyes of children and young adults change their optical power to focus nearby objects at the retina. But does accommodation function by trial and error to minimize blur and maximize contrast as is generally accepted? Three experiments in monocular and monochromatic vision were performed under two conditions while aberrations were being corrected. In the first condition, feedback was available to the eye from both optical vergence and optical blur. In the second, feedback was only available from target blur. Accommodation was less precise for the second condition, suggesting that it is more than a trial-and-error function. Optical vergence itself seems to be an important cue for accommodation

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

Disrupting the DREAM transcriptional repressor complex induces apolipoprotein overexpression and systemic amyloidosis in mice

DREAM (Dp, Rb-like, E2F, and MuvB) is a transcriptional repressor complex that regulates cell proliferation, and its loss causes neonatal lethality in mice. To investigate DREAM function in adult mice, we used an assembly-defective p107 protein and conditional deletion of its redundant family member p130. In the absence of DREAM assembly, mice displayed shortened survival characterized by systemic amyloidosis but no evidence of excessive cellular proliferation. Amyloid deposits were found in the heart, liver, spleen, and kidneys but not the brain or bone marrow. Using laser-capture microdissection followed by mass spectrometry, we identified apolipoproteins as the most abundant components of amyloids. Intriguingly, apoA-IV was the most detected amyloidogenic protein in amyloid deposits, suggesting apoA-IV amyloidosis (AApoAIV). AApoAIV is a recently described form, whereby WT apoA-IV has been shown to predominate in amyloid plaques. We determined by ChIP that DREAM directly regulated Apoa4 and that the histone variant H2AZ was reduced from the Apoa4 gene body in DREAM\u27s absence, leading to overexpression. Collectively, we describe a mechanism by which epigenetic misregulation causes apolipoprotein overexpression and amyloidosis, potentially explaining the origins of nongenetic amyloid subtypes