READY, STEADY, AND GO. A Transcranial Magnetic Stimulation Study of Set-Related Inhibitory Activity in the Human Dorsal Precentral Region

Successfully acting largely depends on moving at the right time. Consider a member of an orchestra just few instants before starting to play her piece. She should be ready not only to launch the planned movements when appropriate, but also to stop them if required. Action initiation and control are characteristic features of many of our daily life actions. There is a large amount of evidence in monkeys and humans suggesting that the dorsal premotor cortex (PMD) and the supplementary motor areas (SMA) might be critically involved in these features. However, the distinctive role of these areas is still matter of controversy. The aim of the present thesis is to provide some preliminary steps toward a comprehension of whether and how the human dorsal precentral areas may selectively contribute to action initiation and control. In doing this we shall introduce and discuss a series of transcranial magnetic stimulation (TMS) experiments carried out with two different paradigms, namely dual-coil TMS and single pulse TMS paradigm. These experiments were primarily devoted to explore the structural and functional properties of PMD. They also allowed us to assess whether PMD and SMA may be differentially and selectively involved in action control. In more detail, we first investigated the structural connectivity between PMD and the ipsilateral orofacial M1, introducing a novel dual-coil TMS approach. Results displayed the existence of short-latency influences of the left PMD on the ipsilateral orofacial M1, measured by recording motor evoked potentials (MEPs) in the orofacial muscles. Then, taking advantage of this novel approach, we started to explore the functional PMD-M1 connectivity. We tested the short-latency effects of TMS, as measured by changes in orofacial MEPs, during a delayed motor task. The results showed an inhibitory activity in the PMD-M1 module during the SET-period. We also manipulated the duration of the SET-period, to establish whether the effects were time-locked to the start of the delay period or rather time-locked to the predicted GO-signal. Hence, the investigation of the PMD-M1 connectivity paved us the way to explore, first, the role of PMD in initiating action and, then, the differential role of PMD and SMA in controlling and inhibiting action. Indeed, we run a further study, in which we carried out two single pulse TMS experiments. We first stimulated PMD during a stop-signal task, then we contrasted the PMD stimulation with SMA stimulation when participants underwent the same stop-signal task. There are five chapters to come. In Chapter 1 we shall review some key studies exploring anatomical and functional properties of PMD and SMA in both monkeys and humans, with particular emphasis on their putative role in action initiation and control. In Chapter 2 we shall focus on the methodological aspects of our experimental studies. In particular, we shall introduce the so-called twin- or dual-coil TMS paradigm, discuss its main approaches present in the literature and propose a variant of them. In Chapter 3 we shall present and discuss our first dual-coil TMS study exploring, for the first time, the ipsilateral PMD-corticofacial system connectivity. In Chapter 4 we shall examine three dual-coil TMS studies investigating the functional connectivity between PMD and ipsilateral M1 during a motor delayed task. Finally, in Chapter 5 we shall scrutinize two single pulse TMS studies capitalizing on a stop-signal task in order to assess the role of PMD and SMA in action control. Results and future lines of research will be sketched in the Concluding remarks

Two Models of Mind Blanking

Mind blanking is a mental state in which attention does not bring any perceptual input into conscious awareness. As this state is still largely unexplored, we suggest that a comprehensive understanding of mind blanking can be achieved through a multifaceted approach combining self-assessment methods, neuroimaging, and neuromodulation. In this article, we explain how EEG and TMS could be combined to help determine whether mind blanking is associated with a lack of mental content or a lack of linguistically or conceptually determinable mental content. We also question whether mind blanking occurs spontaneously or intentionally and whether these two forms are instantiated by the same or different neural correlates

Multichannel remote polarization control enabled by nanostructured Liquid Crystalline Networks

In this article we demonstrate that a grating fabricated through nanoscale volumetric crosslinking of a liquid crystalline polymer enables remote polarization control over the diffracted channels. This functionality is a consequence of the responsivity of liquid crystal networks upon light stimuli. Tuning the photonic response of the device is obtained thanks to both a refractive index and a shape change of the grating elements induced by a molecular rearrangement under irradiation. In particular, the material anisotropy allows for nontrivial polarization state management over multiple beams. Absence of any liquid component and a time response down to 0.2 milliseconds make our device appealing in the fields of polarimetry and optical communications.Comment: 16 pages,8 figures, featured article in AL

Antimicrobial activity of a standardized medical honey on bacterial isolates from infected skin lesions of non-traditional companion animals

: In recent years, due to the growing phenomenon of antimicrobial resistance, the search for alternative strategies to antibiotic treatments is increasing and a considerable interest for the use of medical honey in clinical practice has emerged. Honey has been used for the treatment of skin lesions, in both humans and animals. However, knowledge concerning the use of medical honey in non‑traditional companion animals is scarce. The aim of this study was to assess the antibacterial activity of a standardized medical honey (Revamil, BFactory) against bacterial strains isolated from skin lesions of non‑traditional companion animals. The minimum bactericidal concentration (MBC) of Revamil honey against seventeen clinical isolates and three reference strains was established.The medical honey showed antimicrobial activity against both Gram‑positive and Gram‑negative bacteria. Growth was inhibited for all the strains at concentrations of medical honey ranging from 10 to 40%. Pseudomonas oryzihabitans and Alcaligenes faecalis showed the lowest MBC (10%). The reference strain Staphylococcus aureus ATCC25923 showed a higher sensitivity to 20% honey compare to the corresponding clinical isolate (P = 0.001). The observed results suggest that Revamil could represent an effective therapeutic aid, useful for the reduction of antibiotic use, in case of pathological skin infections in non‑traditional companion animals

The prevalence of Pseudomonas aeruginosa and multidrug resistant Pseudomonas aeruginosa in healthy captive ophidian

Background Snakes are globally considered as pet animals, and millions of ophidians are bred in captivity. Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium that can act as an opportunistic pathogen of man and animals and is frequently present in the oral and cloacal microbiota of healthy ophidians. It can cause severe clinical diseases and often shows antibiotic resistance. The aim of this study was to evaluate the prevalence and antibiotic resistance profiles of P. aeruginosa isolated from the cloacal microbiota of a large population sample of healthy captive ophidians and to evaluate the statistical associations with farming conditions. Methods A total of 419 cloacal swabs were collected from snakes belonging to the Boidae (n = 45), Colubridae (n = 48) and Pythonidae (n = 326) families and inoculated onto complete culture media. Food, water and bedding samples were also analyzed. The antimicrobial susceptibility of P. aeruginosa isolates was evaluated through the Kirby-Bauer agar diffusion test. Statistical analyses were performed with the chi-square test. Results The prevalence of P. aeruginosa was 59.9%, and 35.5% of these strains were multidrug resistant (MDR). The prevalence of MDR P. aeruginosa was significantly higher in adult samples than in young samples, and widespread resistance to Cephalosporins, Polymyxins and Sulfonamides was observed. Statistically significant differences in the prevalence of P. aeruginosa were observed depending on the farm size and snake family. Feeding thawed prey was associated with a higher P. aeruginosa and MDR P. aeruginosa prevalence. Moreover, snakes fed home-raised prey had a significantly higher MDR P. aeruginosa prevalence than snakes fed commercially available feed. Less frequent terrarium cleaning was associated with a higher MDR P. aeruginosa prevalence. On the other hand, snake reproductive status was not significantly associated with P. aeruginosa or MDR P. aeruginosa prevalence. All food, water and bedding samples were negative for P. aeruginosa presence. Discussion The overall P. aeruginosa prevalence found in this study was lower than that found by other authors, but a high proportion of the isolates were MDR. This study highlighted the presence of constitutive (such as age and taxonomic family) and managerial (farm size, cleaning cycle frequency and food type) factors associated with P. aeruginosa and/or MDR P. aeruginosa prevalence. Good breeding management and proper antibiotic treatment of P. aeruginosa infections could help reduce the presence of P. aeruginosa and MDR P. aeruginosa in the gut microbiota of snakes and consequently reduce the risk to public health

Stimulation of Different Sectors of the Human Dorsal Premotor Cortex Induces a Shift from Reactive to Predictive Action Strategies and Changes in Motor Inhibition: A Dense Transcranial Magnetic Stimulation (TMS) Mapping Study

Delayed motor tasks require timely interaction between immobility and action. The neural substrates of these processes probably reside in the premotor and motor circuits; however, fine-grained anatomical/functional information is still lacking. Participants performed a delayed simple reaction task, structured as a ready-set-go sequence, with a fixed, predictable, SET-period. Responses were given with lip movements. During the SET-period, we performed a systematic dense-mapping of the bilateral dorsal premotor region (dPM) by means of single transcranial magnetic stimulation (TMS) pulses on an 18-spot mapping grid, interleaved with sham TMS which served as a baseline. Reaction times (RTs) in TMS trials over each grid spot were compared to RTs in sham trials to build a statistical parametric z-map. The results reveal a rostro-caudal functional gradient in the dPM. TMS of the rostral dPM induced a shift from reactive towards predictive response strategies. TMS of the caudal dPM interfered with the SET-period duration. By means of dense TMS mapping, we have drawn a putative functional map of the role of the dPM during the SET-period. A higher-order rostral component is involved in setting action strategies and a caudal, lower-order, part is probably involved in the inhibitory control of motor output

How motor representation shapes action experience?

<div>There is a great deal of studies showing that motor processes and representations are involved in sub-personal processing of observed actions. However, so far little research has directly explored whether our own motor system may affect the way we make experience of others’ actions. How and to what extent our motor processing of others’ actions may influence our perceptual experience of them?</div><div><p>We designed and tested a behavioural model. The protocol consist in two phases: (i) assessing the power of the tool as a good measure for apparent movement judgments (ii) manipulating  the observer’s motor system state.</p></div

The dorsal premotor cortex exerts a powerful and specific inhibitory effect on the ipsilateral corticofacial system: a dual-coil transcranial magnetic stimulation study

A rich pattern of connectivity is present in non-human primates between the dorsal premotor cortex (PMCd) and the motor cortex (M1). By analogy, similar connections are hypothesized in humans between the PMCd and the ipsilateral hand-related M1. However, the technical difficulty of applying transcranial magnetic stimulation (TMS) with a dual-coil paradigm to two cortical regions in such close spatial proximity renders their in vivo demonstration difficult. The present work aims at assessing in humans the existence of short-latency influences of the left PMCd on the ipsilateral corticofacial system by means of TMS. A dual-coil TMS paradigm was used with 16 participants. Test TMS pulses were applied to the left orofacial M1, and conditioning TMS pulses were applied to three distinct points of the ipsilateral PMCd along the caudal part of the superior frontal sulcus. The inter-stimulus interval (ISI) between condTMS and testTMS varied in 2-ms steps between 2 and 8 ms. Motor evoked potentials (MEPs) in the active orbicularis oris muscle were recorded. CondTMS exerted a robust effect on the corticofacial system only when applied to one specific portion of the PMCd and only at one specific ISI (6 ms). The effect consisted in a systematic suppression of facial MEPs compared to those obtained by testTMS alone. No other effect was found. We provide evidence for a specific short-latency inhibitory effect of the PMCd on the ipsilateral M1, likely witnessing direct corticocortical connectivity in humans. We also describe a novel paradigm to test ipsilateral PMCd-M1 in humans

Spatial and temporal characteristics of set-related inhibitory and excitatory inputs from the dorsal premotor cortex to the ipsilateral motor cortex assessed by dual-coil transcranial magnetic stimulation

The capacity to produce movements only at appropriate times is fundamental in successful behavior and requires a fine interplay between motor inhibition and facilitation. Evidence in humans indicates that the dorsal premotor cortex (PMCd) is involved in such preparatory and inhibitory processes, but how PMCd modulates motor output in humans is still unclear. We investigated this issue in healthy human volunteers, using a variant of the dual-coil transcranial magnetic stimulation (TMS) technique that allows testing the short-latency effects of conditioning TMS to the left PMCd on test TMS applied to the ipsilateral orofacial primary motor cortex (M1). Participants performed a delayed cued simple reaction time task. They were asked to produce a lip movement cued by an imperative GO-signal presented after a predictable SET-period, during which TMS was applied at different intervals. Results showed that the area of motor evoked potentials (MEPs) to test TMS was modulated by conditioning TMS. A transient inhibition cortico-bulbar excitability by PMCd stimulation was observed around the middle of the SET-period. Conversely, a ramping excitatory effect of PMCd stimulation appeared towards the end of the SET-period, as the time of the predicted GO-signal approached. The time-course of PMCd-M1 activity scaled to the varying SET-period duration. Our data indicate that inhibition and excitation of motor output during a delayed reaction time task are two distinct neural phenomena. They both originate in PMCd and are conveyed via cortico-cortical connections to the ipsilateral M1, where they are integrated to produce harmonic fluctuations of motor output

Connectivity by the Frontal Aslant Tract (FAT) explains local functional specialization of the superior and inferior frontal gyri in humans when choosing predictive over reactive strategies: a tractography-guided TMS study

Predictive and reactive behaviors represent two mutually exclusive strategies in a sensorimotor task. Predictive behavior consists in internally estimating timing and features of a target stimulus and relies on a cortical medial frontal system (superior frontal gyrus - SFG). Reactive behavior consists in waiting for actual perception of the target stimulus and relies on the lateral frontal cortex (inferior frontal gyrus - IFG). We investigated whether SFG-IFG connections by the frontal aslant tract (FAT) can mediate predictive/reactive interactions. In 19 healthy human volunteers, we applied online transcranial magnetic stimulation (TMS) to 6 spots along the medial and lateral terminations of the FAT, during the set period of a delayed reaction task. Such scenario can be solved using either predictive or reactive strategies. TMS increased the propensity towards reactive behavior if applied to a specific portion of the SFG and increased predictive behavior when applied to a specific IFG spot. The two active spots in the SFG and IFG were directly connected by a sub-bundle of FAT fibers as indicated by DWI-tractography. Since FAT connectivity identifies two distant cortical nodes with opposite functions, we propose that the FAT mediates mutually inhibitory interactions between SFG and IFG to implement a "winner takes all" decisional process. We hypothesize such role of the FAT to be domain-general, whenever competition occurs between internal predictive and external reactive behaviors. Finally, we also show that anatomical connectivity is a powerful factor to explain and predict the spatial distribution of brain stimulation effects.Significance StatementWe interact with sensory cues adopting two main mutually-exclusive strategies: a) trying to anticipate the occurrence of the cue or b) waiting for the GO-signal to be manifest and react to it. Here we showed, by using non-invasive brain stimulation (TMS), that two specific cortical regions in the superior frontal gyrus (SFG) and the inferior frontal gyrus (IFG) have opposite roles in facilitating a predictive or a reactive strategy. Importantly these two very distant regions but with highly interconnected functions are specifically connected by a small white matter bundle, which mediates the direct competition and exclusiveness between predictive and reactive strategies. More generally, implementing anatomical connectivity in TMS studies strongly reduces spatial noise