A review of sample collection and analytical methods for detecting per- and polyfluoroalkyl substances in indoor and outdoor air.

Per- and polyfluoroalkyl substances (PFAS) are a unique class of chemicals synthesized to aid in industrial processes, fire-fighting products, and to benefit consumer products such as clothing, cosmetics, textiles, carpets, and coatings. The widespread use of PFAS and their strong carbon-fluorine bonds has led to their ubiquitous presence throughout the world. Airborne transport of PFAS throughout the atmosphere has also contributed to environmental pollution. Due to the potential environmental and human exposure concerns of some PFAS, research has extensively focused on water, soil, and organismal detection, but the presence of PFAS in the air has become an area of growing concern. Methods to measure polar PFAS in various matrices have been established, while the investigation of polar and nonpolar PFAS in air is still in its early development. This literature review aims to present the last two decades of research characterizing PFAS in outdoor and indoor air, focusing on active and passive air sampling and analytical methods. The PFAS classes targeted and detected in air samples include fluorotelomer alcohols (FTOHs), perfluoroalkane sulfonamides (FASAs), perfluoroalkane sulfonamido ethanols (FASEs), perfluorinated carboxylic acids (PFCAs), and perfluorinated sulfonic acids (PFSAs). Although the manufacturing of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) has been largely phased out, these two PFAS are still often detected in air samples. Additionally, recent estimates indicate that there are thousands of PFAS that are likely present in the air that are not currently monitored in air methods. Advances in air sampling methods are needed to fully characterize the atmospheric transport of PFAS.

A double-blind, sham-controlled, trial of home-administered rhythmic 10-Hz median nerve stimulation for the reduction of tics, and suppression of the urge-to-tic, in individuals with Tourette syndrome and chronic tic disorder.

Tourette syndrome (TS) and chronic tic disorder (CTD) are neurological disorders of childhood onset characterized by the occurrence of tics; repetitive, purposeless, movements or vocalizations of short duration which can occur many times throughout a day. Currently, effective treatment for tic disorders is an area of considerable unmet clinical need. We aimed to evaluate the efficacy of a home-administered neuromodulation treatment for tics involving the delivery of rhythmic pulse trains of median nerve stimulation (MNS) delivered via a wearable 'watch-like' device worn at the wrist. We conducted a UK-wide parallel double-blind sham-controlled trial for the reduction of tics in individuals with tic disorder. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1-19 mA) electrical stimulation to the median nerve for a pre-determined duration each day, and was intended to be used by each participant in their home once each day, 5 days each week, for a period of 4 weeks. Between 18th March 2022 and 26th September 2022, 135 participants (45 per group) were initially allocated, using stratified randomization, to one of the following groups; active stimulation; sham stimulation or to a waitlist (i.e. treatment as usual) control group. Recruited participants were individuals with confirmed or suspected TS/CTD aged 12 years of age or upward with moderate to severe tics. Researchers involved in the collection or processing of measurement outcomes and assessing the outcomes, as well as participants in the active and sham groups and their legal guardians were all blind to the group allocation. The primary outcome measure used to assess the 'offline' or treatment effect of stimulation was the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTSS) assessed at the conclusion of 4 weeks of stimulation. The primary outcome measure used to assess the 'online' effects of stimulation was tic frequency, measured as the number of tics per minute (TPM) observed, based upon blind analysis of daily video recordings obtained while stimulation was delivered. The results demonstrated that after 4-week stimulation, tic severity (YGTSS-TTSS) had reduced by 7.1 points (35 percentile reduction) for the active stimulation group compared to 2.13/2.11 points for the sham stimulation and waitlist control groups. The reduction in YGTSS-TTSS for the active stimulation group was substantially larger, clinically meaningful (effect size = .5) and statistically significant (p = .02) compared to both the sham stimulation and waitlist control groups, which did not differ from one another (effect size = -.03). Furthermore, blind analyses of video recordings demonstrated that tic frequency (tics per minute) reduced substantially (-15.6 TPM) during active stimulation compared to sham stimulation (-7.7 TPM). This difference represents a statistically significant (p < .03) and clinically meaningful reduction in tic frequency (>25 percentile reduction: effect size = .3). These findings indicate that home-administered rhythmic MNS delivered through a wearable wrist-worn device has the potential to be an effective community-based treatment for tic disorders.

The use of gas chromatography - high resolution mass spectrometry for suspect screening and non-targeted analysis of per- and polyfluoroalkyl substances.

This study is a workflow development for the analysis, identification, and categorization of per- and polyfluoroalkyl substances (PFAS) using gas chromatography-high resolution mass spectrometry (GC-HRMS) with non-targeted analysis (NTA) and suspect screening techniques. The behavior of various PFAS in a GC-HRMS was studied with regards to retention indices, ionization susceptibility, fragmentation patterns, etc. A custom PFAS database was constructed from 141 diverse PFAS. The database contains mass spectra from electron ionization (EI) mode, as well as MS and MS/MS spectra from positive and negative chemical ionization (PCI and NCI, respectively) modes. Common fragments of PFAS were identified across a diverse set of 141 PFAS analyzed. A workflow for suspect screening of PFAS and partially fluorinated products of incomplete combustion/destruction (PICs/PIDs) was developed which utilized both the custom PFAS database and external databases. PFAS and other fluorinated compounds were identified in both a challenge sample (designed to test the identification workflow) and incineration samples suspected to contain PFAS and fluorinated PICs/PIDs. The challenge sample resulted in a 100% true positive rate (TPR) for PFAS which were present in the custom PFAS database. Several fluorinated species were tentatively identified in the incineration samples using the developed workflow.

Characterization of PFAS air emissions from thermal application of fluoropolymer dispersions on fabrics.

During thermal processes utilized in affixing fluoropolymer coatings dispersion to fibers and fabrics, coating components are vaporized. It is suspected that per- and polyfluoroalkyl substances (PFAS) from the dispersions may undergo chemical transformations at the temperatures used, leading to additional emitted PFAS thermal byproducts. It is important to characterize these emissions to support evaluation of the resulting environmental and health impacts. In this study, a bench-scale system was built to simulate this industrial process via thermal application of dispersions to fiberglass utilizing relevant temperatures and residence times in sequential drying, baking, and sintering steps. Experiments were performed with two commercially available dispersions and a simple model mixture containing a single PFAS (6:2 fluorotelomer alcohol [6:2 FTOH]). Vapor-phase emissions were sampled and characterized by several off-line and real-time mass spectrometry techniques for targeted and nontargeted PFAS. Results indicate that multiple PFAS thermal transformation products and multiple nonhalogenated organic species were emitted from the exit of the high temperature third (sintering) furnace when 6:2 FTOH was the only PFAS present in the aqueous mixture. This finding supports the hypothesis that temperatures typical of these industrial furnaces may also induce chemical transformations within the fluorinated air emissions. Experiments using the two commercial fluoropolymer dispersions indicate air emissions of part-per-million by volume (ppmv) concentrations of heptafluoropropyl-1,2,2,2-tetrafluoroethyl ether (Fluoroether E1), as well as other PFAS at operationally relevant temperatures. We suspect that E1 is a direct thermal decomposition product (via decarboxylation) of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid (commonly referred to as HFPO-DA) present in the dispersions. Other thermal decomposition products, including the monomer, tetrafluoroethene, may originate from the PFAS used to stabilize the dispersion or from the polymer particles in suspension. This study represents the first researcher-built coating application simulator to report nontargeted PFAS emission characterization, real-time analyses, and the quantification of 30 volatile target PFAS.Implications: Thermal processes used to affix fluoropolymers to fabrics are believed to be a source of PFAS air emissions. These coating operations are used by many large and small manufacturers and typically do not currently require any air emissions control. This research designed and constructed a bench-scale system that simulates these processes and used several off-line and advanced real-time mass spectroscopy techniques to characterize PFAS air emissions from two commercial fluoropolymer dispersions. Further, as the compositions of commercial dispersions are largely unknown, a model three-component solution containing a single PFAS was used to characterize emissions of multiple PFAS thermal transformation products at operationally relevant conditions. This research shows that fluoropolymer fabric coating facilities can be sources of complex mixtures of PFAS air emissions that include volatile and semivolatile PFAS present in the dispersions, as well as PFAS byproducts formed by the thermal transformation of fluorocarbon and hydrocarbon species present in these dispersions.

Pilot-Scale Thermal Destruction of Per- and Polyfluoroalkyl Substances in a Legacy Aqueous Film Forming Foam.

The destruction of per- and polyfluoroalkyl substances (PFAS) is critical to ensure effective remediation of PFAS contaminated matrices. The destruction of hazardous chemicals within incinerators and other thermal treatment processes has historically been determined by calculating the destruction efficiency (DE) or the destruction and removal efficiency (DRE). While high DEs, >99.99%, are deemed acceptable for most hazardous compounds, many PFAS can be converted to other PFAS at low temperatures resulting in high DEs without full mineralization and the potential release of the remaining fluorocarbon portions to the environment. Many of these products of incomplete combustion (PICs) are greenhouse gases, most have unknown toxicity, and some can react to create new perfluorocarboxylic acids. Experiments using aqueous film forming foam (AFFF) and a pilot-scale research combustor varied the combustion environment to determine if DEs indicate PFAS mineralization. Several operating conditions above 1090 °C resulted in high DEs and few detectable fluorinated PIC emissions. However, several conditions below 1000 °C produced DEs >99.99% for the quantifiable PFAS and mg/m3 emission concentrations of several non-polar PFAS PICs. These results suggest that DE alone may not be the best indication of total PFAS destruction, and additional PIC characterization may be warranted.

Task-dependent plasticity in distributed neural circuits after transcranial direct current stimulation of the human motor cortex: A proof-of-concept study.

The ability of non-invasive brain stimulation to induce neuroplasticity and cause long-lasting functional changes is of considerable interest for the reversal of chronic pain and disability. Stimulation of the primary motor cortex (M1) has provided some of the most encouraging after-effects for therapeutic purposes, but little is known about its underlying mechanisms. In this study we combined transcranial Direct Current Stimulation (tDCS) and fMRI to measure changes in task-specific activity and interregional functional connectivity between M1 and the whole brain. Using a randomized counterbalanced sham-controlled design, we applied anodal and cathodal tDCS stimulation over the left M1. In agreement with previous studies, we demonstrate that tDCS applied to the target region induces task-specific facilitation of local brain activity after anodal tDCS, with the stimulation effects having a negative relationship to the resting motor threshold. Beyond the local effects, tDCS also induced changes in multiple downstream regions distinct from the motor system that may be important for therapeutic efficacy, including the operculo-insular and cingulate cortex. These results offer opportunities to improve outcomes of tDCS for the individual patient based on the degree of presumed neuroplasticity. Further research is still warranted to address the optimal stimulation targets and parameters for those with disease-specific symptoms of chronic pain.

The oscillatory effects of rhythmic median nerve stimulation.

Entrainment of brain oscillations can be achieved using rhythmic non-invasive brain stimulation, and stimulation of the motor cortex at a frequency associated with sensorimotor inhibition can impair motor responses. Despite the potential for therapeutic application, these techniques do not lend themselves to use outside of a clinical setting. Here, the aim was to investigate whether rhythmic median nerve stimulation (MNS) could be used to entrain oscillations related to sensorimotor inhibition. MEG data were recorded from 20 participants during 400 trials, where for each trial 10 pulses of MNS were delivered either rhythmically or arrhythmically at 12 or 20 Hz. Our results demonstrate a frequency specific increase in relative amplitude in the contralateral somatosensory cortex during rhythmic but not arrhythmic stimulation. This was coupled with an increase in inter-trial phase coherence at the same frequency, suggesting that the oscillations synchronised with the pulses of MNS. The results show that 12 and 20 Hz rhythmic peripheral nerve stimulation can produce entrainment. Rhythmic MNS resulted in synchronous firing of neuronal populations within the contralateral somatosensory cortex meaning these neurons were engaged in processing of the afferent input. Therefore, MNS could prove therapeutically useful in disorders associated with hyperexcitability within the sensorimotor cortices.

Feasibility of a Selective Epoxidation Technique for Use in Quantification of Peracetic Acid in Air Samples Collected on Sorbent Tubes.

Peracetic acid is a disinfection agent used in medical and food processing facilities, and occupational exposures have been documented. To facilitate characterization of daily occupational exposures, the current work describes the development of a personal sampling technique to quantify the peracetic acid concentration in air samples. Peracetic acid atmospheres were generated in 100 L Teflon chambers, and samples were collected on 350 mg XAD-7 solid sorbent tubes for 4 h at a flow rate of 250 mL/min using a personal sampling pump. Indirect measurement of peracetic acid was achieved by desorption from the sorbent and subsequent treatment with cyclohexene to initiate an epoxidation reaction, formally known as the Prilezhaev reaction. The epoxidation product, cyclohexene oxide, was quantified by gas chromatography-mass spectrometry. The reaction enabled quantification of peracetic acid with high specificity over the common co-contaminants hydrogen peroxide and acetic acid, which were introduced in 10-fold and 100-fold excess to challenge the reaction. The technique also demonstrated an overall estimate of bias and precision of 11 and 8%, respectively, and a limit of detection of 60 ppbv was estimated. Preliminary storage experiments indicate that unreacted peracetic acid is stable on the sorbent tubes for 72 h when stored at -20 °C following collection. Overall, the specificity of the reaction and capability to sample for longer time periods than current methods, in addition to the use of safer personal sampling materials, demonstrate the utility of this technique for peracetic acid measurement in air.

Examining the neural antecedents of tics in Tourette syndrome using electroencephalography.

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit dysfunction and hyper-excitability of cortical limbic and motor regions that lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by premonitory sensory/urge phenomena (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as an urge for motor discharge. While tics are most often referred to as involuntary movements, it has been argued by some that tics should be viewed as voluntary movements that are executed in response to the presence of PU. To investigate this issue further, we conducted a study using electroencephalography (EEG). We recorded movement-related EEG (mu- and beta-band oscillations) during (1) the immediate period leading up to the execution of voluntary movements by a group of individuals with TS and a group of matched healthy control participants, and (2) the immediate period leading up to the execution of a tic in a group of individuals with TS. We demonstrate that movement-related mu and beta oscillations are not reliably observed prior to tics in individuals with TS. We interpret this effect as reflecting the greater involvement of a network of brain areas, including the insular and cingulate cortices, the basal ganglia and the cerebellum, in the generation of tics in TS. We also show that beta-band desynchronization does occur when individuals with TS initiate voluntary movements, but, in contrast to healthy controls, desynchronization of mu-band oscillations is not observed during the execution of voluntary movements for individuals with TS. We interpret this finding as reflecting a dysfunction of physiological inhibition in TS, thereby contributing to an impaired ability to suppress neuronal populations that may compete with movement preparation processes.

The role of the cingulate cortex in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome.

Tourette syndrome (TS) is a neurological disorder of childhood onset that is characterized by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction and hyper-excitability of cortical limbic and motor regions that are thought to lead to the occurrence of tics. Individuals with TS often report that their tics are preceded by 'premonitory sensory/urge phenomena' (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as a strong urge for motor discharge. While the precise role played by PU in the occurrence of tics is largely unknown, they are nonetheless of considerable theoretical and clinical importance as they form a core component of many behavioural therapies used in the treatment of tic disorders. Recent evidence indicates that the cingulate cortex may play an important role in the generation of PU in TS, and in 'urges-for-action' more generally. In the current study, we utilized voxel-based morphometry (VBM) techniques, together with 'seed-to-voxel' structural covariance network (SCN) mapping, to investigate the putative role played by the cingulate cortex in the generation of motor tics and the experience of PU in a relatively large group of young people with TS. Whole-brain VBM analysis revealed that TS was associated with clusters of significantly reduced grey matter volumes bilaterally within: the orbito-frontal cortex; the cerebellum; and the anterior and mid-cingulate cortex. Similarly, analysis of SCNs associated with bilateral mid- and anterior cingulate 'seed' regions demonstrated that TS is associated with increased structural covariance primarily with the bilateral motor cerebellum; the inferior frontal cortex; and the posterior cingulate cortex.

Operculo-insular and anterior cingulate plasticity induced by transcranial magnetic stimulation in the human motor cortex: a dynamic casual modeling study.

The ability to induce neuroplasticity with noninvasive brain stimulation techniques offers a unique opportunity to examine the human brain systems involved in pain modulation. In experimental and clinical settings, the primary motor cortex (M1) is commonly targeted to alleviate pain, but its mechanism of action remains unclear. Using dynamic causal modeling (DCM) and Bayesian model selection (BMS), we tested seven competing hypotheses about how transcranial magnetic stimulation (TMS) modulates the directed influences (or effective connectivity) between M1 and three distinct cortical areas of the medial and lateral pain systems, including the insular cortex (INS), anterior cingulate cortex (ACC), and parietal operculum cortex (PO). The data set included a novel fMRI acquisition collected synchronously with M1 stimulation during rest and while performing a simple hand motor task. DCM and BMS showed a clear preference for the fully connected model in which all cortical areas receive input directly from M1, with facilitation of the connections INS→M1, PO→M1, and ACC→M1, plus increased inhibition of their reciprocal connections. An additional DCM analysis comparing the reduced models only corresponding to networks with a sparser connectivity within the full model showed that M1 input into the INS is the second-best model of plasticity following TMS manipulations. The results reported here provide a starting point for investigating whether pathway-specific targeting involving M1↔INS improves analgesic response beyond conventional targeting. We eagerly await future empirical data and models that tests this hypothesis.NEW & NOTEWORTHY Transcranial magnetic stimulation of the primary motor cortex (M1) is a promising treatment for chronic pain, but its mechanism of action remains unclear. Competing dynamic causal models of effective connectivity between M1 and medial and lateral pain systems suggest direct input into the insular, anterior cingulate cortex, and parietal operculum. This supports the hypothesis that analgesia produced from M1 stimulation most likely acts through the activation of top-down processes associated with intracortical modulation.

Solvent Suitability for HFPO-DA ("GenX" Parent Acid) in Toxicological Studies.

Per- and polyfluorinated alkyl substances (PFAS) are of significant interest because of their prevalence and environmental persistence. Further, for many PFAS, including fluorinated ethers, such as hexafluoropropylene oxide dimer acid (HFPO-DA, or the parent acid of "GenX"), toxicological data are sparse. In general, in vitro testing frequently uses dimethyl sulfoxide (DMSO) as a carrier solvent due to its low toxicity, solubility across vast chemical space, and permeation across biological barriers. For PFAS, laboratory practice has assumed that the materials are stable across a wide range of solvents, pHs, and temperatures. In this study, HFPO-DA stability was evaluated with DMSO and other commonly used solvents to determine each solvent's suitability for use in toxicity assays. The formation of HFPO-DA's degradation product, heptafluoropropyl 1,2,2,2-tetrafluoroethyl ether (Fluoroether E-1), was monitored by headspace gas chromatography-mass spectrometry (GC-MS) over time. These experiments revealed degradation of HFPO-DA to Fluoroether E-1 in DMSO and other aprotic, polar solvents, with half-lives on the order of hours (1 h, 1.25 h, and 5.2 h for DMSO, acetone, and acetonitrile, respectively). This rapid degradation suggests the need for caution when performing or using data from toxicity assessments on HFPO-DA and closely related PFAS compounds.

A feasibility study for somatomotor cortical mapping in Tourette syndrome using neuronavigated transcranial magnetic stimulation.

Tourette syndrome (TS) is a hyperkinetic movement disorder characterised by the occurrence of chronic motor and vocal tics, and is associated with alterations in the balance of excitatory and inhibitory signalling within key brain networks; in particular the cortical-striatal-thalamic-cortical (CSTC) brain circuits that are implicated in movement selection and habit learning. Converging evidence indicates abnormal brain network function in TS may be largely due to the impaired operation of GABA signalling within the striatum and within cortical motor areas, leading to the occurrence of tics. TS has been linked to a heightened sensitivity to somatic stimulation and altered processing of somatosensory information, and there is evidence to indicate that alterations in GABAergic function is likely to contribute to altered somatomotor function. Based upon this evidence, we hypothesised that the specificity of somatomotor representations in primary motor cortex would likely be reduced in individuals with TS. To test this, we used a rapid acquisition method together with neuronavigated transcranial magnetic stimulation (nTMS) to measure the cortical representation of a several different muscles in a group of young adults with TS and a matched group of typically developing individuals.

Tic frequency and behavioural measures of cognitive control are improved in individuals with Tourette syndrome by aerobic exercise training.

Previous observations of improvements in cognition in typically developing children following moderate to vigorous exercise (e.g., Budde, Voelcker-Rehage, Pietrabyk-Kendziorra, Ribeiro, & Tidow, 2008; Hillman et al., 2009) have led to increased interest in the potential benefits of exercise for children with neurodevelopmental disorders, involving difficulties in self-regulation (e.g., Halperin & Healey, 2011; Archer & Kostrzewa, 2012). Using a within-sample design, the current study looked at the beneficial effects of non-aerobic movement training (Tai Chi), compared to aerobic movement training (Kick Boxing), on behavioural measures of cognitive control and clinical measures of tic severity in a group of young people with Tourette Syndrome (TS). We demonstrate that Kick Boxing, but not Tai Chi, led to a significant enhancement in cognitive control task performance. Furthermore, while tic frequency (tics per minute) was reduced during both types of exercise, this reduction was significantly greater, and sustained for longer, following Kick Boxing. Importantly, the magnitude of the increase in cognitive control following Kick Boxing predicted the degree of reduction in tic frequency. These findings suggest that aerobic exercise may be a useful intervention for improving self-regulation of tics in young people with TS, probably through enhancements in associated cognitive control circuits.

Entraining Movement-Related Brain Oscillations to Suppress Tics in Tourette Syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by the occurrence of vocal and motor tics. Tics are involuntary, repetitive movements and vocalizations that occur in bouts, typically many times in a single day, and are often preceded by a strong urge-to-tic-referred to as a premonitory urge (PU). TS is associated with the following: dysfunction within cortical-striatal-thalamic-cortical (CSTC) brain circuits implicated in the selection of movements, impaired operation of GABA signaling within the striatum, and hyper-excitability of cortical sensorimotor regions that might contribute to the occurrence of tics. Non-invasive brain stimulation delivered to cortical motor areas can modulate cortical motor excitability, entrain brain oscillations, and reduce tics in TS. However, these techniques are not optimal for treatment outside of the clinic. We investigated whether rhythmic pulses of median nerve stimulation (MNS) could entrain brain oscillations linked to the suppression of movement and influence the initiation of tics in TS. We demonstrate that pulse trains of rhythmic MNS, delivered at 12 Hz, entrain sensorimotor mu-band oscillations, whereas pulse trains of arrhythmic MNS do not. Furthermore, we demonstrate that although rhythmic mu stimulation has statistically significant but small effects on the initiation of volitional movements and no discernable effect on performance of an attentionally demanding cognitive task, it nonetheless leads to a large reduction in tic frequency and tic intensity in individuals with TS. This approach has considerable potential, in our view, to be developed into a therapeutic device suitable for use outside of the clinic to suppress tics and PU in TS.

Modulating Brain Networks With Transcranial Magnetic Stimulation Over the Primary Motor Cortex: A Concurrent TMS/fMRI Study.

Stimulating the primary motor cortex (M1) using transcranial magnetic stimulation (TMS) causes unique multisensory experience such as the targeted muscle activity, afferent/reafferent sensory feedback, tactile sensation over the scalp and "click" sound. Although the human M1 has been intensively investigated using TMS, the experience of the M1 stimulation has not been elucidated at the whole brain. Here, using concurrent TMS/fMRI, we investigated the acute effect of the M1 stimulation of functional brain networks during task and at rest. A short train of 1 Hz TMS pulses applied to individuals' hand area in the M1 during motor execution or at rest. Employing the independent component analysis (ICA), we showed the M1 stimulation decreased the motor networks activity when the networks were engaged in the task and increased the deactivation of networks when the networks were not involved in the ongoing task. The M1 stimulation induced the activation in the key networks involved in bodily self-consciousness (BSC) including the insular and rolandic operculum systems regardless of states. The degree of activation in these networks was prominent at rest compared to task conditions, showing the state-dependent TMS effect. Furthermore, we demonstrated that the M1 stimulation modulated other domain-general networks such as the default mode network (DMN) and attention network and the inter-network connectivity between these networks. Our results showed that the M1 stimulation induced the widespread changes in the brain at the targeted system as well as non-motor, remote brain networks, specifically related to the BSC. Our findings shed light on understanding the neural mechanism of the complex and multisensory experience of the M1 stimulation.

Alterations in cerebellar grey matter structure and covariance networks in young people with Tourette syndrome.

Tourette syndrome (TS) is a childhood-onset neurological disorder characterised by the occurrence of motor and vocal tics and the presence of premonitory sensory/urge phenomena. Functional neuroimaging studies in humans, and experimental investigations in animals, have shown that the genesis of tics in TS involve a complex interaction between cortical-striatal-thalamic-cortical brain circuits and additionally appears to involve the cerebellum. Furthermore, structural brain imaging studies have demonstrated alterations in grey matter (GM) volume in TS across a wide range of brain areas, including alterations in GM volume within the cerebellum. Until now, no study to our knowledge has yet investigated how GM structural covariance networks linked to the cerebellum may be altered in individuals with TS. In this study we employed voxel-based morphometry, and a 'seed-to-voxel' structural covariance network (SCN) mapping approach, to investigate alterations in GM cerebellar volume in people with TS, and alterations in cerebellar SCNs associated with TS. Data from 64 young participants was entered in the final analysis, of which 28 had TS while 36 were age-and sex-matched healthy volunteers. Using the spatially unbiased atlas template of the cerebellum and brainstem (SUIT) atlas, we found reduced GM volume in cerebellar lobule involved in higher-order cognitive functions and sensorimotor processing, in patients. In addition, we found that several areas located in frontal and cingulate cortices and sensorimotor network in addition to subcortical areas show altered structural covariance with our cerebellar seed compared to age-matched controls. These results add to the increasing evidence that cortico-basal ganglia-cerebellar interactions play an important role in tic symptomology.

The role of the insula in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome.

Tourette syndrome (TS) is a neurological disorder of childhood onset that is characterised by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction and hyper-excitability of cortical limbic and motor regions that are thought to lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by 'premonitory sensory/urge phenomena' (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as a strong urge for motor discharge. While the precise role played by PU in the occurrence of tics is largely unknown, they are nonetheless of considerable theoretical and clinical importance, not least because they form the core component in many behavioural therapies used in the treatment of tic disorders. Several lines of evidence indicate that the insular cortex may play a particularly important role in the generation of PU in TS and 'urges-for-action' more generally. In the current study we utilised voxel-based morphometry techniques together with 'seed-to-voxel' structural covariance network (SCN) mapping to investigate the putative role played by the right insular cortex in the generation of motor tics and the experience of PU in a relatively large group of young people TS. We demonstrate that clinical measures of motor tic severity and PU are uncorrelated with one another, that motor tic severity and PU scores are associated with separate regions of the insular cortex, and that the insula is associated with different structural covariance networks in individuals with TS compared to a matched group of typically developing individuals.

Acrylonitrile butadiene styrene (ABS) and polycarbonate (PC) filaments three-dimensional (3-D) printer emissions-induced cell toxicity.

During extrusion of some polymers, fused filament fabrication (FFF) 3-D printers emit billions of particles per minute and numerous organic compounds. The scope of this study was to evaluate FFF 3-D printer emission-induced toxicity in human small airway epithelial cells (SAEC). Emissions were generated from a commercially available 3-D printer inside a chamber, while operating for 1.5 h with acrylonitrile butadiene styrene (ABS) or polycarbonate (PC) filaments, and collected in cell culture medium. Characterization of the culture medium revealed that repeat print runs with an identical filament yield various amounts of particles and organic compounds. Mean particle sizes in cell culture medium were 201 ±â€¯18 nm and 202 ±â€¯8 nm for PC and ABS, respectively. At 24 h post-exposure, both PC and ABS emissions induced a dose dependent significant cytotoxicity, oxidative stress, apoptosis, necrosis, and production of pro-inflammatory cytokines and chemokines in SAEC. Though the emissions may not completely represent all possible exposure scenarios, this study indicate that the FFF could induce toxicological effects. Further studies are needed to quantify the detected chemicals in the emissions and their corresponding toxicological effects.