Search

Introduction: Tacrolimus-associated neurotoxicity (TAN) manifests with wide clinical spectrum, ranging from mild tremors to severe encephalopathy. The isolated involvement of the brainstem is a rarely documented presentation of TAN, and its clinical and diagnostic characteristics are unclear. Methods: We report two cases of brainstem-isolated TAN (bi-TAN). Moreover, we performed a systematic review of the literature on bi-TAN and extracted data concerning demographics, clinical characteristics, radiological features, and management. The systematic literature search followed PRISMA guidelines and a pre-defined protocol. Results: Eleven patients, including our two, were identified (mean age: 41.3 years, ± 18.8; five males, 45%). Speech disturbance was the most common clinical presentation (45%). The mean latency from Tacrolimus initiation to bi-TAN onset was 26 days (± 30.8). Tacrolimus serum level tested above the reference range in three patients (mean: 26.83 ± 5.48). Brain MRI showed T2-FLAIR hyperintensities; three showed restricted diffusion on ADC maps. Neurological symptoms resolved completely in seven patients (63%) after Tacrolimus withdrawal or dose reduction. Conclusions: Our findings suggest that bi-TAN could represent a brainstem variant of posterior reversible encephalopathy syndrome. Recognition of bi-TAN as a potential cause of isolated brainstem lesions is crucial to disentangle the diagnostic work-up and ensure prompt withdrawal or reduction of the offending agent. [ABSTRACT FROM AUTHOR]

• Transcranial oscillatory currents may stimulate the vestibular cortex in the range of its physiological activity (1 or 2 Hz) • Induced behavioral effects (motion sickness and postural sways) are not due to a peripheral spread of the current towards vestibular receptors. • Motion sickness represents a previously neglected possible side effect of slow-frequency tACS. The vestibular cortex is a multisensory associative region that, in neuroimaging investigations, is activated by slow-frequency (1–2 Hz) galvanic stimulation of peripheral receptors. We aimed to directly activate the vestibular cortex with biophysically modeled transcranial oscillatory current stimulation (tACS) in the same frequency range. Thirty healthy subjects and one rare patient with chronic bilateral vestibular deafferentation underwent, in a randomized, double-blind, controlled trial, to tACS at slow (1 or 2 Hz) or higher (10 Hz) frequency and sham stimulations, over the Parieto-Insular Vestibular Cortex (PIVC), while standing on a stabilometric platform. Subjective symptoms of motion sickness were scored by Simulator Sickness Questionnaire and subjects' postural sways were monitored on the platform. tACS at 1 and 2 Hz induced symptoms of motion sickness, oscillopsia and postural instability, that were supported by posturographic sway recordings. Both 10 Hz-tACS and sham stimulation on the vestibular cortex did not affect vestibular function. As these effects persisted in a rare patient with bilateral peripheral vestibular areflexia documented by the absence of the Vestibular-Ocular Reflex, the possibility of a current spread toward peripheral afferents is unlikely. Conversely, the 10 Hz-tACS significantly reduced his chronic vestibular symptoms in this patient. Weak electrical oscillations in a frequency range corresponding to the physiological cortical activity of the vestibular system may generate motion sickness and postural sways, both in healthy subjects and in the case of bilateral vestibular deafferentation. This should be taken into account as a new side effect of tACS in future studies addressing cognitive functions. Higher frequencies of stimulation applied to the vestibular cortex may represent a new interventional option to reduce motion sickness in different scenarios. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment and care of patients with cancer owing to unique features, including the occurrence of the so-called immune-related adverse events (irAEs). A multidisciplinary team, possibly including a cardio-oncology specialist, is warranted to achieve a favorable patient outcome. Cardiovascular toxicity, especially myocarditis, emerged as a life-threatening irAE in the real-word setting, and the European Society of Cardiology has recently published the first guideline on cardio-oncology to increase awareness and promote a standardized approach to tackle this complex multimodal issue, including diagnostic challenges, assessment, treatment, and surveillance of patients with cancer receiving ICIs. In this article, through a question & answer format made up of case vignettes, we offer a clinically oriented overview on the latest advancements of ICI-related cardiovascular toxicity, focusing on myocarditis and associated irAEs (myositis and myasthenia gravis within the so-called overlap syndrome), with the purpose of assisting clinicians and healthcare professionals in daily clinical practice. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) represent an effective cancer immunotherapy yet are associated with immune-related adverse events (irAEs). The aim of this study was to characterize irAEs involving the peripheral nervous system (PNS-irAEs) in a real-world cohort of ICI-treated patients. Methods: Cancer patients treated with ICIs between January 2014 and March 2022 were included. Patients with PNS-irAEs were identified and divided into two groups: (1) cranial/peripheral neuropathies and (2) myasthenia gravis (MG) and/or myositis. Clinical characteristics and outcomes, measured with the modified Rankin Scale (mRS), were compared among the two groups. Results: Among 920 ICI-treated patients, 20 patients (2.17%) developed a PNS-irAEs. The median latency from ICI exposure was 8.8 weeks and the median time from onset to clinical nadir was 3.5 weeks. Eleven patients developed a neuropathy: polyneuropathy (n = 4), cranial neuropathy (n = 3), small-fiber neuropathy (n = 3), brachial plexopathy (n = 1). Nine patients presented MG and/or myositis: concomitant MG and myositis (n = 6), isolated myositis (n = 2), exacerbation of MG (n = 1). Immunosuppressive treatment and/or ICI withdrawal determined a significant clinical improvement, expressed by a mRS reduction, in the neuropathy group (p = 0.004), but not in the MG/myositis group (p = 0.11). Overall, death due to irAEs occurred in four patients (20%), all with MG/myositis. Compared to patients with neuropathies, those with MG/myositis had a shorter latency onset (p = 0.036), developed more frequently concomitant non-neurologic irAEs (p = 0.028) and showed a higher mortality rate (p = 0.026). Conclusions: In our large cohort of ICI-treated patients, 2.17% developed PNS-irAEs. Compared to ir-neuropathies, ir-MG/myositis tend to occur earlier from ICI exposure and present a worse response to treatment and a higher mortality. [ABSTRACT FROM AUTHOR]

Score-based diffusion models are a class of generative models whose dynamics is described by stochastic differential equations that map noise into data. While recent works have started to lay down a theoretical foundation for these models, a detailed understanding of the role of the diffusion time T is still lacking. Current best practice advocates for a large T to ensure that the forward dynamics brings the diffusion sufficiently close to a known and simple noise distribution; however, a smaller value of T should be preferred for a better approximation of the score-matching objective and higher computational efficiency. Starting from a variational interpretation of diffusion models, in this work we quantify this trade-off and suggest a new method to improve quality and efficiency of both training and sampling, by adopting smaller diffusion times. Indeed, we show how an auxiliary model can be used to bridge the gap between the ideal and the simulated forward dynamics, followed by a standard reverse diffusion process. Empirical results support our analysis; for image data, our method is competitive with regard to the state of the art, according to standard sample quality metrics and log-likelihood. [ABSTRACT FROM AUTHOR]

Background: We aimed to verify the usefulness of electroencephalographic (EEG) activity recording (that is mandatory according to the Italian law), in addition to two clinical evaluations spaced 6 h, among the procedures of brain death determination (BDD) in adult individuals. Methods: The study is a monocentric, retrospective analysis of all BDDs performed in the last 10 years at Policlinico Le Scotte in Siena (Italy). Results: Of the 428 cases revised (mean age 67.6 ± 15.03 years; range 24–92 years), 225 were males and 203 females. In total, 212 out of 428 patients (49.5%) were donors. None of the BDD procedures were interrupted due to the reappearance of EEG activity (neither for clinical reasons) at any sampling time, with the exception of one case that was considered a false negative at critical reinspection of the EEG. In 6/428 cases (1.4%), a cardiac arrest occurred during the 6 h between the first and second evaluation, thus missing the opportunity to take organs from these patients because the BDD procedure was not completed. Conclusions: Once the initial clinical examination before convening the BDD Commission has ascertained the absence of brainstem reflexes and of spontaneous breathing, and these clinical findings are supported by a flat EEG recording, the repetition of a 30-min EEG twice over a 6 h period seems not to add additional useful information to clinical findings. Current data, if confirmed in other centers and possibly in prospective studies, may help to promote a scientific and bioethical debate in Italy, as well as in other countries where the EEG is still mandatory, for eventually updating the procedures of BDD. [ABSTRACT FROM AUTHOR]

The Rashba effect in Ge/Si0.15Ge0.85 multiple quantum wells embedded in a p‐i‐n diode is studied through polarization and time‐resolved photoluminescence. In addition to a sizeable redshift arising from the quantum‐confined Stark effect, a threefold enhancement of the circular polarization degree of the direct transition is obtained by increasing the pump power over a 2 kW cm−2 range. This marked variation reflects an efficient modulation of the spin population and is further supported by dedicated investigations of the indirect gap transition. This study demonstrates a viable strategy to engineer the spin‐orbit Hamiltonian through contactless optical excitation and opens the way toward the electro‐optical manipulation of spins in quantum devices based on group‐IV heterostructures. [ABSTRACT FROM AUTHOR]

Introduction: Nonketotic hyperglycemic hyperosmolar state (NKHHS) is associated with a wide spectrum of neurological syndromes including acute stroke-like deficits. Clinical features and etiology have not been established yet. Methods: Here we provide a case illustration and systematic review on non-epileptic acute neurological deficits in NKHSS. The systematic literature search followed PRISMA guidelines and a predefined protocol, including cases of NKHSS with acute stroke-like presentation. Results: The database search yielded 18 cases. Hemianopia was the most common clinical presentation (73%), followed by partial or total anterior circulation syndrome (26%). Patients with symptoms of acute anterior circulation infarct were significantly older (69.5 ± 5.1 vs. 52.2 ± 13.9 years; p = 0.03) and showed higher mean glucose levels at the admission vs. those with hemianopia (674.8 ± 197.2 vs. 529.4 ± 190.8 mg/dL; p = 0.16). Brain MRI was performed in 89% of patients, resulting abnormal in 71% of them, especially hemianopic (91%). Subcortical hypointensities in T2-FLAIR MR sequences were present in all the analyzed cases. Cortical DWI hyperintensities were also common (64%). EEG showed diffuse or focal slow wave activity in 68% of patients, especially with visual hallucinations (85%). Neurological symptoms completely resolved in 78% of patients within 6 (IQR 3–10) days, following aggressive treatment and glucose normalization. Conclusions: Our results suggest neuronal dysfunction on a metabolic basis as the leading cause of acute neurological deficits in NKHHS. Despite the generally favorable prognosis, prompt identification and aggressive treatment are crucial to avoid irreversible damage. Larger cohort studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Objectives: This work aimed to report the demographic and clinical characteristics of two new cases with non-paraneoplastic anti-Hu-associated gut motility impairment, and perform a thorough revision covering anti-Hu-associated paraneoplastic (PGID) and non-paraneoplastic (nPGID) gastrointestinal dysmotility. Background: Several case series have clearly established a relationship between certain type of cancers, the development of circulating anti-Hu antibodies, and the concomitant usually severe gastrointestinal dysmotility; in contrast, a few studies focused on anti-Hu-associated nPGID. Methods: We searched for studies regarding anti-Hu-associated gastrointestinal manifestations and extracted data concerning clinical characteristics of patients, including specific demographic, oncological, neurological, gastrointestinal, histological, and treatment response features. Results: Forty-nine articles with a total of 59 cases of anti-Hu-associated gastrointestinal dysmotility were analyzed. The patients' age at symptom onset significantly differed between PGID and nPGID (median 61 vs 31 years, p < 0.001). Most cancers (95%) in PGID were detected within 24 months from the beginning of gastrointestinal symptoms. The impairment of gastrointestinal motility was generalized (i.e., involving the whole gut) in 59.3% of patients, with no significant differences between PGID vs nPGID group. nPGID patients showed a better response to immunomodulatory/immunosuppressive treatment and a longer life expectancy. Conclusions: Anti-Hu-associated gastrointestinal dysmotility covers a wide clinical spectrum. Patients with otherwise unexplained gastrointestinal dysmotility, especially when associated with other neurological symptoms, should be tested for anti-Hu antibodies regardless age of onset and disease duration. Compared to PGID, nPGID occurs in younger patients with a long duration of disease. [ABSTRACT FROM AUTHOR]

Cerebrovascular dysregulation syndromes are a heterogeneous group of disorders caused by abnormal cerebrovascular tone and endothelial dysfunction [[1]]. CT angiography was unremarkable, while CT venography showed a mild enlargement of dural venous sinuses, without signs of venous thrombosis. [Extracted from the article]

• This article traces the development of ECT from its origin until today. • The advent of rTMS in the neuropsychiatric field is described. • ECT and rTMS play a complementary role in treatment of neuropsychiatric disorders. Electroconvulsive therapy (ECT) was applied for the first time in humans in 1938: after 80 years, it remains conceptually similar today except for modifications of the original protocol aimed to reduce adverse effects (as persistent memory deficits) without losing clinical efficacy. We illustrate the stages of development as well as ups and downs of ECT use in the last eighty years, and the impact that it still maintains for treatment of certain psychiatric conditions. Targeted, individualized and safe noninvasive neuromodulatory interventions are now possible for many neuropsychiatric disorders thanks to repetitive transcranial magnetic stimulation (rTMS) that injects currents in the brain through electromagnetic induction, powerful enough to depolarize cortical neurons and related networks. Although ECT and rTMS differ in basic concepts, mechanisms, tolerability, side effects and acceptability, and beyond their conceptual remoteness (ECT) or proximity (rTMS) to "precision medicine" approaches, the two brain stimulation techniques may be considered as complementary rather than competing in the current treatment of certain neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

The Bayesian treatment of neural networks dictates that a prior distribution is specified over their weight and bias parameters. This poses a challenge because modern neural networks are characterized by a large number of parameters, and the choice of these priors has an uncontrolled effect on the induced functional prior, which is the distribution of the functions obtained by sampling the parameters from their prior distribution. We argue that this is a hugely limiting aspect of Bayesian deep learning, and this work tackles this limitation in a practical and effective way. Our proposal is to reason in terms of functional priors, which are easier to elicit, and to "tune" the priors of neural network parameters in a way that they reflect such functional priors. Gaussian processes offer a rigorous framework to define prior distributions over functions, and we propose a novel and robust framework to match their prior with the functional prior of neural networks based on the minimization of their Wasserstein distance. We provide vast experimental evidence that coupling these priors with scalable Markov chain Monte Carlo sampling offers systematically large performance improvements over alternative choices of priors and state-of-the-art approximate Bayesian deep learning approaches. We consider this work a considerable step in the direction of making the long-standing challenge of carrying out a fully Bayesian treatment of neural networks, including convolutional neural networks, a concrete possibility. [ABSTRACT FROM AUTHOR]

It is likely that when using an artificially augmented hand with six fingers, the natural five plus a robotic one, corticospinal motor synergies controlling grasping actions might be different. However, no direct neurophysiological evidence for this reasonable assumption is available yet. We used transcranial magnetic stimulation of the primary motor cortex to directly address this issue during motor imagery of objects' grasping actions performed with or without the Soft Sixth Finger (SSF). The SSF is a wearable robotic additional thumb patented for helping patients with hand paresis and inherent loss of thumb opposition abilities. To this aim, we capitalized from the solid notion that neural circuits and mechanisms underlying motor imagery overlap those of physiological voluntary actions. After a few minutes of training, healthy humans wearing the SSF rapidly reshaped the pattern of corticospinal outputs towards forearm and hand muscles governing imagined grasping actions of different objects, suggesting the possibility that the extra finger might rapidly be encoded into the user's body schema, which is integral part of the frontal-parietal grasping network. Such neural signatures might explain how the motor system of human beings is open to very quickly welcoming emerging augmentative bioartificial corticospinal grasping strategies. Such an ability might represent the functional substrate of a final common pathway the brain might count on towards new interactions with the surrounding objects within the peripersonal space. Findings provide a neurophysiological framework for implementing augmentative robotic tools in humans and for the exploitation of the SSF in conceptually new rehabilitation settings. [ABSTRACT FROM AUTHOR]

• This article updates the previous safety guidelines from 2009. • Safety of new devices and techniques is considered. • Operational guidelines for future protocols using TMS are provided. This article is based on a consensus conference, promoted and supported by the International Federation of Clinical Neurophysiology (IFCN), which took place in Siena (Italy) in October 2018. The meeting intended to update the ten-year-old safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings (Rossi et al., 2009). Therefore, only emerging and new issues are covered in detail, leaving still valid the 2009 recommendations regarding the description of conventional or patterned TMS protocols, the screening of subjects/patients, the need of neurophysiological monitoring for new protocols, the utilization of reference thresholds of stimulation, the managing of seizures and the list of minor side effects. New issues discussed in detail from the meeting up to April 2020 are safety issues of recently developed stimulation devices and pulse configurations; duties and responsibility of device makers; novel scenarios of TMS applications such as in the neuroimaging context or imaging-guided and robot-guided TMS; TMS interleaved with transcranial electrical stimulation; safety during paired associative stimulation interventions; and risks of using TMS to induce therapeutic seizures (magnetic seizure therapy). An update on the possible induction of seizures, theoretically the most serious risk of TMS, is provided. It has become apparent that such a risk is low, even in patients taking drugs acting on the central nervous system, at least with the use of traditional stimulation parameters and focal coils for which large data sets are available. Finally, new operational guidelines are provided for safety in planning future trials based on traditional and patterned TMS protocols, as well as a summary of the minimal training requirements for operators, and a note on ethics of neuroenhancement. [ABSTRACT FROM AUTHOR]

Background and objective: In a proof-of-concept study, we aimed to verify whether the wearable haptic anklets, a device that delivers personalized suprathreshold alternating exteroceptive stimulation at the anklets on demand, may improve the quality of walking, including the freezing of gate (FOG), in idiopathic Parkinson's disease (PD) patients. The clinical relevance of the presented device as a walking pacemaker to compensate the disturbed locomotion through the generation of a more physiological internal walking rhythm should be verified in a dedicated clinical trial. Methods: We tested 15 patients diagnosed as idiopathic PD, during their regular treatment regimen. Patients were evaluated during walking with the device switched on and off, personalized at their most comfortable cadence. Stride velocity, variance, and length, as well as FOG episode duration during walking or turning of 180°, were quantified by an optical high-performance motion capture VICON system. Results: The alternating, rhythmic, sensory stimulation significantly improved either walking velocity or reduced inter-stride variance. Effects were more variable on stride length. The significant reduction of FOG episodes' duration correlated with clinical severity of scales rating gate and balance. No safety problems occurred. Conclusions: The WEARHAP-PD device, whose Technology Readiness Level (TRL) is 6, significantly improved some walking abilities (walking velocity and stride variance) and reduced the duration of FOG episodes in idiopathic PD patients. Unlike the traditional auditory and visual explicit cues that require the user's allocation of attention for correct functioning, the interaction of the patients with the surrounding environment was preserved, due to the likely implicit processing of haptic stimuli. [ABSTRACT FROM AUTHOR]

• We tested how music reading facilitates the corticospinal excitability in musicians. • TMS was applied while pianists and non-pianists read treble or bass clef scores. • Music reading induced inter- and intra-hemispheric modulation of the motor cortex. • Similarly to word reading also music reading modulates the excitability of the motor system at rest. Neurophysiological studies suggest that music reading facilitates sensorimotor cortex. The aim of this study was to evaluate (1) whether in pianists, reading notes in bass and treble clef selectively enhances right and left primary motor cortex (M1) excitability; and (2) whether reading notes played with the thumb or little finger selectively modulates the excitability of specific muscles. Twenty musicians (11 pianists, 9 non-pianists) participated. Transcranial magnetic stimulation (TMS) was applied while subjects read the bass or the treble clef of sheets music and during the observation of a blank staff (baseline). When pianists read the treble clef, the excitability of the left M1 was higher compared to that recorded in the right M1. Moreover, in the treble clef condition motor evoked potentials (MEPs) induced by TMS of the left M1 were higher when pianists read notes to be played with the 5° finger (little finger) with respect to 1° finger (thumb) notes, whereas in the bass clef condition TMS of the right M1 induced higher MEPs for 1° finger note compared to 5° finger notes. No significant modulation was observed in non-pianists. These data support the view that music reading may induce specific inter- and intra-hemispheric modulation of the motor cortex excitability. [ABSTRACT FROM AUTHOR]

The research work presented herein deals with the analysis of light-frame wood (LFW) buildings under lateral seismic loading. The paper aim was to define the relationship between the global building ductility and the local ductility of the components via non-linear static analyses. Firstly, the different failure mechanisms were isolated and their influence over the building ductility was determined by focusing on single-storey buildings. Then, the study was extended to multi-storey buildings in order to evaluate how the number of storeys affects the ductility. In order to obtain results of general validity, the analyses were performed by varying the most relevant mechanical-geometrical parameters as well as the seismic input and the ductility of the base components. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation was used to investigate corticospinal output changes in 10 professional piano players during motor imagery of triad chords in C major to be "mentally" performed with three fingers of the right hand (thumb, index, and little finger). Five triads were employed in the task; each composed by a stable 3rd interval (C4-E4) and a varying third note that could generate a 5th (G4), a 6th (A4), a 7th (B4), a 9th (D5), or a 10th (E5) interval. The 10th interval chord was thought to be impossible in actual execution for biomechanical reasons, as long as the thumb and the index finger remained fixed on the 3rd interval. Chords could be listened from loudspeakers, read on a staff, or listened and read at the same time while performing the imagery task. The corticospinal output progressively increased along with task demands in terms of mental representation of hand extension. The effects of audio, visual, or audiovisual musical stimuli were generally similar, unless motor imagery of kinetically impossible triads was required. A specific three-effector motor synergy was detected, governing the representation of the progressive mental extension of the hand. Results demonstrate that corticospinal facilitation in professional piano players can be modulated according to the motor plan, even if simply "dispatched" without actual execution. Moreover, specific muscle synergies, usually encoded in the motor cortex, emerge along the cross-modal elaboration of musical stimuli and in motor imagery of musical performances. [ABSTRACT FROM AUTHOR]

In standard models of cardiac electrophysiology, including the bidomain and monodomain models, local perturbations can propagate at infinite speed. We address this unrealistic property by developing a hyperbolic bidomain model that is based on a generalization of Ohm's law with a Cattaneo-type model for the fluxes. Further, we obtain a hyperbolic monodomain model in the case that the intracellular and extracellular conductivity tensors have the same anisotropy ratio. In one spatial dimension, the hyperbolic monodomain model is equivalent to a cable model that includes axial inductances, and the relaxation times of the Cattaneo fluxes are strictly related to these inductances. A purely linear analysis shows that the inductances are negligible, but models of cardiac electrophysiology are highly nonlinear, and linear predictions may not capture the fully nonlinear dynamics. In fact, contrary to the linear analysis, we show that for simple nonlinear ionic models, an increase in conduction velocity is obtained for small and moderate values of the relaxation time. A similar behavior is also demonstrated with biophysically detailed ionic models. Using the Fenton-Karma model along with a low-order finite element spatial discretization, we numerically analyze differences between the standard monodomain model and the hyperbolic monodomain model. In a simple benchmark test, we show that the propagation of the action potential is strongly influenced by the alignment of the fibers with respect to the mesh in both the parabolic and hyperbolic models when using relatively coarse spatial discretizations. Accurate predictions of the conduction velocity require computational mesh spacings on the order of a single cardiac cell. We also compare the two formulations in the case of spiral break up and atrial fibrillation in an anatomically detailed model of the left atrium, and we examine the effect of intracellular and extracellular inductances on the virtual electrode phenomenon. [ABSTRACT FROM AUTHOR]

We propose a variational multiscale method stabilization of a linear finite element method for nonlinear poroelasticity. Our approach is suitable for the implicit time integration of poroelastic formulations in which the solid skeleton is anisotropic and incompressible. A detailed numerical methodology is presented for a monolithic formulation that includes both structural dynamics and Darcy flow. Our implementation of this methodology is verified using several hyperelastic and poroelastic benchmark cases, and excellent agreement is obtained with the literature. Grid convergence studies for both anisotropic hyperelastodynamics and poroelastodynamics demonstrate that the method is second-order accurate. The capabilities of our approach are demonstrated using a model of the left ventricle (LV) of the heart derived from human imaging data. Simulations using this model indicate that the anisotropicity of the myocardium has a substantial influence on the pore pressure. Furthermore, the temporal variations of the various components of the pore pressure (hydrostatic pressure and pressure resulting from changes in the volume of the pore fluid) are correlated with the variation of the added mass and dynamics of the LV, with maximum pore pressure being obtained at peak systole. The order of magnitude and the temporal variation of the pore pressure are in good agreement with the literature. [ABSTRACT FROM AUTHOR]

Insight processes that peak in “unpredictable moments of exceptional thinking” are often referred to as Aha! or Eureka moments. During insight, connections between previously unrelated concepts are made and new patterns arise at the perceptual level while new solutions to apparently insolvable problems suddenly emerge to consciousness. Given its unpredictable nature, the definition, and behavioral and neurophysiological measurement of insight problem solving represent a major challenge in contemporary cognitive neuroscience. Numerous attempts have been made, yet results show limited consistency across experimental approaches. Here we provide a comprehensive overview of available neuroscience of insight, including: i) a discussion about the theoretical definition of insight and an overview of the most widely accepted theoretical models, including those debating its relationship with creativity and intelligence; ii) an overview of available tasks used to investigate insight; iii) an ad-hoc quantitative meta-analysis of functional magnetic resonance imaging studies investigating the Eureka moment, using activation likelihood estimation maps; iv) a review of electroencephalographic evidence in the time and frequency domains, as well as v) an overview of the application of non-invasive brain stimulation techniques to causally assess the neurobiological basis of insight as well as enhance insight-related cognition. [ABSTRACT FROM AUTHOR]

Favored by increased life expectancy and reduced birth rate, worldwide demography is rapidly shifting to older ages. The golden age of aging is not only an achievement but also a big challenge because of the load of the elderly on social and medical health care systems. Moreover, the impact of age-related decline of attention, memory, reasoning and executive functions on self-sufficiency emphasizes the need of interventions to maintain cognitive abilities at a useful degree in old age. Recently, neuroscientific research explored the chance to apply Non-Invasive Brain Stimulation (NiBS) techniques (as transcranial electrical and magnetic stimulation) to healthy aging population to preserve or enhance physiologically-declining cognitive functions. The present review will update and address the current state of the art on NiBS in healthy aging. Feasibility of NiBS techniques will be discussed in light of recent neuroimaging (either structural or functional) and neurophysiological models proposed to explain neural substrates of the physiologically aging brain. Further, the chance to design multidisciplinary interventions to maximize the efficacy of NiBS techniques will be introduced as a necessary future direction. [ABSTRACT FROM AUTHOR]

Ge quantum wells, group IV heterostructures, photoluminescence, Rashba effect Keywords: Ge quantum wells; group IV heterostructures; photoluminescence; Rashba effect EN Ge quantum wells group IV heterostructures photoluminescence Rashba effect 1 1 1 09/21/22 20220915 NES 220915 In article number 2201082, Simone Rossi, Fabio Pezzoli and co-workers present an all-optical approach to engineer the strength of the so-called Rashba effect emerging in biased germanium quantum wells. [Extracted from the article]

Neuromodulation refers to invasive, minimally invasive or non-invasive techniques to stimulate discrete cortical or subcortical brain regions with therapeutic purposes in otherwise intractable patients: for example, thousands of advanced Parkinsonian patients, as well as patients with tremor or dystonia, benefited by deep brain stimulation (DBS) procedures (neural targets: basal ganglia nuclei). A new era for DBS is currently opening for patients with drug-resistant depression, obsessive-compulsive disorders, severe epilepsy, migraine and chronic pain (neural targets: basal ganglia and other subcortical nuclei or associative fibres). Vagal nerve stimulation (VNS) has shown clinical benefits in patients with pharmacoresistant epilepsy and depression. Non-invasive brain stimulation neuromodulatory techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are also being increasingly investigated for their therapeutic potential in several neurological and psychiatric disorders. In this review, we first address the most common neural targets of each of the mentioned brain stimulation techniques, and the known mechanisms of their neuromodulatory action on stimulated brain networks. Then, we discuss how DBS, VNS, rTMS and tDCS could impact on the function of brainstem centres controlling vital functions, critically reviewing their acute and long-term effects on brain sympathetic outflow controlling heart function and blood pressure. Finally, as there is clear experimental evidence in animals that brain stimulation can affect autonomic and heart functions, we will try to give a critical perspective on how it may enhance our understanding of the cortical/subcortical mechanisms of autonomic cardiovascular regulation, and also if it might find a place among therapeutic opportunities in patients with otherwise intractable autonomic dysfunctions. [ABSTRACT FROM AUTHOR]

The Global Fire Emissions Database (GFED3) and the FAOSTAT Emissions database, containing estimates of greenhouse gas (GHG) emissions from biomass burning and peat fires, are compared. The two datasets formed the basis for several analyses in the fifth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC AR5), and thus represent a critical source of information for emissions inventories at national, regional and global level. The two databases differ in their level of computational complexity in estimating emissions. While both use the same burned area information from remote sensing, estimates of available biomass are computed in GFED3 at tier 3 using a complex dynamic vegetation model, while they are computed in FAOSTAT using default, tier 1 parameters from the Intergovernmental Panel on Climate Change (IPCC). Over the analysis period 1997-2011, the two methods were found to produce very similar global GHG emissions estimates for each of the five GFED aggregated biomass fire classes: i) Savanna; ii) Woodland; iii) Forest; iv) Deforestation; v) Peatlands; with total emissions ranging 6-8 Gt CO2eq yr. The main differences between the two datasets were found with respect to peat fires, with FAOSTAT showing a lower 1997-1998 peak in emissions compared with GFED3, within an otherwise good agreement for the rest of the study period, when limited to the three tropical countries covered by GFED. Conversely, FAOSTAT global emissions from peat fires, including both boreal and tropical regions, were several times larger than those currently estimated by GFED3. Results show that FAOSTAT activity data and emission estimates for biomass fires offer a robust alternative to the more sophisticated GFED data, representing a valuable resource for national GHG inventory experts, especially in countries where technical and institutional constraints may limit access, generation and maintenance of more complex methodologies and data. [ABSTRACT FROM AUTHOR]

This paper presents a predictive analytical model for the elasto-plastic behaviour of a light timber-frame wall under horizontal loading. The possibility to represent the total force carried by all fasteners (allowing for their sequential yielding) in one nonlinear spring is shown to be a key benefit. The development of this spring was investigated via a parametric study in which the variables were the sheathing panel aspect ratio and the fastener spacing. By developing equivalent springs for the other components, a rheological model for elasto-plastic behaviour of a sheathed timber-frame as function of the mechanical properties of connections was also defined. [ABSTRACT FROM AUTHOR]

This paper deals with the static and dynamic seismic analysis of light timber-frame buildings. Through the use of the UNITN-model proposed in a previous work, the study is here extended to full-scale buildings. An iterative procedure to properly distribute a horizontal load to the shear-walls, considering the coupled action of the vertical-load and the hold-downs state, is developed; three methods for the application of the response spectrum analysis are proposed as well. These methods may be used to predict the seismic-behaviour and to design non-regular timber shear-walls buildings. A numerical example illustrates the application of the procedures. [ABSTRACT FROM AUTHOR]

A simplified and reliable tool for the elastic analysis of one-storey timber shear-walls under simultaneous horizontal and vertical loads is presented. This approach is suitable for the analysis both of light timber-frame walls and CLT walls. The analytical expressions to determine the horizontal displacement and the elastic stiffness of a single wall are provided, these expressions are then extended to walls placed in series. A simplified numerical model suitable for F.E. analysis is also developed. In the last part of the paper a comparison between an analytical example and the results of a laboratory test is shown. [ABSTRACT FROM AUTHOR]

Our view is that intelligence, as expression of the complexity of the human brain and of its evolutionary path, represents an intriguing example of "system level brain plasticity": tangible proofs of this assertion lie in the strong links intelligence has with vital brain capacities as information processing (i.e., pure, rough capacity to transfer information in an efficient way), resilience (i.e., the ability to cope with loss of efficiency and/or loss of physical elements in a network) and adaptability (i.e., being able to efficiently rearrange its dynamics in response to environmental demands). Current evidence supporting this view move from theoretical models correlating intelligence and individual response to systematic "lesions" of brain connectivity, as well as from the field of Noninvasive Brain Stimulation (NiBS). Perturbation-based approaches based on techniques as transcranial magnetic stimulation (TMS) and transcranial alternating current stimulation (tACS), are opening new in vivo scenarios which could allow to disclose more causal relationship between intelligence and brain plasticity, overcoming the limitations of brain-behavior correlational evidence. [ABSTRACT FROM AUTHOR]

In ten healthy subjects and in ten patients suffering from Multiple Sclerosis (MS), we investigated the cortical functional changes induced by a standard fatiguing repetitive tapping task. The Cortical Silent Period (CSP), an intracortical, mainly GABAB-mediated inhibitory phenomenon, was recorded by two different hand muscles, one acting as prime mover of the fatiguing index-thumb tapping task (First Dorsal Interosseous, FDI) and the other one not involved in the task but sharing largely overlapping central, spinal, and peripheral innervation (Abductor Digiti Minimi, ADM). At baseline, the CSP was shorter in patients than in controls. As fatigue developed, CSP changes involved both the “fatigued” FDI and the “unfatigued” ADM muscles, suggesting a cortical spread of central fatigue mechanisms. Chronic therapy with amantadine annulled differences in CSP duration between controls and patients, possibly through restoration of more physiological levels of intracortical inhibition in the motor cortex. These inhibitory changes correlated with the improvement of fatigue scales. The CSP may represent a suitable marker of neurophysiological mechanisms accounting for central fatigue generation either in controls or in MS patients, involving corticospinal neural pools supplying not only the fatigued muscle but also adjacent muscles sharing an overlapping cortical representation. [ABSTRACT FROM AUTHOR]

The complex phenomena underlying mechanical contraction of cardiac cells and their influence in the dynamics of ventricular contraction are extremely important in understanding the overall function of the heart. In this paper we generalize previous contributions on the active strain formulation and propose a new model for the excitation-contraction coupling process. We derive an evolution equation for the active fiber contraction based on configurational forces, which is thermodynamically consistent. Geometrically, we link microscopic and macroscopic deformations giving rise to an orthotropic contraction mechanism that is able to represent physiologically correct thickening of the ventricular wall. A series of numerical tests highlights the importance of considering orthotropic mechanical activation in the heart and illustrates the main features of the proposed model. [ABSTRACT FROM AUTHOR]

Noninvasive brain stimulation techniques (NiBS) have gathered substantial interest in the study of dementia, considered their possible role in help defining diagnostic biomarkers of altered neural activity for early disease detection and monitoring of its pathophysiological course, as well as for their therapeutic potential of boosting residual cognitive functions. Nevertheless, current approaches suffer from some limitations. In this study, we review and discuss experimental NiBS applications that might help improve the efficacy of future NiBS uses in Alzheimer's Disease (AD), including perturbation-based biomarkers for early diagnosis and disease tracking, solutions to enhance synchronization of oscillatory electroencephalographic activity across brain networks, enhancement of sleep-related memory consolidation, image-guided stimulation for connectome control, protocols targeting interneuron pathology and protein clearance, and finally hybrid-brain models for in-silico modeling of AD pathology and personalized target selection. The present work aims to stress the importance of multidisciplinary, translational, model-driven interventions for precision medicine approaches in AD. [Display omitted] • The use of Noninvasive Brain Stimulation in Alzheimer's Disease is promising. • The rising of precision-medicine strives towards the personalization of protocols. • We review and discuss the most innovative solutions to tailor stimulation interventions. • Multidisciplinary approaches might be the key to increase the efficacy of protocols. [ABSTRACT FROM AUTHOR]

Abstract: Low-frequency repetitive transcranial magnetic stimulation (rTMS) to supplementary motor area (SMA) showed clinical benefit in obsessive-compulsive disorder (OCD). Here we tested whether clinical improvement was associated with enhanced cortical inhibition as measured by single and paired-pulse TMS variables. In 18 OCD patients receiving 4 weeks of either active or sham rTMS in a double-blind randomized trial, we assessed bilateral resting and active motor thresholds (RMT and AMT), cortical silent period (CSP), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). We tested correlations between changes in Yale-Brown Obsessive Compulsive Scale-Self-report (Y-BOCS-SR), Clinical Global Impression-Severity subscale (CGI-S) and cortical excitability measures. Active rTMS increased right hemisphere RMT whose change correlated with Y-BOCS-SR improvement. Baseline RMT hemispheric asymmetry, defined as the difference between left and right hemispheres RMT, and its normalization after active rTMS correlated with Y-BOCS-SR and CGI-S improvements. Active rTMS also increased right hemisphere SICI whose change correlated with Y-BOCS-SR and CGI-S at week 4, and with normalization of baseline RMT hemispheric asymmetry. Treatment-induced changes in cortical excitability measures are consistent with an inhibitory action of SMA rTMS on dysfunctional motor circuits in OCD. Correlations of neurophysiology measures with therapeutic outcome are supportive of the role of SMA in the modulation of OCD symptoms. [Copyright &y& Elsevier]

The current study was designed to evaluate activity-dependent changes intrinsic to the spinal motoneurones (MNs) associated with sustained contractions. The excitability of spinal MNs (reflected by the antidromically evoked F-wave) innervating the abductor digiti minimi muscle (ADM) was measured in 12 healthy subjects following maximum voluntary contractions (MVCs) of ADM lasting 5 s, 15 s, 30 s, and 60 s. Upon cessation of the contractions, F-waves showed a depression, which increased in depth and duration with increasing duration of contraction. Following a 5-s contraction, there was a 20% decrease, which waned in 2 min, whereas a 60-s contraction produced a 40% decrease and waned in over 15 min. The changes in excitability of peripheral motor axons produced by the MVCs were measured by recording an ADM compound muscle action potential (CMAP) of ~50% of maximum to a constant ulnar nerve electrical stimulation. On cessation of the contractions, there was a prominent decrease in size of the CMAP: following a 5-s MVC, it produced a 10% decrease in the size of the test CMAP, which recovered in 2 min, whereas following a 60-s MVC, it produced a 30% decrease, which recovered in over 15 min. Statistical analysis (correntropy) showed a high-order mutual dependence between F-wave and CMAP, and both were significantly dependent on MVC duration. Because of the parallel excitability changes in peripheral axons and spinal MNs, our interpretation is that intrinsic excitability of the axon initial segment (i.e., where the action potential is generated) and peripheral axon segments changed in a similar, activity-dependent manner. [ABSTRACT FROM AUTHOR]

SUMMARY A model for the active deformation of cardiac tissue considering orthotropic constitutive laws is introduced and studied. In particular, the passive mechanical properties of the myocardium are described by the Holzapfel-Ogden relation, whereas the activation model is based on the concept of active strain. There, an incompatible intermediate configuration is considered, which entails a multiplicative decomposition between active and passive deformation gradients. The underlying Euler-Lagrange equations for minimizing the total energy are written in terms of these deformation factors, where the active part is assumed to depend, at the cell level, on the electrodynamics and on the specific orientation of the cardiomyocytes. The active strain formulation is compared with the classical active stress model from both numerical and modeling perspectives. The well-posedness of the linear system derived from a generic Newton iteration of the original problem is analyzed, and different mechanical activation functions are considered. Taylor-Hood and MINI finite elements are used in the discretization of the overall mechanical problem. The results of several numerical experiments show that the proposed formulation is mathematically consistent and is able to represent the main features of the phenomenon, while allowing savings in computational costs. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The number of drugs with boxed warnings and the detail in the box are much greater in the USA than Australia. US warnings are up to ten times longer and often include a great deal of detail and qualified advice. Australian warnings are usually just a few sentences long and the expected response unequivocal. Other details are relegated to the relevant section within the product information. The restriction of warnings such that they are succinct and used sparingly are explicitly highlighted in the guidelines for boxed warnings in Australia. In addition, the range of other risk management strategies used may be broader. Widespread prescription drug subsidies and mechanisms set up to implement the ''Quality Use of Medicines'' policy provide a complementary range of options. Withdrawal of registration, removal of subsidies for all or selected indications, changed product information and labels, consumer-targeted information, prescriber mail outs, education programmes, restriction to authorised prescribers, and changed pack size and packaging have all been applied at some time in response to safety concerns. The diversity of approaches around the world provides an opportunity for a systematic approach to look at the effects of boxed warnings on prescribing practices so that we might discover what works best. While there are many studies on the effect of warnings from the USA, there are few comparable studies done where different approaches are used. Further, it is not possible to easily examine the total number and purpose of boxed warnings via any government websites. If there were always explicit and potentially verifiable changes in practice as the stated goal for each boxed warning in each jurisdiction and a requirement that the effectiveness of the intervention was measured against these goals, then we might have the evidence base for better policy around boxed warnings. [ABSTRACT FROM AUTHOR]

A number of cortical and spinal excitability variables have been tested in a patient with Stiff Person Syndrome (SPS), before and after immunotherapy with mycophenolate mofetil, intravenous immunoglobulin and corticosteroids, which normalized plasma levels of anti-GAD antibodies and dramatically improved the clinical picture. The overlapping time-course of neurophysiological, clinical and bio-umoral findings suggests that immunotherapy might have changed GABA/Glutamate balance at cortical level, favoring the former, as reflected by normalization of the startle reflex, lengthening of the cortical silent period and clear-cut reduction of intracortical facilitation to paired-pulse transcranial magnetic stimulation. This represents the first report investigating effects of immunotherapy on cortical excitability in SPS. [ABSTRACT FROM AUTHOR]

Abstract: This article is based on a consensus conference, which took place in Certosa di Pontignano, Siena (Italy) on March 7–9, 2008, intended to update the previous safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings. Over the past decade the scientific and medical community has had the opportunity to evaluate the safety record of research studies and clinical applications of TMS and repetitive TMS (rTMS). In these years the number of applications of conventional TMS has grown impressively, new paradigms of stimulation have been developed (e.g., patterned repetitive TMS) and technical advances have led to new device designs and to the real-time integration of TMS with electroencephalography (EEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Thousands of healthy subjects and patients with various neurological and psychiatric diseases have undergone TMS allowing a better assessment of relative risks. The occurrence of seizures (i.e., the most serious TMS-related acute adverse effect) has been extremely rare, with most of the few new cases receiving rTMS exceeding previous guidelines, often in patients under treatment with drugs which potentially lower the seizure threshold. The present updated guidelines review issues of risk and safety of conventional TMS protocols, address the undesired effects and risks of emerging TMS interventions, the applications of TMS in patients with implanted electrodes in the central nervous system, and safety aspects of TMS in neuroimaging environments. We cover recommended limits of stimulation parameters and other important precautions, monitoring of subjects, expertise of the rTMS team, and ethical issues. While all the recommendations here are expert based, they utilize published data to the extent possible. [Copyright &y& Elsevier]

Background: The investigation of a wide set of transcranial magnetic stimulation (TMS)-related variables in both hemispheres might help to identify a pattern of cortical excitability changes in posttraumatic stress disorder (PTSD) patients, reflecting γ-amino-butiric acid (GABA)/glutamate balance and dysfunction, and to determine whether some of these variables are related to clinical features. Methods: In 20 drug-naive PTSD patients without comorbidity and 16 matched healthy control subjects we tested bilaterally with standard TMS procedures: resting motor threshold (RMT) to single-pulse TMS (reflecting ion channel function), paired-pulse short-latency intracortical inhibition (SICI; mainly reflecting GABAA function) and intracortical facilitation (ICF; mainly reflecting glutamatergic function), single-pulse cortical silent period (CSP; mainly reflecting GABAB-ergic function), and paired-pulse short-latency afferent inhibition (SAI; reflecting cholinergic mechanisms and their presynaptic GABAA-mediated modulation). Results: The PTSD patients showed widespread impairment of GABAA-ergic SICI, which was reversed toward facilitation in both hemispheres in one-half of the patients, marked increase of glutamatergic ICF in the right hemisphere, and right-sided impairment of SAI. Illness duration and avoidance symptoms but not anxiety correlated with right-lateralized dysfunctions of cortical excitability. Conclusions: Although the neurobiological complexity of each TMS variable makes current results theoretical, the pattern of cortical excitability accompanying PTSD symptoms suggests a bilateral decrease of the GABAA-ergic function. This prevails in the right hemisphere, in association with a relative prevalence of the glutamatergic tone, a new finding that current neuroimaging investigations cannot provide due to the lack of reliable glutamate tracers. Results might help to disclose new pathophysiological aspects of PTSD symptoms, providing a rationale for future neuromodulatory strategies of treatment. [Copyright &y& Elsevier]

Background: Converging evidence indicates that action observation and action-related sounds activate cross-modally the human motor system. Since olfaction, the most ancestral sense, may have behavioural consequences on human activities, we causally investigated by transcranial magnetic stimulation (TMS) whether food odour could additionally facilitate the human motor system during the observation of grasping objects with alimentary valence, and the degree of specificity of these effects. Methodology/Principal Findings: In a repeated-measure block design, carried out on 24 healthy individuals participating to three different experiments, we show that sniffing alimentary odorants immediately increases the motor potentials evoked in hand muscles by TMS of the motor cortex. This effect was odorant-specific and was absent when subjects were presented with odorants including a potentially noxious trigeminal component. The smell-induced corticospinal facilitation of hand muscles during observation of grasping was an additive effect which superimposed to that induced by the mere observation of grasping actions for food or non-food objects. The odour-induced motor facilitation took place only in case of congruence between the sniffed odour and the observed grasped food, and specifically involved the muscle acting as prime mover for hand/fingers shaping in the observed action. Conclusions/Significance: Complex olfactory cross-modal effects on the human corticospinal system are physiologically demonstrable. They are odorant-specific and, depending on the experimental context, muscle- and action-specific as well. This finding implies potential new diagnostic and rehabilitative applications. [ABSTRACT FROM AUTHOR]

Abstract: Physiological brain aging is characterized by a loss of synaptic contacts and neuronal apoptosis that provokes age-dependant decline of sensory processing, motor performance, and cognitive function. Neural redundancy and plastic remodelling of brain networking, also secondary to mental and physical training, promotes maintenance of brain activity in healthy elderly for everyday life and fully productive affective and intellectual capabilities. However, age is the main risk factor for neurodegenerative disorders such as Alzheimer''s disease (AD) that impact on cognition. Oscillatory electromagnetic brain activity is a hallmark of neuronal network function in various brain regions. Modern neurophysiological techniques including electroencephalography (EEG), event-related potential (ERP), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS) can accurately index normal and abnormal brain aging to facilitate non-invasive analysis of cortico–cortical connectivity and neuronal synchronization of firing and coherence of rhythmic oscillations at various frequencies. The present review provides a perspective of these issues by assaying different neurophysiological methods and integrating the results with functional brain imaging findings. It is concluded that discrimination between physiological and pathological brain aging clearly emerges at the group level, with applications at the individual level also suggested. Integrated approaches utilizing neurophysiological techniques together with biological markers and structural and functional imaging are promising for large-scale, low-cost and non-invasive evaluation of at-risk populations. Practical implications of the methods are emphasized. [Copyright &y& Elsevier]

Background: Chronic tinnitus is a disabling, almost untreatable, condition, usually accompanied by psychiatric distress. In patients with complex neuropsychiatric diseases, such as chronic pain, with which tinnitus shares pathophysiological similarities, placebo effects may be pronounced. Moreover, it may be difficult to distinguish actual repetitive transcranial magnetic stimulation (rTMS) induced clinical benefits beyond placebo effects in neuropsychiatric patients. Methods: 16 patients with chronic tinnitus underwent a randomised, double blind, crossover, placebo controlled trial of 1 Hz rTMS (120% of motor threshold; 1200 stimuli/day for 5 days) of the left temporoparietal region. Patients were screened for psychiatric comorbidity; additionally, anxiety and depression were monitored throughout the study. Moreover, an original placebo rTMS procedure produced the same activation of ipsilateral face muscles (a condition which may per se change the subjective rating of tinnitus) as the real rTMS. Results: There were 8 out of 14 responders. Two patients dropped out for transient worsening of tinnitus. Active rTMS induced an overall significant, but transient, improvement (35% of the basal score) of subjective tinnitus perception that was independent of either tinnitus laterality or mood or anxiety changes. No correlations were found between response to rTMS and tinnitus duration, initial subjective score or patient age. When asked after the study was over, 71.4% of patients failed to identify the temporal sequence of the real or sham rTMS interventions. Conclusion: The beneficial effects of rTMS on tinnitus are independent of mood changes. Moreover, they appear in the context of an original placebo stimulation designed to more closely replicate the somatic sensation of active stimulation. Because of the limited temporal duration of the clinical benefit, these neuromodulatory effects could be mediated by transient functional changes taking place in the neural circuits underlying tinnitus processing. [ABSTRACT FROM AUTHOR]

Abstract: Objective: There is growing interest in neuropsychiatry for repetitive transcranial magnetic stimulation (rTMS) as a neuromodulatory treatment. However, there are limitations in interpreting rTMS effects as a real consequence of physiological brain changes or as placebo-mediated unspecific effects, which may be particularly strong in psychiatric patients. This is due to the fact that existing sham rTMS procedures are less than optimal. A new placebo tool is introduced here, called real electro-magnetic placebo (REMP) device, which can simulate the scalp sensation induced by the real TMS, while leaving both the visual impact and acoustic sensation of real TMS unaltered. Methods: Physical, neurophysiological and behavioural variables of monophasic and biphasic single-pulse TMS and biphasic 1Hz and 20Hz rTMS procedures (at different intensities) were tested in subjects who were expert or naïve of TMS. Results of the real TMS were compared with those induced by the REMP device and with two other currently used sham procedures, namely the commercially available Magstim sham coil and tilting the real coil by 90°. Results: The REMP device, besides producing scalp sensations similar to the real TMS, attenuated the TMS-induced electric field (as measured by a dipole probe) to a biologically inactive level. Behaviourally, neither expert nor naïve TMS subjects identified the “coil at 90°” or the “Magstim sham coil” as a real TMS intervention, whilst naïve subjects were significantly more likely to identify the REMP-attenuated TMS as real. Conclusions: The “goodness of sham” of the REMP device is demonstrated by physical, neurophysiological, and behavioural results. Significance: Such placebo TMS is superior to the available sham procedures when applied on subjects naïve to TMS, as in case of patients undergoing a clinical rTMS trial. [Copyright &y& Elsevier]

Purpose: To assess the effectiveness of slow repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for drug-resistant epilepsy. Methods: Forty-three patients with drug-resistant epilepsy from eight Italian Centers underwent a randomized, double-blind, sham-controlled, crossover study on the clinical and EEG effects of slow rTMS. The stimulus frequency was 0.3 Hz. One thousand stimuli per day were given at the resting motor threshold intensity for 5 consecutive days, with a round coil at the vertex. Results:“Active” rTMS was no better than placebo for seizure reduction. However, it decreased interictal EEG epileptiform abnormalities significantly (p < 0.05) in one-third of the patients, which supports a detectable biologic effect. No correlation linked the rTMS effects on seizure frequency to syndrome or anatomic classification, seizure type, EEG changes, or resting motor threshold (an index of motor cortex excitability). Conclusions: Although the antiepileptic action was not significant (p > 0.05), the individual EEG reactivity to “active” rTMS may be encouraging for the development of more-powerful, noninvasive neuromodulatory strategies. [ABSTRACT FROM AUTHOR]

Neuroimaging findings, including repetitive transcranial magnetic stimulation (rTMS) interference, point to an engagement of prefrontal cortex (PFC) in learning and memory. Whether parietal cortex (PC) activity is causally linked to successful episodic encoding and retrieval is still uncertain. We compared the effects of event-related active or sham rTMS (a rapid-rate train coincident to the very first phases of memoranda presentation) to the left or right intraparietal sulcus, during a standardized episodic memory task of visual scenes, with those obtained in a fully matched sample of subjects who received rTMS on left or right dorsolateral PFC during the same task. In these subjects, specific hemispheric effects of rTMS included interference with encoding after left stimulation and disruption of retrieval after right stimulation. The interference of PC-rTMS on encoding/retrieval performance was negligible, lacking specificity even when higher intensities of stimulation were applied. However, right PC-rTMS of the same intensity lengthened reaction times in the context of a purely attentive visuospatial task. These results suggest that the activity of intraparietal sulci shown in several funtional magnetic resonance studies on memory, unlike that of the dorsolateral PFC, is not causally engaged to a useful degree in memory encoding and retrieval of visual scenes. The parietal activations accompanying the memorization processes could reflect the engagement of a widespread brain attentional network, in which interference on a single ‘node’ is insufficient for an overt disruption of memory performance. [ABSTRACT FROM AUTHOR]

Background: In obsessive-compulsive disorder (OCD) patients, functional abnormalities in basal ganglia/precentral circuitries cause cortical hyperexcitability and lack of inhibitory control. These loops can be partly explored by median-nerve somatosensory evoked potentials (SEPs), which functionally reflect the brain responsiveness to somatosensory stimuli. In healthy humans, SEPs’ amplitude during voluntary finger movements is lower than during muscular relaxation (i.e., sensory gating). Cortical hyperexcitability in OCD could be eventually responsible for a reduction of sensory gating. This might have pathophysiologic implications for motor compulsions. Methods: Median-nerve SEPs were recorded in 11 OCD patients and 9 healthy volunteers during muscle relaxation (“Relax”) or finger movements of the stimulated hand (“Move”). Latencies and amplitudes of pre- and postcentral SEP components were compared between groups during “Relax” and “Move” conditions. Results: In OCD patients, the responsiveness to sensory stimuli was enhanced for precentral SEPs. Sensory gating (“Relax” vs. “Move”) in control subjects involved both pre- and postcentral SEPs, the former being reduced in amplitude by approximately 60%. In OCD patients, sensory gating was spatially restricted to precentral SEP components and was significantly reduced compared with control subjects (approximately 30%). Conclusions: Enhanced precentral SEPs and hypofunctioning of centrifugal sensory gating in OCD might reflect the inability to modulate sensory information due to a “tonic” high level of cortical excitability of motor and related areas, likely resulting from basal ganglia dysfunction. This might offer new insights into the pathophysiology of OCD. [Copyright &y& Elsevier]

Neuroimaging findings suggest that the lateralization of prefrontal cortex activation associated with episodic memory performance is reduced by aging. It is still a matter of debate whether this loss of asymmetry during encoding and retrieval reflects compensatory mechanisms or de-differentiation processes. We addressed this issue by the transient interference produced by repetitive transcranial magnetic stimulation (rTMS), which directly assesses causal relationships between performance and stimulated regions. We compared the effects of rTMS (a rapid-rate train occurring simultaneously to the presentation of memoranda) applied to the left or right dorsolateral prefrontal cortex (DLPFC) on visuospatial recognition memory in 66 healthy subjects divided in two classes of age (< 45 and > 50 years). In young subjects, rTMS of the right DLPFC interfered with retrieval more than left DLPFC stimulation. The asymmetry of the effect progressively vanished with aging, as indicated by bilateral interference effects on recognition performance. Conversely, the predominance of left DLPFC effect during encoding was not abolished in elders, thus probing its causal role for encoding along the life span. Findings confirm that the neural correlates of retrieval modify along aging, suggesting that the bilateral engagement of the DLPFC has a compensatory role on the elders' episodic memory performance. [ABSTRACT FROM AUTHOR]

Cognitive neuroscientists use transcranial magnetic stimulation (TMS) in several ways, from aiming to increase understanding of brain–behavior relationships to transiently improving performance, both in normals and in patients with neurological and neuropsychological deficits. Different types of TMS (single-pulse, paired-pulse, repetitive) are able to interfere with higher brain functions that require the cooperation of different brain areas and complex neuronal networks. Currently, behavioral TMS effects on the brain are usually short-lived and their underlying mechanisms not yet wholly understood. However, the aim of using TMS to develop rehabilitative strategies for motor, perceptive and cognitive functions represents an intriguing challenge. [Copyright &y& Elsevier]