Mathematical modeling of the human heart and its function can expand our understanding of various cardiac diseases, which remain the most common cause of death in the developed world. Like other ...physiological systems, the heart can be understood as a complex multiscale system involving interacting phenomena at the molecular, cellular, tissue, and organ levels. This article addresses the numerical modeling of many aspects of heart function, including the interaction of the cardiac electrophysiology system with contractile muscle tissue, the sub-cellular activation–contraction mechanisms, as well as the hemodynamics inside the heart chambers. Resolution of each of these sub-systems requires separate mathematical analysis and specially developed numerical algorithms, which we review in detail. By using specific sub-systems as examples, we also look at systemic stability, and explain for example how physiological concepts such as microscopic force generation in cardiac muscle cells, translate to coupled systems of differential equations, and how their stability properties influence the choice of numerical coupling algorithms. Several numerical examples illustrate three fundamental challenges of developing multiphysics and multiscale numerical models for simulating heart function, namely: (i) the correct upscaling from single-cell models to the entire cardiac muscle, (ii) the proper coupling of electrophysiology and tissue mechanics to simulate electromechanical feedback, and (iii) the stable simulation of ventricular hemodynamics during rapid valve opening and closure.
Working memory (WM) refers to a set of cognitive processes that allows for the temporary storage and manipulation of information, crucial for everyday life skills. WM deficits are present in several ...neurological, psychiatric, and neurodevelopmental disorders, thus making the full understanding of its neural correlates a key aspect for the implementation of cognitive training interventions. Here, we present a quantitative meta‐analysis focusing on the underlying neural substrates upon which the n‐back, one of the most commonly used tasks for WM assessment, is believed to rely on, as highlighted by functional magnetic resonance imaging and positron emission tomography findings. Relevant published work was scrutinized through the activation likelihood estimate (ALE) statistical framework in order to generate a set of task‐specific activation maps, according to n‐back difficulty. Our results confirm the known involvement of frontoparietal areas across different types of n‐back tasks, as well as the recruitment of subcortical structures, cerebellum and precuneus. Specific activations maps for four stimuli types, six presentation modalities, three WM loads and their combination are provided and discussed. Moreover, functional overlap with resting‐state networks highlighted a strong similarity between n‐back nodes and the Dorsal Attention Network, with less overlap with other networks like Salience, Language, and Sensorimotor ones. Additionally, neural deactivations during n‐back tasks and their functional connectivity profile were examined. Clinical and functional implications are discussed in the context of potential noninvasive brain stimulation and cognitive enhancement/rehabilitation programs.
•rTMS can produce significant clinical improvement in various neurological and psychiatric disorders.•Updated guidelines on the therapeutic use of rTMS are presented, including 2014–2018 ...publications.•Higher evidence of efficacy is present in the areas of depression, pain, and postacute motor stroke.
A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 Lefaucheur et al., Clin Neurophysiol 2014;125:2150–206. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a H1-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respectively, in Parkinson’s disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spasticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recommendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance.
Imperceptible transcranial alternating current stimulation (tACS) changes the endogenous cortical oscillatory activity in a frequency-specific manner. In the human motor system, tACS coincident with ...the idling beta rhythm of the quiescent motor cortex increased the corticospinal output. We reasoned that changing the initial state of the brain (i.e., from quiescence to a motor imagery task that desynchronizes the local beta rhythm) might also change the susceptibility of the corticospinal system to resonance effects induced by beta-tACS. We tested this hypothesis by delivering tACS at different frequencies (theta, alpha, beta, and gamma) on the primary motor cortex at rest and during motor imagery. Motor-evoked potentials (MEPs) were obtained by transcranial magnetic stimulation (TMS) on the primary motor cortex with an online-navigated TMS-tACS setting. During motor imagery, the increase of corticospinal excitability was maximal with theta-tACS, likely reflecting a reinforcement of working memory processes required to mentally process and "execute" the cognitive task. As expected, the maximal MEPs increase with subjects at rest was instead obtained with beta-tACS, substantiating previous evidence. This dissociation provides new evidence of state and frequency dependency of tACS effects on the motor system and helps discern the functional role of different oscillatory frequencies of this brain region. These findings may be relevant for rehabilitative neuromodulatory interventions.
Different corticothalamic brain modules intrinsically oscillate at a "natural frequency" in a topographically organized manner. In "quiescent" human sensorimotor regions, the main detectable ...oscillatory activity peaks at ∼20 Hz, and partly contributes to determine the state of corticospinal excitability. Here, we showed that the transcranial application of an imperceptible, short-lasting (90 s) electric field oscillating at a physiological range increases corticospinal excitability online, with well defined frequency dependence and regional specificity. Indeed, the size of motor evoked potentials (MEPs) induced by navigated single-pulse TMS over the motor cortex significantly increased only during the local application of transcranial alternating current stimulation (tACS) at 20 Hz (β range). Other tACS frequencies (5, 10, and 40 Hz) applied on the motor cortex did not impact MEPs' size. Moreover, tACS applied on a control site (parietal cortex) and on a peripheral site (ulnar nerve) also failed to modulate MEPs. These results help clarifying the functional significance of the 20 Hz idling β rhythm of sensorimotor regions and suggest potential clinical applications of this approach.
Highlights • NiBS techniques seem able to enhance cognitive abilities in the elderly. • Major concerns derive from the variability and volatility of tES-induced effects. • Protocols based on imaging ...and electrophysiology are needed to control for individual variability.
Highlights • A group of European experts reviewed current evidence for therapeutic efficacy of tDCS. • Level B evidence (probable efficacy) was found for fibromyalgia, depression and craving. • The ...therapeutic relevance of tDCS needs to be further explored in these and other indications.
Greenhouse gas (GHG) emissions from agriculture, including crop and livestock production, forestry and associated land use changes, are responsible for a significant fraction of anthropogenic ...emissions, up to 30% according to the Intergovernmental Panel on Climate Change (IPCC). Yet while emissions from fossil fuels are updated yearly and by multiple sources-including national-level statistics from the International Energy Agency (IEA)-no comparable efforts for reporting global statistics for agriculture, forestry and other land use (AFOLU) emissions exist: the latest complete assessment was the 2007 IPCC report, based on 2005 emission data. This gap is critical for several reasons. First, potentially large climate funding could be linked in coming decades to more precise estimates of emissions and mitigation potentials. For many developing countries, and especially the least developed ones, this requires improved assessments of AFOLU emissions. Second, growth in global emissions from fossil fuels has outpaced that from AFOLU during every decade of the period 1961-2010, so the relative contribution of the latter to total climate forcing has diminished over time, with a need for regular updates. We present results from a new GHG database developed at FAO, providing a complete and coherent time series of emission statistics over a reference period 1961-2010, at country level, based on FAOSTAT activity data and IPCC Tier 1 methodology. We discuss results at global and regional level, focusing on trends in the agriculture sector and net deforestation. Our results complement those available from the IPCC, extending trend analysis to a longer historical period and, critically, beyond 2005 to more recent years. In particular, from 2000 to 2010, we find that agricultural emissions increased by 1.1% annually, reaching 4.6 Gt CO2 yr−1 in 2010 (up to 5.4-5.8 Gt CO2 yr−1 with emissions from biomass burning and organic soils included). Over the same decade 2000-2010, the ratio of agriculture to fossil fuel emissions has decreased, from 17.2% to 13.7%, and the decrease is even greater for the ratio of net deforestation to fossil fuel emissions: from 19.1% to 10.1%. In fact, in the year 2000, emissions from agriculture have been consistently larger-about 1.2 Gt CO2 yr−1 in 2010-than those from net deforestation.
Highlights • Numerous studies have shown that repetitive transcranial magnetic stimulation (rTMS) produced significant clinical effects in patients with various neurological and psychiatric ...disorders. • This review presents guidelines on the therapeutic use of rTMS issued by a group of European experts. • Level A or B evidence supports an efficacy of rTMS protocols in depression, pain, motor stroke and schizophrenia.
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