Tacrolimus-associated neurotoxicity isolated to the brainstem: two illustrative cases and a systematic review of the literature.

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.

Suitability of electroencephalography in brain death determination: a monocentric, 10-year retrospective, observational investigation of 428 cases.

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.

Non-invasive Brain Stimulation Techniques for the Improvement of Upper Limb Motor Function and Performance in Activities of Daily Living After Stroke: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To compare the efficacy of non-invasive brain stimulation (NiBS) such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), and transcutaneous vagus nerve stimulation (taVNS) in upper limb stroke rehabilitation. DATA SOURCES: PubMed, Web of Science, and Cochrane databases were searched from January 2010 to June 2022. DATA SELECTION: Randomized controlled trials (RCTs) assessing the effects of "tDCS", "rTMS", "TBS", or "taVNS" on upper limb motor function and performance in activities of daily livings (ADLs) after stroke. DATA EXTRACTION: Data were extracted by 2 independent reviewers. Risk of bias was evaluated with the Cochrane Risk of Bias tool. DATA SYNTHESIS: 87 RCTs with 3750 participants were included. Pairwise meta-analysis showed that all NiBS except continuous TBS (cTBS) and cathodal tDCS were significantly more efficacious than sham stimulation for motor function (standardized mean difference [SMD] range 0.42-1.20), whereas taVNS, anodal tDCS, and both low and high frequency rTMS were significantly more efficacious than sham stimulation for ADLs (SMD range 0.54-0.99). NMA showed that taVNS was more effective than cTBS (SMD:1.00; 95% CI (0.02-2.02)), cathodal tDCS (SMD:1.07; 95% CI (0.21-1.92)), and Physical rehabilitation alone (SMD:1.46; 95% CI (0.59-2.33)) for improving motor function. P-score found that taVNS is best ranked treatment in improving motor function (SMD: 1.20; 95% CI (0.46-1.95)) and ADLs (SMD:1.20; 95% CI (0.45-1.94)) after stroke. After taVNS, excitatory stimulation protocols (intermittent TBS, anodal tDCS, and HF-rTMS) are most effective in improving motor function and ADLs after acute/sub-acute (SMD range 0.53-1.63) and chronic stroke (SMD range 0.39-1.16). CONCLUSIONS: Evidence suggests that excitatory stimulation protocols are the most promising intervention in improving upper limb motor function and performance in ADLs. taVNS appeared to be a promising intervention for stroke patients, but further large RCTs are required to confirm its relative superiority.

A stabilized linear finite element method for anisotropic poroelastodynamics with application to cardiac perfusion.

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.

How Much Is Enough? A Study on Diffusion Times in Score-Based Generative Models.

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.

Hands-feet wireless devices: Test-retest reliability and discriminant validity of motor measures in Parkinson's disease telemonitoring.

BACKGROUND: Telemonitoring, a branch of telemedicine, involves the use of technological tools to remotely detect clinical data and evaluate patients. Telemonitoring of patients with Parkinson's disease (PD) should be performed using reliable and discriminant motor measures. Furthermore, the method of data collection and transmission, and the type of subjects suitable for telemonitoring must be well defined. OBJECTIVE: To analyze differences in patients with PD and healthy controls (HC) with the wearable inertial device SensHands-SensFeet (SH-SF), adopting a standardized acquisition mode, to verify if motor measures provided by SH-SF have a high discriminating capacity and high intraclass correlation coefficient (ICC). METHODS: Altogether, 64 patients with mild-to-moderate PD and 50 HC performed 14 standardized motor activities for assessing bradykinesia, postural and resting tremors, and gait parameters. SH-SF inertial devices were used to acquire movements and calculate objective motor measures of movement (total: 75). For each motor task, five or more biomechanical parameters were measured twice. The results were compared between patients with PD and HC. RESULTS: Fifty-eight objective motor measures significantly differed between patients with PD and HC; among these, 32 demonstrated relevant discrimination power (Cohen's d > 0.8). The test-retest reliability was excellent in patients with PD (median ICC = 0.85 right limbs, 0.91 left limbs) and HC (median ICC = 0.78 right limbs, 0.82 left limbs). CONCLUSION: In a supervised environment, the SH-SF device provides motor measures with good results in terms of reliability and discriminant ability. The reliability of SH-SF measurements should be evaluated in an unsupervised home setting in future studies.

Mortality of Parkinson's disease in Italy from 1980 to 2015.

OBJECTIVE: To evaluate mortality for Parkinson's disease (PD) in Italy during a long time period (1980-2015) and to discuss the role of possible general and specific influencing factors. METHODS: Based on mortality data provided by the Italian National Institute of Statistics, sex- and age-specific crude mortality rates were computed, for the whole country and for its main geographical sub-areas. Rates were standardized using both direct (annual mortality rates AMRs) and indirect (standardized mortality rates SMRs) methods. SMRs were used to evaluate geographical differences, whereas AMRs and joinpoint linear regression analysis to study mortality trends. RESULTS: Considering the entire period, highest mortality rates were observed in males (AMR/100,000: 9.0 in males, 5.25 in females), in North-West and Central Italy (SMR > 100). Overall PD mortality decreased from mid-eighties onwards and then rapidly reversed the trend in the period 1998-2002, rising up to a maximum in 2015, with some differences according to sex and geographical areas. CONCLUSIONS: Several factors may have contributed to the rapid inversion of decreasing trend in mortality observed in the last part of XX century. Possible explanations of this rising trend are related to the increasing burden of PD (especially in males and in certain Italian regions), caused by different factors as population aging, physiological prevalence rise due to incidence exceeding mortality, and growing exposure to environmental or occupational risk factors. In addition, the accuracy of death certificate compilation could account for geographical differences and for the temporal trend. The role of levodopa and recently introduced dopaminergic drugs is also discussed.

Acute stroke-like deficits associated with nonketotic hyperglycemic hyperosmolar state: an illustrative case and systematic review of literature.

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.

Neural correlates of N-back task performance and proposal for corresponding neuromodulation targets in psychiatric and neurodevelopmental disorders.

AIM: Working memory (WM) deficit represents the most common cognitive impairment in psychiatric and neurodevelopmental disorders, making the identification of its neural substrates a crucial step towards the conceptualization of restorative interventions. We present a meta-analysis focusing on neural activations associated with the most commonly used task to measure WM, the N-back task, in patients with schizophrenia, depressive disorder, bipolar disorder, and attention-deficit/hyperactivity disorder. Showing qualitative similarities and differences in WM processing between patients and healthy controls, we propose possible targets for cognitive enhancement approaches. METHODS: Selected studies, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, were analyzed through the activation likelihood estimate statistical framework, with subsequent generation of disorder-specific N-back activation maps. RESULTS: Despite similar WM deficits shared across all disorders, results highlighted different brain activation patterns for each disorder compared with healthy controls. In general, results showed brain activity in frontal, parietal, subcortical, and cerebellar regions; however, reduced engagement of specific nodes of the fronto-parietal network emerged in patients compared with healthy controls. In particular, neither bipolar nor depressive disorders showed detectable activations in the dorsolateral prefrontal cortices, while their parietal activation patterns were lateralized to the left and right hemispheres, respectively. On the other hand, patients with attention-deficit/hyperactivity disorder showed a lack of activation in the left parietal lobe, whereas patients with schizophrenia showed lower activity over the left prefrontal cortex. CONCLUSION: These results, together with biophysical modeling, were then used to discuss the design of future disorder-specific cognitive enhancement interventions based on noninvasive brain stimulation.

Local and Distributed fMRI Changes Induced by 40 Hz Gamma tACS of the Bilateral Dorsolateral Prefrontal Cortex: A Pilot Study.

Over the past few years, the possibility of modulating fast brain oscillatory activity in the gamma (γ) band through transcranial alternating current stimulation (tACS) has been discussed in the context of both cognitive enhancement and therapeutic scenarios. However, the effects of tACS targeting regions outside the motor cortex, as well as its spatial specificity, are still unclear. Here, we present a concurrent tACS-fMRI block design study to characterize the impact of 40 Hz tACS applied over the left and right dorsolateral prefrontal cortex (DLPFC) in healthy subjects. Results suggest an increase in blood oxygenation level-dependent (BOLD) activity in the targeted bilateral DLPFCs, as well as in surrounding brain areas affected by stimulation according to biophysical modeling, i.e., the premotor cortex and anterior cingulate cortex (ACC). However, off-target effects were also observed, primarily involving the visual cortices, with further effects on the supplementary motor areas (SMA), left subgenual cingulate, and right superior temporal gyrus. The specificity of 40 Hz tACS over bilateral DLPFC and the possibility for network-level effects should be considered in future studies, especially in the context of recently promoted gamma-induction therapeutic protocols for neurodegenerative disorders.

Overlapping and dissociable brain activations for fluid intelligence and executive functions.

Cognitive enhancement interventions aimed at boosting human fluid intelligence (gf) have targeted executive functions (EFs), such as updating, inhibition, and switching, in the context of transfer-inducing cognitive training. However, even though the link between EFs and gf has been demonstrated at the psychometric level, their neurofunctional overlap has not been quantitatively investigated. Identifying whether and how EFs and gf might share neural activation patterns could provide important insights into the overall hierarchical organization of human higher-order cognition, as well as suggest specific targets for interventions aimed at maximizing cognitive transfer. We present the results of a quantitative meta-analysis of the available fMRI and PET literature on EFs and gf in humans, showing the similarity between gf and (i) the overall global EF network, as well as (ii) specific maps for updating, switching, and inhibition. Results highlight a higher degree of similarity between gf and updating (80% overlap) compared with gf and inhibition (34%), and gf and switching (17%). Moreover, three brain regions activated for both gf and each of the three EFs also were identified, located in the left middle frontal gyrus, left inferior parietal lobule, and anterior cingulate cortex. Finally, resting-state functional connectivity analysis on two independent fMRI datasets showed the preferential behavioural correlation and anatomical overlap between updating and gf. These findings confirm a close link between gf and EFs, with implications for brain stimulation and cognitive training interventions.

Mindfulness-based stress reduction training modulates striatal and cerebellar connectivity.

Mindfulness is a meditation practice frequently associated with changes in subjective evaluation of cognitive and sensorial experience, as well as with modifications of brain activity and morphometry. Aside from the anatomical localization of functional changes induced by mindfulness practice, little is known about changes in functional and effective functional magnetic resonance imaging (fMRI) connectivity. Here we performed a connectivity fMRI analysis in a group of healthy individuals participating in an 8-week mindfulness-based stress reduction (MBSR) training program. Data from both a "mind-wandering" and a "meditation" state were acquired before and after the MBSR course. Results highlighted decreased local connectivity after training in the right anterior putamen and insula during spontaneous mind-wandering and the right cerebellum during the meditative state. A further effective connectivity analysis revealed (a) decreased modulation by the anterior cingulate cortex over the anterior portion of the putamen, and (b) a change in left and right posterior putamen excitatory input and inhibitory output with the cerebellum, respectively. Results suggest a rearrangement of dorsal striatum functional and effective connectivity in response to mindfulness practice, with changes in cortico-subcortical-cerebellar modulatory dynamics. Findings might be relevant for the understanding of widely documented mindfulness behavioral effects, especially those related to pain perception.

Balancing Microalgae and Nitrifiers for Wastewater Treatment: Can Inorganic Carbon Limitation Cause an Environmental Threat?

The first objective of this study is to assess the predictive capability of the ALBA (ALgae-BActeria) model for a pilot-scale (3.8 m2) high-rate algae-bacteria pond treating agricultural digestate. The model, previously calibrated and validated on a one-year data set from a demonstrative-scale raceway (56 m2), successfully predicted data from a six-month monitoring campaign with a different wastewater (urban wastewater) under different climatic conditions. Without changing any parameter value from the previous calibration, the model accurately predicted both online monitored variables (dissolved oxygen, pH, temperature) and off-line measurements (nitrogen compounds, algal biomass, total and volatile suspended solids, chemical oxygen demand). Supported by the universal character of the model, different scenarios under variable weather conditions were tested, to investigate the effect of key operating parameters (hydraulic retention time, pH regulation, kLa) on algae biomass productivity and nutrient removal efficiency. Surprisingly, despite pH regulation, a strong limitation for inorganic carbon was found to hinder the process efficiency and to generate conditions that are favorable for N2O emission. The standard operating parameters have a limited effect on this limitation, and alkalinity turns out to be the main driver of inorganic carbon availability. This investigation offers new insights in algae-bacteria processes and paves the way for the identification of optimal operational strategies.

Impact of network-targeted multichannel transcranial direct current stimulation on intrinsic and network-to-network functional connectivity.

Dynamics within and between functional resting-state networks have a crucial role in determining both healthy and pathological brain functioning in humans. The possibility to noninvasively interact and selectively modulate the activity of networks would open to relevant applications in neuroscience. Here we tested a novel approach for multichannel, network-targeted transcranial direct current stimulation (net-tDCS), optimized to increase excitability of the sensorimotor network (SMN) while inducing cathodal inhibitory modulation over prefrontal and parietal brain regions negatively correlated with the SMN. Using an MRI-compatible multichannel transcranial electrical stimulation (tES) device, 20 healthy participants underwent real and sham tDCS while at rest in the MRI scanner. Changes in functional connectivity (FC) during and after stimulation were evaluated, looking at the intrinsic FC of the SMN and the strength of the negative connectivity between SMN and the rest of the brain. Standard, bifocal tDCS targeting left motor cortex (electrode ~C3) and right frontopolar (~Fp2) regions was tested as a control condition in a separate sample of healthy subjects to investigate network specificity of multichannel stimulation effects. Net-tDCS induced greater FC increase over the SMN compared to bifocal tDCS, during and after stimulation. Moreover, exploratory analysis of the impact of net-tDCS on negatively correlated networks showed an increase in the negative connectivity between SMN and prefrontal/parietal areas targeted by cathodal stimulation both during and after real net-tDCS. Results suggest preliminary evidence of the possibility of manipulating distributed network connectivity patterns through net-tDCS, with potential relevance for the development of cognitive enhancement and therapeutic tES solutions.

Wearable haptic anklets for gait and freezing improvement in Parkinson's disease: a proof-of-concept study.

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.

Pearl and pitfalls in brain functional analysis by event-related potentials: a narrative review by the Italian Psychophysiology and Cognitive Neuroscience Society on methodological limits and clinical reliability-part II.

This review focuses on new and/or less standardized event-related potentials methods, in order to improve their knowledge for future clinical applications. The olfactory event-related potentials (OERPs) assess the olfactory functions in time domain, with potential utility in anosmia and degenerative diseases. The transcranial magnetic stimulation-electroencephalography (TMS-EEG) could support the investigation of the intracerebral connections with very high temporal discrimination. Its application in the diagnosis of disorders of consciousness has achieved recent confirmation. Magnetoencephalography (MEG) and event-related fields (ERF) could improve spatial accuracy of scalp signals, with potential large application in pre-surgical study of epileptic patients. Although these techniques have methodological limits, such as high inter- and intraindividual variability and high costs, their diffusion among researchers and clinicians is hopeful, pending their standardization.

Pearls and pitfalls in brain functional analysis by event-related potentials: a narrative review by the Italian Psychophysiology and Cognitive Neuroscience Society on methodological limits and clinical reliability-part I.

Event-related potentials (ERPs) are obtained from the electroencephalogram (EEG) or the magnetoencephalogram (MEG, event-related fields (ERF)), extracting the activity that is time-locked to an event. Despite the potential utility of ERP/ERF in cognitive domain, the clinical standardization of their use is presently undefined for most of procedures. The aim of the present review is to establish limits and reliability of ERP medical application, summarize main methodological issues, and present evidence of clinical application and future improvement. The present section of the review focuses on well-standardized ERP methods, including P300, Contingent Negative Variation (CNV), Mismatch Negativity (MMN), and N400, with a chapter dedicated to laser-evoked potentials (LEPs). One section is dedicated to proactive preparatory brain activity as the Bereitschaftspotential and the prefrontal negativity (BP and pN). The P300 and the MMN potentials have a limited but recognized role in the diagnosis of cognitive impairment and consciousness disorders. LEPs have a well-documented usefulness in the diagnosis of neuropathic pain, with low application in clinical assessment of psychophysiological basis of pain. The other ERP components mentioned here, though largely applied in normal and pathological cases and well standardized, are still confined to the research field. CNV, BP, and pN deserve to be largely tested in movement disorders, just to explain possible functional changes in motor preparation circuits subtending different clinical pictures and responses to treatments.

Stabilization approaches for the hyperelastic immersed boundary method for problems of large-deformation incompressible elasticity.

The immersed boundary method is a mathematical framework for modeling fluid-structure interaction. This formulation describes the momentum, viscosity, and incompressibility of the fluid-structure system in Eulerian form, and it uses Lagrangian coordinates to describe the structural deformations, stresses, and resultant forces. Integral transforms with Dirac delta function kernels connect the Eulerian and Lagrangian frames. The fluid and the structure are both typically treated as incompressible materials. Upon discretization, however, the incompressibility of the structure is only maintained approximately. To obtain an immersed method for incompressible hyperelastic structures that is robust under large structural deformations, we introduce a volumetric energy in the solid region that stabilizes the formulation and improves the accuracy of the numerical scheme. This formulation augments the discrete Lagrange multiplier for the incompressibility constraint, thereby improving the original method's accuracy. This volumetric energy is incorporated by decomposing the strain energy into isochoric and dilatational components, as in standard solid mechanics formulations of nearly incompressible elasticity. We study the performance of the stabilized method using several quasi-static solid mechanics benchmarks, a dynamic fluid-structure interaction benchmark, and a detailed three-dimensional model of esophageal transport. The accuracy achieved by the stabilized immersed formulation is comparable to that of a stabilized finite element method for incompressible elasticity using similar numbers of structural degrees of freedom.

Thalamic morphometric changes induced by first-person action videogame training.

Cross-sectional data suggest videogaming as promoting modifications in perceptual and cognitive skills of players, as well as inducing structural brain changes. However, whether such changes are both possible after a systematic gaming exposure, and last beyond the training period, is not known. Here, we originally quantified immediate and long-lasting cognitive and morphometric impact of a systematic gaming experience on a first-person shooter (FPS) game. Thirty-five healthy participants, assigned to a videogaming and a control group, underwent a cognitive assessment and structural magnetic resonance imaging at baseline (T0), immediately post-gaming (T1) and after  3 months (T2). Enhancements of cognitive performance were found on perceptual and attentional measures at both T1 and T2. Morphometric analysis revealed immediate structural changes involving bilateral medial and posterior thalamic nuclei, as well as bilateral superior temporal gyrus, right precentral gyrus, and left middle occipital gyrus. Notably, significant changes in pulvinar volume were still present at T2, while a voxel-wise regression analysis also linked baseline pulvinar volume and individual changes in gaming performance. Present findings extend over the notion that videogame playing might impact cognitive and brain functioning in a beneficial way, originally showing long-term brain structural changes even months after gaming practice. The involvement of posterior thalamic structures highlights a potential link between FPS games and thalamo-cortical networks related to attention mechanisms and multisensory integration processing.

Stimuli, presentation modality, and load-specific brain activity patterns during n-back task.

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.