Brain Correlates of Persistent Postural-Perceptual Dizziness: A Review of Neuroimaging Studies.

Persistent postural-perceptual dizziness (PPPD), defined in 2017, is a vestibular disorder characterized by chronic dizziness that is exacerbated by upright posture and exposure to complex visual stimuli. This review focused on recent neuroimaging studies that explored the pathophysiological mechanisms underlying PPPD and three conditions that predated it. The emerging picture is that local activity and functional connectivity in multimodal vestibular cortical areas are decreased in PPPD, which is potentially related to structural abnormalities (e.g., reductions in cortical folding and grey-matter volume). Additionally, connectivity between the prefrontal cortex, which regulates attentional and emotional responses, and primary visual and motor regions appears to be increased in PPPD. These results complement physiological and psychological data identifying hypervigilant postural control and visual dependence in patients with PPPD, supporting the hypothesis that PPPD arises from shifts in interactions among visuo-vestibular, sensorimotor, and emotional networks that overweigh visual over vestibular inputs and increase the effects of anxiety-related mechanisms on locomotor control and spatial orientation

Neuroticism modulates brain visuo-vestibular and anxiety systems during a virtual rollercoaster task.

Different lines of research suggest that anxiety-related personality traits may influence the visual and vestibular control of balance, although the brain mechanisms underlying this effect remain unclear. To our knowledge, this is the first functional magnetic resonance imaging (fMRI) study that investigates how individual differences in neuroticism and introversion, two key personality traits linked to anxiety, modulate brain regional responses and functional connectivity patterns during a fMRI task simulating self-motion. Twenty-four healthy individuals with variable levels of neuroticism and introversion underwent fMRI while performing a virtual reality rollercoaster task that included two main types of trials: (1) trials simulating downward or upward self-motion (vertical motion), and (2) trials simulating self-motion in horizontal planes (horizontal motion). Regional brain activity and functional connectivity patterns when comparing vertical versus horizontal motion trials were correlated with personality traits of the Five Factor Model (i.e., neuroticism, extraversion-introversion, openness, agreeableness, and conscientiousness). When comparing vertical to horizontal motion trials, we found a positive correlation between neuroticism scores and regional activity in the left parieto-insular vestibular cortex (PIVC). For the same contrast, increased functional connectivity between the left PIVC and right amygdala was also detected as a function of higher neuroticism scores. Together, these findings provide new evidence that individual differences in personality traits linked to anxiety are significantly associated with changes in the activity and functional connectivity patterns within visuo-vestibular and anxiety-related systems during simulated vertical self-motion. Hum Brain Mapp 38:715-726, 2017. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.Italian University Ministry. Grant Number: PRIN grant 2010MEFNF7_002 ; Italian Space Agency. Grant Number: COREA grant 2013-084-R.0This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/hbm.2341

Functional connectome of the five-factor model of personality

A key objective of the emerging field of personality neuroscience is to link the great variety of the enduring dispositions of human behaviour with reliable markers of brain function. This can be achieved by analyzing large sets of data with methods that model whole-brain connectivity patterns. To meet these expectations, we exploited a large repository of personality and neuroimaging measures made publicly available via the Human Connectome Project. Using connectomic analyses based on graph theory, we computed global and local indices of functional connectivity (e.g., nodal strength, efficiency, clustering, betweenness centrality) and related these metrics to the five-factor-model (FFM) personality traits (i.e., neuroticism, extraversion, openness, agreeableness, and conscientiousness). The maximal information coefficient was used to assess for linear and non-linear statistical dependencies across the graph ‘nodes’, which were defined as distinct brain circuits identified via independent component analysis. Multi-variate regression models and ‘train/test’ machine-learning approaches were also used to examine the associations between FFM traits and connectomic indices as well as to test for the generalizability of the main findings, whilst accounting for age and sex differences. Conscientiousness was the sole FFM trait linked to measures of higher functional connectivity in the fronto-parietal and default mode networks. This might provide a mechanistic explanation of the behavioural observation that conscientious people are reliable and efficient in goal-setting or planning. Our study provides new inputs to understanding the neurological basis of personality and contributes to the development of more realistic models of the brain dynamics that mediate personality differences.Roberta Riccelli is funded by the University “Tor Vergata” of Rome, Italy, whereas Luca Passamonti is funded by the Medical Research Council (MRC) (MR/P01271X/1) at the University of Cambridge, UK. Antonio Terracciano is supported by the National Institute On Aging of the National Institutes of Health under Award Number R01AG053297 and R03AG051960. Iole Indovina is funded by the Italian Ministry of Health (PE-2013-02355372). Data collection and sharing for this project was provided by the MGH-USC Human Connectome Project (HCP; Principal Investigators: Bruce Rosen, MD, PhD, Arthur W. Toga, PhD, Van J. Weeden, MD). The HCP project is supported by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute of Mental Health (NIMH), and the National Institute of Neurological Disorders and Stroke (NINDS) (Principal Investigators: Bruce Rosen, MD, PhD, Martinos Center at Massachusetts General Hospital; Arthur W. Toga, PhD, University of Southern California, Van J. Weeden, MD, Martinos Center at Massachusetts General Hospital)

Altered Insular and Occipital Responses to Simulated Vertical Self-Motion in Patients with Persistent Postural-Perceptual Dizziness.

BACKGROUND: Persistent postural-perceptual dizziness (PPPD) is a common functional vestibular disorder characterized by persistent symptoms of non-vertiginous dizziness and unsteadiness that are exacerbated by upright posture, self-motion, and exposure to complex or moving visual stimuli. Recent physiologic and neuroimaging data suggest that greater reliance on visual cues for postural control (as opposed to vestibular cues-a phenomenon termed visual dependence) and dysfunction in central visuo-vestibular networks may be important pathophysiologic mechanisms underlying PPPD. Dysfunctions are thought to involve insular regions that encode recognition of the visual effects of motion in the gravitational field. METHODS: We tested for altered activity in vestibular and visual cortices during self-motion simulation obtained via a visual virtual-reality rollercoaster stimulation using functional magnetic resonance imaging in 15 patients with PPPD and 15 healthy controls (HCs). We compared between groups differences in brain responses to simulated displacements in vertical vs horizontal directions and correlated the difference in directional responses with dizziness handicap in patients with PPPD. RESULTS: HCs showed increased activity in the anterior bank of the central insular sulcus during vertical relative to horizontal motion, which was not seen in patients with PPPD. However, for the same comparison, dizziness handicap correlated positively with activity in the visual cortex (V1, V2, and V3) in patients with PPPD. CONCLUSION: We provide novel insight into the pathophysiologic mechanisms underlying PPPD, including functional alterations in brain processes that affect balance control and reweighting of space-motion inputs to favor visual cues. For patients with PPPD, difficulties using visual data to discern the effects of gravity on self-motion may adversely affect balance control, particularly for individuals who simultaneously rely too heavily on visual stimuli. In addition, increased activity in the visual cortex, which correlated with severity of dizziness handicap, may be a neural correlate of visual dependence

Personalized Automation of Treatment Planning for Linac-Based Stereotactic Body Radiotherapy of Spine Cancer

Purpose/Objective(s)Stereotactic ablative body radiotherapy (SBRT) for vertebral metastases is a challenging treatment process. Planning automation has recently reported the potential to improve plan quality and increase planning efficiency. We performed a dosimetric evaluation of the new Personalized engine implemented in Pinnacle3 for full planning automation of SBRT spine treatments in terms of plan quality, treatment efficiency, and delivery accuracy. Materials/MethodsThe Pinnacle3 treatment planning system was used to reoptimize six patients with spinal metastases, employing two separate automated engines. These two automated engines, the existing Autoplanning and the new Personalized, are both template-based algorithms that employ a wishlist to construct planning goals and an iterative technique to replicate the planning procedure performed by skilled planners. The boost tumor volume (BTV) was defined as the macroscopically visible lesion on RM examination, and the planning target volume (PTV) corresponds with the entire vertebra. Dose was prescribed according to simultaneous integrated boost strategy with BTV and PTV irradiated simultaneously over 3 fractions with a dose of 30 and 21 Gy, respectively. Dose-volume histogram (DVH) metrics and conformance indices were used to compare clinically accepted manual plans (MP) with automated plans developed using both Autoplanning (AP) and Personalized engines (Pers). All plans were evaluated for planning efficiency and dose delivery accuracy. ResultsFor similar spinal cord sparing, automated plans reported a significant improvement of target coverage and dose conformity. On average, Pers plans increased near-minimal dose D98% by 10.4% and 8.9% and target coverage D95% by 8.0% and by 4.6% for BTV and PTV, respectively. Automated plans provided significantly superior dose conformity and dose contrast by 37%-47% and by 4.6%-5.7% compared with manual plans. Overall planning times were dramatically reduced to about 15 and 23 min for Pers and AP plans, respectively. The average beam-on times were found to be within 3 min for all plans. Despite the increased complexity, all plans passed the 2%/2 mm gamma-analysis for dose verification. ConclusionAutomated planning for spine SBRT through the new Pinnacle3 Personalized engine provided an overall increase of plan quality in terms of dose conformity and a major increase in efficiency. In this complex anatomical site, Personalized strongly reduce the tradeoff between optimal accurate dosimetry and planning time

Heterogeneity of Antiphospholipid Syndrome (APS) as Characterized by Brain Perfusion Techniques. Towards New Ways of Syndrome Characterization

Antiphospholipid Syndrome (APS) syndrome is an autoimmune condition that affects the way that blood cells in humans bind together. Though the cause of APS is unclear, researchers believe that many factors have an impact on developing this pathological condition. Phospholipids (PLs) play numerous central roles in biological systems, and processes of biological systems regulation act through the liberation of a vast amount of different signalling molecules, which are also involved in the modulation of cell proliferation, inflammation, oxidative stress, neurotransmission and many other processes.A global landmark, holistic, is required to evaluate different phenotypes in APS. All thecriteria validated for the APS diagnosislead to an extremely heterogeneous landmark of the pathology and related to several manifestations in different systems. Heterogeneity also characterizes the SPECT acquisition of the patients and it is connected to several neurological and underestimates symptoms of the pathology. We present some examples to highlight the connection between heterogeneity in SPECT and APS markers of pathology indicating the needs to approach to the Syndrome in a holistic way. At the end of the paper we suggested the multidisciplinary approach that we are tuning for our analysis, approach based on Imaging, Metabolomic and Clinical evaluation, including mental health test for a neuropsychiatric characterization of the pathology

The place of allogeneic stem cell transplantation in aggressive B-cell non-Hodgkin lymphoma in the era of CAR-T-cell therapy

Chimeric antigen receptor T (CAR-T) cells are a treatment option for patients with relapse/refractory (R/R) non-Hodgkin lymphoma (NHL), acute lymphoid leukemia and multiple myeloma. To date, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL) have been successfully treated with CAR-T cells directed against the CD19 antigen. However, when R/R disease persists after several treatment lines, patients with these diseases are often referred to transplantation centres to receive allogeneic stem cell transplantation (ALLO-SCT). ALLO-SCT and CAR-T cells share mechanism of actions, inducing immune effects of T-cells (and other cells after transplantation) against lymphoma cells, but they differ in several other characteristics. These differences justify unique positioning of each therapy within treatment algorithms. In this paper, we analyzed the results obtained after ALLO-SCT and CAR-T-cell therapy in patients with aggressive lymphomas (large B-cell lymphoma and MCL) to identify the ideal scenarios in which these 2 immunological therapies should be employed

Motion and dosimetric criteria for selecting gating technique for apical lung lesions in magnetic resonance guided radiotherapy

IntroductionPatients treatment compliance increases during free-breathing (FB) treatment, taking generally less time and fatigue with respect to deep inspiration breath-hold (DIBH). This study quantifies the gross target volume (GTV) motion on cine-MRI of apical lung lesions undergoing a SBRT in a MR-Linac and supports the patient specific treatment gating pre-selection.Material and methodsA total of 12 patients were retrospectively enrolled in this study. During simulation and treatment fractions, sagittal 0.35 T cine-MRI allows real-time GTV motion tracking. Cine-MRI has been exported, and an in-house developed MATLAB script performed image segmentation for measuring GTV centroid position on cine-MRI frames. Motion measurements were performed during the deep inspiration phase of DIBH patient and during all the session for FB patient. Treatment plans of FB patients were reoptimized using the same cost function, choosing the 3 mm GTV-PTV margin used for DIBH patients instead of the original 5 mm margin, comparing GTV and OARs DVH for the different TP.ResultsGTV centroid motion is <2.2 mm in the antero-posterior and cranio-caudal direction in DIBH. For FB patients, GTV motion is lower than 1.7 mm, and motion during the treatment was always in agreement with the one measured during the simulation. No differences have been observed in GTV coverage between the TP with 3-mm and 5-mm margins. Using a 3-mm margin, the mean reduction in the chest wall and trachea–bronchus Dmax was 2.5 Gy and 3.0 Gy, respectively, and a reduction of 1.0 Gy, 0.6 Gy, and 2.3% in Dmax, Dmean, and V5Gy, respectively, of the homolateral lung and 1.7 Gy in the contralateral lung Dmax.DiscussionsCine-MRI allows to select FB lung patients when GTV motion is <2 mm. The use of narrower PTV margins reduces OARs dose and maintains target coverage

A Novel Method for Spectrometry Based on Imaging Systems

γ-ray spectrometry is a well-known technique in environmental radioactivity measurements where easily handled systems are needed. Scintillators coupled to a photomultiplier tube (PMT), are typically favoured over solid-state detectors as mobile spectrometers. Replacing PMT with position sensitive devices represents an innovative solution that provides the evaluation of the interaction point of the incident radiation. The knowledge of spectrometry as a function of the depth of interaction (DoI) assures a better understanding of the spectrum and a more reliable identification of the source. In this paper, the efficiency of a simple DoI estimator has been studied using a CRY018 monolithic crystal coupled to a multi-anode photomultiplier tube. The DoI estimator has been evaluated studying charge distributions and the dependency of spectrometric properties on the DoI has been qualitatively analyzed. The estimator has shown to be highly sensitive to the DoI, enabling a better understanding of the internal interaction processes of light and an efficient rejection of the background component on the spectra. The novelty of this work lies in the application of the DoI selection in spectrometry made available by the use of MAPMT. The proposed method is practical since it does not require complicated hardware solutions or complex computational procedures

Monte Carlo and Biophysics Analysis in a Criminal Trial

In this paper a real court case, held in Italy at the Court of Nola, in which a correct physical description, conducted with both a Monte Carlo and biophysical analysis, would have been sufficient to arrive at conclusions confirmed by documentary evidence, is considered. This will be an example of how forensic physics can be useful in confirming documentary evidence in order to reach hardly questionable conclusions. This was a libel trial in which the defendant, Mr. DS (Defendant for Slander), had falsely accused one of his neighbors, Mr. OP (Offended Person), of having caused him some damages. The damages would have been caused by an external plaster piece that would have detached from the neighbor's property and would have hit Mr DS while he was in his garden, much more than a meter far away from the facade of the building from which the plaster piece would have detached. In the trial, Mr. DS claimed to have suffered a scratch on his forehead, but he never showed the plaster that had hit him, nor was able to tell from where the plaster would have arrived. Furthermore, Mr. DS presented a medical certificate with a diagnosis of contusion of the cerebral cortex. On the contrary, the images of Mr. OP's security cameras do not show any movement in the garden of Mr. DS in a long interval of time (about 2 hours) around the time of the alleged accident, nor do they show any people entering or coming out from the house of Mr. DS in the same interval of time. Biophysical analysis shows that both the diagnosis of the medical certificate and the wound declared by the defendant, already in conflict with each other, are not compatible with the fall of external plaster pieces too small to be found. The wind was at a level 1 of the Beaufort scale, that is, unable to raise even dust (level 4 of the Beaufort scale). Therefore, the motion of the plaster pieces can be described as a projectile motion, whereas collisions with the building cornice can be treated using Newtons law of coefficients of restitution. Numerous numerical Monte Carlo simulations show that the pieces of plaster would not have been able to reach even the garden of Mr. DS, let alone a distance over 1.30 meters. Results agree with the documentary evidence (images of Mr. OP's security cameras) that Mr. DS could not have been hit by plaster pieces coming from Mr. OP's property