A "glympse" into neurodegeneration: Diffusion MRI and cerebrospinal fluid aquaporin-4 for the assessment of glymphatic system in Alzheimer's disease and other dementias.

The glymphatic system (GS) is a whole-brain perivascular network, consisting of three compartments: the periarterial and perivenous spaces and the interposed brain parenchyma. GS dysfunction has been implicated in neurodegenerative diseases, particularly Alzheimer's disease (AD). So far, comprehensive research on GS in humans has been limited by the absence of easily accessible biomarkers. Recently, promising non-invasive methods based on magnetic resonance imaging (MRI) along with aquaporin-4 (AQP4) quantification in the cerebrospinal fluid (CSF) were introduced for an indirect assessment of each of the three GS compartments. We recruited 111 consecutive subjects presenting with symptoms suggestive of degenerative cognitive decline, who underwent 3 T MRI scanning including multi-shell diffusion-weighted images. Forty nine out of 111 also underwent CSF examination with quantification of CSF-AQP4. CSF-AQP4 levels and MRI measures-including perivascular spaces (PVS) counts and volume fraction (PVSVF), white matter free water fraction (FW-WM) and mean kurtosis (MK-WM), diffusion tensor imaging analysis along the perivascular spaces (DTI-ALPS) (mean, left and right)-were compared among patients with AD (n = 47) and other neurodegenerative diseases (nAD = 24), patients with stable mild cognitive impairment (MCI = 17) and cognitively unimpaired (CU = 23) elderly people. Two runs of analysis were conducted, the first including all patients; the second after dividing both nAD and AD patients into two subgroups based on gray matter atrophy as a proxy of disease stage. Age, sex, years of education, and scanning time were included as confounding factors in the analyses. Considering the whole cohort, patients with AD showed significantly higher levels of CSF-AQP4 (exp(b) = 2.05, p = .005) and FW-WM FW-WM (exp(b) = 1.06, p = .043) than CU. AQP4 levels were also significantly higher in nAD in respect to CU (exp(b) = 2.98, p < .001). CSF-AQP4 and FW-WM were significantly higher in both less atrophic AD (exp(b) = 2.20, p = .006; exp(b) = 1.08, p = .019, respectively) and nAD patients (exp(b) = 2.66, p = .002; exp(b) = 1.10, p = .019, respectively) compared to CU subjects. Higher total (exp(b) = 1.59, p = .013) and centrum semiovale PVS counts (exp(b) = 1.89, p = .016), total (exp(b) = 1.50, p = .036) and WM PVSVF (exp(b) = 1.89, p = .005) together with lower MK-WM (exp(b) = 0.94, p = .006), mean and left ALPS (exp(b) = 0.91, p = .043; exp(b) = 0.88, p = .010 respectively) were observed in more atrophic AD patients in respect to CU. In addition, more atrophic nAD patients exhibited higher levels of AQP4 (exp(b) = 3.39, p = .002) than CU. Our results indicate significant changes in putative MRI biomarkers of GS and CSF-AQP4 levels in AD and in other neurodegenerative dementias, suggesting a close interaction between glymphatic dysfunction and neurodegeneration, particularly in the case of AD. However, the usefulness of some of these biomarkers as indirect and standalone indices of glymphatic activity may be hindered by their dependence on disease stage and structural brain damage.

Speech and lexico-semantic errors during direct cortical stimulation mapping of the language-dominant hemisphere: effects of object and action naming.

OBJECTIVE: In this retrospective study, the authors aimed to establish the stereotactically defined probability distribution for speech (i.e., anarthria, speech arrest) and lexico-semantic errors (i.e., anomia) through direct cortical stimulation (DCS) by using two tasks: action naming and object naming. They also analyzed the patterns of interindividual variability in the localization of the language sites involved, and investigated whether any patient or lesion location factors were associated with greater variability. METHODS: Eighty-one Italian-speaking patients who underwent awake surgery between 2010 and 2021 for low- and high-grade gliomas in eloquent areas of the language-dominant hemisphere were entered in the analyses. The intraoperative DCS protocol included automatic speech tasks, object naming, and action naming. The position of the tags, as depicted on the intraoperative video or photograph, was transposed into Montreal Neurological Institute space. Subsequently, a 2D scatterplot and cluster analysis were performed. Associations between various clinical and radiological characteristics and the quantity of positive stimulated sites were determined by univariate analyses using binary logistic regression. Associated variables (p < 0.2) were included in stepwise multivariate logistic regression with backward elimination (p < 0.05). RESULTS: A total of 1380 cortical sites were stimulated, with a positive response in 511 cases (37%). Most anarthric errors were triggered when stimulating the left precentral gyrus, and most speech arrest errors were elicited when stimulating the left posterior inferior frontal gyrus. Anomias were found in the left inferior frontal gyrus and in the posterior part of the left temporal lobe for object naming. DCS to the left dorsal premotor cortex elicited anomic errors for action naming. Anomias were also elicited during DCS to the left posterior temporal lobe, with both object and action naming. CONCLUSIONS: The distribution of speech and lexico-semantic errors is in line with the current literature. The action-naming results are new and mostly involve the dorsal premotor cortex. These findings stress the importance of maximizing the use of different language tasks during surgery, because even when looking for the same type of errors, different tasks may be better suited to map specific brain regions. DCS with action and object naming identifies more positive sites than object naming alone.

Developing Iron Nanochelating Agents: Preliminary Investigation of Effectiveness and Safety for Central Nervous System Applications.

Excessive iron levels are believed to contribute to the development of neurodegenerative disorders by promoting oxidative stress and harmful protein clustering. Novel chelation treatments that can effectively remove excess iron while minimizing negative effects on the nervous system are being explored. This study focuses on the creation and evaluation of innovative nanobubble (NB) formulations, shelled with various polymers such as glycol-chitosan (GC) and glycol-chitosan conjugated with deferoxamine (DFO), to enhance their ability to bind iron. Various methods were used to evaluate their physical and chemical properties, chelation capacity in diverse iron solutions and impact on reactive oxygen species (ROS). Notably, the GC-DFO NBs demonstrated the ability to decrease amyloid-ß protein misfolding caused by iron. To assess potential toxicity, in vitro cytotoxicity testing was conducted using organotypic brain cultures from the substantia nigra, revealing no adverse effects at appropriate concentrations. Additionally, the impact of NBs on spontaneous electrical signaling in hippocampal neurons was examined. Our findings suggest a novel nanochelation approach utilizing DFO-conjugated NBs for the removal of excess iron in cerebral regions, potentially preventing neurotoxic effects.

Comparison of anatomical-based vs. nTMS-based risk stratification model for predicting postoperative motor outcome and extent of resection in brain tumor surgery.

BACKGROUND: Two statistical models have been established to evaluate characteristics associated with postoperative motor outcome in patients with glioma associated to the motor cortex (M1) or the corticospinal tract (CST). One model is based on a clinicoradiological prognostic sum score (PrS) while the other one relies on navigated transcranial magnetic stimulation (nTMS) and diffusion-tensor-imaging (DTI) tractography. The objective was to compare the models regarding their prognostic value for postoperative motor outcome and extent of resection (EOR) with the aim of developing a combined, improved model. METHODS: We retrospectively analyzed a consecutive prospective cohort of patients who underwent resection for motor associated glioma between 2008 and 2020, and received a preoperative nTMS motor mapping with nTMS-based diffusion tensor imaging tractography. The primary outcomes were the EOR and the motor outcome (on the day of discharge and 3 months postoperatively according to the British Medical Research Council (BMRC) grading). For the nTMS model, the infiltration of M1, tumor-tract distance (TTD), resting motor threshold (RMT) and fractional anisotropy (FA) were assesed. For the PrS score (ranging from 1 to 8, lower scores indicating a higher risk), we assessed tumor margins, volume, presence of cysts, contrast agent enhancement, MRI index (grading white matter infiltration), preoperative seizures or sensorimotor deficits. RESULTS: Two hundred and three patients with a median age of 50 years (range: 20-81 years) were analyzed of whom 145 patients (71.4%) received a GTR. The rate of transient new motor deficits was 24.1% and of permanent new motor deficits 18.8%. The nTMS model demonstrated a good discrimination ability for the short-term motor outcome at day 7 of discharge (AUC = 0.79, 95 %CI: 0.72-0.86) and the long-term motor outcome after 3 months (AUC = 0.79, 95 %CI: 0.71-0.87). The PrS score was not capable to predict the postoperative motor outcome in this cohort but was moderately associated with the EOR (AUC = 0.64; CI 0.55-0.72). An improved, combined model was calculated to predict the EOR more accurately (AUC = 0.74, 95 %CI: 0.65-0.83). CONCLUSION: The nTMS model was superior to the clinicoradiological PrS model for potentially predicting the motor outcome. A combined, improved model was calculated to estimate the EOR. Thus, patient counseling and surgical planning in patients with motor-associated tumors should be performed using functional nTMS data combined with tractography.

Neural network-derived perfusion maps: A model-free approach to computed tomography perfusion in patients with acute ischemic stroke.

Objective: In this study, we investigate whether a Convolutional Neural Network (CNN) can generate informative parametric maps from the pre-processed CT perfusion data in patients with acute ischemic stroke in a clinical setting. Methods: The CNN training was performed on a subset of 100 pre-processed perfusion CT dataset, while 15 samples were kept for testing. All the data used for the training/testing of the network and for generating ground truth (GT) maps, using a state-of-the-art deconvolution algorithm, were previously pre-processed using a pipeline for motion correction and filtering. Threefold cross validation had been used to estimate the performance of the model on unseen data, reporting Mean Squared Error (MSE). Maps accuracy had been checked through manual segmentation of infarct core and total hypo-perfused regions on both CNN-derived and GT maps. Concordance among segmented lesions was assessed using the Dice Similarity Coefficient (DSC). Correlation and agreement among different perfusion analysis methods were evaluated using mean absolute volume differences, Pearson correlation coefficients, Bland-Altman analysis, and coefficient of repeatability across lesion volumes. Results: The MSE was very low for two out of three maps, and low in the remaining map, showing good generalizability. Mean Dice scores from two different raters and the GT maps ranged from 0.80 to 0.87. Inter-rater concordance was high, and a strong correlation was found between lesion volumes of CNN maps and GT maps (0.99, 0.98, respectively). Conclusion: The agreement between our CNN-based perfusion maps and the state-of-the-art deconvolution-algorithm perfusion analysis maps, highlights the potential of machine learning methods applied to perfusion analysis. CNN approaches can reduce the volume of data required by deconvolution algorithms to estimate the ischemic core, and thus might allow the development of novel perfusion protocols with lower radiation dose deployed to the patient.

Synthetic MRI with Magnetic Resonance Spin TomogrAphy in Time-Domain (MR-STAT): Results from a Prospective Cross-Sectional Clinical Trial.

BACKGROUND: Magnetic Resonance Spin TomogrAphy in Time-domain (MR-STAT) can reconstruct whole-brain multi-parametric quantitative maps (eg, T1 , T2 ) from a 5-minute MR acquisition. These quantitative maps can be leveraged for synthetization of clinical image contrasts. PURPOSE: The objective was to assess image quality and overall diagnostic accuracy of synthetic MR-STAT contrasts compared to conventional contrast-weighted images. STUDY TYPE: Prospective cross-sectional clinical trial. POPULATION: Fifty participants with a median age of 45 years (range: 21-79 years) consisting of 10 healthy participants and 40 patients with neurological diseases (brain tumor, epilepsy, multiple sclerosis or stroke). FIELD STRENGTH/SEQUENCE: 3T/Conventional contrast-weighted imaging (T1 /T2 weighted, proton density [PD] weighted, and fluid-attenuated inversion recovery [FLAIR]) and a MR-STAT acquisition (2D Cartesian spoiled gradient echo with varying flip angle preceded by a non-selective inversion pulse). ASSESSMENT: Quantitative T1 , T2 , and PD maps were computed from the MR-STAT acquisition, from which synthetic contrasts were generated. Three neuroradiologists blinded for image type and disease randomly and independently evaluated synthetic and conventional datasets for image quality and diagnostic accuracy, which was assessed by comparison with the clinically confirmed diagnosis. STATISTICAL TESTS: Image quality and consequent acceptability for diagnostic use was assessed with a McNemar's test (one-sided α = 0.025). Wilcoxon signed rank test with a one-sided α = 0.025 and a margin of Δ = 0.5 on the 5-level Likert scale was used to assess non-inferiority. RESULTS: All data sets were similar in acceptability for diagnostic use (≥3 Likert-scale) between techniques (T1 w:P = 0.105, PDw:P = 1.000, FLAIR:P = 0.564). However, only the synthetic MR-STAT T2 weighted images were significantly non-inferior to their conventional counterpart; all other synthetic datasets were inferior (T1 w:P = 0.260, PDw:P = 1.000, FLAIR:P = 1.000). Moreover, true positive/negative rates were similar between techniques (conventional: 88%, MR-STAT: 84%). DATA CONCLUSION: MR-STAT is a quantitative technique that may provide radiologists with clinically useful synthetic contrast images within substantially reduced scan time. EVIDENCE LEVEL: 1 Technical Efficacy: Stage 2.

Embolic Stroke of Undetermined Source: Role of Implantable Loop Recorder in Secondary Prevention.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most important cause of embolic stroke of undetermined source (ESUS). Implantable loop recorder (ILR) demonstrated the highest sensitivity for detecting it. This register was created to confirm the high prevalence of AF in patients after ESUS and to verify possible benefits on clinical outcomes such as TIA (Transient Ischaemic Attack)/stroke recurrence and death using ILR. METHODS: A total of 278 patients admitted to "Molinette" Hospital in Stroke Unit department between 2011 and 2016, diagnosed with ESUS, underwent ILR implantation if they had at least one risk factor for AF. A total of 165 patients admitted to other departments in the same center for the same pathology, without ILR, represent the control group. We used propensity score to select 132 patients from each group (matching age, sex, CHADS-VASC, and HAS-BLEED baseline characteristics). RESULTS: The detection rate of AF episodes was significantly higher in the ILR group (p < 0.001). No significant protective role of ILR for clinical endpoints was found on univariate analysis, although a trend towards significance has been pointed for the composite outcome of death and ischemic events recurrence (OR 0.52, CI 0.26-1.04, p = 0.06). A protective role of ILR was found for deaths (OR 0.4, CI 0.17-0.94, p 0.03) and for the composite outcome (OR 0.41, CI 0.19-0.87, p 0.02) on multivariate analysis in the best subsets. CONCLUSION: With our statistical models, we identified a significant clinical benefit from ILR monitoring, evidenced by a trend of less death and TIA/stroke recurrence and relevant ILR protection for prediction of TIA/stroke recurrence.

Investigation of Brain Activation Patterns Related to the Feminization or Masculinization of Body and Face Images across Genders.

Previous studies demonstrated sex-related differences in several areas of the human brain, including patterns of brain activation in males and females when observing their own bodies and faces (versus other bodies/faces or morphed versions of themselves), but a complex paradigm touching multiple aspects of embodied self-identity is still lacking. We enrolled 24 healthy individuals (12 M, 12 F) in 3 different fMRI experiments: the vision of prototypical body silhouettes, the vision of static images of the face of the participants morphed with prototypical male and female faces, the vision of short videos showing the dynamic transformation of the morphing. We found differential sexual activations in areas linked to self-identity and to the ability to attribute mental states: In Experiment 1, the male group activated more the bilateral thalamus when looking at sex congruent body images, while the female group activated more the middle and inferior temporal gyrus. In Experiment 2, the male group activated more the supplementary motor area when looking at their faces; the female group activated more the dorsomedial prefrontal cortex (dmPFC). In Experiment 3, the female group activated more the dmPFC when observing either the feminization or the masculinization of their face. The defeminization produced more activations in females in the left superior parietal lobule and middle occipital gyrus. The performance of all classifiers built using single ROIs exceeded chance level, reaching an area under the ROC curves > 0.85 in some cases (notably, for Experiment 2 using the V1 ROI). The results of the fMRI tasks showed good agreement with previously published studies, even if our sample size was small. Therefore, our functional MRI protocol showed significantly different patterns of activation in males and females, but further research is needed both to investigate the gender-related differences in activation when observing a morphing of their face/body, and to validate our paradigm using a larger sample.

Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group.

BACKGROUND: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. METHODS: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). RESULTS: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. CONCLUSIONS: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

Cerebellum and Emotion Recognition.

In this chapter, after having clarified which definition of emotion we followed, starting from Darwin and evolutionary psychology, we tried to examine the main mechanisms of emotional recognition from a behavioral and cerebral point of view: emotional contagion and cognitive empathy. The link between these skills and social cognition has been discussed. We tried to understand through the description of comparative studies on animals, studies on populations with cerebellar lesions in animals and humans, neurostimulation studies, and studies on neuropsychiatric pathologies with alterations to the cerebellar networks the possible involvement of the cerebellum in these mechanisms, also investigating its possible causal role. The evidence, even if mainly of a correlational type, is numerous and robust enough to be able to affirm the existence of significant involvement of the cerebellum in social cognition and in the recognition of negative emotions, especially fear.

Are convexity meningiomas all the same? A clinico-radiological analysis of surgically treated eloquent areas convexity meningiomas.

BACKGROUND: Convexity meningiomas are considered low-risk tumors, with high possibility of cure and low risk of relapse after resection. Very few studies have investigated meningiomas located in or around highly eloquent regions (namely perirolandic and perisylvian fissures). This study aimed to determine the differences in preoperative characteristics and postoperative outcomes between convexity meningiomas at eloquent area and non-eloquent areas. METHODS: Retrospective study on patients who underwent surgical resection for convexity meningioma. Patients were divided into eloquent and non-eloquent area. Statistical analysis was made comparing preoperative and postoperative data of both groups. RESULTS: The study included a total of 117 patients: 80 with eloquent area tumor and 37 with non-eloquent area tumor. Statistically significant differences were detected between the groups in preoperative KPS (93±10 in eloquent vs. 97±6 in non-eloquent; P=0.008) and in large-caliber vein involvement (76.3% in cases vs. 16.2% in controls; P<0.001). Postoperatively, patients with eloquent area tumors showed initial deterioration in neurological status followed by recovery; final outcomes were comparable to that of patients with non-eloquent area tumors. However, patients with eloquent area meningiomas had higher propensity to suffer from seizures postoperatively. Postoperative complications and long-term outcomes were not significantly different between the two groups. CONCLUSIONS: Patients with eloquent areas convexity meningiomas do not appear to have higher surgical risk. Neurological status is more likely to worsen immediately after surgery, but long-term recovery is satisfactory. Seizure control after surgery appears to be poorer in patients with perirolandic meningioma.

Sulcal characteristics patterns and gyrification gradient at different stages of Anorexia Nervosa: A structural MRI evaluation.

Previous research evidenced alterations of different cortical parameters in patients with acute Anorexia Nervosa (AN), but no study to date investigated the morphology of individual sulci and their relationship with other structural indices. Our study aims at exploring the depth and width of 16 major cortical sulci in AN at different stages of the disorder and their relationships with the gyrification gradient. Two samples were included in the study. The first involved 38 patients with acute AN, 20 who fully recovered from AN, and 38 healthy women (HW); the second included 16 patients with AN and 16 HW. Sulcal width and depth were estimated for 16 sulci and outlined with a factorial analysis. An anterior-posterior gradient of gyrification was also extracted. Compared to HW, patients with acute AN displayed higher width and depth values in specific cortical sulci, and an altered gyrification gradient in areas encompassing the Central Sulcus, and Parieto-Temporal and Frontal Lobe regions. Sulcal width negatively correlated with gyrification gradient in areas where these values are altered in AN patients. Our results suggest the presence of alterations in sulcal morphology with a pattern similar to the gyrification gradient one and which seems to be related with malnutrition.

Step-by-Step Design of New Theranostic Nanoformulations: Multifunctional Nanovectors for Radio-Chemo-Hyperthermic Therapy under Physical Targeting.

While investigating the possible synergistic effect of the conventional anticancer therapies, which, taken individually, are often ineffective against critical tumors, such as central nervous system (CNS) ones, the design of a theranostic nanovector able to carry and deliver chemotherapy drugs and magnetic hyperthermic agents to the target radiosensitizers (oxygen) was pursued. Alongside the original formulation of polymeric biodegradable oxygen-loaded nanostructures, their properties were fine-tuned to optimize their ability to conjugate therapeutic doses of drugs (doxorubicin) or antitumoral natural substances (curcumin). Oxygen-loaded nanostructures (diameter = 251 ± 13 nm, ζ potential = -29 ± 5 mV) were finally decorated with superparamagnetic iron oxide nanoparticles (SPIONs, diameter = 18 ± 3 nm, ζ potential = 14 ± 4 mV), producing stable, effective and non-agglomerating magnetic nanovectors (diameter = 279 ± 17 nm, ζ potential = -18 ± 7 mV), which could potentially target the tumoral tissues under magnetic driving and are monitorable either by US or MRI imaging.

Investigating Neuroimaging Correlates of Early Frailty in Patients With Behavioral Variant Frontotemporal Dementia: A MRI and FDG-PET Study.

Frailty is a dynamic clinical condition characterized by the reduction of interconnections among different psychobiological domains, which leads to a homeostatic vulnerability. The association between physical frailty and cognitive dysfunctions is a possible predictor of poor prognosis in patients with neurodegenerative disorders. However, this construct has not been fully analyzed by a multidimensional neuropsychogeriatric assessment matched with multimodal neuroimaging methods in patients with behavioral variant frontotemporal dementia (bvFTD). We have investigated cognitive dysfunctions and frailty status, assessed by both a neuropsychological evaluation and the Multidimensional Prognostic Index (MPI), in a sample of 18 bvFTD patients and compared to matched healthy controls. Gray matter (GM) volume (as assessed by voxel-based morphometry) and metabolism (on 18fluorodeoxyglucose positron emission tomography) were first separately compared between groups, then voxelwise compared and correlated to each other within patients. Linear regression of the MPI was performed on those voxels presenting a significant correlation between altered GM volume and metabolism. The neuropsychological assessment reflected the diagnoses and the functional-anatomical alterations documented by neuroimaging analyses. In particular, the majority of patients presented significant executive dysfunction and mood changes in terms of apathy, depression, and anxiety. In the overall MPI score, the patients fell in the lower range (indicating an early frailty status). On imaging, they exhibited a bilateral decrease of GM density and hypometabolism involving the frontal pole, the anterior opercular region, and the anterior cingulate cortex. Greater atrophy than hypometabolism was observed in the bilateral orbitofrontal cortex, the triangular part of the inferior frontal gyrus, and the ventral striatum, whereas the contrary was detected in the bilateral dorsal anterior cingulate cortex and pre-supplementary motor area. MPI scores significantly correlated only with the co-occurrence of a decrease of GM density and hypometabolism in the right anterior insular cortex, but not with the separate pathological phenomena. Our results show a correlation between a specific pattern of co-occurring GM atrophy and hypometabolism with early frailty in bvFTD patients. These aspects, combined with executive dysfunction and mood changes, may lead to an increased risk of poor prognosis, highlighting a potentially critical and precocious role of the insula in the pathogenesis of frailty.

Emotional imagination of negative situations: Functional neuroimaging in anorexia and bulimia.

AIM: The present study aims to extend the knowledge of the neural correlates of emotion processing in first episode subjects affected by anorexia nervosa (AN) or bulimia nervosa (BN). We applied an emotional distress paradigm targeting negative emotions thought to be relevant for interpersonal difficulties and therapeutic resistance mechanisms. METHODS: The current study applied to 44 female participants with newly diagnosed AN or BN and 20 matched controls a neuroimaging paradigm eliciting affective responses. The measurements also included an extensive assessment comprising clinical scales, neuropsychological tests, measures of emotion processing and empathy. RESULTS: AN and BN did not differ from controls in terms of emotional response, emotion matching, self-reported empathy and cognitive performance. However, eating disorder and psychopathological clinical scores, as well as alexithymia levels, were increased in AN and BN. On a neural level, no significant group differences emerged, even when focusing on a region of interest selected a priori: the amygdala. Some interesting findings put in relation the hippocampal activity with the level of Body Dissatisfaction of the participants, the relative importance of the key nodes for the common network in the decoding of different emotions (BN = right amygdala, AN = anterior cingulate area), and the qualitative profile of the deactivations. CONCLUSIONS: Our data do not support the hypothesis that participants with AN or BN display reduced emotional responsiveness. However, peculiar characteristics in emotion processing could be associated to the three different groups. Therefore, relational difficulties in eating disorders, as well as therapeutic resistance, could be not secondary to a simple difficulty in feeling and identifying basic negative emotions in AN and BN participants.

Machine Learning Profiling of Alzheimer's Disease Patients Based on Current Cerebrospinal Fluid Markers and Iron Content in Biofluids.

Alzheimer's disease (AD) is the most common form of dementia, characterized by a complex etiology that makes therapeutic strategies still not effective. A true understanding of key pathological mechanisms and new biomarkers are needed, to identify alternative disease-modifying therapies counteracting the disease progression. Iron is an essential element for brain metabolism and its imbalance is implicated in neurodegeneration, due to its potential neurotoxic effect. However, the role of iron in different stages of dementia is not clearly established. This study aimed to investigate the potential impact of iron both in cerebrospinal fluid (CSF) and in serum to improve early diagnosis and the related therapeutic possibility. In addition to standard clinical method to detect iron in serum, a precise quantification of total iron in CSF was performed using graphite-furnace atomic absorption spectrometry in patients affected by AD, mild cognitive impairment, frontotemporal dementia, and non-demented neurological controls. The application of machine learning techniques, such as clustering analysis and multiclassification algorithms, showed a new potential stratification of patients exploiting iron-related data. The results support the involvement of iron dysregulation and its potential interaction with biomarkers (Tau protein and Amyloid-beta) in the pathophysiology and progression of dementia.

Difference Between Young and Old Adults' Performance on the Psychology Experiment Building Language (PEBL) Test Battery: What Is the Role of Familiarity With Technology in Cognitive Performance?

Objective: The Psychology Experiment Building Language (PEBL) Test Battery is a recent computerized software for the assessment of cognitive functioning in clinical and healthy populations. However, its applicability for the assessment of old adults and the role of level of familiarity with technology on performance have not been tested. Method: To verify if PEBL Test Battery is sensitive to aging cognitive decline, we assessed young and older adults' performance on the neuropsychological tests relative to the following domains: verbal and visuospatial short-term memory, selective attention, inhibition to interference, planning and problem-solving, set-shifting, and cognitive flexibility. The difference between the two groups was studied taking into account the self-reported level of familiarity with technology, measured through the Attitudes Toward Computers Questionnaire. Results: Old participants showed a lower level of cognitive performance compared with the younger group, in line with the traditional literature about cognitive function decline in aging. However, this difference was not related to the level of familiarity with technology. Conclusion: Our descriptive study seemed to support the applicability of PEBL Test Battery for testing old adults' cognitive functioning. However, some criticisms and future improvements about this computerized battery were discussed for its applicability in clinical, rehabilitative and research contexts.

Hippocampal volumes in anorexia nervosa at different stages of the disorder.

INTRODUCTION: Hippocampus is involved in a range of cognitive and behavioural processes, and its volume has been found to be reduced in different psychiatric disorders. The present study aims at exploring hippocampal volumes in anorexia nervosa (AN) at different stages of the disorder (a few months after onset, more than 1 year after onset and after recovery). METHODS: Two samples were included in the present study. The first was composed of 58 patients (38 with present AN, 20 full recovered from AN) and 38 age-matched healthy women (HW); the second, recruited at a different site, included 20 patients with AN and 16 HW. Hippocampal volume has been estimated using an automated segmentation algorithm. Age, site of scanning and total intracranial volumes were used as covariates in the statistical analyses. RESULTS: AN patients showed a reduced hippocampal volume in comparison to HW, with no substantial differences between patients with recent onset and those with a longer duration of illness. Among patients, hippocampal volumes correlated with body mass index, anxiety and drive for thinness. DISCUSSION: Our findings suggest an early role of malnutrition in the morphologic alterations of the hippocampus in AN and a possible role of this brain structure in mediating specific psychopathological traits.

Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System.

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.

Deep learning-based image reconstruction and motion estimation from undersampled radial k-space for real-time MRI-guided radiotherapy.

To enable magnetic resonance imaging (MRI)-guided radiotherapy with real-time adaptation, motion must be quickly estimated with low latency. The motion estimate is used to adapt the radiation beam to the current anatomy, yielding a more conformal dose distribution. As the MR acquisition is the largest component of latency, deep learning (DL) may reduce the total latency by enabling much higher undersampling factors compared to conventional reconstruction and motion estimation methods. The benefit of DL on image reconstruction and motion estimation was investigated for obtaining accurate deformation vector fields (DVFs) with high temporal resolution and minimal latency. 2D cine MRI acquired at 1.5 T from 135 abdominal cancer patients were retrospectively included in this study. Undersampled radial golden angle acquisitions were retrospectively simulated. DVFs were computed using different combinations of conventional- and DL-based methods for image reconstruction and motion estimation, allowing a comparison of four approaches to achieve real-time motion estimation. The four approaches were evaluated based on the end-point-error and root-mean-square error compared to a ground-truth optical flow estimate on fully-sampled images, the structural similarity (SSIM) after registration and time necessary to acquire k-space, reconstruct an image and estimate motion. The lowest DVF error and highest SSIM were obtained using conventional methods up to [Formula: see text]. For undersampling factors [Formula: see text], the lowest DVF error and highest SSIM were obtained using conventional image reconstruction and DL-based motion estimation. We have found that, with this combination, accurate DVFs can be obtained up to [Formula: see text] with an average root-mean-square error up to 1 millimeter and an SSIM greater than 0.8 after registration, taking 60 milliseconds. High-quality 2D DVFs from highly undersampled k-space can be obtained with a high temporal resolution with conventional image reconstruction and a deep learning-based motion estimation approach for real-time adaptive MRI-guided radiotherapy.