Mapping the emotional homunculus with fMRI.

Emotions are commonly associated with bodily sensations, e.g., boiling with anger when overwhelmed with rage. Studies have shown that emotions are related to specific body parts, suggesting that somatotopically organized cortical regions that commonly respond to somatosensory and motor experiences might be involved in the generation of emotions. We used functional magnetic resonance imaging to investigate whether the subjective feelings of emotion are accompanied by the activation of somatotopically defined sensorimotor brain regions, thus aiming to reconstruct an "emotional homunculus." By defining the convergence of the brain activation patterns evoked by self-generated emotions during scanning onto a sensorimotor map created on participants' tactile and motor brain activity, we showed that all the evoked emotions activated parts of this sensorimotor map, yet with considerable overlap among different emotions. Although we could not find a highly specific segmentation of discrete emotions over sensorimotor regions, our results support an embodied experience of emotions.

A ROI-based quantitative pipeline for 18F-FDG PET metabolism and pCASL perfusion joint analysis: Validation of the 18F-FDG PET line.

In Mild Cognitive Impairment (MCI), the study of brain metabolism, provided by 18F-FluoroDeoxyGlucose Positron Emission Tomography (18F-FDG PET) can be integrated with brain perfusion through pseudo-Continuous Arterial Spin Labeling Magnetic Resonance sequences (MR pCASL). Cortical hypometabolism identification generally relies on wide control group datasets; pCASL control groups are instead not publicly available yet, due to lack of standardization in the acquisition parameters. This study presents a quantitative pipeline to be applied to PET and pCASL data to coherently analyze metabolism and perfusion inside 16 matching cortical regions of interest (ROIs) derived from the AAL3 atlas. The PET line is tuned on 36 MCI patients and 107 healthy control subjects, to agree in identifying hypometabolic regions with clinical reference methods (visual analysis supported by a vendor tool and Statistical Parametric Mapping, SPM, with two parametrizations here identified as SPM-A and SPM-B). The analysis was conducted for each ROI separately. The proposed PET analysis pipeline obtained accuracy 78 % and Cohen's к 60 % vs visual analysis, accuracy 79 % and Cohen's к 58 % vs SPM-A, accuracy 77 % and Cohen's к 54 % vs SPM-B. Cohen's к resulted not significantly different from SPM-A and SPM-B Cohen's к when assuming visual analysis as reference method (p-value 0.61 and 0.31 respectively). Considering SPM-A as reference method, Cohen's к is not significantly different from SPM-B Cohen's к as well (p-value = 1.00). The complete PET-pCASL pipeline was then preliminarily applied on 5 MCI patients and metabolism-perfusion regional correlations were assessed. The proposed approach can be considered as a promising tool for PET-pCASL joint analyses in MCI, even in the absence of a pCASL control group, to perform metabolism-perfusion regional correlation studies, and to assess and compare perfusion in hypometabolic or normo-metabolic areas.

MesenchymAl stromal cells for Traumatic bRain Injury (MATRIx): a study protocol for a multicenter, double-blind, randomised, placebo-controlled phase II trial.

BACKGROUND: Traumatic brain injury (TBI) is a significant cause of death and disability, with no effective neuroprotective drugs currently available for its treatment. Mesenchymal stromal cell (MSC)-based therapy shows promise as MSCs release various soluble factors that can enhance the injury microenvironment through processes, such as immunomodulation, neuroprotection, and brain repair. Preclinical studies across different TBI models and severities have demonstrated that MSCs can improve functional and structural outcomes. Moreover, clinical evidence supports the safety of third-party donor bank-stored MSCs in adult subjects. Building on this preclinical and clinical data, we present the protocol for an academic, investigator-initiated, multicenter, double-blind, randomised, placebo-controlled, adaptive phase II dose-finding study aiming to evaluate the safety and efficacy of intravenous administration of allogeneic bone marrow-derived MSCs to severe TBI patients within 48 h of injury. METHODS/DESIGN: The study will be conducted in two steps. Step 1 will enrol 42 patients, randomised in a 1:1:1 ratio to receive 80 million MSCs, 160 million MSCs or a placebo to establish safety and identify the most promising dose. Step 2 will enrol an additional 36 patients, randomised in a 1:1 ratio to receive the selected dose of MSCs or placebo. The activity of MSCs will be assessed by quantifying the plasmatic levels of neurofilament light (NfL) at 14 days as a biomarker of neuronal damage. It could be a significant breakthrough if the study demonstrates the safety and efficacy of MSC-based therapy for severe TBI patients. The results of this trial could inform the design of a phase III clinical trial aimed at establishing the efficacy of the first neurorestorative therapy for TBI. DISCUSSION: Overall, the MATRIx trial is a critical step towards developing an effective treatment for TBI, which could significantly improve the lives of millions worldwide affected by this debilitating condition. Trial Registration EudraCT: 2022-000680-49.

Exoscopic Microsurgery: A Change of Paradigm in Brain Tumor Surgery? Comparison with Standard Operative Microscope.

BACKGROUND: The exoscope is a high-definition telescope recently introduced in neurosurgery. In the past few years, several reports have described the advantages and disadvantages of such technology. No studies have compared results of surgery with standard microscope and exoscope in patients with glioblastoma multiforme (GBM). METHODS: Our retrospective study encompassed 177 patients operated on for GBM (WHO 2021) between February 2017 and August 2022. A total of 144 patients were operated on with a microscope only and the others with a 3D4K exoscope only. All clinical and radiological data were collected. Progression-free survival (PFS) and overall survival (OS) have been estimated in the two groups and compared by the Cox model adjusting for potential confounders (e.g., sex, age, Karnofsky performance status, gross total resection, MGMT methylated promoter, and operator's experience). RESULTS: IDH was mutated in 9 (5.2%) patients and MGMT was methylated in 76 (44.4%). Overall, 122 patients received a gross total resection, 14 patients received a subtotal resection, and 41 patients received a partial resection. During follow-up, 139 (73.5%) patients experienced tumor recurrence and 18.7% of them received a second surgery. After truncation to 12 months, the median PFS for patients operated on with the microscope was 8.82 months, while for patients operated on with the exoscope it was >12 months. Instead, the OS was comparable in the two groups. The multivariable Cox model showed that the use of microscope compared to the exoscope was associated with lower progression-free survival (hazard ratio = 3.55, 95%CI = 1.66-7.56, p = 0.001). CONCLUSIONS: The exoscope has proven efficacy in terms of surgical resection, which was not different to that of the microscope. Furthermore, patients operated on with the exoscope had a longer PFS. A comparable OS was observed between microscope and exoscope, but further prospective studies with longer follow-up are needed.

Case Report: Potential role of selective venous sampling for liquid biopsy in complex clinical settings: Three case presentations.

Tumor mutation profiling from a blood sample, known as liquid biopsy, is a reality that has already been approved for some cancers. This molecular diagnostic method complements tissue biopsy but is less invasive and therefore more easily applied, especially during tumor evolution. Its use should allow detection of residual disease, evaluation of treatment response or resistance, and selection of targeted treatments. However, implementation of liquid biopsy in routine clinical practice is hindered by unsolved issues, one of which is the scarcity of circulating tumor DNA in blood samples drawn from peripheral veins. To address this problem, we propose minimally invasive selective venous sampling from the region of interest, as used for some hormonal studies and for mapping of endocrine tumors. Intuitively, selective sampling should improve the sensitivity of liquid biopsy by avoiding the dilution of tumor biomarkers that occurs in the peripheral circulation. We report three cases that illustrate the potential utility of selective liquid biopsy in complex clinical settings, providing implications for diagnosis and treatment as well as for monitoring over time, disease localization, identification of drug resistance, and differential diagnosis.

Neural bases of loss aversion when choosing for oneself versus known or unknown others.

Despite the ubiquitous interdependence between one's own decisions and others' welfare, and the controversial evidence on the behavioral effect of choosing for others, the neural bases of making decisions for another versus oneself remain unexplored. We investigated whether loss aversion (LA; the tendency to avoid losses over approaching equivalent gains) is modulated by (i) choosing for oneself, other individuals, or both; (ii) knowing or not knowing the other recipients; or (iii) an interaction between these factors. We used fMRI to assess the brain activations associated with choosing whether to accept or reject mixed gambles, either for oneself, for another player, or both, in 2 groups of 28 participants who had or had not briefly interacted with the other players before scanning. Participants displayed higher LA for choices involving their payoff compared with those affecting only the payoff of other, known, players. This "social" modulation of decision-making was found to engage the dorsomedial prefrontal cortex and its inhibitory connectivity to the middle cingulate cortex. This pattern might underpin decision-making for known others via self-other distinction processes associated with dorsomedial prefrontal areas, with this in turn promoting the inhibition of socially oriented responses through the downregulation of the midcingulate node of the empathy network.

Perilesional resection technique of glioblastoma: intraoperative ultrasound and histological findings of the resection borders in a single center experience.

INTRODUCTION: The surgical goal in glioblastoma treatment is the maximal safe resection of the tumor. Currently the lack of consensus on surgical technique opens different approaches. This study describes the "perilesional technique" and its outcomes in terms of the extent of resection, progression free survival and overall survival. METHODS: Patients included (n = 40) received a diagnosis of glioblastoma and underwent surgery using the perilesional dissection technique at "San Gerardo Hospital"between 2018 and 2021. The tumor core was progressively isolated using a circumferential movement, healthy brain margins were protected with Cottonoid patties in a "shingles on the roof" fashion, then the tumorwas removed en bloc. Intraoperative ultrasound (iOUS) was used and at least 1 bioptic sample of "healthy" margin of the resection was collected and analyzed. The extent of resection was quantified. Extent of surgical resection (EOR) and progression free survival (PFS)were safety endpoints of the procedure. RESULTS: Thirty-four patients (85%) received a gross total resection(GTR) while 3 (7.5%) patients received a sub-total resection (STR), and 3 (7.5%) a partial resection (PR). The mean post-operative residual volume was 1.44 cm3 (range 0-15.9 cm3).During surgery, a total of 76 margins were collected: 51 (67.1%) were tumor free, 25 (32.9%) were infiltrated. The median PFS was 13.4 months, 15.3 in the GTR group and 9.6 months in the STR-PR group. CONCLUSIONS: Perilesional resection is an efficient technique which aims to bring the surgeon to a safe environment, carefully reaching the "healthy" brain before removing the tumoren bloc. This technique can achieve excellent tumor margins, extent of resection, and preservation of apatient's functions.

The peritumoral brain zone in glioblastoma: where we are and where we are going.

Glioblastoma (GBM) is the most aggressive and invasive primary brain tumor. Current therapies are not curative, and patients' outcomes remain poor with an overall survival of 20.9 months after surgery. The typical growing pattern of GBM develops by infiltrating the surrounding apparent normal brain tissue within which the recurrence is expected to appear in the majority of cases. Thus, in the last decades, an increased interest has developed to investigate the cellular and molecular interactions between GBM and the peritumoral brain zone (PBZ) bordering the tumor tissue. The aim of this review is to provide up-to-date knowledge about the oncogenic properties of the PBZ to highlight possible druggable targets for more effective treatment of GBM by limiting the formation of recurrence, which is almost inevitable in the majority of patients. Starting from the description of the cellular components, passing through the illustration of the molecular profiles, we finally focused on more clinical aspects, represented by imaging and radiological details. The complete picture that emerges from this review could provide new input for future investigations aimed at identifying new effective strategies to eradicate this still incurable tumor.

Depressive Pseudodementia with Reversible AD-like Brain Hypometabolism: A Case Report and a Review of the Literature.

Recent European guidelines recommend using brain FDG-PET to differentiate between Alzheimer's disease (AD) and depressive pseudodementia (DP), with specific hypometabolism patterns across the former group, and typically normal or frontal hypometabolism in the latter. We report the case of a 74 years-old man with DP (MMSE 16/30), whose FDG-PET visual rating and semiquantitative analysis closely mimicked the typical AD pattern, showing severe hypometabolism in bilateral precuneus, parietal and temporal lobes, and sparing frontal areas, suggesting the diagnosis of moderate AD. Shortly after starting antidepressant polytherapy, he underwent formal NPS testing, which revealed moderate impairment of episodic memory and mild impairment on executive and visuospatial tests, judged consistent with neurodegenerative dementia and concomitant depression. Over the following two years, he improved dramatically: repeated NPS assessment did not show significant deficits, and FDG-PET showed restoration of cerebral metabolism. The confirmation of PET findings via semiquantitative analysis, and their reversion to normality with antidepressant treatment, proved the non-neurodegenerative origin of the initial AD-like FDG-PET abnormalities. We review similar cases and provide a comprehensive analysis of their implications, concluding that reversible FDG-PET widespread hypometabolism might represent a biomarker of pseudodementia. Therefore, we suggest caution when interpreting FDG-PET scans of depressed patients with cognitive impairment.

Computation of contrast-enhanced perfusion using only two CT scan phases: a proof-of-concept study on abdominal organs.

BACKGROUND: Computed tomography perfusion imaging (CTPI) by repeated scanning has clinical relevance but implies relatively high radiation exposure. We present a method to measure perfusion from two CT scan phases only, considering tissue enhancement, feeding vessel (aortic) peak enhancement, and bolus shape. METHODS: CTPI scans (each with 40 frames acquired every 1.5 s) of 11 patients with advanced hepatocellular carcinoma (HCC) enrolled between 2012 and 2016 were retrospectively analysed (aged 69 ± 9 years, 8/11 males). Perfusion was defined as the maximal slope of the time-enhancement curve divided by the peak enhancement of the feeding vessel (aorta). Perfusion was computed two times, first using the maximum slope derived from all data points and then using the peak tissue enhancement and the bolus shape obtained from the aortic curve. RESULTS: Perfusion values from the two methods were linearly related (r2 = 0.92, p < 0.001; Bland-Altman analysis bias -0.12). The mathematical model showed that the perfusion ratio of two ROIs with the same feeding vessel (aorta) corresponds to their peak enhancement ratio (r2 = 0.55, p < 0.001; Bland-Altman analysis bias -0.68). The relationship between perfusion and tissue enhancement is predicted to be linear in the clinical range of interest, being only function of perfusion, peak feeding vessel enhancement, and bolus shape. CONCLUSIONS: This proof-of-concept study showed that perfusion values of HCC, kidney, and pancreas could be computed using enhancement measured only with two CT scan phases, if aortic peak enhancement and bolus shape are known.

Association of Microglial Activation With Spontaneous ARIA-E and CSF Levels of Anti-Aß Autoantibodies.

BACKGROUND AND OBJECTIVES: Amyloid-related imaging abnormalities suggestive of vasogenic edema or sulcal effusion (ARIA-E) are the most common adverse events complicating Alzheimer disease (AD) immunotherapy with anti-ß-amyloid (Aß) monoclonal antibodies. ARIA-E can also occur spontaneously in cerebral amyloid angiopathy-related inflammation (CAA-ri), a rare autoimmune encephalopathy associated with increased CSF levels of anti-Aß autoantibodies. Although the pathophysiologic mechanisms of ARIA-E remain to be fully elucidated, experimental evidence from ex vivo studies suggests that gantenerumab and aducanumab enable microglial activation. However, the in vivo evidence for a direct association between neuroinflammation and ARIA-E in patients with high CSF anti-Aß (auto)antibody levels has never been demonstrated. METHODS: The spatial distribution and temporal variations of microglial activation associated with levels of anti-Aß autoantibodies at (sub)acute presentation of ARIA-E and after corticosteroid therapy were evaluated in a longitudinal case series of patients with CAA-ri, the spontaneous variant of the iatrogenic ARIA-E reported in Aß-lowering immunotherapy with monoclonal antibodies. Multimodal and multiparametric MRI was used for CAA and ARIA-E severity quantification, according to validated scoring system; CSF testing for anti-Aß autoantibodies and AD biomarkers; 11C-PK11195 PET for activated microglia. RESULTS: At (sub)acute presentation, we found focal peaks of microglial activation having a greater spatial colocalization with ARIA-E compared with chronic age-related white matter change imaging abnormalities. The severity of ARIA-E and the magnitude of the associated microglial activation were greater in patients having AD and severe CAA concomitant disease compared with patients having CAA only. CSF anti-Aß autoantibodies at presentation were high in all patients and markedly decreased at posttreatment follow-up, in parallel with clinical resolution of acute symptoms, reduced ARIA-E severity, and reduced microglial activation. DISCUSSION: Our findings extend the current notion of ARIA-E by providing the first in vivo 11C-PK11195 PET evidence for an association between microglial activation and the magnitude and severity of ARIA-E in patients with increased CSF concentration of anti-Aß autoantibodies and comorbid AD and CAA disease. Our results highlight CSF testing for anti-Aß autoantibodies as a promising diagnostic, prognostic, and therapy response biomarker to help guide future treatment and management decisions in real clinical practice and clinical trials.

Altered striatal-opercular intrinsic connectivity reflects decreased aversion to losses in alcohol use disorder.

The persistence of addictive behaviours despite their adverse consequences highlights decreased punishment sensitivity as a facet of decision-making impairments in Alcohol Use Disorder (AUD). This attitude departs from the typical loss aversion (LA) pattern, i.e. the stronger sensitivity to negative than positive outcomes, previously associated with striatal and limbic-somatosensory responsiveness in healthy individuals. Consistent evidence highlights decreased LA as a marker of disease severity in AUD, but its neural bases remain largely unexplored. AUD-specific modulations of frontolateral activity by LA were previously related to the higher executive demands of anticipating losses than gains, but the relationship between LA and executive/working-memory performance in AUD is debated. Building on previous evidence of overlapping neural bases of LA during decision-making and at rest, we investigated a possible neural signature of altered LA in AUDs, and its connections with executive skills, in terms of complementary facets of resting-state functioning. In patients, smaller LA than controls, unrelated to executive performance, reflected reduced connectivity within striatal and medial temporal networks, and altered connectivity from these regions to the insular-opercular cortex. AUD-specific loss-related modulations of intrinsic connectivity thus involved structures previously associated both with drug-seeking and with coding the trade-off between appetitive and aversive motivational drives. These findings fit the hypothesis that altered striatal coding of choice-related incentive value, and interoceptive responsiveness to prospective outcomes, enhance neural sensitivity to drug-related stimuli in addictions. LA and its neural bases might prove useful markers of AUD severity and effectiveness of rehabilitation strategies targeting the salience of negative choice outcomes.

Posterior fronto-medial atrophy reflects decreased loss aversion, but not executive impairment, in alcohol use disorder.

Decreased punishment sensitivity in alcohol use disorder (AUD) might reflect a reduction in the typical human tendency to overweigh negative choice outcomes compared with equivalent positive ones, that is, 'loss aversion.' While this hypothesis is supported by previous reports of reduced loss aversion in AUD, it is still unknown whether such decreased sensitivity to prospective losses represents a specific facet of altered decision-making or a secondary effect of executive/working-memory impairments. We addressed this issue by assessing whether lower loss aversion in 22 AUD patients compared with 19 healthy controls is explained by their differential executive or working-memory performance and by investigating its neural basis in terms of grey matter density and cortical thickness via voxel- and surface-based morphometry, respectively. A significant decrease of loss aversion in patients, unrelated to their impaired executive/working-memory performance, reflected the reduction of posterior fronto-medial grey matter density and right frontopolar cortical thickness. Rather than their executive deficits, patients' reduced loss aversion reflects the structural damage of the posterior fronto-medial cortex previously associated with solving conflicts at the response level, where earlier functional magnetic resonance imaging (fMRI) studies have shown a 'neural loss aversion' pattern of steeper deactivation for losses than activation for gains, and of the frontopolar cortex in charge of managing competing goals. These findings highlight possible directions for addressing AUD patients' high relapse rate, for example, cognitive-behavioural rehabilitative interventions enhancing the awareness of the adverse outcomes of addiction or neurostimulation protocols targeting the regions processing their salience.

Functional Coherence in Intrinsic Frontal Executive Networks Predicts Cognitive Impairments in Alcohol Use Disorder.

Growing evidence highlights the potential of innovative rehabilitative interventions such as cognitive remediation and neuromodulation, aimed at reducing relapses in Alcohol Use Disorder (AUD). Enhancing their effectiveness requires a thorough description of the neural correlates of cognitive alterations in AUD. Past related attempts, however, were limited by the focus on selected neuro-cognitive variables. We aimed to fill this gap by combining, in 22 AUD patients and 18 controls, an extensive neuro-cognitive evaluation and metrics of intrinsic connectivity as highlighted by resting-state brain activity. We addressed an inherent property of intrinsic activity such as intra-network coherence, the temporal correlation of the slow synchronous fluctuations within resting-state networks, representing an early biomarker of alterations in the functional brain architecture underlying cognitive functioning. AUD patients displayed executive impairments involving working-memory, attention and visuomotor speed, reflecting abnormal coherence of activity and grey matter atrophy within default mode, in addition to the attentional and the executive networks. The stronger relationship between fronto-lateral coherent activity and executive performance in patients than controls highlighted possible compensatory mechanisms counterbalancing the decreased functionality of networks driving the switch from automatic to controlled behavior. These results provide novel insights into AUD patients' cognitive impairments, their neural bases, and possible targets of rehabilitative interventions.

Increased decision latency in alcohol use disorder reflects altered resting-state synchrony in the anterior salience network.

Increased decision latency in alcohol use disorder (AUD) has been generally explained in terms of psychomotor slowing. Recent results suggest that AUD patients' slowed decision-making might rather reflect alterations in the neural circuitry underlying the engagement of controlled processing by salient stimuli. We addressed this hypothesis by testing a relationship between decision latency at the Cambridge Gambling Task (CGT) and intrinsic brain activity in 22 individuals with AUD and 19 matched controls. CGT deliberation time was related to two complementary facets of resting-state fMRI activity, i.e. coherence and intensity, representing early biomarkers of functional changes in the intrinsic brain architecture. For both metrics, we assessed a multiple regression (to test a relationship with deliberation time in the whole sample), and an interaction analysis (to test a significantly different relationship with decision latency across groups). AUD patients' slowed deliberation time (p < 0.025) reflected distinct facets of altered intrinsic activity in the cingulate node of the anterior salience network previously associated with the "output" motor stage of response selection. Its heightened activity in AUD patients compared with controls, tracking choice latency (p < 0.025 corrected), might represent a compensation mechanism counterbalancing the concurrent decrease of its internal coherent activity (p < 0.025 corrected). These findings provide novel insights into the intrinsic neural mechanisms underlying increased decision latency in AUD, involving decreased temporal synchronicity in networks promoting executive control by behaviourally relevant stimuli. These results pave the way to further studies assessing more subtle facets of decision-making in AUD, and their possible changes with rehabilitative treatment.

Spontaneous ARIA-like Events in Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Prospective Longitudinal Cohort Study.

BACKGROUND AND OBJECTIVES: The goal of this work was to investigate the natural history and outcomes after treatment for spontaneous amyloid-related imaging abnormalities (ARIA)-like in cerebral amyloid angiopathy-related inflammation (CAA-ri). METHODS: This was a multicenter, hospital-based, longitudinal, prospective observational study of inpatients meeting CAA-ri diagnostic criteria recruited through the Inflammatory Cerebral Amyloid Angiopathy and Alzheimer's Disease ßiomarkers International Network from January 2013 to March 2017. A protocol for systematic data collection at first-ever presentation and at subsequent in-person visits, including T1-weighted, gradient recalled echo-T2*, fluid-suppressed T2-weighted (fluid-attenuated inversion recovery), and T1 postgadolinium contrast-enhanced images acquired on 1.5T MRI, was used at the 3-, 6-, 12-, and 24-month follow-up. Centralized reads of MRIs were performed by investigators blinded to clinical, therapeutic, and time-point information. Main outcomes were survival, clinical and radiologic recovery, intracerebral hemorrhage (ICH), and recurrence of CAA-ri. RESULTS: The study enrolled 113 participants (10.6% definite, 71.7% probable, and 17.7% possible CAA-ri). Their mean age was 72.9 years; 43.4% were female; 37.1% were APOEε4 carriers; 36.3% had a history of Alzheimer disease; and 33.6% had a history of ICH. A history of ICH and the occurrence of new ICH at follow-up were more common in patients with cortical superficial siderosis at baseline (52.6% vs 14.3%, p < 0.0001 and 19.3% vs 3.6%, p < 0.009, respectively). After the first-ever presentation of CAA-ri, 70.3% (95% confidence interval [CI] 61.6%-78.5%) and 84.1% (95% CI 76.2%-90.6%) clinically recovered within 3 and 12 months, followed by radiologic recovery in 45.1% (95% CI 36.4%-54.8%) and 77.4% (95% CI 67.7%-85.9%), respectively. After clinicoradiologic resolution of the first-ever episode, 38.3% (95% CI 22.9%-59.2%) had at least 1 recurrence within the following 24 months. Recurrence was more likely if IV high-dose corticosteroid pulse therapy was suddenly stopped compared to slow oral tapering off (hazard ratio 4.68, 95% CI 1.57-13.93; p = 0.006). DISCUSSION: These results from the largest longitudinal cohort registry of patients with CAA-ri support the transient and potentially relapsing inflammatory nature of the clinical-radiologic acute manifestations of the disease and the effectiveness of slow oral tapering off after IV corticosteroid pulse therapy in preventing recurrences. Our results highlight the importance of differential diagnosis for spontaneous ARIA-like events in ß-amyloid-driven diseases, including treatment-related ARIA in patients with Alzheimer disease exposed to immunotherapy drugs.

Perspectives on (A)symmetry of Arcuate Fasciculus. A Short Review About Anatomy, Tractography and TMS for Arcuate Fasciculus Reconstruction in Planning Surgery for Gliomas in Language Areas.

Gliomas are brain tumors that are treated with surgical resection. Prognosis is influenced by the extent of resection and postoperative neurological status. As consequence, given the extreme interindividual and interhemispheric variability of subcortical white matter (WM) surgical planning requires to be patient's tailored. According to the "connectionist model," there is a huge variability among both cortical areas and subcortical WM in all human beings, and it is known that brain is able to reorganize itself and to adapt to WM lesions. Brain magnetic resonance imaging diffusion tensor imaging (DTI) tractography allows visualization of WM bundles. Nowadays DTI tractography is widely available in the clinical setting for presurgical planning. Arcuate fasciculus (AF) is a long WM bundle that connects the Broca's and Wernicke's regions with a complex anatomical architecture and important role in language functions. Thus, its preservation is important for the postoperative outcome, and DTI tractography is usually performed for planning surgery within the language-dominant hemisphere. High variability among individuals and an asymmetrical pattern has been reported for this WM bundle. However, the functional relevance of AF in the contralateral non-dominant hemisphere in case of tumoral or surgical lesion of the language-dominant AF is unclear. This review focuses on AF anatomy with special attention to its asymmetry in both normal and pathological conditions and how it may be explored with preoperative tools for planning surgery on gliomas in language areas. Based on the findings available in literature, we finally speculate about the potential role of preoperative evaluation of the WM contralateral to the surgical site.

Decreased information processing speed and decision-making performance in alcohol use disorder: combined neurostructural evidence from VBM and TBSS.

Alcohol Use Disorder (AUD) is a chronic relapsing condition characterized by excessive alcohol consumption despite its multifaceted adverse consequences, associated with impaired performance in several cognitive domains including decision-making. While choice deficits represent a core component of addictive behavior, possibly consecutive to brain changes preceding the onset of the addiction cycle, the evidence on grey-matter and white-matter damage underlying abnormal choices in AUD is still limited. To fill this gap, we assessed the neurostructural bases of decision-making performance in 22 early-abstinent alcoholic patients and 18 controls, by coupling the Cambridge Gambling Task (CGT) with quantitative magnetic resonance imaging metrics of grey-matter density and white-matter integrity. Regardless of group, voxel based morphometry highlighted an inverse relationship between deliberation time and grey-matter density, with alcoholics displaying slower choices related to grey-matter atrophy in key nodes of the motor control network. In particular, grey-matter density in the supplementary motor area, reduced in alcoholic patients, explained a significant amount of variability in their increased deliberation time. Tract-based spatial statistics revealed a significant relationship between CGT deliberation time and all white-matter indices, involving the most relevant commissural, projection and associative tracts. The lack of choice impairments other than increased deliberation time highlights reduced processing speed, mediated both by grey-matter and white-matter alterations, as a possible marker of a generalized executive impairment extending to the output stages of decision-making. These results pave the way to further studies aiming to tailor novel rehabilitation strategies and assess their functional outcomes.

Increased pSTS activity and decreased pSTS-mPFC connectivity when processing negative social interactions.

We have previously shown that activity and connectivity within and between the action observation and mentalizing brain systems reflect the degree of positive dimensions expressed by social interactions such as cooperativity and affectivity, respectively. Here we aim to extend this evidence by investigating the neural bases of processing negative dimensions of observed interactions, such as competition and affective conflict, possibly representing a benchmark for different pathological conditions. In this fMRI study 34 healthy participants were shown pictures depicting interactions characterized by two crossed dimensions, i.e. positively- vs. negatively- connotated social intentions mainly expressed in terms of motor acts vs. mental states, i.e. cooperative, competitive, affective and conflicting interactions. We confirmed the involvement of the action observation and mentalizing networks in processing intentions mainly expressed through motor acts (cooperative/competitive) vs. mental states (affective/conflicting), respectively. Results highlighted the selective role of the left pSTS/TPJ in decoding social interactions, even when compared with parallel actions by non-interacting individuals. Its right-hemispheric homologue displayed stronger responses to negative than positive social intentions, regardless of their motor/mental status, and decreased connectivity with the medial prefrontal cortex (mPFC) when processing negative interactions. The resulting mPFC downregulation by negative social scenes might reflect an adaptive response to socio-affective threats, via decreased mentalizing when facing negative social stimuli. This evidence on the brain mechanisms underlying the decoding of real complex interactions represents a baseline for assessing both the neural correlates of impaired social cognition, and the effects of rehabilitative treatments, in neuro-psychiatric diseases or borderline conditions such as loneliness.