Ipsilesional Impairments of Visual Awareness After Right-Hemispheric Stroke

Unilateral brain damage following stroke frequently hampers the processing of contralesional space. Whether and how it also affects the processing of stimuli appearing on the same side of the lesion is still poorly understood. Three main alternative hypotheses have been proposed, namely that ipsilesional processing is functionally (i) hyperefficient, (ii) impaired, or (iii) spared. Here, we investigated ipsilesional space awareness through a computerized paradigm that exploits a manipulation of concurrent information processing demands (i.e., multitasking). Twelve chronic right-hemisphere stroke patients with a total lack of awareness for the contralesional side of space were administered a task that required the spatial monitoring of two locations within the ipsilesional hemispace. Targets were presented immediately to the right of a central fixation point (3° eccentricity), or farther to the right toward the screen edge (17° eccentricity), or on both locations. Response to target position occurred either in isolation or while performing a concurrent visual or auditory task. Results showed that most errors occurred when two targets were simultaneously presented and patients were faced with additional task demands (in the visual or auditory modalities). In the context of concurrent visual load, ipsilesional targets presented at the rightmost location were omitted more frequently than those presented closer to fixation. This pattern qualifies ipsilesional processing in right-hemisphere stroke patients as functionally impaired, arguing against the notion of ipsilesional hyperperformance, especially when under visual load

The Presence of ANCA in IgA Crescentic Nephropathy Does Not Lead to Worse Prognosis with Intensive Rescue Treatment

Nefropatía por IgA; Autoanticuerpos anticitoplasma de neutrófilosIgA nephropathy; Antineutrophil cytoplasmic autoantibodiesNefropatia per IgA; Anticossos anticitoplasma de neutròfilsBackground: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. The concomitant presence of both crescentic proliferation and anti-neutrophil cytoplasmic autoantibodies (ANCA) in this pathology represents a rare coincidence. However, it is not clear to what extent the presence of ANCA (IgA or IgG) in these patients could have any clinical significance. The aim of the current work is to describe the presence of ANCA (IgA or IgG) in patients with IgAN and crescentic proliferation and its possible clinical implications. Methods: We retrospectively recruited all patients in our center with a histological diagnosis of IgAN with crescentic proliferation between January 2013 and December 2020. The main demographic and clinicopathologic data, fundamental histological characteristics, as well as the treatments implemented and main kidney outcomes, were collected and analyzed at a 6 and 12-month follow-up. Results: Between January 2013 and December 2020, a total of 17 adults were diagnosed with concomitant crescentic proliferation through a kidney biopsy of IgAN. Five (29.4%) patients showed ANCA, three (60%) showed IgA-ANCA and two (40%) showed IgG-ANCA. All ANCA-positive patients had some degree of crescentic proliferation. At diagnosis, the mean age of patients was 48 years old (range: 27–75). Nine of them were women (52%) and the most common clinical presentation was hypertension (71%). At the time of biopsy, the mean serum creatinine and proteinuria were 2.2 mg/dL (DS 1.42) and 3.5 g/mgCr (DS 1.22), respectively, with no statistical differences between ANCA-positive and -negative patients. Histological analyses showed that 11 out of the 12 (91%) ANCA-negative IgAN patients displayed less than 25% cellular crescents, whereas 100% of ANCA-positive IgAN patients displayed more than 25% cellular crescents (p = 0.04). Notably, five (30%) patients displayed fibrinoid necrosis, with four of them (80%) being IgAN-ANCA-positive (p = 0.01). Only one ANCA-negative patient needed renal replacement therapy (RRT) upon admission (5%). The mean serum creatinine and proteinuria were 1.94 mg/dL (DS 1.71) and 1.45 g/gCr (DS 1.78), respectively, within 6 months of immunosuppressive therapy. At 12-month follow-up, the mean creatinine was 1.57 mg/dL (DS 1). Four (23.5%) patients needed RRT at the end of the follow-up and four (23.5%) patients died. Conclusions: Probably due to the limited number of IgAN-ANCA-positive and IgAN-ANCA-negative patients, no significant differences were found between the clinical and laboratory characteristics. IgAN-ANCA-negative patients seemed to display less extracapillary proliferation than IgAN-ANCA-positive patients, who tended to show significantly higher fibrinoid necrosis. There were no differences regarding renal prognosis and patient survival after aggressive immunosuppressive therapy within 6 and 12 months when comparing the two samples

The cognitive demand of multitasking under visuo-spatial processing: Assessment, ERPs and electrophysiology of brain networks in chronic stroke patients

This thesis investigates several aspects of visuo-spatial processing from a clinical, electrophysiological and neurofunctional perspective, with the aim of enriching our understanding of neurological syndromes that affect such fundamental perceptual-cognitive skill. A common thread is the use of cognitive load as a mean to study spatial awareness deficits following brain stroke. We show that increased task demands uncovers pathological spatial asymmetries both in right and left hemisphere damaged patients that performed at ceiling in standard paper-and-pencil tests. Although visuo-spatial deficits are commonly considered infrequent after left hemisphere lesions, the comparison between the two clinical populations showed that multitasking reveals patterns of neglect and extinction regardless of the affected hemisphere. A similar multitasking paradigm was then administered to young healthy participants in order to study the electrophysiological signatures of spatial monitoring, examining correct and erroneous processing of peripheral visual stimuli. Task difficulty was increased compared to the clinical version in order to obtain a consistent number of missed targets, thereby simulating patients’ performance. Our results support the hypothesis that processing of visual information under multitasking is regulated by a threshold criterion: the target is successfully detected only when the electrophysiological activity reaches a critical amplitude. Finally, we conducted a resting state electroencephalographic (EEG) study in order to correlate patterns of spontaneous brain activity with neuropsychological scores and multitasking costs indices. This investigation builds on the hypothesis that cognition is not only associated with the specialization of brain regions, but also with the large-scale organization of functionally connected networks. A state-of-art methodology was used to reconstruct 14 brain networks, previously detected in fMRI studies, from electrophysiological signals in chronic stroke patients. The integration of critical clusters within each network was then examined, exploring also its correlation with behavioural measures and the contribution of specific frequency bands. Overall, this empirical work provides an original contribution to the study of the mechanisms underlying brain organization after unilateral damage and the consequent implications for cognitive performance.Questo lavoro di tesi indaga diversi aspetti relativi all’elaborazione visuo-spaziale da un punto di vista clinico, elettrofisiologico e neurofunzionale, al fine di contribuire allo studio dei disturbi neurologici che comportano deficit a livello percettivo. Il filo conduttore è stato l’utilizzo del carico cognitivo per studiare deficit di consapevolezza spaziale che possono emergere a seguito di un ictus cerebrale. Abbiamo mostrato come l’aumento della difficoltà di un compito sia in grado di rilevare asimmetrie spaziali patologiche in pazienti con lesioni cerebrali all’emisfero destro o sinistro che avevano una prestazione nella norma ai classici test neuropsicologici “carta e matita”. Sebbene i disturbi visuo-spaziali siano ritenuti infrequenti a seguito di lesioni emisferiche sinistre, sorprendentemente il confronto di queste due popolazioni cliniche mette in luce l’efficacia del multitasking nell’individuare pattern di negligenza ed estinzione indipendentemente dal lato della lesione. Una versione modificata del nostro paradigma di multitasking è stata inoltre somministrata ad un gruppo di giovani partecipanti sani al fine di studiare i correlati elettrofisiologici del monitoraggio spaziale, confrontando l’elaborazione corretta ed incorretta di stimoli apparsi nella periferia del campo visivo. La difficoltà del compito è stata aumentata rispetto alla versione clinica al fine di ottenere un consistente numero di stimoli non individuati e dunque di simulare la prestazione di pazienti neurologici. I nostri risultati supportano l’ipotesi che in condizione di multitasking l’elaborazione di informazioni visive sia regolata da un criterio di soglia. Nello specifico, la corretta percezione di uno stimolo è determinata dal raggiungimento di un’ampiezza critica dell’attività corticale. Infine, abbiamo condotto uno studio in resting state al fine di studiare la correlazione tra attività cerebrale spontanea e prestazione comportamentale, misurata attraverso classici indici neuropsicologici ed indici di costo al multitasking. Questo studio prende in considerazione l’ipotesi che la cognizione non sia associata soltanto alla specializzazione delle regioni cerebrali, ma anche all’organizzazione su larga scala di reti neuronali funzionalmente connesse. Attraverso l’utilizzo di un metodo di analisi allo stato dell’arte, 14 reti cerebrali, precedentemente studiate con tecniche di risonanza magnetica funzionale, sono state estratte dal segnale elettroencefalografico in un gruppo di pazienti con esiti di ictus in fase cronica. Inoltre, è stata analizzata l’integrazione di particolari cluster all’interno di ciascuna rete, indagando anche la relativa correlazione con indici comportamentali ed il contributo di specifiche bande di frequenza. In sintesi, questo lavoro empirico offre un contributo originale allo studio dei meccanismi sottostanti l’organizzazione cerebrale a seguito di ictus e delle relative ripercussioni sulla prestazione cognitiva

Hearing voices in the head: Two meta-analyses on structural correlates of auditory hallucinations in schizophrenia

Past voxel-based morphometry (VBM) studies demonstrate reduced grey matter volume (GMV) in schizophrenia (SZ) patients' brains in various cortical and subcortical regions. Probably due to SZ symptoms' heterogeneity, these results are often inconsistent and difficult to integrate. We hypothesized that focusing on auditory verbal hallucinations (AVH) - one of the most common SZ symptoms - would allow reducing heterogeneity and discovering further compelling evidence of SZ neural correlates. We carried out two voxel-based meta-analyses of past studies that investigated the structural correlates of AVH in SZ. The review of whole-brain VBM studies published until June 2022 in PubMed and PsychInfo databases yielded (a) 13 studies on correlations between GMV and AVH severity in SZ patients (n = 472; 86 foci), and (b) 11 studies involving comparisons between hallucinating SZ patients (n = 504) and healthy controls (n = 524; 74 foci). Data were analyzed using the Activation Likelihood Estimation method. AVH severity was associated with decreased GMV in patients' left superior temporal gyrus (STG) and left posterior insula. Compared with healthy controls, hallucinating SZ pa-tients showed reduced GMV on the left anterior insula and left inferior frontal gyrus (IFG). Our findings revealed important structural dysfunctions in a left lateralized cluster of brain regions, including the insula and temporo-frontal regions, that significantly contribute to the severity and persistence of AVH. Structural atrophy found in circuits involved in generating and perceiving speech, as well as in auditory signal processing, might reasonably be considered a biological marker of AVH in SZ

Comparison of Slides and Video Clips as Different Methods for Inducing Emotions: An Electroencephalographic Alpha Modulation Study

Films, compared with emotional static pictures, represent true-to-life dynamic stimuli that are both ecological and effective in inducing an emotional response given the involvement of multimodal stimulation (i.e., visual and auditory systems). We hypothesized that a direct comparison between the two methods would have shown greater efficacy of movies, compared to standardized slides, in eliciting emotions at both subjective and neurophysiological levels. To this end, we compared these two methods of emotional stimulation in a group of 40 young adults (20 females). Electroencephalographic (EEG) Alpha rhythm (8–12 Hz) was recorded from 64 scalp sites while participants watched (in counterbalanced order across participants) two separate blocks of 45 slides and 45 clips. Each block included three groups of 15 validated stimuli classified as Erotic, Neutral and Fear content. Greater self-perceived arousal was found after the presentation of Fear and Erotic video clips compared with the same slide categories. sLORETA analysis showed a different lateralization pattern: slides induced decreased Alpha power (greater activation) in the left secondary visual area (Brodmann Area, BA, 18) to Erotic and Fear compared with the Neutral stimuli. Instead, video clips elicited reduced Alpha in the homologous right secondary visual area (BA 18) again to both Erotic and Fear contents compared with Neutral ones. Comparison of emotional stimuli showed smaller Alpha power to Erotic than to Fear stimuli in the left precuneus/posterior cingulate cortex (BA 7/31) for the slide condition, and in the left superior parietal lobule (BA 7) for the clip condition. This result matched the parallel analysis of the overlapped Mu rhythm (corresponding to the upper Alpha band) and can be interpreted as Mu/Alpha EEG suppression elicited by greater motor action tendency to Erotic (approach motivation) compared to Fear (withdrawal motivation) stimuli. Correlation analysis found lower Alpha in the left middle temporal gyrus (BA 21) associated with greater pleasantness to Erotic slides (r38 = –0.62, p = 0.009), whereas lower Alpha in the right supramarginal/angular gyrus (BA 40/39) was associated with greater pleasantness to Neutral clips (r38 = –0.69, p = 0.012). Results point to stronger emotion elicitation of movies vs. slides, but also to a specific involvement of the two hemispheres during emotional processing of slides vs. video clips, with a shift from the left to the right associative visual areas

Effects of voluntary orienting of attention on temporal estimation

Exogenous orienting of attention can affect the mental processing of time, suggesting the existence of a spatial representation for temporal durations, with shorter and longer durations represented on the left and on the right of a mental time line, respectively. In this study, we investigated the effects of voluntary shifts of attention on the perception of temporal durations. Participants were asked to follow with their gaze a dot moving on the screen (smooth pursuit conditions), or to fix a central dot (control condition), while listening to an acoustic stimulus (pink noise) varying in duration (from 600ms to 1400ms). Upon stimuli offset, they had to reproduce the temporal duration of the acoustic stimulus by pressing a button on the keyboard. Data from two experiments were collected online. In Experiment 1 the dot moved horizontally, either leftward or rightward from the screen centre. In Experiment 2 the dot moved vertically, either upward or downward from the screen centre. Experiment 3 was a laboratory-based replication of Experiment 1. The results showed, across the three experiments, a tendency to overestimate stimulus duration, which decreased with increasing duration. When the dot moved horizontally (Experiments 1 and 3), smooth pursuit induced smaller overestimation as compared to the control condition. We observed an effect of pursuit direction only in Experiment 3, where rightward pursuit induced larger overestimation as compared to leftward pursuit. This effect, however, was not consistent across all the analyses. Taken together, our results indicate that the spatialization of time is not systematic. We suggest that different effects of voluntary and involuntary attention on time processing, as well as task characteristics, might contribute to explaining these contrasting findings

Language Network Connectivity of Euthymic Bipolar Patients Is Altered at Rest and during a Verbal Fluency Task

Abnormalities of the Language Network (LN) have been found in different psychiatric conditions (e.g., schizophrenia and bipolar disorder), supporting the hypothesis that language plays a central role in a high-level integration/connectivity of second-level cognitive processes and the underlying cortical regions. This view implies a continuum of shared neural alterations along the psychotic disorder spectrum. In particular, bipolar disorder (BD) patients were recently documented to have an altered LN asymmetry during resting state. The extent to which the LN architecture is altered and stable also during a language task has yet to be investigated. To address this question, we analyzed fMRI data recorded during an open-eyes resting state session and a silent verbal fluency task in 16 euthymic BD patients and 16 matched healthy controls (HC). Functional connectivity in the LN of both groups was computed using spatial independent component analysis, and group comparisons were carried out to assess the network organization during both rest and active linguistic task conditions. The LN of BD patients involved left and right brain areas during both resting state and linguistic task. Compared to the left-lateralized network found in HC, the BD group was characterized by two anterior clusters (in left frontal and right temporo-insular regions) and the disengagement of the posterior language areas, especially during the verbal fluency task. Our findings support the hypothesis that reduced language lateralization may represent a biological marker across different psychotic disorders and that the altered language network connectivity found at rest in bipolar patients is stable and pervasive as it is also impaired during a verbal fluency task