Bizarre behaviors (BB) are elicited in animals during stressful conditions and behavioral markers of disease/sickness relevant to animal welfare. These behaviors are disregarded in most experimental screenings due to their low incidence and short duration, despite their translational value mimicking disruptive behaviors associated with neurological/psychiatric diseases. However, we previously reported experimental conditions with conspicuous BB incidence: 1) the 3xTg-AD mice for Alzheimer's disease vs. wild-types; 2) the open-field test (OF) vs. other tests; 3) + 6 months of age and female sex; 4) at older ages (+13 months) male 3xTg-AD mice also exhibit more circling behavior (BB-CB) than control mice; 5) early neonatal handling reduces BB; whereas 6) they are enhanced by d-galactose-induced accelerated aging. In the present work, we studied the BB patterns elicited in the OF using a longitudinal design with sixty-six 13-month-old male/female mice with normal/AD-pathological aging under social/isolated housing conditions, aimed to explore the effects of intrinsic (genotype, sex) and extrinsic (environment) factors (n=7-8/group). BB were recorded in 39% of animals. Sex, re-test at an older age, and genotype factors differentiated two BB patterns: higher circling behavior (BB-CB, n=12) in wild-type and males, whereas higher backward movements (BB-BM, n=14) in 3xTg-AD, females, and older age. Isolation increased the incidence of freezing, mostly in 3xTg-AD mice, and exerted a modulatory role in BB, but interaction effects with other factors led to residual significance. The results point to BB-BM as the most pervasive BB pattern in this animal model, which is also sensitive to the progress of aging/disease.

The severity of sensory involution during aging is critical for perceiving and recognizing the world. In addition, sensory deficits significantly increase the risk of older adults’ biological, mental, and social decline. Conversely, loss of smell is an early biomarker of neurodegeneration in Alzheimer's (AD) and Parkinson's diseases. The worsening of these neurodegenerative diseases also involves physical deterioration, social deficits, and isolation. In the present translational work, a new food finding test (FFT) olfactory paradigm without food deprivation was used to investigate olfaction in old animals. The effects of social isolation in 16-months-old female 3xTg-AD mice, a genetic model of AD, and their age-matched wild-type counterparts, the gold-standard C57BL/6 mice were also studied. Animals were placed in a test cage and were observed until reaching the criteria for three goal-directed behaviors,‘Sniffing’, ‘Finding’ and ‘Eating’, towards the hidden food. Video recordings were analyzed blind to the genotype and social condition to determine the behaviors' ethogram and functional correlations. The results showed that the FFT paradigm without food deprivation elicited longer ethograms than previously reported with the standard overnight food deprivation protocol. However, it identified the genotype-dependent olfactory signatures in normal and AD-pathological aging. Social isolation slightly increased the latencies, but the olfactory signatures were preserved. However, a functional derangement was detected since the internal correlation among the three goal-directed behaviors was lost under isolation. In conclusion, the new paradigm without overnight deprivation was sensitive to genotype and isolation changes in the ethogram and function and can be used to study old animals.

Perceptual oscillations between different interpretations of unchanging, ambiguous stimuli have been studied for decades, being this special phenomenon considered a key towards the understanding of perceptual awareness and, ultimately, consciousness. The finding that brain dynamics (as registered, for example, through magneto- and electro-encephalography; M/EEG) of the spontaneous alternations between the percepts reflect the intrinsic dynamic properties of the (unconscious) perceptual processing has brought to many theoretical scenarios which consider perception as an inference process, and all other subserving cognitive processes working in a coordinated and coherent way. Amongst cognitive processes, cognitive flexibility is the one sharing most characteristics with the perceptual alternations, typical of bistable phenomena, being the ability to change a rule or accordingly inhibit certain information different between individuals; this "switching" ability has been shown to be correlated with the general “functioning” of a person (in turn, being this reflected by the individual neural system organization and dynamics). A preliminar, behavioral study (N=26) has been performed to provide evidence that all these aspects are, indeed, correlated. Performances in computerized classic experimental paradigms (Stroop, Simon Task, Task-switching Tests, Wisconsin Card Sorting Test) have been correlated to perceptual switches and percept durations of spontaneous and voluntary alternations of the Necker Cube and with scores in Cognitive Flexibility, Barrat's Impulsiveness, DASS-21 and the short version of Big Five questionnaires. Future studies with EEG and brain connectivity measures are going to provide a more direct insight on the brain dynamics of these perceptual and cognitive processing, shedding light on the mechanisms at the basis of this supposed, concerted coherent synchronization.

Objective: The aim of this study was to describe the presentation and outcomes of patients with granulomatosis with polyangiitis (GPA) presenting with neurologic involvement according to ACR criteria.

Methods: Consecutive newly diagnosed GPA patients who had follow-up for at least six months between 2013 and 2018 at Amir-A'lam hospital, Tehran University of Medical Sciences, were retrospectively analyzed.

Results: Patients were divided into two groups, those with nervous system involvement at either disease diagnosis or follow-up (89 patients) and those without neurological symptoms until the last follow-up (131 patients). From all patients reviewed in this study, 68 (30.9%) patients died during the follow-up period. Among dead patients, 18 (20.2%) were in the non-neurologic, and 50 (38.2%) were in the neurologic group. The median (IQR) of Birmingham Vasculitis Activity Score (BVAS) in 220 patients was 11.0 (18.0-8.0) in total, 10.0 (14.5-7.50), and 12.0 (21.0-8.0) in non-neurologic and neurologic groups, respectively. The score of BVAS in the neurologic group was significantly higher than in the non-neurologic group (p=0.039). Of 131 patients, sensory neuropathy was found in 99 patients (75.5%). 95 patients (72.5%) complained of hearing loss, diagnosed as sensory-neural hearing loss and 27 patients (20.6%) complained of headache. 13 patients (9.9%) had cerebrovascular events, 5 (3.8%) had an episode of seizure or loss of consciousness (LOC), and 3 (2.3%) had mononeuritis multiplex. Two patients (1.5%) were diagnosed with meningitis and 2 (1.7%) with encephalitis.

Conclusion: According to this study, neurological symptoms are an undeniable part of GPA patients, which are associated with disease severity, prognosis, and response to treatment.