Longitudinal evolution of cognitive functions in patients with multiple system atrophy: a prospective study

Introduction and Background: Multiple system atrophy (MSA) is a sporadic, adult-onset, progressive neurodegenerative disease characterized clinically by parkinsonism, cerebellar ataxia, and autonomic failure. We investigated cognitive functions longitudinally in a group of probable MSA patients, matching data with sleep parameters. Patients and Methods: 10 patients (7m/3f) underwent a detailed interview, a general and neurological examination, laboratory exams, MRI scans, a cardiovascular reflexes study, a battery of neuropsychological tests, and video-polysomnographic recording (VPSG). Patients were revaluated (T1) a mean of 16±5 (range: 12-28) months after the initial evaluation (T0). At T1, the neuropsychological assessment and VPSG were repeated. Results: The mean patient age was 57.8±6.4 years (range: 47-64) with a mean age at disease onset of 53.2±7.1 years (range: 43-61) and symptoms duration at T0 of 60±48 months (range: 12-144). At T0, 7 patients showed no cognitive deficits while 3 patients showed isolated cognitive deficits. At T1, 1 patient worsened developing multiple cognitive deficits from a normal condition. At T0 and T1, sleep efficiency was reduced, REM latency increased, NREM sleep stages 1-2 slightly increased. Comparisons between T1 and T0 showed a significant worsening in two tests of attention and no significant differences of VPSG parameters. No correlation was found between neuropsychological results and VPSG findings or RBD duration. Discussion and Conclusions: The majority of our patients do not show any cognitive deficits at T0 and T1, while isolated cognitive deficits are present in the remaining patients. Attention is the cognitive function which significantly worsened. Our data confirm the previous findings concerning the prevalence, type and the evolution of cognitive deficits in MSA. Regarding the developing of a condition of dementia, our data did not show a clear-cut diagnosis of dementia. We confirm a mild alteration of sleep structure. RBD duration does not correlate with neuropsychological findings.

Nuovo modello animale per lo studio della working memory: validazione farmacologica e applicazioni

The present study was performed to validate a spatial working memory task using pharmacological manipulations. The water escape T-maze, which combines the advantages of the Morris water maze and the T-maze while minimizes the disadvantages, was used. Scopolamine, a drug that affects cognitive function in spatial working memory tasks, significantly decreased the rat performance in the present delayed alternation task. Since glutamate neurotransmission plays an important role in the maintaining of working memory, we evaluated the effect of ionotropic and metabotropic glutamatergic receptors antagonists, administered alone or in combination, on rat behaviour. As the acquisition and performance of memory tasks has been linked to the expression of the immediately early gene cFos, a marker of neuronal activation, we also investigated the neurochemical correlates of the water escape T-maze after pharmacological treatment with glutamatergic antagonists, in various brain areas. Moreover, we focused our attention on the involvement of perirhinal cortex glutamatergic neurotransmission in the acquisition and/or consolidation of this particular task. The perirhinal cortex has strong and reciprocal connections with both specific cortical sensory areas and some memory-related structures, including the hippocampal formation and amygdala. For its peculiar position, perirhinal cortex has been recently regarded as a key region in working memory processes, in particular in providing temporary maintenance of information. The effect of perirhinal cortex lesions with ibotenic acid on the acquisition and consolidation of the water escape T-maze task was evaluated. In conclusion, our data suggest that the water escape T-maze could be considered a valid, simple and quite fast method to assess spatial working memory, sensible to pharmacological manipulations. Following execution of the task, we observed cFos expression in several brain regions. Furthermore, in accordance to literature, our results suggest that glutamatergic neurotransmission plays an important role in the acquisition and consolidation of working memory processes.

Integration of cognitive and affective processes in perception and decision-making

The relationship between emotion and cognition is a topic that raises great interest in research. Recently, a view of these two processes as interactive and mutually influencing each other has become predominant. This dissertation investigates the reciprocal influences of emotion and cognition, both at behavioral and neural level, in two specific fields, such as attention and decision-making. Experimental evidence on how emotional responses may affect perceptual and attentional processes has been reported. In addition, the impact of three factors, such as personality traits, motivational needs and social context, in modulating the influence that emotion exerts on perception and attention has been investigated. Moreover, the influence of cognition on emotional responses in decision-making has been demonstrated. The current experimental evidence showed that cognitive brain regions such as the dorsolateral prefrontal cortex are causally implicated in regulation of emotional responses and that this has an effect at both pre and post decisional stages. There are two main conclusions of this dissertation: firstly, emotion exerts a strong influence on perceptual and attentional processes but, at the same time, this influence may also be modulated by other factors internal and external to the individuals. Secondly, cognitive processes may modulate emotional prepotent responses, by serving a regulative function critical to driving and shaping human behavior in line with current goals.

Residual function, spontaneous reorganisation and treatment plasticity in homonymous visual field defects

This thesis will focus on the residual function and visual and attentional deficits in human patients, which accompany damage to the visual cortex or its thalamic afferents, and plastic changes, which follow it. In particular, I will focus on homonymous visual field defects, which comprise a broad set of central disorders of vision. I will present experimental evidence that when the primary visual pathway is completely damaged, the only signal that can be implicitly processed via subcortical visual networks is fear. I will also present data showing that in a patient with relative deafferentation of visual cortex, changes in the spatial tuning and response gain of the contralesional and ipsilesional cortex are observed, which are accompanied by changes in functional connectivity with regions belonging to the dorsal attentional network and the default mode network. I will also discuss how cortical plasticity might be harnessed to improve recovery through novel treatments. Moreover, I will show how treatment interventions aimed at recruiting spared subcortical pathway supporting multisensory orienting can drive network level change.