Roberta Rasetti

Role of glutamate δ-2 receptors in activity-dependent competition between heterologous afferent fibers

A principle that regulates detailed architecture in the brain is that active terminals have a competitive advantage over less active terminals in establishing synaptic connections. This principle is known to apply to fibers within a single neuronal population competing for a common target domain. Here we uncover an additional rule that applies when two neuronal populations compete for two contiguous territories. The cerebellar Purkinje cell dendrites have two different synaptic domains with spines innervated by two separate excitatory inputs, parallel fibers (PFs) and climbing fibers (CFs). Glutamate δ-2 receptors are normally present only on the PF spines where they are important for their innervation. After block of activity by tetrodotoxin, numerous new spines form in the CF domain and become innervated mainly by PFs; all spines, including those still innervated by the CFs, bear δ-2 receptors. Thus, in the absence of activity, PFs gain a competitive advantage over CFs. The entire dendritic arbor becomes a uniform territory with the molecular cues associated with the PFs. To access their proper territory and maintain synaptic contacts, CFs must be active and locally repress the cues of the competitor afferents.

The effect of gender on planning: An fMRI study using the Tower of London task.

Since the introduction of brain mapping, evidences of functional gender differences have been corroborating previous behavioral and neuropsychological results showing a sex-specific brain organization. We investigated gender differences in brain activation during the performance of the Tower of London (TOL) task which is a standardized test to assess executive functions. Eighteen healthy subjects (9 females and 9 males) underwent fMRI scanning while solving a series of TOL problems with different levels of difficulty. Data were analyzed by modeling both genders and difficulty task load. Task-elicited brain activations comprised a bilateral fronto-parietal network, common to both genders; within this network, females activated more than males in dorsolateral prefrontal cortex (DLPFC) and right parietal cortex, whereas males showed higher activity in precuneus. A prominent parietal activity was found at low level of difficulty while, with heavier task demand, several frontal regions and subcortical structures were recruited. Our results suggest peculiar gender strategies, with males relying more on visuospatial abilities and females on executive processing.

Neuropsychological correlates of reality distortion in schizophrenic patients

The present study aims at exploring the relationship between content-related aspects of delusions and hallucinations in schizophrenia and the basic domains of cognition, controlling for the other clinical and demographic variables that could produce bias in the interpretation of the results. Seventy stable schizophrenic patients were evaluated through psychiatric assessment and a neuropsychological battery including tests on attention, memory, perceptual-motor speed and executive functions. We found that the severity of negative symptoms was strongly correlated with poor performance in almost all domains of cognitive functions, while only the attentional deficit was correlated with positive symptoms. The relationships between different cognitive domains and specific types of delusions and hallucinations showed that thought insertion, guilt, grandiose, religious and somatic delusions were associated with impairment in different cognitive functions (verbal and visual memory, attention and executive functions). Voices arguing and tactile hallucinations were correlated to delay-recall memory function. Our results suggest that no specific cognitive pattern is associated with typical-content delusions and hallucinations. On the basis of our findings, cognitive impairments associated with delusions and hallucinations, as measured by our battery, seem not to play a central role in the genesis and the maintenance of these symptoms, suggesting a more complex model of pathogenesis.

A comparison of paroxetine versus paroxetine plus amisulpride in the treatment of dysthymic disorder: efficacy and psychosocial outcomes

Dysthymic disorder is a chronic depressive condition with considerable psychosocial impairment. Even if DD patients respond to various antidepressant medications, there has been little systematic study on antidepressant-refractory DD. Only a few trials have evaluated the effects of treatment on psychosocial functioning of dysthymic patients. In this 3-month, open-label study, 60 outpatients with DSM-IV criteria for dysthymic disorder who failed to respond to 3-month treatment with paroxetine 20 mg/day were randomly assigned to treatment with paroxetine 40 mg/day or paroxetine 20 mg/day plus amisulpride 50 mg/day. The effects of the two treatments were assessed for both mood symptoms (21-item Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression, severity and improvement) and psychosocial outcomes (DSM-IV Global Assessment of Functioning, Social Adaptation Self-evaluation Scale). Analysis of variance on all rating scales showed that both treatments were effective over this observation period. Response and remission rates did not differ in the treatment groups. A significantly greater psychosocial improvement was observed in the group receiving combined treatment compared with patients receiving paroxetine alone. Both treatments appeared to be effective in our sample of dysthymic subjects. Combined treatment with paroxetine and amisulpride resulted in a better outcome in terms of social functioning.

Exploring the role of face processing in facial emotion recognition in schizophrenia

Objective: Impairment in emotion perception represents a fundamental feature of schizophrenia with important consequences in social functioning. A fundamental unresolved issue is the relationship between emotion perception and face perception. The aim of the present study was to examine whether facial identity recognition (Identity Discrimination) is a factor predicting facial emotion recognition in the context of the other factors, known as contributing to emotion perception, such as cognitive functions and symptoms. Methods: We enrolled 58 stable schizophrenic out-patients and 47 healthy subjects. Facial identity recognition and emotion perception were assessed with the Comprehensive Affect Testing System. Different multiple regression models with backward elimination were performed in order to discover the relation of each significant variable with emotion perception. Results: In a regression including the six significant variables (age, positive symptomatology, Identity Discrimination, attentive functions, verbal memory-learning, executive functions) versus emotion processing, only attentive functions (standardised β = 0.264, p = 0.038) and Identity Discrimination (standardised β = 0.279, p = 0.029) reached a significant level. Two partial regressions were performed including five variables, one excluding attentive functions and the other excluding Identity Discrimination. When we excluded attentive functions, the only significant variable was Identity Discrimination (standardised β = 0.278, p = 0.032). When we excluded Identity Discrimination, both verbal memory-learning (standardised β = 0.261, p = 0.042) and executive functions (standardised β = 0.253, p = 0.048) were significant. Conclusions: Our results emphasised the role of face perception and attentional abilities on affect perception in schizophrenia. We additionally found a role of verbal memory-learning and executive functions on emotion perception. The relationship between those above-mentioned variables and emotion processing could have implications for cognitive rehabilitation.

Spontaneous electrical activity and dendritic spine size in mature cerebellar Purkinje cells

Previous experiments have shown that in the mature cerebellum both blocking of spontaneous electrical activity and destruction of the climbing fibres by a lesion of the inferior olive have a similar profound effect on the spine distribution on the proximal dendrites of the Purkinje cells. Many new spines develop that are largely innervated by parallel fibers. Here we show that blocking electrical activity leads to a significant decrease in size of the spines on the branchlets. We have also compared the size of the spines of the proximal dendritic domain that appear during activity block and after an inferior olive lesion. In this region also, the spines in the absence of activity are significantly smaller. In the proximal dendritic domain, the new spines that develop in the absence of activity are innervated by parallel fibers and are not significantly different in size from those of the branchlets, although they are shorter. Thus, the spontaneous activity of the cerebellar cortex is necessary not only to maintain the physiological spine distribution profile in the Purkinje cell dendritic tree, but also acts as a signal that prevents spines from shrinking.