Francesca Federico

Environmental enrichment promotes improved spatial abilities and enhanced dendritic growth in the rat.

An enriched environment consists of a combination of enhanced social relations, physical exercise and interactions with non-social stimuli that leads to behavioral and neuronal modifications. In the present study, we analyzed the behavioral effects of environmental complexity on different facets of spatial function, and we assessed dendritic arborisation and spine density in a cortical area mainly involved in the spatial learning, as the parietal cortex. Wistar rat pups (21 days old) were housed in enriched conditions (10 animals in a large cage with toys and a running wheel), or standard condition (two animals in a standard cage, without objects). At the age of 3 months, both groups were tested in the radial maze task and Morris water maze (MWM). Morphological analyses on layer-III pyramidal neurons of parietal cortex were performed in selected animals belonging to both experimental groups. In the radial maze task, enriched animals exhibited high performance levels, by exploiting procedural competencies and working memory abilities. Furthermore, when the requirements of the context changed, they promptly reorganized their strategies by shifting from prevalently using spatial procedures to applying mnesic competencies. In the Morris water maze, enriched animals more quickly acquired tuned navigational strategies. Environmental enrichment provoked increased dendritic arborisation as well as increased density of dendritic spines in layer-III parietal pyramidal neurons.

Environmental enrichment provides a cognitive reserve to be spent in the case of brain lesion

To experimentally verify the reserve hypothesis, the influence of rearing conditions on the cognitive performances and on dendritic spines following basal forebrain lesions was analyzed. Adult rats reared in enriched or standard conditions were depleted of the cholinergic projection to the neocortex by 192 IgG-saporin injection into Ch4 region of basal forebrain. Their performance in spatial tasks was compared with that of intact animals reared in analogous conditions. Furthermore, number and density of dendritic spines of the layer-III parietal pyramidal neurons were analyzed. Cholinergic depletion of forebrain cortex resulted in impaired performances in most behavioral tasks in animals reared in standard conditions. Conversely, the enriched lesioned animals did not exhibit most deficits evoked by cholinergic lesion, even if some deficits, such as perseverative behaviors, were still present. The pyramidal neurons exhibited an increased spine number and density in the lesioned animals reared in standard conditions. In the enriched lesioned animals, the enhancement of spine number and density elicited by the rearing condition was fully maintained but not further increased in the presence of the lesion. Thus, rearing in an enriched environment results in the development of brain and cognitive reserves that reduce the cognitive impairment following forebrain lesions.

Cognitive performances of cholinergically depleted rats following chronic donepezil administration

Since acute and chronic administration of the acetylcholinesterase inhibitors, namely donepezil, improves cognitive functions in patients afflicted by mild to moderate dementia and reverses memory deficits in experimental models of learning and memory, it seemed interesting to assess the effects of chronic donepezil treatment on cognitive functions in adult rats with forebrain cholinergic depletion. Lesions were performed by means of intracerebroventricular injections of the immunotoxin 192 IgG-saporin. The cognitive functions of lesioned animals treated or not treated with donepezil were compared with those of intact animals. Cholinergic depletion affected working memory functions, weakened procedural competencies, affected the acquisition of localizing knowledge, and evoked remarkable compulsive and perseverative behaviors. In lesioned animals, chronic donepezil treatment ameliorated localizatory capabilities, performances linked to cognitive flexibility and procedural abilities. Furthermore, it attenuated compulsive deficits. The present data indicate positive effects of chronic donepezil treatment on specific cognitive performances, suggesting that an aimed use of acetylcholinesterase inhibitors, targeting some symptoms more than others, may be beneficial in the case of cholinergic hypofunction. The animal model used in the present research may provide an efficient method for analyzing cognition-enhancing drugs before clinical trials.

NMDA receptor activity in learning spatial procedural strategies: II. The influence of cerebellar lesions

Experimental data support the involvement of cerebellar circuits in the acquisition of spatial procedural competences. Since the ability to acquire new procedural competences is lost when cerebellar regions are lesioned or when NMDA receptor activity is blocked, we analyzed whether the learning of explorative strategies is affected by blocking NMDA receptor activity in the presence of cerebellar lesions. To this aim, the NMDA receptor antagonist (CGS 19755, 7 mg/kg) was administered i.p. to un-lesioned rats, or rats subjected to total ablation of the cerebellum or to hemi-cerebellectomy. CGS 19755 and cerebellectomy both produced water maze behavior characterized by circling. Administration of CGS 19755 did not modify the Morris Water Maze (MWM) peripheral circling behavior of cerebellectomized animals. Circling was the dominant strategy of hemicerebellectomized animals in the absence of drugs. However, increasingly compulsive circling was observed under the action of CGS 19755. Circling was not observed if the drug-treated animals (un-lesioned or lesioned) had been previously trained. In conclusion, the NMDA antagonist caused severe impairment in the acquisition of spatial procedures, thus mimicking the consequences of cerebellar ablation on spatial procedural learning. Based on the present findings, we hypothesize that cerebellar NMDA receptor activity is involved in the acquisition of procedural spatial competence.

Relationship between brain abnormalities and cognitive profile in williams syndrome

Previous studies have shown inconsistent results when reporting brain abnormalities in Williams syndrome (WS). This makes an interpretation of clinical and behavioural data uncertain in terms of anatomical localization of brain tissue changes. In this study we employed voxel based morphometry to directly investigate the regional distribution of grey matter (GM) density as a function of individual neuropsychological profiles in individuals with WS. GM maps were regressed against the neuropsychological measures on which WS individuals performed worse than controls. Results showed an association between the regional GM density in the cerebellum, bilaterally, the right Supplementary Motor Area, the right fusiform gyrus, and measures of morpho-syntactic ability. An association was also found between measures of visuo-spatial and visuo-motor abilities and regional GM density in the left cerebellum, left parietal lobule, right superior and left orbital frontal gyri. The study shows the potential to clarify the anatomical substrate underlying specific cognitive deficits in WS.

Attention network test — The impact of social information on executive control, alerting and orienting

According to the attention network approach, attention is best understood in terms of three functionally and neuroanatomically distinct networks - alerting, orienting, and executive attention. An important question is whether social information influences the efficiency of these networks. Using the same structure as the Attentional Network Test (ANT), we developed a variant of this test to examine attentional effects in response to stimuli with and without social-cognitive content. Fish, drawings or photographs of faces looking to the left or right were used as target stimuli. Results collected from twenty-four university students showed that photographs of faces positively affected attentional orienting and executive control, whereas reduced the efficiency of alerting, as compared to both face drawings and fish. These results support the status of human faces as a special class of visual stimuli for the human attentional systems.

Learning by Observation: Insights from Williams Syndrome

Observing another person performing a complex action accelerates the observer’s acquisition of the same action and limits the time-consuming process of learning by trial and error. Observational learning makes an interesting and potentially important topic in the developmental domain, especially when disorders are considered. The implications of studies aimed at clarifying whether and how this form of learning is spared by pathology are manifold. We focused on a specific population with learning and intellectual disabilities, the individuals with Williams syndrome. The performance of twenty-eight individuals with Williams syndrome was compared with that of mental age- and gender-matched thirty-two typically developing children on tasks of learning of a visuo-motor sequence by observation or by trial and error. Regardless of the learning modality, acquiring the correct sequence involved three main phases: a detection phase, in which participants discovered the correct sequence and learned how to perform the task; an exercise phase, in which they reproduced the sequence until performance was error-free; an automatization phase, in which by repeating the error-free sequence they became accurate and speedy. Participants with Williams syndrome beneficiated of observational training (in which they observed an actor detecting the visuo-motor sequence) in the detection phase, while they performed worse than typically developing children in the exercise and automatization phases. Thus, by exploiting competencies learned by observation, individuals with Williams syndrome detected the visuo-motor sequence, putting into action the appropriate procedural strategies. Conversely, their impaired performances in the exercise phases appeared linked to impaired spatial working memory, while their deficits in automatization phases to deficits in processes increasing efficiency and speed of the response. Overall, observational experience was advantageous for acquiring competencies, since it primed subjects’ interest in the actions to be performed and functioned as a catalyst for executed action.

Peer and Teacher-Selected Peer Buddies for Adolescents With Autism Spectrum Disorders: The Role of Social, Emotional, and Mentalizing Abilities

ABSTRACT This study examined mentalizing abilities, social behavior, and social impact of adolescents who expressed the willingness to become peer buddies for adolescents with Autism Spectrum Disorders, and adolescents selected by their teachers and peers. Twenty-seven teachers and 395 adolescents from public high schools completed mentalizing abilities, social status, behavioral, and peer buddy nomination measures. Findings suggest that social status and preference play a significant role in the selection of peer buddies by both teachers and classmates. Furthermore, more advanced Theory of Mind (ToM) abilities and the engagement in prosocial behaviors differentiated peers selected as buddies from other classmates. When compared with nonparticipating students, adolescents who expressed willingness to participate were more often girls, and were more prosocial. Agreement between teacher and peer nominations of best peer was moderate.