Francesca Foti

On whether the environmental enrichment may provide cognitive and brain reserves

The construct of brain and cognitive reserves holds that cognitive enrichment fosters the development of neuroplasticity properties, which permit normal cognitive functioning even in the presence of brain pathology. Interpreting the experience-dependent increase of neuronal connectivity and efficiency in the light of the reserve theory provides an interesting approach for explaining the maintenance of cognitive function observed in some subjects affected by neurodegenerative disorders. In fact, mental and physical engagement with complex environments strengthens synaptic connectivity and provides the means by which preexisting neuronal networks are efficiently utilized and alternative networks are recruited to meet environmental demands and to cope with brain damage. There is considerable interest in determining the biological factors that allow the development of these reserves. To investigate these factors, it is possible to model situations of environmental enrichment in animals that parallel human cognitive enrichment. Experimental findings indicate that early onset and extended housing in an environment with enhanced sensorimotor, cognitive, and social stimulations results in significant changes in brain biochemistry, synaptic connectivity, and neuronal function in enriched animals. These changes provide the groundwork for the improvement of behavioral performance and maintenance of performance following brain damage. As this is the fundamental assumption of the reserve hypothesis, it is possible that as human educational attainment and occupational status, environmental enrichment develops reserves to be spent in the case of a subsequent lesion.

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.

n-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice

As major components of neuronal membranes, omega-3 polyunsaturated acids (n-3 PUFA) exhibit a wide range of regulatory functions, modulating from synaptic plasticity to neuroinflammation, from oxidative stress to neuroprotection. Recent human and animal studies indicated the n-3 PUFA neuroprotective properties in aging, with a clear negative correlation between n-3 PUFA levels and hippocampal deficits. The present multidimensional study was aimed at associating cognition, hippocampal neurogenesis, volume, neurodegeneration and metabolic correlates to verify n-3 PUFA neuroprotective effects in aging. To this aim 19 month-old mice were given n-3 PUFA mixture, or olive oil or no dietary supplement for 8 weeks during which hippocampal-dependent mnesic functions were tested. At the end of behavioral testing morphological and metabolic correlates were analyzed. n-3 PUFA supplemented aged mice exhibited better object recognition memory, spatial and localizatory memory, and aversive response retention, without modifications in anxiety levels in comparison to controls. These improved hippocampal cognitive functions occurred in the context of an enhanced cellular plasticity and a reduced neurodegeneration. In fact, n-3 PUFA supplementation increased hippocampal neurogenesis and dendritic arborization of newborn neurons, volume, neuronal density and microglial cell number, while it decreased apoptosis, astrocytosis and lipofuscin accumulation in the hippocampus. The increased levels of some metabolic correlates (blood Acetyl-L-Carnitine and brain n-3 PUFA concentrations) found in n-3 PUFA supplemented mice also pointed toward an effective neuroprotection. On the basis of the present results n-3 PUFA supplementation appears to be a useful tool in health promotion and cognitive decline prevention during aging.

Spatial competences in Williams syndrome: a radial arm maze study.

This study was aimed at evaluating spatial function in subjects with Williams syndrome by using the radial arm maze task and comparing their spatial abilities with those of mental age‐matched control subjects. Two different paradigms were administered: the free‐choice version for analyzing the aspects linked mainly to procedural and mnesic components, the forced‐choice version for disentangling components linked to spatial working memory from the procedural ones.

Environmental enrichment mitigates the effects of basal forebrain lesions on cognitive flexibility

The aim of the present study was to investigate whether basal forebrain lesions were able to impair a task requiring cognitive flexibility abilities and analyzing the effect of the rearing in an enriched environment on such form of flexibility in rats with or without basal forebrain cholinergic lesions. In adult rats reared in enriched or standard conditions of the cholinergic projection to the neocortex damage was inflicted by 192 IgG-saporin injection into Ch4 region of basal forebrain. Their performance was compared with those of intact animals reared in analogous conditions in a four-choice serial learning task which taps flexibility in adapting to changing response rules. The results underlined the crucial role of the basal forebrain in mediating cognitive flexibility behaviors and revealed that the increase in social interactions, cognitive stimulation and physical activity of the rearing in enriched environment attenuated impairments caused by the cholinergic lesion. These findings demonstrate that rearing in an enriched environment can improve the ability to cope with brain damage suffered in adulthood.

Implicit learning in individuals with autism spectrum disorders: a meta-analysis

BACKGROUND Individuals with autism spectrum disorders (ASDs) are characterized by social communication difficulties and behavioural rigidity. Difficulties in learning from others are one of the most devastating features of this group of conditions. Nevertheless, the nature of learning difficulties in ASDs is still unclear. Given the relevance of implicit learning for social and communicative functioning, a link has been hypothesized between ASDs and implicit learning deficit. However, studies that have employed formal testing of implicit learning in ASDs provided mixed results. METHOD We undertook a systematic search of studies that examined implicit learning in ASDs using serial reaction time (SRT), alternating serial reaction time (ASRT), pursuit rotor (PR), and contextual cueing (CC) tasks, and synthesized the data using meta-analysis. A total of 11 studies were identified, representing data from 407 individuals with ASDs and typically developing comparison participants. RESULTS The results indicate that individuals with ASDs do not differ in any task considered [SRT and ASRT task: standardized mean difference (SMD) -0.18, 95% confidence interval (CI) -0.71 to 0.36; PR task: SMD -0.34, 95% CI -1.04 to 0.36; CC task: SMD 0.27, 95% CI -0.07 to 0.60]. CONCLUSIONS Based on our synthesis of the existing literature, we conclude that individuals with ASDs can learn implicitly, supporting the hypothesis that implicit learning deficits do not represent a core feature in ASDs.

Enriched environment improves motor function and increases neurotrophins in hemicerebellar lesioned rats.

Background. Environmental enrichment (EE) defined as “a combination of complex inanimate and social stimulation” influences brain function and anatomy by enhancing sensory, cognitive, motor, and social stimulation. The beneficial effects of EE in the presence of brain damage have been partially attributed to upregulation of neurotrophins, proteins involved in neuronal survival and in activity-dependent plasticity. Objective. The authors tested the hypothesis that EE may have advantageous effects on recovery of motor function after cerebellar damage, associated with changes in local neurotrophin production. Methods. They performed a hemicerebellectomy in rats previously exposed to EE or reared in standard conditions. The time course of compensation of motor symptoms was analyzed in both lesioned groups. Then, the local production of the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the spared hemicerebellum and other extracerebellar regions was evaluated. Results. Long-term exposure to EE accelerated the motor recovery in hemicerebellectomized rats and elicited an increase in NGF levels in the spared hemicerebellum, as compared with nonenriched lesioned and control rats. BDNF levels were higher in hemicerebellectomized rats but not influenced by EE. In the frontal cortex, both NGF and BDNF levels were upregulated in hemicerebellectomized enriched rats as compared with hemicerebellectomized nonenriched and control rats. Conclusions. This study suggests that the beneficial effects of EE on motor symptoms after cerebellar damage may be, at least partly, because of modulation of neurotrophic proteins involved in the regeneration processes.

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.

Exposure to an Enriched Environment Accelerates Recovery from Cerebellar Lesion

The exposure to enriched environments allows the maintenance of normal cognitive functioning even in the presence of brain pathology. Up until now, clinical and experimental studies have investigated environmental effects mainly on the symptoms linked to the presence of neuro-degenerative diseases, and no study has yet analyzed whether prolonged exposure to complex environments allows modifying the clinical expression and compensation of deficits of cerebellar origin. In animals previously exposed to complex stimulations, the effects of cerebellar lesions have been analyzed to verify whether a prolonged and intense exposure to complex stimulations affected the compensation of motor and cognitive functions following a cerebellar lesion. Hemicerebellectomized or intact animals housed in enriched or standard conditions were administered spatial tests. Postural asymmetries and motor behavior were also assessed. Exposure to the enriched environment almost completely compensated the effects of the hemicerebellectomy. In fact, the motor and cognitive performances of the enriched hemicerebellectomized animals were similar to those of the intact animals. The plastic changes induced by enhanced mental and physical activity seem to provide the development of compensatory responses against the disrupting motor and cognitive consequences of the cerebellar damage.

Before or after does it matter? Different protocols of environmental enrichment differently influence motor, synaptic and structural deficits of cerebellar origin

Cerebellar compensation is a reliable model of lesion-induced plasticity occurring through profound synaptic and neurochemical modifications in cortical and sub-cortical regions. As the recovery from cerebellar deficits progresses, the firstly enhanced glutamate striatal transmission is then normalized. The time course of cerebellar compensation and the concomitant striatal modifications might be influenced by protocols of environmental enrichment (EE) differently timed in respect to cerebellar lesion. In the present study, we analyzed the effects of different EE protocols on postural and locomotor behaviors (by means of a neurological rating scale), and on striatal synaptic activity (by means of recordings of spontaneous glutamate-mediated excitatory postsynaptic currents (sEPSCs)) and on morphological correlates (by means of density and dendritic length of Fast Spiking (FS) interneurons) following hemicerebellectomy (HCb) in rats. Cerebellar motor deficits were reduced faster in the enriched animals in comparison to standard housed HCbed rats. The beneficial influence of EE was higher in the animals enriched before the HCb than in rats enriched only after the lesion. In parallel, the HCb-induced increase in striatal sEPSCs was not observed in rats enriched before HCb and attenuated in rats enriched after HCb. Furthermore, the EE prevented the shrinkage of dendritic arborization of FS striatal interneurons. Also this effect was more marked in animals enriched before than after the HCb. The exposure to EE exerted either neuro-protective or therapeutic actions on the cerebellar deficits. The experience-dependent changes of the synaptic and neuronal connectivity observed in the striatal neurons may represent one of the mechanisms through which the enrichment facilitates functional compensation following the cerebellar damage.