Efficacy of a perceptual and visual-motor skill intervention program for students with dyslexia

Purpose: To verify the efficacy of a perceptual and visual-motor skill intervention program for students with dyslexia. Methods: The participants were 20 students from third to fifth grade of a public elementary school in Marília, São Paulo, aged from 8 years to 11 years and 11 months, distributed into the following groups: Group I (GI; 10 students with developmental dyslexia) and Group II (GII; 10 students with good academic performance). A perceptual and visual-motor intervention program was applied, which comprised exercises for visual-motor coordination, visual discrimination, visual memory, visual-spatial relationship, shape constancy, sequential memory, visual figure-ground coordination, and visual closure. In pre- and post-testing situations, both groups were submitted to the Test of Visual-Perceptual Skills (TVPS-3), and the quality of handwriting was analyzed using the Dysgraphia Scale. Results: The analyzed statistical results showed that both groups of students had dysgraphia in pretesting situation. In visual perceptual skills, GI presented a lower performance compared to GII, as well as in the quality of writing. After undergoing the intervention program, GI increased the average of correct answers in TVPS-3 and improved the quality of handwriting. Conclusion: The developed intervention program proved appropriate for being applied to students with dyslexia, and showed positive effects because it provided improved visual perception skills and quality of writing for students with developmental dyslexia.

Tests of the Dynamic Field Theory and the Spatial Precision Hypothesis: Capturing a Qualitative Developmental Transition in Spatial Working Memory

This study tested a dynamic field theory (DFT) of spatial working memory and an associated spatial precision hypothesis (SPH). Between 3 and 6 years of age, there is a qualitative shift in how children use reference axes to remember locations: 3-year-olds’ spatial recall responses are biased toward reference axes after short memory delays, whereas 6-year-olds’ responses are biased away from reference axes. According to the DFT and the SPH, quantitative improvements over development in the precision of excitatory and inhibitory working memory processes lead to this qualitative shift. Simulations of the DFT in Experiment 1 predict that improvements in precision should cause the spatial range of targets attracted toward a reference axis to narrow gradually over development, with repulsion emerging and gradually increasing until responses to most targets show biases away from the axis. Results from Experiment 2 with 3- to 5-year-olds support these predictions. Simulations of the DFT in Experiment 3 quantitatively fit the empirical results and offer insights into the neural processes underlying this developmental change.

Assessing Needs for Computer Pest Management Software in Nebraska Agriculture

A mail survey was conducted to assess current computer hardware use and perceived needs of potential users for software related to crop pest management in Nebraska. Surveys were sent to University of Nebraska-Lincoln agricultural extension agents, agribusiness personnel (including independent crop consultants), and crop producers identified by extension agents as computer users. There were no differences between the groups in several aspects of computer hardware use (percentage computer use, percentage IBM-compatible computer, amount of RAM memory, percentage with hard drive, hard drive size, or monitor graphics capability). Responses were similar among the three groups in several areas that are important to crop pest management (pest identification, pest biology, treatment decision making, control options, and pesticide selection), and a majority of each group expressed the need for additional sources of such information about insects, diseases, and weeds. However, agents mentioned vertebrate pest management information as a need more often than the other two groups. Also, majorities of each group expressed an interest in using computer software, if available, to obtain information in these areas. Appropriate software to address these needs should find an audience among all three groups.

Temporal memory of emotional experience

The few studies that have investigated judgments of time have suggested that the memory of duration is distorted more for emotional events than for neutral events, while in contrast there is abundant evidence that other aspects of memories of emotional events are more accurate. To reconcile this apparent discrepancy, we used a procedure in which the participants learned a standard duration over several trials under three emotional conditions: a threatening, a nonthreatening, and a neutral control condition. They were then tested either immediately or 24 h after learning. In this test phase, they had to indicate whether presented comparison durations were or were not the same as the previously learned standard duration. We found that durations were recalled better in the emotional than in the neutral condition, and that this occurred to a greater extent in the threatening than in the nonthreatening condition. Arousing emotions thus enhanced temporal memory, just as they enhance memory for other aspects of emotional events.

Juvenile myoclonic epilepsy: The impact of clinical variables and psychiatric disorders on executive profile assessed with a comprehensive neuropsychological battery

Executive dysfunction is reported in juvenile myoclonic epilepsy (JME). However, batteries employed in previous studies included no more than three tests of executive function. In this study, we aimed to assess executive and attentional functions in JME using a comprehensive battery of eight tests (encompassing fifteen subtests). We also evaluated neuropsychological profiles using a clinical criterion of severity and correlated these findings with epilepsy clinical variables and the presence of psychiatric disorders. We prospectively evaluated 42 patients with JME and a matched control group with Digit Span tests (forward and backward), Stroop Color-Word Test, Trail Making Test, Wisconsin Card-Sorting Test, Matching Familiar Figures Test and Word Fluency Test. We estimated IQ with the Matrix Reasoning and Vocabulary subtests of the Wechsler Abbreviated Intelligence Scale. The patients with JME showed specific deficits in working memory, inhibitory control, concept formation, goal maintenance, mental flexibility, and verbal fluency. We observed attentional deficits in processes such as alertness and attention span and those requiring sustained and divided attention. We found that 83.33% of the patients had moderate or severe executive dysfunction. In addition, attentional and executive impairment was correlated with higher frequency of seizures and the presence of psychiatric disorders. Furthermore, executive dysfunction correlated with a longer duration of epilepsy. Our findings indicate the need for comprehensive neuropsychological batteries in patients with JME, in order to provide a more extensive evaluation of attentional and executive functions and to show that some relevant deficits have been overlooked. (C) 2012 Elsevier Inc. All rights reserved.

Exponential stability for a plate equation with p-Laplacian and memory terms

This paper is concerned with the energy decay for a class of plate equations with memory and lower order perturbation of p-Laplacian type, utt+?2u-?pu+?0tg(t-s)?u(s)ds-?ut+f(u)=0inOXR+, with simply supported boundary condition, where O is a bounded domain of RN, g?>?0 is a memory kernel that decays exponentially and f(u) is a nonlinear perturbation. This kind of problem without the memory term models elastoplastic flows.

Memory in children with temporal lobe epilepsy is at least partially explained by executive dysfunction

An association between memory and executive dysfunction (ED) has been demonstrated in patients with mixed neurological disorders. We aimed to investigate the impact of ED in memory tasks of children with temporal lobe epilepsy (TLE). We evaluated 36 children with TLE and 28 controls with tests for memory, learning, attention, mental flexibility, and mental tracking. Data analysis was composed of comparison between patients and controls in memory and executive function; correlation between memory and executive function tests; and comparison between patients with mild and severe ED in memory tests. Children with TLE had worse performance in focused attention, immediate and delayed recall, phonological memory, mental tracking, planning, and abstraction. Planning, abstraction, and mental tracking were correlated with visual and verbal memory. Children with severe ED had worse performance in verbal and visual memory and learning tests. This study showed that ED was related to memory performance in children with TLE. (C) 2012 Elsevier Inc. All rights reserved.

Space and Motion Perception and Discomfort in Air Travel

RAMOS RT, MATTOS DA, REBOUCAS ITS, RANVAUD RD. Space and motion perception and discomfort in air travel. Aviat Space Environ Med 2012; 83:1162-6. Introduction: The perception of comfort during air trips is determined by several factors. External factors like cabin design and environmental parameters (temperature, humidity, air pressure, noise, and vibration) interact with individual characteristics (anxiety traits, fear of flying, and personality) from arrival at the airport to landing at the destination. In this study, we investigated the influence of space and motion discomfort (SMD), fear of heights, and anxiety on comfort perception during all phases of air travel. Methods: We evaluated 51 frequent air travelers through a modified version of the Flight Anxiety Situations Questionnaire (FAS), in which new items were added and where the subjects were asked to report their level of discomfort or anxiety (not fear) for each phase of air travel (Chronbach's alpha = 0.974). Correlations were investigated among these scales: State-Trait Anxiety Inventory (STAB, Cohen's Acrophobia Questionnaire, and the Situational Characteristics Questionnaire (SitQ, designed to estimate SMD levels). Results: Scores of SitQ correlated with discomfort in situations involving space and movement perception (Pearson's rho = 0.311), while discomfort was associated with cognitive mechanisms related to scores in the anxiety scales (Pearson's rho = 0.375). Anxiety traits were important determinants of comfort perception before and after flight, while the influence of SMD was more significant during the time spent in the aircraft cabin. Discussion: SMD seems to be an important modulator of comfort perception in air travel. Its influence on physical well being and probably on cognitive performance, with possible effects on flight safety, deserves further investigation.

Speech perception and cortical auditory evoked potentials in cochlear implant users with auditory neuropathy spectrum disorders

Objective: To characterize the PI component of long latency auditory evoked potentials (LLAEPs) in cochlear implant users with auditory neuropathy spectrum disorder (ANSD) and determine firstly whether they correlate with speech perception performance and secondly whether they correlate with other variables related to cochlear implant use. Methods: This study was conducted at the Center for Audiological Research at the University of Sao Paulo. The sample included 14 pediatric (4-11 years of age) cochlear implant users with ANSD, of both sexes, with profound prelingual hearing loss. Patients with hypoplasia or agenesis of the auditory nerve were excluded from the study. LLAEPs produced in response to speech stimuli were recorded using a Smart EP USB Jr. system. The subjects' speech perception was evaluated using tests 5 and 6 of the Glendonald Auditory Screening Procedure (GASP). Results: The P-1 component was detected in 12/14 (85.7%) children with ANSD. Latency of the P-1 component correlated with duration of sensorial hearing deprivation (*p = 0.007, r = 0.7278), but not with duration of cochlear implant use. An analysis of groups assigned according to GASP performance (k-means clustering) revealed that aspects of prior central auditory system development reflected in the P-1 component are related to behavioral auditory skills. Conclusions: In children with ANSD using cochlear implants, the P-1 component can serve as a marker of central auditory cortical development and a predictor of the implanted child's speech perception performance. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

Management and routing algorithms for ad-hoc and sensor networks

Large scale wireless adhoc networks of computers, sensors, PDAs etc. (i.e. nodes) are revolutionizing connectivity and leading to a paradigm shift from centralized systems to highly distributed and dynamic environments. An example of adhoc networks are sensor networks, which are usually composed by small units able to sense and transmit to a sink elementary data which are successively processed by an external machine. Recent improvements in the memory and computational power of sensors, together with the reduction of energy consumptions, are rapidly changing the potential of such systems, moving the attention towards datacentric sensor networks. A plethora of routing and data management algorithms have been proposed for the network path discovery ranging from broadcasting/floodingbased approaches to those using global positioning systems (GPS). We studied WGrid, a novel decentralized infrastructure that organizes wireless devices in an adhoc manner, where each node has one or more virtual coordinates through which both message routing and data management occur without reliance on either flooding/broadcasting operations or GPS. The resulting adhoc network does not suffer from the deadend problem, which happens in geographicbased routing when a node is unable to locate a neighbor closer to the destination than itself. WGrid allow multidimensional data management capability since nodes' virtual coordinates can act as a distributed database without needing neither special implementation or reorganization. Any kind of data (both single and multidimensional) can be distributed, stored and managed. We will show how a location service can be easily implemented so that any search is reduced to a simple query, like for any other data type. WGrid has then been extended by adopting a replication methodology. We called the resulting algorithm WRGrid. Just like WGrid, WRGrid acts as a distributed database without needing neither special implementation nor reorganization and any kind of data can be distributed, stored and managed. We have evaluated the benefits of replication on data management, finding out, from experimental results, that it can halve the average number of hops in the network. The direct consequence of this fact are a significant improvement on energy consumption and a workload balancing among sensors (number of messages routed by each node). Finally, thanks to the replications, whose number can be arbitrarily chosen, the resulting sensor network can face sensors disconnections/connections, due to failures of sensors, without data loss. Another extension to {WGrid} is {W*Grid} which extends it by strongly improving network recovery performance from link and/or device failures that may happen due to crashes or battery exhaustion of devices or to temporary obstacles. W*Grid guarantees, by construction, at least two disjoint paths between each couple of nodes. This implies that the recovery in W*Grid occurs without broadcasting transmissions and guaranteeing robustness while drastically reducing the energy consumption. An extensive number of simulations shows the efficiency, robustness and traffic road of resulting networks under several scenarios of device density and of number of coordinates. Performance analysis have been compared to existent algorithms in order to validate the results.

Design and Performance Evaluation of Network-on-Chip Communication Protocols and Architectures

The scale down of transistor technology allows microelectronics manufacturers such as Intel and IBM to build always more sophisticated systems on a single microchip. The classical interconnection solutions based on shared buses or direct connections between the modules of the chip are becoming obsolete as they struggle to sustain the increasing tight bandwidth and latency constraints that these systems demand. The most promising solution for the future chip interconnects are the Networks on Chip (NoC). NoCs are network composed by routers and channels used to inter- connect the different components installed on the single microchip. Examples of advanced processors based on NoC interconnects are the IBM Cell processor, composed by eight CPUs that is installed on the Sony Playstation III and the Intel Teraflops pro ject composed by 80 independent (simple) microprocessors. On chip integration is becoming popular not only in the Chip Multi Processor (CMP) research area but also in the wider and more heterogeneous world of Systems on Chip (SoC). SoC comprehend all the electronic devices that surround us such as cell-phones, smart-phones, house embedded systems, automotive systems, set-top boxes etc... SoC manufacturers such as ST Microelectronics , Samsung, Philips and also Universities such as Bologna University, M.I.T., Berkeley and more are all proposing proprietary frameworks based on NoC interconnects. These frameworks help engineers in the switch of design methodology and speed up the development of new NoC-based systems on chip. In this Thesis we propose an introduction of CMP and SoC interconnection networks. Then focusing on SoC systems we propose: • a detailed analysis based on simulation of the Spidergon NoC, a ST Microelectronics solution for SoC interconnects. The Spidergon NoC differs from many classical solutions inherited from the parallel computing world. Here we propose a detailed analysis of this NoC topology and routing algorithms. Furthermore we propose aEqualized a new routing algorithm designed to optimize the use of the resources of the network while also increasing its performance; • a methodology flow based on modified publicly available tools that combined can be used to design, model and analyze any kind of System on Chip; • a detailed analysis of a ST Microelectronics-proprietary transport-level protocol that the author of this Thesis helped developing; • a simulation-based comprehensive comparison of different network interface designs proposed by the author and the researchers at AST lab, in order to integrate shared-memory and message-passing based components on a single System on Chip; • a powerful and flexible solution to address the time closure exception issue in the design of synchronous Networks on Chip. Our solution is based on relay stations repeaters and allows to reduce the power and area demands of NoC interconnects while also reducing its buffer needs; • a solution to simplify the design of the NoC by also increasing their performance and reducing their power and area consumption. We propose to replace complex and slow virtual channel-based routers with multiple and flexible small Multi Plane ones. This solution allows us to reduce the area and power dissipation of any NoC while also increasing its performance especially when the resources are reduced. This Thesis has been written in collaboration with the Advanced System Technology laboratory in Grenoble France, and the Computer Science Department at Columbia University in the city of New York.

Emotional engagement and orienting: the effects of picture size on affective response

For their survival, humans and animals can rely on motivational systems which are specialized in assessing the valence and imminence of dangers and appetitive cues. The Orienting Response (OR) is a fundamental response pattern that an organism executes whenever a novel or significant stimulus is detected, and has been shown to be consistently modulated by the affective value of a stimulus. However, detecting threatening stimuli and appetitive affordances while they are far away compared to when they are within reach constitutes an obvious evolutionary advantage. Building on the linear relationship between stimulus distance and retinal size, the present research was aimed at investigating the extent to which emotional modulation of distinct processes (action preparation, attentional capture, and subjective emotional state) is affected when reducing the retinal size of a picture. Studies 1-3 examined the effects of picture size on emotional response. Subjective feeling of engagement, as well as sympathetic activation, were modulated by picture size, suggesting that action preparation and subjective experience reflect the combined effects of detecting an arousing stimulus and assessing its imminence. On the other hand, physiological responses which are thought to reflect the amount of attentional resources invested in stimulus processing did not vary with picture size. Studies 4-6 were conducted to substantiate and extend the results of studies 1-3. In particular, it was noted that a decrease in picture size is associated with a loss in the low spatial frequencies of a picture, which might confound the interpretation of the results of studies 1-3. Therefore, emotional and neutral images which were either low-pass filtered or reduced in size were presented, and affective responses were measured. Most effects which were observed when manipulating image size were replicated by blurring pictures. However, pictures depicting highly arousing unpleasant contents were associated with a more pronounced decrease in affective modulation when pictures were reduced in size compared to when they were blurred. The present results provide important information for the study of processes involved in picture perception and in the genesis and expression of an emotional response. In particular, the availability of high spatial frequencies might affect the degree of activation of an internal representation of an affectively charged scene, and might modulate subjective emotional state and preparation for action. Moreover, the manipulation of stimulus imminence revealed important effects of stimulus engagement on specific components of the emotional response, and the implications of the present data for some models of emotions have been discussed. In particular, within the framework of a staged model of emotional response, the tactic and strategic role of response preparation and attention allocation to stimuli varying in engaging power has been discussed, considering the adaptive advantages that each might represent in an evolutionary view. Finally, the identification of perceptual parameters that allow affective processing to be carried out has important methodological applications in future studies examining emotional response in basic research or clinical contexts.

Mathematical models of cognitive processes

The research activity carried out during the PhD course was focused on the development of mathematical models of some cognitive processes and their validation by means of data present in literature, with a double aim: i) to achieve a better interpretation and explanation of the great amount of data obtained on these processes from different methodologies (electrophysiological recordings on animals, neuropsychological, psychophysical and neuroimaging studies in humans), ii) to exploit model predictions and results to guide future research and experiments. In particular, the research activity has been focused on two different projects: 1) the first one concerns the development of neural oscillators networks, in order to investigate the mechanisms of synchronization of the neural oscillatory activity during cognitive processes, such as object recognition, memory, language, attention; 2) the second one concerns the mathematical modelling of multisensory integration processes (e.g. visual-acoustic), which occur in several cortical and subcortical regions (in particular in a subcortical structure named Superior Colliculus (SC)), and which are fundamental for orienting motor and attentive responses to external world stimuli. This activity has been realized in collaboration with the Center for Studies and Researches in Cognitive Neuroscience of the University of Bologna (in Cesena) and the Department of Neurobiology and Anatomy of the Wake Forest University School of Medicine (NC, USA). PART 1. Objects representation in a number of cognitive functions, like perception and recognition, foresees distribute processes in different cortical areas. One of the main neurophysiological question concerns how the correlation between these disparate areas is realized, in order to succeed in grouping together the characteristics of the same object (binding problem) and in maintaining segregated the properties belonging to different objects simultaneously present (segmentation problem). Different theories have been proposed to address these questions (Barlow, 1972). One of the most influential theory is the so called “assembly coding”, postulated by Singer (2003), according to which 1) an object is well described by a few fundamental properties, processing in different and distributed cortical areas; 2) the recognition of the object would be realized by means of the simultaneously activation of the cortical areas representing its different features; 3) groups of properties belonging to different objects would be kept separated in the time domain. In Chapter 1.1 and in Chapter 1.2 we present two neural network models for object recognition, based on the “assembly coding” hypothesis. These models are networks of Wilson-Cowan oscillators which exploit: i) two high-level “Gestalt Rules” (the similarity and previous knowledge rules), to realize the functional link between elements of different cortical areas representing properties of the same object (binding problem); 2) the synchronization of the neural oscillatory activity in the γ-band (30-100Hz), to segregate in time the representations of different objects simultaneously present (segmentation problem). These models are able to recognize and reconstruct multiple simultaneous external objects, even in difficult case (some wrong or lacking features, shared features, superimposed noise). In Chapter 1.3 the previous models are extended to realize a semantic memory, in which sensory-motor representations of objects are linked with words. To this aim, the network, previously developed, devoted to the representation of objects as a collection of sensory-motor features, is reciprocally linked with a second network devoted to the representation of words (lexical network) Synapses linking the two networks are trained via a time-dependent Hebbian rule, during a training period in which individual objects are presented together with the corresponding words. Simulation results demonstrate that, during the retrieval phase, the network can deal with the simultaneous presence of objects (from sensory-motor inputs) and words (from linguistic inputs), can correctly associate objects with words and segment objects even in the presence of incomplete information. Moreover, the network can realize some semantic links among words representing objects with some shared features. These results support the idea that semantic memory can be described as an integrated process, whose content is retrieved by the co-activation of different multimodal regions. In perspective, extended versions of this model may be used to test conceptual theories, and to provide a quantitative assessment of existing data (for instance concerning patients with neural deficits). PART 2. The ability of the brain to integrate information from different sensory channels is fundamental to perception of the external world (Stein et al, 1993). It is well documented that a number of extraprimary areas have neurons capable of such a task; one of the best known of these is the superior colliculus (SC). This midbrain structure receives auditory, visual and somatosensory inputs from different subcortical and cortical areas, and is involved in the control of orientation to external events (Wallace et al, 1993). SC neurons respond to each of these sensory inputs separately, but is also capable of integrating them (Stein et al, 1993) so that the response to the combined multisensory stimuli is greater than that to the individual component stimuli (enhancement). This enhancement is proportionately greater if the modality-specific paired stimuli are weaker (the principle of inverse effectiveness). Several studies have shown that the capability of SC neurons to engage in multisensory integration requires inputs from cortex; primarily the anterior ectosylvian sulcus (AES), but also the rostral lateral suprasylvian sulcus (rLS). If these cortical inputs are deactivated the response of SC neurons to cross-modal stimulation is no different from that evoked by the most effective of its individual component stimuli (Jiang et al 2001). This phenomenon can be better understood through mathematical models. The use of mathematical models and neural networks can place the mass of data that has been accumulated about this phenomenon and its underlying circuitry into a coherent theoretical structure. In Chapter 2.1 a simple neural network model of this structure is presented; this model is able to reproduce a large number of SC behaviours like multisensory enhancement, multisensory and unisensory depression, inverse effectiveness. In Chapter 2.2 this model was improved by incorporating more neurophysiological knowledge about the neural circuitry underlying SC multisensory integration, in order to suggest possible physiological mechanisms through which it is effected. This endeavour was realized in collaboration with Professor B.E. Stein and Doctor B. Rowland during the 6 months-period spent at the Department of Neurobiology and Anatomy of the Wake Forest University School of Medicine (NC, USA), within the Marco Polo Project. The model includes four distinct unisensory areas that are devoted to a topological representation of external stimuli. Two of them represent subregions of the AES (i.e., FAES, an auditory area, and AEV, a visual area) and send descending inputs to the ipsilateral SC; the other two represent subcortical areas (one auditory and one visual) projecting ascending inputs to the same SC. Different competitive mechanisms, realized by means of population of interneurons, are used in the model to reproduce the different behaviour of SC neurons in conditions of cortical activation and deactivation. The model, with a single set of parameters, is able to mimic the behaviour of SC multisensory neurons in response to very different stimulus conditions (multisensory enhancement, inverse effectiveness, within- and cross-modal suppression of spatially disparate stimuli), with cortex functional and cortex deactivated, and with a particular type of membrane receptors (NMDA receptors) active or inhibited. All these results agree with the data reported in Jiang et al. (2001) and in Binns and Salt (1996). The model suggests that non-linearities in neural responses and synaptic (excitatory and inhibitory) connections can explain the fundamental aspects of multisensory integration, and provides a biologically plausible hypothesis about the underlying circuitry.

Role of nitric oxide and endocannabinoids in synaptic plasticity in the perirhinal cortex and in visual recognition memory

Introduction and aims of the research Nitric oxide (NO) and endocannabinoids (eCBs) are major retrograde messengers, involved in synaptic plasticity (long-term potentiation, LTP, and long-term depression, LTD) in many brain areas (including hippocampus and neocortex), as well as in learning and memory processes. NO is synthesized by NO synthase (NOS) in response to increased cytosolic Ca2+ and mainly exerts its functions through soluble guanylate cyclase (sGC) and cGMP production. The main target of cGMP is the cGMP-dependent protein kinase (PKG). Activity-dependent release of eCBs in the CNS leads to the activation of the Gαi/o-coupled cannabinoid receptor 1 (CB1) at both glutamatergic and inhibitory synapses. The perirhinal cortex (Prh) is a multimodal associative cortex of the temporal lobe, critically involved in visual recognition memory. LTD is proposed to be the cellular correlate underlying this form of memory. Cholinergic neurotransmission has been shown to play a critical role in both visual recognition memory and LTD in Prh. Moreover, visual recognition memory is one of the main cognitive functions impaired in the early stages of Alzheimer’s disease. The main aim of my research was to investigate the role of NO and ECBs in synaptic plasticity in rat Prh and in visual recognition memory. Part of this research was dedicated to the study of synaptic transmission and plasticity in a murine model (Tg2576) of Alzheimer’s disease. Methods Field potential recordings. Extracellular field potential recordings were carried out in horizontal Prh slices from Sprague-Dawley or Dark Agouti juvenile (p21-35) rats. LTD was induced with a single train of 3000 pulses delivered at 5 Hz (10 min), or via bath application of carbachol (Cch; 50 μM) for 10 min. LTP was induced by theta-burst stimulation (TBS). In addition, input/output curves and 5Hz-LTD were carried out in Prh slices from 3 month-old Tg2576 mice and littermate controls. Behavioural experiments. The spontaneous novel object exploration task was performed in intra-Prh bilaterally cannulated adult Dark Agouti rats. Drugs or vehicle (saline) were directly infused into the Prh 15 min before training to verify the role of nNOS and CB1 in visual recognition memory acquisition. Object recognition memory was tested at 20 min and 24h after the end of the training phase. Results Electrophysiological experiments in Prh slices from juvenile rats showed that 5Hz-LTD is due to the activation of the NOS/sGC/PKG pathway, whereas Cch-LTD relies on NOS/sGC but not PKG activation. By contrast, NO does not appear to be involved in LTP in this preparation. Furthermore, I found that eCBs are involved in LTP induction, but not in basal synaptic transmission, 5Hz-LTD and Cch-LTD. Behavioural experiments demonstrated that the blockade of nNOS impairs rat visual recognition memory tested at 24 hours, but not at 20 min; however, the blockade of CB1 did not affect visual recognition memory acquisition tested at both time points specified. In three month-old Tg2576 mice, deficits in basal synaptic transmission and 5Hz-LTD were observed compared to littermate controls. Conclusions The results obtained in Prh slices from juvenile rats indicate that NO and CB1 play a role in the induction of LTD and LTP, respectively. These results are confirmed by the observation that nNOS, but not CB1, is involved in visual recognition memory acquisition. The preliminary results obtained in the murine model of Alzheimer’s disease indicate that deficits in synaptic transmission and plasticity occur very early in Prh; further investigations are required to characterize the molecular mechanisms underlying these deficits.

Molecular approach to Neurodegenerative Disorders: Role of Nociceptin/Orphanin FQ - NOP System in Parkinson and Epigenetic Mechanism in Alzheimer's Disease

With life expectancies increasing around the world, populations are getting age and neurodegenerative diseases have become a global issue. For this reason we have focused our attention on the two most important neurodegenerative diseases: Parkinson’s and Alzheimer’s. Parkinson’s disease is a chronic progressive neurodegenerative movement disorder of multi-factorial origin. Environmental toxins as well as agricultural chemicals have been associated with PD. Has been observed that N/OFQ contributes to both neurotoxicity and symptoms associated with PD and that pronociceptin gene expression is up-regulated in rat SN of 6-OHDA and MPP induced experimental parkinsonism. First, we investigated the role of N/OFQ-NOP system in the pathogenesis of PD in an animal model developed using PQ and/or MB. Then we studied Alzheimer's disease. This disorder is defined as a progressive neurologic disease of the brain leading to the irreversible loss of neurons and the loss of intellectual abilities, including memory and reasoning, which become severe enough to impede social or occupational functioning. Effective biomarker tests could prevent such devastating damage occurring. We utilized the peripheral blood cells of AD discordant monozygotic twin in the search of peripheral markers which could reflect the pathology within the brain, and also support the hypothesis that PBMC might be a useful model of epigenetic gene regulation in the brain. We investigated the mRNA levels in several genes involve in AD pathogenesis, as well DNA methylation by MSP Real-Time PCR. Finally by Western Blotting we assess the immunoreactivity levels for histone modifications. Our results support the idea that epigenetic changes assessed in PBMCs can also be useful in neurodegenerative disorders, like AD and PD, enabling identification of new biomarkers in order to develop early diagnostic programs.