Extinction, applied after retrieval of auditory fear memory, selectively increases zinc-finger protein 268 and phosphorylated ribosomal protein S6 expression in prefrontal cortex and lateral amygdala

Abstract Retrieval of consolidated memories induces a labile phase during which memory can be disrupted or updated through a reconsolidation process. A central component of behavioral updating during reconsolidation using a retrieval–extinction manipulation (Ret + Ext) is the synaptic removal of a calcium-permeable-α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (CP-AMPARs) in the lateral amygdala—a metabotropic GluR1 receptor (mGluR1) dependent mechanism. In the present study, we investigate the effect of Ret + Ext on the expression of molecular markers that could play a role in the reconsolidation process. Specifically, we tested the effects of Ret + Ext on the global expression of zinc-finger 268 protein (Zif268), a marker previously found to be implicated in memory reconsolidation, to confirm its occurrence after retrieval (Ret) and Ret + Ext. We also evaluated the global expression of phosphorylated ribosomal protein S6 (rpS6P), here proposed as a marker of the mGluR1-mediated memory process induced by Ret + Ext. The expression of both markers (zif268, rpS6P) was assessed by immunolocalization in prelimbic cortex (PRL), infralimbic cortex (IL), ventral subdivision of the lateral amygdala (LA) and hippocampus CA1 (CA1) in fear-conditioned rats. Our results showed that retrieval and Ret + Ext, but not extinction alone, increased Zif268 expression in prefrontal cortex and lateral amygdala. Ret + Ext, but not retrieval, retrieval followed by context exposure or extinction alone, increased the expression of rpS6P in prefrontal cortex and LA. In summary, (i) Zif268 increased after retrieval confirming that reconsolidation is engaged in our conditions, (ii) Zif268 increased after Ret + Ext confirming that it does not simply reflect an extinction or reconsolidation disruption (Zif268 level of expression should be lower in both cases) and (iii) rpS6P increased after Ret + Ext, but not after extinction, suggesting, as expected, a potential mGluR1 mediated molecular mechanism specific for Ret + Ext. Together with the Zif268 increase, our results suggest that the Ret + Ext induced memory process is more similar to reconsolidation updating than extinction facilitation

Continuous Infusion of Flumazenil in the Management of Benzodiazepines Detoxification

An effective approach in the treatment of benzodiazepine (BZD) overdosing and detoxification is flumazenil (FLU). Studies in chronic users who discontinued BZD in a clinical setting suggested that multiple slow bolus infusions of FLU reduce BZD withdrawal symptoms. The aim of this study was to confirm FLU efficacy for reducing BZD withdrawal syndrome by means of continuous elastomeric infusion, correlated to drugs plasma level and patients\u2019 compliance. Methods: Seven-day FLU 1 mg/day subcutaneously injected through an elastomeric pump and BZDs lormetazepam, clonazepam, and lorazepam were assessed by HPLC-MS/MS in serum of patients before and after 4 and 7 days of FLU continuous infusion treatment. Changes in withdrawal severity were assessed by using the BZD Withdrawal Scale (BWS). Results: Fourteen patients (mean age \ub1 SD 42.5 \ub1 8.0 years, 5 male and 9 female), admitted to the hospital for high-dose BZD detoxification, were enrolled in the study. Serum FLU concentrations significantly decreased from 0.54 \ub1 0.33 ng/ml (mean \ub1 SD) after 4 days of treatment to 0.1 \ub1 0.2 ng/ml at the end of infusion. Lormetazepam concentrations were 502.5 \ub1 610.0 ng/ml at hospital admission, 26.2 \ub1 26.8 ng/ml after 4 days, and 0 at the end of treatment. BWS values decreased during FLU treatment temporal period. FLU was well-tolerated by patients. Conclusions: Elastomeric FLU infusion for BZD detoxification is a feasible administration device to maintain adequate, constant, and tolerated FLU concentrations for reducing BZD withdrawal symptoms

Telemedicine and Virtual Reality for Cognitive Rehabilitation: A Roadmap for the COVID-19 Pandemic

The current COVID-19 pandemic presents unprecedented new challenges to public health and medical care delivery. To control viral transmission, social distancing measures have been implemented all over the world, interrupting the access to routine medical care for many individuals with neurological diseases. Cognitive disorders are common in many neurological conditions, e.g., stroke, traumatic brain injury, Alzheimer's disease, and other types of dementia, Parkinson's disease and parkinsonian syndromes, and multiple sclerosis, and should be addressed by cognitive rehabilitation interventions. To be effective, cognitive rehabilitation programs must be intensive and prolonged over time; however, the current virus containment measures are hampering their implementation. Moreover, the reduced access to cognitive rehabilitation might worsen the relationship between the patient and the healthcare professional. Urgent measures to address issues connected to COVID-19 pandemic are, therefore, needed. Remote communication technologies are increasingly regarded as potential effective options to support health care interventions, including neurorehabilitation and cognitive rehabilitation. Among them, telemedicine, virtual reality, augmented reality, and serious games could be in the forefront of these efforts. We will briefly review current evidence-based recommendations on the efficacy of cognitive rehabilitation and offer a perspective on the role of tele- and virtual rehabilitation to achieve adequate cognitive stimulation in the era of social distancing related to COVID-19 pandemic. In particular, we will discuss issues related to their diffusion and propose a roadmap to address them. Methodological and technological improvements might lead to a paradigm shift to promote the delivery of cognitive rehabilitation to people with reduced mobility and in remote regions

Smoking-related cue reactivity in a virtual reality setting: association between craving and EEG measures

BACKGROUND: Cue-reactivity is the array of responses that smokers exhibit when exposed to conditioned and contextual stimuli previously associated to substance use. The difficulty to experimentally recreate the complexity of smokers' spatial experience and context requires more ecological models. Virtual reality (VR) creates a state of immersion close to reality allowing controlled assessments of behavioral responses. To date, no studies investigated brain activation associated to smoking cue-reactivity in VR using electroencephalography (EEG).AIMS: To investigate whether a VR cue-reactivity paradigm (a) may increase smoking craving, (b) is feasible with EEG recording, and (c) induces craving levels associated to EEG desynchronization.METHODS: Smokers (N=20) and non-smokers (N=20) were exposed to neutral and smoking-related VR scenarios, without and with smoking conditioned stimuli, respectively. EEG was recorded from occipital and parietal leads throughout the sessions to assess alpha band desynchronization. Smoking and food craving and presence visual analogue scales (VAS) were assessed during the session.RESULTS: To be smoker, but not non-smoker, significantly influenced smoking craving VAS induced by smoking cue VR but not by neutral VR. No significant food craving changes was observed during the VR sessions. The new finding was that EEG alpha band power in posterior leads was significantly increased by the smoking context scenario only in smokers, and that the degree of smoking (i.e., heavy vs. light) was significantly associated to this neurophysiological measure.CONCLUSIONS: This study demonstrated, for the first time, the feasibility of EEG recording in a VR setting, suggesting that EEG desynchronization may be a neurophysiological marker of smoking cue-reactivity

Virtual Reality for Neuroarchitecture: Cue Reactivity in Built Spaces

Domestic and urban environments are associated to our life experiences and behaviors. These environments may acquire an emotional and motivational value and, in turn, shape our behaviors. Although there is a well-established knowledge of the effects of built space features on perception, feelings, and affective responses (Ulrich, 1991), only a limited attention has been however paid to physical space-induced motivated behaviors. There is still a strong attitude to consider the control of motivated behaviors as a matter of individual desires, free will, moral choices, executive control, etc.—and not as the interaction between environment and personality, genetics, and brain mechanisms. Recently, there has been a convergent agreement from architects, designers, psychologists, and neuroscientists about the multifactorial nature of the reciprocal interaction between humans and built space, and how it could impact on well-being psychological distress and risky behaviors (Sternberg, 2009). The emerging interdisciplinary field of “neuroarchitecture” developed conceptual paradigms and empirical frameworks based on the interaction between brain and built spaces (see Academy of Neuroscience for Architecture; www.anfarch.org). Within this framework, we would like to propose the “Cue Reactivity” phenomenon as a paradigmatic example of such as interaction. Cue reactivity (C-R) is the adaptive response to salient information in the environment (Niaura et al., 1988). Salient information is that associated to drugs, sex, palatable food, and to a variety of natural and non-natural rewards (such as gambling, shopping, etc.). Drug C-R manifests itself as an array of responses to stimuli previously associated to drug effect. The detrimental consequence of C-R is relapse to drug-seeking and drug-taking (Rohsenow et al., 1991). On the other hand, C-R is an evolutionary phenotype of the interaction with the environment: in fact, spatial context rich of reward-related cues may stimulate both positive and risky motivated behaviors. In this Opinion paper, we will show that identification and design of specific physical space features may affect mental health, and that indoor and furniture of drinking venues are associated to alcohol use. Based on what we know about C-R, and on the effects of built spaces on psychological and behavioral processes, we think that more research is now possible to plan and design research-based “C-R-free situations.” For instance, investigations on outdoor and indoor features associated to C-R may help to develop “motivational safer built environments.” The complexity of real world investigations is not however easily modeled in the laboratory, but technologies like virtual reality may offer the possibility to increase subject's presence in a spatial context simulation and, in the meantime, the control of the experimental parameters (García-Rodríguez et al., 2012). For these reasons, we propose virtual reality as a methodological approach in-between naturalistic and experimental lab setting for a better understanding of built space features affecting C-R.The “5per mille 2012” research grant by the Italian Cancer League (Lega Italiana Lotta per i Tumori, LILT) supported the study (PI: CC) and research grant for GB. LILT also supported CC and SF with educational grants

A virtual reality study on postretrieval extinction of smoking memory reconsolidation in smokers

Exposure to smoking-related stimuli may induce the reconsolidation of smoking-related memories in smokers. Research has proposed that extinction applied after the retrieval of a smoking memory may inhibit reconsolidation and prevent craving. The aim of this study was to test the effect of postretrieval extinction (PRE) on the reconsolidation of smoking memory by using a virtual reality (VR) simulation in smokers. On the day 1 session, the study exposed 46 smokers to a neutral and then to a smoking VR scenario under a fixed-block protocol. On day 2, the study randomized participants into three groups (G) and exposed them to a 15-s VR immersion in smoking (G1, G3) or neutral (G2) scenario for memory retrieval. After 15 min, the study exposed G1 and G2 to a VR PRE during the temporal window of memory vulnerability, whereas the study exposed G3 to extinction immediately after retrieval. On day 3, the study exposed all groups to neutral and smoking scenarios similar to day 1. All groups significantly increased craving for cigarettes after exposure to the smoking scenario on day 1 (p 0.01). On day 3, VR PRE after a 15-second VR smoking memory retrieval was able to inhibit reconsolidation in G1, but not in G3 exposed to PRE before the window of vulnerability, or in G2 not exposed to the smoking memory retrieval. These findings show the superiority of VR PRE after smoking memory retrieval compared to a standard extinction procedure

AVALIAÇÃO DA INFLUÊNCIA DO TRATAMENTO DE SEMENTES DE FEIJÃO COM INSETICIDA

O tratamento de sementes de Feijão com Inseticidas é bastante utilizado para controle de pragas iniciais e manutenção do estande inicial de plantas. O objetivo desse estudo foi avaliar a germinação de sementes das cultivares de feijão Predileto (PR  e Riqueza(RI), submentendo-as a um tratamento sementes utilizando o Inseticida Tiametoxan 350g/L (CRUISER® 350 FS – Syngenta) na dose de 218 mL/100 kg de sementes. O experimento era composto de quatro tratamentos com quatro repetições cada tratamento, no delineamento inteiramente casualizado e esquema fatorial: Predileto (PR) com tratamento de sementes; Predileto (PR) sem tratamento de sementes; Riqueza (RI) com tratamento de sementes; Riqueza (RI) sem tratamento de sementes. Para a semeadura foram utilizadas bandejas de isopor com 200 células e substrato apropriado para germinação de sementes. Após a semeadura as bandejas foram acondicionadas de forma aleatória em estufa, com irrigação duas vezes ao dia, e eram redistribuídas a cada três dias. O parâmetro utilizado para determinar que as plantas estavam germinadas foi de duas folhas totalmente expandidas. As unidades experimentais foram colhidas 25 dias após a semeadura, sendo submetidas a avaliação de Germinação, Matéria Verde e Matéria Seca. Os dados  foram submetidos a análise de regressão e de variância  com o Ambiente R. Não se observou  efeito significativo de variedade, de tratamento de sementes ou interação

ANÁLISE QUANTITATIVA E QUALITATIVA DE DIFERENTES MARCAS DE IOGURTE

O consumidor escolhe um alimento pelo seu nível de qualidade sensorial, formado do conjunto de aparência, textura, sabor e aroma, que provocam reações de desejo ou rejeição do consumidor ao alimento. A avaliação sensorial é essencial para pesquisar o mercado consumidor e melhorar a qualidade do alimento. O experimento foi conduzido em laboratório, utilizando quatro marcas comerciais de Iogurte, sabor morango, sendo elas Aurora, Elegê, Frimesa e Tirol. Foi utilizado o delineamento experimental em Quadrado Latino, buscando avaliar Cor, Sabor, Textura, Impressão, Aroma e pH. Para realizar as avaliações foram utilizados quatro avaliadores, e as amostras dos iogurtes foram enumerados e colocados em recipientes de 50 ml. As amostras foram sorteadas aleatoriamente e colocadas em ordem de sorteio em frente ao avaliador, após cada amostra foi submetida a análise e os avaliadores atribuíam notas de 1 a 9 para cada amostra em perguntas comumente feitas pelos consumidores. Os valores obtidos foram submetidos ao teste de comparação de médias, sendo que dentre os aspectos avaliados, somente o pH apresentou diferiu significativamente dentre as amostras analisadas