Auditory Event-Related P300 Potentials in Rheumatoid Arthritis Patients

The aim of the study was to assess P300 event-related potentials (ERPs) in patients suffering from rheumatoid arthritis (RA) in relation to the duration of illness, degree of disease activity, anatomical and functional stage of the disease, pain intensity, and pain unpleasantness. The cross-sectional study included 53 women with RA (RA group; mean age 50.58 ± 0.93 years) and 27 healthy women (control group, C; 49.41 ± 1.08 years). The intensity and unpleasantness of pain were determined using a visual analog scale (VAS); the functional status was assessed using HAQ (Health Assessment Questionnaire), and the disease activity was estimated using the disease activity scale (DAS28). The P300 waves initiated by auditory stimulations according to the oddball paradigm were recorded from leads Fz and Cz. There were no significant differences between the P300 latencies in both leads. At the same time, the average P300 amplitudes in both leads were found to be considerably lower (P < 0.05) in the RA group compared to the C group. Thus, there is a statistically significant amplitude difference between the P300 cognitive ERPs in RA patients and control subjects.Були досліджені параметри пов’язаних із подією потенціалів (ППП) P300 у пацієнтів, що страждають на ревматоїдний артрит (РА), та зв’язок цих параметрів із тривалістю та інтенсивністю захворювання, анатомічною та функціональною стадіями останнього, інтенсивністю та неприємністю відчуттів болю. У порівняльне дослідження були залучені 53 жінки з РА (група RA, середній вік 50.58 ± ± 0.94 року) та 27 здорових жінок (контрольна група C, 49.41 ± 1.08 року). Інтенсивність та рівень неприємності болю визначали за допомогою візуальної аналогової шкали (VAS), функціональний статус – згідно з опитувальником HAQ, а інтенсивність хвороби – за шкалою DAS28. Потенціали P300 ініціювали акустичною стимуляцією відповідно до oddball-парадигми та відводили від точок Fz та Cz. Усереднені значення латентних періодів хвилі P300 в групах RA та C не демонстрували якихось істотних відмінностей. У той же час усереднені амплітуди P300 в обох кортикальних зонах у групі RA були вірогідно нижчими (P < 0.05), ніж відповідні величини в групі C. Таким чином, існує статистично значуща різниця між характеристиками когнітивного ППП P300 у пацієнтів із ревматоїдним артритом та здорових суб’єктів, що вказує на негативні зміни сенсорного процесінга та уваги, а також когнітивні дисфункції, виниклі під впливом хронічного болю

Repeated Labilization-Reconsolidation Processes Strengthen Declarative Memory in Humans

The idea that memories are immutable after consolidation has been challenged. Several reports have shown that after the presentation of a specific reminder, reactivated old memories become labile and again susceptible to amnesic agents. Such vulnerability diminishes with the progress of time and implies a re-stabilization phase, usually referred to as reconsolidation. To date, the main findings describe the mechanisms associated with the labilization-reconsolidation process, but little is known about its functionality from a biological standpoint. Indeed, two functions have been proposed. One suggests that destabilization of the original memory after the reminder allows the integration of new information into the background of the original memory (memory updating), and the other suggests that the labilization-reconsolidation process strengthens the original memory (memory strengthening). We have previously reported the reconsolidation of human declarative memories, demonstrating memory updating in the framework of reconsolidation. Here we deal with the strengthening function attributed to the reconsolidation process. We triggered labilization-reconsolidation processes successively by repeated presentations of the proper reminder. Participants learned an association between five cue-syllables and their respective response-syllables. Twenty-four hours later, the paired-associate verbal memory was labilized by exposing the subjects to one, two or four reminders. The List-memory was evaluated on Day 3 showing that the memory was improved when at least a second reminder was presented in the time window of the first labilization-reconsolidation process prompted by the earlier reminder. However, the improvement effect was revealed on Day 3, only when at least two reminders were presented on Day2 and not as a consequence of only retrieval. Therefore, we propose central concepts for the reconsolidation process, emphasizing its biological role and the parametrical constrains for this function to be operative

Advanced paternal age effects in neurodevelopmental disorders?review of potential underlying mechanisms

Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events. Here we provide a review of the epidemiological and molecular findings to date. Focusing on the latter, we present the evidence for genetic and epigenetic mechanisms underpinning the association between late fatherhood and disorder in offspring. We also discuss the limitations of the APA literature. We propose that different hypotheses relating to the origins of the APA effects are not mutually exclusive. Instead, multiple mechanisms likely contribute, reflecting the etiological complexity of neurodevelopmental disorders

A Mismatch-Based Model for Memory Reconsolidation and Extinction in Attractor Networks

The processes of memory reconsolidation and extinction have received increasing attention in recent experimental research, as their potential clinical applications begin to be uncovered. A number of studies suggest that amnestic drugs injected after reexposure to a learning context can disrupt either of the two processes, depending on the behavioral protocol employed. Hypothesizing that reconsolidation represents updating of a memory trace in the hippocampus, while extinction represents formation of a new trace, we have built a neural network model in which either simple retrieval, reconsolidation or extinction of a stored attractor can occur upon contextual reexposure, depending on the similarity between the representations of the original learning and reexposure sessions. This is achieved by assuming that independent mechanisms mediate Hebbian-like synaptic strengthening and mismatch-driven labilization of synaptic changes, with protein synthesis inhibition preferentially affecting the former. Our framework provides a unified mechanistic explanation for experimental data showing (a) the effect of reexposure duration on the occurrence of reconsolidation or extinction and (b) the requirement of memory updating during reexposure to drive reconsolidation

The CB1 receptor antagonist AM251 impairs reconsolidation of pavlovian fear memory in the rat basolateral amygdala

We have investigated the requirement for signaling at CB1 receptors in the reconsolidation of a previously consolidated auditory fear memory, by infusing the CB1 receptor antagonist AM251, or the FAAH inhibitor URB597, directly into the basolateral amygdala (BLA) in conjunction with memory reactivation. AM251 disrupted memory restabilization, but only when administered after reactivation. URB597 produced a small, transient enhancement of memory restabilization when administered after reactivation. The amnestic effect of AM251 was rescued by coadministration of the GABAA receptor antagonist bicuculline at reactivation, indicating that the disruption of reconsolidation was mediated by altered GABAergic transmission in the BLA. These data show that the endocannabinoid system in the BLA is an important modulator of fear memory reconsolidation and that its effects on memory are mediated by an interaction with the GABAergic system. Thus, targeting the endocannabinoid system may have therapeutic potential to reduce the impact of maladaptive memories in neuropsychiatric disorders such as posttraumatic stress disorder.This work was conducted within the Behavioural and Clinical Neuroscience Institute, a joint initiative funded by the Wellcome Trust and the UK Medical Research Council, in the Department of Psychology at the University of Cambridge. This work was funded by a UK Medical Research Council programme grant (no. G1002231) awarded to BJE and ALM. PR was supported by a Department of Physiology and Pharmacology Fellowship at the Sapienza University of Rome, and an Italian Society of Pharmacology Fellowship. ALM is the Ferreras-Willetts Fellow in Neuroscience at Downing College, Cambridge. The manuscript was partly prepared while ALM was an Erskine Visiting Cambridge Fellow at the University of Canterbury, Christchurch, New Zealand

Mechanisms of memory stabilization andde-stabilization

International audienceMemories become stabilized through a time-dependent process that requires gene expression and is commonly known as consolidation. During this time, memories are labile and can be disrupted by a number of interfering events, including electroconvulsive shock, trauma and other learning or the transient effect of drugs such as protein synthesis inhibitors. Once consolidated, memories are insensitive to these disruptions. However, they can again become fragile if recalled or reactivated. Reactivation creates another time-dependent process, known as reconsolidation, during which the memory is restabilized. Here we discuss some of the questions currently debated in the field of memory consolidation and reconsolidation, the molecular and anatomical requirements for both processes and, finally, their functional relationship