Hippocampal acetylcholine release during memory testing in rats: augmentation by glucose.

Several lines of evidence indicate that a modest increase in circulating glucose levels enhances memory. One mechanism underlying glucose effects on memory may be an increase in acetylcholine (ACh) release. The present experiment determined whether enhancement of spontaneous alternation performance by systemic glucose treatment is related to an increase in hippocampal ACh output. Samples of extracellular ACh were assessed at 12-min intervals using in vivo microdialysis with HPLC-EC. Twenty-four minutes after an intraperitoneal injection of saline or glucose (100, 250, or 1000 mg/kg), rats were tested in a four-arm cross maze for spontaneous alternation behavior combined with microdialysis collection. Glucose at 250 mg/kg, but not 100 or 1000 mg/kg, produced an increase in spontaneous alternation scores (69.5%) and ACh output (121.5% versus baseline) compared to alternation scores (44.7%) and ACh output (58.9% versus baseline) of saline controls. The glucose-induced increase in alternation scores and ACh output was not secondary to changes in locomotor activity. Saline and glucose (100-1000 mg/kg) treatment had no effect on hippocampal ACh output when rats remained in the holding chamber. These findings suggest that glucose may enhance memory by directly or indirectly increasing the release of ACh. The results also indicate that hippocampal ACh release is increased in rats performing a spatial task. Moreover, because glucose enhanced ACh output only during behavioral testing, circulating glucose may modulate ACh release only under conditions in which cholinergic cells are activated.

El papel de la memoria de trabajo en el cálculo mental un cuarto de siglo después de Hitch = The role of working memory in mental arithmetic a quarter of century after Hitch

Desde que Hitch (1978) publicó el primer estudio sobre el rol de la memoria de trabajo en el cálculo han ido aumentando las investigaciones en este campo. Muchos trabajos han estudiado un único subsistema, pero nuestro objetivo es identificar qué subsistema de la memoria de trabajo (bucle fonológico, agenda viso-espacial o ejecutivo central) está más implicado en el cálculo mental. Para ello hemos realizado un estudio correlacional en el que hemos administrado dos pruebas aritméticas y nueve pruebas de la “Bateria de Test de Memòria de Treball” de Pickering, Baqués y Gathercole (1999) a una muestra de 94 niños españoles de 7-8 años. Nuestros resultados indican que el bucle fonológico y sobretodo el ejecutivo central inciden de forma estadísticamente significativa en el rendimiento aritmético

Can postictal memory predict postoperative memory in patients with temporal lobe epilepsy?

We investigated the contribution of postictal memory testing for lateralizing the epileptic focus and predicting memory outcome after surgery for temporal lobe epilepsy (TLE). Forty-five patients with TLE underwent interictal, postictal, and postoperative assessment of verbal and nonverbal memory. Surgery consisted of anterior temporal lobectomy (36), selective isolated amygdalohippocampectomy (6), or amygdalohippocampectomy coupled to lesionectomy (3). Postictal and postoperative but not interictal memory were significantly lower in left TLE than in right TLE. Nonverbal memory showed no significant difference in left TLE versus right TLE in all conditions. Postictal memory was significantly correlated with postoperative memory, but the effect disappeared when the lateralization of the focus was considered. Postictal verbal memory is a useful bedside tool that can help lateralize the epileptic focus. Larger studies are needed to further estimate its predictive value of the postoperative outcome.

Nimodipine prior to alcohol withdrawal prevents memory deficits during the abstinence phase

Effects of the dihydropyridine, nimodipine, an antagonist at L-type calcium channels, on the memory loss in rats caused by long term alcohol consumption were examined. Either a single dose of nimodipine or 2 weeks of repeated administration was given prior to withdrawal from 8 months of alcohol consumption. Memory was measured by the object recognition test and the T maze. Both nimodipine treatments prevented the memory deficits when these were measured between 1 and 2 months after alcohol withdrawal. At the end of the memory testing, 2 months after cessation of chronic alcohol consumption, glucocorticoid concentrations were increased in specific regions of rat brain without changes in plasma concentrations. Both nimodipine treatment schedules substantially reduced these rises in brain glucocorticoid. The data indicate that blockade of L-type calcium channels prior to alcohol withdrawal protects against the memory deficits caused by prolonged alcohol intake. This shows that specific drug treatments, such as nimodipine, given over the acute withdrawal phase, can prevented the neuronal changes responsible for subsequent adverse effects of long term consumption of alcohol. The results also suggest the possibility that regional brain glucocorticoid increases may be involved in the adverse effects of long term alcohol intake on memory. Such local changes in brain glucocorticoid levels would have major effects on neuronal function. The studies indicate that L-type calcium channels and brain glucocorticoid levels could form new targets for the treatment of cognitive deficits in alcoholics.

Memory for emotional faces in major depression following judgement of physical facial characteristics at encoding

The aim of the present study was to establish if patients with major depression (MD) exhibit a memory bias for sad faces, relative to happy and neutral, when the affective element of the faces is not explicitly processed at encoding. To this end, 16 psychiatric out-patients with MD and 18 healthy, never-depressed controls (HC) were presented with a series of emotional faces and were required to identify the gender of the individuals featured in the photographs. Participants were subsequently given a recognition memory test for these faces. At encoding, patients with MD exhibited a non-significant tendency towards slower gender identification (GI) times, relative to HC, for happy faces. However, the GI times of the two groups did not differ for sad or neutral faces. At memory testing, patients with MD did not exhibit the expected memory bias for sad faces. Similarly, HC did not demonstrate enhanced memory for happy faces. Overall, patients with MD were impaired in their memory for the faces relative to the HC. The current findings are consistent with the proposal that mood-congruent memory biases are contingent upon explicit processing of the emotional element of the to-be-remembered material at encoding.

Memory for emotional faces in naturally occurring dysphoria and induced sadness

The aim was to establish if the memory bias for sad faces, reported in clinically depressed patients (Gilboa-Schechtman, Erhard Weiss, & Jeczemien, 2002; Ridout, Astell, Reid, Glen, & O'Carroll, 2003) generalises to sub-clinical depression (dysphoria) and experimentally induced sadness. Study 1: dysphoric (n = 24) and non-dysphoric (n = 20) participants were presented with facial stimuli, asked to identify the emotion portrayed and then given a recognition memory test for these faces. At encoding, dysphoric participants (DP) exhibited impaired identification of sadness and neutral affect relative to the non-dysphoric group (ND). At memory testing, DP exhibited superior memory for sad faces relative to happy and neutral. They also exhibited enhanced memory for sad faces and impaired memory for happy relative to the ND. Study 2: non-depressed participants underwent a positive (n = 24) or negative (n = 24) mood induction (MI) and were assessed on the same tests as Study 1. At encoding, negative MI participants showed superior identification of sadness, relative to neutral affect and compared to the positive MI group. At memory testing, the negative MI group exhibited enhanced memory for the sad faces relative to happy or neutral and compared to the positive MI group. Conclusion: MCM bias for sad faces generalises from clinical depression to these sub-clinical affective states.

Short-term memory for emotional faces in dysphoria

The study aimed to determine if the memory bias for negative faces previously demonstrated in depression and dysphoria generalises from long- to short-term memory. A total of 29 dysphoric (DP) and22 non-dysphoric (ND) participants were presented with a series of faces and asked to identify the emotion portrayed (happiness, sadness, anger, or neutral affect). Following a delay, four faces were presented (the original plus three distractors) and participants were asked to identify the target face. Half of the trials assessed memory for facial emotion, and the remaining trials examined memory for facial identity. At encoding, no group differences were apparent. At memory testing, relative to ND participants, DP participants exhibited impaired memory for all types of facial emotion and for facial identity when the faces featured happiness, anger, or neutral affect, but not sadness. DP participants exhibited impaired identity memory for happy faces relative to angry, sad, and neutral, whereas ND participants exhibited enhanced facial identity memory when faces were angry. In general, memory for faces was not related to performance at encoding. However, in DP participants only, memory for sad faces was related to sadness recognition at encoding. The results suggest that the negative memory bias for faces in dysphoria does not generalise from long- to short-term memory.

Investigation of the effect of intrauterine inflammation and infection on fetal brain injury using human and animal models

In recent years, increased focus has been placed on the role of intrauterine infection and inflammation in the pathogenesis of fetal brain injury leading to neurodevelopmental disorders such as cerebral palsy. At present, the mechanisms by which inflammatory processes during pregnancy cause this effect on the fetus are poorly understood. Our previous work has indicated an association between experimentally-induced intrauterine infection, increased proinflammatory cytokines, and increased white matter injury in the guinea pig fetus. In order to further elucidate the pathways by which inflammation in the maternal system or the fetal membranes leads to fetal impairment, a number of studies investigating aspects of the disease process have been performed. These studies represent a body of work encompassing novel research and results in a number of human and animal studies. Using a guinea pig model of inflammation, increased amniotic fluid proinflammatory cytokines and fetal brain injury were found after a maternal inflammatory response was initiated using endotoxin. In order to more closely monitor the fetal response to chorioamnionitis, a model using the chronically catheterized fetal ovine was carried out. This study demonstrated the adverse effects on fetal white matter after intrauterine exposure to bacterial inoculation, though the physiological parameters of the fetus were relatively stable throughout the experimental protocol, even when challenged with intermittent hypoxic episodes. The placenta is an important mediator between mother and fetus during gestation, though its role in the inflammatory process is largely undefined. Studies on the placental role in the inflammatory process were undertaken, and the limited ability of proinflammatory cytokines and endotoxin to cross the placenta are detailed herein. Neurodevelopmental disorders can be monitored in animal models in order to determine effective disease models for characterization of injury and use in therapeutic strategies. Our characterizations of postnatal behaviour in the guinea pig model using motility monitoring and spatial memory testing have shown small but significant differences in pups exposed to inflammatory processes in utero. The data presented herein contributes a breadth of knowledge to the ongoing elucidation of the pathways by which fetal brain injury occurs. Determining the pathway of damage will lead to discovery of diagnostic criteria, while determining the vulnerabilities of the developing fetus is essential in formulating therapeutic options.

Un análisis comparativo del papel del bucle fonológico versus la agenda visoespacial en el cálculo en niños de 7-8 años = A comparative analysis of the phonological loop versus the visuo-spatial sketchpad in mental arithmetic tasks in 7-8 y.o. children

En esta investigación se ha estudiado la relación entre dos subsistemas de la memoria de trabajo (bucle fonológico y agenda viso-espacial) y el rendimiento en cálculo con una muestra de 94 niños españoles de 7-8 años. Hemos administrado dos pruebas de cálculo diseñadas para este estudio y seis medidas simples de memoria de trabajo (de contenido verbal, numérico y espacial) de la «Batería de Tests de Memoria de Treball» de Pickering, Baqués y Gathercole (1999), y dos pruebas visuales complementarias. Los resultados muestran una correlación importante entre las medidas de contenido verbal y numérico y el rendimiento en cálculo. En cambio, no hemos encontrado ninguna relación con las medidas espaciales. Se concluye, por lo tanto, que en escolares españoles existe una relación importante entre el bucle fonológico y el rendimiento en tareas de cálculo. En cambio, el rol de la agenda viso-espacial es nulo

¿Es posible entrenar la memoria de trabajo?: un programa de entrenamiento para niños de 7-8 años

Este estudio analiza si es posible entrenar la memoria de trabajo en niños, puesto que tendría importantes aplicaciones en el rendimiento escolar. En la primera fase se administraron nueve pruebas de memoria de trabajo a una muestra de 50 niños de 7-8 años. En la segunda fase la muestra se dividió en dos subgrupos de 25 niños: el grupo experimental recibió un programa de entrenamiento, y el resto formaron el grupo control. Al finalizar se administraron de nuevo las nueve pruebas a todos los niños. Los resultados indican que aunque todos mejoran su memoria de trabajo, los niños del grupo experimental presentan incrementos estadísticamente significativos. Estos resultados permiten concluir que es posible entrenar este sistema de memoria en niños

Examining the impact of thought substitution on intentional forgetting in induced and naturally occurring dysphoria

Two experiments were conducted to determine if natural and induced dysphoria is associated with impaired forgetting and, whether a thought-substitution strategy would ameliorate any observed deficits. Study 1: 36 dysphoric & 36 non-dysphoric participants learnt a series of emotional word pairs. Participants were subsequently presented with some of the cues and were asked to recall the targets or prevent the targets from coming to mind. Half of the participants were provided with substitute words to recall instead of the original targets (aided suppression). At final memory testing, participants were asked to recall the targets to all cues. Dysphoric participants exhibited impaired forgetting, even when using a thought substitution strategy. Non-dysphoric participants, however, were able to use substitutes to suppress words. Study 2: 50 healthy participants initially completed the aided condition of the forgetting task. Participants were then given a positive or negative mood-induction, followed by another version of the forgetting task. Although all participants showed a forgetting effect prior to the mood-induction, only the positive group was successful at forgetting after the mood induction. Taken together, these findings do not support the utility of thought-substitution as an aid to forgetting in individuals in a naturally or induced dysphoric mood.

Towards Optimal Testing of Auditory Memory : Methodological development of recording of the mismatch negativity (MMN) of the auditory event-related potential (ERP)

The overlapping sound pressure waves that enter our brain via the ears and auditory nerves must be organized into a coherent percept. Modelling the regularities of the auditory environment and detecting unexpected changes in these regularities, even in the absence of attention, is a necessary prerequisite for orientating towards significant information as well as speech perception and communication, for instance. The processing of auditory information, in particular the detection of changes in the regularities of the auditory input, gives rise to neural activity in the brain that is seen as a mismatch negativity (MMN) response of the event-related potential (ERP) recorded by electroencephalography (EEG). --- As the recording of MMN requires neither a subject s behavioural response nor attention towards the sounds, it can be done even with subjects with problems in communicating or difficulties in performing a discrimination task, for example, from aphasic and comatose patients, newborns, and even fetuses. Thus with MMN one can follow the evolution of central auditory processing from the very early, often critical stages of development, and also in subjects who cannot be examined with the more traditional behavioural measures of auditory discrimination. Indeed, recent studies show that central auditory processing, as indicated by MMN, is affected in different clinical populations, such as schizophrenics, as well as during normal aging and abnormal childhood development. Moreover, the processing of auditory information can be selectively impaired for certain auditory attributes (e.g., sound duration, frequency) and can also depend on the context of the sound changes (e.g., speech or non-speech). Although its advantages over behavioral measures are undeniable, a major obstacle to the larger-scale routine use of the MMN method, especially in clinical settings, is the relatively long duration of its measurement. Typically, approximately 15 minutes of recording time is needed for measuring the MMN for a single auditory attribute. Recording a complete central auditory processing profile consisting of several auditory attributes would thus require from one hour to several hours. In this research, I have contributed to the development of new fast multi-attribute MMN recording paradigms in which several types and magnitudes of sound changes are presented in both speech and non-speech contexts in order to obtain a comprehensive profile of auditory sensory memory and discrimination accuracy in a short measurement time (altogether approximately 15 min for 5 auditory attributes). The speed of the paradigms makes them highly attractive for clinical research, their reliability brings fidelity to longitudinal studies, and the language context is especially suitable for studies on language impairments such as dyslexia and aphasia. In addition I have presented an even more ecological paradigm, and more importantly, an interesting result in view of the theory of MMN where the MMN responses are recorded entirely without a repetitive standard tone. All in all, these paradigms contribute to the development of the theory of auditory perception, and increase the feasibility of MMN recordings in both basic and clinical research. Moreover, they have already proven useful in studying for instance dyslexia, Asperger syndrome and schizophrenia.

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.