The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition:a fMRI study

The functional catechol-O-methyltransferase (COMT Val108/158Met) polymorphism has been shown to have an impact on tasks of executive function, memory and attention and recently, tasks with an affective component. As oestrogen reduces COMT activity, we focused on the interaction between gender and COMT genotype on brain activations during an affective processing task. We used functional MRI (fMRI) to record brain activations from 74 healthy subjects who engaged in a facial affect recognition task; subjects viewed and identified fearful compared to neutral faces. There was no main effect of the COMT polymorphism, gender or genotypegender interaction on task performance. We found a significant effect of gender on brain activations in the left amygdala and right temporal pole, where females demonstrated increased activations over males. Within these regions, Val/Val carriers showed greater signal magnitude compared to Met/Met carriers, particularly in females. The COMT Val108/158Met polymorphism impacts on gender-related patterns of activation in limbic and paralimbic regions but the functional significance of any oestrogen-related COMT inhibition appears modest. Copyright © 2008 CINP.

Aβ(1-42) induced metabolic effects in a stem cell derived neuron and astrocyte network.

Alzheimer’s Disease (AD) is the most common form of dementia currently affecting more than 35 million people worldwide. Hypometabolism is a major feature of AD and appears decades before cognitive decline and pathological lesions. This has a detrimental impact on the brain which has a high energy demand. Current models of AD fail to mimic all the features of the disease, which has an impact on the development of new therapies. Human stem cell derived models of the brain have attracted a lot of attention in recent years as a tool to study neurodegenerative diseases. In this thesis, neurons and astrocytes derived from the human embryonal carcinoma cell line (NT2/D1) were utilised to determine the metabolic coupling between neurons and astrocytes with regards to responses to hypoglycaemia, neuromodulators and increase in neuronal activity. This model was then used to investigate the effects of Aß(1-42) on the metabolism of these NT2-derived co-cultures as well as pure astrocytes. Additionally primary cortical mixed neuronal and glial cultures were utilised to compare this model to a widely accepted in vitro model used in Alzheimer’s disease research. Co-cultures were found to respond to Aß(1-42) in similar way to human and in vivo models. Hypometabolism was characterised by changes in glucose metabolism, as well as lactate, pyruvate and glycogen. This led to a significant decrease in ATP and the ratio of NAD+/NADH. These results together with an increase in calcium oscillations and a decrease in GSH/GSSG ratio, suggests Aß-induces metabolic and oxidative stress. This situation could have detrimental effects in the brain which has a high energy demand, especially in terms of memory formation and antioxidant capacity.

Impaired executive functioning in subclinical compulsive checking with ecologically valid stimuli in a working memory task

We previously showed that working memory (WM) performance of subclinical checkers can be affected if they are presented with irrelevant but misleading information during the retention period (Harkin and Kessler, 2009, 2011). The present study differed from our previous research in the three crucial aspects. Firstly, we employed ecologically valid stimuli in form of electrical kitchen appliances on a kitchen countertop in order to address previous criticism of our research with letters in locations as these may not have tapped into the primary concerns of checkers. Secondly, we tested whether these ecological stimuli would allow us to employ a simpler (un-blocked) design while obtaining similarly robust results. Thirdly, in Experiment 2 we improved the measure of confidence as a metacognitive variable by using a quantitative scale (0–100), which indeed revealed more robust effects that were quantitatively related to accuracy of performance. The task in the present study was to memorize four appliances, including their states (on/off), and their locations on the kitchen countertop. Memory accuracy was tested for the states of appliances in Experiment 1, and for their locations in Experiment 2. Intermediate probes were identical in both experiments and were administered during retention on 66.7% of the trials with 50% resolvable and 50% irresolvable/misleading probes. Experiment 1 revealed the efficacy of the employed stimuli by revealing a general impairment of high- compared to low checkers, which confirmed the ecological validity of our stimuli. In Experiment 2 we observed the expected, more differentiated pattern: High checkers were not generally affected in their WM performance (i.e., no general capacity issue); instead they showed a particular impairment in the misleading distractor-probe condition. Also, high checkers’ confidence ratings were indicative of a general impairment in metacognitive functioning. We discuss how specific executive dysfunction and general metacognitive impairment may affect memory traces in the short- and in the long-term.

Placebo expectancy effects in the relationship between glucose and cognition

The present study investigated the extent of expectancy in the ability of glucose to affect cognitive performance. Using a within-subjects design, subjects (n 26) completed four experimental sessions (in counterbalanced order and after an initial practice session) during which they were given a 500 ml drink 30 min prior to completing a cognitive assessment battery. In addition, all subjects completed a baseline practice session during which they were given no drink. During two of the sessions, subjects were given a drink containing 50 g glucose and on the other two they were given a drink containing aspartame. A balanced placebo design was used, such that for half the sessions subjects were accurately informed as to the content of the drink (glucose or aspartame), whereas in the other two sessions they were misinformed as to the content of the drink. The task battery comprised a 6 min visual analogue of the Bakan vigilance task, an immediate verbal free-recall task, an immediate verbal recognition memory task and a measure of motor speed (two-finger tapping). Blood glucose and self-reported mood were also recorded at several time points during each session. Glucose administration was found to improve recognition memory times, in direct contrast to previous findings in the literature. Glucose administration also improved performance on the Bakan task (relative to the control drink), but only in sessions where subjects were informed that they would receive glucose and not when they were told that they would receive aspartame. There were no effects either of the nature of the drink or expectancy on the other measures. These results are interpreted in terms of there being some contribution of expectancy concerning the positive effects of glucose on cognition in studies which have not used an equi-sweet dose of aspartame as a control drink.

On the persuadability of memory:is changing people's memories no more than changing their minds?

The observation of parallels between the memory distortion and persuasion literatures leads, quite logically, to the appealing notion that people can be 'persuaded' to change their memories. Indeed, numerous studies show that memory can be influenced and distorted by a variety of persuasive tactics, and the theoretical accounts commonly used by researchers to explain episodic and autobiographical memory distortion phenomena can generally predict and explain these persuasion effects. Yet, despite these empirical and theoretical overlaps, explicit reference to persuasion and attitude-change research in the memory distortion literature is surprisingly rare. In this paper, we argue that stronger theoretical foundations are needed to draw the memory distortion and persuasion literatures together in a productive direction. We reason that theoretical approaches to remembering that distinguish (false) beliefs in the occurrence of events from (false) memories of those events - compatible with a source monitoring approach - would be beneficial to this end. Such approaches, we argue, would provide a stronger platform to use persuasion findings to enhance the psychological understanding of memory distortion.

Weakly-constrained codes for suppression of patterning effects in digital communications

We propose weakly-constrained stream and block codes with tunable pattern-dependent statistics and demonstrate that the block code capacity at large block sizes is close to the the prediction obtained from a simple Markov model published earlier. We demonstrate the feasibility of the code by presenting original encoding and decoding algorithms with a complexity log-linear in the block size and with modest table memory requirements. We also show that when such codes are used for mitigation of patterning effects in optical fibre communications, a gain of about 0.5dB is possible under realistic conditions, at the expense of small redundancy 10%). © 2006 IEEE.

Memory conformity: Actors and bystanders

This dissertation explored memory conformity effects on people who interacted with a confederate and of bystanders to that interaction. Two studies were carried out. Study 1 was conducted in the field. A male confederate approached a group of people at the beach and had a brief interaction. About a minute later a research assistant approached the group and administered a target-absent lineup to each person in the group. Analyses revealed that memory conformity occurred during the lineup task. Bystanders were twice as likely to conform as those who interacted with the confederate. Study 2 was carried out in a laboratory under controlled conditions. Participants were exposed to two events during their time in the laboratory. In one event, participants were shown a brief video with no determinate roles assigned. In the other event participants were randomly assigned to interact with a confederate (actor condition) or to witness that interaction (bystander condition). Participants were given memory tests on both events to understand the effects of participant role (actor vs. bystander) on memory conformity. Participants answered second to all questions, following a confederate acting as a participant, who disseminated misinformation on critical questions. Analyses revealed no significant differences in memory conformity between actors and bystanders during the movie memory task. However, differences were found for the interaction memory task such that bystanders conformed more than actors on two of four critical questions. Bystanders also conformed more than actors during a lineup identification task. The results of these studies suggest that the role a person plays in an interaction affects how susceptible they are to information from a co-witness. Theoretical and applied implications are discussed. First, the results are explained through the use of two models of memory. Second, recommendations are made for forensic investigators.

Patterns and effects of notetaking by learning -disabled and nondisabled adolescents: A comparative study

This study analyzes the qualitative and quantitative patterns of notetaking by learning disabled (LD) and nondisabled (ND) adolescents and the effectiveness of notetaking and review as measured by the subjects' ability to recall information presented during a lecture. The study also examines relationships between certain learner characteristics and notetaking. The following notetaking variables were investigated: note completeness, number of critical ideas recorded, levels of processing information, organizational strategies, fluency of notes, and legibility of notes. The learner characteristics examined pertained to measures on achievement, short-term memory, listening comprehension, and verbal ability.^ Students from the 11th and 12th grades were randomly selected from four senior high schools in Dade County, Florida. Seventy learning disabled and 79 nondisabled subjects were shown a video tape lecture and required to take notes. The lecture conditions controlled for presentation rate, prior knowledge, information density, and difficulty level. After 8 weeks, their notes were returned to the subjects for a review period, and a posttest was administered.^ Results of this study suggest significant differences (p $\le$.01) in the patterns of notetaking between LD and ND groups not due to differences in the learner characteristics listed above. In addition, certain notetaking variables such as process levels, number of critical ideas, and note completeness were found to be significantly correlated to learning outcome. Further, deficiencies in the spontaneous use of organizational strategies and abbreviations adversely affected the notetaking effectiveness of learning disabled students.^ Both LD and ND subjects recalled more information recorded in their notes than not recorded. This difference was significant only for the ND group. By contrast, LD subjects compensated for their poor notetaking skills and recalled significantly more information not recorded on their notes than did ND subjects. The major implications of these findings suggest that LD and ND subjects exhibit very different entry behaviors when asked to perform a notetaking task; hence, teaching approaches to notetaking must differ as well. ^

Advertising effects on brand search and preference: Assessing the mediational role of *Aad and *Ab

Most advertising research has focussed at examining effects of advertising on attitudinal responses or brand preference and choice. However, in a natural environment, the time period between advertising exposure and purchase decision is filled with prepurchase search. Prepurchase external search refers to information search from sources other than memory, prior to making a purchase decision. Usually consumers access only a small subset of available information and base their choice decisions on it. Prepurchase search therefore acts as a filter and, the final choice depends critically on the small subset of potential inputs the consumer notes in the environment and integrates into the decision. Previous research has identified a variety of factors that affect consumers' prepurchase search behavior. However, there is little understanding of how specific advertisements designed by marketers impact consumers' prepurchase search. A marketer would like consumers to search information that reflects favorably on his/her brand. Hence, s/he would attempt to influence the brands and attributes on which consumers seek information prior to making a choice. The dissertation investigates the process by which a particular marketer's advertising influences consumers' search on available brands, i.e., the marketer's brand and other competing brands. The dissertation considers a situation where exposure to advertising occurs prior to seeking information from any other source. Hence, the impact of advertising on subsequent search behavior is the topic of interest. The dissertation develops a conceptual model of advertising effects on brand search and conducts two experiments to test the tenets of this model. Specifically, the dissertation demonstrates that attitudinal responses generated by advertising mediate advertising effects on search attitudes and behaviors. The dissertation goes on to examine how attitudinal responses generated by advertising and subsequent effects on search alter brand preference and choice. ^

Realized Matrix-Exponential Stochastic Volatility with Asymmetry, Long Memory and Spillovers

The paper develops a novel realized matrix-exponential stochastic volatility model of multivariate returns and realized covariances that incorporates asymmetry and long memory (hereafter the RMESV-ALM model). The matrix exponential transformation guarantees the positivedefiniteness of the dynamic covariance matrix. The contribution of the paper ties in with Robert Basmann’s seminal work in terms of the estimation of highly non-linear model specifications (“Causality tests and observationally equivalent representations of econometric models”, Journal of Econometrics, 1988, 39(1-2), 69–104), especially for developing tests for leverage and spillover effects in the covariance dynamics. Efficient importance sampling is used to maximize the likelihood function of RMESV-ALM, and the finite sample properties of the quasi-maximum likelihood estimator of the parameters are analysed. Using high frequency data for three US financial assets, the new model is estimated and evaluated. The forecasting performance of the new model is compared with a novel dynamic realized matrix-exponential conditional covariance model. The volatility and co-volatility spillovers are examined via the news impact curves and the impulse response functions from returns to volatility and co-volatility.

Memory-Based Attentional Guidance: A Window to the Relationship between Working Memory and Attention

Attention, the cognitive means by which we prioritize the processing of a subset of information, is necessary for operating efficiently and effectively in the world. Thus, a critical theoretical question is how information is selected. In the visual domain, working memory (WM)—which refers to the short-term maintenance and manipulation of information that is no longer accessible by the senses—has been highlighted as an important determinant of what is selected by visual attention. Furthermore, although WM and attention have traditionally been conceived as separate cognitive constructs, an abundance of behavioral and neural evidence indicates that these two domains are in fact intertwined and overlapping. The aim of this dissertation is to better understand the nature of WM and attention, primarily through the phenomenon of memory-based attentional guidance, whereby the active maintenance of items in visual WM reliably biases the deployment of attention to memory-matching items in the visual environment. The research presented here employs a combination of behavioral, functional imaging, and computational modeling techniques that address: (1) WM guidance effects with respect to the traditional dichotomy of top-down versus bottom-up attentional control; (2) under what circumstances the contents of WM impact visual attention; and (3) the broader hypothesis of a predictive and competitive interaction between WM and attention. Collectively, these empirical findings reveal the importance of WM as a distinct factor in attentional control and support current models of multiple-state WM, which may have broader implications for how we select and maintain information.

Optimizing the Correction of Memory Errors

People are always at risk of making errors when they attempt to retrieve information from memory. An important question is how to create the optimal learning conditions so that, over time, the correct information is learned and the number of mistakes declines. Feedback is a powerful tool, both for reinforcing new learning and correcting memory errors. In 5 experiments, I sought to understand the best procedures for administering feedback during learning. First, I evaluated the popular recommendation that feedback is most effective when given immediately, and I showed that this recommendation does not always hold when correcting errors made with educational materials in the classroom. Second, I asked whether immediate feedback is more effective in a particular case—when correcting false memories, or strongly-held errors that may be difficult to notice even when the learner is confronted with the feedback message. Third, I examined whether varying levels of learner motivation might help to explain cross-experimental variability in feedback timing effects: Are unmotivated learners less likely to benefit from corrective feedback, especially when it is administered at a delay? Overall, the results revealed that there is no best “one-size-fits-all” recommendation for administering feedback; the optimal procedure depends on various characteristics of learners and their errors. As a package, the data are consistent with the spacing hypothesis of feedback timing, although this theoretical account does not successfully explain all of the data in the larger literature.

Expectation Modulates Episodic Memory Formation via Dopaminergic Circuitry

Episodic memory formation is shaped by expectation. Events that generate expectations have the capacity to influence memory. Additionally, whether subsequent events meet or violate expectations has consequences for memory. However, clarification is still required to illuminate the circumstances and direction of memory modulation. In the brain, the mechanisms by which expectation modulates memory formation also require consideration. The dopamine system has been implicated in signaling events associated with different states of expectancy; it has also been shown to modulate episodic memory formation in the hippocampus. Thus, the studies included in this dissertation utilized both functional magnetic resonance imaging (fMRI) and behavioral testing to examine when and how the dopaminergic system supports the modulation of memory by expectation. The work aimed to characterize the activation of dopaminergic circuitry in response to cues that generate expectancy, during periods of anticipation, and in response to outcomes that resolve expectancy. The studies also examined how each of these event types influenced episodic memory formation. The present findings demonstrated that novelty and expectancy violation both drive dopaminergic circuitry capable of contributing to memory formation. Consistent with elevated dopaminergic midbrain and hippocampus activation for each, expected versus expectancy violating novelty did not differentially affect memory success. We also showed that high curiosity expectancy states drive memory formation. This was supported by activation in dopaminergic circuitry that was greater for subsequently remembered information only in the high curiosity state. Finally, we showed that cues that generate high expected reward value versus high reward uncertainty differentially modulate memory formation during reward anticipation. This behavioral result was consistent with distinct temporal profiles of dopaminergic action having differential downstream effects on episodic memory formation. Integrating the present studies with previous research suggests that dopaminergic circuitry signals events that are unpredicted, whether cuing or resolving expectations. It also suggests that contextual differences change the contribution of the dopaminergic system during anticipation, depending on the nature of the expectation. And finally, this work is consistent with a model in which dopamine elevation in response to expectancy events positively modulates episodic memory formation.

Role of Dopamine D2 Receptors in the Consolidation of Amphetamine-Cue Memory in Conditioned Activity in Rats

The neurotransmitter dopamine (DA) plays an essential role in reward-related incentive learning, whereby neutral stimuli gain the ability to elicit approach and other responses. In an incentive learning paradigm called conditioned activity, animals receive a stimulant drug in a specific environment over the course of several days. When then placed in that environment drug-free, they generally display a conditioned hyperactive response. Modulating DA transmission at different time points during the paradigm has been shown to disrupt or enhance conditioning effects. For instance, blocking DA D2 receptors before sessions generally impedes the acquisition of conditioned activity. To date, no studies have examined the role of D2 receptors in the consolidation phase of conditioned activity; this phase occurs immediately after acquisition and involves the stabilization of memories for long-term storage. To investigate this possible role, I trained Wistar rats (N = 108) in the conditioned activity paradigm produced by amphetamine (2.0 mg/kg, intraperitoneally) to examine the effects of the D2 antagonist haloperidol (doses 0.10, 0.25, 0.50, 0.75, 1.0, & 2.0 mg/kg, intraperitoneally) administered 5 min after conditioning sessions. Two positive control groups received haloperidol 1 h before conditioning sessions (doses 1.0 mg/kg and 2.0 mg/kg). The results revealed that post-session haloperidol at all doses tested did not disrupt the consolidation of conditioned activity, while pre-session haloperidol at 2.0 mg/kg prevented acquisition, with the 1.0 mg/kg group trending toward a block. Additionally, post-session haloperidol did not diminish activity during conditioning days, unlike pre-session haloperidol. One possible reason for these findings is that the consolidation phase may have begun earlier than when haloperidol was administered, since the conditioned activity paradigm uses longer learning sessions than those generally used in consolidation studies. Future studies may test if conditioned activity can be achieved with shorter sessions; if so, haloperidol would then be re-tested at an earlier time point. D2 receptor second messenger systems may also be investigated in consolidation. Since drug-related incentive stimuli can evoke cravings in those with drug addiction, a better understanding of the mechanisms of incentive learning may lead to the development of solutions for these individuals.

Electrophysiological study of the effects of arginine vasopressin in the rat juxtacapsular nucleus of the bed nucleus of the stria terminalis

Arginine vasopressin (AVP), a nine amino acid neuropeptide (CYFQNCPRG- NH2) fulfills a dual function: (i) in the periphery, AVP acts as a peptide hormone and (ii) in the CNS, AVP is a neuromodulatory peptide. AVP produces its effects through 3 AVP receptors (AVPRs). AVPR1a and AVPR1b are expressed in the CNS and periphery, whilst AVPR2 is not found centrally but instead solely expressed in the kidneys. Recent evidence revealed a high density of AVP-binding sites in the juxtacapsular nucleus of the bed nucleus of the stria terminalis (jxBNST). While in other regions of the brain, AVP acts at AVPRs to regulate an array of biological processes, including male-typical social behaviours, social memory, stress adaptation, fear, anxiety, and fluid homeostasis, its role in the jxBNST remains elusive. Furthermore, the neurophysiological properties of AVP in the jxBNST are unknown so this study aimed to examine how AVP modulates synaptic transmission in the rat jxBNST. The BNST being one of the most notable sexually dimorphic brain regions and AVPR expression being influenced by gonadal steroids, we investigated the putative influence of sex on the modulatory effects of AVP in the jxBNST. Finally, due to AVP being released at a substantially higher concentration following periods of water deprivation, we examined changes in AVPs modulatory role following water deprivation. Male and female Long Evans rats were euthanized and brain slice whole-cell voltage-clamp electrophysiology was done in the jxBNST to measure the effects of AVP on synaptic transmission of GABA synapses. Exogenous application of AVP produced three responses; either postsynaptic long-term potentiation (LTP) of GABAA-inhibitory postsynaptic currents (IPSC), postsynaptic long-term depression (LTD) of GABAA-IPSC, or no change in GABAA-IPSC amplitudes. Interestingly, the proportion of neurons responding in each of these ways did not differ between sexes and within females was not estrous cycle-dependent. Finally, although not statistically significant, 24-hour water deprivation abolished GABAA-LTD, an effect that was not a consequence of social isolation. Taken together, our data show that AVP modulates GABAA synaptic transmission in the jxBNST in fluid homeostasis- but not sex-dependent manner.