The influence of eating psychopathology on autobiographical memory specificity and social problem-solving

The primary aim was to examine to influence of subclinical disordered eating on autobiographical memory specificity (AMS) and social problem solving (SPS). A further aim was to establish if AMS mediated the relationship between eating psychopathology and SPS. A non-clinical sample of 52 females completed the autobiographical memory test (AMT), where they were asked to retrieve specific memories of events from their past in response to cue words, and the means-end problem-solving task (MEPS), where they were asked to generate means of solving a series of social problems. Participants also completed the Eating Disorders Inventory (EDI) and Hospital Anxiety and Depression Scale. After controlling for mood, high scores on the EDI subscales, particularly Drive-for-Thinness, were associated with the retrieval of fewer specific and a greater proportion of categorical memories on the AMT and with the generation of fewer and less effective means on the MEPS. Memory specificity fully mediated the relationship between eating psychopathology and SPS. These findings have implications for individuals exhibiting high levels of disordered eating, as poor AMS and SPS are likely to impact negatively on their psychological wellbeing and everyday social functioning and could represent a risk factor for the development of clinically significant eating disorders.

The development of functional astrocyte-neuron networks derived from stem cells

There is currently great scientific and medical interest in the potential of tissue grown from stem cells. These cells present opportunities for generating model systems for drug screening and toxicological testing which would be expected to be more relevant to human outcomes than animal based tissue preparations. Newly realised astrocytic roles in the brain have fundamental implications within the context of stem cell derived neuronal networks. If the aim of stem cell neuroscience is to generate functional neuronal networks that behave as networks do in the brain, then it becomes clear that we must include and understand all the cellular components that comprise that network, and which are important to support synaptic integrity and cell to cell signalling. We have shown that stem cell derived neurons exhibit spontaneous and coordinated calcium elevations in clusters and in extended processes, indicating local and long distance signalling (1). Tetrodotoxin sensitive network activity could also be evoked by electrical stimulation. Similarly, astrocytes exhibit morphology and functional properties consistent with this glial cell type. Astrocytes also respond to neuronal activity and to exogenously applied neurotransmitters with calcium elevations, and in contrast to neurons, also exhibited spontaneous rhythmic calcium oscillations. Astroctyes also generate propagating calcium waves that are gap junction and purinergic signalling dependent. Our results show that stem cell derived astrocytes exhibit appropriate functionality and that stem cell neuronal networks interact with astrocytic networks in co-culture. Using mixed cultures of stem cell derived neurons and astrocytes, we have also shown both cell types also modulate their glucose uptake, glycogen turnover and lactate production in response to glutamate as well as increased neuronal activity (2). This finding is consistent with their neuron-astrocyte metabolic coupling thus demonstrating a tractable human model, which will facilitate the study of the metabolic coupling between neurons and astrocytes and its relationship with CNS functional issues ranging from plasticity to neurodegeneration. Indeed, cultures treated with oligomers of amyloid beta 1-42 (Aβ1-42) also display a clear hypometabolism, particularly with regard to utilization of substrates such as glucose (3). Both co-cultures of neurons and astrocytes and purified cultures of astrocytes showed a significant decrease in glucose uptake after treatment with 2 and 0.2 μmol/L Aβ at all time points investigated (p <0.01). In addition, a significant increase in the glycogen content of cells was also measured. Mixed neuron and astrocyte co-cultures as well as pure astrocyte cultures showed an initial decrease in glycogen levels at 6 hours compared with control at 0.2 μmol/L and 2 μmol/L P <0.01. These changes were accompanied by changes in NAD+/NADH (P<0.05), ATP (P<0.05), and glutathione levels (P<0.05), suggesting a disruption in the energy-redox axis within these cultures. The high energy demands associated with neuronal functions such as memory formation and protection from oxidative stress put these cells at particular risk from Aβ-induced hypometabolism. As numerous cell types interact in the brain it is important that any in vitro model developed reflects this arrangement. Our findings indicate that stem cell derived neuron and astrocyte networks can communicate, and so have the potential to interact in a tripartite manner as is seen in vivo. This study therefore lays the foundation for further development of stem cell derived neurons and astrocytes into therapeutic cell replacement and human toxicology/disease models. More recently our data provides evidence for a detrimental effect of Aβ on carbohydrate metabolism in both neurons and astrocytes. As a purely in vitro system, human stem cell models can be readily manipulated and maintained in culture for a period of months without the use of animals. In our laboratory cultures can be maintained in culture for up to 12 months months thus providing the opportunity to study the consequences of these changes over extended periods of time relevant to aspects of the disease progression time frame in vivo. In addition, their human origin provides a more realistic in vitro model as well as informing other human in vitro models such as patient-derived iPSC.

Development of face recognition: Infancy to early childhood

Perception and recognition of faces are fundamental cognitive abilities that form a basis for our social interactions. Research has investigated face perception using a variety of methodologies across the lifespan. Habituation, novelty preference, and visual paired comparison paradigms are typically used to investigate face perception in young infants. Storybook recognition tasks and eyewitness lineup paradigms are generally used to investigate face perception in young children. These methodologies have introduced systematic differences including the use of linguistic information for children but not infants, greater memory load for children than infants, and longer exposure times to faces for infants than for older children, making comparisons across age difficult. Thus, research investigating infant and child perception of faces using common methods, measures, and stimuli is needed to better understand how face perception develops. According to predictions of the Intersensory Redundancy Hypothesis (IRH; Bahrick & Lickliter, 2000, 2002), in early development, perception of faces is enhanced in unimodal visual (i.e., silent dynamic face) rather than bimodal audiovisual (i.e., dynamic face with synchronous speech) stimulation. The current study investigated the development of face recognition across children of three ages: 5 – 6 months, 18 – 24 months, and 3.5 – 4 years, using the novelty preference paradigm and the same stimuli for all age groups. It also assessed the role of modality (unimodal visual versus bimodal audiovisual) and memory load (low versus high) on face recognition. It was hypothesized that face recognition would improve across age and would be enhanced in unimodal visual stimulation with a low memory load. Results demonstrated a developmental trend (F(2, 90) = 5.00, p = 0.009) with older children showing significantly better recognition of faces than younger children. In contrast to predictions, no differences were found as a function of modality of presentation (bimodal audiovisual versus unimodal visual) or memory load (low versus high). This study was the first to demonstrate a developmental improvement in face recognition from infancy through childhood using common methods, measures and stimuli consistent across age.

A Brief Chronicle of CD4 as a Biomarker for HIV/AIDS: A Tribute to the Memory of John L. Fahey.

Foundational cellular immunology research of the 1960s and 1970s, together with the advent of monoclonal antibodies and flow cytometry, provided the knowledge base and the technological capability that enabled the elucidation of the role of CD4 T cells in HIV infection. Research identifying the sources and magnitude of variation in CD4 measurements, standardized reagents and protocols, and the development of clinical flow cytometers all contributed to the feasibility of widespread CD4 testing. Cohort studies and clinical trials provided the context for establishing the utility of CD4 for prognosis in HIV-infected persons, initial assessment of in vivo antiretroviral drug activity, and as a surrogate marker for clinical outcome in antiretroviral therapeutic trials. Even with sensitive HIV viral load measurement, CD4 cell counting is still utilized in determining antiretroviral therapy eligibility and time to initiate therapy. New point of care technologies are helping both to lower the cost of CD4 testing and enable its use in HIV test and treat programs around the world.

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.

Mem Tri: Memory Forensics Triage Tool

This work explores the development of MemTri. A memory forensics triage tool that can assess the likelihood of criminal activity in a memory image, based on evidence data artefacts generated by several applications. Fictitious illegal suspect activity scenarios were performed on virtual machines to generate 60 test memory images for input into MemTri. Four categories of applications (i.e. Internet Browsers, Instant Messengers, FTP Client and Document Processors) are examined for data artefacts located through the use of regular expressions. These identified data artefacts are then analysed using a Bayesian Network, to assess the likelihood that a seized memory image contained evidence of illegal activity. Currently, MemTri is under development and this paper introduces only the basic concept as well as the components that the application is built on. A complete description of MemTri coupled with extensive experimental results is expected to be published in the first semester of 2017.

Increased hippocampal excitability and impaired spatial memory function in mice lacking VGLUT2 selectively in neurons defined by tyrosine hydroxylase promoter activity

Three populations of neurons expressing the vesicular glutamate transporter 2 (Vglut2) were recently described in the A10 area of the mouse midbrain, of which two populations were shown to express the gene encoding, the rate-limiting enzyme for catecholamine synthesis, tyrosine hydroxylase (TH).One of these populations (‘‘TH– Vglut2 Class1’’) also expressed the dopamine transporter (DAT) gene while one did not ("TH–Vglut2 Class2"), and the remaining population did not express TH at all ("TH-Vglut2-only"). TH is known to be expressed by a promoter which shows two phases of activation, a transient one early during embryonal development, and a later one which gives rise to stable endogenous expression of the TH gene. The transient phase is, however, not specific to catecholaminergic neurons, a feature taken to advantage here as it enabled Vglut2 gene targeting within all three A10 populations expressing this gene, thus creating a new conditional knockout. These knockout mice showed impairment in spatial memory function. Electrophysiological analyses revealed a profound alteration of oscillatory activity in the CA3 region of the hippocampus. In addition to identifying a novel role for Vglut2 in hippocampus function, this study points to the need for improved genetic tools for targeting of the diversity of subpopulations of the A10 area

New tools for cognitive and motor rehabilitation: development and clinical validation

Nervous system disorders are associated with cognitive and motor deficits, and are responsible for the highest disability rates and global burden of disease. Their recovery paths are vulnerable and dependent on the effective combination of plastic brain tissue properties, with complex, lengthy and expensive neurorehabilitation programs. This work explores two lines of research, envisioning sustainable solutions to improve treatment of cognitive and motor deficits. Both projects were developed in parallel and shared a new sensible approach, where low-cost technologies were integrated with common clinical operative procedures. The aim was to achieve more intensive treatments under specialized monitoring, improve clinical decision-making and increase access to healthcare. The first project (articles I – III) concerned the development and evaluation of a web-based cognitive training platform (COGWEB), suitable for intensive use, either at home or at institutions, and across a wide spectrum of ages and diseases that impair cognitive functioning. It was tested for usability in a memory clinic setting and implemented in a collaborative network, comprising 41 centers and 60 professionals. An adherence and intensity study revealed a compliance of 82.8% at six months and an average of six hours/week of continued online cognitive training activities. The second project (articles IV – VI) was designed to create and validate an intelligent rehabilitation device to administer proprioceptive stimuli on the hemiparetic side of stroke patients while performing ambulatory movement characterization (SWORD). Targeted vibratory stimulation was found to be well tolerated and an automatic motor characterization system retrieved results comparable to the first items of the Wolf Motor Function Test. The global system was tested in a randomized placebo controlled trial to assess its impact on a common motor rehabilitation task in a relevant clinical environment (early post-stroke). The number of correct movements on a hand-to-mouth task was increased by an average of 7.2/minute while the probability to perform an error decreased from 1:3 to 1:9. Neurorehabilitation and neuroplasticity are shifting to more neuroscience driven approaches. Simultaneously, their final utility for patients and society is largely dependent on the development of more effective technologies that facilitate the dissemination of knowledge produced during the process. The results attained through this work represent a step forward in that direction. Their impact on the quality of rehabilitation services and public health is discussed according to clinical, technological and organizational perspectives. Such a process of thinking and oriented speculation has led to the debate of subsequent hypotheses, already being explored in novel research paths.

This battle was not over: Parade’s End as a transitional text in the development of ‘disenchanted’ First World War literature.

This chapter argues that the novels of Ford's Parade's End tetralogy occupy a significant place in the development of "disenchanted" fiction about the First World War. The values of Ernest Raymond's patriotic Tell England are contrasted with those of C. E Montague's Disenchantment, providing a brief synopsis of the early 1920s response to the conflict. Parade's End is seen as introducing several key themes in to the post-First World War discursive field, including national identity, psychology, memory, and time. The presentation of these aligned with the formal aspects of the novel, allows it to push the boundaries of the readerly horizon of expectations. Frayn argues that Ford's readership, though moderately-sized, was influential from a literary point of view, and thus facilitated the reception of later, more vitriolic, criticisms of war.

A neuroimaging investigation of the association between aerobic fitness, hippocampal volume and memory performance in preadolescent children

Because children are becoming increasingly overweight, unhealthy and unfit, understanding the neurocognitive benefits of an active lifestyle in childhood has important public health and educational implications. Animal research has indicated that aerobic exercise is related to increased cell proliferation and survival in the hippocampus as well as enhanced hippocampal-dependent learning and memory. Recent evidence extends this relationship to elderly humans by suggesting that high aerobic fitness levels in older adults are associated with increased hippocampal volume and superior memory performance. The present study aimed to further extend the link between fitness, hippocampal volume, and memory to a sample of preadolescent children. To this end, magnetic resonance imaging was employed to investigate whether high- and low-fit 9- and 10-year-old children showed differences in hippocampal volume and if the differences were related to performance on an item and relational memory task. Relational but not item memory is primarily supported by the hippocampus. Consistent with predictions, high-fit children showed greater bilateral hippocampal volumes. Furthermore, hippocampal volume was positively associated with performance on the relational but not the item memory task. The findings are the first to suggest that aerobic fitness can impact the structure and function of the developing human brain.

Increased hippocampal excitability and impaired spatial memory function in mice lacking VGLUT2 selectively in neurons defined by tyrosine hydroxylase promoter activity

Three populations of neurons expressing the vesicular glutamate transporter 2 (Vglut2) were recently described in the A10 area of the mouse midbrain, of which two populations were shown to express the gene encoding, the rate-limiting enzyme for catecholamine synthesis, tyrosine hydroxylase (TH).One of these populations (‘‘TH– Vglut2 Class1’’) also expressed the dopamine transporter (DAT) gene while one did not ("TH–Vglut2 Class2"), and the remaining population did not express TH at all ("TH-Vglut2-only"). TH is known to be expressed by a promoter which shows two phases of activation, a transient one early during embryonal development, and a later one which gives rise to stable endogenous expression of the TH gene. The transient phase is, however, not specific to catecholaminergic neurons, a feature taken to advantage here as it enabled Vglut2 gene targeting within all three A10 populations expressing this gene, thus creating a new conditional knockout. These knockout mice showed impairment in spatial memory function. Electrophysiological analyses revealed a profound alteration of oscillatory activity in the CA3 region of the hippocampus. In addition to identifying a novel role for Vglut2 in hippocampus function, this study points to the need for improved genetic tools for targeting of the diversity of subpopulations of the A10 area

Can Intersensory Redundancy and Social Contingency Enhance Memory in Bobwhite Quail Hatchlings?

Recent findings indicate that bimodal-redundant stimulation promotes perceptual learning and recruits attention to amodal properties in non-human as well as human infants. However it is not clear if bimodal-redundant stimulation can also facilitate memory during the postnatal period. Moreover, most animal and human studies have employed an operant paradigm to study memory, but have not compared the effectiveness of contingent versus passive presentation of information on memory. The current study investigated the role of unimodal versus bimodal presentation and, the role of a contingent versus passive exposure in memory retention in the bobwhite quail (Colinus virginianus). Results revealed that contingently trained chicks demonstrated a preference for the familiarized call under both unimodal and bimodal conditions. Between-group analyses revealed that the contingent-bimodal group preferred the familiarized call as compared to the passive-bimodal group. These results indicate that the contingency paradigm accompanied with the bimodal stimulus type facilitated memory during early development.