A role for hippocampal PSA-NCAM and NMDA-NR2B receptor function in flavonoid-induced spatial memory improvements in young rats

The increase in incidence and prevalence of neurodegenerative diseases highlights the need for a more comprehensive understanding of how food components may affect neural systems. In particular, flavonoids have been recognized as promising agents capable of influencing different aspects of synaptic plasticity resulting in improvements in memory and learning in both animals and humans. Our previous studies highlight the efficacy of flavonoids in reversing memory impairments in aged rats, yet little is known about the effects of these compounds in healthy animals, particularly with respect to the molecular mechanisms by which flavonoids might alter the underlying synaptic modifications responsible for behavioral changes. We demonstrate that a 3-week intervention with two dietary doses of flavonoids (Dose I: 8.7 mg/day and Dose II: 17.4 mg/day) facilitates spatial memory acquisition and consolidation (24 recall) (p < 0.05) in young healthy rats. We show for the first time that these behavioral improvements are linked to increased levels in the polysialylated form of the neural adhesion molecule (PSA-NCAM) in the dentate gyrus (DG) of the hippocampus, which is known to be required for the establishment of durable memories. We observed parallel increases in hippocampal NMDA receptors containing the NR2B subunit for both 8.7 mg/day (p < 0.05) and 17.4 mg/day (p < 0.001) doses, suggesting an enhancement of glutamate signaling following flavonoid intervention. This is further strengthened by the simultaneous modulation of hippocampal ERK/CREB/BDNF signaling and the activation of the Akt/mTOR/Arc pathway, which are crucial in inducing changes in the strength of hippocampal synaptic connections that underlie learning. Collectively, the present data supports a new role for PSA-NCAM and NMDA-NR2B receptor on flavonoid-induced improvements in learning and memory, contributing further to the growing body of evidence suggesting beneficial effects of flavonoids in cognition and brain health.

Ethics of care in supporting disabled forced migrants: interactions with professionals and ethical dilemmas in health and social care in the South-East of England

This article explores the interactions between disabled forced migrants with care needs and professionals and the restrictive legal, policy and practice context that health and social care professionals have to confront, based on the findings of a qualitative study with 45 participants in the South-East of England. In-depth interviews were conducted with 15 forced migrants who had diverse impairments and chronic illnesses (8 women and 7 men), 13 family caregivers and 17 support workers and strategic professionals working in social care and the third sector in Slough, Reading and London. The legal status of forced migrants significantly affects their entitlements to health and social care provision, resulting in prolonged periods of destitution for many families. National asylum support policies, difficult working relationships with UK Border Agency, higher eligibility thresholds and reduced social care budgets of local authorities were identified as significant barriers in responding to the support needs of disabled forced migrants and family caregivers. In this context, social workers experienced considerable ethical dilemmas. The research raises profound questions about the potential and limitations of health and social care policies, provision, and practice as means of protection and support in fulfilling the human rights of forced migrants with care needs.

The anterior temporal lobes support residual comprehension in Wernicke’s aphasia

Wernicke’s aphasia occurs following a stroke to classical language comprehension regions in the left temporoparietal cortex. Consequently, auditory-verbal comprehension is significantly impaired in Wernicke’s aphasia but the capacity to comprehend visually presented materials (written words and pictures) is partially spared. This study used fMRI to investigate the neural basis of written word and picture semantic processing in Wernicke’s aphasia, with the wider aim of examining how the semantic system is altered following damage to the classical comprehension regions. Twelve participants with Wernicke’s aphasia and twelve control participants performed semantic animate-inanimate judgements and a visual height judgement baseline task. Whole brain and ROI analysis in Wernicke’s aphasia and control participants found that semantic judgements were underpinned by activation in the ventral and anterior temporal lobes bilaterally. The Wernicke’s aphasia group displayed an “over-activation” in comparison to control participants, indicating that anterior temporal lobe regions become increasingly influential following reduction in posterior semantic resources. Semantic processing of written words in Wernicke’s aphasia was additionally supported by recruitment of the right anterior superior temporal lobe, a region previously associated with recovery from auditory-verbal comprehension impairments. Overall, the results concord with models which indicate that the anterior temporal lobes are crucial for multimodal semantic processing and that these regions may be accessed without support from classic posterior comprehension regions.

Genetic variation in the oxytocin receptor (OXTR) gene is associated with Asperger Syndrome

Background Autism Spectrum Conditions (ASC) are a group of neurodevelopmental conditions characterized by impairments in communication and social interaction, alongside unusually repetitive behaviors and narrow interests. ASC are highly heritable and have complex patterns of inheritance where multiple genes are involved, alongside environmental and epigenetic factors. Asperger Syndrome (AS) is a subgroup of these conditions, where there is no history of language or cognitive delay. Animal models suggest a role for oxytocin (OXT) and oxytocin receptor (OXTR) genes in social-emotional behaviors, and several studies indicate that the oxytocin/oxytocin receptor system is altered in individuals with ASC. Previous studies have reported associations between genetic variations in the OXTR gene and ASC. Methods The present study tested for an association between nine single nucleotide polymorphisms (SNPs) in the OXTR gene and AS in 530 individuals of Caucasian origin, using SNP association test and haplotype analysis. Results There was a significant association between rs2268493 in OXTR and AS. Multiple haplotypes that include this SNP (rs2268493-rs2254298, rs2268490-rs2268493-rs2254298, rs2268493-rs2254298-rs53576, rs237885-rs2268490-rs2268493-rs2254298, rs2268490-rs2268493-rs2254298-rs53576) were also associated with AS. rs2268493 has been previously associated with ASC and putatively alters several transcription factor-binding sites and regulates chromatin states, either directly or through other variants in linkage disequilibrium (LD). Conclusions This study reports a significant association of the sequence variant rs2268493 in the OXTR gene and associated haplotypes with AS.

Memory for medication side effects in younger and older adults: the role of subjective and objective importance

Older adults often experience memory impairments, but can sometimes use selective processing and schematic support to remember important information. The current experiments investigate to what degree younger and healthy older adults remember medication side effects that were subjectively or objectively important to remember. Participants studied a list of common side effects, and rated how negative these effects were if they were to experience them, and were then given a free recall test. In Experiment 1, the severity of the side effects ranged from mild (e.g., itching) to severe (e.g., stroke), and in Experiment 2, certain side effects were indicated as critical to remember (i.e., “contact your doctor if you experience this”). There were no age differences in terms of free recall of the side effects, and older adults remembered more severe side effects relative to mild effects. However, older adults were less likely to recognize critical side effects on a later recognition test, relative to younger adults. The findings suggest that older adults can selectively remember medication side effects, but have difficulty identifying familiar but potentially critical side effects, and this has implications for monitoring medication use in older age.

Parenting difficulties and postnatal depression: implications for primary healthcare assessment and intervention

Postnatal depression (PND) is associated with impairments in the mother–child relationship, and these impairments are themselves associated with adverse child outcomes. Thus, compared to the children of non-depressed mothers, children of mothers with PND are more likely to be insecurely attached, and to have externalising behaviour problems and poor cognitive development. Each of these three child outcomes is predicted by a particular pattern of difficulty in parenting: insecure attachment is related to maternal insensitivity, particularly in relation to infant distress and emotional vulnerability; externalising problems are particularly common in the context of hostile parenting; and poor cognitive development is related to parental difficulties in noticing infant signs of interest and supporting their engagement with the environment. This article sets out procedures for how parenting could be assessed in ways that are sensitive to the domain-specific associations between parenting and child outcome, while remaining sensitive to the child's developmental stage. This set of assessments requires field testing.

Memo test: standardisation of computerised assessment of auditory verbal short-term memory

Short-term memory (STM) impairments are prevalent in adults with acquired brain injuries. While there are several published tests to assess these impairments, the majority require speech production, e.g. digit span (Wechsler, 1987). This feature may make them unsuitable for people with aphasia and motor speech disorders because of word finding difficulties and speech demands respectively. If patients perceive the speech demands of the test to be high, the may not engage with testing. Furthermore, existing STM tests are mainly ‘pen-and-paper’ tests, which can jeopardise accuracy. To address these shortcomings, we designed and standardised a novel computerised test that does not require speech output and because of the computerised delivery it would enable clinicians identify STM impairments with greater precision than current tests. The matching listening span tasks, similar to the non-normed PALPA 13 (Kay, Lesser & Coltheart, 1992) is used to test short-term memory for serial order of spoken items. Sequences of digits are presented in pairs. The person hears the first sequence, followed by the second sequence and s/he decides whether the two sequences are the same or different. In the computerised test, the sequences are presented in live voice recordings on a portable computer through a software application (Molero Martin, Laird, Hwang & Salis 2013). We collected normative data from healthy older adults (N=22-24) using digits, real words (one- and two-syllables) and non-words (one- and two- syllables). Their performance was scored following two systems. The Highest Span system was the highest span length (e.g. 2-8) at which a participant correctly responded to over 7 out of 10 trials at the highest sequence length. Test re-test reliability was also tested in a subgroup of participants. The test will be available as free of charge for clinicians and researchers to use.

Serotonin transporter [corrected] methylation and response to cognitive behaviour therapy in children with anxiety disorders

Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT.

Latent learning in end stage renal disease (ESRD)

Cognitive functions such as attention and memory are known to be impaired in End Stage Renal Disease (ESRD), but the sites of the neural changes underlying these impairments are uncertain. Patients and controls took part in a latent learning task, which had previously shown a dissociation between patients with Parkinson’s disease and those with medial temporal damage. ESRD patients (n=24) and age and education-matched controls (n=24) were randomly assigned to either an exposed or unexposed condition. In Phase 1 of the task, participants learned that a cue (word) on the back of a schematic head predicted that the subsequently seen face would be smiling. For the exposed (but not unexposed) condition, an additional (irrelevant) colour cue was shown during presentation. In Phase 2, a different association, between colour and facial expression, was learned. Instructions were the same for each phase: participants had to predict whether the subsequently viewed face was going to be happy or sad. No difference in error rate between the groups was found in Phase 1, suggesting that patients and controls learned at a similar rate. However, in Phase 2, a significant interaction was found between group and condition, with exposed controls performing significantly worse than unexposed (therefore demonstrating learned irrelevance). In contrast, exposed patients made a similar number of errors to unexposed in Phase 2. The pattern of results in ESRD was different from that previously found in Parkinson’s disease, suggesting a different neural origin.

Imbalanced functional link between executive control network and reward network explain the online-game seeking behaviors in Internet gaming disorder

Literatures have shown that Internet gaming disorder (IGD) subjects show impaired executive control and enhanced reward sensitivities than healthy controls. However, how these two networks jointly affect the valuation process and drive IGD subjects' online-game-seeking behaviors remains unknown. Thirty-five IGD and 36 healthy controls underwent a resting-states scan in the MRI scanner. Functional connectivity (FC) was examined within control and reward network seeds regions, respectively. Nucleus accumbens (NAcc) was selected as the node to find the interactions between these two networks. IGD subjects show decreased FC in the executive control network and increased FC in the reward network when comparing with the healthy controls. When examining the correlations between the NAcc and the executive control/reward networks, the link between the NAcc - executive control network is negatively related with the link between NAcc - reward network. The changes (decrease/increase) in IGD subjects' brain synchrony in control/reward networks suggest the inefficient/overly processing within neural circuitry underlying these processes. The inverse proportion between control network and reward network in IGD suggest that impairments in executive control lead to inefficient inhibition of enhanced cravings to excessive online game playing. This might shed light on the mechanistic understanding of IGD.

A pooled genome-wide association study of Asperger Syndrome

Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

Thirst for knowledge: the effects of curiosity and interest on memory in younger and older adults

Given age-related memory impairments, one’s level of curiosity or interest could enhance memory for certain information. In the current study, younger and older adults read trivia questions, rated how curious they were to learn each answer, provided confidence and interest ratings, and judgments of learning (JOL) after learning the answer. No age-related differences in memory were found. Analyses indicated that curiosity and interest contributed to the formation of JOLs. Additionally, interest had a unique increasing relationship with older, but not younger, adults’ memory performance after a week. The results suggest that subjective interest may serve to enhance older adults’ memory.

I owe you: age-related similarities and differences in associative memory for gains and losses

Older adults often experience associative memory impairments but can sometimes remember important information. The current experiments investigate potential age-related similarities and differences associate memory for gains and losses. Younger and older participants were presented with faces and associated dollar amounts, which indicated how much money the person “owed” the participant, and were later given a cued recall test for the dollar amount. Experiment 1 examined face-dollar amount pairs while Experiment 2 included negative dollar amounts to examine both gains and losses. While younger adults recalled more information relative to older adults, both groups were more accurate in recalling the correct value associated with high value faces compared to lower value faces and remembered gist-information about the values. However, negative values (losses) did not have a strong impact on recall among older adults versus younger adults, illustrating important associative memory differences between younger and older adults.

An analysis of pre-reading strategies in deaf/hard of hearing students

This literature review evaluates print knowledge ability in normally hearing pre-readers with and without specific language impairments. It then discusses implications of print knowledge ability in students who are deaf or hard of hearing and early intervention strategies.

Differential regulation of FGF-2 in neurons and reactive astrocytes of axotomized rat hypoglossal nucleus. A possible therapeutic target for neuroprotection in peripheral nerve pathology

Despite the favorable treatment of cranial nerve neuropathology in adulthood, some cases are resistant to therapy leading to permanent functional impairments In many cases, suitable treatment is problematic as the therapeutic target remains unknown Basic fibroblast growth factor (bFGF, FGF 2) is involved in neuronal maintenance and wound repair following nervous system lesions It is one of few neurotrophic molecules acting in autocrine, paracrine and intracrine fashions depending upon specific circumstances Peripheral cranial somatic motor neurons, i e hypoglossal (XII) neurons, may offer a unique opportunity to study cellular FGF 2 mechanisms as the molecule is present in the cytoplasm of neurons and in the nuclei of astrocytes of the central nervous system FGF-2 may trigger differential actions during development, maintenance and lesion of XII neurons because axotomy of those cells leads to cell death during neonatal ages, but not in adult life Moreover, the modulatory effects of astroglial FGF 2 and the Ca+2 binding protein S100 beta have been postulated in paracrine mechanisms after neuronal lesions In our study, adult Wistar rats received a unilateral crush or transection (with amputation of stumps) of XII nerve, and were sacrificed after 72 h or 11 days Brains were processed for immunohistochemical localization of neurofilaments (NF), with or without counterstaining for Nissl substance, ghat fibrillary acidic protein (GFAP, as a marker of astrocytes), S100 beta and FGF-2 The number of Nissl positive neurons of axotomized XII nucleus did not differ from controls The NF immunoreactivity increased in the perikarya and decreased in the neuropil of axotomized XII neurons 11 days after nerve crush or transection An astrocytic reaction was seen in the ipsilateral XII nucleus of the crushed or transected animals 72 h and 11 days after the surgery The nerve lesions did not change the number of FGF-2 neurons in the ipsilateral XII nucleus, however, the nerve transection increased the number of FGF-2 ghat profiles by 72 h and 11 days Microdensitometric image analysis revealed a short lasting decrease in the intensity of FGF 2 immunoreactivity in axotomized XII neurons by 72 h after nerve crush or transection and also an elevation of FGF-2 in the ipsilateral of ghat nuclei by 72h and 11 days after the two lesions S100 beta decreased in astrocytes of 11-day transected XII nucleus The two-color immunoperoxidase for the simultaneous detection of the GFAP/FGF-2 indicated FGF-2 upregulation in the nuclei of reactive astrocytes of the lesioned XII nucleus Astroglial FGF-2 may exert paracrine trophic actions in mature axotomized XII neurons and might represent a therapeutic target for neuroprotection in peripheral nerve pathology (C) 2009 Elsevier GmbH All rights reserved