Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids

As survival rates of preterm newborns improve as a result of better medical management, these children increasingly show impaired cognition. These adverse cognitive outcomes are associated with decreases in the volume of the cerebellum. Because animals exhibit reduced preterm cerebellar growth after perinatal exposure to glucocorticoids, we sought to determine whether glucocorticoid exposure and other modifiable factors increased the risk for these adverse outcomes in human neonates. We studied 172 preterm neonatal infants from two medical centers, the University of British Columbia and the University of California, San Francisco, by performing serial magnetic resonance imaging examinations near birth and again near term-equivalent age. After we adjusted for associated clinical factors, antenatal betamethasone was not associated with changes in cerebellar volume. Postnatal exposure to clinically routine doses of hydrocortisone or dexamethasone was associated with impaired cerebellar, but not cerebral, growth. Alterations in treatment after preterm birth, particularly glucocorticoid exposure, may help to decrease risk for adverse neurological outcome after preterm birth.

Altered long-range alpha-band synchronization during visual short-term memory retention in children born very preterm

Children born very preterm, even when intelligence is broadly normal, often experience selective difficulties in executive function and visual-spatial processing. Development of structural cortical connectivity is known to be altered in this group, and functional magnetic resonance imaging (fMRI) evidence indicates that very preterm children recruit different patterns of functional connectivity between cortical regions during cognition. Synchronization of neural oscillations across brain areas has been proposed as a mechanism for dynamically assigning functional coupling to support perceptual and cognitive processing, but little is known about what role oscillatory synchronization may play in the altered neurocognitive development of very preterm children. To investigate this, we recorded magnetoencephalographic (MEG) activity while 7-8 year old children born very preterm and age-matched full-term controls performed a visual short-term memory task. Very preterm children exhibited reduced long-range synchronization in the alpha-band during visual short-term memory retention, indicating that cortical alpha rhythms may play a critical role in altered patterns functional connectivity expressed by this population during cognitive and perceptual processing. Long-range alpha-band synchronization was also correlated with task performance and visual-perceptual ability within the very preterm group, indicating that altered alpha oscillatory mechanisms mediating transient functional integration between cortical regions may be relevant to selective problems in neurocognitive development in this vulnerable population at school age.

Neonatal pain, parenting stress and interaction, in relation to cognitive and motor development at 8 and 18 months in preterm infants

Procedural pain in the neonatal intensive care unit triggers a cascade of physiological, behavioral and hormonal disruptions which may contribute to altered neurodevelopment in infants born very preterm, who undergo prolonged hospitalization at a time of physiological immaturity and rapid brain development. The aim of this study was to examine relationships between cumulative procedural pain (number of skin-breaking procedures from birth to term, adjusted for early illness severity and overall intravenous morphine exposure), and later cognitive, motor abilities and behavior in very preterm infants at 8 and 18 months corrected chronological age (CCA), and further, to evaluate the extent to which parenting factors modulate these relationships over time. Participants were N=211 infants (n=137 born preterm 32 weeks gestational age [GA] and n=74 full-term controls) followed prospectively since birth. Infants with significant neonatal brain injury (periventricular leucomalacia, grade 3 or 4 intraventricular hemorrhage) and/or major sensori-neural impairments, were excluded. Poorer cognition and motor function were associated with higher number of skin-breaking procedures, independent of early illness severity, overall intravenous morphine, and exposure to postnatal steroids. The number of skin-breaking procedures as a marker of neonatal pain was closely related to days on mechanical ventilation. In general, greater overall exposure to intravenous morphine was associated with poorer motor development at 8 months, but not at 18 months CCA, however, specific protocols for morphine administration were not evaluated. Lower parenting stress modulated effects of neonatal pain, only on cognitive outcome at 18 months.

Encouraging lifestyle behaviour change in mild cognitive impairment patients:development of appropriate educational material

Objectives: A healthy lifestyle may help maintain cognitive function and reduce the risk of developing dementia. This study employed a focus group approach in order to gain insight into opinions of mild cognitive impairment (MCI) patients, caregivers (CG) and health professionals (HP) regarding lifestyle and its relationship with cognition. The qualitative data were used to design, develop and pilot test educational material (EM) to help encourage lifestyle behaviour change. Method: Data gathering phase: structured interviews were conducted with HP (n = 10), and focus groups with MCI patients (n = 24) and CG (n = 12). EM was developed and pilot tested with a new group of MCI patients (n = 21) and CG (n = 6). Results: HP alluded to the lack of clinical trial evidence for a lifestyle and MCI risk link. Although they felt that lifestyle modifications should be recommended to MCI patients, they appeared hesitant in communicating this information and discussions were often patient-driven. MCI patients lacked awareness of the lifestyle cognition link. Participants preferred EM to be concise, eye-catching and in written format, with personal delivery of information favoured. Most pilot testers approved of the EM but were heterogeneous in terms of lifestyle, willingness to change and support needed to change. Conclusion: MCI patients need to be made more aware of the importance of lifestyle for cognition. EM such as those developed here, which are specifically tailored for this population would be valuable for HP who, currently, appear reticent in initiating lifestyle-related discussions. Following further evaluation, the EM could be used in health promotion activities targeting MCI patients.

Spontaneous and cued gaze-following in autism and Williams syndrome

Background: From a young age the typical development of social functioning relies upon the allocation of attention to socially relevant information, which in turn allows experience at processing such information and thus enhances social cognition. As such, research has attempted to identify the developmental processes that are derailed in some neuro-developmental disorders that impact upon social functioning. Williams syndrome (WS) and Autism are disorders of development that are characterized by atypical yet divergent social phenotypes and atypicalities of attention to people.

Methods: We used eye tracking to explore how individuals with WS and Autism attended to, and subsequently interpreted, an actor’s eye gaze cue within a social scene. Images were presented for three seconds, initially with an instruction simply to look at the picture. The images were then shown again, with the participant asked to identify the object being looked at. Allocation of eye-gaze in each condition was analyzed by ANOVA and accuracy of identification was compared with t-tests.

Results: Participants with WS allocated more gaze time to face and eyes than their matched controls both with and without being asked to identify the item being looked at; while participants with Autism spent less time on face and eyes in both conditions. When cued to follow gaze, participants with WS increased gaze to the correct targets, while those with Autism looked more at the face and eyes but did not increase gaze to the correct targets, while continuing to look much more than their controls at implausible targets. Both groups identified fewer objects than their controls.

Conclusions: The atypicalities found are likely to be entwined with the deficits shown in interpreting social cognitive cues from the images. WS and Autism are characterised by atypicalities of social attention that impact upon socio-cognitive expertise but importantly the type of atypicality is syndrome-specific.

L'accord sujet-verbe en français contemporain: une étude de variation grammaticale et sociale

Dans cet article, nous évaluons le rôle du cotexte (les facteurs internes ou linguistiques) et du contexte (les facteurs externes ou sociaux, et la situation de l’interaction) dans l’accord sujet-verbe induit par les expressions de quantité en français contemporain. Dans l’emploi de ces expressions, par exemple la majorité, le reste etc., il existe une variation entre l’accord singulier et le pluriel, qui est liée à une discordance entre le nombre syntaxique et le nombre sémantique de l’expression. Dans un premier temps, nous présentons la méthodologie d’une première enquête dont le but était d’identifier les principaux facteurs internes et externes qui ont une influence sur les accords de ce type. Dans un deuxième temps, nous présentons les résultats pour les facteurs sociaux avant d’en tirer quelques conclusions pour l’étude principale.

Addressing Selective Polypharmacology of Antipsychotic Drugs Targeting the Bioaminergic Receptors through the Receptor Dynamic Conformational Ensembles

Selective polypharmacology, where a drug acts on multiple rather than single molecular targets involved in a disease, emerges to develop a structure-based system biology approach to design drugs selectively targeting a disease-active protein network. We focus on the bioaminergic receptors that belong to the group of integral membrane signalling proteins coupled to the G protein and represent targets for therapeutic agents against schizophrenia and depression. Among them, it has been shown that the serotonin (5-HT2A and 5-HT6), dopamine (D2 and D3) receptors induce a cognition-enhancing effect (group 1), while the histamine (H1) and serotonin (5-HT2C) receptors lead to metabolic side effects and the 5-HT2B serotonin receptor causes pulmonary hypertension (group 2). Thus, the problem arises to develop an approach that allows identifying drugs targeting only the disease-active receptors, i.e. group 1. The recent release of several crystal structures of the bioaminergic receptors, involving the D3 and H1 receptors provides the possibility to model the structures of all receptors and initiate a study of the structural and dynamic context of selective polypharmacology. In this work, we use molecular dynamics simulations to generate a conformational space of the receptors and subsequently characterize its binding properties applying molecular probe mapping. All-against-all comparison of the generated probe maps of the selected diverse conformations of all receptors with the Tanimoto similarity coefficient (Tc) enable to separate the receptors of group 1 from group 2. The pharmacophore built based on the Tc-selected receptor conformations, using the multiple probe maps discovers structural features that can be used to design molecules selective towards the receptors of group 1. The importance of several predicted residues to ligand selectivity is supported by the available mutagenesis and ligand structure-activity relationships studies. In addition, the Tc-selected conformations of the receptors for group 1 show good performance in isolation of known ligands from a random decoy. Our computational structure-based protocol to tackle selective polypharmacology of antipsychotic drugs could be applied for other diseases involving multiple drug targets, such as oncologic and infectious disorders.

Supernatural Beliefs, Unconscious Threat and Judgment Bias in Tibetan Buddhists

Individuals who have been subtly reminded of death display heightened in-group favouritism, or “worldview defense.” Terror management theory argues (i) that death cues engender worldview defense via psychological mechanisms specifically evolved to suppress death anxiety, and (ii) that the core function of religiosity is to suppress death anxiety. Thus, terror management theory predicts that extremely religious individuals will not evince worldview defense. Here, two studies are presented in support of an alternative perspective. According to the unconscious vigilance hypothesis, subtly processed threats (which need not pertain to death) heighten sensitivity to affectively valenced stimuli (which need not pertain to cultural attitudes). From this perspective, religiosity mitigates the influence of mortality-salience only insofar as afterlife doctrines reduce the perceived threat posed by death. Tibetan Buddhism portrays death as a perilous gateway to rebirth rather than an end to suffering; faith in this doctrine should therefore not be expected to nullify mortality-salience effects. In Study 1, devout Tibetan Buddhists who were subtly reminded of death produced exaggerated aesthetic ratings unrelated to cultural worldviews. In Study 2, devout Tibetan Buddhists produced worldview defense following subliminal exposure to non-death cues of threat. The results demonstrate both the domain-generality of the process underlying worldview defense and the importance of religious doctrinal content in moderating mortality-salience effects.

When our thoughts are not our own: Investigating agency misattributions using the Mind-to-Mind paradigm

At the core ofthe sense ofagency for self-produced action is the sense that I, and not some other agent, am producing and directing those actions. While there is an ever-expanding body of empirical research investigating the sense of agency for bodily action, there has, to date, been little empirical investigation of the sense ofagency for thought.The present study uses the novel Mind-to-Mind paradigm, in which the agentive source of a target thought is ambiguous, to measure misattributions of agency. Seventy-two percent of participants made at least one misattribution of agency during a 5-min trial. Misattributions were significantly more frequent when the target thought was an arousing negative thought as compared to a neutral control.The findings establish a novel protocol for measuring the sense of agency for thought, and suggest that both contextual factors and emotional experience play a role in its generation.

Authority dependence and judgments of utilitarian harm

Three studies tested the conditions under which people judge utilitarian harm to be authority dependent (i.e., whether its right or wrongness depends on the ruling of an authority). In Study 1, participants judged the right or wrongness of physical abuse when used as an interrogation method anticipated to yield useful information for preventing future terrorist attacks. The ruling of the military authority towards the harm was manipulated (prohibited vs. prescribed) and found to significantly influence judgments of the right or wrongness of inflicting harm. Study 2 established a boundary condition with regards to the influence of authority, which was eliminated when the utility of the harm was definitely obtained rather than forecasted. Finally, Study 3 replicated the findings of Studies 1-2 in a completely different context—an expert committee’s ruling about the harming of chimpanzees for biomedical research. These results are discussed as they inform ongoing debates regarding the role of authority in moderating judgments of complex and simple harm. 2013 Elsevier B.V. © All rights reserved.

Moral emotions and the envisioning of mitigating circumstances for wrongdoing

Anger may be more responsive than disgust to mitigating circumstances in judgments of wrongdoing. We tested this hypothesis in two studies where we had participants envision circumstances that could serve to mitigate an otherwise wrongful act. In Study 1, participants provided moral judgments, and ratings of anger and disgust, to a number of transgressions involving either harm or bodily purity. They were then asked to imagine and report whether there might be any circumstances that would make it all right to perform the act. Across transgression type, and controlling for covariance between anger and disgust, levels of anger were found to negatively predict the envisioning of mitigating circumstances for wrongdoing, while disgust was unrelated. Study 2 replicated and extended these findings to less serious transgressions, using a continuous measure of mitigating circumstances, and demonstrated the impact of
anger independent of deontological commitments. These findings highlight the differential relationship that anger and disgust have with the ability to envision mitigating factors.

Making heads or tails of probability:an experiment with random generators

The equiprobability bias is a tendency for individuals to think of probabilistic events as 'equiprobable' by nature, and to judge outcomes that occur with different probabilities as equally likely. The equiprobability bias has been repeatedly found to be related to formal education in statistics, and it is claimed to be based on a misunderstanding of the concept of randomness.

Examining the Neurocognitive Validity of Commercially Available, Smartphone-Based Puzzle Games

Cognitive assessment typically involves assessing a person’s cognitive performance in unfamiliar and ar-guably unnatural clinical surroundings. User-centred approaches to assessment and monitoring, driven by issues such as enjoyability and familiarity, are largely absent. Everyday technologies, for example, smartphones represent an opportunity to obtain an objective assessment of a person’s cognitive capabili-ties in a non-threatening, discreet and familiar way, e.g. by everyday puzzle games undertaken as a leisure activity at home. We examined the strength of relationships that exist between performance on common puzzle games and standard measures of neuropsychological performance. Twenty-nine participants, aged 50 - 65 years, completed a comprehensive neuropsychological test battery and played three smart-phone-based puzzle games in triplicate: a picture puzzle [Matches Plus], a word puzzle [Jumbline] and a number puzzle [Sudoku]. As anticipated, a priori, significant correlations were observed between scores on a picture puzzle and visual memory test (r = 0.49; p = 0.007); a word puzzle and estimated verbal IQ (r = 0.53; p = 0.003) and verbal learning (r = 0.30; p = 0.039) tests; and a number puzzle and reason-ing/problem solving test (r = 0.42; p = 0.023). Further analyses making allowance for multiple compari-sons identified a significant unanticipated correlation (r = 0.49; p = 0.007) between number puzzle scores and a measure of nonverbal working memory. Performance on these smartphone-based games was in-dicative of relative cognitive ability across several cognitive domains at a fixed time point. Smart-phone-based, everyday puzzle games may offer a valid, portable measure of assessing and monitoring cognition in older adults.

Physical Activity and Cognitive Function in the Elderly: a Systematic Review

Background: Physical activity appears important contributor for healthy aging, including cognitive function. However, it is unclear whether late life physical activity alone is beneficial to cognitive function. We performed a systematic review to examine the effect of late life physical activity in maintaining cognitive function in older persons.
Methods: Search Strategy and Selection criteria: The search sources consisted of PubMed, MEDLINE, CINAHL, Cochrane Controlled Trials Register (CENTRAL), and the University of Washington Medical School Library Database between July 15, 2011 and August 15, 2012 with language restricted to English. Studies that were published in journals on or after January 2000 with participants older than 60 years of age were reviewed. Randomized controlled trials including at least 30 participants and lasting for at least 6 months and all observational studies of at least 100 participants and lasting at least 1 year in duration were eligible for inclusion Two reviewers assessed the applicability and results of these studies.
Results: Twenty-six studies fulfilling the inclusion criteria are included. Twenty-one studies reported that late life physical activity resulted in maintenance or enhancement of cognitive function. Three studies reported a dose-response relationship between physical activity and cognition.
Conclusions: Late life physical activity is beneficial for cognitive function in the elderly. However, the majority of the evidence is of medium quality with moderate risk of bias. Larger, randomized controlled trials are needed to better define the association between late life physical activity and cognitive function. Further research is required to determine which types of exercise have the greatest benefits on specific cognitive domains. Despite these caveats, current data are sufficient to recommend that moderate level, late life physical activity may be an effective method to improve cognitive function and delay the onset and progression of cognitive disease in the elderly.

Oxytocin effects on neural correlates of self-referential processing

Oxytocin (OT) influences how humans process information about others. Whether OT affects the processing of information about oneself remains unknown. Using a double-blind, placebo-controlled within-subject design, we recorded event-related potentials (ERPs) from adults during trait judgments about oneself and a celebrity and during judgments on word valence, after intranasal OT or placebo administration. We found that OT vs. placebo treatment reduced the differential amplitudes of a fronto-central positivity at 220-280 ms (P2) during self- vs. valence-judgments. OT vs. placebo treatment tended to reduce the differential amplitude of a late positive potential at 520-1000 ms (LPP) during self-judgments but to increase the differential LPP amplitude during other-judgments. OT effects on the differential P2 and LPP amplitudes to self- vs. celebrity-judgments were positively correlated with a measure of interdependence of self-construals. Thus OT modulates the neural correlates of self-referential processing and this effect varies as a function of interdependence.