Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

Transtorno autístico e doença celíaca : sem evidências de associação

Objective: To evaluate the possible association between celiac disease (CD) and/or gluten sensitivity (GS) and autism spectrum disorder (ASD). Methods: Occurrences of CD were determined in a group of children and adolescents affected by ASD and, conversely, occurrences of ASD were assessed in a group of biopsy-proven celiac patients. To detect the possible existence of GS, the levels of antigliadin antibodies in ASD patients were assessed and compared with the levels in a group of non-celiac children. Results: The prevalence of CD or GS in ASD patients was not greater than in groups originating from the same geographical area. Similarly the prevalence of ASD was not greater than in a group of biopsy-proven CD patients. Conclusion: No statistically demonstrable association was found between CD or GS and ASD. Consequently, routine screening for CD or GS in all patients with ASD is, at this moment, neither justifed nor cost-effective. ___________________________________________________________________________________ RESUMOObjetivo: Avaliar a possível associação entre doença celíaca (DC) e/ou sensibilidade ao glúten (SG) e transtorno do espectro autista (TEA). Métodos: Ocorrências de DC foram determinadas em um grupo de crianças e adolescentes afetados pelo TEA e a ocorrência d TEA foi avaliada em um grupo de pacientes com DC comprovada por biópsia. Para detectar a possível existência de SG, foram determinados níveis de anticorpos antigliadina em pacientes com TEA e comparados ao grupo de crianças sem a doença celíaca. Resultados: A prevalência de DC ou SG não foi maior no grupo de pacientes com TEA quando comparada a grupos de indivíduos originários da mesma região geográfca. De modo similar, a prevalência do TEA não foi maior ao ser comparada ao grupo de pacientes com DC. Conclusão: Não houve associação estatisticamente demonstrável entre DC ou SG e TEA. Consequentemente, não são justifcáveis, no momento, exames de rotina para detecção de DC ou SG em pacientes com TEA

Relationship between chronic pain and cognition in cognitively intact older persons and patients with Alzheimer's disease; the need to control for mood

Background: Brain areas that are involved in cognition and mood also play a role in pain processing. Objective: The goal of the present study was to examine the relationship between chronic pain and cognition [executive functions (EF) and memory], while controlling for mood, in cognitively intact older persons and in patients with Alzheimer's disease (AD). Methods: Two groups of subjects participated: 20 older persons without dementia and 19 patients in an early stage of probable AD who suffered from arthrosis/arthritis. Pain intensity and pain affect were assessed by the Colored Analogue Scale for Pain Intensity and for Pain Affect, the Faces Pain Scale (FPS) and the Number of Words Chosen-Affective (NWC-A). Level of depression and anxiety were evaluated by questionnaires. EF and memory were assessed by neuropsychological tests. Results: The results show that significant correlations between specific cognitive functions, pain intensity and pain affect were lacking in the cognitively intact older persons. Cognition, in particular memory, appeared to be related to depressive symptoms. In contrast, a significant positive correlation was observed between EF, pain intensity and pain affect measured by the FPS in the AD group. Conclusions: Although older persons with depression were excluded, in studies on pain and cognition one should control for the presence of depressive symptoms in older persons with and without dementia. Copyright © 2008 S. Karger AG

Cryo-electron microscopy of viruses

Thin vitrified layers of unfixed, unstained and unsupported virus suspensions can be prepared for observation by cryo-electron microscopy in easily controlled conditions. The viral particles appear free from the kind of damage caused by dehydration, freezing or adsorption to a support that is encountered in preparing biological samples for conventional electron microscopy. Cryo-electron microscopy of vitrified specimens offers possibilities for high resolution observations that compare favourably with any other electron microscopical method

Long-term coding of personal and universal associations underlying the memory web in the human brain

Neurons in the medial temporal lobe (MTL), a critical area for declarative memory, have been shown to change their tuning in associative learning tasks. Yet, it is unclear how durable these neuronal representations are and if they outlast the execution of the task. To address this issue, we studied the responses of MTL neurons in neurosurgical patients to known concepts (people and places). Using association scores provided by the patients and a web-based metric, here we show that whenever MTL neurons respond to more than one concept, these concepts are typically related. Furthermore, the degree of association between concepts could be successfully predicted based on the neurons’ response patterns. These results provide evidence for a long-term involvement of MTL neurons in the representation of durable associations, a hallmark of human declarative memory

Variation, variability, and the origin of the avian endocranium:Insights from the anatomy of alioramus altai (theropoda: Tyrannosauroidea)

The internal braincase anatomy of the holotype of Alioramus altai, a relatively small-bodied tyrannosauroid from the Late Cretaceous of Mongolia, was studied using high-resolution computed tomography. A number of derived characters strengthen the diagnosis of this taxon as both a tyrannosauroid and a unique, new species (e.g., endocranial position of the gasserian ganglion, internal ramification of the facial nerve). Also present are features intermediate between the basal theropod and avialan conditions that optimize as the ancestral condition for Coelurosauria--a diverse group of derived theropods that includes modern birds. The expression of several primitive theropod features as derived character states within Tyrannosauroidea establishes previously unrecognized evolutionary complexity and morphological plasticity at the base of Coelurosauria. It also demonstrates the critical role heterochrony may have played in driving patterns of endocranial variability within the group and potentially reveals stages in the evolution of neuroanatomical development that could not be inferred based solely on developmental observations of the major archosaurian crown clades. We discuss the integration of paleontology with variability studies, especially as applied to the nature of morphological transformations along the phylogenetically long branches that tend to separate the crown clades of major vertebrate groups

Optical Magnetometry

Some of the most sensitive methods of measuring magnetic fields utilize interactions of resonant light with atomic vapor. Recent developments in this vibrant field are improving magnetometers in many traditional areas such as measurement of geomagnetic anomalies and magnetic fields in space, and are opening the door to new ones, including, dynamical measurements of bio-magnetic fields, detection of nuclear magnetic resonance (NMR), magnetic-resonance imaging (MRI), inertial-rotation sensing, magnetic microscopy with cold atoms, and tests of fundamental symmetries of Nature.Comment: 11 pages; 4 figures; submitted to Nature Physic

Developing a utility index for the Aberrant Behavior Checklist (ABC-C) for fragile X syndrome

Purpose This study aimed to develop a utility index (the ABC-UI) from the Aberrant Behavior Checklist-Community (ABC-C), for use in quantifying the benefit of emerging treatments for fragile X syndrome (FXS). Methods The ABC-C is a proxy-completed assessment of behaviour and is a widely used measure in FXS. A subset of ABC-C items across seven dimensions was identified to include in health state descriptions. This item reduction process was based on item performance, factor analysis and Rasch analysis performed on an observational study dataset, and consultation with five clinical experts and a methodological expert. Dimensions were combined into health states using an orthogonal design and valued using time trade-off (TTO), with lead-time TTO methods used where TTO indicated a state valued as worse than dead. Preference weights were estimated using mean, individual level, ordinary least squares and random-effects maximum likelihood estimation [RE (MLE)] regression models. Results A representative sample of the UK general public (n = 349; mean age 35.8 years, 58.2 % female) each valued 12 health states. Mean observed values ranged from 0.92 to 0.16 for best to worst health states. The RE (MLE) model performed best based on number of significant coefficients and mean absolute error of 0.018. Mean utilities predicted by the model covered a similar range to that observed. Conclusions The ABC-UI estimates a wide range of utilities from patient-level FXS ABC-C data, allowing estimation of FXS health-related quality of life impact for economic evaluation from an established FXS clinical trial instrument

Frequency-specific hippocampal-prefrontal interactions during associative learning

Much of our knowledge of the world depends on learning associations (for example, face-name), for which the hippocampus (HPC) and prefrontal cortex (PFC) are critical. HPC-PFC interactions have rarely been studied in monkeys, whose cognitive and mnemonic abilities are akin to those of humans. We found functional differences and frequency-specific interactions between HPC and PFC of monkeys learning object pair associations, an animal model of human explicit memory. PFC spiking activity reflected learning in parallel with behavioral performance, whereas HPC neurons reflected feedback about whether trial-and-error guesses were correct or incorrect. Theta-band HPC-PFC synchrony was stronger after errors, was driven primarily by PFC to HPC directional influences and decreased with learning. In contrast, alpha/beta-band synchrony was stronger after correct trials, was driven more by HPC and increased with learning. Rapid object associative learning may occur in PFC, whereas HPC may guide neocortical plasticity by signaling success or failure via oscillatory synchrony in different frequency bands.National Institute of Mental Health (U.S.) (Conte Center Grant P50-MH094263-03)National Institute of Mental Health (U.S.) (Fellowship F32-MH081507)Picower Foundatio

Developmental differences in children’s interpersonal emotion regulation

Previous research on interpersonal emotion regulation (ER) in childhood has been rather unsystematic, focusing mainly on children’s prosocial behaviour, and has been conducted in the absence of an integrative emotion theoretical framework. The present research relied on the interpersonal affect classification proposed by Niven, Totterdell, and Holman (2009) to investigate children’s use of different interpersonal ER strategies. The study drew on two samples: 180 parents of children aged between 3 and 8 years reported about a situation where their child was able to change what another person was feeling in order to make them feel better. In addition, 126 children between 3- and 8-years old answered two questions about how they could improve others’ mood. Results from both samples showed age differences in children’s use of interpersonal ER strategies. As expected, ‘affective engagement’ (i.e., focusing on the person or the problem) and ‘cognitive engagement’ (i.e., appraising the situation from a different perspective) were mainly used by 7-8 years-old, whereas ‘attention’ (i.e., distracting and valuing) was most used by 3-4 and 5-6 years-old. ‘Humor’ (i.e., laughing with the target) remained stable across the different age groups. The present research provides more information about the developmental patterns for each specific interpersonal emotion regulation strategy