Saccadic eye movement abnormalities in autism spectrum disorder indicate dysfunctions in cerebellum and brainstem

BACKGROUND: Individuals with autism spectrum disorder (ASD) show atypical scan paths during social interaction and when viewing faces, and recent evidence suggests that they also show abnormal saccadic eye movement dynamics and accuracy when viewing less complex and non-social stimuli. Eye movements are a uniquely promising target for studies of ASD as their spatial and temporal characteristics can be measured precisely and the brain circuits supporting them are well-defined. Control of saccade metrics is supported by discrete circuits within the cerebellum and brainstem - two brain regions implicated in magnetic resonance (MR) morphometry and histopathological studies of ASD. The functional integrity of these distinct brain systems can be examined by evaluating different parameters of visually-guided saccades. METHODS: A total of 65 participants with ASD and 43 healthy controls, matched on age (between 6 and 44-years-old), gender and nonverbal IQ made saccades to peripheral targets. To examine the influence of attentional processes, blocked gap and overlap trials were presented. We examined saccade latency, accuracy and dynamics, as well as the trial-to-trial variability of participants’ performance. RESULTS: Saccades of individuals with ASD were characterized by reduced accuracy, elevated variability in accuracy across trials, and reduced peak velocity and prolonged duration. In addition, their saccades took longer to accelerate to peak velocity, with no alteration in the duration of saccade deceleration. Gap/overlap effects on saccade latencies were similar across groups, suggesting that visual orienting and attention systems are relatively spared in ASD. Age-related changes did not differ across groups. CONCLUSIONS: Deficits precisely and consistently directing eye movements suggest impairment in the error-reducing function of the cerebellum in ASD. Atypical increases in the duration of movement acceleration combined with lower peak saccade velocities implicate pontine nuclei, specifically suggesting reduced excitatory activity in burst cells that drive saccades relative to inhibitory activity in omnipause cells that maintain stable fixation. Thus, our findings suggest that both cerebellar and brainstem abnormalities contribute to altered sensorimotor control in ASD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2040-2392-5-47) contains supplementary material, which is available to authorized users

Monte Carlo Study of the Separation of Energy Scales in Quantum Spin 1/2 Chains with Bond Disorder

One-dimensional Heisenberg spin 1/2 chains with random ferro- and antiferromagnetic bonds are realized in systems such as $Sr_3 CuPt_{1-x} Ir_x O_6$. We have investigated numerically the thermodynamic properties of a generic random bond model and of a realistic model of $Sr_3 CuPt_{1-x} Ir_x O_6$ by the quantum Monte Carlo loop algorithm. For the first time we demonstrate the separation into three different temperature regimes for the original Hamiltonian based on an exact treatment, especially we show that the intermediate temperature regime is well-defined and observable in both the specific heat and the magnetic susceptibility. The crossover between the regimes is indicated by peaks in the specific heat. The uniform magnetic susceptibility shows Curie-like behavior in the high-, intermediate- and low-temperature regime, with different values of the Curie constant in each regime. We show that these regimes are overlapping in the realistic model and give numerical data for the analysis of experimental tests.Comment: 7 pages, 5 eps-figures included, typeset using JPSJ.sty, accepted for publication in J. Phys. Soc. Jpn. 68, Vol. 3. (1999

Comments on Sweeny and Gliozzi dynamics for simulations of Potts models in the Fortuin-Kasteleyn representation

We compare the correlation times of the Sweeny and Gliozzi dynamics for two-dimensional Ising and three-state Potts models, and the three-dimensional Ising model for the simulations in the percolation prepresentation. The results are also compared with Swendsen-Wang and Wolff cluster dynamics. It is found that Sweeny and Gliozzi dynamics have essentially the same dynamical critical behavior. Contrary to Gliozzi's claim (cond-mat/0201285), the Gliozzi dynamics has critical slowing down comparable to that of other cluster methods. For the two-dimensional Ising model, both Sweeny and Gliozzi dynamics give good fits to logarithmic size dependences; for two-dimensional three-state Potts model, their dynamical critical exponent z is 0.49(1); the three-dimensional Ising model has z = 0.37(2).Comment: RevTeX, 4 pages, 5 figure

Changes in the relationship between self-reference and emotional valence as a function of dysphoria

The self-positivity bias is found to be an aspect of normal cognitive function. Changes in this bias are usually associated with changes in emotional states, such as dysphoria or depression. The aim of the present study was to clarify the role of emotional valence within self-referential processing. By asking non-dysphoric and dysphoric individuals to rate separately the emotional and self-referential content of a set of 240 words, it was possible to identify the differences in the relationship between self-reference and emotional valence, which are associated with dysphoria. The results support the existence of the self-positivity bias in non-dysphoric individuals. More interestingly, dysphoric individuals were able to accurately identify the emotional content of the word stimuli. They failed, however, to associate this emotional valence with self-reference. These findings are discussed in terms of attributional self-biases and their consequences for cognition

Auger Recombination in Semiconductor Quantum Wells

The principal mechanisms of Auger recombination of nonequilibrium carriers in semiconductor heterostructures with quantum wells are investigated. It is shown for the first time that there exist three fundamentally different Auger recombination mechanisms of (i) thresholdless, (ii) quasi-threshold, and (iii) threshold types. The rate of the thresholdless Auger process depends on temperature only slightly. The rate of the quasi-threshold Auger process depends on temperature exponentially. However, its threshold energy essentially varies with quantum well width and is close to zero for narrow quantum wells. It is shown that the thresholdless and the quasi-threshold Auger processes dominate in narrow quantum wells, while the threshold and the quasi-threshold processes prevail in wide quantum wells. The limiting case of a three-dimensional (3D)Auger process is reached for infinitely wide quantum wells. The critical quantum well width is found at which the quasi-threshold and threshold Auger processes merge into a single 3D Auger process. Also studied is phonon-assisted Auger recombination in quantum wells. It is shown that for narrow quantum wells the act of phonon emission becomes resonant, which in turn increases substantially the coefficient of phonon-assisted Auger recombination. Conditions are found under which the direct Auger process dominates over the phonon-assisted Auger recombination at various temperatures and quantum well widths.Comment: 38 pages, 7 figure

Functional interactions between NADPH oxidase 5 and actin

NADPH oxidase 5 (NOX5) is a transmembrane oxidative signaling enzyme which produces superoxide in response to intracellular calcium flux. Increasing evidence indicates that NOX5 is involved in a variety of physiological processes as well as human disease, however, details of NOX5 signaling pathways and targets of NOX5 mediated oxidative modifications remain poorly resolved. Actin dynamics have previously been shown to be modulated by oxidative modification, however, a direct connection to NOX5 expression and activity has not been fully explored. Here we show that NOX5 and actin interact in the cell, and each modulate the activity of the other. Using actin effector molecules jasplakinolide, cytochalasin D and latrunculin A, we show that changes in actin dynamics affect NOX5 superoxide production. In tandem, NOX5 oxidatively modifies actin, and shifts the ratio of filamentous to monomeric actin. Finally, we show that knockdown of NOX5 in the pancreatic cancer cell line PSN-1 impairs cell migration. Together our findings indicate an important link between actin dynamics and oxidative signaling through NOX5

The Percolation Signature of the Spin Glass Transition

Magnetic ordering at low temperature for Ising ferromagnets manifests itself within the associated Fortuin-Kasteleyn (FK) random cluster representation as the occurrence of a single positive density percolating network. In this paper we investigate the percolation signature for Ising spin glass ordering -- both in short-range (EA) and infinite-range (SK) models -- within a two-replica FK representation and also within the different Chayes-Machta-Redner two-replica graphical representation. Based on numerical studies of the $\pm J$ EA model in three dimensions and on rigorous results for the SK model, we conclude that the spin glass transition corresponds to the appearance of {\it two} percolating clusters of {\it unequal} densities.Comment: 13 pages, 6 figure

Adolescence and the next generation.

Adolescent growth and social development shape the early development of offspring from preconception through to the post-partum period through distinct processes in males and females. At a time of great change in the forces shaping adolescence, including the timing of parenthood, investments in today's adolescents, the largest cohort in human history, will yield great dividends for future generations

Host resources and parasite traits interact to determine the optimal combination of host parasite‐mitigation strategies

Organisms have evolved diverse strategies to manage parasite infections. Broadly, hosts may avoid infection by altering behaviour, resist infection by targeting parasites or tolerate infection by repairing associated damage. The effectiveness of a strategy depends on interactions between, for example, resource availability, parasite traits (virulence, life‐history) and the host itself (nutritional status, immunopathology). To understand how these factors shape host parasite‐mitigation strategies, we developed a mathematical model of within‐host, parasite‐immune dynamics in the context of helminth infections. The model incorporated host nutrition and resource allocation to different mechanisms of immune response: larval parasite prevention; adult parasite clearance; damage repair (tolerance). We also considered a non‐immune strategy: avoidance via anorexia, reducing intake of infective stages. Resources not allocated to immune processes promoted host condition, whereas harm due to parasites and immunopathology diminished it. Maximising condition (a proxy for fitness), we determined optimal host investment for each parasite‐mitigation strategy, singly and combined, across different environmental resource levels and parasite trait values. Which strategy was optimal varied with scenario. Tolerance generally performed well, especially with high resources. Success of the different resistance strategies (larval prevention or adult clearance) tracked relative virulence of larval and adult parasites: slowly maturing, highly damaging larvae favoured prevention; rapidly maturing, less harmful larvae favoured clearance. Anorexia was viable only in the short term, due to reduced host nutrition. Combined strategies always outperformed any lone strategy: these were dominated by tolerance, with some investment in resistance.Choice of parasite mitigation strategy has profound consequences for hosts, impacting their condition, survival and reproductive success. We show that the efficacy of different strategies is highly dependent on timescale, parasite traits and resource availability. Models that integrate such factors can inform the collection and interpretation of empirical data, to understand how those drivers interact to shape host immune responses in natural systems

The Role of Uncertainty, Worry, and Control in Well-Being: Evidence From the COVID-19 Outbreak and Pandemic in U.S. and China

Uncertainty about the future often leads to worries about what the future will bring, which can have negative consequences for health and well-being. However, if worry can act as a motivator to promote efforts to prevent undesirable future outcomes, those negative consequences of worry may be mitigated. In this article, we apply a novel model of uncertainty, worry, and perceived control to predict psychological and physical well-being among four samples collected in China (Study 1; during the early COVID-19 outbreak in China) and the United States (Studies 2–4, during 4 weeks in May 2020, 4 weeks in November 2020, and crosssectionally between April and November 2020). Grounded in the feeling-is-for-doing approach to emotions, we hypothesized (and found) that uncertainty about one’s COVID-19 risk would predict greater worry about the virus and one’s risk of contracting it, and that greater worry would in turn predict poorer well-being. We also hypothesized, and found somewhat mixed evidence, that perceptions of control over 1’s COVID-19 risk moderated the relationship between worry and well-being such that worry was related to diminished well-being when people felt they lacked control over their risk for contracting the virus. This study is one of the first to demonstrate an indirect path from uncertainty to well-being via worry and to demonstrate the role of control in moderating whether uncertainty and worry manifest in poor well-being