Neural correlates of polygenic risk score for autism spectrum disorders in general population

Autism spectrum disorder is a highly prevalent and highly heritable neurodevelopmental condition, but studies have mostly taken traditional categorical diagnosis approach (yes/no for autism spectrum disorder). In contrast, an emerging notion suggests a continuum model of autism spectrum disorder with a normal distribution of autistic tendencies in the general population, where a full diagnosis is at the severe tail of the distribution. We set out to investigate such a viewpoint by investigating the interaction of polygenic risk scores for autism spectrum disorder and Age2 on neuroimaging measures (cortical thickness and white matter connectivity) in a general population (n = 391, with age ranging from 3 to 21 years from the Pediatric Imaging, Neurocognition and Genetics study). We observed that children with higher polygenic risk for autism spectrum disorder exhibited greater cortical thickness for a large age span starting from 3 years up to ∼14 years in several cortical regions localized in bilateral precentral gyri and the left hemispheric postcentral gyrus and precuneus. In an independent case-control dataset from the Autism Brain Imaging Data Exchange (n = 560), we observed a similar pattern: children with autism spectrum disorder exhibited greater cortical thickness starting from 6 years onwards till ∼14 years in wide-spread cortical regions including (the ones identified using the general population). We also observed statistically significant regional overlap between the two maps, suggesting that some of the cortical abnormalities associated with autism spectrum disorder overlapped with brain changes associated with genetic vulnerability for autism spectrum disorder in healthy individuals. Lastly, we observed that white matter connectivity between the frontal and parietal regions showed significant association with polygenic risk for autism spectrum disorder, indicating that not only the brain structure, but the white matter connectivity might also show a predisposition for the risk of autism spectrum disorder. Our findings showed that the fronto-parietal thickness and connectivity are dimensionally related to genetic risk for autism spectrum disorder in general population and are also part of the cortical abnormalities associated with autism spectrum disorder. This highlights the necessity of considering continuum models in studying the aetiology of autism spectrum disorder using polygenic risk scores and multimodal neuroimaging. Keywords: autism spectrum disorders; cortical thickness; genetics; polygenic risk score; structural connectivity

No clear benefit of transcutaneous auricular vagus nerve stimulation for non-native speech sound learning

IntroductionLearning to understand and speak a new language can be challenging and discouraging for adults. One potential tool for improving learning is transcutaneous auricular vagus nerve stimulation (taVNS), which modulates perception, memory, and attention systems. It has recently been reported that taVNS can improve English speakers' ability to perceive unfamiliar Mandarin tones. The current project explored the potential benefits of taVNS for language learning beyond tone perception.MethodsWe studied adults' ability to perceive and produce unfamiliar speech sounds as well as any potential change in language learning motivation from pre- to post-training. Forty-five native English speakers were divided into three groups and were trained to perceive German sounds: one group received stimulation during easier-to-learn sounds (vowels), one group received stimulation during harder-to-learn sounds (fricatives), and a control group received no stimulation.Results and discussionWe did not find evidence that taVNS improved perception or production of the German sounds, but there was evidence that it did improve some aspects of motivation. Specifically, the group that received taVNS during easier sounds showed a significant decrease in feelings of tension/pressure about language learning, while the other groups did not. Overall, the present study does not find that taVNS holds benefits for the acquisition of new speech sounds; however, the field is nascent, and so the potential applications of taVNS for language learning remain to be clarified

Is saccade averaging determined by visual processing or movement planning?

Bhutani N, Ray S, Murthy A. Is saccade averaging determined by visual processing or movement planning? J Neurophysiol 108: 3161-3171, 2012. First published September 26, 2012; doi:10.1152/jn.00344.2012.-Saccadic averaging that causes subjects' gaze to land between the location of two targets when faced with simultaneously or sequentially presented stimuli has been often used as a probe to investigate the nature of computations that transform sensory representations into an oculomotor plan. Since saccadic movements involve at least two processing stages-a visual stage that selects a target and a movement stage that prepares the response-saccade averaging can either occur due to interference in visual processing or movement planning. By having human subjects perform two versions of a saccadic double-step task, in which the stimuli remained the same, but different instructions were provided (REDIRECT gaze to the later-appearing target vs. FOLLOW the sequence of targets in their order of appearance), we tested two alternative hypotheses. If saccade averaging were due to visual processing alone, the pattern of saccade averaging is expected to remain the same across task conditions. However, whereas subjects produced averaged saccades between two targets in the FOLLOW condition, they produced hypometric saccades in the direction of the initial target in the REDIRECT condition, suggesting that the interaction between competing movement plans produces saccade averaging

A comparative evaluation of efficacy of root surface biomodification using MTAD, MTAD+I-PRF on adhesion of fibrin clot to dentin sem study

Root biomodifiers help in removing the smear layer following mechanical debridement. In this context, we evaluated and compared the in vitro efficacy of MTAD, MTAD+I-PRF, and phosphate-buffered saline-conditioned dentin surfaces by examining the distribution of the fibrin network using scanning electron microscopy. It was concluded that MTAD can serve as a potentially useful root conditioner/biomodifier. Further, the adjunct of MTAD+I-P resulted in more fibrin network linkage on the dentinal surface when compared to MTAD alone which can be of great utility in Advanced Regenerative Therapy

Trans-saccadic processing of visual and motor planning during sequential eye movements

How the brain maintains perceptual continuity across eye movements that yield discontinuous snapshots of the world is still poorly understood. In this study, we adapted a framework from the dual-task paradigm, well suited to reveal bottlenecks in mental processing, to study how information is processed across sequential saccades. The pattern of RTs allowed us to distinguish among three forms of trans-saccadic processing (no trans-saccadic processing, trans-saccadic visual processing and trans-saccadic visual processing and saccade planning models). Using a cued double-step saccade task, we show that even though saccade execution is a processing bottleneck, limiting access to incoming visual information, partial visual and motor processing that occur prior to saccade execution is used to guide the next eye movement. These results provide insights into how the oculomotor system is designed to process information across multiple fixations that occur during natural scanning

Parallel activation of prospective motor plans during visually-guided sequential saccades

Behavioural evidences suggest that sequential saccades to multiple stimuli are planned in parallel. However, it remains unclear whether such parallel programming reflects concurrent processing of goals or whether multiple motor plans coexist, unfolding subsequently during execution. Here we use midway saccades, directed at intermediate locations between two targets, as a probe to address this question in a novel double-step adaptation task. The task consisted of trials where subjects had to follow the appearance of two targets presented in succession with two sequential saccades. In some trials, the second target predictably jumped to a new location during the second saccade. Initially, the second saccade was aimed at the final target's location before the jump. As subjects adapted to the target jump, saccades were aimed to the second target's new location. We tested whether the spatial distribution of midway saccades could be explained as an interaction between two concurrent saccade goals, each directed at the two target locations, or between the initial motor plan to the first target location and a prospective motor plan directed from the initial to the final target location. A shift in the midway saccades' distribution towards the jumped location of the second target following adaptation indicated that the brain can make use of prospective motor plans to guide sequential eye movements. Furthermore, we observed that the spatiotemporal pattern of endpoints of midway saccades can be well explained by a motor addition model. These results provide strong evidence of parallel activation of prospective motor plans during sequential saccades

Impaired conflict monitoring in Parkinson's disease patients during an oculomotor redirect task

Fallibility is inherent in human cognition and so a system that will monitor performance is indispensable. While behavioral evidence for such a system derives from the finding that subjects slow down after trials that are likely to produce errors, the neural and behavioral characterization that enables such control is incomplete. Here, we report a specific role for dopamine/basal ganglia in response conflict by accessing deficits in performance monitoring in patients with Parkinson's disease. To characterize such a deficit, we used a modification of the oculomotor countermanding task to show that slowing down of responses that generate robust response conflict, and not post-error per se, is deficient in Parkinson's disease patients. Poor performance adjustment could be either due to impaired ability to slow RT subsequent to conflicts or due to impaired response conflict recognition. If the latter hypothesis was true, then PD subjects should show evidence of impaired error detection/correction, which was found to be the case. These results make a strong case for impaired performance monitoring in Parkinson's patients

A critical role of brain network architecture in a continuum model of autism spectrum disorders spanning from healthy individuals with genetic liability to individuals with ASD

Studies have shown cortical alterations in individuals with autism spectrum disorders (ASD) as well as in individuals with high polygenic risk for ASD. An important addition to the study of altered cortical anatomy is the investigation of the underlying brain network architecture that may reveal brain-wide mechanisms in ASD and in polygenic risk for ASD. Such an approach has been proven useful in other psychiatric disorders by revealing that brain network architecture shapes (to an extent) the disorder-related cortical alterations. This study uses data from a clinical dataset—560 male subjects (266 individuals with ASD and 294 healthy individuals, CTL, mean age at 17.2 years) from the Autism Brain Imaging Data Exchange database, and data of 391 healthy individuals (207 males, mean age at 12.1 years) from the Pediatric Imaging, Neurocognition and Genetics database. ASD-related cortical alterations (group difference, ASD-CTL, in cortical thickness) and cortical correlates of polygenic risk for ASD were assessed, and then statistically compared with structural connectome-based network measures (such as hubs) using spin permutation tests. Next, we investigated whether polygenic risk for ASD could be predicted by network architecture by building machine-learning based prediction models, and whether the top predictors of the model were identified as disease epicenters of ASD. We observed that ASD-related cortical alterations as well as cortical correlates of polygenic risk for ASD implicated cortical hubs more strongly than non-hub regions. We also observed that age progression of ASD-related cortical alterations and cortical correlates of polygenic risk for ASD implicated cortical hubs more strongly than non-hub regions. Further investigation revealed that structural connectomes predicted polygenic risk for ASD (r = 0.30, p < 0.0001), and two brain regions (the left inferior parietal and left suparmarginal) with top predictive connections were identified as disease epicenters of ASD. Our study highlights a critical role of network architecture in a continuum model of ASD spanning from healthy individuals with genetic risk to individuals with ASD. Our study also highlights the strength of investigating polygenic risk scores in addition to multi-modal neuroimaging measures to better understand the interplay between genetic risk and brain alterations associated with ASD