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Importance: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are childhood-onset disorders that may persist into adulthood. Several studies have suggested that they may be associated with an increased risk of mortality; however, the results are inconsistent.; Objective: To assess the risk of mortality among persons with ASD or ADHD and their first-degree relatives.; Data Sources: A search of MEDLINE, Embase, Scopus, Web of Science, and PsycINFO (published from inception to April 1, 2021) was supplemented by searching reference lists of the retrieved articles.; Study Selection: Cohort and case-control studies that reported mortality rate ratios (RRs) in persons with ASD or ADHD and/or their first-degree relatives compared with the general population or those without ASD/ADHD were included.; Data Extraction and Synthesis: Screening, data extraction, and quality assessment were performed by at least 2 researchers independently. A random-effects model was used to meta-analyze individual studies and assessed heterogeneity (I2).; Main Outcomes and Measures: All-cause mortality in association with ASD or ADHD. Secondary outcome was cause-specific mortality.; Results: Twenty-seven studies were included, with a total of 642?260 individuals. All-cause mortality was found to be higher for persons with ASD (154?238 participants; 12 studies; RR, 2.37; 95% CI, 1.97-2.85; I2, 89%; moderate confidence) and persons with ADHD (396?488 participants; 8 studies; RR, 2.13; 95% CI, 1.13-4.02; I2, 98%; low confidence) than for the general population. Among persons with ASD, deaths from natural causes (4 studies; RR, 3.80; 95% CI, 2.06-7.01; I2, 96%; low confidence) and deaths from unnatural causes were increased (6 studies; RR, 2.50; 95% CI, 1.49-4.18; I2, 95%; low confidence). Among persons with ADHD, deaths from natural causes were not significantly increased (4 studies; RR, 1.62; 95% CI, 0.89-2.96; I2, 88%; low confidence), but deaths from unnatural causes were higher than expected (10 studies; RR, 2.81; 95% CI, 1.73-4.55; I2, 92%; low confidence).; Conclusions and Relevance: This systematic review and meta-analysis found that ASD and ADHD are associated with a significantly increased risk of mortality. Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups. The substantial heterogeneity between studies should be explored further.

Introduction Health services generate large amounts of routine health data (eg, administrative databases, disease registries and electronic health records), which have important secondary uses for research. Increases in the availability and the ability to access and analyse large amounts of data represent a major opportunity for conducting studies on the possible relationships between complex diseases. The objective of this study will be to evaluate the design, methods and reporting of studies conducted using observational routinely collected health data for investigating the link between cancer and neurodegenerative diseases. Methods and analysis This is the protocol for a meta-research study. We registered the study protocol within the Open Science Framework: https://ostio/h2qjg. We will evaluate observational studies (eg, cohort and case-control) conducted using routinely collected health data for investigating the associations between cancer and neurodegenerative diseases (such as Alzheimer's disease, amyotrophic lateral sclerosis/motor neuron disease, Huntington's disease, multiple sclerosis and Parkinson's disease). The following electronic databases will be searched (from their inception onwards): MEDLINE, Embase and Web of Science Core Collection. Screening and selection of articles will be conducted by at least two researchers. Potential discrepancies will be resolved via discussion. Design, methods and reporting characteristics in each article will be extracted using a standardised data extraction form. Information on general, methodological and transparency items will be reported. We will summarise our findings with tables and graphs (eg, bar charts, forest plots). Ethics and dissemination Due to the nature of the proposed study, no ethical approval will be required. We plan to publish the full study in an open access peer-reviewed journal and disseminate the findings at scientific conferences and via social media. All data will be deposited in a cross-disciplinary public repository.

Face processing is mediated by interactions between functional areas in the occipital and temporal lobe, and the fusiform face area (FFA) and anterior temporal lobe play key roles in the recognition of facial identity. Individuals with developmental prosopagnosia (DP), a lifelong face recognition impairment, have been shown to have structural and functional neuronal alterations in these areas. The present study investigated how face selectivity is generated in participants with normal face processing, and how functional abnormalities associated with DP, arise as a function of network connectivity. Using functional magnetic resonance imaging and dynamic causal modeling, we examined effective connectivity in normal participants by assessing network models that include early visual cortex (EVC) and face-selective areas and then investigated the integrity of this connectivity in participants with DP. Results showed that a feedforward architecture from EVC to the occipital face area, EVC to FFA, and EVC to posterior superior temporal sulcus (pSTS) best explained how face selectivity arises in both controls and participants with DP. In this architecture, the DP group showed reduced connection strengths on feedforward connections carrying face information from EVC to FFA and EVC to pSTS. These altered network dynamics in DP contribute to the diminished face selectivity in the posterior occipitotemporal areas affected in DP. These findings suggest a novel view on the relevance of feedforward projection from EVC to posterior occipitotemporal face areas in generating cortical face selectivity and differences in face recognition ability. SIGNIFICANCE STATEMENT Areas of the human brain showing enhanced activation to faces compared to other objects or places have been extensively studied. However, the factors leading to this face selectively have remained mostly unknown. We show that effective connectivity from early visual cortex to posterior occipitotemporal face areas gives rise to face selectivity. Furthermore, people with developmental prosopagnosia, a lifelong face recognition impairment, have reduced face selectivity in the posterior occipitotemporal face areas and left anterior temporal lobe. We show that this reduced face selectivity can be predicted by effective connectivity from early visual cortex to posterior occipitotemporal face areas. This study presents the first network-based account of how face selectivity arises in the human brain.

Background: Anorexia nervosa is characterized by a severe restriction of caloric intake, low body weight, fear of gaining weight or of becoming fat, and disturbance of body image. Pathogenesis of the disorder may include genetic predisposition, hormonal changes and a combination of environmental, psychosocial, and cultural factors. Cancer is the second leading cause of death worldwide. At present, no systematic reviews and meta-analyses have evaluated the risk of cancer in people with anorexia nervosa. The objective of this study will be to evaluate the association between anorexia nervosa and the risk of developing or dying from cancer. Methods/design: This study protocol is part of a systematic collection and assessment of multiple systematic reviews and meta-analyses (umbrella review) evaluating the association of cancer and multiple central nervous system disorders. We designed a specific protocol for a new systematic review and meta-analysis of observational studies of anorexia nervosa with risk of developing or dying from any cancer. Data sources will be PubMed, Embase, Scopus, Web of Science, and manual screening of references. Observational studies (case-control and cohort) in humans that examined the association between anorexia nervosa and risk of developing or dying from cancer will be sought. The primary outcomes will be cancer incidence and cancer mortality in association with anorexia nervosa. Secondary outcomes will be site-specific cancer incidence and mortality, respectively. Screening of abstracts and full texts, and data abstraction will be performed by two team members independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. The quality of studies will be assessed by using the Ottawa-Newcastle scale by two team members independently. Random effects models will be conducted where appropriate. Subgroup and additional analyses will be conducted to explore the potential sources of heterogeneity. The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used for determining the quality of evidence for cancer outcomes. Discussion: Findings from this systematic review will inform an ongoing umbrella review on cancer and central nervous system disorders. Our systematic review and meta-analysis of observational studies will establish the extent of the epidemiological evidence underlying the association between anorexia nervosa and cancer. Systematic review registration: PROSPERO CRD42017067462.

Background: The objective of this study will be to synthesize the epidemiological evidence and evaluate the validity of the associations between central nervous system disorders and the risk of developing or dying from cancer. Methods/design: We will perform an umbrella review of systematic reviews and conduct updated meta-analyses of observational studies (cohort and case-control) investigating the association between central nervous system disorders and the risk of developing or dying from any cancer or specific types of cancer. Searches involving PubMed/MEDLINE, EMBASE, SCOPUS and Web of Science will be used to identify systematic reviews and meta-analyses of observational studies. In addition, online databases will be checked for observational studies published outside the time frames of previous reviews. Eligible central nervous system disorders will be Alzheimer's disease, anorexia nervosa, amyotrophic lateral sclerosis, autism spectrum disorders, bipolar disorder, depression, Down's syndrome, epilepsy, Huntington's disease, multiple sclerosis, Parkinson's disease and schizophrenia. The primary outcomes will be cancer incidence and cancer mortality in association with a central nervous system disorder. Secondary outcome measures will be site-specific cancer incidence and mortality, respectively. Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles. Data will be abstracted, and study quality/risk of bias will be appraised by two reviewers independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects meta-analyses of primary observational studies will be conducted where appropriate. Parameters for exploring statistical heterogeneity are pre-specified. The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used for determining the quality of evidence for cancer outcomes. Discussion: Our study will establish the extent of the epidemiological evidence underlying the associations between central nervous system disorders and cancer and will provide a rigorous and updated synthesis of a range of important site-specific cancer outcomes.

Brain areas activated by stimuli in the left visual field of a right parietal patient suffering from left visual extinction were identified using event-related functional magnetic resonance imaging. Left visual field stimuli that were extinguished from awareness still activated the ventral visual cortex, including areas in the damaged right hemisphere. An extinguished face stimulus on the left produced robust category-specific activation of the right fusiform face area. On trials where the left visual stimulus was consciously seen rather than extinguished, greater activity was found in the ventral visual cortex of the damaged hemisphere, and also in frontal and parietal areas of the intact hemisphere. These findings extend recent observations on visual extinction, suggesting distinct neural correlates for conscious and unconscious perception.

Combining transcranial magnetic stimulation (TMS) with concurrent functional magnetic resonance imaging (fMRI) allows study of how local brain stimulation may causally affect activity in remote brain regions. Here, we applied bursts of high- or low-intensity TMS over right posterior parietal cortex, during a task requiring sustained covert visuospatial attention to either the left or right hemifield, or in a neutral control condition, while recording blood oxygenation-level–dependent signal with a posterior MR surface coil. As expected, the active attention conditions activated components of the well-described “attention network,” as compared with the neutral baseline. Also as expected, when comparing left minus right attention, or vice versa, contralateral occipital visual cortex was activated. The critical new finding was that the impact of high- minus low-intensity parietal TMS upon these visual regions depended on the currently attended side. High- minus low-intensity parietal TMS increased the difference between contralateral versus ipsilateral attention in right extrastriate visual cortex. A related albeit less pronounced pattern was found for left extrastriate visual cortex. Our results confirm that right human parietal cortex can exert attention-dependent influences on occipital visual cortex and provide a proof of concept for the use of concurrent TMS–fMRI in studying how remote influences can vary in a purely top–down manner with attentional demands. Key words: concurrent TMS--fMRI, posterior parietal cortex, statedependence, visuospatial attention

Following bilateral extrastriate damage to areas that include the suspected human homologue of V5/MT, the patient LM has a specific deficit in processing moving stimuli. She has difficulty detecting the movement or coding the velocity of single moving dots. Nevertheless, we find that she can report human actions in Johansson “biological motion ”; displays. This requires the accurate coding of the direction and velocity of many moving dots. The implication is that structure can be extracted from motion in regions of visual cortex other than those traditionally associated with motion processing. However, she cannot report the spatial disposition of the actors whose actions she has recognized, not their movement in depth relative to her. A possible interpretation is that coding in these additional regions is primarily object-centred. Adding a small number of random stationary “noise” dots to the display prevents her from identifying the actions, suggesting that segregation by motion is implemented within the...

Three experiments examined spatial links between endogenous attention in vision and audition. In Experiment 1 subjects were presented auditorily with two verbal messages, one from either side of their midline. They had to repeat one message, for which they were also given lip-read information in some conditions. The lip-read information produced a larger improvement in performance when presented on the same side as the target sounds rather than the opposite side, suggesting a difficulty in attending to different locations in the two modalities. This difficulty cannot be attributed to the direction of gaze, as there was no effect of passively fixating meaningless lip-movements on the same versus opposite side as the target sounds. A similar (albeit reduced) difficulty in attending to different locations in the two modalities was observed in Experiment 2, where the auditory and visual tasks were unrelated. The auditory task was shadowing as before, while the visual task was monitoring for a specified target in a stream of visual characters appearing successively at a single location. A decrement in shadowing was observed when the monitored visual events were in a different location to the target sounds. Again, there was no effect of the direction of passive fixation. A final experiment found that the cost of attending to different locations in the two modalities can be observed in the conventional dual-task situation, i.e. with no distractor stimuli. These results demonstrate synergetic links between endogenous spatial attention in vision and audition.

International audience; Periodic crystal lattice rotations within compact clusters of shear bands (SB), developed in copper (purity of 99.98%), have been characterized to examine the role of lattice re-orientation within grains on slip propagation across grain boundaries. Polycrystalline copper (grain size 50 mu m) was deformed 50% in plane strain compression at room temperature to form two sets of well-defined macroscopic shear bands (MSB). The deformation-induced sub-structures and local changes in crystallographic orientations were investigated by FEG-SEM, equipped with high resolution EBSD. In all the deformed grains examined (within MSBs) a strong tendency to strain-induced re-orientation could be observed. Their crystal lattice rotated in such a way that one of the {111} slip planes became nearly parallel to the direction of maximum shear. A natural consequence of this rotation is the formation of a specific MSB microtexture which facilitates slip propagation across grain boundaries without tiny visible variation in the slip direction although the slip plane did not coincide exactly in the adjacent grains.

The authors report a series of 6 experiments investigating crossmodal links between vision and touch in covert endogenous spatial attention. When participants were informed that visual and tactile targets were more likely on 1 side than the other, speeded discrimination responses (continuous vs. pulsed, Experiments 1 and 2; or up vs. down, Experiment 3) for targets in both modalities were significantly faster on the expected side, even though target modality was entirely unpredictable. When participants expected a target on a particular side in just one modality, corresponding shifts of covert attention also took place in the other modality, as evidenced by faster elevation judgments on that side (Experiment 4). Larger attentional effects were found when directing visual and tactile attention to the same position rather than to different positions (Experiment 5). A final study with crossed hands revealed that these visuotactile links in spatial attention apply to common positions in external space.

The authors show that prismatic adaptation can reduce tactile inattention in stroke patients with unilateral neglect. Four patients with visuospatial neglect and tactile extinction underwent 10-minute application of 20degrees right-shifting prismatic lenses during pointing. This improved contralesional tactile perception in all patients, even for a task requiring no exploration or spatial motor responses. This finding suggests a potential role for prismatic adaptation in the rehabilitation of multiple sensory modalities in patients with neglect

Selective neurological impairments can shed light on different aspects of motor cognition. Brain-damaged patients with anosognosia for hemiplegia deny their motor deficit and believe they can still move the paralysed limb. Here we study, for the first time, if the anomalous subjective experience that their affected hand can still move, may have objective consequences that constrain movement execution with the opposite, intact hand. Using a bimanual motor task, in which anosognosic patients were asked to simultaneously trace out lines with their unaffected hand and circles with their paralysed hand, we found that the trajectories of the intact hand were influenced by the requested movement of the paralysed hand, with the intact hand tending to assume an oval trajectory (bimanual coupling effect). This effect was comparable to that of a group of healthy subjects who actually moved both hands. By contrast, brain-damaged patients with motor neglect or actual hemiplegia but no anosognosia did not show this bimanual constraint. We suggest that anosognosic patients may have intact motor intentionality and planning for the plegic hand. Rather than being merely an inexplicable confabulation, anosognosia for the plegic hand can produce objective constraints on what the intact hand does.

We investigated the effects of eye position on auditory spatial deficits in four patients with left neglect and right-hemisphere damage. using three blocked gaze directions (35 degrees to the right, central, or 35 degrees to the left), while preventing any head-movement to ensure that initial auditory inputs remained constant regardless of eye-in-orbit position. The auditory task required speeded discrimination of sound elevation, with patients moving a central lever up or down according to the vertical position of a peripheral target sound, regardless of its side (left or right). Replicating previous auditory research, the patients' vertical discrimination performance was worse for auditory targets on the contralesional (left) versus the ipsilesional side, indicating neglect-related auditory deficits on this task. Critically, while this worse performance for left than right auditory targets was present (for both reaction times and errors) when gaze was directed centrally or rightwards, it was considerably reduced when gaze was directed leftwards. These results demonstrate that lateral gaze-direction can modulate neglect-related auditory spatial deficits, even though eye-position did not alter the initial auditory inputs. This outcome may relate to audio-visual links in spatial orienting and potentially some retinocentric influences on perceived sound location, although the latter alone could not explain all our results. Such findings might involve multisensory brain structures in which responses to sounds are modulated by eye-in-orbit position.

Judging where others look is crucial for many social and cognitive functions. Past accounts of gaze perception emphasize geometrical cues from the seen eye. Human eyes have a unique morphology, with a large white surround (sclera) to the dark iris that may have evolved to enhance gaze processing. Here we show that the contrast polarity of seen eyes has a powerful influence on gaze perception. Adult observers are highly inaccurate in judging gaze direction for images of human eyes with negative contrast polarity (regardless of whether the surrounding face is positive or negative), even though negative images of eyes preserve the geometric properties of positives that are judged accurately. The detrimental effect of negative contrast polarity is much larger for gaze perception than for other directional judgements (e.g. judging which way a head is turned). These results suggest an 'expert' system for gaze perception, which always treats the darker region of a seen eye as the part that does the looking.

Previous work has found a left visual field (LVF) advantage for various judgements on faces, including identity and emotional expression. This has been related to possible right-hemisphere specialisation for face processing, and it has been proposed that this might reflect configural processing. We sought to determine whether a similar LVF advantage may also exist for gaze perception. In two experiments, normal adult subjects made judgements for seen gaze direction (left, right or straight). To assess how visual field may influence perception of gaze direction, eye stimuli were briefly presented unilaterally or bilaterally. In the latter case, the gaze direction of the two seen eyes could be congruent or incongruent (i.e. the two eyes could gaze in the same or different directions). For unilateral displays, performance was more accurate for LVF stimuli than RVF. With bilateral incongruent gaze, the LVF eye influenced judgements more strongly than the RVF eye. No such LVF advantage was found in a control experiment, in which subjects judged pupil size for similar eye stimuli. Taken together, these results reveal a LVF advantage for perception of gaze direction. Since only the eye region was visible, our results cannot be due to a LVF bias in processing the entire face context. Instead they suggest lateralisation specifically in processing the direction of seen gaze.