Vagaries of visual perception in autism

Three classes of perceptual phenomena have repeatedly been associated with autism spectrum disorder (ASD): superior processing of fine detail (local structure), either inferior processing of overall/global structure or an ability to ignore disruptive global/contextual information, and impaired motion perception. This review evaluates the quality of the evidence bearing on these three phenomena. We argue that while superior local processing has been robustly demonstrated, conclusions about global processing cannot be definitively drawn from the experiments to date, which have generally not precluded observers using more local cues. Perception of moving stimuli is impaired in ASD, but explanations in terms of magnocellular/dorsal deficits do not appear to be sufficient. We suggest that abnormalities in the superior temporal sulcus (STS) may provide a neural basis for the range of motion-processing deficits observed in ASD, including biological motion perception. Such an explanation may also provide a link between perceptual abnormalities and specific deficits in social cognition associated with autism.     

Neural basis of genetically determined visuospatial construction deficit in Williams syndrome

A unique opportunity to understand genetic determinants of cognition is offered by Williams syndrome (WS), a well-characterized hemideletion on chromosome 7q11.23 that causes extreme, specific weakness in visuospatial construction (the ability to visualize an object as a set of parts or construct a replica). Using multimodal neuroimaging, we identified a neural mechanism underlying the WS visuoconstructive deficit. Hierarchical assessment of visual processing with fMRI showed isolated hypoactivation in WS in the parietal portion of the dorsal stream. In the immediately adjacent parietooccipital/intraparietal sulcus, structural neuroimaging showed a gray matter volume reduction in participants with WS. Path analysis demonstrated that the functional abnormalities could be attributed to impaired input from this structurally altered region. Our observations confirm a longstanding hypothesis about dorsal stream dysfunction in WS, demonstrate effects of a localized abnormality on visual information processing in humans, and define a systems-level phenotype for mapping genetic determinants of visuoconstructive function.     

Deficit in visual temporal integration in autism spectrum disorders

Individuals with autism spectrum disorders (ASD) are superior in processing local features. Frith and Happe conceptualize this cognitive bias as ‘weak central coherence’, implying that a local enhancement derives from a weakness in integrating local elements into a coherent whole. The suggested deficit has been challenged, however, because individuals with ASD were not found to be inferior to normal controls in holistic perception. In these opposing studies, however, subjects were encouraged to ignore local features and attend to the whole. Therefore, no one has directly tested whether individuals with ASD are able to integrate local elements over time into a whole image. Here, we report a weakness of individuals with ASD in naming familiar objects moved behind a narrow slit, which was worsened by the absence of local salient features. The results indicate that individuals with ASD have a clear deficit in integrating local visual information over time into a global whole, providing direct evidence for the weak central coherence hypothesis.     

Effect of Cardiac Arrest on Cognitive Impairment and Hippocampal Plasticity in Middle-Aged Rats

Cardiopulmonary arrest is a leading cause of death and disability in the United States that usually occurs in the aged population. Cardiac arrest (CA) induces global ischemia, disrupting global cerebral circulation that results in ischemic brain injury and leads to cognitive impairments in survivors. Ischemia-induced neuronal damage in the hippocampus following CA can result in the impairment of cognitive function including spatial memory. In the present study, we used a model of asphyxial CA (ACA) in nine month old male Fischer 344 rats to investigate cognitive and synaptic deficits following mild global cerebral ischemia. These experiments were performed with the goals of 1) establishing a model of CA in nine month old middle-aged rats; and 2) to test the hypothesis that learning and memory deficits develop following mild global cerebral ischemia in middle-aged rats. To test this hypothesis, spatial memory assays (Barnes circular platform maze and contextual fear conditioning) and field recordings (long-term potentiation and paired-pulse facilitation) were performed. We show that following ACA in nine month old middle-aged rats, there is significant impairment in spatial memory formation, paired-pulse facilitation n dysfunction, and a reduction in the number of non-compromised hippocampal Cornu Ammonis 1 and subiculum neurons. In conclusion, nine month old animals undergoing cardiac arrest have impaired survival, deficits in spatial memory formation, and synaptic dysfunction.     

Atypical Integration of Motion Signals in Autism Spectrum Conditions

Vision in Autism Spectrum Conditions (ASC) is characterized by enhanced perception of local elements, but impaired perception of global percepts. Deficits in coherent motion perception seem to support this characterization, but the roots and robustness of such deficits remain unclear. We aimed to investigate the dynamics of the perceptual decision-making network known to support coherent motion perception. In a series of forced-choice coherent motion perception tests, we parametrically varied a single stimulus dimension, viewing duration, to test whether the rate at which evidence is accumulated towards a global decision is atypical in ASC. 40 adult participants (20 ASC) performed a classic motion discrimination task, manually indicating the global direction of motion in a random-dot kinematogram across a range of coherence levels (2–75%) and stimulus-viewing durations (200–1500 ms). We report a deficit in global motion perception at short viewing durations in ASC. Critically, however, we found that increasing the amount of time over which motion signals could be integrated reduced the magnitude of the deficit, such that at the longest duration there was no difference between the ASC and control groups. Further, the deficit in motion integration at the shortest duration was significantly associated with the severity of autistic symptoms in our clinical population, and was independent from measures of intelligence. These results point to atypical integration of motion signals during the construction of a global percept in ASC. Based on the neural correlates of decision-making in global motion perception our findings suggest the global motion deficit observed in ASC could reflect a slower or more variable response from the primary motion area of the brain or longer accumulation of evidence towards a decision-bound in parietal areas.     

Form and motion coherence activate independent, but not dorsal/ventral segregated, networks in the human brain

There is much evidence in primates' visual processing for distinct mechanisms involved in object recognition and encoding object position and motion, which have been identified with 'ventral' and 'dorsal' streams, respectively, of the extra-striate visual areas [1] [2] [3]. This distinction may yield insights into normal human perception, its development and pathology. Motion coherence sensitivity has been taken as a test of global processing in the dorsal stream [4] [5]. We have proposed an analogous 'form coherence' measure of global processing in the ventral stream [6]. In a functional magnetic resonance imaging (fMRI) experiment, we found that the cortical regions activated by form coherence did not overlap with those activated by motion coherence in the same individuals. Areas differentially activated by form coherence included regions in the middle occipital gyrus, the ventral occipital surface, the intraparietal sulcus, and the temporal lobe. Motion coherence activated areas consistent with those previously identified as V5 and V3a, the ventral occipital surface, the intraparietal sulcus, and temporal structures. Neither form nor motion coherence activated area V1 differentially. Form and motion foci in occipital, parietal, and temporal areas were nearby but showed almost no overlap. These results support the idea that form and motion coherence test distinct functional brain systems, but that these do not necessarily correspond to a gross anatomical separation of dorsal and ventral processing streams.     

Decreased Coherent Motion Discrimination in Autism Spectrum Disorder: The Role of Attentional Zoom-Out Deficit

Autism spectrum disorder (ASD) has been associated with decreased coherent dot motion (CDM) performance, a task that measures magnocellular sensitivity as well as fronto-parietal attentional integration processing. In order to clarify the role of spatial attention in CDM tasks, we measured the perception of coherently moving dots displayed in the central or peripheral visual field in ASD and typically developing children. A dorsal-stream deficit in children with ASD should predict a generally poorer performance in both conditions. In our study, however, we show that in children with ASD, CDM perception was selectively impaired in the central condition. In addition, in the ASD group, CDM efficiency was correlated to the ability to zoom out the attentional focus. Importantly, autism symptoms severity was related to both the CDM and attentional zooming-out impairment. These findings suggest that a dysfunction in the attentional network might help to explain decreased CDM discrimination as well as the “core” social cognition deficits of ASD.     

Visual perception skills: a comparison between patients with Noonan syndrome and 22q11.2 deletion syndrome

Ventral and dorsal streams are visual pathways deputed to transmit information from the photoreceptors of the retina to the lateral geniculate nucleus and then to the primary visual cortex (V1). Several studies investigated whether one pathway is more vulnerable than the other during development, and whether these streams develop at different rates. The results are still discordant. The aim of the present study was to understand the functionality of the dorsal and the ventral streams in two populations affected by different genetic disorders, Noonan syndrome (NS) and 22q11.2 deletion syndrome (22q11.2DS), and explore the possible genotype–phenotype relationships. ‘Form coherence’ abilities for the ventral stream and ‘motion coherence’ abilities for the dorsal stream were evaluated in 19 participants with NS and 20 participants with 22q11.2DS. Collected data were compared with 55 age‐matched controls. Participants with NS and 22q11.2DS did not differ in the form coherence task, and their performance was significantly lower than that of controls. However, in the motion coherence task, the group with NS and controls did not differ, and both obtained significantly higher scores than the group with 22q11.2DS. Our findings indicate that deficits in the dorsal stream are related to the specific genotype, and that in our syndromic groups the ventral stream is more vulnerable than the dorsal stream.     

A biased competition account of attention and memory in Alzheimer's disease

The common view of Alzheimer''s disease (AD) is that of an age-related memory disorder, i.e. declarative memory deficits are the first signs of the disease and associated with progressive brain changes in the medial temporal lobes and the default mode network. However, two findings challenge this view. First, new model-based tools of attention research have revealed that impaired selective attention accompanies memory deficits from early pre-dementia AD stages on. Second, very early distributed lesions of lateral parietal networks may cause these attention deficits by disrupting brain mechanisms underlying attentional biased competition. We suggest that memory and attention impairments might indicate disturbances of a common underlying neurocognitive mechanism. We propose a unifying account of impaired neural interactions within and across brain networks involved in attention and memory inspired by the biased competition principle. We specify this account at two levels of analysis: at the computational level, the selective competition of representations during both perception and memory is biased by AD-induced lesions; at the large-scale brain level, integration within and across intrinsic brain networks, which overlap in parietal and temporal lobes, is disrupted. This account integrates a large amount of previously unrelated findings of changed behaviour and brain networks and favours a brain mechanism-centred view on AD.     

Towards an understanding of the mechanisms of weak central coherence effects: experiments in visual configural learning and auditory perception

The weak central coherence hypothesis of Frith is one of the most prominent theories concerning the abnormal performance of individuals with autism on tasks that involve local and global processing. Individuals with autism often outperform matched nonautistic individuals on tasks in which success depends upon processing of local features, and underperform on tasks that require global processing. We review those studies that have been unable to identify the locus of the mechanisms that may be responsible for weak central coherence effects and those that show that local processing is enhanced in autism but not at the expense of global processing. In the light of these studies, we propose that the mechanisms which can give rise to 'weak central coherence' effects may be perceptual. More specifically, we propose that perception operates to enhance the representation of individual perceptual features but that this does not impact adversely on representations that involve integration of features. This proposal was supported in the two experiments we report on configural and feature discrimination learning in high-functioning children with autism. We also examined processes of perception directly, in an auditory filtering task which measured the width of auditory filters in individuals with autism and found that the width of auditory filters in autism were abnormally broad. We consider the implications of these findings for perceptual theories of the mechanisms underpinning weak central coherence effects.     

The Neuropsychology of Starvation: Set-Shifting and Central Coherence in a Fasted Nonclinical Sample

Objectives

Recent research suggests certain neuropsychological deficits occur in anorexia nervosa (AN). The role of starvation in these deficits remains unclear. Studies of individuals without AN can elucidate our understanding of the effect of short-term starvation on neuropsychological performance.

Methods

Using a within-subjects repeated measures design, 60 healthy female participants were tested once after fasting for 18 hours, and once when satiated. Measures included two tasks to measure central coherence and a set-shifting task.

Results

Fasting exacerbated set-shifting difficulties on a rule-change task. Fasting was associated with stronger local and impaired global processing, indicating weaker central coherence.

Conclusions

Models of AN that propose a central role for set-shifting difficulties or weak central coherence should also consider the impact of short-term fasting on these processes.     

Global perception depends on coherent work of bilateral visual cortices: Transcranial magnetic stimulation (TMS) studies

Previous research suggests that the right and left hemispheres dominate global and local perception of hierarchical patterns, respectively. The current work examined whether global perception of hierarchical stimuli requires coherent work of bilateral visual cortices using transcranial magnetic stimulation (TMS). Subjects discriminated global or local properties of compound letters in Experiment 1. Reaction times were recorded when single-pulse real TMS or sham TMS was delivered over the left or right visual cortex. While a global precedence effect (i.e., faster responses to global than local targets and stronger global-to-local interference than the reverse) was observed, TMS decreased global-to-local interference whereas increased local-to-global interference. Experiment 2 ruled out the possibility that the effects observed in Experiment 1 resulted from perceptual learning. Experiment 3 used compound shapes and observed TMS effect similar to that in Experiment 1. Moreover, TMS also slowed global RTs whereas speeded up local RTs in Experiment 3. Finally, the TMS effects observed in Experiments 1 and 3 did not differ between the conditions when TMS was applied over the left and right hemispheres. The results support a coherence hypothesis that global perception of compound stimuli depends upon the coherent work of bilateral visual cortices.     

Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia

Growing genetic evidence is converging in favor of common pathogenic mechanisms for autism spectrum disorders (ASD), intellectual disability (ID or mental retardation) and schizophrenia (SCZ), three neurodevelopmental disorders affecting cognition and behavior. Copy number variations and deleterious mutations in synaptic organizing proteins including NRXN1 have been associated with these neurodevelopmental disorders, but no such associations have been reported for NRXN2 or NRXN3. From resequencing the three neurexin genes in individuals affected by ASD (n = 142), SCZ (n = 143) or non-syndromic ID (n = 94), we identified a truncating mutation in NRXN2 in a patient with ASD inherited from a father with severe language delay and family history of SCZ. We also identified a de novo truncating mutation in NRXN1 in a patient with SCZ, and other potential pathogenic ASD mutations. These truncating mutations result in proteins that fail to promote synaptic differentiation in neuron coculture and fail to bind either of the established postsynaptic binding partners LRRTM2 or NLGN2 in cell binding assays. Our findings link NRXN2 disruption to the pathogenesis of ASD for the first time and further strengthen the involvement of NRXN1 in SCZ, supporting the notion of a common genetic mechanism in these disorders.     

fMRI signal changes in response to forced expiratory loading in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) patients show impaired ventilatory responses to CO2 and hypoxia and reduced drive to breathe during sleep but retain appropriate breathing patterns in response to volition or increased exercise. Breath-by-breath influences on heart rate are also deficient. Using functional magnetic resonance imaging techniques, we examined responses over the brain to voluntary forced expiratory loading, a task that CCHS patients can perform but that results in impaired rapid heart rate variation patterns normally associated with the loading challenge. Increased signals emerged in control (n = 14) over CCHS (n = 13; ventilator dependent during sleep but not waking) subjects in the cingulate and right parietal cortex, cerebellar cortex and fastigial nucleus, and basal ganglia, whereas anterior cerebellar cortical sites and deep nuclei, dorsal midbrain, and dorsal pons showed increased signals in the patient group. The dorsal and ventral medulla showed delayed responses in CCHS patients. Primary motor and sensory areas bordering the central sulcus showed comparable responses in both groups. The delayed responses in medullary sensory and output regions and the aberrant reactions in cerebellar and pontine sensorimotor coordination areas suggest that rapid cardiorespiratory integration deficits in CCHS may stem from defects in these sites. Additional autonomic and perceptual motor deficits may derive from cingulate and parietal cortex aberrations.     

Early Mortality and Primary Causes of Death in Mothers of Children with Intellectual Disability or Autism Spectrum Disorder: A Retrospective Cohort Study

Introduction

Mothers of children with intellectual disability or autism spectrum disorder (ASD) have poorer health than other mothers. Yet no research has explored whether this poorer health is reflected in mortality rates or whether certain causes of death are more likely. We aimed to calculate the hazard ratios for death and for the primary causes of death in mothers of children with intellectual disability or ASD compared to other mothers.

Methods

The study population comprised all mothers of live-born children in Western Australia from 1983–2005. We accessed state-wide databases which enabled us to link socio-demographic details, birth dates, diagnoses of intellectual disability or ASD in the children and dates and causes of death for all mothers who had died prior to 2011. Using Cox Regression with death by any cause and death by each of the three primary causes as the event of interest, we calculated hazard ratios for death for mothers of children intellectual disability or ASD compared to other mothers.

Results and Discussion

During the study period, mothers of children with intellectual disability or ASD had more than twice the risk of death. Mothers of children with intellectual disability were 40% more likely to die of cancer; 150% more likely to die of cardiovascular disease and nearly 200% more likely to die from misadventure than other mothers. Due to small numbers, only hazard ratios for cancer were calculated for mothers of children with ASD. These mothers were about 50% more likely to die from cancer than other mothers. Possible causes and implications of our results are discussed.

Conclusion

Similar studies, pooling data from registries elsewhere, would improve our understanding of factors increasing the mortality of mothers of children with intellectual disability or ASD. This would allow the implementation of informed services and interventions to improve these mothers'' longevity.     

Unveiling functions of the visual cortex using task-specific deep neural networks

The human visual cortex enables visual perception through a cascade of hierarchical computations in cortical regions with distinct functionalities. Here, we introduce an AI-driven approach to discover the functional mapping of the visual cortex. We related human brain responses to scene images measured with functional MRI (fMRI) systematically to a diverse set of deep neural networks (DNNs) optimized to perform different scene perception tasks. We found a structured mapping between DNN tasks and brain regions along the ventral and dorsal visual streams. Low-level visual tasks mapped onto early brain regions, 3-dimensional scene perception tasks mapped onto the dorsal stream, and semantic tasks mapped onto the ventral stream. This mapping was of high fidelity, with more than 60% of the explainable variance in nine key regions being explained. Together, our results provide a novel functional mapping of the human visual cortex and demonstrate the power of the computational approach.     

Inhibitory avoidance memory retention in the elevated T-maze is impaired after perivascular manipulation of the common carotid arteries

Perivascular manipulation promoted by the positioning of a silicone collar around the common carotid arteries causes local inflammation and has been suggested as an animal model of atherosclerosis. This manipulation induces biochemical and morphological changes that are similar to those observed in the early stage of atherosclerosis in humans. Based on evidences showing that atherosclerosis is associated with cognitive deficits in humans, we presently investigated the temporal consequences of the bilateral positioning of silicone collars around the common carotid arteries (n = 15) on inhibitory avoidance memory retention in male Wistar rats tested in the elevated T-maze. The effects of this procedure were compared to those observed in sham-operated animals (n = 15) and to those observed in animals submitted to permanent bilateral occlusion of the common carotid arteries (n = 16). Additionally we studied the effects of the pretreatment with the non-selective anti-inflammatory drug indomethacin (n = 13) or the selective COX-2 inhibitor celecoxib (n = 12) and compared the effects to those of the pretreatment with vehicle (n = 11). The results showed that the silicone collar implants induced deficits in memory retention when animals were tested 2 and 4, but not 15 or 30, days after surgery. Permanent bilateral occlusion of the common carotid arteries impaired avoidance retention up to 30 days after surgery. Pretreatment with indomethacin (2 mg/kg/day) or celecoxib (5 mg/kg/day) post surgery and up to 3 days thereafter did not prevent memory deficits caused by silicone collar implants. Our data suggest that the prostanoids that participate in the inflammatory process triggered by the placement of the silicone collar do not seem responsible for the deficit in memory retention observed during the first days after collar placement.     

Oxidative Stress Induced NMDA Receptor Alteration Leads to Spatial Memory Deficits in Temporal Lobe Epilepsy: Ameliorative Effects of Withania somnifera and Withanolide A

In the present study we investigate the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in restoring spatial memory deficit by inhibiting oxidative stress induced alteration in glutamergic neurotransmission. We demonstrate significant cellular loss in hippocampus of epileptic rats, visualized through decreased TOPRO stained neurons. Impaired spatial memory was observed in epileptic rats after Radial arm maze test. Treatment with WS and WA has resulted in increased number of TOPRO stained neurons. Enhanced performance of epileptic rats treated with WS and WA was observed in Radial arm maze test. The antioxidant activity of WS and WA was studied using superoxide dismutase (SOD) and Catalase (CAT) assays in the hippocampus of experimental rats. The SOD activity and CAT activity decreased significantly in epileptic group, treatment with WS and WA significantly reversed the enzymatic activities to near control. Real time gene expression studies of SOD and GPx showed significant up-regulation in epileptic group compared to control. Treatment with WS and WA showed significant reversal to near control. Lipid peroxidation quantified using TBARS assay, significantly increased in epileptic rats. Treatment with WS and WA showed significant reversal to near control. NMDA receptor expression decreased in epileptic rats. The treatment with WS and WA resulted in physiological expression of NMDA receptors. This data suggests that oxidative stress effects membrane constitution resulting in decreased NMDA receptor density leading to impaired spatial memory. Treatment with WS and WA has ameliorated spatial memory deficits by enhancing antioxidant system and restoring altered NMDA receptor density.     

Diminished medial prefrontal activity behind autistic social judgments of incongruent information

Individuals with autism spectrum disorders (ASD) tend to make inadequate social judgments, particularly when the nonverbal and verbal emotional expressions of other people are incongruent. Although previous behavioral studies have suggested that ASD individuals have difficulty in using nonverbal cues when presented with incongruent verbal-nonverbal information, the neural mechanisms underlying this symptom of ASD remain unclear. In the present functional magnetic resonance imaging study, we compared brain activity in 15 non-medicated adult males with high-functioning ASD to that of 17 age-, parental-background-, socioeconomic-, and intelligence-quotient-matched typically-developed (TD) male participants. Brain activity was measured while each participant made friend or foe judgments of realistic movies in which professional actors spoke with conflicting nonverbal facial expressions and voice prosody. We found that the ASD group made significantly less judgments primarily based on the nonverbal information than the TD group, and they exhibited significantly less brain activity in the right inferior frontal gyrus, bilateral anterior insula, anterior cingulate cortex/ventral medial prefrontal cortex (ACC/vmPFC), and dorsal medial prefrontal cortex (dmPFC) than the TD group. Among these five regions, the ACC/vmPFC and dmPFC were most involved in nonverbal-information-biased judgments in the TD group. Furthermore, the degree of decrease of the brain activity in these two brain regions predicted the severity of autistic communication deficits. The findings indicate that diminished activity in the ACC/vmPFC and dmPFC underlies the impaired abilities of individuals with ASD to use nonverbal content when making judgments regarding other people based on incongruent social information.     

Global perception depends on coherent work of bilateral visual cortices: Transcranial magnetic stimulation (TMS) studies

Previous research suggests that the right and left hemispheres dominate global and local perception of hierarchical patterns, respectively. The current work examined whether global perception of hierarchi-cal stimuli requires coherent work of bilateral visual cortices using transcranial magnetic stimulation (TMS). Subjects discriminated global or local properties of compound letters in Experiment 1. Reaction times were recorded when single-pulse real TMS or sham TMS was delivered over the left or right visual cortex. While a global precedence effect (i.e., faster responses to global than local targets and stronger global-to-local interference than the reverse) was observed, TMS decreased global-to-local interference whereas increased local-to-global interference. Experiment 2 ruled out the possibility that the effects observed in Experiment 1 resulted from perceptual learning. Experiment 3 used compound shapes and observed TMS effect similar to that in Experiment 1. Moreover, TMS also slowed global RTs whereas speeded up local RTs in Experiment 3. Finally, the TMS effects observed in Experiments 1 and 3 did not differ between the conditions when TMS was applied over the left and right hemispheres. The results support a coherence hypothesis that global perception of compound stimuli depends upon the co-herent work of bilateral visual cortices.