Search

Abstract Pupillary contagion occurs when one’s pupil size unconsciously adapts to the pupil size of an observed individual and is presumed to reflect the transfer of arousal. Importantly, when estimating pupil contagion, low level stimuli properties need to be controlled for, to ensure that observations of pupillary changes are due to internal change in arousal rather than the external differences between stimuli. Here, naturalistic images of children’s faces depicting either small or large pupils were presented to a group of children and adolescents with a wide range of autistic traits, a third of whom had been diagnosed with autism. We examined the extent to which pupillary contagion reflects autonomic nervous system reaction through pupil size change, heart rate and skin conductance response. Our second aim was to determine the association between arousal reaction to stimuli and degree of autistic traits. Results show that pupil contagion and concomitant heart rate change, but not skin conductance change, was evident when gaze was restricted to the eye region of face stimuli. A positive association was also observed between pupillary contagion and autistic traits when participants’ gaze was constrained to the eye region. Findings add to a broader understanding of the mechanisms underlying pupillary contagion and its association with autism.

Abstract Eye contact is a central component in face-to-face interactions. It is important in structuring communicative exchanges and offers critical insights into others' interests and intentions. To better understand eye contact in face-to-face interactions, we applied a novel, non-intrusive deep-learning-based dual-camera system and investigated associations between eye contact and autistic traits as well as self-reported eye contact discomfort during a referential communication task, where participants and the experimenter had to guess, in turn, a word known by the other individual. Corroborating previous research, we found that participants’ eye gaze and mutual eye contact were inversely related to autistic traits. In addition, our findings revealed different behaviors depending on the role in the dyad: listening and guessing were associated with increased eye contact compared with describing words. In the listening and guessing condition, only a subgroup who reported eye contact discomfort had a lower amount of eye gaze and eye contact. When describing words, higher autistic traits were associated with reduced eye gaze and eye contact. Our data indicate that eye contact is inversely associated with autistic traits when describing words, and that eye gaze is modulated by the communicative role in a conversation.

Abstract Background Despite the prevalence of Autism Spectrum Disorder (ASD) globally, there’s a knowledge gap pertaining to autism in Arabic nations. Recognizing the need for validated biomarkers for ASD, our study leverages eye-tracking technology to understand gaze patterns associated with ASD, focusing on joint attention (JA) and atypical gaze patterns during face perception. While previous studies typically evaluate a single eye-tracking metric, our research combines multiple metrics to capture the multidimensional nature of autism, focusing on dwell times on eyes, left facial side, and joint attention. Methods We recorded data from 104 participants (41 neurotypical, mean age: 8.21 ± 4.12 years; 63 with ASD, mean age 8 ± 3.89 years). The data collection consisted of a series of visual stimuli of cartoon faces of humans and animals, presented to the participants in a controlled environment. During each stimulus, the eye movements of the participants were recorded and analyzed, extracting metrics such as time to first fixation and dwell time. We then used these data to train a number of machine learning classification algorithms, to determine if these biomarkers can be used to diagnose ASD. Results We found no significant difference in eye-dwell time between autistic and control groups on human or animal eyes. However, autistic individuals focused less on the left side of both human and animal faces, indicating reduced left visual field (LVF) bias. They also showed slower response times and shorter dwell times on congruent objects during joint attention (JA) tasks, indicating diminished reflexive joint attention. No significant difference was found in time spent on incongruent objects during JA tasks. These results suggest potential eye-tracking biomarkers for autism. The best-performing algorithm was the random forest one, which achieved accuracy = 0.76 ± 0.08, precision = 0.78 ± 0.13, recall = 0.84 ± 0.07, and F1 = 0.80 ± 0.09. Conclusions Although the autism group displayed notable differences in reflexive joint attention and left visual field bias, the dwell time on eyes was not significantly different. Nevertheless, the machine algorithm model trained on these data proved effective at diagnosing ASD, showing the potential of these biomarkers. Our study shows promising results and opens up potential for further exploration in this under-researched geographical context.

Abstract Background Prior research has shown that memory for action sentences is stronger when stimuli are enacted during encoding than simply listened to: the so‐called enactment effect. The goal of the present study was to explore how writing during encoding—through handwriting and through keyboarding—fares compared with enacting, in supporting memory recall. Methods One hundred Norwegian high school students (64 girls, 36 boys) aged 16–21 years (M = 17.1) participated in the study. Four lists of verb–noun sentences with 12 sentences in each list were presented in four encoding conditions: (i) motor enactment, (ii) verbal listening, (iii) handwriting, and (iv) keyboarding. Results Results revealed a significant main effect of encoding condition, with the best memory gained in the enactment condition. Regarding writing, results showed that handwriting and keyboarding during encoding produced the lowest recall in comparison with the enactment and verbal listening conditions. Conclusion These results thus provide additional support for the enactment effect. While there has been much discussion on the relative benefits of handwriting versus keyboarding on student performance, both seemed to be equally poor strategies for the particular learning task explored here, potentially through increased cognitive load.

Abstract Several preclinical and clinical lines of evidence suggest a role of neuroinflammation in migraine. Neuroimaging offers the possibility to investigate and localize neuroinflammation in vivo in patients with migraine, and to characterize specific inflammatory constituents, such as vascular permeability, and macrophage or microglia activity. Despite all imaging data accumulated on neuroinflammation across the past three decades, an overview of the imaging evidence of neuroinflammation in migraine is still missing. We conducted a systematic review in the Pubmed and Embase databases to evaluate existing imaging data on inflammation in migraine, and to identify gaps in the literature. We included 20 studies investigating migraine without aura (N = 4), migraine with aura (N = 8), both migraine with and without aura (N = 3), or hemiplegic migraine (N = 5). In migraine without aura, macrophage activation was not evident. In migraine with aura, imaging evidence suggested microglial and parameningeal inflammatory activity. Increased vascular permeability was mostly found in hemiplegic migraine, and was atypical in migraine with and without aura. Based on the weight of existing and emerging data, we show that most studies have concentrated on demonstrating increased vascular permeability as a marker of neuroinflammation, with tools that may not have been optimal. In the future, novel, more sensitive techniques, as well as imaging tracers delineating specific inflammatory pathways may further bridge the gap between preclinical and clinical findings.

Abstract Migraine is a ubiquitous neurologic disease that afflicts people of all ages. Its molecular pathogenesis involves peptides that promote intracranial vasodilation and modulate nociceptive transmission upon release from sensory afferents of cells in the trigeminal ganglion and parasympathetic efferents of cells in the sphenopalatine ganglion. Experimental data have confirmed that intravenous infusion of these vasoactive peptides induce migraine attacks in people with migraine, but it remains a point of scientific contention whether their site of action lies outside or within the central nervous system. In this context, it has been hypothesized that transient dysfunction of brain barriers before or during migraine attacks might facilitate the passage of migraine-inducing peptides into the central nervous system. Here, we review evidence suggestive of brain barrier dysfunction in migraine pathogenesis and conclude with lessons learned in order to provide directions for future research efforts.

Abstract Background An overrepresentation of neurodevelopmental problems (NDPs) has been observed in individuals with avoidant/restrictive food intake disorder (ARFID). Previous studies on the association between ARFID and NDPs have been limited by cross‐sectional data from clinical samples of small size. This study aimed to extend previous research by using prospectively collected data in a non‐clinical child cohort. We examined the occurrence of early NDPs in 4–7‐year‐old children with suspected ARFID and how predictive early NDPs are of ARFID. Methods Data were collected via parent‐report a sub‐sample of the Japan Environment and Children's Study (JECS) including 3728 children born 2011–2014 in Kochi prefecture. NDPs were assessed biannually between 0.5 and 3 years of age with the Ages and Stages Questionnaire‐3, at age 2.5 years with the ESSENCE‐Q, and at age 1 and 3 years via parent‐reported clinical diagnoses. ARFID was identified cross‐sectionally (at age 4–7 years) using a newly developed screening tool. Logistic regressions were used to test association of (1) a composite early NDP risk score, (2) specific early NDPs, and (3) neurodevelopmental trajectories over time with ARFID. Results Children in the highest risk percentiles of the NDP risk score had roughly three times higher odds of having suspected ARFID; the absolute risk of later ARFID for children above the 90th percentile was 3.1%. Early NDPs (excluding early feeding problems) were more predictive of later ARFID than were early feeding problems. Specific NDPs predictive of ARFID were problems with general development, communication/language, attention/concentration, social interaction, and sleep. Neurodevelopmental trajectories of children with and without suspected ARFID started to divert after age 1 year. Conclusions The results mirror the previously observed overrepresentation of NDPs in ARFID populations. In this non‐clinical child cohort, early feeding problems were common and rarely developed into ARFID; however, our findings imply that they should be monitored closely in children with high NDP risk to prevent ARFID.

Abstract To identify newborns at risk of developing ASD and to detect ASD biomarkers early after birth, we compared retrospectively ultrasound and biological measurements of babies diagnosed later with ASD or neurotypical (NT) that are collected routinely during pregnancy and birth. We used a supervised machine learning algorithm with a cross-validation technique to classify NT and ASD babies and performed various statistical tests. With a minimization of the false positive rate, 96% of NT and 41% of ASD babies were identified with a positive predictive value of 77%. We identified the following biomarkers related to ASD: sex, maternal familial history of auto-immune diseases, maternal immunization to CMV, IgG CMV level, timing of fetal rotation on head, femur length in the 3rd trimester, white blood cell count in the 3rd trimester, fetal heart rate during labor, newborn feeding and temperature difference between birth and one day after. Furthermore, statistical models revealed that a subpopulation of 38% of babies at risk of ASD had significantly larger fetal head circumference than age-matched NT ones, suggesting an in utero origin of the reported bigger brains of toddlers with ASD. Our results suggest that pregnancy follow-up measurements might provide an early prognosis of ASD enabling pre-symptomatic behavioral interventions to attenuate efficiently ASD developmental sequels.

Abstract While migraine headaches can be provoked, or predicted by the presence of an aura or premonitory symptoms, the prediction or elicitation of the aura itself is more problematic. Therefore, imaging studies directly examining the aura phenomenon are sparse. There are however interictal imaging studies that can shed light on the pathophysiology of the migraine with aura (MWA) cascade. Here, we review findings pointing to the involvement of cortical spreading depression (CSD) and neuroinflammation in MWA. Whether asymptomatic CSD also happens in some migraine without aura is still under debate. In addition, new evidence points to glial activation in MWA, indicating the involvement of astrocytes in the neuroinflammatory cascade that follows CSD, as well as dural macrophages, supporting the involvement of the trigeminovascular system in migraine pain.

The ARX (Aristaless Related homeoboX) gene was identified in 2002 as responsible for XLAG syndrome, a lissencephaly characterized by an almost complete absence of cortical GABAergic interneurons, and for milder forms of X-linked Intellectual Disability (ID) without apparent brain abnormalities. The most frequent mutation found in the ARX gene, a duplication of 24 base pairs (c.429_452dup24) in exon 2, results in a recognizable syndrome in which patients present ID without primary motor impairment, but with a very specific upper limb distal motor apraxia associated with a pathognomonic hand-grip, described as developmental Limb Kinetic Apraxia (LKA).In this study, we first present ARX expression during human fetal brain development showing that it is strongly expressed in GABAergic neuronal progenitors during the second and third trimester of pregnancy. We show that although ARX expression strongly decreases towards the end of gestation, it is still present after birth in some neurons of the basal ganglia, thalamus and cerebral cortex, suggesting that ARX also plays a role in more mature neuron functioning. Then, using morphometric brain MRI in 13 ARX patients carrying c.429_452dup24 mutation and in 13 sex- and age-matched healthy controls, we show that ARX patients have a significantly decreased volume of several brain structures including the striatum (and more specifically the caudate nucleus), hippocampus and thalamus as well as decreased precentral gyrus cortical thickness. We observe a significant correlation between caudate nucleus volume reduction and motor impairment severity quantified by kinematic parameter of precision grip.As basal ganglia are known to regulate sensorimotor processing and are involved in the control of precision gripping, the combined decrease in cortical thickness of primary motor cortex and basal ganglia volume in ARX dup24 patients is very likely the anatomical substrate of this developmental form of LKA. Keywords: ARX, Human brain development, Intellectual disability, Morphometric MRI, Kinematic, Limb Kinetic Apraxia

Abstract Individuals with Autism Spectrum Disorder (ASD) seem to have difficulties looking others in the eyes, but the substrate for this behavior is not well understood. The subcortical pathway, which consists of superior colliculus, pulvinar nucleus of the thalamus, and amygdala, enables rapid and automatic face processing. A specific component of this pathway – i.e., the amygdala – has been shown to be abnormally activated in paradigms where individuals had to specifically attend to the eye-region; however, a direct examination of the effect of manipulating the gaze to the eye-regions on all the components of the subcortical system altogether has never been performed. The subcortical system is particularly important as it shapes the functional specialization of the face-processing cortex during development. Using functional MRI, we investigated the effect of constraining gaze in the eye-region during dynamic emotional face perception in groups of participants with ASD and typical controls. We computed differences in activation in the subcortical face processing system (superior colliculus, pulvinar nucleus of the thalamus and amygdala) for the same stimuli seen freely or with the gaze constrained in the eye-region. Our results show that when constrained to look in the eyes, individuals with ASD show abnormally high activation in the subcortical system, which may be at the basis of their eye avoidance in daily life.

Migraine, the most frequent neurological ailment, affects visual processing during and between attacks. Most visual disturbances associated with migraine can be explained by increased neural hyperexcitability, as suggested by clinical, physiological and neuroimaging evidence. Here, we review how simple (e.g., patterns, color) visual functions can be affected in patients with migraine, describe the different complex manifestations of the so-called Alice in Wonderland Syndrome, and discuss how visual stimuli can trigger migraine attacks. We also reinforce the importance of a thorough, proactive examination of visual function in people with migraine.

An older adult positivity effect, i.e., the tendency for older adults to favor positive over negative stimulus information more than do younger adults, has been previously shown in attention, memory, and evaluations. This effect has been attributed to greater emotion regulation in older adults. In the case of attention and memory, this explanation has been supported by some evidence that the older adult positivity effect is most pronounced for negative stimuli, which would motivate emotion regulation, and that it is reduced by cognitive load, which would impede emotion regulation. We investigated whether greater older adult positivity in the case of evaluative responses to faces is also enhanced for negative stimuli and attenuated by cognitive load, as an emotion regulation explanation would predict. In two studies, younger and older adults rated trustworthiness of faces that varied in valence both under low and high cognitive load, with the latter manipulated by a distracting backwards counting task. In Study 1, face valence was manipulated by attractiveness (low /disfigured faces, medium, high/fashion models' faces). In Study 2, face valence was manipulated by trustworthiness (low, medium, high). Both studies revealed a significant older adult positivity effect. However, contrary to an emotion regulation account, this effect was not stronger for more negative faces, and cognitive load increased rather than decreased the rated trustworthiness of negatively valenced faces. Although inconsistent with emotion regulation, the latter effect is consistent with theory and research arguing that more cognitive resources are required to process negative stimuli, because they are more cognitively elaborated than positive ones. The finding that increased age and increased cognitive load both enhanced the positivity of trustworthy ratings suggests that the older adult positivity effect in evaluative ratings of faces may reflect age-related declines in cognitive capacity rather than increases in the regulation of negative emotions.

BACKGROUND:Intellectual Disability (ID) is characterized by deficits in intellectual functions such as reasoning, problem-solving, planning, abstract thinking, judgment, and learning. As new avenues are emerging for treatment of genetically determined ID (such as Down's syndrome or Fragile X syndrome), it is necessary to identify objective reliable and sensitive outcome measures for use in clinical trials. OBJECTIVE:We developed a novel visual analogical reasoning paradigm, inspired by the Progressive Raven's Matrices, but appropriate for Intellectually Disabled patients. This new paradigm assesses reasoning and inhibition abilities in ID patients. METHODS:We performed behavioural analyses for this task (with a reaction time and error rate analysis, Study 1) in 96 healthy controls (adults and typically developed children older than 4) and 41 genetically determined ID patients (Fragile X syndrome, Down syndrome and ARX mutated patients). In order to establish and quantify the cognitive strategies used to solve the task, we also performed an eye-tracking analysis (Study 2). RESULTS:Down syndrome, ARX and Fragile X patients were significantly slower and made significantly more errors than chronological age-matched healthy controls. The effect of inhibition on error rate was greater than the matrix complexity effect in ID patients, opposite to findings in adult healthy controls. Interestingly, ID patients were more impaired by inhibition than mental age-matched healthy controls, but not by the matrix complexity. Eye-tracking analysis made it possible to identify the strategy used by the participants to solve the task. Adult healthy controls used a matrix-based strategy, whereas ID patients used a response-based strategy. Furthermore, etiologic-specific reasoning differences were evidenced between ID patients groups. CONCLUSION:We suggest that this paradigm, appropriate for ID patients and developmental populations as well as adult healthy controls, provides an objective and quantitative assessment of visual analogical reasoning and cognitive inhibition, enabling testing for the effect of pharmacological or behavioural intervention in these specific populations.

Visual scanning of faces in individuals with Autism Spectrum Disorder (ASD) has been intensively studied using eye-tracking technology. However, most of studies have relied on the same analytic approach based on the quantification of fixation time, which may have failed to reveal some important features of the scanning strategies employed by individuals with ASD. In the present study, we examined the scanning of faces in a group of 20 preschoolers with ASD and their typically developing (TD) peers, using both classical fixation time approach and a new developed approach based on transition matrices and network analysis. We found between group differences in the eye region in terms of fixation time, with increased right eye fixation time for the ASD group and increased left eye fixation time for the TD group. Our complementary network approach revealed that the left eye might play the role of an anchor in the scanning strategies of TD children but not in that of children with ASD. In ASD, fixation time on the different facial parts was almost exclusively dependent on exploratory activity. Our study highlights the importance of developing innovative measures that bear the potential of revealing new properties of the scanning strategies employed by individuals with ASD.

Intuitive grasping of the meaning of subtle social cues is particularly affected in autism spectrum disorders (ASD). Despite their relevance in social communication, the effect of averted gaze in fearful faces in conveying a signal of environmental threat has not been investigated using real face stimuli in adults with ASD. Here, using functional MRI, we show that briefly presented fearful faces with averted gaze, previously shown to be a strong communicative signal of environmental danger, produce different patterns of brain activation than fearful faces with direct gaze in a group of 26 normally intelligent adults with ASD compared with 26 matched controls. While implicit cue of threat produces brain activation in attention, emotion processing and mental state attribution networks in controls, this effect is absent in individuals with ASD. Instead, individuals with ASD show activation in the subcortical face-processing system in response to direct eye contact. An effect of differences in looking behavior was excluded in a separate eye tracking experiment. Our data suggest that individuals with ASD are more sensitive to direct eye contact than to social signals of danger conveyed by averted fearful gaze.

Evidence from functional neuroimaging indicates that visual perception of human faces and bodies is carried out by distributed networks of face and body-sensitive areas in the occipito-temporal cortex. However, the dynamics of activity in these areas, needed to understand their respective functional roles, are still largely unknown. We monitored brain activity with millisecond time resolution by recording magnetoencephalographic (MEG) responses while participants viewed photographs of faces, bodies, and control stimuli. The cortical activity underlying the evoked responses was estimated with anatomically-constrained noise-normalised minimum-norm estimate and statistically analysed with spatiotemporal cluster analysis. Our findings point to distinct spatiotemporal organization of the neural systems for face and body perception. Face-selective cortical currents were found at early latencies (120-200 ms) in a widespread occipito-temporal network including the ventral temporal cortex (VTC). In contrast, early body-related responses were confined to the lateral occipito-temporal cortex (LOTC). These were followed by strong sustained body-selective responses in the orbitofrontal cortex from 200-700 ms, and in the lateral temporal cortex and VTC after 500 ms latency. Our data suggest that the VTC region has a key role in the early processing of faces, but not of bodies. Instead, the LOTC, which includes the extra-striate body area (EBA), appears the dominant area for early body perception, whereas the VTC contributes to late and post-perceptual processing.

Atypical face processing plays a key role in social interaction difficulties encountered by individuals with autism. In the current fMRI study, the Thatcher illusion was used to investigate several aspects of face processing in 20 young adults with high-functioning autism spectrum disorder (ASD) and 20 matched neurotypical controls. "Thatcherized" stimuli were modified at either the eyes or the mouth and participants discriminated between pairs of faces while cued to attend to either of these features in upright and inverted orientation. Behavioral data confirmed sensitivity to the illusion and intact configural processing in ASD. Directing attention towards the eyes vs. the mouth in upright faces in ASD led to (1) improved discrimination accuracy; (2) increased activation in areas involved in social and emotional processing; (3) increased activation in subcortical face-processing areas. Our findings show that when explicitly cued to attend to the eyes, activation of cortical areas involved in face processing, including its social and emotional aspects, can be enhanced in autism. This suggests that impairments in face processing in autism may be caused by a deficit in social attention, and that giving specific cues to attend to the eye-region when performing behavioral therapies aimed at improving social skills may result in a better outcome.

BACKGROUND: Visual behavior is known to be atypical in Autism Spectrum Disorders (ASD). Monitor-based eye-tracking studies have measured several of these atypicalities in individuals with Autism. While atypical behaviors are known to be accentuated during natural interactions, few studies have been made on gaze behavior in natural interactions. In this study we focused on i) whether the findings done in laboratory settings are also visible in a naturalistic interaction; ii) whether new atypical elements appear when studying visual behavior across the whole field of view. METHODOLOGY/PRINCIPAL FINDINGS: Ten children with ASD and ten typically developing children participated in a dyadic interaction with an experimenter administering items from the Early Social Communication Scale (ESCS). The children wore a novel head-mounted eye-tracker, measuring gaze direction and presence of faces across the child's field of view. The analysis of gaze episodes to faces revealed that children with ASD looked significantly less and for shorter lapses of time at the experimenter. The analysis of gaze patterns across the child's field of view revealed that children with ASD looked downwards and made more extensive use of their lateral field of view when exploring the environment. CONCLUSIONS/SIGNIFICANCE: The data gathered in naturalistic settings confirm findings previously obtained only in monitor-based studies. Moreover, the study allowed to observe a generalized strategy of lateral gaze in children with ASD when they were looking at the objects in their environment.

The discrimination of thatcherized faces from typical faces was explored in two simultaneous alternative forced choice tasks. Reaction times (RTs) and errors were measured in a behavioural task. Brain activation was measured in an equivalent fMRI task. In both tasks, participants were tested with upright and inverted faces. Participants were also tested on churches in the behavioural task. The behavioural task confirmed the face specificity of the illusion (by comparing inversion effects for faces against churches) but also demonstrated that the discrimination was primarily, although not exclusively, driven by attending to eyes. The fMRI task showed that, relative to inverted faces, upright grotesque faces are discriminated via activation of a network of emotion/social evaluation processing areas. On the other hand, discrimination of inverted thatcherized faces was associated with increased activation of brain areas that are typically involved in perceptual processing of faces.

The cerebellum is a complex structure that can be affected by several congenital and acquired diseases leading to alteration of its function and neuronal circuits. Identifying the structural bases of cerebellar neuronal networks in humans in vivo may provide biomarkers for diagnosis and management of cerebellar diseases.To define the anatomy of intrinsic and extrinsic cerebellar circuits using high-angular resolution diffusion spectrum imaging (DSI).We acquired high-resolution structural MRI and DSI of the cerebellum in four healthy female subjects at 3T. DSI tractography based on a streamline algorithm was performed to identify the circuits connecting the cerebellar cortex with the deep cerebellar nuclei, selected brainstem nuclei, and the thalamus.Using in-vivo DSI in humans we were able to demonstrate the structure of the following cerebellar neuronal circuits: (1) connections of the inferior olivary nucleus with the cerebellar cortex, and with the deep cerebellar nuclei (2) connections between the cerebellar cortex and the deep cerebellar nuclei, (3) connections of the deep cerebellar nuclei conveyed in the superior (SCP), middle (MCP) and inferior (ICP) cerebellar peduncles, (4) complex intersections of fibers in the SCP, MCP and ICP, and (5) connections between the deep cerebellar nuclei and the red nucleus and the thalamus.For the first time, we show that DSI tractography in humans in vivo is capable of revealing the structural bases of complex cerebellar networks. DSI thus appears to be a promising imaging method for characterizing anatomical disruptions that occur in cerebellar diseases, and for monitoring response to therapeutic interventions.

Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD observed in animal cortex and aura symptoms mapped to the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value sigma = 1 at the instability point. We predict that human cortex is only weakly susceptible to SD (sigma1), and potentially silent aura occurring below a second bifurcation point at sigma = 0 on the susceptible scale.

Visual categorization may already start within the first 100-ms after stimulus onset, in contrast with the long-held view that during this early stage all complex stimuli are processed equally and that category-specific cortical activation occurs only at later stages. The neural basis of this proposed early stage of high-level analysis is however poorly understood. To address this question we used magnetoencephalography and anatomically-constrained distributed source modeling to monitor brain activity with millisecond-resolution while subjects performed an orientation task on the upright and upside-down presented images of three different stimulus categories: faces, houses and bodies. Significant inversion effects were found for all three stimulus categories between 70-100-ms after picture onset with a highly category-specific cortical distribution. Differential responses between upright and inverted faces were found in well-established face-selective areas of the inferior occipital cortex and right fusiform gyrus. In addition, early category-specific inversion effects were found well beyond visual areas. Our results provide the first direct evidence that category-specific processing in high-level category-sensitive cortical areas already takes place within the first 100-ms of visual processing, significantly earlier than previously thought, and suggests the existence of fast category-specific neocortical routes in the human brain.

Patients suffering from migraine with aura (MWA) and migraine without aura (MWoA) show abnormalities in visual motion perception during and between attacks. Whether this represents the consequences of structural changes in motion-processing networks in migraineurs is unknown. Moreover, the diagnosis of migraine relies on patient's history, and finding differences in the brain of migraineurs might help to contribute to basic research aimed at better understanding the pathophysiology of migraine.To investigate a common potential anatomical basis for these disturbances, we used high-resolution cortical thickness measurement and diffusion tensor imaging (DTI) to examine the motion-processing network in 24 migraine patients (12 with MWA and 12 MWoA) and 15 age-matched healthy controls (HCs). We found increased cortical thickness of motion-processing visual areas MT+ and V3A in migraineurs compared to HCs. Cortical thickness increases were accompanied by abnormalities of the subjacent white matter. In addition, DTI revealed that migraineurs have alterations in superior colliculus and the lateral geniculate nucleus, which are also involved in visual processing.A structural abnormality in the network of motion-processing areas could account for, or be the result of, the cortical hyperexcitability observed in migraineurs. The finding in patients with both MWA and MWoA of thickness abnormalities in area V3A, previously described as a source in spreading changes involved in visual aura, raises the question as to whether a "silent" cortical spreading depression develops as well in MWoA. In addition, these experimental data may provide clinicians and researchers with a noninvasively acquirable migraine biomarker.