Effect of visual stimuli of pain on empathy brain network in people with and without Autism Spectrum Disorder

The extent to which affective empathy is impaired in Autism Spectrum Disorder (ASD) remains unclear, as some—but not all—previous neuroimaging studies investigating empathy for pain in ASD have shown similar activation levels to those of neurotypicals individuals. These inconsistent results could be due to the use of different empathy‐eliciting stimuli. While some studies used pictures of faces exhibiting a painful expression, others used pictures of limbs in painful situations. In this study, we used fMRI to compare activation in areas associated with empathy processing (empathy network) for these two types of stimuli in 31 participants (16 with ASD, 15 controls). We found a group difference in the inferior frontal gyrus (IFG) and the thalamus when participants viewed stimuli of limbs in painful situations, but not when they viewed face stimuli with a painful expression. Both groups of participants activated their empathy network more when viewing pictures of limbs in painful situations than when viewing pictures of faces with a painful expression; this increased activation for limbs versus faces was significantly enhanced in controls relative to ASD participants, especially in the secondary somatosensory cortex (SII). Our findings suggest that empathy defect of people with ASD is contingent upon the type of stimuli used, and may be related to the level of Mirror Neuron System involvement, as brain regions showing group differences (IFG, SII) underlie embodiment. We discuss the potential clinical implications of our findings in terms of developing interventions boosting the empathetic abilities of people with ASD.     

Cyclic Vomiting Syndrome is characterized by altered functional brain connectivity of the insular cortex: A cross‐comparison with migraine and healthy adults

Cyclic Vomiting Syndrome (CVS) has been linked to episodic migraine, yet little is known about the precise brain‐based mechanisms underpinning CVS, and whether these associated conditions share similar pathophysiology. We investigated the functional integrity of salience (SLN) and sensorimotor (SMN) intrinsic connectivity networks in CVS, migraine and healthy controls using brain functional Magnetic Resonance Imaging. CVS, relative to both migraine and controls, showed increased SLN connectivity to middle/posterior insula, a key brain region for nausea and viscerosensory processing. In contrast, this same region showed diminished SMN connectivity in both CVS and migraine. These results highlight both unique and potentially shared pathophysiology between these conditions, and suggest a potential target for therapeutics in future studies.     

Autism classified by magnetic resonance imaging: A pilot study of a potential diagnostic tool

ObjectivesIndividual anatomical biomarkers have limited power for the classification of autism. The present study introduces a multivariate classification approach using structural magnetic resonance imaging data from individuals with and without autism.MethodsThe classifier utilizes z‐normalization, parameter weighting, and interindividual comparison on brain segmentation data, for estimation of an individual summed total index (TI). The TI indicates whether the gross morphological pattern of each individual''s brain is in the direction of cases or controls.ResultsMorphometric analysis found significant differences within subcortical gray matter structures and limbic areas. There was no significant difference in total brain volume. A case‐control pilot‐study of TIs in normally intelligent individuals with autism (24) and without (21) yielded a maximal accuracy of 78.9% following cross‐validation. It showed a high accuracy compared with machine learning methods when tested on the same dataset. The TI correlated well with the autism quotient (R = 0.51) across groups.ConclusionThese results are on par with studies on autism using machine learning. The main contributions are its transparency and simplicity. The possibility of including additional neuroimaging data further increases the potential of the classifier as a diagnostic aid for neuropsychiatric disorders, as well as a research tool for neuroscientific investigations.     

Mechanisms of migraine aura revealed by functional MRI in human visual cortex

Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demonstrated at least eight characteristics of CSD, time-locked to percept/onset of the aura. Initially, a focal increase in BOLD signal (possibly reflecting vasodilation), developed within extrastriate cortex (area V3A). This BOLD change progressed contiguously and slowly (3.5 +/- 1.1 mm/min) over occipital cortex, congruent with the retinotopy of the visual percept. Following the same retinotopic progression, the BOLD signal then diminished (possibly reflecting vasoconstriction after the initial vasodilation), as did the BOLD response to visual activation. During periods with no visual stimulation, but while the subject was experiencing scintillations, BOLD signal followed the retinotopic progression of the visual percept. These data strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex.     

Brain barriers and their potential role in migraine pathophysiology

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.     

Projection of rods and cones within human visual cortex

There are two basic types of photoreceptors in the retina: rods and cones. Using a single stimulus viewed at two different light levels, we tested whether input from rods and input from cones are topographically segregated at subsequent levels of human visual cortex. Here we show that rod-mediated visual input produces robust activation in area MT+, and in the peripheral representations of multiple retinotopic areas. However, such activation was selectively absent in: (1) a cortical area selectively activated by colored stimuli (V8) and (2) the foveal representations of lower tier retinotopic areas. These cortical differences reflect corresponding differences in perception between scotopic and photopic conditions.     

Where is 'dorsal V4' in human visual cortex? Retinotopic, topographic and functional evidence

In flattened human visual cortex, we defined the topographic homologue of macaque dorsal V4 (the 'V4d topologue'), based on neighborhood relations among visual areas (i.e. anterior to V3A, posterior to MT+, and superior to ventral V4). Retinotopic functional magnetic resonance imaging (fMRI) data suggest that two visual areas ('LOC' and 'LOP') are included within this V4d topologue. Except for an overall bias for either central or peripheral stimuli (respectively), the retinotopy within LOC and LOP was crude or nonexistent. Thus the retinotopy in the human V4d topologue differed from previous reports in macaque V4d. Unlike some previous reports in macaque V4d, the human V4d topologue was not significantly color-selective. However, the V4d topologue did respond selectively to kinetic motion boundaries, consistent with previous human fMRI reports. Because striking differences were found between the retinotopy and functional properties of the human topologues of 'V4v' and 'V4d', it is unlikely that these two cortical regions are subdivisions of a singular human area 'V4'.     

Migraine aura and related phenomena: beyond scotomata and scintillations

Migraine affects the cortical physiology and may induce dysfunction both ictally and interictally. Although visual symptoms predominate during aura, other contiguous cortical areas related to less impressive symptoms are also impaired in migraine. Answers from 72.2% migraine with aura and 48.6% of migraine without aura patients on human faces and objects recognition, colour perception, proper names recalling and memory in general showed dysfunctions suggestive of prosopagnosia, dyschromatopsia, ideational apraxia, alien hand syndrome, proper name anomia or aphasia, varying in duration and severity. Symptoms frequently occurred in a successively building-up pattern fitting with the geographical distribution of the various cortical functions. When specifically inquired, migraineurs reveal less evident symptoms that are not usually considered during routine examination. Spreading depression most likely underlies the aura symptoms progression. Interictal involvement indicates that MWA and MWoA are not completely silent outside attacks, and that both subforms of migraine may share common mechanisms.     

The cerebellum and migraine

Clinical and pathophysiological evidences connect migraine and the cerebellum. Literature on documented cerebellar abnormalities in migraine, however, is relatively sparse. Cerebellar involvement may be observed in 4 types of migraines: in the widespread migraine with aura (MWA) and migraine without aura (MWoA) forms; in particular subtypes of migraine such as basilar-type migraine (BTM); and in the genetically driven autosomal dominant familial hemiplegic migraine (FHM) forms. Cerebellar dysfunction in migraineurs varies largely in severity, and may be subclinical. Purkinje cells express calcium channels that are related to the pathophysiology of both inherited forms of migraine and primary ataxias, mostly spinal cerebellar ataxia type 6 (SCA-6) and episodic ataxia type 2 (EA-2). Genetically driven ion channels dysfunction leads to hyperexcitability in the brain and cerebellum, possibly facilitating spreading depression waves in both locations. This review focuses on the cerebellar involvement in migraine, the relevant ataxias and their association with this primary headache, and discusses some of the pathophysiological processes putatively underlying these diseases.