Visual cortex organisation in a macaque monkey with macular degeneration

The visual field is retinotopically represented in early visual areas. It has been suggested that when adult primary visual cortex (V1) is deprived of normal retinal input it is capable of large‐scale reorganisation, with neurons inside the lesion projection zone (LPZ) being visually driven by inputs from intact retinal regions. Early functional magnetic resonance imaging (fMRI) studies in humans with macular degeneration (MD) report > 1 cm spread of activity inside the LPZ border, whereas recent results report no shift of the LPZ border. Here, we used fMRI population receptive field measurements to study, for the first time, the visual cortex organisation of one macaque monkey with MD and to compare it with normal controls. Our results showed that the border of the V1 LPZ remained stable, suggesting that the deafferented area V1 zone of the MD animal has limited capacity for reorganisation. Interestingly, the pRF size of non‐deafferented V1 voxels increased slightly (~20% on average), although this effect appears weaker than that in previous single‐unit recording reports. Area V2 also showed limited reorganisation. Remarkably, area V5/MT of the MD animal showed extensive activation compared to controls stimulated over the part of the visual field that was spared in the MD animal. Furthermore, population receptive field size distributions differed markedly in area V5/MT of the MD animal. Taken together, these results suggest that V5/MT has a higher potential for reorganisation after MD than earlier visual cortex.     

Differential effects of hunger and satiety on insular cortex and hypothalamic functional connectivity

The insula cortex and hypothalamus are implicated in eating behaviour, and contain receptor sites for peptides and hormones controlling energy balance. The insula encompasses multi‐functional subregions, which display differential anatomical and functional connectivities with the rest of the brain. This study aimed to analyse the effect of fasting and satiation on the functional connectivity profiles of left and right anterior, middle, and posterior insula, and left and right hypothalamus. It was hypothesized that the profiles would be altered alongside changes in homeostatic energy balance. Nineteen healthy participants underwent two 7‐min resting state functional magnetic resonance imaging scans, one when fasted and one when satiated. Functional connectivity between the left posterior insula and cerebellum/superior frontal gyrus, and between left hypothalamus and inferior frontal gyrus was stronger during fasting. Functional connectivity between the right middle insula and default mode structures (left and right posterior parietal cortex, cingulate cortex), and between right hypothalamus and superior parietal cortex was stronger during satiation. Differences in blood glucose levels between the scans accounted for several of the altered functional connectivities. The insula and hypothalamus appear to form a homeostatic energy balance network related to cognitive control of eating; prompting eating and preventing overeating when energy is depleted, and ending feeding or transferring attention away from food upon satiation. This study provides evidence of a lateralized dissociation of neural responses to energy modulations.     

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.     

Automatic representation of a visual stimulus relative to a background in the right precuneus

Our brains represent the position of a visual stimulus egocentrically, in either retinal or craniotopic coordinates. In addition, recent behavioral studies have shown that the stimulus position is automatically represented allocentrically relative to a large frame in the background. Here, we investigated neural correlates of the ‘background coordinate’ using an fMRI adaptation technique. A red dot was presented at different locations on a screen, in combination with a rectangular frame that was also presented at different locations, while the participants looked at a fixation cross. When the red dot was presented repeatedly at the same location relative to the rectangular frame, the fMRI signals significantly decreased in the right precuneus. No adaptation was observed after repeated presentations relative to a small, but salient, landmark. These results suggest that the background coordinate is implemented in the right precuneus.     

Selectivity for mid‐level properties of faces and places in the fusiform face area and parahippocampal place area

Regions in the ventral visual pathway, such as the fusiform face area (FFA) and parahippocampal place area (PPA) are selective for images from specific object categories. Yet images from different object categories differ in their image properties. To investigate how these image properties are represented in the FFA and PPA, we compared neural responses to locally‐SCRAMBLED images (in which mid‐level, spatial properties are preserved) and globally‐SCRAMBLED images (in which mid‐level, spatial properties are not preserved). There was a greater response in the FFA and PPA to images from the preferred CATEGORY relative to their non‐preferred category for the scrambled conditions. However, there was a greater selectivity for locally‐scrambled compared to globally‐scrambled images. Next, we compared the magnitude of fMR‐adaptation to intact and scrambled images. fMR‐adaptation was evident to locally‐scrambled images from the preferred category. However, there was no adaptation to globally‐scrambled images from the preferred category. These results show that the selectivity to faces and places in the FFA and PPA is dependent on mid‐level properties of the image that are preserved by local‐scrambling.     

Scene coherence can affect the local response to natural images in human V1

Neurons in primary visual cortex (V1) can be indirectly affected by visual stimulation positioned outside their receptive fields. Although this contextual modulation has been intensely studied, we have little notion of how it manifests with naturalistic stimulation. Here, we investigated how the V1 response to a natural image fragment is affected by spatial context that is consistent or inconsistent with the scene from which it was extracted. Using functional magnetic resonance imaging at 7 T, we measured the blood oxygen level‐dependent signal in human V1 (n = 8) while participants viewed an array of apertures. Most apertures showed fragments from a single scene, yielding a dominant perceptual interpretation which participants were asked to categorize, and the remaining apertures each showed fragments drawn from a set of 20 scenes. We find that the V1 response was significantly increased for apertures showing image structure that was coherent with the dominant scene relative to the response to the same image structure when it was non‐coherent. Additional analyses suggest that this effect was mostly evident for apertures in the periphery of the visual field, that it peaked towards the centre of the aperture, and that it peaked in the middle to superficial regions of the cortical grey matter. These findings suggest that knowledge of typical spatial relationships is embedded in the circuitry of contextual modulation. Such mechanisms, possibly augmented by contributions from attentional factors, serve to increase the local V1 activity under conditions of contextual consistency.     

Attentional load modifies early activity in human primary visual cortex

Recent theories of selective attention assume that the more attention is required by a task, the earlier are irrelevant stimuli filtered during perceptual processing. Previous functional MRI studies have demonstrated that primary visual cortex (V1) activation by peripheral distractors is reduced by higher task difficulty at fixation, but it remains unknown whether such changes affect initial processing in V1 or subsequent feedback. Here we manipulated attentional load at fixation while recording peripheral visual responses with high-density EEG in 28 healthy volunteers, which allowed us to track the exact time course of attention-related effects on V1. Our results show a modulation of the earliest component of the visual evoked potential (C1) as a function of attentional load. Additional topographic and source localization analyses corroborated this finding, with significant load-related differences observed throughout the first 100 ms post-stimulus. However, this effect was observed only when stimuli were presented in the upper visual field (VF), but not for symmetrical positions in the lower VF. Our findings demonstrate early filtering of irrelevant information under increased attentional demands, thus supporting models that assume a flexible mechanism of attentional selection, but reveal important functional asymmetries across the VF.     

The dependencies of fronto‐parietal BOLD responses evoked by covert visual search suggest eye‐centred coding

Visual scenes explored covertly are initially represented in a retinal frame of reference (FOR). On the other hand, ‘later’ stages of the cortical network allocating spatial attention most probably use non‐retinal or non‐eye‐centred representations as they may ease the integration of different sensory modalities for the formation of supramodal representations of space. We tested if the cortical areas involved in shifting covert attention are based on eye‐centred or non‐eye‐centred coding by using functional magnetic resonance imaging. Subjects were scanned while detecting a target item (a regularly oriented ‘L’) amidst a set of distractors (rotated ‘L's). The array was centred either 5° right or left of the fixation point, independent of eye‐gaze orientation, the latter varied in three steps: straight relative to the head, 10° left or 10° right. A quantitative comparison of the blood‐oxygen‐level‐dependent (BOLD) responses for the three eye‐gaze orientations revealed stronger BOLD responses in the right intraparietal sulcus (IPS) and the right frontal eye field (FEF) for search in the contralateral (i.e. left) eye‐centred space, independent of whether the array was located in the right or left head‐centred hemispace. The left IPS showed the reverse pattern, i.e. an activation by search in the right eye‐centred hemispace. In other words, the IPS and the right FEF, members of the cortical network underlying covert search, operate in an eye‐centred FOR.     

Activity patterns in the category‐selective occipitotemporal cortex predict upcoming motor actions

Converging lines of evidence point to the occipitotemporal cortex (OTC) as a critical structure in visual perception. For instance, human functional magnetic resonance imaging (fMRI) has revealed a modular organisation of object‐selective, face‐selective, body‐selective and scene‐selective visual areas in the OTC, and disruptions to the processing within these regions, either in neuropsychological patients or through transcranial magnetic stimulation, can produce category‐specific deficits in visual recognition. Here we show, using fMRI and pattern classification methods, that the activity in the OTC also represents how stimuli will be interacted with by the body – a level of processing more traditionally associated with the preparatory activity in sensorimotor circuits of the brain. Combining functional mapping of different OTC areas with a real object‐directed delayed movement task, we found that the pre‐movement spatial activity patterns across the OTC could be used to predict both the action of an upcoming hand movement (grasping vs. reaching) and the effector (left hand vs. right hand) to be used. Interestingly, we were able to extract this wide range of predictive movement information even though nearly all OTC areas showed either baseline‐level or below baseline‐level activity prior to action onset. Our characterisation of different OTC areas according to the features of upcoming movements that they could predict also revealed a general gradient of effector‐to‐action‐dependent movement representations along the posterior–anterior OTC axis. These findings suggest that the ventral visual pathway, which is well known to be involved in object recognition and perceptual processing, plays a larger than previously expected role in preparing object‐directed hand actions.     

Rapid visual stimulation increases extrasynaptic glutamate receptor expression but not visual‐evoked potentials in the adult rat primary visual cortex

The model most used to study synaptic plasticity, long‐term potentiation (LTP), typically employs electrical stimulation of afferent fibers to induce changes in synaptic strength. It would be beneficial for understanding the behavioral relevance of LTP if a model could be developed that used more naturalistic stimuli. Recent evidence suggests that the adult visual cortex, previously thought to have lost most of its plasticity once past the critical period, is in fact capable of LTP‐like changes in synaptic strength in response to sensory manipulations alone. In a preliminary study, we used a photic tetanus (PT; flashing checkerboard stimulus) to induce an enhancement of the visual‐evoked potential (VEP) in the primary visual cortex of anesthetised adult rats. In the present study, we sought to compare the mechanisms of this novel sensory LTP with those of traditional electrical LTP. Unexpectedly, we found that sensory LTP was not induced as reliably as we had observed previously, as manipulations of several parameters failed to lead to significant potentiation of the VEP. However, we did observe a significant increase in visual cortex glutamate receptor expression on the surface of isolated synapses following the PT. Both AMPA receptor expression and N‐methyl‐d ‐aspartate (NMDA) receptor subunit expression were increased, specifically in extrasynaptic regions of the membrane, in PT animals. These results provide biochemical confirmation of the lack of change in the VEP in response to PT, but suggest that PT may prime synapses for strengthening upon appropriate subsequent activation, through the trafficking of glutamate receptors to the cell surface.     

The selectivity of responses to red‐green colour and achromatic contrast in the human visual cortex: an fMRI adaptation study

There is controversy as to how responses to colour in the human brain are organized within the visual pathways. A key issue is whether there are modular pathways that respond selectively to colour or whether there are common neural substrates for both colour and achromatic (Ach) contrast. We used functional magnetic resonance imaging (fMRI) adaptation to investigate the responses of early and extrastriate visual areas to colour and Ach contrast. High‐contrast red–green (RG) and Ach sinewave rings (0.5 cycles/degree, 2 Hz) were used as both adapting stimuli and test stimuli in a block design. We found robust adaptation to RG or Ach contrast in all visual areas. Cross‐adaptation between RG and Ach contrast occurred in all areas indicating the presence of integrated, colour and Ach responses. Notably, we revealed contrasting trends for the two test stimuli. For the RG test, unselective processing (robust adaptation to both RG and Ach contrast) was most evident in the early visual areas (V1 and V2), but selective responses, revealed as greater adaptation between the same stimuli than cross‐adaptation between different stimuli, emerged in the ventral cortex, in V4 and VO in particular. For the Ach test, unselective responses were again most evident in early visual areas but Ach selectivity emerged in the dorsal cortex (V3a and hMT+). Our findings support a strong presence of integrated mechanisms for colour and Ach contrast across the visual hierarchy, with a progression towards selective processing in extrastriate visual areas.     

Individual left‐hand and right‐hand intra‐digit representations in human primary somatosensory cortex

Individual intra‐digit somatotopy of all phalanges of the middle and little finger of the right and left hand was studied by functional magnetic resonance imaging in 12 healthy subjects. Phalanges were tactilely stimulated and activation in BA 3b of the human primary somatosensory cortex could be observed for each individual phalanx. Activation peaks were further analysed using the Direction/Order (DiOr) method, which identifies somatotopy, if a significantly high number of subjects exhibit ordered distal‐to‐proximal phalanx representions along a similar direction. Based on DiOr, ordered and similar‐direction‐aligned intra‐digit maps across subjects were found at the left hand for the little and middle finger and at the right hand for the little finger. In these digits the proximal phalanges were represented more medially along the course of the central sulcus than the distal phalanges. This is contrasted by the intra‐digit maps for the middle finger of the right hand, which showed larger inter‐subject variations of phalanx alignments without a similar within‐digit representation across subjects. As all subjects were right‐handed and as the middle finger of the dominant hand probably plays a more individual role in everyday tactile performance than the little finger of the right hand and all left‐hand digits, the observed variation might reflect a functional somatotopy based on individual use of that particular digit at the dominant hand.     

Distribution of cytochrome oxidase-rich patches in human primary visual cortex

We studied the tangential distribution of cytochrome oxidase (CytOx)-rich patches (blobs) in the striate cortex (V1) of normally sighted Homo sapiens. We analyzed the spatial density and cross-sectional area of patches in CytOx-reacted tangential sections of flat-mounted preparations of V1 and surrounding areas. CytOx-rich patches were most clearly defined in the supragranular cortical layers of V1, particularly at middle levels of layer III. Variations in patch spatial density were subtle across different visual eccentricity representations. Within the binocular representation of V1, the average patch spatial density decreased slightly with increasing cortical eccentricity, from around 1.0 patch/mm² in the foveal representation to 0.6 patch/mm² at the representation of ∼60° eccentricity, but seemed to increase again at the representation of the monocular crescent. Across the entire sample, the cross-sectional area of patches (i.e., patch size) varied from approximately 0.2–0.8 mm², with a mean value of 0.32 mm². Notably, there was no significant variation in the mean patch size across eccentricity representations. Human patches are on average larger than those reported for nonhuman primate brains, and analysis of species with different brain sizes suggests an approximately linear relationship between V1 area and patch size. The relative constancy of patch metrics across eccentricities is in stark contrast with the exponential variation in V1 cortical magnification, suggesting a nearly invariant modular organization throughout human V1.     

Recent progress in migraine pathophysiology: role of cortical spreading depression and magnetic resonance imaging

Migraine is characterised by debilitating pain, which affects the quality of life in affected patients in both the western and the eastern worlds. The purpose of this article is to give a detailed outline of the pathophysiology of migraine pain, which is one of the most confounding pathologies among pain disorders in clinical conditions. We critically evaluate the scientific basis of various theories concerning migraine pathophysiology, and draw insights from brain imaging approaches that have unraveled the prevalence of cortical spreading depression (CSD) in migraine. The findings supporting the role of CSD as a physiological substrate in clinical pain are discussed. We also give an exhaustive overview of brain imaging approaches that have been employed to solve the genesis of migraine pain, and its possible links to the brainstem, the neocortex, genetic endophenotypes, and pathogenetic factors (such as dopaminergic hypersensitivity). Furthermore, a roadmap is proposed to provide a better understanding of pain pathophysiology in migraine, to enable the development of strategies using leads from brain imaging studies for the identification of early biomarkers, efficient prognosis, and treatment planning, which eventually may help in alleviating some of the devastating impact of pain morbidity in patients afflicted with migraine.     

Computerised working memory‐based cognitive remediation therapy does not affect Reading the Mind in The Eyes test performance or neural activity during a Facial Emotion Recognition test in psychosis

Working memory‐based cognitive remediation therapy (CT) for psychosis has recently been associated with broad improvements in performance on untrained tasks measuring working memory, episodic memory and IQ, and changes in associated brain regions. However, it is unclear whether these improvements transfer to the domain of social cognition and neural activity related to performance on social cognitive tasks. We examined performance on the Reading the Mind in the Eyes test (Eyes test) in a large sample of participants with psychosis who underwent working memory‐based CT (N = 43) compared to a control group of participants with psychosis (N = 35). In a subset of this sample, we used functional magnetic resonance imaging (fMRI) to examine changes in neural activity during a facial emotion recognition task in participants who underwent CT (N = 15) compared to a control group (N = 15). No significant effects of CT were observed on Eyes test performance or on neural activity during facial emotion recognition, either at p < 0.05 family‐wise error or at a p < 0.001 uncorrected threshold, within a priori social cognitive regions of interest. This study suggests that working memory‐based CT does not significantly impact an aspect of social cognition which was measured behaviourally and neurally. It provides further evidence that deficits in the ability to decode mental state from facial expressions are dissociable from working memory deficits, and suggests that future CT programmes should target social cognition in addition to working memory for the purposes of further enhancing social function.     

Brain networks underlying mental imagery of auditory and visual information

Mental imagery is a complex cognitive process that resembles the experience of perceiving an object when this object is not physically present to the senses. It has been shown that, depending on the sensory nature of the object, mental imagery also involves correspondent sensory neural mechanisms. However, it remains unclear which areas of the brain subserve supramodal imagery processes that are independent of the object modality, and which brain areas are involved in modality‐specific imagery processes. Here, we conducted a functional magnetic resonance imaging study to reveal supramodal and modality‐specific networks of mental imagery for auditory and visual information. A common supramodal brain network independent of imagery modality, two separate modality‐specific networks for imagery of auditory and visual information, and a common deactivation network were identified. The supramodal network included brain areas related to attention, memory retrieval, motor preparation and semantic processing, as well as areas considered to be part of the default‐mode network and multisensory integration areas. The modality‐specific networks comprised brain areas involved in processing of respective modality‐specific sensory information. Interestingly, we found that imagery of auditory information led to a relative deactivation within the modality‐specific areas for visual imagery, and vice versa. In addition, mental imagery of both auditory and visual information widely suppressed the activity of primary sensory and motor areas, for example deactivation network. These findings have important implications for understanding the mechanisms that are involved in generation of mental imagery.     

Slow fluctuations in eye position and resting‐state functional magnetic resonance imaging brain activity during visual fixation

The neuronal circuitry that supports voluntary changes in eye position in tasks that require attention‐driven oculo‐motor control is well known. However, less is known about the neuronal basis for eye control during visual fixation. This, together with the fact that visual fixation is one of the most commonly used baseline conditions in resting‐state functional magnetic resonance imaging (fMRI) studies, prompted us to conduct a study in which we employed resting‐state fMRI and concurrent recordings of eye gaze to investigate the relationship between spontaneous changes in eye position during passive visual fixation and intrinsic brain activity. As a control experiment, we recorded fMRI brain activity related to cued voluntary vertical and horizontal changes in eye position in a block‐related task‐evoked fMRI experiment. Our results for the voluntarily performed changes in eye position elicited brain activity in the bilateral occipitotemporal cortex, supplementary motor cortex and frontal eye fields. In contrast, we show that slow fluctuations in eye position during passive visual fixation are linked to intrinsic brain activity, foremost in midline cortical brain regions located in the posteromedial parietal cortex and the medial prefrontal cortex, brain regions that act as core cortical hubs in the brain's default mode network. Our results suggest that subconscious and sustained changes in behavior are tied to intrinsic brain activity on a moment‐by‐moment basis.     

Decoding attention control and selection in visual spatial attention

Event‐related potentials (ERPs) are used extensively to investigate the neural mechanisms of attention control and selection. The univariate ERP approach, however, has left important questions inadequately answered. We addressed two questions by applying multivariate pattern classification to multichannel ERPs in two cued visual spatial attention experiments (N = 56): (a) impact of cueing strategies (instructional vs. probabilistic) on attention control and selection and (b) neural and behavioral effects of individual differences. Following cue onset, the decoding accuracy (cue left vs. cue right) began to rise above chance level earlier and remained higher in instructional cueing (~80 ms) than in probabilistic cueing (~160 ms), suggesting that unilateral attention focus leads to earlier and more distinct formation of the attention control set. A similar temporal sequence was also found for target‐related processing (cued target vs. uncued target), suggesting earlier and stronger attention selection under instructional cueing. Across the two experiments: (a) individuals with higher cue‐related decoding accuracy showed higher magnitude of attentional modulation of target‐evoked N1 amplitude, suggesting that better formation of anticipatory attentional state leads to stronger modulation of target processing, and (b) individuals with higher target‐related decoding accuracy showed faster reaction times (or larger cueing effects), suggesting that stronger selection of task‐relevant information leads to better behavioral performance. Taken together, multichannel ERPs combined with machine learning decoding yields new insights into attention control and selection that complement the univariate ERP approach, and along with the univariate ERP approach, provides a more comprehensive methodology to the study of visual spatial attention.