Dysfunction of early-stage visual processing in schizophrenia.

OBJECTIVE: Schizophrenia is associated with deficits in higher-order processing of visual information. This study evaluated the integrity of early visual processing in order to evaluate the overall pattern of visual dysfunction in schizophrenia. METHOD: Steady-state visual-evoked potential responses were recorded over the occipital cortex in patients with schizophrenia and in age- and sex-matched comparison volunteers. Visual-evoked potentials were obtained for stimuli composed of isolated squares that were modulated sinusoidally in luminance contrast, number of squares, or chromatic contrast in order to emphasize magnocellular or parvocellular visual pathway activity. RESULTS: Responses of patients to magnocellular-biased stimuli were significantly lower than those of comparison volunteers. These lower response levels were observed in conditions using both low luminance contrast and large squares that biased processing toward the magnocellular pathway. In contrast, responses to stimuli that biased processing toward the parvocellular pathway were not significantly different between schizophrenia patients and comparison volunteers. A significant interaction of group and stimulus type was observed in the condition using low luminance contrast. CONCLUSIONS: These findings suggest a dysfunction of lower-level visual pathways, which was more prominent for magnocellular than parvocellular biased stimuli. The magnocellular pathway helps in orienting toward salient stimuli. A magnocellular pathway deficit could contribute to higher-level visual cognitive deficits in schizophrenia.     

The contribution of color to motion processing in Macaque middle temporal area.

The chromatic properties of an image yield strong cues for object boundaries and thus hold the potential to facilitate the detection of object motion. The extent to which cortical motion detectors exploit chromatic information, however, remains a matter of debate. To address this further, we quantified the strength of chromatic input to directionally selective neurons in the middle temporal area (MT) of macaque cerebral cortex using an equivalent luminance contrast (EqLC) paradigm. This paradigm, in which two sinusoidal gratings, one heterochromatic and the other achromatic, are superimposed and moved in opposite directions, allows the sensitivity of motion detectors to heterochromatic stimuli to be quantified and expressed relative to the benchmark of sensitivity for a luminance-defined stimulus. The results of these experiments demonstrate that the chromatic contrast in a moving red-green heterochromatic grating strongly influences directional responses in MT when the luminance contrast in that same grating is relatively low; for such stimuli, EqLC is at least 5%. When luminance contrast is added to the heterochromatic grating, however, EqLC wanes sharply and becomes negative (-4%) when luminance contrast is sufficiently high (>17-23%). Thus, the chromatic properties of an object appear to confer little or no benefit to motion processing by MT neurons when sufficient luminance contrast concurrently exists. These data support a simple model in which chromatic motion processing in MT is almost exclusively determined by magnocellular input. Additionally, a comparison of neuronal and psychophysical data suggests that MT may not be the sole contributor to the perceptual experience elicited by motion of heterochromatic patterns, or that only a subset of MT neurons serve this function.     

Striate cortex and visual acuity functions in the cat.

Using a two-choice visual discrimination paradigm, thresholds for size (gratings), parallelness (parallel vs. non-parallel lines), contour alignment (vernier offset), and angularity (polygon figures) were behaviorally determined in cats before and after ablations of portions of the geniculo-cortical system. Animals with a total loss of cortical area 17, and with a loss, in some cases, of up to 90% of areas 18 (with and without infringement into area 19), showed about a 30% reduction in grating acuity, a three-fold increase in parallelness and angularity thresholds, and a total loss of contour alignment ability. Control animals with ablations sparing area 17 showed no significant threshold changes. All animals were able to learn classic form discriminations postoperatively, but those with area 17-18 lesions at a somewhat slower than normal rate. Control procedures indicated that all tested discrimination capabilities did not depend on luminance differences between targets, local flux cues within the targets, or on the animals' use of residual portions of area 17 representing the peripheral visual field. Since the cat has multiple thalamo-cortical visual pathways, the results of the present study are consistent with the hypothesis that pathways parallel to the geniculo-striate system are capable of processing spatial information of considerable detail. The results also suggest, however, that the geniculo-striate system is uniquely necessary for the processing of the finest attributes of spatial contours.     

Thalamocortical interactions underlying visual fear conditioning in humans

Despite a strong focus on the role of the amygdala in fear conditioning, recent works point to a more distributed network supporting fear conditioning. We aimed to elucidate interactions between subcortical and cortical regions in fear conditioning in humans. To do this, we used two fearful faces as conditioned stimuli (CS) and an electrical stimulation at the left hand, paired with one of the CS, as unconditioned stimulus (US). The luminance of the CS was rhythmically modulated leading to “entrainment” of brain oscillations at a predefined modulation frequency. Steady‐state responses (SSR) were recorded by MEG. In addition to occipital regions, spectral analysis of SSR revealed increased power during fear conditioning particularly for thalamus and cerebellum contralateral to the upcoming US. Using thalamus and amygdala as seed‐regions, directed functional connectivity was calculated to capture the modulation of interactions that underlie fear conditioning. Importantly, this analysis showed that the thalamus drives the fusiform area during fear conditioning, while amygdala captures the more general effect of fearful faces perception. This study confirms ideas from the animal literature, and demonstrates for the first time the central role of the thalamus in fear conditioning in humans. Hum Brain Mapp 36:4592–4603, 2015. © 2015 Wiley Periodicals, Inc.     

Luminance and spatial attention effects on early visual processing

Event-related potentials (ERPs) were recorded from healthy subjects in response to unilaterally flashed high and low luminance bar stimuli presented randomly to left and right field locations. Their task was to covertly and selectively attend to either the left or right stimulus locations (separate blocks) in order to detect infrequent shorter target bars of either luminance. Independent of attention, higher stimulus luminance resulted in higher ERP amplitudes for the posterior N95 (80–110 ms), occipital P1 (110–140 ms), and parietal N1 (130–180 ms). Brighter stimuli also resulted in shorter peak latency for the occipital N1 component (135–220 ms); this effect was not observed for the N1 components over parietal, central or frontal regions. Significant attention-related amplitude modulations were obtained for the occipital P1, occipital, parietal and central N1, the occipital and parietal P2, and the parietal N2 components; these components were larger to stimuli at the attended location. In contrast to the relatively short latencies of both spatial attention and luminance effects, the first interaction between luminance and spatial attention effects was observed for the P3 component to the target stimuli (350–750 ms). This suggests that interactions of spatial attention and stimulus luminance previously reported for reaction time measures may not reflect the earliest stages of sensory/perceptual processing. Differences in the way in which luminance and attention affected the occipital P1, occipital N1 and parietal N1 components suggest dissociations among these ERPs in the mechanisms of visual and attentional processing they reflect. Nonetheless, scalp current density mappings of the attention effects throughout the latency ranges of the P1 and N1 components show the most prominent attention-related activity to be in lateral occipital scalp areas. Such a pattern is consistent with the spatially selective filtering of information into the ventral stream of visual processing which is reponsible for complex feature analysis and object identification.     

Cross-modal emotional attention: emotional voices modulate early stages of visual processing

Emotional attention, the boosting of the processing of emotionally relevant stimuli, has, up to now, mainly been investigated within a sensory modality, for instance, by using emotional pictures to modulate visual attention. In real-life environments, however, humans typically encounter simultaneous input to several different senses, such as vision and audition. As multiple signals entering different channels might originate from a common, emotionally relevant source, the prioritization of emotional stimuli should be able to operate across modalities. In this study, we explored cross-modal emotional attention. Spatially localized utterances with emotional and neutral prosody served as cues for a visually presented target in a cross-modal dot-probe task. Participants were faster to respond to targets that appeared at the spatial location of emotional compared to neutral prosody. Event-related brain potentials revealed emotional modulation of early visual target processing at the level of the P1 component, with neural sources in the striate visual cortex being more active for targets that appeared at the spatial location of emotional compared to neutral prosody. These effects were not found using synthesized control sounds matched for mean fundamental frequency and amplitude envelope. These results show that emotional attention can operate across sensory modalities by boosting early sensory stages of processing, thus facilitating the multimodal assessment of emotionally relevant stimuli in the environment.     

The effect of spatial frequency on chromatic and achromatic steady-state visual evoked potentials.

OBJECTIVE: Little is known about the physiological properties of the major components of steady-state visual evoked potentials (VEPs). Based on the hypothesis that isoluminant color and high contrast pattern differentially activate the parvo- and magnocellular pathways, we studied difference in spatial frequency function between chromatic and achromatic VEPs to sinusoidal gratings. METHODS: Steady-state VEPs to isoluminant chromatic (red-green) and high contrast (90%) achromatic (black-white) sinusoidal gratings with nine spatial frequencies (0.5 to 8.0 cycles/degrees (cpd)) at 4 Hz (8 reversals/s) were recorded in 13 normal subjects. VEPs were Fourier analyzed to obtain phase and amplitude of the second (2F) and fourth (4F) harmonic responses. RESULTS: The 2F amplitude of chromatic VEPs decreased above 4.0 cpd in a low-pass function while that of achromatic VEPs showed a band-pass function with a peak at 4.0 cpd. The 4F amplitude of chromatic VEPs was not affected significantly by spatial frequency whereas that of achromatic VEPs exhibited a high-pass function. The phases of 2F and 4F showed a non-monotonic function of spatial frequency in both chromatic and achromatic stimuli with peaks at middle spatial frequencies. CONCLUSION: Chromatic and achromatic visual stimuli differently affected 2F and 4F components, which thus suggests that 2F and 4F components are generated from different neuronal subgroups largely in the parvocellular pathway.     

Spatial attention has different effects on the magno- and parvocellular pathways.

Attention was directed to the left or to the right of the fixation point by the lateral presentation of a target on which the subject had to perform an attention demanding task. A (task-irrelevant) grating displayed in the left visual field was the visual evoked potential (VEP) stimulus. Gratings modulated either in luminance or colour contrast at various temporal frequencies were used in order to maximise the activation of magno- or parvocellular pathways. VEPs recorded in attended and unattended conditions were compared. For luminance stimuli, both latency and amplitude of VEPs were modified by attention. For chromatic stimuli, attention affected the amplitude but not the latency of VEPs. Spatial attention uses different mechanisms when magno- or parvocellular systems are involved.     

Effects of emotional conditioning on early visual processing: temporal dynamics revealed by ERP single-trial analysis

Studies using event-related potentials (ERPs) have shown that affectively arousing stimuli enhance attention and perception. In addition, simple neutral stimuli, when paired with emotionally engaging unconditioned stimuli (i.e., the CS+) in classical conditioning paradigms, were found to evoke increased sensory responses as learning progresses, compared to responses elicited by the same stimuli not paired with a noxious stimulus (CS-). To date the detailed trial-to-trial temporal dynamics of this sensory facilitation process is not known. Signal averaging required for the ERP analysis eliminates trial-to-trial information of temporal cortical dynamics. In the current study, a novel single-trial analysis method called Analysis of Single-trial ERP and Ongoing activity (ASEO) was adopted to study the detailed electrocortical dynamics of sensory processing during classical aversive conditioning. Focusing on the P1 component of the ERP evoked by simple grating patterns serving as CS+ and CS-, we found that over a session of conditioning trials, there were three phases of P1 amplitude changes for both CS+ and CS-: (1) an initial decrease phase, (2) a subsequent increase phase, and (3) a final habituating phase. Tests on the rates of P1 amplitude changes in each of the three phases between CS+ and CS- conditions revealed differential effects of CS+ and CS- for all three phases. No such effects were found for a session of control trials where the same grating patterns were paired with checkerboards. We interpret these results as providing evidence supporting the view that emotional experience can modulate early visual processing and dynamics of perceptual learning.     

Atypical cortical representation of peripheral visual space in children with an autism spectrum disorder

A key feature of early visual cortical regions is that they contain discretely organized retinotopic maps. Titration of these maps must occur through experience, and the fidelity of their spatial tuning will depend on the consistency and accuracy of the eye movement system. Anomalies in fixation patterns and the ballistics of eye movements are well documented in autism spectrum disorder (ASD), with off‐center fixations a hallmark of the phenotype. We hypothesized that these atypicalities might affect the development of visuo‐spatial maps and specifically that peripheral inputs might receive altered processing in ASD. Using high‐density recordings of visual evoked potentials (VEPs) and a novel system‐identification approach known as VESPA (visual evoked spread spectrum analysis), we assessed sensory responses to centrally and peripherally presented stimuli. Additionally, input luminance was varied to bias responsiveness to the magnocellular system, given previous suggestions of magnocellular‐specific deficits in ASD. Participants were 22 ASD children (7–17 years of age) and 31 age‐ and performance‐IQ‐matched neurotypical controls. Both VEP and VESPA responses to central presentations were indistinguishable between groups. In contrast, peripheral presentations resulted in significantly greater early VEP and VESPA amplitudes in the ASD cohort. We found no evidence that anomalous enhancement was restricted to magnocellular‐biased responses. The extent of peripheral response enhancement was related to the severity of stereotyped behaviors and restricted interests, cardinal symptoms of ASD. The current results point to differential visuo‐spatial cortical mapping in ASD, shedding light on the consequences of peculiarities in gaze and stereotyped visual behaviors often reported by clinicians working with this population.     

An electrophysiological study on the interaction between emotional content and spatial frequency of visual stimuli

Previous studies suggest that the magnocellular pathway, a visual processing system that rapidly provides low spatial frequency information to fast-responding structures such as the amygdala, is more involved in the processing of emotional facial expressions than the parvocellular pathway (which conveys all spatial frequencies). The present experiment explored the spatio-temporal characteristics of the spatial frequency modulation of affect-related neural processing, as well as its generalizability to non-facial stimuli. To that aim, the event-related potentials (ERPs) elicited by low-pass filtered (i.e., high spatial frequencies are eliminated) and intact non-facial emotional images were recorded from 31 participants using a 60-electrode array. The earliest significant effect of spatial frequency was observed at 135 ms from stimulus onset: N135 component of the ERPs. In line with previous studies, the origin of N135 was localized at secondary visual areas for low-pass filtered stimuli and at primary areas for intact stimuli. Importantly, this component showed an interaction between spatial frequency and emotional content: within low-pass filtered pictures, negative stimuli elicited the highest N135 amplitudes. By contrast, within intact stimuli, neutral pictures were those eliciting the highest amplitudes. These results suggest that high spatial frequencies are not essential for the initial affect-related processing of visual stimuli, which would mainly rely on low spatial frequency visual information. According to present data, high spatial frequencies would come into play later on.     

Preservation of visual cortical function following retinal pigment epithelium transplantation in the RCS rat using optical imaging techniques

The aim of this study was to determine the extent of cortical functional preservation following retinal pigment epithelium (RPE) transplantation in the Royal College of Surgeons (RCS) rat using single-wavelength optical imaging and spectroscopy. The cortical responses to visual stimulation in transplanted rats at 6 months post-transplantation were compared with those from age-matched untreated dystrophic and non-dystrophic rats. Our results show that cortical responses were evoked in non-dystrophic rats to both luminance changes and pattern stimulation, whereas no response was found in untreated dystrophic animals to any of the visual stimuli tested. In contrast, a cortical response was elicited in most of the transplanted rats to luminance changes and in many of those a response was also evoked to pattern stimulation. Although the transplanted rats did not respond to high spatial frequency information we found evidence of preservation in the cortical processing of luminance changes and low spatial frequency stimulation. Anatomical sections of transplanted rat retinas confirmed the capacity of RPE transplantation to rescue photoreceptors. Good correlation was found between photoreceptor survival and the extent of cortical function preservation determined with optical imaging techniques. This study determined the efficacy of RPE transplantation to preserve visual cortical processing and established optical imaging as a powerful technique for its assessment.     

BOLD human responses to chromatic spatial features

Animal physiological and human psychophysical studies suggest that an early step in visual processing involves the detection and identification of features such as lines and edges, by neural mechanisms with even‐ and odd‐symmetric receptive fields. Functional imaging studies also demonstrate mechanisms with even‐ and odd‐receptive fields in early visual areas, in response to luminance‐modulated stimuli. In this study we measured fMRI BOLD responses to 2‐D stimuli composed of only even or only odd symmetric features, and to an amplitude‐matched random noise control, modulated in red–green equiluminant colour contrast. All these stimuli had identical power but different phase spectra, either highly congruent (even or odd symmetry stimuli) or random (noise). At equiluminance, V1 BOLD activity showed no preference between congruent‐ and random‐phase stimuli, as well as no preference between even and odd symmetric stimuli. Areas higher in the visual hierarchy, both along the dorsal pathway (caudal part of the intraparietal sulcus, dorsal LO and V3A) and the ventral pathway (V4), responded preferentially to odd symmetry over even symmetry stimuli, and to congruent over random phase stimuli. Interestingly, V1 showed an equal increase in BOLD activity at each alternation between stimuli of different symmetry, suggesting the existence of specialised mechanisms for the detection of edges and lines such as even‐ and odd‐chromatic receptive fields. Overall the results indicate a high selectivity of colour‐selective neurons to spatial phase along both the dorsal and the ventral pathways in humans.     

Visual response of neurons in the lateral intraparietal area and saccadic reaction time during a visual detection task

During visual detection with saccades, a target with higher luminance is detected with reduced reaction times. In such visual detection behaviors, luminance‐related sensory signals should be converted into movement‐related signals for saccade initiation. At the site where the visuomotor transformation takes place, there is the possibility that visual activity not only encodes the target luminance but also affects the generation of an upcoming saccade. To assess this possibility, we recorded single‐cell activity from visually responsive neurons in the lateral intraparietal area (LIP) when monkeys made a saccade to an isolated target over five luminance levels. We found that as stimulus luminance increased, visual response strength increased, and response onset latency decreased. These luminance‐related changes in activity were significantly correlated with changes in reaction time. In particular, changes in response onset latency accounted for a substantial part of the observed changes in reaction time, suggesting that luminance‐related changes in response onset latency may propagate to the saccade generation process. However, the length of time from response onset to saccade onset was not constant but increased as luminance was reduced, suggesting the existence of other luminance‐dependent processing in downstream and/or parallel pathways before saccade generation. Additionally, we failed to find strong covariance between response strength or latency and reaction time when the effect of luminance changes was removed. Thus, the present results reveal how visually responsive LIP neurons contribute to saccade generation in visual detection.     

Parvocellular pathway impairment in autism spectrum disorder: Evidence from visual evoked potentials

In humans, visual information is processed via parallel channels: the parvocellular (P) pathway analyzes color and form information, whereas the magnocellular (M) stream plays an important role in motion analysis. Individuals with autism spectrum disorder (ASD) often show superior performance in processing fine detail, but impaired performance in processing global structure and motion information. To date, no visual evoked potential (VEP) studies have examined the neural basis of atypical visual performance in ASD. VEPs were recorded using 128-channel high density EEG to investigate whether the P and M pathways are functionally altered in ASD. The functioning of the P and M pathways within primary visual cortex (V1) were evaluated using chromatic (equiluminant red–green sinusoidal gratings) and achromatic (low contrast black–white sinusoidal gratings) stimuli, respectively. Unexpectedly, the N1 component of VEPs to chromatic gratings was significantly prolonged in ASD patients compared to controls. However, VEP responses to achromatic gratings did not differ significantly between the two groups. Because chromatic stimuli preferentially stimulate the P-color but not the P-form pathway, our findings suggest that ASD is associated with impaired P-color pathway activity. Our study provides the first electrophysiological evidence for P-color pathway impairments with preserved M function at the V1 level in ASD.     

Modulation of auditory neural responses by a visual context in human fear conditioning.

Responses to a stimulus signaling danger depend not only on the nature of that stimulus, but also on the context in which it is presented. A large body of work has been conducted in experimental animals investigating the neural correlates of contextual modulation of fear responses. However, much less is known about this process in humans. In this study we used functional MRI in a fear conditioning paradigm to explore this phenomenon. Responses to acoustic conditioned stimuli in auditory cortex were modulated by the presence of a visual context which signaled the likelihood of receiving an aversive unconditioned stimulus. Furthermore, the presence of the aversive visual context was associated with enhanced activity in parietal cortex, which may reflect an increase in attention to the presence of environmental threat stimuli.     

Timing the fearful brain: unspecific hypervigilance and spatial attention in early visual perception

Numerous studies suggest that anxious individuals are more hypervigilant to threat in their environment than nonanxious individuals. In the present event-related potential (ERP) study, we sought to investigate the extent to which afferent cortical processes, as indexed by the earliest visual component C1, are biased in observers high in fear of specific objects. In a visual search paradigm, ERPs were measured while spider-fearful participants and controls searched for discrepant objects (e.g. spiders, butterflies, flowers) in visual arrays. Results showed enhanced C1 amplitudes in response to spatially directed target stimuli in spider-fearful participants only. Furthermore, enhanced C1 amplitudes were observed in response to all discrepant targets and distractors in spider-fearful compared with non-anxious participants, irrespective of fearful and non-fearful target contents. This pattern of results is in line with theoretical notions of heightened sensory sensitivity (hypervigilance) to external stimuli in high-fearful individuals. Specifically, the findings suggest that fear facilitates afferent cortical processing in the human visual cortex in a non-specific and temporally sustained fashion, when observers search for potential threat cues.     

How the parallel channels of the retina contribute to depth processing

Reconstructing the third dimension in the visual scene from the two dimensional images that impinge on the retinal surface is one of the major tasks of the visual system. We have devised a visual display that makes it possible to study stereoscopic depth cues and motion parallax cues separately or in concert using rhesus macaques. By varying the spatial frequency of the display and its luminance and chrominance, it is possible to selectively activate channels that originate in the primate retina. Our results show that (i) the parasol system plays a central role in processing motion parallax cues; (ii) the midget system plays a central role in stereoscopic depth perception at high spatial frequencies, and (iii) red/green colour selective neurons can effectively process both cues but blue/yellow neurons cannot do so.     

Role of the basolateral amygdala and NMDA receptors in higher-order conditioned fear

Laboratory rats learn to fear relatively innocuous stimuli which signal the imminent arrival of an innate source of danger, typically brief but aversive foot shock. Much is now known about the neural substrates underlying the acquisition, consolidation and subsequent expression of this fear. Rats also learn to fear stimuli which signal learned sources of danger but relatively little is known about the neural substrates underlying this form of fear. Two Pavlovian conditioning paradigms used to study this form of fear are second-order conditioning and sensory preconditioning. In second-order conditioning, rats are first exposed to a signaling relationship between one stimulus, such as a tone, and aversive foot shock, and then to a signaling relationship between a second stimulus, such as a light, and the now dangerous tone. In sensory preconditioning, these phases are reversed: rats are first exposed to a signaling relationship between the light and the tone and then to a signaling relationship between the tone and the foot shock. In both paradigms, rats exhibit fear when tested with the light. In this review paper, we describe the evidence for higher-order forms of conditioning, the conditions which promote this learning and its contents. We compare and contrast the substrates of the learning underlying second-order and sensory preconditioning fear with those known to underlie the better studied first-order conditioned fear. We conclude with some comments as to the role of higher-order processes in anxiety disorders.     

Adaptive contextualization: A new role for the default mode network in affective learning

Safety learning describes the ability to learn that certain cues predict the absence of a dangerous or threatening event. Although incidental observations of activity within the default mode network (DMN) during the processing of safety cues have been reported previously, there is as yet no evidence demonstrating that the DMN plays a functional rather than a corollary role in safety learning. Using functional magnetic resonance imaging and a Pavlovian fear conditioning and extinction paradigm, we investigated the neural correlates of danger and safety learning. Our results provide evidence for a functional role of the DMN by showing that (i) the DMN is activated by safety but not danger cues, (ii) the DMN is anti‐correlated with a fear‐processing network, and (iii) DMN activation increases with safety learning. Based on our results, we formulate a novel proposal, arguing that activity within the DMN supports the contextualization of safety memories, constrains the generalization of fear, and supports adaptive fear learning. Our findings have important implications for our understanding of affective and stress disorders, which are characterized by aberrant DMN activity, as they suggest that therapies targeting the DMN through mindfulness practice or brain stimulation might help prevent pathological over‐generalization of fear associations. Hum Brain Mapp 38:1082–1091, 2017. © 2016 Wiley Periodicals, Inc.