The psychosis human connectome project: Design and rationale for studies of visual neurophysiology.

Visual perception is abnormal in psychotic disorders such as schizophrenia. In addition to hallucinations, laboratory tests show differences in fundamental visual processes including contrast sensitivity, center-surround interactions, and perceptual organization. A number of hypotheses have been proposed to explain visual dysfunction in psychotic disorders, including an imbalance between excitation and inhibition. However, the precise neural basis of abnormal visual perception in people with psychotic psychopathology (PwPP) remains unknown. Here, we describe the behavioral and 7 tesla MRI methods we used to interrogate visual neurophysiology in PwPP as part of the Psychosis Human Connectome Project (HCP). In addition to PwPP (n = 66) and healthy controls (n = 43), we also recruited first-degree biological relatives (n = 44) in order to examine the role of genetic liability for psychosis in visual perception. Our visual tasks were designed to assess fundamental visual processes in PwPP, whereas MR spectroscopy enabled us to examine neurochemistry, including excitatory and inhibitory markers. We show that it is feasible to collect high-quality data across multiple psychophysical, functional MRI, and MR spectroscopy experiments with a sizable number of participants at a single research site. These data, in addition to those from our previously described 3 tesla experiments, will be made publicly available in order to facilitate further investigations by other research groups. By combining visual neuroscience techniques and HCP brain imaging methods, our experiments offer new opportunities to investigate the neural basis of abnormal visual perception in PwPP.

Weakened untuned gain control is associated with schizophrenia while atypical orientation-tuned suppression depends on visual acuity.

Perceptual distortions are core features of psychosis. Weakened contrast surround suppression has been proposed as a neural mechanism underlying atypical perceptual experiences. Although previous work has measured suppression by asking participants to report the perceived contrast of a low-contrast target surrounded by a high-contrast surround, it is possible to modulate perceived contrast solely by manipulating the orientation of a matched-contrast center and surround. Removing the bottom-up segmentation cue of contrast difference and isolating orientation-dependent suppression may clarify the neural processes responsible for atypical surround suppression in psychosis. We examined surround suppression across a spectrum of psychotic psychopathology including people with schizophrenia (PSZ; N = 31) and people with bipolar disorder (PBD; N = 29), first-degree biological relatives of these patient groups (PBDrel, PSZrel; N = 28, N = 21, respectively), and healthy controls (N = 29). PSZ exhibited reduced surround suppression across orientations; although group differences were minimal at the condition that produced the strongest suppression. PBD and PSZrel exhibited intermediate suppression, whereas PBDrel performed most similarly to controls. Intriguingly, group differences in orientation-dependent surround suppression magnitude were moderated by visual acuity. A simulation in which visual acuity and/or focal attention interact with untuned gain control reproduces the observed pattern of results, including the lack of group differences when orientation of center and surround are the same. Our findings further elucidate perceptual mechanisms of impaired center-surround processing in psychosis and provide insights into the effects of visual acuity on orientation-dependent suppression in PSZ.

Depth-dependent functional MRI responses to chromatic and achromatic stimuli throughout V1 and V2.

In the primate visual system, form (shape, location) and color information are processed in separate but interacting pathways. Recent access to high-resolution neuroimaging has facilitated the exploration of the structure of these pathways at the mesoscopic level in the human visual cortex. We used 7T fMRI to observe selective activation of the primary visual cortex to chromatic versus achromatic stimuli in five participants across two scanning sessions. Achromatic checkerboards with low spatial frequency and high temporal frequency targeted the color-insensitive magnocellular pathway. Chromatic checkerboards with higher spatial frequency and low temporal frequency targeted the color-selective parvocellular pathway. This work resulted in three main findings. First, responses driven by chromatic stimuli had a laminar profile biased towards superficial layers of V1, as compared to responses driven by achromatic stimuli. Second, we found stronger preference for chromatic stimuli in parafoveal V1 compared with peripheral V1. Finally, we found alternating, stimulus-selective bands stemming from the V1 border into V2 and V3. Similar alternating patterns have been previously found in both NHP and human extrastriate cortex. Together, our findings confirm the utility of fMRI for revealing details of mesoscopic neural architecture in human cortex.

The psychosis human connectome project: An overview.

Investigations within the Human Connectome Project have expanded to include studies focusing on brain disorders. This paper describes one of the investigations focused on psychotic psychopathology: The psychosis Human Connectome Project (P-HCP). The data collected as part of this project were multimodal and derived from clinical assessments of psychopathology, cognitive assessments, instrument-based motor assessments, blood specimens, and magnetic resonance imaging (MRI) data. The dataset will be made publicly available through the NIMH Data Archive. In this report we provide specific information on how the sample of participants was obtained and characterized and describe the experimental tasks and procedures used to probe neural functions involved in psychotic disorders that may also mark genetic liability for psychotic psychopathology. Our goal in this paper is to outline the data acquisition process so that researchers intending to use these publicly available data can plan their analyses. MRI data described in this paper are limited to data acquired at 3 Tesla. A companion paper describes the study's 7 Tesla image acquisition protocol in detail, which is focused on visual perceptual functions in psychotic psychopathology.

Assessing methods for geometric distortion compensation in 7 T gradient echo functional MRI data.

Echo planar imaging (EPI) is widely used in functional and diffusion-weighted MRI, but suffers from significant geometric distortions in the phase encoding direction caused by inhomogeneities in the static magnetic field (B0 ). This is a particular challenge for EPI at very high field (≥7 T), as distortion increases with higher field strength. A number of techniques for distortion correction exist, including those based on B0 field mapping and acquiring EPI scans with opposite phase encoding directions. However, few quantitative comparisons of distortion compensation methods have been performed using human EPI data, especially at very high field. Here, we compared distortion compensation using B0 field maps and opposite phase encoding scans in two different software packages (FSL and AFNI) applied to 7 T gradient echo (GE) EPI data from 31 human participants. We assessed distortion compensation quality by quantifying alignment to anatomical reference scans using Dice coefficients and mutual information. Performance between FSL and AFNI was equivalent. In our whole-brain analyses, we found superior distortion compensation using GE scans with opposite phase encoding directions, versus B0 field maps or spin echo (SE) opposite phase encoding scans. However, SE performed better when analyses were limited to ventromedial prefrontal cortex, a region with substantial dropout. Matching the type of opposite phase encoding scans to the EPI data being corrected (e.g., SE-to-SE) also yielded better distortion correction. While the ideal distortion compensation approach likely varies depending on methodological differences across experiments, this study provides a framework for quantitative comparison of different distortion compensation methods.

Reduced influence of perceptual context in schizophrenia: behavioral and neurophysiological evidence.

BACKGROUND: Accurate perception of visual contours is essential for seeing and differentiating objects in the environment. Both the ability to detect visual contours and the influence of perceptual context created by surrounding stimuli are diminished in people with schizophrenia (SCZ). The central aim of the present study was to better understand the biological underpinnings of impaired contour integration and weakened effects of perceptual context. Additionally, we sought to determine whether visual perceptual abnormalities reflect genetic factors in SCZ and are present in other severe mental disorders. METHODS: We examined behavioral data and event-related potentials (ERPs) collected during the perception of simple linear contours embedded in similar background stimuli in 27 patients with SCZ, 23 patients with bipolar disorder (BP), 23 first-degree relatives of SCZ, and 37 controls. RESULTS: SCZ exhibited impaired visual contour detection while BP exhibited intermediate performance. The orientation of neighboring stimuli (i.e. flankers) relative to the contour modulated perception across all groups, but SCZ exhibited weakened suppression by the perceptual context created by flankers. Late visual (occipital P2) and cognitive (centroparietal P3) neural responses showed group differences and flanker orientation effects, unlike earlier ERPs (occipital P1 and N1). Moreover, behavioral effects of flanker context on contour perception were correlated with modulation in P2 & P3 amplitudes. CONCLUSION: In addition to replicating and extending findings of abnormal contour integration and visual context modulation in SCZ, we provide novel evidence that the abnormal use of perceptual context is associated with higher-order sensory and cognitive processes.

Cortical Correlates of Attention to Auditory Features.

Pitch and timbre are two primary features of auditory perception that are generally considered independent. However, an increase in pitch (produced by a change in fundamental frequency) can be confused with an increase in brightness (an attribute of timbre related to spectral centroid) and vice versa. Previous work indicates that pitch and timbre are processed in overlapping regions of the auditory cortex, but are separable to some extent via multivoxel pattern analysis. Here, we tested whether attention to one or other feature increases the spatial separation of their cortical representations and if attention can enhance the cortical representation of these features in the absence of any physical change in the stimulus. Ten human subjects (four female, six male) listened to pairs of tone triplets varying in pitch, timbre, or both and judged which tone triplet had the higher pitch or brighter timbre. Variations in each feature engaged common auditory regions with no clear distinctions at a univariate level. Attending to one did not improve the separability of the neural representations of pitch and timbre at the univariate level. At the multivariate level, the classifier performed above chance in distinguishing between conditions in which pitch or timbre was discriminated. The results confirm that the computations underlying pitch and timbre perception are subserved by strongly overlapping cortical regions, but reveal that attention to one or other feature leads to distinguishable activation patterns even in the absence of physical differences in the stimuli.SIGNIFICANCE STATEMENT Although pitch and timbre are generally thought of as independent auditory features of a sound, pitch height and timbral brightness can be confused for one another. This study shows that pitch and timbre variations are represented in overlapping regions of auditory cortex, but that they produce distinguishable patterns of activation. Most importantly, the patterns of activation can be distinguished based on whether subjects attended to pitch or timbre even when the stimuli remained physically identical. The results therefore show that variations in pitch and timbre are represented by overlapping neural networks, but that attention to different features of the same sound can lead to distinguishable patterns of activation.

Representations of Pitch and Timbre Variation in Human Auditory Cortex.

Pitch and timbre are two primary dimensions of auditory perception, but how they are represented in the human brain remains a matter of contention. Some animal studies of auditory cortical processing have suggested modular processing, with different brain regions preferentially coding for pitch or timbre, whereas other studies have suggested a distributed code for different attributes across the same population of neurons. This study tested whether variations in pitch and timbre elicit activity in distinct regions of the human temporal lobes. Listeners were presented with sequences of sounds that varied in either fundamental frequency (eliciting changes in pitch) or spectral centroid (eliciting changes in brightness, an important attribute of timbre), with the degree of pitch or timbre variation in each sequence parametrically manipulated. The BOLD responses from auditory cortex increased with increasing sequence variance along each perceptual dimension. The spatial extent, region, and laterality of the cortical regions most responsive to variations in pitch or timbre at the univariate level of analysis were largely overlapping. However, patterns of activation in response to pitch or timbre variations were discriminable in most subjects at an individual level using multivoxel pattern analysis, suggesting a distributed coding of the two dimensions bilaterally in human auditory cortex. SIGNIFICANCE STATEMENT: Pitch and timbre are two crucial aspects of auditory perception. Pitch governs our perception of musical melodies and harmonies, and conveys both prosodic and (in tone languages) lexical information in speech. Brightness-an aspect of timbre or sound quality-allows us to distinguish different musical instruments and speech sounds. Frequency-mapping studies have revealed tonotopic organization in primary auditory cortex, but the use of pure tones or noise bands has precluded the possibility of dissociating pitch from brightness. Our results suggest a distributed code, with no clear anatomical distinctions between auditory cortical regions responsive to changes in either pitch or timbre, but also reveal a population code that can differentiate between changes in either dimension within the same cortical regions.

Hemifield columns co-opt ocular dominance column structure in human achiasma.

In the absence of an optic chiasm, visual input to the right eye is represented in primary visual cortex (V1) in the right hemisphere, while visual input to the left eye activates V1 in the left hemisphere. Retinotopic mapping In V1 reveals that in each hemisphere left and right visual hemifield representations are overlaid (Hoffmann et al., 2012). To explain how overlapping hemifield representations in V1 do not impair vision, we tested the hypothesis that visual projections from nasal and temporal retina create interdigitated left and right visual hemifield representations in V1, similar to the ocular dominance columns observed in neurotypical subjects (Victor et al., 2000). We used high-resolution fMRI at 7T to measure the spatial distribution of responses to left- and right-hemifield stimulation in one achiasmic subject. T2-weighted 2D Spin Echo images were acquired at 0.8mm isotropic resolution. The left eye was occluded. To the right eye, a presentation of flickering checkerboards alternated between the left and right visual fields in a blocked stimulus design. The participant performed a demanding orientation-discrimination task at fixation. A general linear model was used to estimate the preference of voxels in V1 to left- and right-hemifield stimulation. The spatial distribution of voxels with significant preference for each hemifield showed interdigitated clusters which densely packed V1 in the right hemisphere. The spatial distribution of hemifield-preference voxels in the achiasmic subject was stable between two days of testing and comparable in scale to that of human ocular dominance columns. These results are the first in vivo evidence showing that visual hemifield representations interdigitate in achiasmic V1 following a similar developmental course to that of ocular dominance columns in V1 with intact optic chiasm.

Responses in early visual areas to contour integration are context dependent.

It has been shown that early visual areas are involved in contour processing. However, it is not clear how local and global context interact to influence responses in those areas, nor has the interarea coordination that yields coherent structural percepts been fully studied, especially in human observers. In this study, we used functional magnetic resonance imaging (fMRI) to measure activity in early visual cortex while observers performed a contour detection task in which alignment of Gabor elements and background clutter were manipulated. Six regions of interest (two regions, containing either the cortex representing the target or the background clutter, in each of areas V1, V2, and V3) were predefined using separate target versus background functional localizer scans. The first analysis using a general linear model showed that in the presence of background clutter, responses in V1 and V2 target regions of interest were significantly stronger to aligned than unaligned contours, whereas when background clutter was absent, no significant difference was observed. The second analysis using interarea correlations showed that with background clutter, there was an increase in V1-V2 coordination within the target regions when perceiving aligned versus unaligned contours; without clutter, however, correlations between V1 and V2 were similar no matter whether aligned contours were present or not. Both the average response magnitude and the connectivity analysis suggest different mechanisms support contour processing with or without background distractors. Coordination between V1 and V2 may play a major role in coherent structure perception, especially with complex scene organization.

The effects of orientation and attention during surround suppression of small image features: A 7 Tesla fMRI study.

Although V1 responses are driven primarily by elements within a neuron's receptive field, which subtends about 1° visual angle in parafoveal regions, previous work has shown that localized fMRI responses to visual elements reflect not only local feature encoding but also long-range pattern attributes. However, separating the response to an image feature from the response to the surrounding stimulus and studying the interactions between these two responses demands both spatial precision and signal independence, which may be challenging to attain with fMRI. The present study used 7 Tesla fMRI with 1.2-mm resolution to measure the interactions between small sinusoidal grating patches (targets) at 3° eccentricity and surrounds of various sizes and orientations to test the conditions under which localized, context-dependent fMRI responses could be predicted from either psychophysical or electrophysiological data. Targets were presented at 8%, 16%, and 32% contrast while manipulating (a) spatial extent of parallel (strongly suppressive) or orthogonal (weakly suppressive) surrounds, (b) locus of attention, (c) stimulus onset asynchrony between target and surround, and (d) blocked versus event-related design. In all experiments, the V1 fMRI signal was lower when target stimuli were flanked by parallel versus orthogonal context. Attention amplified fMRI responses to all stimuli but did not show a selective effect on central target responses or a measurable effect on orientation-dependent surround suppression. Suppression of the V1 fMRI response by parallel surrounds was stronger than predicted from psychophysics but showed a better match to previous electrophysiological reports.

A voxel-wise encoding model for early visual areas decodes mental images of remembered scenes.

Recent multi-voxel pattern classification (MVPC) studies have shown that in early visual cortex patterns of brain activity generated during mental imagery are similar to patterns of activity generated during perception. This finding implies that low-level visual features (e.g., space, spatial frequency, and orientation) are encoded during mental imagery. However, the specific hypothesis that low-level visual features are encoded during mental imagery is difficult to directly test using MVPC. The difficulty is especially acute when considering the representation of complex, multi-object scenes that can evoke multiple sources of variation that are distinct from low-level visual features. Therefore, we used a voxel-wise modeling and decoding approach to directly test the hypothesis that low-level visual features are encoded in activity generated during mental imagery of complex scenes. Using fMRI measurements of cortical activity evoked by viewing photographs, we constructed voxel-wise encoding models of tuning to low-level visual features. We also measured activity as subjects imagined previously memorized works of art. We then used the encoding models to determine if putative low-level visual features encoded in this activity could pick out the imagined artwork from among thousands of other randomly selected images. We show that mental images can be accurately identified in this way; moreover, mental image identification accuracy depends upon the degree of tuning to low-level visual features in the voxels selected for decoding. These results directly confirm the hypothesis that low-level visual features are encoded during mental imagery of complex scenes. Our work also points to novel forms of brain-machine interaction: we provide a proof-of-concept demonstration of an internet image search guided by mental imagery.

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.

What insights can fMRI offer into the structure and function of mid-tier visual areas?

Inferring neural responses from functional magnetic resonance imaging (fMRI) data is challenging. Even if we take advantage of high-field systems to acquire data with submillimeter resolution, we are still acquiring data in which a single datum summarizes the responses of tens of thousands of neurons. Excitation and inhibition, spikes and subthreshold membrane potential modulations, local and long-range computations, and tuned and nonselective responses are mixed together in one signal. With a priori knowledge of the underlying neural population responses, careful experiment design allows us to manipulate the experiment or task design so that subpopulations are selectively modulated, and our experiments can reveal those tuning functions. However, because we want to be able to use fMRI to discover new kinds of tuning functions and selectivity, we cannot limit ourselves to experiments in which we already know what we are looking for. Broadly speaking, analyses that rely on classification of responses that are distributed across the local neural population [multi-voxel pattern analyses (MVPA)] offer the ability to discover new kinds of information representation and selectivities in neural subpopulations. There is, however, no way to determine how the information discovered with MVPA or other analyses is related to the underlying neuronal tuning functions. Therefore, we must continue to rely on behavioral, computational, and animal models to develop theories of information representation in mid-tier visual cortical areas. Once encoding models exist, fMRI can be powerful for testing these a priori models of information representation. As an aide in developing these models, an important contribution that fMRI can make to our understanding of mid-tier visual areas is derived from connectivity analyses and experiments that study information sharing between visual areas. This ability to quantify localized population average responses throughout the brain is the strength we can best leverage to discover new properties of local and long-range neural networks.

Regions of mid-level human visual cortex sensitive to the global coherence of local image patches.

The global structural arrangement and spatial layout of the visual environment must be derived from the integration of local signals represented in the lower tiers of the visual system. This interaction between the spatially local and global properties of visual stimulation underlies many of our visual capacities, and how this is achieved in the brain is a central question for visual and cognitive neuroscience. Here, we examine the sensitivity of regions of the posterior human brain to the global coordination of spatially displaced naturalistic image patches. We presented observers with image patches in two circular apertures to the left and right of central fixation, with the patches drawn from either the same (coherent condition) or different (noncoherent condition) extended image. Using fMRI at 7T (n = 5), we find that global coherence affected signal amplitude in regions of dorsal mid-level cortex. Furthermore, we find that extensive regions of mid-level visual cortex contained information in their local activity pattern that could discriminate coherent and noncoherent stimuli. These findings indicate that the global coordination of local naturalistic image information has important consequences for the processing in human mid-level visual cortex.

Surround Suppression of Broadband Images.

Visual perception is profoundly sensitive to context. Surround suppression is a well-known visual context effect in which the firing rate of a neuron is suppressed by stimulation of its extra-classical receptive field. The majority of contrast surround suppression studies exclusively use narrowband, sinusoidal grating stimuli; however, it is unclear whether the results produced by such artificial stimuli generalize to real-world, naturalistic visual experiences. To address this issue, we developed a contrast discrimination paradigm that includes both naturalistic broadband textures and narrowband grating textures. All textures were matched for first order image statistics and overall perceptual salience. We observed surround suppression across broadband textures (F(1,6)=19.01, p=.005); however, effect sizes were largest for narrowband, sinusoidal gratings (Cohen's d=1.83). Among the three broadband texture types, we observed strongest suppression for the texture with a clear dominant orientation (stratified: Cohen's d=1.29), while the textures with a more even distribution of orientation information produced weaker suppression (fibrous: Cohen's d=0.63; braided: Cohen's d=0.65). We also observed an effect of texture identity on the slope of psychometric functions (F(1.98,11.9)=7.29, p=0.01), primarily driven by smaller slopes for the texture with the most uniform distribution of orientations. Our results suggest that well-known contextual modulation effects only partially generalize to more ecologically valid stimuli.

Impaired contour object perception in psychosis.

Contour integration, the process of joining spatially separated elements into a single unified line, has consistently been found to be impaired in schizophrenia. Recent work suggests that this deficit could be associated with psychotic symptomatology, rather than a specific diagnosis such as schizophrenia. Examining a transdiagnostic sample of participants with psychotic psychopathology, we obtained quantitative indices of contour perception in a psychophysical behavioral task. We found impaired contour discrimination performance among people with psychotic psychopathology (PwPP, n = 62) compared to healthy controls (n = 34) and biological relatives of PwPP (n = 44). Participants with schizophrenia (n = 31) showed impaired task performance compared to participants with bipolar disorder (n = 18). We also measured responses during an analogous task using ultra-high field (7T) functional MRI and found higher responses in the lateral occipital cortex of PwPP compared to controls. Using task-based functional connectivity analyses, we observed abnormal connectivity between visual brain areas during contour perception among PwPP. These connectivity differences only emerged when participants had to distinguish the contour object from background distractors, suggesting that a failure to suppress noise elements relative to contour elements may underlie impaired contour processing in PwPP. Our results are consistent with impaired contour integration in psychotic psychopathology, and especially schizophrenia, that is related to cognitive dysfunction, and may be linked to impaired functional connectivity across visual regions.

Consequences of polar form coherence for fMRI responses in human visual cortex.

Relevant features in the visual image are often spatially extensive and have complex orientation structure. Our perceptual sensitivity to such spatial form is demonstrated by polar Glass patterns, in which an array of randomly-positioned dot pairs that are each aligned with a particular polar displacement (rotation, for example) yield a salient impression of spatial structure. Such patterns are typically considered to be processed in two main stages: local spatial filtering in low-level visual cortex followed by spatial pooling and complex form selectivity in mid-level visual cortex. However, it remains unclear both whether reciprocal interactions within the cortical hierarchy are involved in polar Glass pattern processing and which mid-level areas identify and communicate polar Glass pattern structure. Here, we used functional magnetic resonance imaging (fMRI) at 7T to infer the magnitude of neural response within human low-level and mid-level visual cortex to polar Glass patterns of varying coherence (proportion of signal elements). The activity within low-level visual areas V1 and V2 was not significantly modulated by polar Glass pattern coherence, while the low-level area V3, dorsal and ventral mid-level areas, and the human MT complex each showed a positive linear coherence response functions. The cortical processing of polar Glass patterns thus appears to involve primarily feedforward communication of local signals from V1 and V2, with initial polar form selectivity reached in V3 and distributed to multiple pathways in mid-level visual cortex.

Segmentation decreases the magnitude of the tilt illusion.

In the tilt illusion, the perceived orientation of a target grating depends strongly on the orientation of a surround. When the orientations of the center and surround gratings differ by a small angle, the center grating appears to tilt away from the surround orientation (repulsion), whereas for a large difference in angle, the center appears to tilt toward the surround orientation (attraction). In order to understand how segmentation/perceptual grouping of the center and surround affect the magnitude of the tilt illusion, we conducted three psychophysical experiments in which we measured observers' perception of center orientation as a function of center-surround relative contrast, relative disparity depth, and geometric features such as occlusion and collinearity. All of these manipulations affected the strength of perceived orientation bias in the center. Our results suggest that if stronger segmentation/perceptual grouping is induced between the center and surround, the tilt repulsion bias decreases/increases. A grouping-dependent tilt illusion plays an important role in visual search and detection by enhancing the sensitivity of our visual system to feature discrepancies, especially in relatively homogenous environments.

What multiplexing means for the interpretation of functional MRI data.

Despite technology advances that have enabled routine acquisition of functional MRI data with sub-millimeter resolution, the inferences that cognitive neuroscientists must make to link fMRI data to behavior are complicated. Thus, a single dataset subjected to different analyses can be interpreted in different ways. This article presents two optical analogies that can be useful for framing fMRI analyses in a way that allows for multiple interpretations of fMRI data to be valid simultaneously without undermining each other. The first is reflection: when an object is reflected in a mirrored surface, it appears as if the reflected object is sharing space with the mirrored object, but of course it is not. This analogy can be a good guide for interpreting the fMRI signal, since even at sub-millimeter resolutions the signal is determined by a mixture of local and long-range neural computations. The second is refraction. If we view an object through a multi-faceted prism or gemstone, our view will change-sometimes dramatically-depending on our viewing angle. In the same way, interpretation of fMRI data (inference of underlying neuronal activity) can and should be different depending on the analysis approach. Rather than representing a weakness of the methodology, or the superiority of one approach over the other (for example, simple regression analysis versus multi-voxel pattern analysis), this is an expected consequence of how information is multiplexed in the neural networks of the brain: multiple streams of information are simultaneously present in each location. The fact that any one analysis typically shows only one view of the data also puts some parentheses around fMRI practitioners' constant search for ground truth against which to compare their data. By holding our interpretations lightly and understanding that many interpretations of the data can all be true at the same time, we do a better job of preparing ourselves to appreciate, and eventually understand, the complexity of the brain and the behavior it produces.