Learning stable and predictive network-based patterns of schizophrenia and its clinical symptoms.

Schizophrenia is often associated with disrupted brain connectivity. However, identifying specific neuroimaging-based patterns pathognomonic for schizophrenia and related symptom severity remains a challenging open problem requiring large-scale data-driven analyses emphasizing not only statistical significance but also stability across multiple datasets, contexts and cohorts. Accurate prediction on previously unseen subjects, or generalization, is also essential for any useful biomarker of schizophrenia. In order to build a predictive model based on functional network feature patterns, we studied whole-brain fMRI functional networks, both at the voxel level and lower-resolution supervoxel level. Targeting Auditory Oddball task data on the FBIRN fMRI dataset (n = 95), we considered node-degree and link-weight network features and evaluated stability and generalization accuracy of statistically significant feature sets in discriminating patients vs. CONTROLS: We also applied sparse multivariate regression (elastic net) to whole-brain functional connectivity features, for the first time, to derive stable predictive features for symptom severity. Whole-brain link-weight features achieved 74% accuracy in identifying patients and were more stable than voxel-wise node-degrees. Link-weight features predicted severity of several negative and positive symptom scales, including inattentiveness and bizarre behavior. The most-significant, stable and discriminative functional connectivity changes involved increased correlations between thalamus and primary motor/primary sensory cortex, and between precuneus (BA7) and thalamus, putamen, and Brodmann areas BA9 and BA44. Precuneus, along with BA6 and primary sensory cortex, was also involved in predicting severity of several symptoms. Overall, the proposed multi-step methodology may help identify more reliable multivariate patterns allowing for accurate prediction of schizophrenia and its symptoms severity.

Orientation tuning of binocular summation: a comparison of colour to achromatic contrast.

A key function of the primary visual cortex is to combine the input from the two eyes into a unified binocular percept. At low, near threshold, contrasts a process of summation occurs if the visual inputs from the two eyes are similar. Here we measure the orientation tuning of binocular summation for chromatic and equivalent achromatic contrast. We derive estimates of orientation tuning by measuring binocular summation as a function of the orientation difference between two sinusoidal gratings presented dichoptically to different eyes. We then use a model to estimate the orientation bandwidth of the neural detectors underlying the binocular combination. We find that orientation bandwidths are similar for chromatic and achromatic stimuli at both low (0.375 c/deg) and mid (1.5 c/deg) spatial frequencies, with an overall average of 29 ± 3 degs (HWHH, s.e.m). This effect occurs despite the overall greater binocular summation found for the low spatial frequency chromatic stimuli. These results suggest that similar, oriented processes underlie both chromatic and achromatic binocular contrast combination. The non-oriented detection process found in colour vision at low spatial frequencies under monocular viewing is not evident at the binocular combination stage.

Contrast normalization in colour vision: the effect of luminance contrast on colour contrast detection.

While contrast normalization is well known to occur in luminance vision between overlaid achromatic contrasts, and in colour vision between overlaid colour contrasts, it is unknown whether it transfers between colour and luminance contrast. Here we investigate whether contrast detection in colour vision can be normalized by achromatic contrast, or whether this is a selective process driven only by colour contrast. We use a method of cross-orientation masking, in which colour detection is masked by cross-oriented achromatic contrast, over a range of spatio-temporal frequencies (0.375-1.5 cpd, 2-8 Hz). We find that there is virtually no cross-masking of colour by achromatic contrast under monocular or binocular conditions for any of the spatio-temporal frequencies tested, although we find significant facilitation at low spatio-temporal conditions (0.375 cpd, 2 Hz). These results indicate that the process of contrast normalization is colour selective and independent of achromatic contrast, and imply segregated chromatic signals in early visual processing. Under dichoptic conditions, however, we find a strikingly different result with significant masking of colour by achromatic contrast. This indicates that the dichoptic site of suppression is unselective, responding similarly to colour and luminance contrast, and suggests that dichoptic suppression has a different origin from monocular or binocular suppression.

Orientation tuning in human colour vision at detection threshold.

We measure the orientation tuning of red-green colour and luminance vision at low (0.375 c/deg) and mid (1.5 c/deg) spatial frequencies using the low-contrast psychophysical method of subthreshold summation. Orientation bandwidths of the underlying neural detectors are found using a model involving Minkowski summation of the rectified outputs of a bank of oriented filters. At 1.5 c/deg, we find orientation-tuned detectors with similar bandwidths for chromatic and achromatic contrast. At 0.375 c/deg, orientation tuning is preserved with no change in bandwidth for achromatic stimuli, however, for chromatic stimuli orientation tuning becomes extremely broad, compatible with detection by non-oriented colour detectors. A non-oriented colour detector, previously reported in single cells in primate V1 but not psychophysically in humans, can transmit crucial information about the color of larger areas or surfaces whereas orientation-tuned detectors are required to detect the colour or luminance edges that delineate an object's shape.

Cross-orientation masking in human color vision: application of a two-stage model to assess dichoptic and monocular sources of suppression.

Cross-orientation masking (XOM) occurs when the detection of a test grating is masked by a superimposed grating at an orthogonal orientation, and is thought to reveal the suppressive effects mediating contrast normalization. Medina and Mullen (2009) reported that XOM was greater for chromatic than achromatic stimuli at equivalent spatial and temporal frequencies. Here we address whether the greater suppression found in binocular color vision originates from a monocular or interocular site, or both. We measure monocular and dichoptic masking functions for red-green color contrast and achromatic contrast at three different spatial frequencies (0.375, 0.75, and 1.5 cpd, 2 Hz). We fit these functions with a modified two-stage masking model (Meese & Baker, 2009) to extract the monocular and interocular weights of suppression. We find that the weight of monocular suppression is significantly higher for color than achromatic contrast, whereas dichoptic suppression is similar for both. These effects are invariant across spatial frequency. We then apply the model to the binocular masking data using the measured values of the monocular and interocular sources of suppression and show that these are sufficient to account for color binocular masking. We conclude that the greater strength of chromatic XOM has a monocular origin that transfers through to the binocular site.

Blobs versus bars: psychophysical evidence supports two types of orientation response in human color vision.

The classic hypothesis of Livingstone and Hubel (1984, 1987) proposed two types of color pathways in primate visual cortex based on recordings from single cells: a segregated, modular pathway that signals color but provides little information about shape or form and a second pathway that signals color differences and so defines forms without the need to specify their colors. A major problem has been to reconcile this neurophysiological hypothesis with the behavioral data. A wealth of psychophysical studies has demonstrated that color vision has orientation-tuned responses and little impairment on form related tasks, but these have not revealed any direct evidence for nonoriented mechanisms. Here we use a psychophysical method of subthreshold summation across orthogonal orientations for isoluminant red-green gratings in monocular and dichoptic viewing conditions to differentiate between nonoriented and orientation-tuned responses to color contrast. We reveal nonoriented color responses at low spatial frequencies (0.25-0.375 c/deg) under monocular conditions changing to orientation-tuned responses at higher spatial frequencies (1.5 c/deg) and under binocular conditions. We suggest that two distinct pathways coexist in color vision at the behavioral level, revealed at different spatial scales: one is isotropic, monocular, and best equipped for the representation of surface color, and the other is orientation-tuned, binocular, and selective for shape and form. This advances our understanding of the organization of the neural pathways involved in human color vision and provides a strong link between neurophysiological and behavioral data.