Spatial selectivity in the temporoparietal junction, inferior frontal sulcus, and inferior parietal lobule.

Spatial selectivity, as measured by functional magnetic resonance imaging (fMRI) activity patterns that vary consistently with the location of visual stimuli, has been documented in many human brain regions, notably the occipital visual cortex and the frontal and parietal regions that are active during endogenous, goal-directed attention. We hypothesized that spatial selectivity also exists in regions that are active during exogenous, stimulus-driven attention. To test this hypothesis, we acquired fMRI data while subjects maintained passive fixation. At jittered time intervals, a briefly presented wedge-shaped array of rapidly expanding circles appeared at one of three contralateral or one of three ipsilateral locations. Positive fMRI activations were identified in multiple brain regions commonly associated with exogenous attention, including the temporoparietal junction, the inferior parietal lobule, and the inferior frontal sulcus. These activations were not organized as a map across the cortical surface. However, multivoxel pattern analysis of the fMRI activity correctly classified every pair of stimulus locations, demonstrating that patterns of fMRI activity were correlated with spatial location. These observations held for both contralateral and ipsilateral stimulus pairs as well as for stimuli of different textures (radial checkerboard) and shapes (squares and rings). Permutation testing verified that the obtained accuracies were not due to systematic biases and demonstrated that the findings were statistically significant.

Effects of Prior Knowledge on Decisions Made Under Perceptual vs. Categorical Uncertainty.

Humans use prior knowledge to bias decisions made under uncertainty. In this fMRI study we predicted that different brain dynamics play a role when prior knowledge is added to decisions made under perceptual vs. categorical uncertainty. Subjects decided whether shapes belonged to Category S - smoother - or Category B - bumpier - under both uncertainty conditions, with or without prior knowledge cues. When present, the prior knowledge cue, 80/20 or 50/50, indicated that 80 and 20% (or 50 and 50%) were the chances that responding "S" and "B" (or vice versa) would be correct. During perceptual uncertainty, shapes were degraded with noise. During categorical uncertainty, shapes were ambiguous. Adding the 80/20 cue increased activation during perceptual uncertainty in bilateral lateral occipital (LO) cortex and left middle frontal gyrus (MidFG), and decreased activity in bilateral LO cortex during categorical uncertainty. Right MidFG and other frontoparietal regions were active in all conditions. The results demonstrate that left MidFG shows activation changes, suggestive of an influence on visual cortex, that depend on the factor that makes the decisions difficult. When sensory evidence is difficult to perceive, prior knowledge increases visual cortical activity. When the sensory evidence is easy to perceive but difficult to interpret, prior knowledge decreases visual cortical activity.

Human brain activity predicts individual differences in prior knowledge use during decisions.

Studies by cognitive psychologists, psychophysicists, neuroscientists, and economists provide ample evidence that humans use prior knowledge to bias decisions adaptively. In this study, we sought to locate and investigate the brain areas mediating this behavior. Participants viewed ambiguous abstract shapes and decided whether a shape was of Category A (smoother) or B (bumpier). The decision was made in the context of one of two prior knowledge cues, 80/20 and 50/50. The 80/20 cue indicated that upcoming shapes had an 80% probability of being of one category, for example, B, and a 20% probability of being of the other. The 50/50 cue indicated that upcoming shapes had an equal probability of being of either category. The shift in bias produced by the 80/20 cue relative to the 50/50 cue was of the predicted sign for every subject but varied in magnitude. We searched for brain regions in which activity changes correlated with the extent of the bias shift; these were dorsolateral pFC (middle frontal gyrus), inferior frontal junction, anterior insula, inferior parietal lobule, intraparietal sulcus, head of the caudate, posterior cingulate cortex, and fusiform gyrus. The findings indicate that an individual's brain activity in these regions reflects the extent to which that individual makes use of prior knowledge to bias decisions. We also created within-ROI tuning curves by binning the shape curvature levels and plotting brain activity levels at each of the nine bins. In the fronto-parietal and anterior insula ROIs, the tuning curves peaked at targets contraindicated by the prior knowledge cue (e.g., Category B targets if the 80/20 cue meant 20% probability B). The increased activity in these regions likely indicates a no-go response when sufficient perceptual evidence favored the alternative contraindicated by the 80/20 cue.

Persistency of priors-induced bias in decision behavior and the FMRI signal.

It is well known that people take advantage of prior knowledge to bias decisions. To investigate this phenomenon behaviorally and in the brain, we acquired fMRI data while human subjects viewed ambiguous abstract shapes and decided whether a shape was of Category A (smoother) or B (bumpier). The decision was made in the context of one of two prior knowledge cues, 80/20 and 50/50. The 80/20 cue indicated that upcoming shapes had an 80% probability of being of one category, e.g., B, and a 20% probability of being of the other. The 50/50 cue indicated that upcoming shapes had an equal probability of being of either category. The ideal observer would bias decisions in favor of the indicated alternative at 80/20 and show zero bias at 50/50. We found that subjects did bias their decisions in the predicted direction at 80/20 but did not show zero bias at 50/50. Instead, at 50/50 the subjects retained biases of the same sign as their 80/20 biases, though of diminished magnitude. The signature of a persistent though diminished bias at 50/50 was also evident in fMRI data from frontal and parietal regions previously implicated in decision-making. As a control, we acquired fMRI data from naïve subjects who experienced only the 50/50 stimulus distributions during both the pre-scan training and the fMRI experiment. The behavioral and fMRI data from the naïve subjects reflected decision biases closer to those of the ideal observer than those of the prior knowledge subjects at 50/50. The results indicate that practice making decisions in the context of non-equal prior probabilities biases decisions made later when prior probabilities are equal. This finding may be related to the "anchoring and adjustment" strategy described in the psychology, economics, and marketing literatures, in which subjects adjust a first approximation response - the "anchor" - based on additional information, typically applying insufficient adjustment relative to the ideal observer.

Modeling low-frequency fluctuation and hemodynamic response timecourse in event-related fMRI.

Functional magnetic resonance imaging (fMRI) suffers from many problems that make signal estimation difficult. These include variation in the hemodynamic response across voxels and low signal-to-noise ratio (SNR). We evaluate several analysis techniques that address these problems for event-related fMRI. (1) Many fMRI analyses assume a canonical hemodynamic response function, but this assumption may lead to inaccurate data models. By adopting the finite impulse response model, we show that voxel-specific hemodynamic response functions can be estimated directly from the data. (2) There is a large amount of low-frequency noise fluctuation (LFF) in blood oxygenation level dependent (BOLD) time-series data. To compensate for this problem, we use polynomials as regressors for LFF. We show that this technique substantially improves SNR and is more accurate than high-pass filtering of the data. (3) Model overfitting is a problem for the finite impulse response model because of the low SNR of the BOLD response. To reduce overfitting, we estimate a hemodynamic response timecourse for each voxel and incorporate the constraint of time-event separability, the constraint that hemodynamic responses across event types are identical up to a scale factor. We show that this technique substantially improves the accuracy of hemodynamic response estimates and can be computed efficiently. For the analysis techniques we present, we evaluate improvement in modeling accuracy via 10-fold cross-validation.

Topographic organization in and near human visual area V4.

The existence and location of a human counterpart of macaque visual area V4 are disputed. To resolve this issue, we used functional magnetic resonance imaging to obtain topographic maps from human subjects, using visual stimuli and tasks designed to maximize accuracy of topographic maps of the fovea and parafovea and to measure the effects of attention on topographic maps. We identified multiple topographic transitions, each clearly visible in > or = 75% of the maps, that we interpret as boundaries of distinct cortical regions. We call two of these regions dorsal V4 and ventral V4 (together comprising human area V4) because they share several defining characteristics with the macaque regions V4d and V4v (which together comprise macaque area V4). Ventral V4 is adjacent to V3v, and dorsal V4 is adjacent to parafoveal V3d. Ventral V4 and dorsal V4 meet in the foveal confluence shared by V1, V2, and V3. Ventral V4 and dorsal V4 represent complementary regions of the visual field, because ventral V4 represents the upper field and a subregion of the lower field, whereas dorsal V4 represents lower-field locations that are not represented by ventral V4. Finally, attentional modulation of spatial tuning is similar across dorsal and ventral V4, but attention has a smaller effect in V3d and V3v and a larger effect in a neighboring lateral occipital region.

Parametric reverse correlation reveals spatial linearity of retinotopic human V1 BOLD response.

Many experiments measuring blood oxygen level dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) data assume that the BOLD signal is predominantly linear in space and time. Previous investigations of temporal linearity have reported that the temporal BOLD response contains both linear and nonlinear components. Here, we used a novel method to investigate spatial linearity of BOLD within area V1. The visual field was divided into regions shaped like wedges, rings, or the intersections of the wedges and rings. The appearance of a flickering checkerboard texture within each region was governed by an independent M-sequence. fMRI data were acquired as the human subjects maintained visual fixation on a central cross. The time series data from each voxel were cross-correlated with every stimulus sequence to estimate each voxel's BOLD responses to all independent regions of the visual field. Linearity by spatial summation was assessed directly by comparing responses to wedges and rings with sums of responses to component patches. The BOLD responses of voxels responding positively to stimuli, measured with independent stimuli subtending several degrees of visual angle, were well predicted by linear spatial summation.

Adeno-associated virus encoding green fluorescent protein as a label for retinal pigment epithelium.

PURPOSE: To determine whether transduction with adeno-associated virus encoding green fluorescent protein (AAV-GFP) is useful for labeling transplanted retinal pigment epithelial cells (RPE). METHODS: Transduction was performed by infection of confluent or subconfluent cultured feline RPE or by subretinal injection. Cells transduced in vitro were analyzed to determine label stability over time and label conservation with cell division. RPE transduced in vivo were harvested at 5 weeks for transplantation or immunohistochemical detection. Two cats received subretinal injections of harvested cells and were killed at 3 or 7 days. RESULTS: In vitro transduction of confluent RPE resulted in stable GFP fluorescence for at least 3 months. There was a marked decline in fluorescence after cell division. Nonconfluent transduced cells conserved label after cell division but showed a marked decline in the number of cells, due to cell death. In vivo transduction resulted in a high level of labeling, allowing labeled cells to be harvested and transplanted. Transplanted cells were detected immunohistochemically. Photoreceptor labeling was detected over areas containing a high density of transplanted, labeled RPE derived from cells transduced in vivo. Possible light toxicity to transduced RPE was observed. CONCLUSIONS: AAV-GFP-labeling of confluent cultured RPE and RPE in situ can be used to identify transplanted RPE, with some reservations. Cell division may cause dilution of the label, and release of cell contents into the subretinal space may cause label transfer to photoreceptors. Exposure to light of transduced cells should be limited.