Effective Connectivity within Human Primary Visual Cortex Predicts Interindividual Diversity in Illusory Perception

Neural responses to visual stimuli are modulated by spatial and temporal context. For example, in primary visual cortex (V1), responses to an oriented target stimulus will be suppressed when embedded within an oriented surround stimulus. This suppression is orientation-specific, with the largest suppression observed when stimuli in the neuron's classical receptive field and surround are of similar orientation. In human psychological experiments, the tilt illusion and tilt aftereffect demonstrate an effect of context on perceived orientation of a target stimulus. Similar to the neurophysiological data, the strength of these effects is modulated by the orientation difference between the target stimulus and context. It has been hypothesized that the neural mechanism underlying both the tilt illusion and tilt aftereffect involves orientation-tuned inhibition in V1. However, to date there is no direct evidence linking human perception of these illusions with measurements of inhibition from human visual cortex. Here, we measured context-induced suppression of neural responses in human visual cortex using functional magnetic resonance imaging (fMRI). In the same participants, we also measured magnitudes of their tilt illusion and tilt aftereffect. Our data revealed a significant relationship between the magnitude of neural suppression in V1 and size of the tilt illusion and tilt aftereffect. That is, participants who showed stronger blood oxygenation level dependent (BOLD) suppression in V1 also perceived stronger shifts in illusory tilt. This agreement between perception and neural responses in human V1 suggests a shared inhibitory mechanism that mediates both spatial and temporal effects of context in human perception.

A paired-stimuli paradigm combined with fMRI was utilized to study the effect of gradient acoustic noise on fMRI response in the human primary visual cortex (V1) in terms of the auditory-visual cross-modal neural interaction. The gradient noise generated during the fMRI acquisition was used as the primary stimulus, and a single flashing light was used as the secondary stimulus. An interstimulus interval (ISI) separated the two. Six tasks were designed with different ISIs ranging from 50 to 700 ms. Both BOLD signal intensity and the number of activated pixels in V1 were analyzed and examined, and they showed a significant reduction when the gradient noise preceded the flashing light by approximately 300 ms. These results indicate that the gradient acoustic noise generated during fMRI acquisitions does interfere with neural behavior and the BOLD signal in the human visual cortex. This interference is modulated by the delay between the gradient noise and visual stimulation, and it can be studied quantitatively when the stimulation paradigm is designed appropriately. This study provides evidence of the auditory-visual interaction during fMRI studies, and the results should have an impact on fMRI applications.

The processing of orientations is at the core of our visual experience. Orientation selectivity in human visual cortex has been inferred from psychophysical experiments and more recently demonstrated with functional magnetic resonance imaging (fMRI). One method to identify orientation-selective responses is fMRI adaptation, in which two stimuli-either with the same or with different orientations-are presented successively. A region containing orientation-selective neurons should demonstrate an adapted response to the "same orientation" condition in contrast to the "different orientation" condition. So far, human primary visual cortex (V1) showed orientation-selective fMRI adaptation only in experimental designs using prolonged pre-adaptation periods (∼40 s) in combination with top-up stimuli that are thought to maintain the adapted level. This finding has led to the notion that orientation-selective short-term adaptation in V1 (but not V2 or V3) cannot be demonstrated using fMRI. The present study aimed at re-evaluating this question by testing three differently timed adaptation designs. With the use of a more sensitive analysis technique, we show robust orientation-selective fMRI adaptation in V1 evoked by a short-term adaptation design.

Conventional functional connectivity analysis using functional magnetic resonance imaging (fMRI) measures the correlation of temporally synchronized brain activities between brain regions. Lag structure analysis relaxes the synchronicity constraint of fMRI signals, and thus, this approach might be better at explaining functional connectivity. However, the sources of the lag structure in fMRI are primarily unknown. Here, we applied lag structure analysis to the human visual cortex to identify the possible sources of lag structure. A total of 1,250 fMRI data from two independent databases were considered. We explored the temporal lag patterns between the central and peripheral visual fields in early visual cortex and those in two visual pathways of dorsal and ventral streams. We also compared the lag patterns with effective connectivity obtained with dynamic causal modeling. We found that the lag structure in early visual cortex flows from the central to peripheral visual fields and the order of the lag structure flow was consistent with the order of signal flows in visual pathways. The effective connectivity computed by dynamic causal modeling exhibited similar patterns with the lag structure results. This study suggests that signal flows in visual streams are possible sources of the lag structure in human visual cortex.

The Missing Temporal Crescent

Purpose We studied clinically the representation of the monocular temporal crescent in the human visual cortex and noted the importance of using the perimetric techniques best suited to detect this visual field defect and to study patients in whom the temporal crescent is missing. Methods Goldmann perimetry and high-resolution magnetic resonance imaging were performed in two patients with vascular lesions located in the anterior striate cortex. Results A monocular visual field defect, the missing temporal crescent, was found on the side contralateral to the lesion. Conclusions The perimetric-magnetic resonance imaging correlation is in exquisite agreement with recent information about the representation of the visual field in the human primary visual cortex. Reports of this specific perimetric finding are rare, in part because of underdetection with currently used perimetric techniques that concentrate on the central 30 degrees of the visual field.

In vivo functional localization of the temporal monocular crescent representation in human primary visual cortex

Traditionally, human primary visual cortex (V1) has been thought to mature within the first few years of life, based on anatomical studies of synapse formation, and establishment of intracortical and intercortical connections. Human vision, however, develops well beyond the first few years. Previously, we found prolonged development of some GABAergic proteins in human V1 (Pinto et al., 2010). Yet as >80% of synapses in V1 are excitatory, it remains unanswered whether the majority of synapses regulating experience-dependent plasticity and receptive field properties develop late, like their inhibitory counterparts. To address this question, we used Western blotting of postmortem tissue from human V1 (12 female, 18 male) covering a range of ages. Then we quantified a set of postsynaptic glutamatergic proteins (PSD-95, GluA2, GluN1, GluN2A, GluN2B), calculated indices for functional pairs that are developmentally regulated (GluA2:GluN1; GluN2A:GluN2B), and determined interindividual variability. We found early loss of GluN1, prolonged development of PSD-95 and GluA2 into late childhood, protracted development of GluN2A until ∼40 years, and dramatic loss of GluN2A in aging. The GluA2:GluN1 index switched at ∼1 year, but the GluN2A:GluN2B index continued to shift until ∼40 year before changing back to GluN2B in aging. We also identified young childhood as a stage of heightened interindividual variability. The changes show that human V1 develops gradually through a series of five orchestrated stages, making it likely that V1 participates in visual development and plasticity across the lifespan.SIGNIFICANCE STATEMENT Anatomical structure of human V1 appears to mature early, but vision changes across the lifespan. This discrepancy has fostered two hypotheses: either other aspects of V1 continue changing, or later changes in visual perception depend on extrastriate areas. Previously, we showed that some GABAergic synaptic proteins change across the lifespan, but most synapses in V1 are excitatory leaving unanswered how they change. So we studied expression of glutamatergic proteins in human V1 to determine their development. Here we report prolonged maturation of glutamatergic proteins, with five stages that map onto life-long changes in human visual perception. Thus, the apparent discrepancy between development of structure and function may be explained by life-long synaptic changes in human V1.

Functional magnetic resonance imaging (fMRI) studies of early sensory cortex often measure stimulus-driven increases in the blood oxygenation level-dependent (BOLD) signal. However, these positive responses are frequently accompanied by reductions in the BOLD signal in adjacent regions of cortex. Although this negative BOLD response (NBR) is thought to result from neuronal suppression, the precise relationship between local activity, suppression and perception remains unknown. By measuring BOLD signals in human primary visual cortex while varying the baseline contrast levels in the region affected by the NBR, we tested three physiologically-plausible computational models of neuronal modulation which could explain this phenomenon: a subtractive model, a response gain model and a contrast gain model. We also measured the ability of isoluminant contrast to generate an NBR. We show that the NBR can be modeled as a pathway-specific contrast gain modulation that is strongest outside the fovea. We found a similar spatial bias in a psychophysical study using identical stimuli, although these data indicated a response- rather than a contrast-gain mechanism. We reconcile these findings by proposing 1) that the NBR is associated with a long-range suppressive mechanism that hyperpolarizes a subset of magnocellularly-driven neurons at the input to V1; 2) that this suppression is broadly-tuned to match the spatial features of the mask region; 3) that increasing the baseline contrast in the suppressed region drives all neurons in the input layer, reducing the relative contribution of the suppressing subpopulation in the fMRI signal.

The distribution of the calcium-binding protein calbindin D-28K (CB) was investigated in human fetal primary visual cortex. CB is present in Cajal-Retzius cells of layer I, in sparse neurons of the ventricular and intermediate zones (VZ, IZ), and in tangential fibres in IZ by 15 weeks (W) of gestation. Cajal-Retzius cells lose their staining by 30W. CB appears in layers II-VI mainly from 26W, following an inside-outside sequence. Until 34W, CB labelling is in somata and neuropil located primarily in layers IVA, IVC and V. Then reactive perikarya and puncta increase in layers II-IVA and deep IVB and C, but are reduced in infragranular layers from 34W to term. From 30W positive somata form clusters in the cell-rich bands in layers IV and V and labelled neuropil in layers III and IV has a periodic pattern from 34W. Also from 34W, numerous lightly reactive pyramidal cells are present in layers II to IVA in primary, but not secondary, visual cortex. Our results show precocious expression of CB before full laminar differentiation of the cortex and that some of this expression is transient.

Sharply contoured theta waves are the human correlate of ponto-geniculo-occipital waves in the primary visual cortex

Changes in cerebral blood flow (CBF) and metabolism are now widely used to map and quantify neural activity, although the underlying mechanism for these changes is still incompletely understood. Magnetic resonance spectroscopy (MRS) at 3T, synchronized with a 32-s block design visual stimulation paradigm, was employed to investigate activation-induced changes in temperature and metabolism in the human primary visual cortex. A marginally significant increase in the local temperature of the visual cortex was found (0.1 degrees C, P = 0.09), excluding the possibility of a temperature decrease (95% confidence interval (CI) = 0.0-0.2 degrees C), which was previously suggested. A comparison with models of thermal equilibrium in the presence of blood flow suggests that an increase in heat production during activation, greater than or at least equal to that produced by the complete oxidative metabolism of the elevated glucose (Glc) utilization accompanying activation, would be required to offset the cooling effects of the increased blood flow. The total pools of glutamate (Glu), glutamine (Gln), myo-Inositol (mI), N-acetylaspartate (NAA), choline (Cho), and lactate (Lac) were not significantly affected by activation. Limits on Lac concentration changes were too weak to constrain theories of the metabolic use of elevated Glc consumption during stimulation, and emphasize the challenges of measuring even large Lac changes accompanying stimulation.

Modulations of sensory processing in early visual areas are thought to play an important role in conscious perception. To date, most empirical studies focused on effects occurring before or during visual presentation. By contrast, several emerging theories postulate that sensory processing and conscious visual perception may also crucially depend on late top-down influences, potentially arising after a visual display. To provide a direct test of this, we performed an fMRI study using a postcued report procedure. The ability to report a target at a specific spatial location in a visual display can be enhanced behaviorally by symbolic auditory postcues presented shortly after that display. Here we showed that such auditory postcues can enhance target-specific signals in early human visual cortex (V1 and V2). For postcues presented 200 msec after stimulus termination, this target-specific enhancement in visual cortex was specifically associated with correct conscious report. The strength of this modulation predicted individual levels of performance in behavior. By contrast, although later postcues presented 1000 msec after stimulus termination had some impact on activity in early visual cortex, this modulation no longer related to conscious report. These results demonstrate that within a critical time window of a few hundred milliseconds after a visual stimulus has disappeared, successful conscious report of that stimulus still relates to the strength of top-down modulation in early visual cortex. We suggest that, within this critical time window, sensory representation of a visual stimulus is still under construction and so can still be flexibly influenced by top-down modulatory processes.

Spatial attention increases high-frequency gamma synchronisation in human medial visual cortex

Differential Glial Chitotriosidase 1 and Chitinase 3-like Protein 1 Expression in the Human Primary Visual Cortex and Cerebellum after Global Hypoxia-Ischemia