宽周边视视网膜皮层映射的核磁共振研究

目的:人类视觉皮层的组织方式是视网膜皮层映射组织,先前研究已经证实视觉皮层在中心视采用这种组织方式,本文主要研究宽周边视的视觉皮层组织方式.方法:本文采用一种可以在核磁共振室中使用的光纤设备,设计了30度、40度、50度、60度的类圆环block刺激,使用1.5T的功能性核磁共振仪器,T1高分辨率图像分辨率为1*1*5.5mm,T2加权图像分辨率为4*4*5.5mm,TR反应时间为60,矩阵大小为64*64.核磁共振数据分析使用了SPM2和Brain voyager软件.结果:通过对试验者的数据处理分析,周边视的刺激的反应区域在枕叶上,主要分布在枕叶的前部,刺激反应区域随着偏心率的增大而沿着距状沟从距状沟的后部向前部移动.结论:周边视的视网膜皮层映射组织特性和中心视的特性非常相似.     

Characterization of visual percepts evoked by noninvasive stimulation of the human posterior parietal cortex

Phosphenes are commonly evoked by transcranial magnetic stimulation (TMS) to study the functional organization, connectivity, and excitability of the human visual brain. For years, phosphenes have been documented only from stimulating early visual areas (V1-V3) and a handful of specialized visual regions (V4, V5/MT+) in occipital cortex. Recently, phosphenes were reported after applying TMS to a region of posterior parietal cortex involved in the top-down modulation of visuo-spatial processing. In the present study, we systematically characterized parietal phosphenes to determine if they are generated directly by local mechanisms or emerge through indirect activation of other visual areas. Using technology developed in-house to record the subjective features of phosphenes, we found no systematic differences in the size, shape, location, or frame-of-reference of parietal phosphenes when compared to their occipital counterparts. In a second experiment, discrete deactivation by 1 Hz repetitive TMS yielded a double dissociation: phosphene thresholds increased at the deactivated site without producing a corresponding change at the non-deactivated location. Overall, the commonalities of parietal and occipital phosphenes, and our ability to independently modulate their excitability thresholds, lead us to conclude that they share a common neural basis that is separate from either of the stimulated regions.     

Retinotopic maps, spatial tuning, and locations of human visual areas in surface coordinates characterized with multifocal and blocked FMRI designs

The localization of visual areas in the human cortex is typically based on mapping the retinotopic organization with functional magnetic resonance imaging (fMRI). The most common approach is to encode the response phase for a slowly moving visual stimulus and to present the result on an individual's reconstructed cortical surface. The main aims of this study were to develop complementary general linear model (GLM)-based retinotopic mapping methods and to characterize the inter-individual variability of the visual area positions on the cortical surface. We studied 15 subjects with two methods: a 24-region multifocal checkerboard stimulus and a blocked presentation of object stimuli at different visual field locations. The retinotopic maps were based on weighted averaging of the GLM parameter estimates for the stimulus regions. In addition to localizing visual areas, both methods could be used to localize multiple retinotopic regions-of-interest. The two methods yielded consistent retinotopic maps in the visual areas V1, V2, V3, hV4, and V3AB. In the higher-level areas IPS0, VO1, LO1, LO2, TO1, and TO2, retinotopy could only be mapped with the blocked stimulus presentation. The gradual widening of spatial tuning and an increase in the responses to stimuli in the ipsilateral visual field along the hierarchy of visual areas likely reflected the increase in the average receptive field size. Finally, after registration to Freesurfer's surface-based atlas of the human cerebral cortex, we calculated the mean and variability of the visual area positions in the spherical surface-based coordinate system and generated probability maps of the visual areas on the average cortical surface. The inter-individual variability in the area locations decreased when the midpoints were calculated along the spherical cortical surface compared with volumetric coordinates. These results can facilitate both analysis of individual functional anatomy and comparisons of visual cortex topology across studies.     

Manipulation of pre-target activity on the right frontal eye field enhances conscious visual perception in humans

The right Frontal Eye Field (FEF) is a region of the human brain, which has been consistently involved in visuo-spatial attention and access to consciousness. Nonetheless, the extent of this cortical site's ability to influence specific aspects of visual performance remains debated. We hereby manipulated pre-target activity on the right FEF and explored its influence on the detection and categorization of low-contrast near-threshold visual stimuli. Our data show that pre-target frontal neurostimulation has the potential when used alone to induce enhancements of conscious visual detection. More interestingly, when FEF stimulation was combined with visuo-spatial cues, improvements remained present only for trials in which the cue correctly predicted the location of the subsequent target. Our data provide evidence for the causal role of the right FEF pre-target activity in the modulation of human conscious vision and reveal the dependence of such neurostimulatory effects on the state of activity set up by cue validity in the dorsal attentional orienting network.     

Cell-type-specific synchronization of neural activity in FEF with V4 during attention

Shifts of gaze and shifts of attention are closely linked and it is debated whether they result from the same neural mechanisms. Both processes involve the frontal eye fields (FEF), an area which is also a source of top-down feedback to area V4 during covert attention. To test the relative contributions of oculomotor and attention-related FEF signals to such feedback, we recorded simultaneously from both areas in a covert attention task and in a saccade task. In the attention task, only visual and visuomovement FEF neurons showed enhanced responses, whereas movement cells were unchanged. Importantly, visual, but not movement or visuomovement cells, showed enhanced gamma frequency synchronization with activity in V4 during attention. Within FEF, beta synchronization was increased for movement cells during attention but was suppressed in the saccade task. These findings support the idea that the attentional modulation of visual processing is not mediated by movement neurons.     

Area-specific amblyopic effects in human occipitotemporal object representations

The role of early visual experience in the establishment of human high-order visual areas is poorly understood. Here we investigated this issue using human amblyopia--a developmental visual disorder, which manifests a central vision (acuity) deficit. Previous fMRI studies of amblyopes have described abnormal functional activations in early retinotopic areas. Here we report the surprising finding of a selective object-related abnormality in high-order occipitotemporal cortex. Specifically, we found that face-related cortical areas show a severe disconnection from the amblyopic eye, while building-related regions remain essentially normal. The selectivity of the deficit highlights the differential computations performed in the different object-related areas and is compatible with the suggested association of face regions with analysis of fine detail.     

Frontal non-invasive neurostimulation modulates antisaccade preparation in non-human primates

A combination of oculometric measurements, invasive electrophysiological recordings and microstimulation have proven instrumental to study the role of the Frontal Eye Field (FEF) in saccadic activity. We hereby gauged the ability of a non-invasive neurostimulation technology, Transcranial Magnetic Stimulation (TMS), to causally interfere with frontal activity in two macaque rhesus monkeys trained to perform a saccadic antisaccade task. We show that online single pulse TMS significantly modulated antisaccade latencies. Such effects proved dependent on TMS site (effects on FEF but not on an actively stimulated control site), TMS modality (present under active but not sham TMS on the FEF area), TMS intensity (intensities of at least 40% of the TMS machine maximal output required), TMS timing (more robust for pulses delivered at 150 ms than at 100 post target onset) and visual hemifield (relative latency decreases mainly for ipsilateral AS). Our results demonstrate the feasibility of using TMS to causally modulate antisaccade-associated computations in the non-human primate brain and support the use of this approach in monkeys to study brain function and its non-invasive neuromodulation for exploratory and therapeutic purposes.     

Modulation of visual processing by attention and emotion: windows on causal interactions between human brain regions

Visual processing is not determined solely by retinal inputs. Attentional modulation can arise when the internal attentional state (current task) of the observer alters visual processing of the same stimuli. This can influence visual cortex, boosting neural responses to an attended stimulus. Emotional modulation can also arise, when affective properties (emotional significance) of stimuli, rather than their strictly visual properties, influence processing. This too can boost responses in visual cortex, as for fear-associated stimuli. Both attentional and emotional modulation of visual processing may reflect distant influences upon visual cortex, exerted by brain structures outside the visual system per se. Hence, these modulations may provide windows onto causal interactions between distant but interconnected brain regions. We review recent evidence, noting both similarities and differences between attentional and emotional modulation. Both can affect visual cortex, but can reflect influences from different regions, such as fronto-parietal circuits versus the amygdala. Recent work on this has developed new approaches for studying causal influences between human brain regions that may be useful in other cognitive domains. The new methods include application of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) measures in brain-damaged patients to study distant functional impacts of their focal lesions, and use of transcranial magnetic stimulation concurrently with fMRI or EEG in the normal brain. Cognitive neuroscience is now moving beyond considering the putative functions of particular brain regions, as if each operated in isolation, to consider, instead, how distinct brain regions (such as visual cortex, parietal or frontal regions, or amygdala) may mutually influence each other in a causal manner.     

Optical Imaging of Retinotopic Maps in a Small Songbird,the Zebra Finch

Background

The primary visual cortex of mammals is characterised by a retinotopic representation of the visual field. It has therefore been speculated that the visual wulst, the avian homologue of the visual cortex, also contains such a retinotopic map. We examined this for the first time by optical imaging of intrinsic signals in zebra finches, a small songbird with laterally placed eyes. In addition to the visual wulst, we visualised the retinotopic map of the optic tectum which is homologue to the superior colliculus in mammals.

Methodology/Principal Findings

For the optic tectum, our results confirmed previous accounts of topography based on anatomical studies and conventional electrophysiology. Within the visual wulst, the retinotopy revealed by our experiments has not been illustrated convincingly before. The frontal part of the visual field (0°±30° azimuth) was not represented in the retinotopic map. The visual field from 30°–60° azimuth showed stronger magnification compared with more lateral regions. Only stimuli within elevations between about 20° and 40° above the horizon elicited neuronal activation. Activation from other elevations was masked by activation of the preferred region. Most interestingly, we observed more than one retinotopic representation of visual space within the visual wulst, which indicates that the avian wulst, like the visual cortex in mammals, may show some compartmentation parallel to the surface in addition to its layered structure.

Conclusion/Significance

Our results show the applicability of the optical imaging method also for small songbirds. We obtained a more detailed picture of retinotopic maps in birds, especially on the functional neuronal organisation of the visual wulst. Our findings support the notion of homology of visual wulst and visual cortex by showing that there is a functional correspondence between the two areas but also raise questions based on considerable differences between avian and mammalian retinotopic representations.     

The Frontal Eye Field Is Involved in Visual Vector Inversion in Humans – A Theta Burst Stimulation Study

In the antisaccade task, subjects are requested to suppress a reflexive saccade towards a visual target and to perform a saccade towards the opposite side. In addition, in order to reproduce an accurate saccadic amplitude, the visual saccade vector (i.e., the distance between a central fixation point and the peripheral target) must be exactly inverted from one visual hemifield to the other. Results from recent studies using a correlational approach (i.e., fMRI, MEG) suggest that not only the posterior parietal cortex (PPC) but also the frontal eye field (FEF) might play an important role in such a visual vector inversion process. In order to assess whether the FEF contributes to visual vector inversion, we applied an interference approach with continuous theta burst stimulation (cTBS) during a memory-guided antisaccade task. In 10 healthy subjects, one train of cTBS was applied over the right FEF prior to a memory-guided antisaccade task. In comparison to the performance without stimulation or with sham stimulation, cTBS over the right FEF induced a hypometric gain for rightward but not leftward antisaccades. These results obtained with an interference approach confirm that the FEF is also involved in the process of visual vector inversion.     

The Human Frontal Oculomotor Cortical Areas Contribute Asymmetrically to Motor Planning in a Gap Saccade Task

Background

Saccadic eye movements are used to rapidly align the fovea with the image of objects of interest in peripheral vision. We have recently shown that in children there is a high preponderance of quick latency but poorly planned saccades that consistently fall short of the target goal. The characteristics of these multiple saccades are consistent with a lack of proper inhibitory control of cortical oculomotor areas on the brainstem saccade generation circuitry.

Methodology/Principal Findings

In the present paper, we directly tested this assumption by using single pulse transcranial magnetic stimulation (TMS) to transiently disrupt neuronal activity in the frontal eye fields (FEF) and supplementary eye fields (SEF) in adults performing a gap saccade task. The results showed that the incidence of multiple saccades was increased for ispiversive but not contraversive directions for the right and left FEF, the left SEF, but not for the right SEF. Moreover, this disruption was most substantial during the ∼50 ms period around the appearance of the peripheral target. A control condition in which the dorsal motor cortex was stimulated demonstrated that this was not due to any non-specific effects of the TMS influencing the spatial distribution of attention.

Conclusions/Significance

Taken together, the results are consistent with a direction-dependent role of the FEF and left SEF in delaying the release of saccadic eye movements until they have been fully planned.     

A step towards non-invasive characterization of the human frontal eye fields of individual subjects

Background

Identifying eye movement related areas in the frontal lobe has a long history, with microstimulation in monkeys producing the most clear-cut results. For humans, however, there is still no consensus about the location and the extent of the frontal eye field (FEF). There is also no simple non-invasive method for unambiguously defining the FEF in individual subjects, a prerequisite for clinical applications. Here we explore the use of magnetoencephalography (MEG) for the non-invasive identification and characterization of FEF activity in an individual subject.

Methods

We mapped human brain activity before, during and after saccades by applying tomographic analysis to MEG data. Statistical parametric maps and circular statistics produced plausible FEF loci, but no unambiguous definition for individual subjects. Here we first computed the spectral decomposition and correlation with electrooculogram (EOG) of the tomographic brain activations. For each of these two measures statistical comparisons were made between different saccades.

Results

In this paper, we first review the frontal cortex activations identified in earlier animal and human studies and place the putative human FEFs in a well-defined anatomical framework. This framework is then used as reference for describing the results of new Fourier analysis of the tomographic solutions comparing active saccade tasks and their controls. The most consistent change in the dorsal frontal cortex was at the putative left FEF, for both saccades to the left and right. The asymmetric result is consistent with the 1-way callosal traffic theory. We also showed that the new correlation analysis had its most consistent change in the contralateral putative FEF. This result was obtained for EOG latencies before saccade onset with delays of a few hundreds of milliseconds (FEF activity leading the EOG) and only for visual cues signaling the execution of a saccade in a previously defined saccade direction.

Conclusions

The FEF definition derived from microstimulation describes only one of the areas in the dorsal lateral frontal lobe that act together to plan, prepare and execute a saccade. The definition and characterization of these areas in an individual subject can be obtained from non-invasive MEG measurements.

     

Increased activity in human visual cortex during directed attention in the absence of visual stimulation

When subjects direct attention to a particular location in a visual scene, responses in the visual cortex to stimuli presented at that location are enhanced, and the suppressive influences of nearby distractors are reduced. What is the top-down signal that modulates the response to an attended versus an unattended stimulus? Here, we demonstrate increased activity related to attention in the absence of visual stimulation in extrastriate cortex when subjects covertly directed attention to a peripheral location expecting the onset of visual stimuli. Frontal and parietal areas showed a stronger signal increase during this expectation than did visual areas. The increased activity in visual cortex in the absence of visual stimulation may reflect a top-down bias of neural signals in favor of the attended location, which derives from a fronto-parietal network.     

Electrical Neuroimaging Reveals Timing of Attentional Control Activity in Human Brain

Voluntarily shifting attention to a location of the visual field improves the perception of events that occur there. Regions of frontal cortex are thought to provide the top-down control signal that initiates a shift of attention, but because of the temporal limitations of functional brain imaging, the timing and sequence of attentional-control operations remain unknown. We used a new analytical technique (beamformer spatial filtering) to reconstruct the anatomical sources of low-frequency brain waves in humans associated with attentional control across time. Following a signal to shift attention, control activity was seen in parietal cortex 100–200 ms before activity was seen in frontal cortex. Parietal cortex was then reactivated prior to anticipatory biasing of activity in occipital cortex. The magnitudes of early parietal activations were strongly predictive of the degree of attentional improvement in perceptual performance. These results show that parietal cortex, not frontal cortex, provides the initial signals to shift attention and indicate that top-down attentional control is not purely top down.     

Abnormal attentional modulation of retinotopic cortex in parietal patients with spatial neglect

Brain regions beyond visual cortex are thought to be responsible for attention-related modulation of visual processing [1, 2], but most evidence is indirect. Here, we applied functional magnetic resonance imaging (fMRI), including retinotopic mapping of visual areas, to patients with focal right-parietal lesions and left spatial neglect [3, 4]. When attentional load at fixation was minimal, retinotopic areas in right visual cortex showed preserved responses to task-irrelevant checkerboards in the contralateral left hemifield, analogously to left visual cortex for right-hemifield checkerboards, indicating a "symmetric" pattern in both hemispheres with respect to contralateral stimulation under these conditions. But when attentional load at fixation was increased, a functional asymmetry emerged for visual cortex, with contralateral responses in right visual areas being pathologically reduced (even eliminated for right V4/TEO), whereas left visual areas showed no such reduction in their contralateral response. These results reveal attention-dependent abnormalities in visual cortex after lesions in distant (parietal) regions. This may explain otherwise puzzling aspects of neglect [5, 6], as confirmed here by additional behavioral testing.     

Spike suppression in a local cortical circuit induced by transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) noninvasively interferes with human cortical function, and is widely used as an effective technique for probing causal links between neural activity and cognitive function. However, the physiological mechanisms underlying TMS-induced effects on neural activity remain unclear. We examined the mechanism by which TMS disrupts neural activity in a local circuit in early visual cortex using a computational model consisting of conductance-based spiking neurons with excitatory and inhibitory synaptic connections. We found that single-pulse TMS suppressed spiking activity in a local circuit model, disrupting the population response. Spike suppression was observed when TMS was applied to the local circuit within a limited time window after the local circuit received sensory afferent input, as observed in experiments investigating suppression of visual perception with TMS targeting early visual cortex. Quantitative analyses revealed that the magnitude of suppression was significantly larger for synaptically-connected neurons than for isolated individual neurons, suggesting that intracortical inhibitory synaptic coupling also plays an important role in TMS-induced suppression. A conventional local circuit model of early visual cortex explained only the early period of visual suppression observed in experiments. However, models either involving strong recurrent excitatory synaptic connections or sustained excitatory input were able to reproduce the late period of visual suppression. These results suggest that TMS targeting early visual cortex disrupts functionally distinct neural signals, possibly corresponding to feedforward and recurrent information processing, by imposing inhibitory effects through intracortical inhibitory synaptic connections.     

Feedback contributions to visual awareness in human occipital cortex

It has traditionally been assumed that processing within the visual system proceeds in a bottom-up, feedforward manner from retina to higher cortical areas. In addition to feedforward processing, it is now clear that there are also important contributions to sensory encoding that rely upon top-down, feedback (reentrant) projections from higher visual areas to lower ones. By utilizing transcranial magnetic stimulation (TMS) in a metacontrast masking paradigm, we addressed whether feedback processes in early visual cortex play a role in visual awareness. We show that TMS of visual cortex, when timed to produce visual suppression of an annulus serving as a metacontrast mask, induces recovery of an otherwise imperceptible disk. In addition to producing disk recovery, TMS suppression of an annulus was greater when a disk preceded it than when an annulus was presented alone. This latter result suggests that there are effects of the disk on the perceptibility of the subsequent mask that are additive and are revealed with TMS of the visual cortex. These results demonstrate spatial and temporal interactions of conscious vision in visual cortex and suggest that a prior visual stimulus can influence subsequent perception at early stages of visual encoding via feedback projections.     

Exploring BOLD Changes during Spatial Attention in Non-Stimulated Visual Cortex

Blood oxygen level-dependent (BOLD) responses were measured in parts of primary visual cortex that represented unstimulated visual field regions at different distances from a stimulated central target location. The composition of the visual scene varied by the presence or absence of additional peripheral distracter stimuli. Bottom-up effects were assessed by comparing peripheral activity during central stimulation vs. no stimulation. Top-down effects were assessed by comparing active vs. passive conditions. In passive conditions subjects simply watched the central letter stimuli and in active conditions they had to report occurrence of pre-defined targets in a rapid serial letter stream. Onset of the central letter stream enhanced activity in V1 representations of the stimulated region. Within representations of the periphery activation decreased and finally turned into deactivation with increasing distance from the stimulated location. This pattern was most pronounced in the active conditions and during the presence of peripheral stimuli. Active search for a target did not lead to additional enhancement at areas representing the attentional focus but to a stronger deactivation in the vicinity. Suppressed neuronal activity was also found in the non distracter condition suggesting a top-down attention driven effect. Our observations suggest that BOLD signal decreases in primary visual cortex are modulated by bottom-up sensory-driven factors such as the presence of distracters in the visual field as well as by top-down attentional processes.     

Is visual processing in the dorsal stream accessible to consciousness?

There are two highly interconnected clusters of visually responsive areas in the primate cortex. These two clusters have relatively few interconnections with each other, though those interconnections are undoubtedly important. One of the two main clusters (the dorsal stream) links the primary visual cortex (V1) to superior regions of the occipito-parietal cortex, while the other (the ventral stream) links V1 to inferior regions of the occipito-temporal cortex. According to our current understanding of the functional anatomy of these two systems, the dorsal stream's principal role is to provide real-time 'bottom-up' visual guidance of our movements online. In contrast, the ventral stream, in conjunction with top-down information from visual and semantic memory, provides perceptual representations that can serve recognition, visual thought, planning and memory offline. In recent years, this interpretation, initially based chiefly on studies of non-human primates and human neurological patients, has been well supported by functional MRI studies in humans. This perspective presents empirical evidence for the contention that the dorsal stream governs the visual control of movement without the intervention of visual awareness.     

Correction of Distortion in Flattened Representations of the Cortical Surface Allows Prediction of V1-V3 Functional Organization from Anatomy

Several domains of neuroscience offer map-like models that link location on the cortical surface to properties of sensory representation. Within cortical visual areas V1, V2, and V3, algebraic transformations can relate position in the visual field to the retinotopic representation on the flattened cortical sheet. A limit to the practical application of this structure-function model is that the cortex, while topologically a two-dimensional surface, is curved. Flattening of the curved surface to a plane unavoidably introduces local geometric distortions that are not accounted for in idealized models. Here, we show that this limitation is overcome by correcting the geometric distortion induced by cortical flattening. We use a mass-spring-damper simulation to create a registration between functional MRI retinotopic mapping data of visual areas V1, V2, and V3 and an algebraic model of retinotopy. This registration is then applied to the flattened cortical surface anatomy to create an anatomical template that is linked to the algebraic retinotopic model. This registered cortical template can be used to accurately predict the location and retinotopic organization of these early visual areas from cortical anatomy alone. Moreover, we show that prediction accuracy remains when extrapolating beyond the range of data used to inform the model, indicating that the registration reflects the retinotopic organization of visual cortex. We provide code for the mass-spring-damper technique, which has general utility for the registration of cortical structure and function beyond the visual cortex.