Analysis and use of FMRI response delays.

In this study, we implemented a new method for measuring the temporal delay of functional magnetic resonance imaging (fMRI) responses and then estimated the statistical distribution of response delays evoked by visual stimuli (checkered annuli) within and across voxels in human visual cortex. We assessed delay variability among different cortical sites and between parenchyma and blood vessels. Overall, 81% of all responsive voxels showed activation in phase with the stimulus while the remaining voxels showed antiphase, suppressive responses. Mean delays for activated and suppressed voxels were not significantly different (P < 0.001). Cortical flat maps showed that the pattern of activated and suppressed voxels was dynamically induced and depended on stimulus size. Mean delays for blood vessels were 0.7-2.4 sec longer than for parenchyma (P < 0.01). However, both parenchyma and blood vessels produced responses with long delays. We developed a model to identify and quantify different components contributing to variability in the empirical delay measurements. Within-voxel changes in delay over time were fully accounted for by the effects of empirically measured fMRI noise with virtually no measurable variability associated with the stimulus-induced response itself. Across voxels, as much as 47% of the delay variance was also the result of fMRI noise, with the remaining variance reflecting fixed differences in response delay among brain sites. In all cases, the contribution of fMRI noise to the delay variance depended on the noise power at the stimulus frequency. White noise models significantly underestimated the fMRI noise effects.

Neuropsychological evidence for a topographical learning mechanism in parahippocampal cortex.

The Parahippocampal Place Area (PPA; Epstein & Kanwisher, 1998) is a region within posterior parahippocampal cortex that responds selectively to visual stimuli that convey information about the layout of local space. Here we describe two patients who suffered damage to the PPA after vascular incidents. Both subsequently exhibited memory problems for topographical materials and were unable to navigate unassisted in unfamiliar environments. Performance on a continuous n-back visual memory test was significantly lower for novel scene-like stimuli than for novel object-like stimuli. In contrast, performance was normal on a famous landmark recognition task and on two perceptual tasks that required on-line analysis of scene geometry. Both patients were able to produce accurate maps of premorbidly learned places but were unable to produce accurate maps of new places. These results converge with previous neuroimaging work to demonstrate that the PPA (1) is selectively involved in processing information about the geometry of surrounding space, and (2) may play a more critical role in the encoding of this information into memory than in the initial perceptual processing, recognition, or recall of this information.

A comparison of visual and auditory motion processing in human cerebral cortex.

Visual and auditory motion information can be used together to provide complementary information about the movement of objects. To investigate the neural substrates of such cross-modal integration, functional magnetic resonance imaging was used to assess brain activation while subjects performed separate visual and auditory motion discrimination tasks. Areas of unimodal activation included the primary and/or early sensory cortex for each modality plus additional sites extending toward parietal cortex. Areas conjointly activated by both tasks included lateral parietal cortex, lateral frontal cortex, anterior midline and anterior insular cortex. The parietal site encompassed distinct, but partially overlapping, zones of activation in or near the intraparietal sulcus (IPS). A subsequent task requiring an explicit cross-modal speed comparison revealed several foci of enhanced activity relative to the unimodal tasks. These included the IPS, anterior midline, and anterior insula but not frontal cortex. During the unimodal auditory motion task, portions of the dorsal visual motion system showed signals depressed below resting baseline. Thus, interactions between the two systems involved either enhancement or suppression depending on the stimuli present and the nature of the perceptual task. Together, these results identify human cortical regions involved in polysensory integration and the attentional selection of cross-modal motion information.

A functional MRI case study of acquired cerebral dyschromatopsia.

Evidence from imaging studies suggests that primary visual cortex and multiple areas in ventral occipitotemporal cortex subserve color perception in humans. To learn more about the organization of these areas, we used structural and functional MRI (fMRI) to examine a patient with damage to ventral cortex. An art professor, KG, suffered a cerebrovascular accident during heart surgery that impaired his ability to perceive color. The Farnsworth-Munsell 100-Hue test was used to assess the extent of his deficit. When tested 12 months after the lesion, KG performed worse than 95% of age-matched normals on the 100-Hue test, but well above chance. Structural and functional MRI studies were conducted 3 years after the lesion to investigate the neuroanatomical correlates of KG'ss remaining color ability. Structural MRI revealed bilateral damage to ventral occipitotemporal cortex. In young and age-matched normal controls, an fMRI version of the 100-Hue reliably activated bilateral, color-selective regions in primary visual cortex and anterior and posterior ventral cortex. In subject KG, color-selective cortex was found in bilateral primary visual cortex. In ventral cortex, no color-selective activity was observed in right ventral cortex, and only a small area of activity was observed in left anterior ventral cortex. However, significant color-selective activity was observed in posterior left ventral cortex spared by the lesion. This posterior left ventral activation was similar in extent, position, and degree of color-selectivity to the posterior left posterior activation observed in normal controls, suggesting that this focus may be the cortical substrate underlying KG's remaining color perception.

An fMRI version of the Farnsworth-Munsell 100-Hue test reveals multiple color-selective areas in human ventral occipitotemporal cortex.

Studies of patients with cerebral achromatopsia have suggested that ventral occipitotemporal cortex is important for color perception. We created a functional magnetic resonance imaging (fMRI) version of a clinical test commonly used to assess achromatopsia, the Farnsworth-Munsell 100-Hue test. The test required normal subjects to use color information in the visual stimulus to perform a color sequencing task. A modification of the test requiring ordering by luminance was used as a control task. Subjects were also imaged as they passively viewed colored stimuli. A limited number of areas responded more to chromatic than achromatic stimulation, including primary visual cortex. Most color-selective activity was concentrated in ventral occipitotemporal cortex. Several areas in ventral cortex were identified. The most posterior, located in posterior fusiform gyrus, corresponded to the area activated by passive viewing of colored stimuli. More anterior and medial color-selective areas were located in the collateral sulcus and fusiform gyrus. These more anterior areas were not identified in previous imaging studies which used passive viewing of colored stimuli, and were most active in our study when visual color information was behaviorally relevant, suggesting that attention influences activity in color-selective areas. The fMRI version of the Farnsworth-Munsell test may be useful in the study of achromatopsia.

A physiological correlate of the 'spotlight' of visual attention.

Here we identify a neural correlate of the ability to precisely direct visual attention to locations other than the center of gaze. Human subjects performed a task requiring shifts of visual attention (but not of gaze) from one location to the next within a dense array of targets and distracters while functional MRI was used to map corresponding displacements of neural activation within visual cortex. The cortical topography of the purely attention-driven activity precisely matched the topography of activity evoked by the cued targets when presented in isolation. Such retinotopic mapping of attention-related activation was found in primary visual cortex, as well as in dorsomedial and ventral occipital visual areas previously implicated in processing the attended target features. These results identify a physiological basis for the effects of spatially directed visual attention.

Graded effects of spatial and featural attention on human area MT and associated motion processing areas.

Functional magnetic resonance imaging was used to quantify the effects of changes in spatial and featural attention on brain activity in the middle temporal visual area and associated motion processing regions (hMT+) of normal human subjects. When subjects performed a discrimination task that directed their spatial attention to a peripherally presented annulus and their featural attention to the speed of points in the annulus, activity in hMT+ was maximal. If subjects were instead asked to discriminate the color of points in the annulus, the magnitude and volume of activation in hMT+ fell to 64 and 35%, respectively, of the previously observed maximum response. In another experiment, subjects were asked to direct their spatial attention away from the annulus toward the fixation point to detect a subtle change in luminance. The response magnitude and volume dropped to 40 and 9% of maximum. These experiments demonstrate that both spatial and featural attention modulate hMT+ and that their effects can work in concert to modulate cortical activity. The high degree of modulation by attention suggests that an understanding of the stimulus-driven properties of visual cortex needs to be complemented with an investigation of the effects of task-related factors on visual processing.

Mapping striate and extrastriate visual areas in human cerebral cortex.

Functional magnetic resonance imaging (fMRI) was used to identify and map the representation of the visual field in seven areas of human cerebral cortex and to identify at least two additional visually responsive regions. The cortical locations of neurons responding to stimulation along the vertical or horizontal visual field meridia were charted on three-dimensional models of the cortex and on unfolded maps of the cortical surface. These maps were used to identify the borders among areas that would be topographically homologous to areas V1, V2, V3, VP, and parts of V3A and V4 of the macaque monkey. Visually responsive areas homologous to the middle temporal/medial superior temporal area complex and unidentified parietal visual areas were also observed. The topography of the visual areas identified thus far is consistent with the organization in macaque monkeys. However, these and other findings suggest that human and simian cortical organization may begin to differ in extrastriate cortex at, or beyond, V3A and V4.

Reduction of physiological fluctuations in fMRI using digital filters.

Data obtained from functional magnetic resonance imaging are often limited by a low signal-to-noise ratio. The time-course data obtained from activated regions contain both system noise and physiological noise, primarily linked to the heart and respiratory rates, that are superimposed on task induced signals. Time averaging of a practical number of data sets is not very effective in improving the signal-to-noise ratio because neither system nor physiological noise is truly random. In this paper, a method is presented for filtering unwanted physiological fluctuations, including aliased signals that are formed as a result of long repetition time (TR) values. A pulse oximeter was used to obtain cardiac and respiratory information during the scanning period. Finite impulse response band-reject digital filters were designed to remove the physiological fluctuations. For comparison, cross-correlation analyses were performed at the same level of statistical significance on both filtered and unfiltered data. We demonstrate that this method can improve the detection of weak signals without increasing the probability of false positives.

Activity correlates of cytochrome oxidase-defined compartments in granular and supragranular layers of primary visual cortex of the macaque monkey.

To determine if changes in metabolic capacity revealed by cytochrome oxidase (CO) histochemistry are related to sustained changes in energy-utilizing neuronal activity, we assayed CO levels and recorded multiunit firing rates along nearly tangential penetrations of V1 in seven adult macaque monkeys before and after single, monocular injections of TTX. Within as little as 14 h, TTX blockade began to reduce CO staining in zones of layer 4C that received dominant input from the injected eye. Since simple monocular occlusion has only minor effects on cortical CO levels (Trusk et al., 1990), the changes in activity that were specifically associated with CO depletion were isolated by comparing spike rates during monocular TTX blockade and during monocular occlusion. Five second samples of multiunit spike rate were obtained after 2-min adaptation to each of four adapting fields: black, gray, white, and textured. Results were similar for these four conditions. In layer 4C, ocular dominance zones with input from the TTX eye had ongoing spike rates that were 48% of the rates in zones with input from a normal but occluded eye. In six animals, it was possible to record activity at a single site before, during, and after the onset of TTX blockade. Background activity at these interpuff sites decreased as much as 3-fold in less than 1 h but stabilized within 3-4 h to an average of 53% of pre-TTX rates. These data support the interpretation that energy utilization linked to sustained spike rates partially regulates CO levels under normal conditions, at least in layer 4. Furthermore, changes in neuronal activity induced by retinal TTX preceded the detectable reduction in CO activity in V1 suggesting that the adjustment of CO levels was in response to the altered activity.

Functional magnetic resonance imaging (FMRI) of the human brain.

Functional magnetic resonance imaging (FMRI) can provide detailed images of human brain that reflect localized changes in cerebral blood flow and oxygenation induced by sensory, motor, or cognitive tasks. This review presents methods for gradient-recalled echo-planar functional magnetic resonance imaging (FMRI). Also included is a discussion of the hypothesized basis of FMRI, imaging hardware, a unique visual stimulation apparatus, image post-processing and statistical analysis. Retinotopic mapping of striate and extrastriate visual cortex is discussed as an example application. The described echo-planar technique permitted acquisition of an image in 40 ms with a repetition rate of up to 2 per second. However, FMRI responses are slow compared to changes in neural activity. Onset of a visual checkerboard test pattern evoked a response that was delayed by 1-2 s and reached 90% of peak in 5 s. Return to baseline following stimulation was slightly slower. Alternating control (blank) and test (checkerboard) patterns every 20 s induced a cyclic response that was detected in the presence of noise using a cross-correlation technique that was verified by parametric statistics. FMRI revealed retinotopically organized patterns of visually evoked activity in response to annular stimuli that increased in visual field eccentricity. Retinotopy was also observed with test patterns rotated around the fixation point (center of gaze). Results from repeated tests 1 week apart were highly similar. Compared to passive viewing, an active visual discrimination task enhanced responses from extrastriate association cortex.

Multiple processing streams in occipitotemporal visual cortex.

The earliest stages of cortical visual processing in areas V1 and V2 of the macaque monkey contain internal subdivisions ('blobs' and 'interblobs' in layer 4B in V1; thin, thick and interstripes in V2) that are selectively interconnected and contain neurons with distinctive visual response properties. Here we use anatomical pathway tracing to demonstrate that higher visual areas, V4 and the ventral posterior inferotemporal cortex, each contain anatomical subdivisions that have distinct input and output projections. These findings, in conjunction with others, suggest that modularity and multistream processing within individual cortical areas are widespread features of neocortical organization.

Neural responses to visual texture patterns in middle temporal area of the macaque monkey.

1. We studied how neurons in the middle temporal visual area (MT) of anesthetized macaque monkeys responded to textured and nontextured visual stimuli. Stimuli contained a central rectangular "figure" that was either uniform in luminance or consisted of an array of oriented line segments. The figure moved at constant velocity in one of four orthogonal directions. The region surrounding the figure was either uniform in luminance or contained a texture array (whose elements were identical or orthogonal in orientation to those of the figure), and it either was stationary or moved along with the figure. 2. A textured figure moving across a stationary textured background ("texture bar" stimulus) often elicited vigorous neural responses, but, on average, the responses to texture bars were significantly smaller than to solid (uniform luminance) bars. 3. Many cells showed direction selectivity that was similar for both texture bars and solid bars. However, on average, the direction selectivity measured when texture bars were used was significantly smaller than that for solid bars, and many cells lost significant direction selectivity altogether. The reduction in direction selectivity for texture bars generally reflected a combination of decreased responsiveness in the preferred direction and increased responsiveness in the null (opposite to preferred) direction. 4. Responses to a texture bar in the absence of a texture background ("texture bar alone") were very similar to the responses to solid bars both in the magnitude of response and in the degree of direction selectivity. Conversely, adding a static texture surround to a moving solid bar reduced direction selectivity on average without a reduction in response magnitude. These results indicate that the static surround is largely responsible for the differences in direction selectivity for texture bars versus solid bars. 5. In the majority of MT cells studied, responses to a moving texture bar were largely independent of whether the elements in the bar were of the same orientation as the background elements or of the orthogonal orientation. Thus, for the class of stimuli we used, orientation contrast does not markedly affect the responses of MT neurons to moving texture patterns. 6. The optimum figure length and the shapes of the length tuning curves determined with the use of solid bars and texture bars differed significantly in most of the cells examined. Thus neurons in MT are not simply selective for a particular figure shape independent of whatever cues are used to delineate the figure.

Antibody labeling of functional subdivisions in visual cortex: Cat-301 immunoreactivity in striate and extrastriate cortex of the macaque monkey.

We have examined the distribution of immunoreactivity for the monoclonal antibody Cat-301 in visual cortex of the macaque monkey. Remarkably, those portions of striate cortex (V1) and extrastriate cortex that are most immunoreactive for Cat-301 are anatomically interconnected and are dominated by inputs arising from the magnocellular layers of the LGN (which are themselves highly immunoreactive). In particular, we found that a band of Cat-301 labeled neurons known to exist in layer 4 of V1 is centered on the boundary between layers 4C alpha and 4B and thus includes portions of both the primary target of the magnocellular LGN and its subsequent relay through layer 4B. We also demonstrated consistently strong Cat-301 immunoreactivity in all three extrastriate targets of layer 4B: areas V3, MT, and the cytochrome-oxidase (CO) enriched thick stripes of V2. In V2, there was a close correlation between Cat-301 labeling and clusters of cells projecting to MT but not to V4. This was true even in regions where the CO pattern was equivocal or irregular, indicating that Cat-301 is a more reliable marker than CO for the thick-stripe subregions of V2. Finally, we found strong Cat-301 immunoreactivity in at least parts of areas V3A, the MST complex, and the posterior parietal complex, but not in area V4 or inferotemporal cortex. The molecular specificity revealed by this single marker thus correlates with functionally specific subdivisions at each hierarchical level over nearly the entire known extent of the visual pathway in macaques. This supports the notion that these subdivisions form an anatomically, physiologically, and now molecularly distinct pathway known as the M-stream.

Segregation of efferent connections and receptive field properties in visual area V2 of the macaque.

V2 is a visual area of the macaque monkey which is at the second level in a recently proposed hierarchy of cortical visual areas. Histochemical staining for cytochrome oxidase (CO) in V2 reveals a pattern of alternate thick and thin CO-rich stripes separated by CO-sparse interstripes. These subregions receive distinct inputs from neurones in CO-rich and CO-sparse zones arrayed within the superficial layers of V1 (refs 4, 5). Are output projections from V2 to higher visual areas also segregated? Using an anatomical double-label paradigm, we have now demonstrated that V2 cells projecting to two of its major target areas, MT and V4 (refs 6, 7), are arranged in stripe-like clusters which are largely segregated from one another and which are closely related to the pattern of CO stripes. Concomitant electrophysiological recordings from V2 indicate that groups of cells having similar receptive field properties are clustered within the subregions defined by these anatomical techniques.

Rarity of luxotonic responses in cortical visual areas of the cat.

Neuronal responses to continuous, diffuse white light or darkness were studied in cortical visual areas 17, 18, 19 and Clare-Bishop of the unanesthetized cat. In contrast to squirrel monkeys and macaques in which about 40 or 25% of the units in striate cortex are luxotonic (response to continuous light or darkness sustained > 2.0 min), all of the visual areas in the cat had fewer than 4.0% of the units exhibiting such luxotonic activity. The functional basis of this difference may be related to differences between the two species in the quantitative balance of antagonistic receptive field properties.