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A Grinvald

Publications and source records attributed to A Grinvald.

At least 19 recordsLinked to original sources

The cortical representation of the hand in macaque and human area S-I: high resolution optical imaging.

High-resolution images of the somatotopic hand representation in macaque monkey primary somatosensory cortex (area S-I) were obtained by optical imaging based on intrinsic signals. To visualize somatotopic maps, we imaged optical responses to mild tactile stimulation of each individual fingertip. The activation evoked by stimulation of a single finger was strongest in a narrow transverse band ( approximately 1 x 4 mm) across the postcentral gyrus. As expected, a sequential organization of these bands was found. However, a significant overlap, especially for the activated areas of fingers 3-5, was found. Surprisingly, in addition to the finger-specific domains, we found that for each of the fingers, weak stimulation activated also a second "common patch" of cortex, located just medially to the representation of the finger. These results were confirmed by targeted multiunit and single-unit recordings guided by the optical maps. The maps remained very stable over many hours of recording. By optimizing the imaging procedures, we were able to obtain the functional maps extremely rapidly (e.g., the map of five fingers in the macaque monkey could be obtained in as little as 5 min). Furthermore, we describe the intraoperative optical imaging of the hand representation in the human brain during neurosurgery and then discuss the implications of the present results for the spatial resolution accomplishable by other neuroimaging techniques, relying on responses of the microcirculation to sensory-evoked electrical activity. This study demonstrates the feasibility of using high-resolution optical imaging to explore reliably short- and long-term plasticity of cortical representations, as well as for applications in the clinical setting.

Action Potentials↗

Long-term optical imaging and spectroscopy reveal mechanisms underlying the intrinsic signal and stability of cortical maps in V1 of behaving monkeys.

Explorations of learning and memory, other long-term plastic changes, and additional cognitive functions in the behaving primate brain would greatly benefit from the ability to image the functional architecture within the same patch of cortex, at the columnar level, for a long period of time. We developed methods for long-term optical imaging based on intrinsic signals and repeatedly visualized the same functional domains in behaving macaque cortex for a period extending over 1 year. Using optical imaging and imaging spectroscopy, we first explored the relationship between electrical activity and hemodynamic events in the awake behaving primate and compared it with anesthetized preparations. We found that, whereas the amplitude of the intrinsic signal was much larger in the awake animal, its temporal pattern was similar to that observed in the anesthetized animals. In both groups, deoxyhemoglobin concentration reached a peak 2-3 sec after stimulus onset. Furthermore, the early activity-dependent increase in deoxyhemoglobin concentration (the "initial dip") was far more tightly colocalized with electrical activity than the delayed increase in oxyhemoglobin concentration, known to be associated with an increase in blood flow. The implications of these results for improvement of the spatial resolution of blood oxygenation level-dependent functional magnetic resonance imaging are discussed. After the characterization of the intrinsic signal in the behaving primate, we used this new imaging method to explore the stability of cortical maps in the macaque primary visual cortex. Functional maps of orientation and ocular dominance columns were found to be stable for a period longer than 1 year.

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Coexistence of linear zones and pinwheels within orientation maps in cat visual cortex.

Revealing the layout of cortical maps is important both for understanding the processes involved in their development and for uncovering the mechanisms underlying neural computation. The typical organization of orientation maps in the cat visual cortex is radial; complete orientation cycles are mapped around orientation singularities. In contrast, long linear zones of orientation representation have been detected in the primary visual cortex of the tree shrew. In this study, we searched for the existence of long linear sequences and wide linear zones within orientation preference maps of the cat visual cortex. Optical imaging based on intrinsic signals was used. Long linear sequences and wide linear zones of preferred orientation were occasionally detected along the border between areas 17 and 18, as well as within area 18. Adjacent zones of distinct radial and linear organizations were observed across area 18 of a single hemisphere. However, radial and linear organizations were not necessarily segregated; long (7.5 mm) linear sequences of preferred orientation were found embedded within a typical pinwheel-like organization of orientation. We conclude that, although the radial organization is dominant, perfectly linear organization may develop and perform the processing related to orientation in the cat visual cortex.

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Visual cortex maps are optimized for uniform coverage.

Cat visual cortex contains a topographic map of visual space, plus superimposed, spatially periodic maps of ocular dominance, spatial frequency and orientation. It is hypothesized that the layout of these maps is determined by two constraints: continuity or smooth mapping of stimulus properties across the cortical surface, and coverage uniformity or uniform representation of combinations of map features over visual space. Here we use a quantitative measure of coverage uniformity (c') to test the hypothesis that cortical maps are optimized for coverage. When we perturbed the spatial relationships between ocular dominance, spatial frequency and orientation maps obtained in single regions of cortex, we found that cortical maps are at a local minimum for c'. This suggests that coverage optimization is an important organizing principle governing cortical map development.

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Linking spontaneous activity of single cortical neurons and the underlying functional architecture.

The relation between the activity of a single neocortical neuron and the dynamics of the network in which it is embedded was explored by single-unit recordings and real-time optical imaging. The firing rate of a spontaneously active single neuron strongly depends on the instantaneous spatial pattern of ongoing population activity in a large cortical area. Very similar spatial patterns of population activity were observed both when the neuron fired spontaneously and when it was driven by its optimal stimulus. The evoked patterns could be used to reconstruct the spontaneous activity of single neurons.

Action Potentials↗

Increased cortical oxidative metabolism due to sensory stimulation: implications for functional brain imaging.

Modern functional brain mapping relies on interactions of neuronal electrical activity with the cortical microcirculation. The existence of a highly localized, stimulus-evoked initial deoxygenation has remained a controversy. Here, the activity-dependent oxygen tension changes in the microcirculation were measured directly, using oxygen-dependent phosphorescence quenching of an exogenous indicator. The first event after sensory stimulation was an increase in oxygen consumption, followed by an increase in blood flow. Because oxygen consumption and neuronal activity are colocalized but the delayed blood flow is not, functional magnetic resonance imaging focused on this initial phase will yield much higher spatial resolution, ultimately enabling the noninvasive visualization of fundamental processing modules in the human brain.

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Imaging cortical dynamics at high spatial and temporal resolution with novel blue voltage-sensitive dyes.

Conventional imaging techniques have provided high-resolution imaging either in the spatial domain or in the temporal domain. Optical imaging utilizing voltage-sensitive dyes has long had the unrealized potential to achieve high resolution in both domains simultaneously, providing subcolumnar spatial detail with millisecond precision. Here, we present a series of developments in voltage-sensitive dyes and instrumentation that make functional imaging of cortical dynamics practical, in both anesthetized and awake behaving preparations, greatly facilitating exploration of the cortex. We illustrate this advance by analyzing the millisecond-by-millisecond emergence of orientation maps in cat visual cortex.

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Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation.

Modern functional neuroimaging methods, such as positron-emission tomography (PET), optical imaging of intrinsic signals, and functional MRI (fMRI) utilize activity-dependent hemodynamic changes to obtain indirect maps of the evoked electrical activity in the brain. Whereas PET and flow-sensitive MRI map cerebral blood flow (CBF) changes, optical imaging and blood oxygenation level-dependent MRI map areas with changes in the concentration of deoxygenated hemoglobin (HbR). However, the relationship between CBF and HbR during functional activation has never been tested experimentally. Therefore, we investigated this relationship by using imaging spectroscopy and laser-Doppler flowmetry techniques, simultaneously, in the visual cortex of anesthetized cats during sensory stimulation. We found that the earliest microcirculatory change was indeed an increase in HbR, whereas the CBF increase lagged by more than a second after the increase in HbR. The increased HbR was accompanied by a simultaneous increase in total hemoglobin concentration (Hbt), presumably reflecting an early blood volume increase. We found that the CBF changes lagged after Hbt changes by 1 to 2 sec throughout the response. These results support the notion of active neurovascular regulation of blood volume in the capillary bed and the existence of a delayed, passive process of capillary filling.

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Spatial relationships among three columnar systems in cat area 17.

In the primary visual cortex, neurons with similar response properties are arranged in columns. As more and more columnar systems are discovered it becomes increasingly important to establish the rules that govern the geometric relationships between different columns. As a first step to examine this issue we investigated the spatial relationships between the orientation, ocular dominance, and spatial frequency domains in cat area 17. Using optical imaging of intrinsic signals we obtained high resolution maps for each of these stimulus features from the same cortical regions. We found clear relationships between orientation and ocular dominance columns: many iso-orientation lines intersected the borders between ocular dominance borders at right angles, and orientation singularities were concentrated in the center regions of the ocular dominance columns. Similar, albeit weaker geometric relationships were observed between the orientation and spatial frequency domains. The ocular dominance and spatial frequency maps were also found to be spatially related: there was a tendency for the low spatial frequency domains to avoid the border regions of the ocular dominance columns. This specific arrangement of the different columnar systems might ensure that all possible combinations of stimulus features are represented at least once in any given region of the visual cortex, thus avoiding the occurrence of functional blind spots for a particular stimulus attribute in the visual field.

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Spatio-temporal frequency domains and their relation to cytochrome oxidase staining in cat visual cortex.

Spatial and temporal frequencies are important attributes of the visual scene. It is a long-standing question whether these attributes are represented in a spatially organized way in cat primary visual cortex. Using optical imaging of intrinsic signals, we show here that grating stimuli of different spatial frequencies drifting at various speeds produce distinct activity patterns. Rather than observing a map of continuously changing spatial frequency preference across the cortical surface, we found only two distinct sets of domains, one preferring low spatial frequency and high speed, and the other high spatial frequency and low speed. We compared the arrangement of these spatio-temporal frequency domains with the cytochrome oxidase staining pattern, which, based on work in primate striate cortex, is thought to reflect the partition of the visual cortex into different processing streams. We found that the cytochrome oxidase blobs in cat striate cortex coincide with domains engaged in the processing of low spatial and high temporal frequency contents of the visual scene. Together with other recent results, our data suggest that spatiotemporal frequency domains are a manifestation of parallel streams in cat visual cortex, with distinct patterns of thalamic inputs and extrastriate projections.

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Functional organization for direction of motion and its relationship to orientation maps in cat area 18.

The goal of this study was to explore the functional organization of direction of motion in cat area 18. Optical imaging was used to record the activity of populations of neurons. We found a patchy distribution of cortical regions exhibiting preference for one direction over the opposite direction of motion. The degree of clustering according to preference of direction was two to four times smaller than that observed for orientation. In general, direction preference changed smoothly along the cortical surface; however, discontinuities in the direction maps were observed. These discontinuities formed lines that separated pairs of patches with preference for opposite directions. The functional maps for direction and for orientation preference were closely related; typically, an iso-orientation patch was divided into regions that exhibited preference for opposite directions, orthogonal to the orientation. In addition, the lines of discontinuity within the direction map often connected points of singularity in the orientation map. Although the organization of both domains was related, the direction and the orientation selective responses were separable; whereas the selective response according to direction of motion was nearly independent of the length of bars used for visual stimulation, the selective response to orientation decreased significantly with decreasing length of the bars. Extensive single and multiunit electrical recordings, targeted to selected domains of the functional maps, confirmed the features revealed by optical imaging. We conclude that significant processing of direction of motion is performed early in the cat visual pathway.

Age Factors↗

Dynamics of ongoing activity: explanation of the large variability in evoked cortical responses.

Evoked activity in the mammalian cortex and the resulting behavioral responses exhibit a large variability to repeated presentations of the same stimulus. This study examined whether the variability can be attributed to ongoing activity. Ongoing and evoked spatiotemporal activity patterns in the cat visual cortex were measured with real-time optical imaging; local field potentials and discharges of single neurons were recorded simultaneously, by electrophysiological techniques. The evoked activity appeared deterministic, and the variability resulted from the dynamics of ongoing activity, presumably reflecting the instantaneous state of cortical networks. In spite of the large variability, evoked responses in single trials could be predicted by linear summation of the deterministic response and the preceding ongoing activity. Ongoing activity must play an important role in cortical function and cannot be ignored in exploration of cognitive processes.

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Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping.

Modern neuroimaging techniques use signals originating from microcirculation to map brain function. In this study, activity-dependent changes in oxyhemoglobin, deoxyhemoglobin, and light scattering were characterized by an imaging spectroscopy approach that offers high spatial, temporal, and spectral resolution. Sensory stimulation of cortical columns initiates tissue hypoxia and vascular responses that occur within the first 3 seconds and are highly localized to individual cortical columns. However, the later phase of the vascular response is less localized, spreading over distances of 3 to 5 millimeters.

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Optical imaging of the layout of functional domains in area 17 and across the area 17/18 border in cat visual cortex.

Optical imaging based on intrinsic signals was used to investigate the functional architecture of cat area 17 and the border between areas 17 and 18. The visual stimuli were gratings of different spatial frequencies moving at different angles, in different directions and with different speeds. In area 17 the iso-orientation domains were usually organized in patches rather than as elongated bands. Patches with different orientation preferences were arranged radially forming 'pinwheels' around 'orientation centres'. The pinwheel density was approximately 1.7-fold higher than in area 18. To explore clustering according to direction of motion, stimuli having the same orientation but moving in opposite directions were used. These two stimuli yielded very similar activity maps giving no indication of robust directionality clustering. Using near infrared light we were able to simultaneously image ocular-dominance and iso-orientation domains. A quantitative assessment of the relative strengths of the two subsystems showed that in upper cortical layers clustering according to orientation preference was three-fold stronger than clustering according to ocular dominance. The functional organization of spatial frequency was also examined. When we compared the activated regions by stimuli having different spatial frequency and moving at different velocities we observed that neurons were clustered also in these respects. We also investigated the functional architecture at the area 17/18 border and found that orientation maps at both sides of the border were not independent of each other. The map of area 17 smoothly blended into that of area 18. Similarly, the preferred spatial frequency of the neurons changed gradually over a distance of approximately 0.8 mm at the region of the area 17/18 border.

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Coherent spatiotemporal patterns of ongoing activity revealed by real-time optical imaging coupled with single-unit recording in the cat visual cortex.

1. We examined the spatiotemporal organization of ongoing activity in cat visual areas 17 and 18, in relation to the spontaneous activity of individual neurons. To search for coherent activity, voltage-sensitive dye signals were correlated with the activity of single neurons by the use of spike-triggered averaging. In each recording session an area of at least 2 x 2 mm of cortex was imaged, with 124 diodes. In addition, electrical recordings from two isolated units, the local field potential (LFP) from the same microelectrodes, and the surface electroencephalogram (EEG) were recorded simultaneously. 2. The optical signals recorded from the dye were similar to the LFP recorded from the same site. Optical signals recorded from different cortical sites exhibited a different time course. Therefore real-time optical imaging provides information that is equivalent in many ways to multiple-site LFP recordings. 3. The spontaneous firing of single neurons was highly correlated with the optical signals and with the LFP. In 88% of the neurons recorded during spontaneous activity, a significant correlation was found between the occurrence of a spike and the optical signal recorded in a large cortical region surrounding the recording site. This result indicates that spontaneous activity of single neurons is not an independent process but is time locked to the firing or to the synaptic inputs from numerous neurons, all activated in a coherent fashion even without a sensory input. 4. For the cases showing correlation with the optical signal, 27-36% of the optical signal during spike occurrence was directly related to the occurrence of spontaneous spikes in a single neuron, over an area of 2 x 2 mm. In the same cortical area, 43-55% of the activity was directly related to the visual stimulus. 5. Surprisingly, we found that the amplitude of this coherent ongoing activity, recorded optically, was often almost as large as the activity evoked by optimal visual stimulation. The amplitude of the ongoing activity that was directly and reproducibly related to the spontaneous spikes of a single neuron was, on average, as high as 54% of the amplitude of the visually evoked response that was directly related to optimal sensory stimulation, recorded optically. 6. Coherent activity was detected even at distant cortical sites up to 6 mm apart.(ABSTRACT TRUNCATED AT 400 WORDS)

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