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PubMed2002

Biexponential transverse relaxation (T(2)) of the proton MRS creatine resonance in human brain.

Differences in proton MRS T(2) values for phosphocreatine (PCr) and creatine (Cr) methyl groups (3.0 ppm) were investigated in studies of phantoms and human brain. Results from phantom studies revealed that T(2) of PCr in solution is significantly shorter than T(2) of Cr. Curve-fitting results indicated that the amplitude-TE curves of the total Cr resonance at 3.0 ppm in human brain (N = 26) fit a biexponential decay model significantly better than a monoexponential decay model (P < 0.006), yielding mean T(2) values of 117 +/- 21 ms and 309 +/- 21 ms. Using a localized, long-TE (272 ms) point-resolved spectroscopy (PRESS) proton MRS during 2 min of photic stimulation (PS), an increase of 12.1% +/- 3.5% in the mean intensity of the total Cr resonance in primary visual cortex (VI) was observed at the end of stimulation (P < 0.021). This increase is consistent with the conversion of 26% of PCr in VI to Cr, which is concordant with (31)P MRS findings reported by other investigators. These results suggest a significantly shorter T(2) for PCr than for Cr in vivo. This difference possibly could be exploited to quantify regional activation in functional spectroscopy studies, and could also lead to inaccuracies in some circumstances when the Cr resonance is used as an internal standard for (1)H MRS studies in vivo.

Adult↗
PubMed2003

Measuring the change in CBV upon cortical activation with high temporal resolution using look-locker EPI and Gd-DTPA.

A method of simultaneously measuring the changes in cerebral blood volume (CBV) and T(*) (2) that occur on brain activation with high temporal resolution was developed. The method involves measuring the change in the longitudinal relaxation time (T(1)) that occurs following a bolus injection of Gd-DTPA and converting this measurement to a change in blood volume assuming fast exchange. The sequence was optimized for the measurement of changes in CBV with high temporal resolution. A change in CBV of 27 +/- 4% on activation of the primary visual cortex (V1) was measured across four subjects. The time course of changes in T(*) (2) showed a poststimulus undershoot (P = 0.008) corresponding approximately to a period over which CBV was still elevated above baseline, but falling (P = 0.01). The effects of perfusion, nonfulfillment of the assumption of fast exchange and of intrinsic T(1) changes on activation on the model used to calculate the change in CBV are discussed.

Adult↗
PubMed1996

Dynamic uncoupling and recoupling of perfusion and oxidative metabolism during focal brain activation in man.

Changes in glucose consumption, lactate production, and blood oxygenation were measured during prolonged neuronal activation (4-6 min) in human primary visual cortex using dynamic magnetic resonance spectroscopy and imaging. A decrease of steady-state glucose by 40% because of enhanced use by 21% was accompanied by a transient accumulation of lactate with a peak value of 170% 2.5 min after stimulation onset. Rapid blood hyperoxygenation indicating "uncoupling" of blood flow and oxidative metabolism was followed by a return to basal levels over 3 min. Thus, initial nonoxidative glucose consumption during functional activation is gradually complemented by a slower adjustment of oxidative phosphorylation that "recouples" perfusion and oxygen consumption at a new equilibrium.

Adult↗
PubMed1998

Mapping of lateral geniculate nucleus activation during visual stimulation in human brain using fMRI.

Functional magnetic resonance imaging has been successfully used to map the activation in the lateral geniculate nucleus (LGN) in both hemispheres as well as the primary visual cortex (V1) during a checkerboard visual stimulation. The average blood oxygenation level dependent (BOLD) change in LGN was less than that in V1. However, the BOLD temporal responses were similar between LGN and V1. The activation in the pulvinar nucleus during visual perception was also detected, and its activated location could be separated from LGN in 3D images. The LGN activation between intersubject and intrasubject multiple trials was compared. The results demonstrate that fMRI can reliably and robustly detect small subcortical nucleus activation in the human brain.

Adult↗
PubMed1998

A new correlation-based fuzzy logic clustering algorithm for fMRI.

Fuzzy logic clustering algorithms are a new class of processing strategies for functional MRI (fMRI). In this study, the ability of such methods to detect brain activation on application of a stimulus task is demonstrated. An optimization of the selected algorithm with regard to different parameters is proposed. These parameters include (a) those defining the pre-processing procedure of the data set; (b) the definition of the distance between two time courses, considered as p-dimensional vectors, where p is the number of sequential images in the fMRI data set; and (c) the number of clusters to be considered. Based on the assumption that such a clustering algorithm should cluster the pixel time courses according to their similarity and not their proximity (in terms of distance), cross-correlation-based distances are defined. A clear mathematical description of the algorithm is proposed, and its convergence is proven when similarity measures are used instead of conventional Euclidean distance. The differences between the membership function given by the algorithm and the probability are clearly exposed. The algorithm was tested on artificial data sets, as well as on data sets from six volunteers undergoing stimulation of the primary visual cortex. The fMRI maps provided by the fuzzy logic algorithm are compared to those achieved by the well established cross-correlation technique.

Algorithms↗
PubMed2003

Systematic regulation of spine sizes and densities in pyramidal neurons.

Dendritic spines receive most excitatory inputs in the CNS. Recent evidence has demonstrated that the spine head volume is linearly correlated with the readily releasable pool of neurotransmitter and the PSD size. These correlations can be used to functionally interpret spine morphology. Using Golgi impregnations and light microscopy, we reconstructed 23000 spines from pyramidal neurons in layers 2/3, 4, 5 and 6 of mouse primary visual cortex and CA1 hippocampal region and measured their spine head diameters and densities. Spine head diameters and densities are variable within and across cells, although they are similar between apical and basal dendrites. When compared to other regions, layer 5 neurons have larger spine heads and CA1 neurons higher spine densities. Interestingly, we detect a correlation between spine head diameter and interspine distance within and across cells, whereby larger spines are spaced further away from each other than smaller spines. Finally, in CA1 neurons, spine head diameters are larger, and spine density lower, in distal apical dendrites (>200 microm from soma) compared to proximal regions. These results reveal that spine morphologies and densities, and therefore synaptic properties, are jointly modulated with respect to cortical region, laminar position, and, in some cases, even the position of the spine along the dendritic tree. Individual neurons also appear to regulate their apical and basal spine densities and morphologies in concert. Our data provide evidence for a homeostatic control of excitatory synaptic strength.

Animals↗
PubMed1989

Presence of ghost doublets of coded neuronal patterns: relation to synaptic memory storage.

Recent evidence demonstrates that controlled visual stimuli cause the generation, in the primary visual cortex of rhesus monkey cells, of large numbers of very precisely replicating copies of complex patterns of discharge consisting of three or more spikes, the patterns of which presumedly code for specific qualities of the stimuli presented. We present evidence that the copies of precisely replicating triplets of spikes, generally not exceeding 100 ms in duration, occur in close time proximity to many copies of highly precise "ghost" doublets. These doublets are defined as patterns consisting of two pulses, with precise separations in time, specifically those that would be generated if any one of the pulses making up a given replicating triplet were missing. In striking contrast, nonreplicating triplets (also present in these records)--that is, triplets made up of intervals that are not present in replicating triplets--are not accompanied by such ghost doublets. The persistence (memory) of capacity to produce such ghost doublets decays according to two independent kinetic rules. The first of these results in the disappearance of such doublets within about 0.1 s as measured by two independent methods, whereas the second disappears only after several minutes or longer. These results provide strong evidence consistent with the notion that at least some parts of the brain transmit, store representations of, and retrieve qualitative information through the use of a code consisting of specific patterns of nerve discharges in time.

Animals↗
PubMed1998

Effects of unseen stimuli on reaction times to seen stimuli in monkeys with blindsight.

In three macaque monkeys with unilateral removal of primary visual cortex and in one unoperated monkey, we measured reaction times to a visual target that was presented at a lateral eccentricity of 20 degrees in the normal, left, visual hemifield. When an additional stimulus was presented at the corresponding position in the right hemifield (hemianopic in three of the monkeys), it significantly slowed the reaction time to the left target if it preceded it by delays from 100-500 msec. The most effective delay depended on the particular experimental paradigm and perhaps on the experience of the monkey with the task. The results show that reaction times to seen targets in the normal hemifield of monkeys are influenced by the presentation of "unseen" targets in the anopic hemifield, as in some patients with cortically blind visual field defects.

Animals↗
PubMed1998

Grasping spatial relationships: failure to demonstrate allocentric visual coding in a patient with visual form agnosia.

The cortical visual mechanisms involved in processing spatial relationships remain subject to debate. According to one current view, the "dorsal stream" of visual areas, emanating from primary visual cortex and culminating in the posterior parietal cortex, mediates this aspect of visual processing. More recently, others have argued that while the dorsal stream provides egocentric coding of visual location for motor control, the separate "ventral" stream is needed for allocentric spatial coding. We have assessed the visual form agnosic patient DF, whose lesion mainly affects the ventral stream, on a prehension task requiring allocentric spatial coding. She was presented with transparent circular disks. Each disk had circular holes cut in it. DF was asked to reach out and grasp the disk by placing her fingers through the holes. The disks either had three holes (for forefinger, middle finger, and thumb) or two holes (for forefinger and thumb). The distance between the forefinger and thumb holes, and the orientation of the line formed by them, were independently varied. DF was quite unable to adjust her grip aperture or her hand orientation in the three-hole task. Although she was able to orient her hand appropriately for the two-hole disks, she still remained unable to adjust her grip aperture to the distance between the holes. These findings are consistent with the idea that allocentric processing of spatial information requires a functioning ventral stream, even when the information is being used to guide a motor response.

Agnosia↗
PubMed1994

Age-related effects of triphenyl phosphite-induced delayed neuropathy on central visual pathways in the European ferret (Mustela putorius furo).

The objective of this study was to investigate the relationship between the maturation of visual system neurons and the onset of their susceptibility to triphenyl phosphite (TPP)-induced delayed neurotoxicity in the European ferret. We administered single subcutaneous doses of TPP (1184 mg/kg body wt) to 1- to 10-week-old ferret kits to assess the effects on connections and neurons of the developing lateral geniculate thalamic nucleus (LGN) and primary visual cortex. Brains were processed with a modified Fink-Heimer silver-impregnation method. Axonal and terminal degeneration were first noted in the LGN of kits injected at 5 weeks of age. The severity of the degeneration increased in kits injected at later ages and reached adult densities and configurations in ferrets injected at 10 weeks of age. Degenerating neuronal cell bodies were also present in the LGN of kits injected at 7 weeks of age and older. In the visual cortex, axonal and terminal degeneration were consistently present in kits injected at 8 weeks of age and attained adult-like densities in kits injected at 10 weeks of age. Previous studies have reported that the ferret visual system appears to reach anatomical maturity (as defined by mature LGN lamination patterns, the location and density of axon terminals originating from neurons in the retina and LGN, and the migration and synaptic connections of cortical neurons) by 4-5 weeks of age. A temporal comparison of these normal developmental data with the degeneration data obtained in the present study suggests that immature neurons in the visual system of the ferret are not susceptible to TPP-induced delayed neurotoxicity but only become so after they have achieved some degree of maturity. Whether the LGN neurons undergoing degeneration are directly affected by TPP or are showing a transneuronal response to loss of afferent input remains unresolved.

Age Factors↗
PubMed2000

Hippocampal anatomy and water maze performance are affected by neonatal cryoanesthesia in rats of both sexes.

There is recent evidence that cryoanesthesia, commonly used during neonatal hormone manipulations (e.g., gonadectomy), has deleterious effects on the morphology of the splenium of the corpus callosum and primary visual cortex in adult rats of both sexes. (Nuñez and Juraska, 1998; Nuñez, Kim, and Juraska, 1998). In the present study, the effect of neonatal cryoanesthesia on the morphology of the hippocampus and dentate gyrus and on performance in the Morris water maze was investigated. Cold exposure for as brief as 30 min (5 degrees C) on Postnatal Day 1 resulted in a significant decrease in the volume of the hippocampus and in brain weight of adults. Performance on the water maze was also impaired in cold-exposed animals. This study indicates that not only morphology but also behavioral performance in adulthood are affected by neonatal cryoanesthesia.

Adjuvants, Anesthesia↗
PubMed1998

Nonlinear aspects of the BOLD response in functional MRI.

Functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) contrast has progressed rapidly and is commonly used to study function in many regions of the human brain. This paper introduces a method for characterizing the linear and nonlinear properties of the hemodynamic response. Such characterization is essential for accurate prediction of time-course behavior. Linearity of the BOLD response was examined in the primary visual cortex for manipulations of the stimulus amplitude and duration. Stimuli of 1, 2, 4, and 8 s duration (80% contrast) and 10, 20, 40, and 80% contrast (4 s duration) were used to test the hemodynamic response. Superposition of the obtained responses was performed to determine if the BOLD response is nonlinear. The nonlinear characteristics of the BOLD response were assessed using a Laplacian linear system model cascaded with a broadening function. Discrepancies between the model and the observed response provide an indirect measure of the nonlinearity of the response. The Laplacian linear system remained constant within subjects so the broadening function can be used to absorb nonlinearities in the response. The results show that visual stimulation under 4 s in duration and less than 40% contrast yield strong nonlinear responses.

Algorithms↗
PubMed1999

Stimulus-dependent BOLD and perfusion dynamics in human V1.

Blood oxygenation level-dependent (BOLD) fMRI signals often exhibit pronounced over- or undershoot upon changes in stimulation state. Current models postulate that this is due to the delayed onset or decay of perfusion-dependent attenuating responses such as increased cerebral blood volume or oxygen consumption, which are presumed to lag behind the rapid adjustment of blood flow rate to a new steady-state level. If this view is correct, then BOLD overshoot amplitudes in a specific tissue volume should be correlated with steady-state increases in perfusion, independent of stimulus type. To test this prediction, we simultaneously recorded BOLD and relative perfusion signals in primary visual cortex while inducing graded perfusion increases with three types of visual stimulus. Two of these, a diffuse chromatic stimulus with no luminance variation and a very high spatial frequency luminance grating, did not produce detectable BOLD overshoot (or undershoot) when an equal mean luminance baseline was used. Radial checkerboard stimuli, however, caused pronounced over/undershoot of both BOLD and perfusion signals even when temporal mean luminance was held constant and stimulus contrast was adjusted to produce the same steady-state blood flow increases evoked by the other stimuli. Transient amplitudes were relatively invariant in spite of large changes in steady-state response, demonstrating nonlinear BOLD and perfusion step responses in human V1. These findings suggest that, rather than a purely tissue-specific biomechanical or metabolic phenomenon, BOLD overshoot and undershoot represent transient features in the perfusion signal whose effects may be amplified by slowly evolving blood volume changes.

Cerebrovascular Circulation↗
PubMed2001

Is V1 necessary for conscious vision in areas of relative cortical blindness?

Visual field defects result from postgeniculate lesions. It is generally assumed that absolute defects are caused by total destruction or denervation of primary visual cortex (V1) and that the degraded but conscious vision that remains or returns in relative or partial defects is mediated by compromised V1 cortex that retains a sufficiently large population of functional neurons. We here report the results of three patients with long-standing postgeniculate lesions who underwent functional magnetic resonance imaging while their partial defect was stimulated with high-contrast reversing checkerboard stimuli. Although the stimulation evoked conscious visual impressions in all three, in only one patient did it activate perilesional V1. In the other two we found no evidence for perilesional activation, indicating that some conscious vision may return in the absence of functional ipsilesional V1.

Adult↗
PubMed2001

Mental imagery of high- and low-resolution gratings activates area 17.

Some, but not all, previous neuroimaging studies of visual mental imagery have found that Area 17 (primary visual cortex) is activated when people visualize objects. The present study was designed to test the hypothesis that the necessary degree of resolution of the mental image is a determining factor in whether Area 17 is activated during imagery. Eight male subjects visualized and compared sets of stripes that required high or low resolution to resolve, while their brains were scanned using 15O(CO2) positron emission tomography (PET). When imagery in general (visualization of high- and low-resolution gratings stimuli combined) was compared to an auditory baseline condition where subjects did not visualize, Area 17 was activated. However, region of interest (ROI) and statistical parametric mapping (SPM) analyses revealed no difference between imagery conditions using high- and low-resolution stimuli. These results indicate that the resolution of the stimuli alone does not necessarily determine whether Area 17 will be activated during visual mental imagery.

Adolescent↗
PubMed2001

Effect of respiratory CO(2) changes on the temporal dynamics of the hemodynamic response in functional MR imaging.

Increasing end-expiratory CO(2) levels (PETCO(2)) increases the dispersion and the time of maximum of the hemodynamic response curve in human primary visual cortex. This was demonstrated using event-related multislice functional magnetic resonance imaging (fMRI) with short repetition time and 3-s flicker light stimulation. Measurements were performed at 5 different PETCO(2) levels between 20 and 60 mmHg using hyperventilation or by adding CO(2) to the inspired air. Between 30 and 60 mmHg the full-width-at-half-maximum of the hemodynamic response curve induced by visual stimulation increased nearly linearly at 130 ms per mmHg PETCO(2). Consistent with previous studies a concomitant decrease of the signal amplitude was observed at PETCO(2) values below 40 mmHg and above 50 mmHg. The relevance of these findings for the temporal resolution of fMRI and especially of event-related methods is discussed.

Adult↗
PubMed2002

Single-trial variability in event-related BOLD signals.

Most current analysis methods for fMRI data assume a priori knowledge of the time course of the hemodynamic response (HR) to experimental stimuli or events in brain areas of interest. In addition, they typically assume homogeneity of both the HR and the non-HR "noise" signals, both across brain regions and across similar experimental events. When HRs vary unpredictably, from area to area or from trial to trial, an alternative approach is needed. Here, we use Infomax independent component analysis (ICA) to detect and visualize variations in single-trial HRs in event-related fMRI data. Six subjects participated in four fMRI sessions each in which ten bursts of 8-Hz flickering-checkerboard stimulation were presented for 0.5-s (short) or 3-s (long) durations at 30-s intervals. Five axial slices were acquired by a Bruker 3-T magnetic resonance imager at interscan intervals of 500 ms (TR). ICA decomposition of the resulting blood oxygenation level-dependent (BOLD) data from each session produced an independent component active in primary visual cortex (V1) and, in several sessions, another active in medial temporal cortex (MT/V5). Visualizing sets of BOLD response epochs with novel BOLD-image plots demonstrated that component HRs varied substantially and often systematically across trials as well as across sessions, subjects, and brain areas. Contrary to expectation, in four of the six subjects the V1 component HR contained two positive peaks in response to short-stimulus bursts, while components with nearly identical regions of activity in long-stimulus sessions from the same subjects were associated with single-peaked HRs. Thus, ICA combined with BOLD-image visualization can reveal dramatic and unforeseen HR variations not apparent to researchers analyzing their data with event-related response averaging and fixed HR templates.

Adult↗
PubMed2002

The effect of image scrambling on visual cortical BOLD activity in the anesthetized monkey.

We have investigated BOLD signal changes associated with scrambling natural images into different numbers of segments in visually modulated regions of the macaque monkey (macacca mulatta) brain. For 10 degrees x 10 degrees images, we observed that BOLD activity in primary visual cortex (V1) increased with scrambling, and then dramatically dropped for very highly scrambled images (128 x 128 segments). In extrastriate visual areas, BOLD signal levels did not distinguish between natural images and scrambled images, except that as in V1 very highly scrambled images led to a drop in BOLD activity. Finally in the superior temporal sulcus region and inferior temporal cortex, BOLD activity decreased systematically with scrambling. Our results are consistent with the view that the BOLD signal might reflect average activation of local orienation detectors in V1, and sensitivity to more global object representations in higher visual areas. In addition, we quantify the effects of scrambling on the Fourier amplitude spectrum of the images. This analysis shows that scrambling causes substantial changes to the spatial frequency content of images. This suggests that low-level accounts for reduced BOLD activation in higher visual areas cannot be completely ruled out based on scrambling data.

Animals↗