Simultaneous oxygenation and perfusion imaging study of functional activity in primary visual cortex at different visual stimulation frequency: quantitative correlation between BOLD and CBF changes

A relationship between regional cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) changes in the primary visual cortex (V1) at varied visual stimulation frequency has been examined quantitatively using the multislice FAIR technique. A linear correlation in the common activation areas between functional BOLD and CBF maps was observed. This supports the hypothesis that the task-stimulated BOLD changes in microvasculature are correlated with the CBF changes that presumably reflect the degree of neuronal activity. The linear correlation coefficients for intrasubject comparisons are more significant than those for intersubject comparisons. This suggests that using intrasubject comparisons for quantitative studies of neuronal activity related to different task stimuli and task performances should be more reliable than using intersubject comparisons.     

Molecular pathophysiology of cystic fibrosis based on the rescued knockout mouse model

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.     

Circulating levels of Locusta diuretic hormone: the effects of feeding

The most widely-used functional magnetic resonance imaging (fMRI) technique is based on the blood oxygenation level dependent (BOLD) effect, which requires at least partial uncoupling between cerebral blood flow (CBF) and oxygen consumption changes during increased mental activity. To compare BOLD and CBF effects during tasking, BOLD and flow-sensitive alternating inversion recovery (FAIR) images were acquired during visual stimulation with red goggles at a frequency of 8 Hz in an interleaved fashion. With the FAIR technique, absolute and relative CBF changes were determined. Relative oxygen consumption changes can be estimated using the BOLD and relative CBF changes. In gray matter areas in the visual cortex, absolute and relative CBF changes in humans during photic stimulation were 31 +/- 11 SD ml/100 g tissue/min and 43 +/- 16 SD % (n = 12), respectively, while the relative oxygen consumption change was close to zero. These findings agree extremely well with previous results using positron emission tomography. The BOLD signal change is not linearly correlated with the relative CBF increase across subjects and negatively correlates with the oxygen consumption change. Caution should be exercised when interpreting the BOLD percent change as a quantitative index of the CBF change, especially in inter-subject comparisons.     

Functional MRI reveals spatially specific attentional modulation in human primary visual cortex

Selective visual attention can strongly influence perceptual processing, even for apparently low-level visual stimuli. Although it is largely accepted that attention modulates neural activity in extrastriate visual cortex, the extent to which attention operates in the first cortical stage, striate visual cortex (area V1), remains controversial. Here, functional MRI was used at high field strength (3 T) to study humans during attentionally demanding visual discriminations. Similar, robust attentional modulations were observed in both striate and extrastriate cortical areas. Functional mapping of cortical retinotopy demonstrates that attentional modulations were spatially specific, enhancing responses to attended stimuli and suppressing responses when attention was directed elsewhere. The spatial pattern of modulation reveals a complex attentional window that is consistent with object-based attention but is inconsistent with a simple attentional spotlight. These data suggest that neural processing in V1 is not governed simply by sensory stimulation, but, like extrastriate regions, V1 can be strongly and specifically influenced by attention.     

Regional changes in cerebral haemodynamics as a result of a visual stimulus measured by near infrared spectroscopy

Near infrared spectroscopy (NIRS) is used to measure global changes in cerebral haemodynamics. We have adapted the technique to measure regional changes in response to a visual stimulus. Ten volunteers were exposed to a computer generated visual stimulus designed to activate a large area of the visual cortex, including V1, V2, V3, V4 and V5. The stimulus was on for 30 s and off for 30 s. Changes in the concentrations of oxyhaemoglobin ([HbO2]) and deoxyhaemoglobin ([Hb]) were measured using a commercial spectrometer (NIRO500), over the occipital cortex. The data were summed over ten cycles. As a control, the experiment was repeated over the frontal cortex. For each subject [HbO2] increased during stimulation, and decreased when the stimulus was off. The mean (+/- s.e.m.) change in [HbO2] was 0.54 +/0 0.14 micromol 1(-1). The change in total haemoglobin concentration, given by [HbO2] + [Hb] was 0.61 +/- 0.21 micromol 1(-1), equivalent to a rise in cerebral blood volume of 0.04 +/- 0.01 ml 100 g(-1) which is about 2% of the total cerebral blood volume. There was no significant change in [HbO2] over the frontal cortex, implying that the changes in blood volume originated in the occipital lobe. This demonstrates that NIRS provides a non-invasive method of measuring regional changes in cerebral haemodynamics as a result of visual stimulation.     

Figure-ground activity in primary visual cortex is suppressed by anesthesia

By means of their small receptive fields (RFs), neurons in primary visual cortex perform highly localized analyses of the visual scene, far removed from our normal unified experience of vision. Local image elements coded by the RF are put into more global context, however, by means of modulation of the responses of the V1 neurons. Contextual modulation has been shown to follow closely the perceptual interpretation of the scene as a whole. This would suggest that some aspects of contextual modulation can be recorded only in awake and perceiving animals. In this study, multi-unit activity was recorded with implanted electrodes from primary visual cortex of awake, fixating monkeys viewing textured displays in which figure and ground regions were segregated by differences in either orientation or motion. Contextual modulation was isolated from local RF processing, by keeping RF stimulation identical across trials while sampling responses for various positions of the RF relative to figure and ground. Contextual modulation was observed to unfold spatially and temporally in a way that closely resembles the figure-ground percept. When recording was repeated, but with the animals anesthetized, the figure-ground related modulatory activity was selectively suppressed. RF tuning properties, however, remained unaffected. The results show that the modulatory activity is functionally distinct from the RF properties. V1 thus hosts distinct regimes of activity that are mediated by separate mechanisms and that depend differentially on the animal being awake or anesthetized.     

Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation

Dynamic measurements of regional changes in cerebral blood volume (CBV) were performed in rat models of hypercarbia and focal neuronal activation using T2-weighted imaging after injection of an intravascular contrast agent with a very long blood half-life. Calculated percent CBV change during hypercarbia was consistent with literature results from other non-invasive modalities. Equivalent percent CBV increases were found using spin- and gradient-echo images, suggesting proportional changes in blood volume for capillaries and small veins. During electrical stimulation of rat forepaw, focal CBV response to stimulation (24+/-4%) was significantly delayed relative to blood oxygen level dependent (BOLD) signal after both onset and cessation of stimulation. Poststimulus CBV decay was temporally consistent with the BOLD poststimulus undershoot. The use of exogenous agent increased the functional contrast-to-noise ratio relative to BOLD imaging by 5.7+/-1.3 at a magnetic field strength of 2 Tesla and 1.5+/-0.2 at 4.7 Tesla.     

Synchronization of visual responses between the cortex, lateral geniculate nucleus, and retina in the anesthetized cat

Synchronization of spatially distributed responses in the cortex is often associated with periodic activity. Recently, synchronous oscillatory patterning was described for visual responses in retinal ganglion cells that is reliably transmitted by the lateral geniculate nucleus (LGN), raising the question of whether oscillatory inputs contribute to synchronous oscillatory responses in the cortex. We have made simultaneous multi-unit recordings from visual areas 17 and 18 as well as the LGN and the retina to examine the interactions between subcortical and cortical synchronization mechanisms. Strong correlations of oscillatory responses were observed between retina, LGN, and cortex, indicating that cortical neurons can become synchronized by oscillatory activity relayed through the LGN. This feedforward synchronization occurred with oscillation frequencies in the range of 60-120 Hz and was most pronounced for responses to stationary flashed stimuli and more frequent for cells in area 18 than in area 17. In response to moving stimuli, by contrast, subcortical and cortical oscillations dissociated, proving the existence of independent subcortical and cortical mechanisms. Subcortical oscillations maintained their high frequencies but became transient. Cortical oscillations were now dominated by a cortical synchronizing mechanism operating in the 30-60 Hz frequency range. When the cortical mechanism dominated, LGN responses could become phase-locked to the cortical oscillations via corticothalamic feedback. In summary, synchronization of cortical responses can result from two independent but interacting mechanisms. First, a transient feedforward synchronization to high-frequency retinal oscillations, and second, an intracortical mechanism, which operates in a lower frequency range and induces more sustained synchronization.     

Physiological basis for BOLD MR signal changes due to neuronal stimulation: separation of blood volume and magnetic susceptibility effects

An NMR method is applied for separating blood volume and magnetic susceptibility effects in response to neuronal stimulation in a rat model. The method uses high susceptibility contrast agents to enhance blood volume induced signal changes. In the absence of exogenous agent, the dominant source of signal change on neuronal activation is associated with the signal increase from the blood oxygen level dependent (BOLD) effect. The relative negative contribution of blood volume changes to BOLD changes is maximally estimated to be 34%. The blood volume changes associated with median nerve stimulation (7 Hz) in the motor cortex are 26+/-7% and the corresponding blood susceptibility changes are 0.021+/-0.006 ppm. These methods can be applied to enhance the sensitivity of fMRI signal response and provide accurate quantitative measures of blood volume response to stimulation.     

Xenon effects on regional cerebral blood flow assessed by 15O-H2O positron emission tomography: implications for hyperpolarized xenon MRI

Subjective and physiologic effects of 33% inhaled Xe were measured with 15O-water positron emission tomography (PET) in 3 subjects at rest and during visual stimulation. The procedure was well tolerated. Robust functional activations of the visual cortex were obtained after xenon (Xe) inhalation as well as air breathing. However, Xe inhalation was followed by smaller size, but significant decreases of regional cerebral blood flow (rCBF) in visual cortex relative to the air-breathing baseline, both during visual stimulation and at rest. No such decreases were found in other sensory or motor regions.     

Cocaine decreases cortical cerebral blood flow but does not obscure regional activation in functional magnetic resonance imaging in human subjects

The authors used functional magnetic resonance imaging (fMRI) to determine whether acute intravenous (i.v.) cocaine use would change global cerebral blood flow (CBF) or visual stimulation-induced functional activation. They used flow-sensitive alternating inversion recovery (FAIR) scan sequences to measure CBF and blood oxygen level-dependent (BOLD) sensitive T2* scan sequences during visual stimulation to measure neuronal activation before and after cocaine and saline infusions. Cocaine (0.6 mg/kg i.v. over 30 seconds) increased heart rate and mean blood pressure and decreased end tidal carbon dioxide (CO2). All measures returned to baseline by 2 hours, the interinfusion interval, and were unchanged by saline. Flow-sensitive alternating inversion recovery imaging demonstrated that cortical gray matter CBF was unchanged after saline infusion (-2.4 +/- 6.5%) but decreased (-14.1 +/- 8.5%) after cocaine infusion (n = 8, P < 0.01). No decreases were detected in white matter, nor were changes found comparing BOLD signal intensity in cortical gray matter immediately before cocaine infusion with that measured 10 minutes after infusion. Visual stimulation resulted in comparable BOLD signal increases in visual cortex in all conditions (before and after cocaine and saline infusion). Despite a small (14%) but significant decrease in global cortical gray matter CBF after acute cocaine infusion, specific regional increases in BOLD imaging, mediated by neurons, can be measured reliably.     

Optical intrinsic signal imaging responses are modulated in rodent somatosensory cortex during simultaneous whisker and forelimb stimulation

Optical intrinsic signal imaging (OIS) was used to investigate physiologic interactions between spatially and functionally distinct cortical somatosensory systems. The OIS response magnitude was evaluated after simultaneous stimulation of single whiskers and forelimb digits. Whisker C1 was deflected at a frequency of 10 Hz for 2 seconds while low- or high-intensity vibratory stimuli were applied to forelimb digits. The OIS responses to simultaneous whisker and forelimb stimulation were compared with lone whisker stimulated controls. Overall, addition of a second stimulus caused decreases in barrel cortex response magnitude. Three different response patterns were detected within individual trial sets. Modulation of barrel cortex evoked potentials provided evidence that changes in OIS responses observed here may be partially influenced by vascular responses to changes in neuronal activity. However, OIS responses in the barrel region during lone forelimb stimulation that were unaccompanied by evoked potentials suggested the possibility of independent vascular dynamic influences on response modulation. This study demonstrates that cortical responses at the level of primary sensory processing may be significantly influenced by activity in adjacent regions. Furthermore, it reveals that vascular and neuronal characteristics of interregional modulation do not co-localize and may produce responses in which one component increases while the other decreases.     

Biweekly cyclophosphamide, epirubicin, vincristine and prednisolone (CEOP) chemotherapy for the elderly patients with aggressive non-Hodgkin''s lymphoma. Tochigi Malignant Lymphoma Study Group for the Elderly Patients

Changes in cerebral blood oxygenation and flow during prolonged activation of human visual cortex (6-min video projection) were monitored using high-resolution T2*- and T1-weighted gradient-echo MRI in identical sessions. Oxygenation-sensitive recordings displayed an initial signal increase (oxygenation "overshoot"), a subsequent signal decrease extending over 4-5 min (relative deoxygenation), and a signal drop after the end of stimulation that mirrored the initial response (oxygenation "undershoot"). Flow-sensitive MRI demonstrated that the inflow effect remained elevated during the entire period of stimulation. The observation of gradually decreasing cerebral blood oxygenation, despite persisting elevation of blood flow, may be understood to be an accumulation of deoxyhemoglobin due to the progressive up-regulation of oxidative phosphorylation. The present findings support a concept in which transitions between functional states lead to an uncoupling of perfusion (oxygen delivery) from oxidative metabolism (oxygen consumption) whereas steady-state activity achieves their recoupling.     

Congenital thrombophilia

Previous functional imaging studies have demonstrated a number of discrete brain structures that increase activity with noxious stimulation. Of the commonly identified central structures, only the anterior cingulate cortex shows a consistent response during the experience of pain. The insula and thalamus demonstrate reasonable consistency while all other regions, including the lentiform nucleus, somatosensory cortex and prefrontal cortex, are active in no more than half the current studies. The reason for such discrepancy is likely to be due in part to methodological variability and in part to individual variability. One aspect of the methodology which is likely to contribute is the stimulus intensity. Studies vary considerably regarding the intensity of the noxious and non-noxious stimuli delivered. This is likely to produce varying activation of central structures coding for the intensity, affective and cognitive components of pain. Using twelve healthy volunteers and positron emission tomography (PET), the regional cerebral blood flow (rCBF) responses to four intensities of stimulation were recorded. The stimulation was delivered by a CO2 laser and was described subjectively as either warm (not painful), pain threshold just painful), mildly painful or moderately painful. The following group subtractions were made to examine the changing cerebral responses as the stimulus intensity increased: (1) just painful - warm; (2) mild pain - warm; and (3) moderate pain - warm. In addition, rCBF changes were correlated with the subjective stimulus ratings. The results for comparison '1' indicated activity in the contralateral prefrontal (area 10/46/44), bilateral inferior parietal (area 40) and ipsilateral premotor cortices (area 6), possibly reflecting initial orientation and plans for movement. The latter comparisons and correlation analysis indicated a wide range of active regions including bilateral prefrontal, inferior parietal and premotor cortices and thalamic responses, contralateral hippocampus, insula and primary somatosensory cortex and ipsilateral perigenual cingulate cortex (area 24) and medial frontal cortex (area 32). Decreased rCBF was observed in the amygdala region. These responses were interpreted with respect to their contribution to the multidimensional aspects of pain including fear avoidance, affect, sensation and motivation or motor initiation. It is suggested that future studies examine the precise roles of each particular region during the central processing of pain.     

Impact of valence and age on olfactory induced brain activation in healthy women.

The aim of the present study was to assess the effect of age on cerebral correlates of olfactory induced negative emotions. We investigated 15 healthy women (aged 21–47) in a functional MRI (fMRI) study during passive smelling of one negative odor (rotten yeast) and two control conditions presenting a neutral odor (vanilla) and odorless ambient air. Besides odor-specific differences in ratings of valence (yeast less pleasant than vanilla and air), intensity (yeast more intense than vanilla and air), and arousal (yeast more arousing than vanilla and air), self-ratings verified the intended mood induction effect: subjects experienced more disgust during yeast stimulation compared to ambient air and vanilla. Along with the superior temporal cortex, medial, and lateral orbitofrontal activations were found to discriminate between negative and neutral olfactory stimulation (yeast and vanilla) directly. Activations of the dorsolateral prefrontal cortex and the caudate were correlated with age and showed stronger valence-related responses (yeast vs. vanilla) in younger compared to older women. Stronger BOLD signals within the anterior cingulate gyrus, insula and motor areas were found during negative compared to neutral stimulation and are considered to represent an attempt to down-regulate the strong emotional experience and the organisms' preparation for withdrawal, respectively. Our results stress the role of orbitofrontal and superior temporal brain regions in odor-related valence coding and stress the necessity to consider age as a modulating factor for further studies, even in relatively young samples. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experiences with functional magnetic resonance imaging at 1 tesla

Functional magnetic resonance imaging (fMRI) has been performed on a standard 1 T system using a pulse sequence developed to utilize blood oxygen level dependent (BOLD) contrast and an off-line analysis routine using correlation techniques. The sequence and the data analysis routine have been validated by reproducing the conventional hand movement paradigm studies reported by numerous other workers. Our work has then been extended to investigate cerebral foci for a tonic pain stimulus and the cortical representation of oesophageal stimulation. Both these studies relate to paradigms where the expected BOLD signal is significantly less than that encountered for motor or visual cortex paradigms. The results show good agreement with other modalities (positron emission tomography, magnetoencephalography and cortical evoked potentials). Performing fMRI at 1 T is slightly controversial. However, our successful study of demanding paradigms, using a standard clinical 1 T imaging system, has important implications for many other users operating at this field strength.     

In vivo tracing of pathways and spatio-temporal activity patterns in rat visual cortex using voltage sensitive dyes

We monitored optical signals from cortex stained with a voltage sensitive dye to study activity evoked by intracortical electrical stimulation. The objectives were to study the spatial and temporal spread of activity from intrinsic connections near the stimulating electrode and to develop a new technique to study extrinsic projections from striate cortex to extrastriate target areas. Various measures were made of the time course of the optical signal (latency, rise time, decay time, temporal summation, facilitation versus depression, and presence or absence of a slow undershoot); in general, these measures were found to vary significantly across different response positions, different experiments, and even different runs within the same experiment. The spatial distribution of responses near the stimulating electrode in striate cortex was usually elliptical and was most often elongated along the anterior-posterior axis, with a typical size (full width at 75% max) of 1.3 mm (anterior-posterior axis) by 0.75 mm (medio-lateral axis). In some cases, complex spatio-temporal patterns were observed, in which the position of the maximum optical signal shifted with time or split into multiple peaks. In eight experiments, a response focus was found in extrastriate cortex at an expected location within the lateromedial area (LM). The response focus in LM was typically about half the size of that in striate cortex. In some experiments we observed additional focal responses in the anterolateral visual area (AL). The extrastriate responses showed a significant delay (3-10 ms) in onset and time to peak relative to the striate response. The validity of this technique for determining extrinsic projections was tested in two types of experiments. In the first, stimulation from two electrodes in striate cortex generated response foci consistent with the known topographic organization of area LM. In the second, the optically measured response focus was shown to correlate with the histologically reconstructed projection of a chemical tracer injected near the site of stimulation. We discuss the chain of neurophysiological events that occur during and after focal electrical stimulation and how they relate to the observed optical signal. We conclude that direct passive responses were a small component of our signal, that the component due to action potentials in directly stimulated neurons should have occurred in the first 1-2 ms post stimulus and is small compared to the peak signal, and that overall our signals were probably dominated by a combination of asynchronously occurring action potentials and excitatory and inhibitory synaptic potentials.(ABSTRACT TRUNCATED AT 400 WORDS)     

Abnormal error-related antisaccade activation in premanifest and early manifest Huntington disease.

Objective: Individuals with the trinucleotide CAG expansion (CAG+) that causes Huntington's disease (HD) have impaired performance on antisaccade (AS) tasks that require directing gaze in the mirror opposite direction of visual targets. This study aimed to identify the neural substrates underlying altered antisaccadic performance. Method: Three groups of participants were recruited: (1) Imminent and early manifest HD (early HD, n = 8); (2) premanifest (presymptomatic) CAG+ (preHD, n = 10); and (3) CAG unexpanded (CAG?) controls (n = 12). All participants completed a uniform study visit that included a neurological evaluation, neuropsychological battery, molecular testing, and functional MRI during an AS task. The blood oxygenation level dependent (BOLD) response was obtained during saccade preparation and saccade execution for both correct and incorrect responses using regression analysis. Results: Significant group differences in BOLD response were observed when comparing incorrect AS to correct AS execution. Specifically, as the percentage of incorrect AS increased, BOLD responses in the CAG? group decreased progressively in a well-documented reward detection network that includes the presupplementary motor area and dorsal anterior cingulate cortex. In contrast, AS errors in the preHD and early HD groups lacked this relationship with BOLD signal in the error detection network, and BOLD responses to AS errors were smaller in the two CAG+ groups as compared with the CAG? group. Conclusions: These results are the first to suggest that abnormalities in an error-related response network may underlie early changes in AS eye movements in premanifest and early manifest HD. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Transient and steady-state electroretinograms and visual evoked potentials to pattern and uniform-field stimulation in humans

I recorded simultaneously transient and steady-state electroretinograms (ERGs) and visual evoked potentials (VEPs) in response to pattern and uniform-field stimulation in 21 normal subjects, in order to study their physiological characteristics. ERGs and VEPs to pattern stimulation (P-ERGs and P-VEPs, respectively) showed different physiological features from those to uniform-field stimulation (U-ERGs and U-VEPs, respectively). With transient stimulation at a rate of 1Hz for both pattern and uniform-field stimulation, the b-wave latency of U-ERG tended to be shorter than that of P-ERG, while the P100 latency of P-VEP was significantly shorter than that of U-VEP. With steady-state stimulation at a rate of 4Hz for pattern stimulation and of 8Hz for uniform-field stimulation, the phase analysis revealed the first (1F) and the second (2F) harmonics as stable components for the U-ERG and U-VEP, while only 2F harmonic was a stable component for the P-ERG and P-VEP. The phase values of these components were different each other, and the maximal amplitude of the ERGs was shown by the 1F of U-ERG while that of the VEPs was shown by the 2F of P-VEP. These results suggest that the pattern and uniform-field stimulation allows us to separate pattern (contrast)-specific responses from luminance-specific responses both in ERGs and VEPs. Four patients with optic atrophy showed normal U-ERG while all of them showed abnormal P-ERG, U-VEP and P-VEP except one, who showed normal U-VEP. P-ERGs and P-VEPs may offer the information about the proximal inner retinal layer (or the ganglion cells) and the contrast channel of the visual cortex. U-ERGs and U-VEPs may be useful in evaluating the functions of the preganglionic cell activity in the retina and the luminance channel of the visual cortex. Therefore, simultaneous recording of ERGs and VEPs to pattern and uniform-field stimulation under both transient and steady-state conditions increase the diagnostic value of electrophysiologic testing in the visual pathways.     

Temporal neocortical injuries in rats impair attending but not complex visual processing.

The effects of variations of the distance between the relevant stimuli and the animals' response sites were observed upon the performances of a black–white discrimination habit for normal rats or subjects prepared with either bilateral injuries to the visual or temporal neocortex. In addition, the animals were given a strict test of visual form perception. Subjects with injuries to the visual cortex failed the test of visual form perception but performed like normals in discriminating a spatially discontiguous problem. In contrast, subjects with temporal injuries exhibited enormous performance deficits when trained on a spatially discontiguous problem but performed like normals on the test of form perception. The findings parallel the results of studies using primates and suggest that bitemporal injuries result in impairments of attending and not of complex visual processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)