Vertical asymmetries in pre-attentive detection of changes in motion direction.

Stimulus localization affects visual motion processing. Vertical asymmetries favouring lower visual field have been reported in event-related potentials (ERPs) and behavioural studies under different attention conditions. However, there are no studies examining such asymmetries to non-attended motion changes. The present study investigated whether the asymmetry in processing information from the upper and lower visual fields also affects the automatic detection of motion-direction changes as indexed by visual Mismatch Negativity (vMMN). We recorded vMMN to changes in sinusoidal gratings differing in motion direction presented in the periphery of visual field in three different locations: upper and lower (ULVF), upper (UVF) and lower (LVF) along the vertical meridian. The N2 component elicited to peripheral motion presented lower amplitudes when the UVF was stimulated. The vMMN elicited to infrequent motion-direction changes was present in all stimulation conditions. However, it was reduced to UVF stimulation. These results suggest that the visual system automatically detects motion-direction changes presented at both upper-lower visual fields; however they also indicate that the process is favoured when stimuli are presented in the LVF alone.     

Time course of blood oxygenation level-dependent signal response after theta burst transcranial magnetic stimulation of the frontal eye field

The aim of the current study was to examine the effect of theta burst repetitive transcranial magnetic stimulation (rTMS) on the blood oxygenation level-dependent (BOLD) activation during repeated functional magnetic resonance imaging (fMRI) measurements. Theta burst rTMS was applied over the right frontal eye field in seven healthy subjects. Subsequently, repeated fMRI measurements were performed during a saccade-fixation task (block design) 5, 20, 35, and 60 min after stimulation. We found that theta burst rTMS induced a strong and long-lasting decrease of the BOLD signal response of the stimulated frontal eye field at 20 and 35 min. Furthermore, less pronounced alterations of the BOLD signal response with different dynamics were found for remote oculomotor areas such as the left frontal eye field, the pre-supplementary eye field, the supplementary eye field, and both parietal eye fields. Recovery of the BOLD signal changes in the anterior remote areas started earlier than in the posterior remote areas. These results show that a) the major inhibitory impact of theta burst rTMS occurs directly in the stimulated area itself, and that b) a lower effect on remote, oculomotor areas can be induced.     

A lower visual field advantage for endpoint stability but no advantage for online movement precision

It has been proposed that visually guided reaching movements performed in the lower visual field (LVF) of peripersonal space are more effective and efficient than their upper visual field (UVF) counterparts (Danckert and Goodale 2001). In the present investigation we sought to determine whether this purported visual field asymmetry reflects advantaged processing of online visual feedback. To accomplish that objective, participants performed discrete reaching movements to each of three target locations in the LVF and UVF. In addition, reaches were completed under conditions wherein target location remained constant throughout a reaching response (i.e., control trials) and a separate condition wherein target location unexpectedly perturbed at movement onset (i.e., experimental trials). We reasoned that the target perturbation paradigm would provide a novel means to assess a possible superior-inferior visual field asymmetry for online reaching control. In terms of the impact of a target perturbation, both visual fields demonstrated equal proficiency integrating visual feedback for online limb adjustments. Interestingly, however, the spatial distribution of movement endpoints in the LVF was less than UVF counterparts (cf. Binsted and Heath 2005). Taken together, the present findings suggest that although LVF and UVF reaches readily use visual feedback to accommodate an unexpected target perturbation, reaches in the LVF elicit advantaged spatial benefits influencing the effectiveness of online limb corrections.     

Cortical and subcortical correlates of electroencephalographic alpha rhythm modulation

Neural correlates of electroencephalographic (EEG) alpha rhythm are poorly understood. Here, we related EEG alpha rhythm in awake humans to blood-oxygen-level-dependent (BOLD) signal change determined by functional magnetic resonance imaging (fMRI). Topographical EEG was recorded simultaneously with fMRI during an open versus closed eyes and an auditory stimulation versus silence condition. EEG was separated into spatial components of maximal temporal independence using independent component analysis. Alpha component amplitudes and stimulus conditions served as general linear model regressors of the fMRI signal time course. In both paradigms, EEG alpha component amplitudes were associated with BOLD signal decreases in occipital areas, but not in thalamus, when a standard BOLD response curve (maximum effect at approximately 6 s) was assumed. The part of the alpha regressor independent of the protocol condition, however, revealed significant positive thalamic and mesencephalic correlations with a mean time delay of approximately 2.5 s between EEG and BOLD signals. The inverse relationship between EEG alpha amplitude and BOLD signals in primary and secondary visual areas suggests that widespread thalamocortical synchronization is associated with decreased brain metabolism. While the temporal relationship of this association is consistent with metabolic changes occurring simultaneously with changes in the alpha rhythm, sites in the medial thalamus and in the anterior midbrain were found to correlate with short time lag. Assuming a canonical hemodynamic response function, this finding is indicative of activity preceding the actual EEG change by some seconds.     

Temporal resolving power of perfusion- and BOLD-based event-related functional MRI

Functional magnetic resonance imaging (fMRI) based on both perfusion and blood oxygenation level-dependent (BOLD) contrasts has been widely applied in spatiotemporal mapping of the human brain function. Temporal resolving power of fMRI is limited by the smoothed hemodynamic response function dispersed from the neuronal activity. In this study, temporal modulation transfer functions were utilized to quantify the resolving powers of perfusion and BOLD fMR signals in time domain. The impulse response function was determined using brief visual stimulations and event-related image acquisition schemes. An important feature of arterial spin labeling techniques is that quantitative perfusion and BOLD signals could be simultaneously acquired. This simultaneous BOLD response may arise from signals that are more proximal to capillary beds, and its temporal resolution may be different from that of the typical BOLD response. Therefore, we assessed and compared the temporal resolving capabilities of perfusion, simultaneous BOLD, and the typical BOLD response obtained from the gradient echo EPI pulse sequence. Full-width-at-half-maximums of perfusion and simultaneous BOLD measurements were significantly smaller than that of BOLD ones (4.3+/- 0.6 s vs 5.5 +/- 0.9 s, p<0.02 and 4.7 +/- 1.3 s vs 5.5 +/- 0.9 s, p<0.01, respectively). The corresponding temporal resolving powers of perfusion and simultaneous BOLD signals were statistically better than that of BOLD signals (0.23 +/- 0.03 Hz vs 0.17 +/- 0.02 Hz, p<0.01 and 0.21 +/- 0.04 Hz vs 0.17 +/- 0.02 Hz, p<0.01, respectively). Our results showed that the typical BOLD response was significantly smoothed from the perfusion response, thus resulting in a degraded temporal resolving power. However, results from the simultaneous BOLD and perfusion measurements were not significantly different. Biophysical implications of the experimental outcomes were further investigated using a computer simulation based on the Balloon model. By fitting the measured data into the model, an apparently longer transit time was obtained for the typical BOLD signal (1.7 s), comparing to that for the simultaneous BOLD one (1.2 s). Therefore, the simultaneous BOLD signal was regarded as less susceptible to the variations from local draining veins. Combining the simulation result with the significantly discrepant resolving powers between the two BOLD signals, we speculated that the blurred effects from large vessels played a predominant role that further reduced the temporal resolution of the BOLD-based fMRI from the perfusion response.     

Functional magnetic resonance imaging evidence for binocular interactions in human visual cortex

Using functional magnetic resonance imaging (fMRI), we explored the binocular interactions occurring when subjects viewed dichoptically presented checkerboard stimuli. A flickering radial checkerboard was presented to each eye of the subject, while T2*-weighted images were acquired over the visual cortex with gradient-echo, echoplanar sequences. We compared responses in striate and extrastriate visual cortex under four conditions: both eyes were stimulated at the same time (binocular condition), each eye was stimulated in alternation (monocular condition) or first the one eye then the other eye was stimulated (left eye first - right eye trailing, or vice versa). The results indicate that only the striate area, in and near the calcarine fissure, shows significant differences for these stimulation conditions. These differences are not evident in more remote extrastriate or associational visual areas, although the BOLD response in the stimulation-rest comparison was robust. These results suggest that the effect could be related to inhibitory interactions across ocular dominance columns in striate visual cortex.     

Gain control in the response of human visual cortex to plaids

A recent intrinsic signal optical imaging study in tree shrew showed, surprisingly, that the population response of V1 to plaid patterns comprising grating components of equal contrast is predicted by the average of the responses to the individual components (MacEvoy SP, Tucker TR, Fitzpatrick D. Nat Neurosci 12: 637-645, 2009). This prompted us to compare responses to plaids and gratings in human visual cortex as a function of contrast and orientation. We found that the functional MRI (fMRI) blood oxygenation level-dependent (BOLD) responses of areas V1-V3 to a plaid comprising superposed grating components of equal contrast are significantly higher than the responses to a single component. Furthermore, the orientation response profile of a plaid is poorly predicted from a linear combination of the responses to its components. Together, these results indicate that the model of MacEvoy et al. (2009) cannot, without modification, account for the fMRI BOLD response to plaids in human visual cortex.     

Divergence of fMRI and neural signals in V1 during perceptual suppression in the awake monkey

The role of primary visual cortex (V1) in determining the contents of perception is controversial. Human functional magnetic resonance imaging (fMRI) studies of perceptual suppression have revealed a robust drop in V1 activity when a stimulus is subjectively invisible. In contrast, monkey single-unit recordings have failed to demonstrate such perception-locked changes in V1. To investigate the basis of this discrepancy, we measured both the blood oxygen level-dependent (BOLD) response and several electrophysiological signals in two behaving monkeys. We found that all signals were in good agreement during conventional stimulus presentation, showing strong visual modulation to presentation and removal of a stimulus. During perceptual suppression, however, only the BOLD response and the low-frequency local field potential (LFP) power showed decreases, whereas the spiking and high-frequency LFP power were unaffected. These results demonstrate that the coupling between the BOLD and electrophysiological signals in V1 is context dependent, with a marked dissociation occurring during perceptual suppression.     

Dietary supplementation of creatine monohydrate reduces the human fMRI BOLD signal

Creatine monohydrate is an organic acid that plays a key role in ATP re-synthesis. Creatine levels in the human brain vary considerably and dietary supplementation has been found to enhance cognitive performance in healthy individuals. To explore the possibility that the fMRI Blood Oxygen Level Dependent (BOLD) response is influenced by creatine levels, BOLD responses to visual stimuli were measured in visual cortex before and after a week of creatine administration in healthy human volunteers. The magnitude of the BOLD response decreased by 16% following creatine supplementation of a similar dose to that previously shown to increase cerebral levels of phosphocreatine. We also confirmed that cognitive performance (memory span) is increased. These changes were not found in a placebo group. Possible mechanisms of BOLD change are considered. The results offer potential for insight into the coupling between neural activity and the BOLD response and the more immediate possibility of accounting for an important source of variability during fMRI analysis in clinical studies and other investigations where between-subjects variance is an issue.     

Brain activation during dichoptic presentation of optic flow stimuli

The processing of optic flow fields in motion-sensitive areas in human visual cortex was studied with BOLD (blood oxygen level dependent) contrast in functional magnetic resonance imaging (fMRI). Subjects binocularly viewed optic flow fields in plane (monoptic) or in stereo depth (dichoptic) with various degrees of disparity and increasing radial speed. By varying the directional properties of the stimuli (expansion, spiral motion, random), we explored whether the BOLD effect reflected neuronal responses to these different forms of optic flow. The results suggest that BOLD contrast as assessed by fMRI methods reflects the neural processing of optic flow information in motion-sensitive cortical areas. Furthermore, small but replicable disparity-selective responses were found in parts of Brodmann's area 19.     

High-resolution mapping of iso-orientation columns by fMRI

Blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is an important tool for localizing brain functions in vivo. However, the ability of BOLD fMRI to map cortical columnar structures is highly controversial, as the ultimate functional specificity of BOLD remains unknown. Here we report a biphasic BOLD response to visual stimulation in the primary visual cortex of cats. In functional imaging, the initial BOLD signal decrease accurately labeled individual iso-orientation columns. In contrast, the delayed positive BOLD changes indicated the pattern of overall activation in the visual cortex, but were less suited to discriminate active from inactive columns.     

Hemispheric asymmetry in cerebrovascular reactivity of the human primary motor cortex: an in vivo study at 7 T

Current functional MRI (fMRI) approaches assess underlying neuronal activity through monitoring the related local variations in cerebral blood oxygenation, blood volume and blood flow. This vascular response is likely to vary across brain regions and across individuals, depending on the composition of the local vascular bed and on the vascular capacity to dilate. The most widely used technique uses the blood oxygen level dependent (BOLD) fMRI signal, which arises from a complex combination of all of these factors. The model of handedness provides a case where one brain region (dominant motor cortex) is known to have a stronger BOLD response over another (non‐dominant motor cortex) during hand motor task performance. We predict that this is accompanied by a higher vascular reactivity in the dominant motor cortex, when compared with the non‐dominant motor cortex. Precise measurement of end‐tidal CO₂ and a novel sinusoidal CO₂ respiratory challenge were combined with the high sensitivity and finer spatial resolution available for fMRI at 7 T to measure BOLD cerebrovascular reactivity (CVR) in eight healthy male participants. BOLD CVR was compared between the left (dominant) and right (non‐dominant) primary motor cortices of right‐handed adults. Hemispheric asymmetry in vascular reactivity was predicted and observed in the primary motor cortex (left CVR = 0.60 ± 0.15%/mm Hg; right CVR = 0.47 ± 0.08%/mm Hg; left CVR > right CVR, P = 0.04), the first reported evidence of such a vascular difference. These findings demonstrate a cerebral vascular asymmetry between the left and right primary motor cortex. The origin of this asymmetry largely arises from the contribution of large draining veins. This work has implications for future motor laterality studies that use BOLD, and it is also suggestive of a vascular plasticity in the human primary motor cortex. Copyright © 2015 John Wiley & Sons, Ltd.     

Hemispheric asymmetries in vigilance and cerebral arousal mechanisms in younger and older adults

Younger and older adults responded to an asterisk presented to either the left or right visual field, with delay interval between onset of a fixation cross and onset of the asterisk varied. At delay intervals longer than 3 s, reaction time was faster when the same visual field was stimulated on 2 successive trials than when different visual fields were stimulated. This prefield effect was larger in the left visual field (right hemisphere), consistent with hypotheses of hemispheric asymmetry for arousal and vigilance. For older adults, these results were obtained only when participants responded with the left hand, suggesting that some aspects of hemispheric asymmetry for attention-related processing or the efficiency of interhemispheric transfer may change in an age-related fashion.     

Left-right asymmetry of visual evoked potentials in brain-damaged patients: A mathematical model and experimental results

The left-right asymmetry in the potential amplitude on the scalp was studied in poststroke patients by using flash visual evoked potential (VEP) and a numerical two-dimensional model of the head. The left-right asymmetry of the VEP was measured in three patients after thrombosis, in one after hemorrhage, and in one healthy subject. The numerical model used computed tomography images to define the different comparttential distribution created by a dipole source in the occipital region was solved numerically with use of a finite volume method. Left-right asymmetry was calculated with serveral values of conductivity of the damaged region. The experimental results revealed a negative asymmetry in the three patients after thrombosis (i. e., the potential amplitude over the ischemic hemisphere was smaller than that over the intact hemisphere), whereas, in the patient after hemorrhage, a positive asymmetry was found. Nonsignificant left-right asymmetry was found in the healthy subject. The numerical model revealed that the electrical conductivity of the damaged tissue has a major effect on the left-right asymmetry. Negative asymmetry, such as that found for patients after thrombosis, was obtained when the conductivity of the damaged region was greater than that of the brain, whereas positive asymmetry (hemorrhage patient) was obtained when that conductivity was smaller than that of the brain. This finding indicates that the left-right asymmetry in the scalp VEP of patients after brain damage may be a result of changes in the conductivity of the volume conductor (the ischemic region) between the source and the electrodes.     

Delayed discrimination of spatial frequency for gratings of different orientation: behavioral and fMRI evidence for low-level perceptual memory stores in early visual cortex

The concept of perceptual memory refers to the neural and cognitive processes underlying the storage of specific stimulus features such as spatial frequency, orientation, shape, contrast, and color. Psychophysical studies of perceptual memory indicate that observers can retain visual information about the spatial frequency of Gabor patterns independent of the orientation with which they are presented. Compared to discrimination of gratings with the same orientation, reaction times to orthogonally oriented gratings, however, increase suggesting additional processing. Using event-related fMRI we examined the pattern of neural activation evoked when subjects discriminated the spatial frequency of Gabors presented with the same or orthogonal orientation. Blood-oxygen level dependent BOLD fMRI revealed significantly elevated bilateral activity in visual areas (V1, V2) when the gratings to be compared had an orthogonal orientation, compared to when they had the same orientation. These findings suggest that a change in an irrelevant stimulus dimension requires additional processing in primary and secondary visual areas. The finding that the task-irrelevant stimulus property (orientation) had no significant effect on the prefrontal and intraparietal cortex supports a model of working memory in which discrimination and retention of basic stimulus dimensions is based on low-level perceptual memory stores that are located at an early stage in the visual process. Our findings suggest that accessing different stores requires time and has higher metabolic costs. Supported by: BMBF Project “Visuospatial Cognition” and Norwegian Research Council.     

Age dependence of hemodynamic response characteristics in human functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) studies of cognitive aging have generally compared the amplitude and extent of blood oxygen level-dependent (BOLD) signal increases evoked by a task in older and younger groups. BOLD is thus used as a direct index of neuronal activation and it is assumed that the relationship between neuronal activity and the hemodynamic response is unchanged across the lifespan. However, even in healthy aging, differences in vascular and metabolic function have been observed that could affect the coupling between neuronal activity and the BOLD signal. Here we use a calibrated fMRI method to explore vascular and metabolic changes that might bias such BOLD comparisons. Though BOLD signal changes evoked by a cognitive task were found to be similar between a group of younger and older adults (e.g., 0.50 ± 0.04% vs. 0.50 ± 0.05% in right frontal areas), comparison of BOLD and arterial spin labelling (ASL) responses elicited in the same set of structures by a controlled global hypercapnic manipulation revealed significant differences between the 2 groups. Older adults were found to have lower responses in BOLD and flow responses to hypercapnia (e.g., 1.48 ± 0.07% vs. 1.01 ± 0.06% over gray matter for BOLD and 24.92 ± 1.37% vs. 20.67 ± 2.58% for blood flow), and a generally lower maximal BOLD response M (5.76 ± 0.2% vs. 5.00 ± 0.3%). This suggests that a given BOLD response in the elderly might represent a larger change in neuronal activity than the same BOLD response in a younger cohort. The results of this study highlight the importance of ancillary measures such as ASL for the correct interpretation of BOLD responses when fMRI responses are compared across populations who might exhibit differences in vascular physiology.     

Quantitative characterization of unit response in the visual system

Summary A quantitative approach to characterization of unit response in the visual system was proposed. Temporal parameters of response were analyzed by post stimulus time-histograms obtained from point visual stimulation. Explicit temporal intervals were chosen to coincide with discrete response components. By calculating net firing rate within these intervals as a function of stimulus position, quantitative receptive field maps were constructed. To estimate response between stimulated matrix mesh points, a general contouring program was described. Latency, and synchronicity — a logarithmic probability function sensitive to temporal consistency of response — were also mapped as functions of stimulus position.Representative firing rate maps morphologically resembled previously described receptive fields; latency and synchronicity maps, it is argued, allow for additional mechanistic and functional analysis of striate units. By explicitly separating temporal and spatial variables and quantifying unit response, the present methods will hopefully enlarge the scope and sensitivity of receptive field analysis.Supported by AF 33(615)-5453 and AF 49(643)-201 and the Digital Equipment Corporation     

Evoked local field potentials can explain temporal variation in blood oxygenation level-dependent responses in rat somatosensory cortex

The aim of this study was to explain the temporal variations between subjects in the blood oxygenation level-dependent (BOLD) response. Somatosensory responses were elicited with the electrical forepaw stimulus at a frequency of 10 Hz in urethane-anesthetized rats, and functional magnetic resonance imaging (fMRI) with BOLD contrast and local field potential (LFP) measurements were performed simultaneously. BOLD fMRI activation was evaluated by two different models, one based on the stimulus paradigm (the block model) and the other on the simultaneously measured evoked LFP responses. In the initial analysis, the LFP model captured the BOLD activation in the primary somatosensory cortex in all cases, and the block model in 10 of 12 rats. A statistical comparison of the two models revealed that the LFP-derived model was able to explain additional BOLD variation over the block model in the somatosensory cortex in nine of 12 rats. These results suggest that there is more information regarding neuronal activity in the BOLD signal than can be exploited using the block model alone. Furthermore, the hemodynamic coupling remains unchanged in the case of temporally variable BOLD signals.     

Relationship between saccadic eye movements and cortical activity as measured by fMRI: quantitative and qualitative aspects

We investigated the quantitative relationship between saccadic activity (as reflected in frequency of occurrence and amplitude of saccades) and blood oxygenation level dependent (BOLD) changes in the cerebral cortex using functional magnetic resonance imaging (fMRI). Furthermore, we investigated quantitative changes in cortical activity associated with qualitative changes in the saccade task for comparable levels of saccadic activity. All experiments required the simultaneous acquisition of eye movement and fMRI data. For this purpose we used a new high-resolution limbus-tracking technique for recording eye movements in the magnetic resonance tomograph. In the first two experimental series we varied both frequency and amplitude of saccade stimuli (target jumps). In the third series we varied task difficulty; subjects performed either pro-saccades or anti-saccades. The brain volume investigated comprised the frontal and supplementary eye fields, parietal as well as striate cortex, and the motion sensitive area of the parieto-occipital cortex. All these regions showed saccade-related BOLD responses. The responses in these regions were highly correlated with saccade frequency, indicating that repeated processing of saccades is integrated over time in the BOLD response. In contrast, there was no comparable BOLD change with variation of saccade amplitude. This finding speaks for a topological rather than activity-dependent coding of saccade amplitudes in most cortical regions. In the experiments comparing pro- vs anti-saccades we found higher BOLD activation in the "anti" task than in the "pro" task. A comparison of saccade parameters revealed that saccade frequency and cumulative amplitude were comparable between the two tasks, whereas reaction times were longer in the "anti" task than the pro task. The latter finding is taken to indicate a more demanding cortical processing in the "anti" task than the "pro" task, which could explain the observed difference in BOLD activation. We hold that a quantitative analysis of saccade parameters (especially saccade frequency and latency) is important for the interpretation of the BOLD changes observed with visual stimuli in fMRI.     

Blood oxygenation level-dependent (BOLD) functional MRI of visual stimulation in the rat retina at 11.7 T

Although optically based imaging techniques provide valuable functional and physiological information of the retina, they are mostly limited to the probing of the retinal surface and require an unobstructed light path. MRI, in contrast, could offer physiological and functional data without depth limitation. Blood oxygenation level-dependent functional MRI (BOLD fMRI) of the thin rat retina is, however, challenging because of the need for high spatial resolution, and the potential presence of eye movement and susceptibility artifacts. This study reports a novel application of high-resolution (111 × 111 × 1000 μm(3)) BOLD fMRI of visual stimulation in the anesthetized rat retina at 11.7 T. A high-field MRI scanner was utilized to improve the signal-to-noise ratio, spatial resolution and BOLD sensitivity. Visual stimuli (8 Hz diffuse achromatic light) robustly increased BOLD responses in the retina [5.0 ± 0.8% from activated pixels and 3.1 ± 1.1% from the whole-retina region of interest (mean ± SD), n = 12 trials on six rats, p < 0.05 compared with baseline]. Some activated pixels were detected surrounding the pupil and ciliary muscle because of accommodation reflex to visual stimuli, and were reduced with atropine and phenylephrine eye drops. BOLD fMRI scans without visual stimulations showed no significantly activated pixels (whole-retina BOLD changes were 0.08 ± 0.34%, n = 6 trials on five rats, not statistically different from baseline, p > 0.05). BOLD fMRI of visual stimulation has the potential to provide clinically relevant data to probe hemodynamic neurovascular coupling and dysfunction of the retina with depth resolution.