Midazolam sedation increases fluctuation and synchrony of the resting brain BOLD signal

The blood oxygen level-dependent (BOLD) magnetic resonance signal of functional brain cortices is dominated by very low frequency (VLF) fluctuations in anesthetized child patients. The temporal synchrony of the BOLD signal is also higher in anesthetized children compared with awake adults. The origin of the synchronous fluctuations can be related to maturation, pathological status or the anesthesia used in the imaging. Two of the three confounding variables (maturation and pathology) were controlled in this study. The effect of midazolam (4+/-0.8 mg) sedation on the BOLD signal was assessed in 12 healthy adults (aged 24+/-1.5 years) at 1.5 T. The VLF fluctuation power and temporal synchrony of the BOLD signal increased significantly after the sedation in the auditory and visual cortices. The fast Fourier transformation power spectral baseline fit parameters of the BOLD signal were also found to change significantly after sedation. It is concluded that the VLF fluctuation and temporal synchrony of the BOLD signal become increased after sedation in functional brain regions.     

Phase vs. magnitude information in functional magnetic resonance imaging time series: toward understanding the noise

Although it has been shown that the phase of the MR signal from the brain is particularly prone to variation due to respiration, the overall physiological information contained in phase time series is not well understood. Here, we explore the different physiological processes contributing to the phase time series noise, identify their spatiotemporal characteristics and examine their relationship to BOLD-related and non-BOLD-related physiological noise in the magnitude time series. This was performed by manipulating the contribution of physiological noise to the total signal variance by modulating the TE and voxel volume, and using a short TR in order to adequately sample physiological signal fluctuations. The phase and magnitude signals were compared both before and after removal of signal fluctuations at the primary respiratory and cardiac frequencies with RETROICOR. We found that the temporal phase noise increased with TE at a faster rate than predicted by 1/TSNR as a result of physiological noise. As suggested by previous studies, the primary contributor to phase physiological noise was respiration-related effects which were manifested at a large scale (>1 cm). Notably, RETROICOR removed respiration-related large-scale artifacts and this resulted in considerable improvements in the temporal phase stability (7–90%). Physiological noise in the magnitude time series after RETROICOR consisted of low-frequency BOLD-related fluctuations (<0.13 Hz) localized to gray matter and the vasculature, and fluctuations in the vasculature correlated with slow (<0.1 Hz) variations in respiration volume and cardiac rhythm. Physiological noise in the phase signal after RETROICOR also occurred in frequencies below 0.13 Hz and was consistent with (1) residual large-scale magneto-mechanical effects correlated with slow variations in respiration volume and cardiac rhythm over time, and (2) local scale (<1 cm) effects localized in gray matter and vasculature most likely due to vascular dephasing mediated by a BOLD susceptibility change. While BOLD-related magnitude noise exhibited a TE dependence similar to BOLD, the ‘BOLD-related’ noise in the phase data increased with increasing TE and thus caused the overall phase noise to increase at a faster rate with TE than predicted by 1/TSNR. Interestingly, the spatial specificity of this effect was more evident for the higher resolution phase data, as opposed to the magnitude data, suggesting that at a higher spatial resolution the phase signal may contain more information on physiological processes than the magnitude signal.     

Brain modifications after acute alcohol consumption analyzed by resting state fMRI

Resting-state functional magnetic resonance imaging (fMRI) is a recent breakthrough in neuroimaging research able to describe “in vivo” the spontaneous baseline neuronal activity characterized by blood oxygen level dependent (BOLD) signal fluctuations at slow frequency (0.01–0.1 Hz) that, in the absence of any task, forms spatially distributed functional connectivity networks, called resting state networks (RSNs). The aim of this study was to investigate, in the young and healthy population, the changing of the RSNs after acute ingestion of an alcohol dose able to determine a blood concentration (0.5 g/L) that barely exceeds the legal limits for driving in the majority of European Countries. Fifteen healthy volunteers underwent two fMRI sessions using a 1.5 T MR scanner before and after alcohol oral consumption. The main sequence acquired was EPI 2D BOLD, one per each session. To prevent the excessive alcohol consumption the subjects underwent the estimation of blood rate by breath test and after the stabilization of blood alcohol level (BAL) at 0.5 g/L the subjects underwent the second fMRI session. Functional data elaboration was carried out using the probabilistic independent component analysis (PICA). Spatial maps so obtained were further organized, with MELODIC multisession temporal concatenation FSL option, in a cluster representing the group of pre-alcohol sessions and the group of post-alcohol sessions, followed by the dual regression approach in order to evaluate the increase or decrease in terms of connectivity in the RSNs between the two sessions at group level.The results we obtained reveal that acute consumption of alcohol reduces in a significant way the BOLD signal fluctuations in the resting brain selectively in the sub-callosal cortex (SCC), in left temporal fusiform cortex (TFC) and left inferior temporal gyrus (ITG), which are cognitive regions known to be part of the reward brain network and the ventral visual system.     

A kernel machine-based fMRI physiological noise removal method

Functional magnetic resonance imaging (fMRI) technique with blood oxygenation level dependent (BOLD) contrast is a powerful tool for noninvasive mapping of brain function under task and resting states. The removal of cardiac- and respiration-induced physiological noise in fMRI data has been a significant challenge as fMRI studies seek to achieve higher spatial resolutions and characterize more subtle neuronal changes. The low temporal sampling rate of most multi-slice fMRI experiments often causes aliasing of physiological noise into the frequency range of BOLD activation signal. In addition, changes of heartbeat and respiration patterns also generate physiological fluctuations that have similar frequencies with BOLD activation. Most existing physiological noise-removal methods either place restrictive limitations on image acquisition or utilize filtering or regression based post-processing algorithms, which cannot distinguish the frequency-overlapping BOLD activation and the physiological noise. In this work, we address the challenge of physiological noise removal via the kernel machine technique, where a nonlinear kernel machine technique, kernel principal component analysis, is used with a specifically identified kernel function to differentiate BOLD signal from the physiological noise of the frequency. The proposed method was evaluated in human fMRI data acquired from multiple task-related and resting state fMRI experiments. A comparison study was also performed with an existing adaptive filtering method. The results indicate that the proposed method can effectively identify and reduce the physiological noise in fMRI data. The comparison study shows that the proposed method can provide comparable or better noise removal performance than the adaptive filtering approach.     

Large-amplitude, spatially correlated fluctuations in BOLD fMRI signals during extended rest and early sleep stages

A number of recent studies of human brain activity using blood-oxygen-level-dependent (BOLD) fMRI and EEG have reported the presence of spatiotemporal patterns of correlated activity in the absence of external stimuli. Although these patterns have been hypothesized to contain important information about brain architecture, little is known about their origin or about their relationship to active cognitive processes such as conscious awareness and monitoring of the environment. In this study, we have investigated the amplitude and spatiotemporal characteristics of resting-state activity patterns and their dependence on the subjects' alertness. For this purpose, BOLD fMRI was performed at 3.0 T on 12 normal subjects using a visual stimulation protocol, followed by a 27 min rest period, during which subjects were allowed to fall asleep. In subjects who were asleep at the end of the scan, we found (a) a higher amplitude of BOLD signal fluctuation during rest compared with subjects who were awake at the end of the scan; (b) spatially independent patterns of correlated activity that involve all of gray matter, including deep brain nuclei; (c) many patterns that were consistent across subjects; (d) that average percentage levels of fluctuation in visual cortex (VC) and whole brain were higher in subjects who were asleep (up to 1.71% and 1.16%, respectively) than in those who were awake (up to 1.15% and 0.96%) at the end of the scan and were comparable with those levels evoked by intense visual stimulation (up to 1.85% and 0.76% for two subject groups); (e) no confirmation of correlation, positive or negative, between thalamus and VC found in earlier studies. These findings suggest that resting-state activity continues during sleep and does not require active cognitive processes or conscious awareness.     

Visual cortex reactivity in sedated children examined with perfusion MRI (FAIR)

Sleeping and sedated children can respond to visual stimulation with a decrease in blood oxygenation level dependent (BOLD) functional MRI signal response. The contribution of metabolic and hemodynamic parameters to this inverse signal response is incompletely understood. It has been hypothesized that it is caused by a relatively greater increase of oxygen consumption compared to rCBF (regional cerebral blood flow) increase. We studied the rCBF changes during visual stimulation in four sedated children, aged 4-71 months, and four alert adults, with an arterial water spin labeling technique (FAIR) and BOLD fMRI in a 1.5T MR scanner. In the children, FAIR signal decreased by a mean of 0.96% (range 0.77-1.05) of the baseline periods of the non-selective images, while BOLD signal decreased by 2.03% (range 1.99-2.93). In the adults, FAIR and BOLD signal increased by 0.88% (range 0.8-0.99) and 2.63% (range 1.99-2.93), respectively. Thus, in the children, an rCBF increase could not be detected by perfusion MRI, but indications of a FAIR signal decrease were found. An rCBF decrease in the primary visual cortex during stimulation has not been reported previously, but it is a possible explanation for the negative BOLD response. Future studies will have to address if this response pattern is a consequence of age or sleep/sedation.     

Impact of intravenous nicotine on BOLD signal response to photic stimulation

Functional magnetic resonance imaging (fMRI) is increasingly being applied in the study of brain effects of nicotine. In addition, because tobacco smoking is common, many subjects studied with fMRI for other reasons may have appreciable levels of nicotine in plasma and brain during scanning. However, there is concern that the vascular effects of nicotine may alter the coupling between blood oxygen level dependent (BOLD) signal and neuronal activity. The objective of this study was to test for evidence of alteration of BOLD signal response of occipital cortex, a region with a relatively low concentration of neuronal nicotine receptors, to photic stimulation during intravenous infusion of nicotine. Nine nicotine dependent healthy smokers were withdrawn from nicotine under controlled conditions and then scanned while receiving photic stimulation and successive intravenous infusions of saline and nicotine. No evidence for an effect of nicotine on BOLD signal response to photic stimulation was detected at the doses studied. This observation suggests that nicotine does not alter the coupling between BOLD signal and neuronal activity in the visual cortex.     

Non-neural BOLD variability in block and event-related paradigms

Block and event-related stimulus designs are typically used in fMRI studies depending on the importance of detection power or estimation efficiency. The extent of vascular contribution to variability in block and event-related fMRI-BOLD response is not known. With scaling, the extent of vascular variability in the fMRI-BOLD response during block and event-related design tasks was investigated. Blood oxygen level-dependent (BOLD) contrast data from healthy volunteers performing a block design motor task and an event-related memory task requiring performance of a motor response were analyzed from the regions of interest (ROIs) surrounding the primary and supplementary motor cortices. Average BOLD signal change was significantly larger during the block design compared to the event-related design. In each subject, BOLD signal change across voxels in the ROIs had higher variation during the block design task compared to the event-related design task. Scaling using the resting state fluctuation of amplitude (RSFA) and breath-hold (BH), which minimizes BOLD variation due to vascular origins, reduced the within-subject BOLD variability in every subject during both tasks but significantly reduced BOLD variability across subjects only during the block design task. The strong non-neural source of intra- and intersubject variability of BOLD response during the block design compared to event-related task indicates that study designs optimizing for statistical power through enhancement of the BOLD contrast (for, e.g., block design) can be affected by enhancement of non-neural sources of BOLD variability.     

BOLD responses to trigeminal nerve stimulation

The current study investigates a new model of barrel cortex activation using stimulation of the infraorbital branch of the trigeminal nerve. A robust and reproducible activation of the rat barrel cortex was obtained following trigeminal nerve stimulation. Blood oxygen level-dependent (BOLD) effects were obtained in the primary somatosensory barrel cortex (S1BF), the secondary somatosensory cortex (S2) and the motor cortex. These cortical areas were reached from afferent pathways from the trigeminal ganglion, the trigeminal nuclei and thalamic nuclei from which neurons project their axons upon whisker stimulation. The maximum BOLD responses were obtained for a stimulus frequency of 1 Hz, a stimulus pulse width of 100 μs and for current intensities between 1.5 and 3 mA. The BOLD response was nonlinear as a function of frequency and current intensity. Additionally, modeling BOLD responses in the rat barrel cortex from separate cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO₂) measurements showed good agreement with the shape and amplitude of measured BOLD responses as a function of stimulus frequency and will potentially allow to identify the sources of BOLD nonlinearities. Activation of the rat barrel cortex using trigeminal nerve stimulation will contribute to the interpretation of the BOLD signals from functional magnetic resonance imaging studies.     

The effects of respiratory CO2 fluctuations in the resting-state BOLD signal differ between eyes open and eyes closed

Resting fluctuations in arterial CO₂ (a cerebral vasodilator) are believed to be an important source of low-frequency blood oxygenation level dependent (BOLD) signal fluctuations. In this study we focus on the two commonly used resting-states in functional magnetic resonance imaging experiments, eyes open and eyes closed, and quantify the degree to which measured spontaneous fluctuations in the partial pressure of end-tidal CO₂ (Pet_co2) relate to BOLD signal time series. A significantly longer latency of BOLD signal changes following Pet_co2 fluctuations was found in the eyes closed condition compared to with eyes open, which may reveal different intrinsic vascular response delays in CO₂ reactivity or an alteration in the net BOLD signal arising from Pet_co2 fluctuations and altered neural activity with eyes closed. By allowing a spatially varying time delay for the compensation of this temporal difference, a more spatially consistent CO₂ correlation map can be obtained. Finally, Granger-causality analysis demonstrated a “causal” relationship between Pet_co2 and BOLD. The identified dominant Pet_co2→BOLD directional coupling supports the notion that Pet_co2 fluctuations are indeed a cause of resting BOLD variance in the majority of subjects.     

Computed narrow-band azimuthal time-reversing array retrofocusing in shallow water.

The process of acoustic time reversal sends sound waves back to their point of origin in reciprocal acoustic environments even when the acoustic environment is unknown. The properties of the time-reversed field commonly depend on the frequency of the original signal, the characteristics of the acoustic environment, and the configuration of the time-reversing transducer array (TRA). In particular, vertical TRAs are predicted to produce horizontally confined foci in environments containing random volume refraction. This article validates and extends this prediction to shallow water environments via monochromatic Monte Carlo propagation simulations (based on parabolic equation computations using RAM). The computational results determine the azimuthal extent of a TRA's retrofocus in shallow-water sound channels either having random bottom roughness or containing random internal-wave-induced sound speed fluctuations. In both cases, randomness in the environment may reduce the predicted azimuthal angular width of the vertical TRA retrofocus to as little as several degrees (compared to 360 degrees for uniform environments) for source-array ranges from 5 to 20 km at frequencies from 500 Hz to 2 kHz. For both types of randomness, power law scalings are found to collapse the calculated azimuthal retrofocus widths for shallow sources over a variety of acoustic frequencies, source-array ranges, water column depths, and random fluctuation amplitudes and correlation scales. Comparisons are made between retrofocusing on shallow and deep sources, and in strongly and mildly absorbing environments.     

Steady-state activation in somatosensory cortex after changes in stimulus rate during median nerve stimulation

Passive electrical stimulation activates various human somatosensory cortical systems including the contralateral primary somatosensory area (SI), bilateral secondary somatosensory area (SII) and bilateral insula. The effect of stimulation frequency on blood oxygenation level-dependent (BOLD) activity remains unclear. We acquired 3-T functional magnetic resonance imaging (fMRI) in eight healthy volunteers during electrical median nerve stimulation at frequencies of 1, 3 and 10 Hz. During stimulation BOLD signal changes showed activation in the contralateral SI, bilateral SII and bilateral insula. Results of fMRI analysis showed that these areas were progressively active with the increase of rate of stimulation. As a major finding, the contralateral SI showed an increase of peak of BOLD activation from 1 to 3 Hz but reached a plateau during 10-Hz stimulation. Our finding is of interest for basic research and for clinical applications in subjects unable to perform cognitive tasks in the fMRI scanner.     

Identification of activated regions during a language task

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in neural activity are accompanied by modulation in the blood-oxygenation-level-dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed in many fMRI experiments, which show regions of cortex that seem to respond in antiphase with primary stimulus. The existence of this so-called negative BOLD response (NBR) has been observed and investigated in many functional studies. Several theoretical mechanisms have been proposed to account for it, but its origin has never been fully explained. In this study, the variability of fMRI activation, including the sources of the negative BOLD signal, during phonological and semantic language tasks, was investigated in six right-handed healthy subjects. We found significant activations in the brain regions, mainly in the left hemisphere, involved in the language stimuli [prominent in the inferior frontal gyrus, approximately Brodmann Areas (BA)7, BA44, BA45 and BA47, and in the precuneus]. Moreover, we observed activations in motor regions [precentral gyrus and supplementary motor area (SMA)], a result that suggests a specific role of these areas (particularly the SMA) in language processing. Functional analysis have also shown that certain brain regions, including the posterior cingulate cortex and the anterior cingulate cortex, have consistently greater activity during resting states compared to states of performing cognitive tasks. In our study, we observed diffuse NBR at the cortical level and a stronger negative response in correspondence to the main sinuses. These phenomena seem to be unrelated to a specific neural activity, appearing to be expressions of a mechanical variation in hemodynamics. We discussed about the importance of these responses that are anticorrelated with the stimulus. Our data suggest that particular care must be considered in the interpretation of fMRI findings, especially in the case of presurgical studies.     

Spectro-temporal processing in the envelope-frequency domain

The frequency selectivity for amplitude modulation applied to tonal carriers and the role of beats between modulators in modulation masking were studied. Beats between the masker and signal modulation as well as intrinsic envelope fluctuations of narrow-band-noise modulators are characterized by fluctuations in the "second-order" envelope (referred to as the "venelope" in the following). In experiment 1, masked threshold patterns (MTPs), representing signal modulation threshold as a function of masker-modulation frequency, were obtained for signal-modulation frequencies of 4, 16, and 64 Hz in the presence of a narrow-band-noise masker modulation, both applied to the same sinusoidal carrier. Carrier frequencies of 1.4, 2.8, and 5.5 kHz were used. The shape and relative bandwidth of the MTPs were found to be independent of the signal-modulation frequency and the carrier frequency. Experiment 2 investigated the extent to which the detection of beats between signal and masker modulation is involved in tone-in-noise (TN), noise-in-tone (NT), and tone-in-tone (TT) modulation masking, whereby the TN condition was similar to the one used in the first experiment. A signal-modulation frequency of 64 Hz, applied to a 2.8-kHz carrier, was tested. Thresholds in the NT condition were always lower than in the TN condition, analogous to the masking effects known from corresponding experiments in the audio-frequency domain. TT masking conditions generally produced the lowest thresholds and were strongly influenced by the detection of beats between the signal and the masker modulation. In experiment 3, TT masked-threshold patterns were obtained in the presence of an additional sinusoidal masker at the beat frequency. Signal-modulation frequencies of 32, 64, and 128 Hz, applied to a 2.8-kHz carrier, were used. It was found that the presence of an additional modulation at the beat frequency hampered the subject's ability to detect the envelope beats and raised thresholds up to a level comparable to that found in the TN condition. The results of the current study suggest that (i) venelope fluctuations play a similar role in modulation masking as envelope fluctuations do in spectral masking, and (ii) envelope and venelope fluctuations are processed by a common mechanism. To interpret the empirical findings, a general model structure for the processing of envelope and venelope fluctuations is proposed.     

Effects of mild hypoxic hypoxia on poststimulus undershoot of blood-oxygenation-level-dependent fMRI signal in the human visual cortex

Characteristics of the blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal poststimulus undershoot in the visual cortex were studied at varying levels of arterial blood oxygen saturation (Ysat). Undershoot with an amplitude of -0.6+/-0.2% appeared after positive BOLD response (+1.7+/-0.5%) under control conditions. Cerebral blood volume (CBV), as determined with vascular-space-occupancy-dependent fMRI, increased by 26-43% during the positive BOLD peak, but the CBV proceeded at baseline level during the BOLD poststimulus undershoot. Mild hypoxic hypoxia (Ysat ranging from 0.82 to 0.89) had no effect on the amplitude or duration of poststimulus undershoot in activated BOLD pixels. Hypoxia did not influence CBV during the BOLD poststimulus undershoot. In contrast, the positive BOLD signal at the level of all activated pixels was smaller in hypoxia than in normoxia. The present results show that the BOLD poststimulus undershoot is not influenced by curtailed oxygen availability and that, during the undershoot, CBV is not different from resting state.     

Growth of simultaneous masking for fm < fs: effects of overall frequency and level.

Growth-of-masking (GOM) functions were obtained in three groups of normal-hearing subjects using a simultaneous-masking paradigm. In all cases, the signal frequency (fs) was higher than the masker frequency (fm), either by a certain ratio (1.44) or by a certain distance [3 equivalent rectangular bandwidths (ERBs)]. The purpose was to evaluate the effect of overall frequency on the slope of the steep portion of the GOM function, and to evaluate the change in slope that can occur at high levels. Signal frequency ranged from 400 to 5000 Hz, and masker level ranged from 40 to 95 dB SPL. On average, the slope of the steep portion of the GOM function was about 1.4 for signal frequencies from 400 to 750 Hz, and 2.0 for signal frequencies from 1944 to 5000 Hz. This is consistent with the possibility that the cochlea may behave more linearly at the apical (low-frequency) region than at the basal (high-frequency) region. In addition, for signal frequencies at and above 750 Hz, the slope of the masking function changed from a value much greater than 1.0 to a value of 1.0 at high levels. The change in slope was better correlated with signal sensation level (i.e., amount of masking) than with either signal or masker SPL: the lack of a change at the lower signal frequencies may reflect the smaller amounts of masking there. The change to a linear growth of masking may represent a change in the response to the signal from compressive to linear at high levels.     

Decoding neural events from fMRI BOLD signal: A comparison of existing approaches and development of a new algorithm

Neuroimaging methodology predominantly relies on the blood oxygenation level dependent (BOLD) signal. While the BOLD signal is a valid measure of neuronal activity, variances in fluctuations of the BOLD signal are not only due to fluctuations in neural activity. Thus, a remaining problem in neuroimaging analyses is developing methods that ensure specific inferences about neural activity that are not confounded by unrelated sources of noise in the BOLD signal. Here, we develop and test a new algorithm for performing semiblind (i.e., no knowledge of stimulus timings) deconvolution of the BOLD signal that treats the neural event as an observable, but intermediate, probabilistic representation of the system's state. We test and compare this new algorithm against three other recent deconvolution algorithms under varied levels of autocorrelated and Gaussian noise, hemodynamic response function (HRF) misspecification and observation sampling rate. Further, we compare the algorithms' performance using two models to simulate BOLD data: a convolution of neural events with a known (or misspecified) HRF versus a biophysically accurate balloon model of hemodynamics. We also examine the algorithms' performance on real task data. The results demonstrated good performance of all algorithms, though the new algorithm generally outperformed the others (3.0% improvement) under simulated resting-state experimental conditions exhibiting multiple, realistic confounding factors (as well as 10.3% improvement on a real Stroop task). The simulations also demonstrate that the greatest negative influence on deconvolution accuracy is observation sampling rate. Practical and theoretical implications of these results for improving inferences about neural activity from fMRI BOLD signal are discussed.     

Spontaneous low-frequency blood oxygenation level-dependent fluctuations and functional connectivity analysis of the 'resting' brain

Functional magnetic resonance imaging techniques using the blood oxygenation level-dependent (BOLD) contrast are widely used to map human brain function by relating local hemodynamic responses to neuronal stimuli compared to control conditions. There is increasing interest in spontaneous cerebral BOLD fluctuations that are prominent in the low-frequency range (<0.1 Hz) and show intriguing spatio-temporal correlations in functional networks. The nature of these signal fluctuations remains unclear, but there is accumulating evidence for a neural basis opening exciting new avenues to study human brain function and its connectivity at rest. Moreover, an increasing number of patient studies report disease-dependent variation in the amplitude and spatial coherence of low-frequency BOLD fluctuations (LFBF) that may afford greater diagnostic sensitivity and easier clinical applicability than standard fMRI. The main disadvantage of this emerging tool relates to physiological (respiratory, cardiac and vasomotion) and motion confounds that are challenging to disentangle requiring thorough preprocessing. Technical aspects of functional connectivity fMRI analysis and the neuroscientific potential of spontaneous LFBF in the default mode and other resting-state networks have been recently reviewed. This review will give an update on the current knowledge of the nature of LFBF, their relation to physiological confounds and potential for clinical diagnostic and pharmacological studies.     

Transient and sustained BOLD responses to sustained visual stimulation

Examining the transients of the blood-oxygenation-level-dependent (BOLD) signal using functional magnetic resonance imaging is a tool to probe basic brain physiology. In addition to the so-called initial dip and poststimulus undershoot of the BOLD signal, occasionally, overshoot at the beginning and at the end of stimulation and stimulus onset and offset ('phasic') responses are observed. Hemifield visual stimulation was used in human subjects to study the latter transients. As expected, sustained ('tonic') stimulus-correlated contralateral activation in the visual cortex and LGN was observed. Interestingly, bilateral phasic responses were observed, which only partly overlapped with the tonic network and which would have been missed using a standard analysis. A biomechanical model of the BOLD signal ('balloon model') indicated that, in addition to phasic neuronal activity, vascular uncoupling can also give rise to phasic BOLD signals. Thus, additional physiological information (i.e., cerebral blood flow) and examination of spatial distribution of the activity might help to assess the BOLD signal transients correctly. In the current study, although vascular uncoupled responses cannot be ruled out as an explanation of the observed phasic BOLD network, the spatial distribution argues that sustained hemifield visual stimulation evokes both bilateral phasic and contralateral sustained neuronal responses. As a consequence, in rapid event-related experimental designs, both the phasic and tonic networks cannot be separated, possibly confounding the interpretation of BOLD signal data. Furthermore, a combination of phasic and tonic responses in the same region of interest might also mimic a BOLD response typically observed in adaptation experiments.     

Detectability of a pulsed tone in the presence of a masker with time-varying interaural correlation.

Detectability of a filtered probe tone (250, 500, or 1000 Hz) was measured in the presence of a narrow-band Gaussian masker centered at the signal frequency. The signal was interaurally phase-reversed (Spi), and the masker's interaural correlation varied sinusoidally between +1.00 (NO) and -1.00 (Npi) at a varaible rate (fm = 0--4 Hz). The signal was presented at various points on the masker's modulation cycle. For 0-Hz modulation (fixed interaural correlation) signal threshold decreased monotonically as the masker's interaural correlation was changed from -1.00 to +1.00 (by a total of about 20, 16, and 8 dB, respectively, for 250-, 500-, and 1000-Hz signals). For fm greater than 0 the function relating signal threshold to the masker's interaural correlation at the moment of signal presentation became progressively flatter with increasing fm for all signal frequencies. For fm = 4 Hz the function was flat; there was no measurable effect of masker interaural correlation on signal detectability. Estimates of minimum binaural integration time based on these data ranged from 44--243 ms, supporting previous studies which have noted the binaural system's relative insensitivity to dynamic stimulation. Additionally, the estimated time constants were approximately twice as large at 250 Hz as at 500 Hz, indicating observers could follow binaural fluctuations better at 500 Hz. The time-constant estimates at 1000 Hz were not suggiciently reliable to permit comparisons with the lower-frequency data.