Separation of physiological very low frequency fluctuation from aliasing by switched sampling interval fMRI scans

Anesthetized children have dominant blood-oxygen-level-dependent (BOLD) signal sources presenting high-power fluctuations at very low frequencies (VLF <0.05 Hz). Aliasing of frequencies higher than critically sampled has been regarded as one probable origin of the VLF fluctuations. Aliased signal frequencies change when the sampling rate of the data is altered. In this study, the aliasing of VLF BOLD signal fluctuation was analysed by switching the repetition time (TR) of magnetic resonance (MR) images. Eleven anesthetized children were imaged at 1.5 T using TRs of 500 and 1200 ms. The BOLD signal sources were separated with independent component analysis (ICA). Occipital cortex signal sources had nonaliased VLF fluctuation ( approximately 0.03 Hz) in 9 of 11 subjects. Arterial signal sources failed to present stable power peaks at frequencies lower than 0.42 Hz presumably due to aliasing. Cerebrospinal fluid (CSF)-related signal sources showed nonaliased VLF in four subjects. In conclusion, the VLF BOLD signal fluctuation in the occipital cortex is a true physiological fluctuation, not a result of signal aliasing.     

Comparison of α-chloralose,medetomidine and isoflurane anesthesia for functional connectivity mapping in the rat

Functional connectivity measures based upon low-frequency blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) signal fluctuations have become a widely used tool for investigating spontaneous brain activity in humans. Still unknown, however, is the precise relationship between neural activity, the hemodynamic response and fluctuations in the MRI signal. Recent work from several groups had shown that correlated low-frequency fluctuations in the BOLD signal can be detected in the anesthetized rat — a first step toward elucidating this relationship. Building on this preliminary work, through this study, we demonstrate that functional connectivity observed in the rat depends strongly on the type of anesthesia used. Power spectra of spontaneous fluctuations and the cross-correlation-based connectivity maps from rats anesthetized with α-chloralose, medetomidine or isoflurane are presented using a high-temporal-resolution imaging sequence that ensures minimal contamination from physiological noise. The results show less localized correlation in rats anesthetized with isoflurane as compared with rats anesthetized with α-chloralose or medetomidine. These experiments highlight the utility of using different types of anesthesia to explore the fundamental physiological relationships of the BOLD signal and suggest that the mechanisms contributing to functional connectivity involve a complicated relationship between changes in neural activity, neurovascular coupling and vascular reactivity.     

Neonatal auditory activation detected by functional magnetic resonance imaging

The objective of this study was to detect auditory cortical activation in non-sedated neonates employing functional magnetic resonance imaging (fMRI). Using echo-planar functional brain imaging, subjects were presented with a frequency-modulated pure tone; the BOLD signal response was mapped in 5 mm-thick slices running parallel to the superior temporal gyrus. Twenty healthy neonates (13 term, 7 preterm) at term and 4 adult control subjects. Blood oxygen level-dependent (BOLD) signal in response to auditory stimulus was detected in all 4 adults and in 14 of the 20 neonates. FMRI studies of adult subjects demonstrated increased signal in the superior temporal regions during auditory stimulation. In contrast, signal decreases were detected during auditory stimulation in 9 of 14 newborns with BOLD response. fMRI can be used to detect brain activation with auditory stimulation in human infants.     

Comparison of methods for detecting nondeterministic BOLD fluctuation in fMRI

Functional MR imaging (fMRI) has been used in detecting neuronal activation and intrinsic blood flow fluctuations in the brain cortex. This article is aimed for comparing the methods for analyzing the nondeterministic flow fluctuations. Fast Fourier Transformation (FFT), cross correlation (CC), spatial principal component analysis (sPCA), and independent component analysis (sICA) were compared. 15 subjects were imaged at 1.5 T. Three quantitative measures were compared: (1) The number of subjects with identifiable fluctuation, (2) the volume, and (3) mean correlation coefficient (MCC) of the detected voxels. The focusing on cortical structures and the overall usability were qualitatively assessed. sICA was spatially most accurate but time consuming, robust, and detected voxels with high temporal synchrony. The CC and FFT were fast suiting primary screening. The CC detected highest temporal synchrony but the subjective detection for reference vector produced excess variance of the detected volumes. The FFT and sPCA were not spatially accurate and did not detect adequate temporal synchrony of the voxels.     

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.     

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.     

Changes in MRI signal intensity during hypercapnic challenge under conscious and anesthetized conditions

Most functional magnetic resonance imaging (fMRI) studies in animals are conducted under anesthesia to minimize motion artifacts. However, methods and techniques have been developed recently for imaging fully conscious rats. Functional MRI studies on conscious animals report enhanced BOLD signal changes as compared to the anesthetized condition. In this study, rats were exposed to different concentrations of carbon dioxide (CO(2)) while conscious and anesthetized to test whether cerebrovascular reactivity may be contributing to these enhanced BOLD signal changes. Hypercapnia produced significantly greater increases in MRI signal intensity in fully conscious animals (6.7-13.3% changes) as when anesthetized with 1% isoflurane (3.2-4.9% changes). In addition, the response to hypercapnia was more immediate in the conscious condition (< 30s) with signal risetimes twice as fast as in the anesthetized state (60s). Both cortical and subcortical brain regions showed a robust, dose- dependent increase in MRI signal intensity with hypercapnic challenge while the animals were conscious but little or no change when anesthetized. Baseline variations in MRI signal were higher while animals were conscious but this was off set by greater signal intensity changes leading to a greater contrast-to-noise ratio, 13.1 in conscious animals, as compared to 8.0 in the anesthetized condition. In summary, cerebral vasculature appears to be more sensitive to hypercapnic challenge in the conscious condition resulting in enhanced T2* MRI signal intensity and the potential for better BOLD signal changes during functional imaging.     

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.     

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.     

SNR and functional sensitivity of BOLD and perfusion-based fMRI using arterial spin labeling with spiral SENSE at 3 T

Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies using parallel imaging to reduce the readout window have reported a loss in temporal signal-to-noise ratio (SNR) that is less than would be expected given a purely thermal noise model. In this study, the impact of parallel imaging on the noise components and functional sensitivity of both BOLD and perfusion-based fMRI data was investigated. Dual-echo arterial spin labeling data were acquired on five subjects using sensitivity encoding (SENSE), at reduction factors (R) of 1, 2 and 3. Direct recording of cardiac and respiratory activity during data acquisition enabled the retrospective removal of physiological noise. The temporal SNR of the perfusion time series closely followed the thermal noise prediction of a √R loss in SNR as the readout window was shortened, with temporal SNR values (relative to the R=1 data) of 0.72 and 0.56 for the R=2 and R=3 data, respectively, after accounting for physiological noise. However, the BOLD temporal SNR decreased more slowly than predicted even after accounting for physiological noise, with relative temporal SNR values of 0.80 and 0.63 for the R=2 and R=3 data, respectively. Spectral analysis revealed that the BOLD trends were dominated by low-frequency fluctuations, which were not dominant in the perfusion data due to signal processing differences. The functional sensitivity, assessed using mean F values over activated regions of interest (ROIs), followed the temporal SNR trends for the BOLD data. However, results for the perfusion data were more dependent on the threshold used for ROI selection, most likely due to the inherently low SNR of functional perfusion data.     

Quantification of the power changes in BOLD signals using Welch spectrum method during different single-hand motor imageries

Motor imagery is an experimental paradigm implemented in cognitive neuroscience and cognitive psychology. To investigate the asymmetry of the strength of cortical functional activity due to different single-hand motor imageries, functional magnetic resonance imaging (fMRI) data from right handed normal subjects were recorded and analyzed during both left-hand and right-hand motor imagery processes. Then the average power of blood oxygenation level-dependent (BOLD) signals in temporal domain was calculated using the developed tool that combines Welch power spectrum and the integral of power spectrum approach of BOLD signal changes during motor imagery. Power change analysis results indicated that cortical activity exhibited a stronger power in the precentral gyrus and medial frontal gyrus with left-hand motor imagery tasks compared with that from right-hand motor imagery tasks. These observations suggest that right handed normal subjects mobilize more cortical nerve cells for left-hand motor imagery. Our findings also suggest that the approach based on power differences of BOLD signals is a suitable quantitative analysis tool for quantification of asymmetry of brain activity intensity during motor imagery tasks.     

To smooth or not to smooth? ROC analysis of perfusion fMRI data

Blood oxygenation level dependent (BOLD) contrast has been widely used for visualizing regional neural activation. Temporal filtering and parameter estimation algorithms are generally used to account for the intrinsic temporal autocorrelation present in BOLD data. Arterial spin labeling perfusion imaging is an emerging methodology for visualizing regional brain function both at rest and during activation. Perfusion contrast manifests different noise properties compared with BOLD contrast, represented by the even distribution of noise power and spatial coherence across the frequency spectrum. Consequently, different strategies are expected to be employed in the statistical analysis of functional magnetic resonance imaging (fMRI) data based on perfusion contrast. In this study, the effect of different analysis methods upon signal detection efficacy, as assessed by receiver operator characteristic (ROC) measures, was examined for perfusion fMRI data. Simulated foci of neural activity of varying amplitude and spatial extent were added to resting perfusion data, and the accuracy of each analysis was evaluated by comparing the results with the known distribution of pseudo-activation. In contrast to the BOLD fMRI, temporal smoothing or filtering reduces the power of perfusion fMRI data analyses whereas spatial smoothing is beneficial to the efficacy of analyses.     

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.     

Origins of intersubject variability of blood oxygenation level dependent and arterial spin labeling fMRI: implications for quantification of brain activity

Accurate localization of brain activity using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been challenged because of the large BOLD signal within distal veins. Arterial spin labeling (ASL) techniques offer greater sensitivity to the microvasculature but possess low temporal resolution and limited brain coverage. In this study, we show that the physiological origins of BOLD and ASL depend on whether percent change or statistical significance is being considered. For BOLD and ASL fMRI data collected during a simple unilateral hand movement task, we found that in the area of the contralateral motor cortex the centre of gravity (CoG) of the intersubject coefficient of variation (CV) of BOLD fMRI was near the brain surface for percent change in signal, whereas the CoG of the intersubject CV for Z-score was in close proximity of sites of brain activity for both BOLD and ASL. These findings suggest that intersubject variability of BOLD percent change is vascular in origin, whereas the origin of inter-subject variability of Z-score is neuronal for both BOLD and ASL. For longer duration tasks (12 s or greater), however, there was a significant correlation between BOLD and ASL percent change, which was not evident for short duration tasks (6 s). These findings suggest that analyses directly comparing percent change in BOLD signal between pre-defined regions of interest using short duration stimuli, as for example in event-related designs, may be heavily weighted by large-vessel responses rather than neuronal responses.     

Comparison between end-tidal CO₂ and respiration volume per time for detecting BOLD signal fluctuations during paced hyperventilation

Respiratory motion and capnometry monitoring were performed during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) of the brain while a series of paced hyperventilation tasks were performed that caused significant hypocapnia. Respiration volume per time (RVT) and end-tidal carbon dioxide (ETCO(2)) were determined and compared for their ability to explain BOLD contrast changes in the data. A 35% decrease in ETCO(2) was observed along with corresponding changes in RVT. A best-fit ETCO(2) response function, with an average initial peak delay time of 12 s, was empirically determined. ETCO(2) data convolved with this response function was more strongly and prevalently correlated to BOLD signal changes than RVT data convolved with the corresponding respiration response function. The results suggest that ETCO(2) better models BOLD signal fluctuations in fMRI experiments with significant transient hypocapnia. This is due to hysteresis in the ETCO(2) response when moving from hypocapnia to normocapnia, compared to moving from normocapnia to hypocapnia.     

Relationship between neural and hemodynamic signals during spontaneous activity studied with temporal kernel CCA

Functional magnetic resonance imaging (fMRI) based on the so-called blood oxygen level-dependent (BOLD) contrast is a powerful tool for studying brain function not only locally but also on the large scale. Most studies assume a simple relationship between neural and BOLD activity, in spite of the fact that it is important to elucidate how the “when” and “what” components of neural activity are correlated to the “where” of fMRI data. Here we conducted simultaneous recordings of neural and BOLD signal fluctuations in primary visual (V1) cortex of anesthetized monkeys. We explored the neurovascular relationship during periods of spontaneous activity by using temporal kernel canonical correlation analysis (tkCCA). tkCCA is a multivariate method that can take into account any features in the signals that univariate analysis cannot. The method detects filters in voxel space (for fMRI data) and in frequency–time space (for neural data) that maximize the neurovascular correlation without any assumption of a hemodynamic response function (HRF). Our results showed a positive neurovascular coupling with a lag of 4–5 s and a larger contribution from local field potentials (LFPs) in the γ range than from low-frequency LFPs or spiking activity. The method also detected a higher correlation around the recording site in the concurrent spatial map, even though the pattern covered most of the occipital part of V1. These results are consistent with those of previous studies and represent the first multivariate analysis of intracranial electrophysiology and high-resolution fMRI.     

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.     

Synchronized detection of minute electrical currents with MRI using Lorentz effect imaging

The blood oxygenation level-dependent (BOLD) effect is the most commonly used contrast mechanism in functional magnetic resonance imaging (fMRI), due to its relatively high spatial resolution and sensitivity. However, the ability of BOLD fMRI to accurately localize neuronal activation in space and time is limited by the inherent hemodynamic modulation. There is hence a need to develop alternative MRI methods that can directly image neuroelectric activity, thereby achieving both a high temporal resolution and spatial specificity as compared to conventional BOLD fMRI. In this paper, we extend the Lorentz effect imaging technique, which can detect spatially incoherent yet temporally synchronized minute electrical activity in a strong magnetic field, and demonstrate its feasibility for imaging randomly oriented electrical currents on the order of microamperes with a temporal resolution on the order of milliseconds in gel phantoms. This constitutes a promising step towards its application to direct imaging of neuroelectric activity in vivo, which has the same order of current density and temporal synchrony.     

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.     

Percept-related activity in the human somatosensory system: functional magnetic resonance imaging studies

In this paper, we review blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies addressing the neural correlates of touch, thermosensation, pain and the mechanisms of their cognitive modulation in healthy human subjects. There is evidence that fMRI signal changes can be elicited in the parietal cortex by stimulation of single mechanoceptive afferent fibers at suprathreshold intensities for conscious perception. Positive linear relationships between the amplitude or the spatial extents of BOLD fMRI signal changes, stimulus intensity and the perceived touch or pain intensity have been described in different brain areas. Some recent fMRI studies addressed the role of cortical areas in somatosensory perception by comparing the time course of cortical activity evoked by different kinds of stimuli with the temporal features of touch, heat or pain perception. Moreover, parametric single-trial functional MRI designs have been adopted in order to disentangle subprocesses within the nociceptive system.

Available evidence suggest that studies that combine fMRI with psychophysical methods may provide a valuable approach for understanding complex perceptual mechanisms and top-down modulation of the somatosensory system by cognitive factors specifically related to selective attention and to anticipation. The brain networks underlying somatosensory perception are complex and highly distributed. A deeper understanding of perceptual-related brain mechanisms therefore requires new approaches suited to investigate the spatial and temporal dynamics of activation in different brain regions and their functional interaction.