Cortical laminar resting‐state signal fluctuations scale with the hypercapnic blood oxygenation level‐dependent response

Calibrated functional magnetic resonance imaging can remove unwanted sources of signal variability in the blood oxygenation level‐dependent (BOLD) response. This is achieved by scaling, using information from a perfusion‐sensitive scan during a purely vascular challenge, typically induced by a gas manipulation or a breath‐hold task. In this work, we seek for a validation of the use of the resting‐state fluctuation amplitude (RSFA ) as a scaling factor to remove vascular contributions from the BOLD response. Given the peculiarity of depth‐dependent vascularization in gray matter, BOLD and vascular space occupancy (VASO) data were acquired at submillimeter resolution and averaged across cortical laminae. RSFA from the primary motor cortex was, thus, compared to the amplitude of hypercapnia‐induced signal changes (tSD_hc ) and with the M factor of the Davis model on a laminar level. High linear correlations were observed for RSFA and tSD_hc ( R² = 0.92 ± 0.06 ) and somewhat reduced for RSFA and M ( R² = 0.62 ± 0.19 ). Laminar profiles of RSFA ‐normalized BOLD signal changes yielded good agreement with corresponding VASO profiles. Overall, this suggests that RSFA contains strong vascular components and is also modulated by baseline quantities contained in the M factor. We conclude that RSFA may replace the scaling factor tSD_hc for normalizing the laminar BOLD response.     

Large enhancement of perfusion contribution on fMRI signal

The perfusion contribution to the total functional magnetic resonance imaging (fMRI) signal was investigated using a rat model with mild hypercapnia at 9.4 T, and human subjects with visual stimulation at 4 T. It was found that the total fMRI signal change could be approximated as a linear superposition of ‘true'' blood oxygenation level-dependent (BOLD; T₂/T₂^*) effect and the blood flow-related (T₁) effect. The latter effect was significantly enhanced by using short repetition time and large radiofrequency pulse flip angle and became comparable to the ‘true'' BOLD signal in response to a mild hypercapnia in the rat brain, resulting in an improved contrast-to-noise ratio (CNR). Bipolar diffusion gradients suppressed the intravascular signals but had no significant effect on the flow-related signal. Similar results of enhanced fMRI signal were observed in the human study. The overall results suggest that the observed flow-related signal enhancement is likely originated from perfusion, and this enhancement can improve CNR and the spatial specificity for mapping brain activity and physiology changes. The nature of mixed BOLD and perfusion-related contributions in the total fMRI signal also has implication on BOLD quantification, in particular, the BOLD calibration model commonly used to estimate the change of cerebral metabolic rate of oxygen.     

Layer‐specific BOLD activation in human V1

The neocortex is known to have a distinct laminar structure which has previously been probed in animals using high‐resolution fMRI. Detection of layer‐specific activation in humans has however to date proven elusive. In this study we demonstrate for the first time such layer‐specific activation, specifically at a depth corresponding to layer IV of human primary visual cortex (V1). We used a gradient‐echo (GE) sequence at 3T with an isotropic resolution of 0.75 mm, in which a stria at the depth of layer IV was visible in the averaged time series, and could be used as an anatomical landmark. Upon visual stimulation (7.5 Hz flickering checkerboard) the signal increase of 3% in layer IV was significantly higher than in the neighboring laminae. The width of this activation peak was 0.8–1 mm. Based on this result and known laminar organization of the intracortical vasculature we conclude that in the direction perpendicular to the cortical surface the intrinsic spatial resolution of the GE‐BOLD fMRI signal is in the submillimetre range. Human laminar fMRI is a significant development which may improve our understanding of intracortical activation patterns and of the way in which different cortical regions interact. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

The spatial dependence of the poststimulus undershoot as revealed by high-resolution BOLD- and CBV-weighted fMRI.

The hemodynamic response to neural activity consists of changes in blood flow, blood volume and oxygen metabolism. Changes in the vascular state after sensory stimulation have different spatial and temporal characteristics in the brain. This has been shown using imaging techniques, such as BOLD functional magnetic resonance imaging (fMRI), which monitor vascular changes once the stimulus is turned on, and the eventual return to baseline levels, once the stimulus is turned off. The BOLD fMRI signal during sensory stimulation has been well characterized and modeled in terms of the spatial and temporal characteristics of the vascular response. However, the return of the signals to baseline levels after sensory stimulation is not as well characterized. During this period, a poststimulus undershoot in the BOLD signal is observed. This poststimulus undershoot has been modeled and investigated to characterize the physiological mechanisms (cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral oxygen consumption) associated with the response. However, the data in the literature, which lack any spatially dependent information, appear to be contradictory in terms of the mechanisms associated with this poststimulus response. With a high spatial resolution cat model at 9.4 T, we show that CBV changes in the tissue persist once the stimulus is turned off, while CBV changes in the surface vessels quickly return to baseline levels, despite a concurrent undershoot in the BOLD signal in both the tissue and surface vessel areas. In addition, the BOLD data alone indicate that different physiological mechanisms regulate the poststimulus response in the tissue versus the surface vessel regions.     

Exploring the post‐stimulus undershoot with spin‐echo fMRI: Implications for models of neurovascular response

As a consequence of neural stimulation the blood oxygenation‐level dependent (BOLD) contrast in gradient‐echo echo‐planar imaging (GE‐EPI) based functional MRI (fMRI) leads to an increased MR signal in activated brain regions. Following this, a BOLD signal undershoot below baseline is generally observed with GE‐EPI. The origin of this undershoot has been the focus of many investigations using fMRI and optical modalities, but the underlying mechanisms remain disputed. Here, we investigate the BOLD undershoot following visual stimulation by using a purely T₂‐weighted fMRI sequence at 1.5 and 3 T. By taking advantage of the field strength dependency of the T₂ BOLD contrast and complete absence of static dephasing effects due to the pure spin echoes, one can draw conclusions about the origin of the BOLD undershoot and test the hypotheses in the literature. We observe a significant undershoot at both field strengths, with constant undershoot‐to‐main response ratio. This provides strong evidence that the undershoot is caused by BOLD changes due to elevated post‐stimulus deoxyhaemoglobin concentration in the small vessels. ‘Delayed vascular compliance’ as suggested by the well‐known Balloon and Windkessel models does not appear capable of explaining the undershoot. Our results also suggest that blood volume changes in arterioles and capillaries, for which there is consistent evidence from optical imaging studies, cannot alone cause the undershoot. This has important implications for models of neurovascular response and provides further support for the decoupling of changes in the rate of oxygen metabolism and blood flow. In addition, we found that an ‘arteriolar balloon’ (delayed arterial compliance) may provide a plausible explanation for the temporal characteristics of the BOLD undershoot. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Cortical depth profiles of auditory and visual 7 T functional MRI responses in human superior temporal areas

Invasive neurophysiological studies in nonhuman primates have shown different laminar activation profiles to auditory vs. visual stimuli in auditory cortices and adjacent polymodal areas. Means to examine the underlying feedforward vs. feedback type influences noninvasively have been limited in humans. Here, using 1‐mm isotropic resolution 3D echo‐planar imaging at 7 T, we studied the intracortical depth profiles of functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) signals to brief auditory (noise bursts) and visual (checkerboard) stimuli. BOLD percent‐signal‐changes were estimated at 11 equally spaced intracortical depths, within regions‐of‐interest encompassing auditory (Heschl''s gyrus, Heschl''s sulcus, planum temporale, and posterior superior temporal gyrus) and polymodal (middle and posterior superior temporal sulcus) areas. Effects of differing BOLD signal strengths for auditory and visual stimuli were controlled via normalization and statistical modeling. The BOLD depth profile shapes, modeled with quadratic regression, were significantly different for auditory vs. visual stimuli in auditory cortices, but not in polymodal areas. The different depth profiles could reflect sensory‐specific feedforward versus cross‐sensory feedback influences, previously shown in laminar recordings in nonhuman primates. The results suggest that intracortical BOLD profiles can help distinguish between feedforward and feedback type influences in the human brain. Further experimental studies are still needed to clarify how underlying signal strength influences BOLD depth profiles under different stimulus conditions.     

Distinct fine‐scale fMRI activation patterns of contra‐ and ipsilateral somatosensory areas 3b and 1 in humans

Inter‐areal and ipsilateral cortical responses to tactile stimulation have not been well described in human S1 cortex. By taking advantage of the high signal‐to‐noise ratio at 7 T, we quantified blood oxygenation level dependent (BOLD) response patterns and time courses to tactile stimuli on individual distal finger pads at a fine spatial scale, and examined whether there are inter‐areal (area 3b versus area 1) and interhemispheric response differences to unilateral tactile stimulation in healthy human subjects. We found that 2‐Hz tactile stimulation of individual fingertips evoked detectable BOLD signal changes in both contralateral and ipsilateral area 3b and area 1. Contralateral digit activations were organized in an orderly somatotopic manner, and BOLD responses in area 3b were more digit selective than those in area 1. However, the area of cortex that was responsive to stimulation of a single digit (stimulus–response field) was similar across areas. In the ipsilateral hemisphere, response magnitudes in both areas 3b and 1 were significantly weaker than those of the contralateral hemisphere. Digit activations exhibited no clear somatotopic organizational pattern in either area 3b or area 1, yet digit selectivity was retained in area 1 but not in area 3b. The observation of distinct digit‐selective responses of contralateral area 3b versus area 1 supports a higher order function of contralateral area 1 in spatial integration. In contrast, ipsilateral cortices may play a less discriminative role in the perception of unilateral tactile sensation in humans. Hum Brain Mapp 35:4841–4857, 2014. © 2014 Wiley Periodicals, Inc.     

Characterization of the functional MRI response temporal linearity via optical control of neocortical pyramidal neurons

The blood oxygenation level-dependent (BOLD) signal serves as the basis for human functional MRI (fMRI). Knowledge of the properties of the BOLD signal, such as how linear its response is to sensory stimuli, is essential for the design and interpretation of fMRI experiments. Here, we combined the cell-type and site-specific causal control provided by optogenetics and fMRI (opto-fMRI) in mice to test the linearity of BOLD signals driven by locally induced excitatory activity. We employed high-resolution mouse fMRI at 9.4 tesla to measure the BOLD response, and extracellular electrophysiological recordings to measure the effects of stimulation on single unit, multiunit, and local field potential activity. Optically driven stimulation of layer V neocortical pyramidal neurons resulted in a positive local BOLD response at the stimulated site. Consistent with a linear transform model, this locally driven BOLD response summated in response to closely spaced trains of stimulation. These properties were equivalent to responses generated through the multisynaptic method of driving neocortical activity by tactile sensory stimulation, and paralleled changes in electrophysiological measures. These results illustrate the potential of the opto-fMRI method and reinforce the critical assumption of human functional neuroimaging that--to first approximation--the BOLD response tracks local neural activity levels.     

Tonotopic maps in human auditory cortex using arterial spin labeling

A tonotopic organization of the human auditory cortex (AC) has been reliably found by neuroimaging studies. However, a full characterization and parcellation of the AC is still lacking. In this study, we employed pseudo‐continuous arterial spin labeling (pCASL) to map tonotopy and voice selective regions using, for the first time, cerebral blood flow (CBF). We demonstrated the feasibility of CBF‐based tonotopy and found a good agreement with BOLD signal‐based tonotopy, despite the lower contrast‐to‐noise ratio of CBF. Quantitative perfusion mapping of baseline CBF showed a region of high perfusion centered on Heschl's gyrus and corresponding to the main high‐low‐high frequency gradients, co‐located to the presumed primary auditory core and suggesting baseline CBF as a novel marker for AC parcellation. Furthermore, susceptibility weighted imaging was employed to investigate the tissue specificity of CBF and BOLD signal and the possible venous bias of BOLD‐based tonotopy. For BOLD only active voxels, we found a higher percentage of vein contamination than for CBF only active voxels. Taken together, we demonstrated that both baseline and stimulus‐induced CBF is an alternative fMRI approach to the standard BOLD signal to study auditory processing and delineate the functional organization of the auditory cortex. Hum Brain Mapp 38:1140–1154, 2017. © 2016 Wiley Periodicals, Inc.     

Comparing functional MRI protocols for small,iron‐rich basal ganglia nuclei such as the subthalamic nucleus at 7 T and 3 T

The basal ganglia (BG) form a network of subcortical nuclei. Functional magnetic resonance imaging (fMRI) in the BG could provide insight in its functioning and the underlying mechanisms of Deep Brain Stimulation (DBS). However, fMRI of the BG with high specificity is challenging, because the nuclei are small and variable in their anatomical location. High resolution fMRI at field strengths of 7 Tesla (T) could help resolve these challenges to some extent. A set of MR protocols was developed for functional imaging of the BG nuclei at 3 T and 7 T. The protocols were validated using a stop‐signal reaction task (Logan et al. [ 1984 ]: J Exp Psychol: Human Percept Perform 10:276–291). Compared with sub‐millimeter 7 T fMRI protocols aimed at cortex, a reduction of echo time and spatial resolution was strictly necessary to obtain robust Blood Oxygen Level Dependent (BOLD) sensitivity in the BG. An fMRI protocol at 3 T with identical resolution to the 7 T showed no robust BOLD sensitivity in any of the BG nuclei. The results suggest that the subthalamic nucleus, as well as the substantia nigra, red nucleus, and the internal and external parts of the globus pallidus show increased activation in failed stop trials compared with successful stop and go trials. Hum Brain Mapp 38:3226–3248, 2017. © 2017 Wiley Periodicals, Inc.     

Evidence that neurovascular coupling underlying the BOLD effect increases with age during childhood

Functional MRI using blood–oxygen‐level‐dependent (BOLD) imaging has provided unprecedented insights into the maturation of the human brain. Task‐based fMRI studies have shown BOLD signal increases with age during development (ages 5–18) for many cognitive domains such as language and executive function, while functional connectivity (resting‐state) fMRI studies investigating regionally synchronous BOLD fluctuations have revealed a developing functional organization of the brain from a local into a more distributed architecture. However, interpretation of these results is confounded by the fact that the BOLD signal is directly related to blood oxygenation driven by changes in blood flow and only indirectly related to neuronal activity, and may thus be affected by changing neuronal–vascular coupling. BOLD signal and cerebral blood flow (CBF) were measured simultaneously in a cohort of 113 typically developing awake participants ages 3–18 performing a narrative comprehension task. Using a novel voxelwise wild bootstrap analysis technique, an increased ratio of BOLD signal to relative CBF signal change with age (indicative of increased neuronal–vascular coupling) was seen in the middle temporal gyri and the left inferior frontal gyrus. Additionally, evidence of decreased relative oxygen metabolism (indicative of decreased neuronal activity) with age was found in the same regions. These findings raise concern that results of developmental BOLD studies cannot be unambiguously attributed to neuronal activity. Astrocytes and astrocytic processes may significantly affect the maturing functional architecture of the brain, consistent with recent research demonstrating a key role for astrocytes in mediating increased CBF following neuronal activity and for astrocyte processes in modulating synaptic connectivity. Hum Brain Mapp, 36:1–15, 2015. © 2014 Wiley Periodicals, Inc .     

Methods for olfactory fMRI studies: Implication of respiration

Human olfactory system is under‐studied using fMRI compared with other sensory systems. Because the perception (intensity, threshold, and valence) and detection of odors are tightly involved with respiration, the subject's respiration pattern modulates and interacts with the experimental paradigm, which presents difficulties for olfactory fMRI data acquisition, post‐processing, and interpretation. Based on our investigation on the interactions of odor presentation and subject's respiration, we propose a respiration‐triggered event‐related olfactory fMRI technique and a data post‐processing method that effectively captures precise onsets of olfactory blood‐oxygen‐level‐dependent (BOLD) signal in the primary olfactory cortex. We compared the olfactory BOLD signals from seventeen normal healthy adults with diverse respiratory patterns and showed that the subjects' respiratory patterns modulated the olfactory stimulation paradigm, which significantly confounded the BOLD signal. The presented experimental technique provides a simple and effective means for generating reliable olfactory fMRI results. Hum Brain Mapp 35:3616–3624, 2014. © 2013 Wiley Periodicals, Inc .     

Investigation of BOLD fMRI resonance frequency shifts and quantitative susceptibility changes at 7 T

Although blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) experiments of brain activity generally rely on the magnitude of the signal, they also provide frequency information that can be derived from the phase of the signal. However, because of confounding effects of instrumental and physiological origin, BOLD related frequency information is difficult to extract and therefore rarely used. Here, we explored the use of high field (7 T) and dedicated signal processing methods to extract frequency information and use it to quantify and interpret blood oxygenation and blood volume changes. We found that optimized preprocessing improves detection of task‐evoked and spontaneous changes in phase signals and resonance frequency shifts over large areas of the cortex with sensitivity comparable to that of magnitude signals. Moreover, our results suggest the feasibility of mapping BOLD quantitative susceptibility changes in at least part of the activated area and its largest draining veins. Comparison with magnitude data suggests that the observed susceptibility changes originate from neuronal activity through induced blood volume and oxygenation changes in pial and intracortical veins. Further, from frequency shifts and susceptibility values, we estimated that, relative to baseline, the fractional oxygen saturation in large vessels increased by 0.02–0.05 during stimulation, which is consistent to previously published estimates. Together, these findings demonstrate that valuable information can be derived from fMRI imaging of BOLD frequency shifts and quantitative susceptibility changes. Hum Brain Mapp 35:2191–2205, 2014. © 2013 Wiley Periodicals, Inc .     

Simultaneous blood oxygenation level-dependent and cerebral blood flow functional magnetic resonance imaging during forepaw stimulation in the rat.

The blood oxygenation level-dependent (BOLD) contrast mechanism can be modeled as a complex interplay between CBF, cerebral blood volume (CBV), and CMRO2. Positive BOLD signal changes are presumably caused by CBF changes in excess of increases in CMRO2. Because this uncoupling between CBF and CMRO2 may not always be present, the magnitude of BOLD changes may not be a good index of CBF changes. In this study, the relation between BOLD and CBF was investigated further. Continuous arterial spin labeling was combined with a single-shot, multislice echo-planar imaging to enable simultaneous measurements of BOLD and CBF changes in a well-established model of functional brain activation, the electrical forepaw stimulation of alpha-chloralose-anesthetized rats. The paradigm consisted of two 18- to 30-second stimulation periods separated by a 1-minute resting interval. Stimulation parameters were optimized by laser Doppler flowmetry. For the same cross-correlation threshold, the BOLD and CBF active maps were centered within the size of one pixel (470 microm). However, the BOLD map was significantly larger than the CBF map. Measurements taken from 15 rats at 9.4 T using a 10-millisecond echo-time showed 3.7 +/- 1.7% BOLD and 125.67 +/- 81.7% CBF increases in the contralateral somatosensory cortex during the first stimulation, and 2.6 +/- 1.2% BOLD and 79.3 +/- 43.6% CBF increases during the second stimulation. The correlation coefficient between BOLD and CBF changes was 0.89. The overall temporal correlation coefficient between BOLD and CBF time-courses was 0.97. These results show that under the experimental conditions of the current study, the BOLD signal changes follow the changes in CBF.     

Functional localization in the human brain: Gradient‐echo,spin‐echo,and arterial spin‐labeling fMRI compared with neuronavigated TMS

A spatial mismatch of up to 14 mm between optimal transcranial magnetic stimulation (TMS) site and functional magnetic resonance imaging (fMRI) signal has consistently been reported for the primary motor cortex. The underlying cause might be the effect of magnetic susceptibility around large draining veins in Gradient‐Echo blood oxygenation level‐dependent (GRE‐BOLD) fMRI. We tested whether alternative fMRI sequences such as Spin‐Echo (SE‐BOLD) or Arterial Spin‐Labeling (ASL) assessing cerebral blood flow (ASL‐CBF) may localize neural activity closer to optimal TMS positions and primary motor cortex than GRE‐BOLD. GRE‐BOLD, SE‐BOLD, and ASL‐CBF signal changes during right thumb abductions were obtained from 15 healthy subjects at 3 Tesla. In 12 subjects, tissue at fMRI maxima was stimulated with neuronavigated TMS to compare motor‐evoked potentials (MEPs). Euclidean distances between the fMRI center‐of‐gravity (CoG) and the TMS motor mapping CoG were calculated. Highest SE‐BOLD and ASL‐CBF signal changes were located in the anterior wall of the central sulcus [Brodmann Area 4 (BA4)], whereas highest GRE‐BOLD signal changes were significantly closer to the gyral surface. TMS at GRE‐BOLD maxima resulted in higher MEPs which might be attributed to significantly higher electric field strengths. TMS‐CoGs were significantly anterior to fMRI‐CoGs but distances were not statistically different across sequences. Our findings imply that spatial differences between fMRI and TMS are unlikely to be caused by spatial unspecificity of GRE‐BOLD fMRI but might be attributed to other factors, e.g., interactions between TMS‐induced electric field and neural tissue. Differences between techniques should be kept in mind when using fMRI coordinates as TMS (intervention) targets. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Enhanced phase regression with savitzky‐golay filtering for high‐resolution BOLD fMRI

Phase regression exploits the temporal evolution of phase in individual voxels to suppress blood oxygenation level dependent (BOLD) signal fluctuations caused by larger vessels and draining veins while preserving signal changes from microvascular effects. However, this process does not perform well when phase time series have low signal‐to‐noise ratios because of high levels of physiological noise. We demonstrate that Savitzky‐Golay filters may be used to recover the underlying change in phase and completely restore the efficacy of phase regression. We do not make a priori assumptions regarding phase evolution and perform a data‐driven exploration of parameter space to select the Savitzky‐Golay filter parameters that minimize temporal variance in each voxel after phase regression. This approach is shown to work well on data acquired with single‐shot and multi‐shot pulse sequences, and should therefore be useful for both human and animal gradient‐echo fMRI at high spatial resolutions at high fields. The ability to improve the spatial specificity of BOLD activation may be especially advantageous for clinical applications of fMRI that rely upon the accuracy of individual subject's activation maps to assist with presurgical planning and clinical decision‐making. Enhanced phase regression with Savitzky‐Golay filtering may also find other uses in analyses of resting state functional connectivity. Hum Brain Mapp 35:3832–3840, 2014. © 2014 Wiley Periodicals, Inc.     

Noninvasive dynamic imaging of seizures in epileptic patients

Epileptic seizures are due to abnormal synchronized neuronal discharges. Techniques measuring electrical changes are commonly used to analyze seizures. Neuronal activity can be also defined by concomitant hemodynamic and metabolic changes. Simultaneous electroencephalogram (EEG)‐functional MRI (fMRI) measures noninvasively with a high‐spatial resolution BOLD changes during seizures in the whole brain. Until now, only a static image representing the whole seizure was provided. We report in 10 focal epilepsy patients a new approach to dynamic imaging of seizures including the BOLD time course of seizures and the identification of brain structures involved in seizure onset and discharge propagation. The first activation was observed in agreement with the expected location of the focus based on clinical and EEG data (three intracranial recordings), thus providing validity to this approach. The BOLD signal preceded ictal EEG changes in two cases. EEG‐fMRI may detect changes in smaller and deeper structures than scalp EEG, which can only record activity form superficial cortical areas. This method allowed us to demonstrate that seizure onset zone was limited to one structure, thus supporting the concept of epileptic focus, but that a complex neuronal network was involved during propagation. Deactivations were also found during seizures, usually appearing after the first activation in areas close or distant to the activated regions. Deactivations may correspond to actively inhibited regions or to functional disconnection from normally active regions. This new noninvasive approach should open the study of seizure generation and propagation mechanisms in the whole brain to groups of patients with focal epilepsies. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Basal cerebral blood volume during the poststimulation undershoot in BOLD MRI of the human brain

One of the characteristics of the blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) response to functional challenges of the brain is the poststimulation undershoot, which has been suggested to originate from a delayed recovery of either cerebral blood volume (CBV) or cerebral metabolic rate of oxygen to baseline. Using bolus-tracking MRI in humans, we recently showed that relative CBV rapidly normalizes after the end of stimulation. As this observation contradicts at least part of the blood-pool contrast agent studies performed in animals, we reinvestigated the CBV contribution by dynamic T1-weighted three-dimensional MRI (8 seconds temporal resolution) and Vasovist at 3 T (12 subjects). Initially, we determined the time constants of individual BOLD responses. After injection of Vasovist, CBV-related T1-weighted signal changes revealed a signal increase during visual stimulation (1.7%±0.4%), but no change relative to baseline in the poststimulation phase (0.2%±0.3%). This finding renders the specific nature of the contrast agent unlikely to be responsible for the discrepancy between human and animal studies. With the assumption of normalized cerebral blood flow after stimulus cessation, a normalized CBV lends support to the idea that the BOLD MRI undershoot reflects a prolonged elevation of oxidative metabolism.     

Memory‐Related Hippocampal Activity Can Be Measured Robustly Using fMRI at 7 Tesla

High field strength functional magnetic resonance imaging (fMRI) has developed rapidly. However, it suffers from increased artifacts in brain regions such as the medial temporal lobe (MTL), challenging functional imaging of the hippocampus with the objective of high‐spatial resolution, which is particularly useful for this region both from a clinical and cognitive neuroscience perspective. We set out to compare a BOLD sequence at 7 T versus 3 T to visualize the MTL activity during an associative memory‐encoding task. Twenty‐eight healthy volunteers underwent a blocked‐design fMRI at either 3 T or 7 T while performing a face‐profession associative memory encoding task. Qualitative analyses of overall image quality revealed that functional images at 7 T were of high quality, showing a good white/gray matter contrast, with reasonably acceptable signal dropouts and artifacts at the lower portion of the temporal lobe. Analyses of task‐related fMRI data revealed robust activations in the bilateral MTL during associative memory encoding at both field strengths. Notably, we observed significantly stronger memory‐related hippocampal activation at 7 T than at 3 T, suggesting higher BOLD sensitivity at 7 T. These results are discussed in the light of the feasibility of 7 T scanning protocols for the MTL.     

Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient

Recent studies on spontaneous fluctuations in the functional MRI blood oxygen level‐dependent (BOLD) signal in awake healthy subjects showed the presence of coherent fluctuations among functionally defined neuroanatomical networks. However, the functional significance of these spontaneous BOLD fluctuations remains poorly understood. By means of 3 T functional MRI, we demonstrate absent cortico‐thalamic BOLD functional connectivity (i.e. between posterior cingulate/precuneal cortex and medial thalamus), but preserved cortico‐cortical connectivity within the default network in a case of vegetative state (VS) studied 2.5 years following cardio‐respiratory arrest, as documented by extensive behavioral and paraclinical assessments. In the VS patient, as in age‐matched controls, anticorrelations could also be observed between posterior cingulate/precuneus and a previously identified task‐positive cortical network. Both correlations and anticorrelations were significantly reduced in VS as compared to controls. A similar approach in a brain dead patient did not show any such long‐distance functional connectivity. We conclude that some slow coherent BOLD fluctuations previously identified in healthy awake human brain can be found in alive but unaware patients, and are thus unlikely to be uniquely due to ongoing modifications of conscious thoughts. Future studies are needed to give a full characterization of default network connectivity in the VS patients population. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.