Jeroen C.W. Siero

probabilistic tractography recovers a rostrocaudal trajectory of connectivity variability in the human insular cortex.

The insular cortex of macaques has a wide spectrum of anatomical connections whose distribution is related to its heterogeneous cytoarchitecture. Although there is evidence of a similar cytoarchitectural arrangement in humans, the anatomical connectivity of the insula in the human brain has not yet been investigated in vivo. In the present work, we used in vivo probabilistic white‐matter tractography and Laplacian eigenmaps (LE) to study the variation of connectivity patterns across insular territories in humans. In each subject and hemisphere, we recovered a rostrocaudal trajectory of connectivity variation ranging from the anterior dorsal and ventral insula to the dorsal caudal part of the long insular gyri. LE suggested that regional transitions among tractography patterns in the insula occur more gradually than in other brain regions. In particular, the change in tractography patterns was more gradual in the insula than in the medial premotor region, where a sharp transition between different tractography patterns was found. The recovered trajectory of connectivity variation in the insula suggests a relation between connectivity and cytoarchitecture in humans resembling that previously found in macaques: tractography seeds from the anterior insula were mainly found in limbic and paralimbic regions and in anterior parts of the inferior frontal gyrus, while seeds from caudal insular territories mostly reached parietal and posterior temporal cortices. Regions in the putative dysgranular insula displayed more heterogeneous connectivity patterns, with regional differences related to the proximity with either putative granular or agranular regions. Hum Brain Mapp 33:2005–2034, 2012.

Cortical depth-dependent temporal dynamics of the BOLD response in the human brain

Recent animal studies at high field have shown that blood oxygen level-dependent (BOLD) contrast can be specific to the laminar vascular architecture of the cortex, by differences in its temporal dynamics in reference to cortical depth. In this study, we characterize the temporal dynamics of the hemodynamic response (HDR) across cortical depth in the human primary motor and visual cortex, at 7T and using very short stimuli and with high spatial and temporal resolution. We find that the shape and temporal dynamics of the HDR changed in an orderly manner across cortical depth. Compared with the pial vasculature, HDRs in deeper gray matter are significantly faster in onset time (by ∼ 0.5 second) and peak time (∼2 seconds), and are narrower (by ∼1 second) and with smaller amplitude, in line with the known vascular organization across cortical depth and the transit of deoxygenated blood through the vasculature. The width of the HDR in deeper gray matter was as short as 2.1 seconds, indicating that neurovascular coupling takes place at a shorter timescale than previously reported in the human brain. These findings open the possibility to probe layer-specific hemodynamics and neurovascular coupling mechanisms in human gray matter.

BOLD matches neuronal activity at the mm scale: A combined 7 T fMRI and ECoG study in human sensorimotor cortex

High resolution BOLD fMRI has the potential to map activation patterns of small neuronal populations at the scale of cortical columns. However, BOLD fMRI does not measure neuronal activity, but only a correlate thereof, since it measures blood dynamics. To confirm that BOLD activation maps reflect neuronal population activity patterns, a direct comparison with neuro-electrophysiological data from the same cortical patch is necessary. Here, we compare BOLD activation patterns obtained with fMRI at 7 T to electrophysiological patterns obtained with implanted high density electrocorticography (ECoG) grids in the same patch of human sensorimotor cortex, and with similar resolution (1.5mm). We used high spatially sampled high-frequency broadband (HFB) power from ECoG, which reflects local neuronal population activity. The spatial distribution of 7 T BOLD activation matched the spatial distribution of ECoG HFB-power changes in the covered patch of sensorimotor cortex. BOLD fMRI activation foci were located within 1-3mm of the HFB-power ECoG foci. Both methods distinguished individual finger movement activation within a 1cm cortical patch, revealing a topographical medial to lateral layout for the little finger to index to thumb. These findings demonstrate that the BOLD signal at 7 T is strongly correlated with the underlying electrophysiology, and is capable of discriminating patterns of neuronal population activity at a millimeter scale. The results further indicate the utility of 7 T fMRI for investigation of intra-area organization of function and network dynamics.

Bolus arrival time and cerebral blood flow responses to hypercarbia

The purpose of this study was to evaluate how cerebral blood flow and bolus arrival time (BAT) measures derived from arterial spin labeling (ASL) MRI data change for different hypercarbic gas stimuli. Pseudocontinuous ASL (pCASL) was applied (3.0T; spatial resolution = 4 × 4 × 7 mm 3 ; repetition time/echo time (TR/TE) = 3,600/11 ms) sequentially in healthy volunteers (n = 12; age = 30±4 years) for separate experiments in which (i) normocarbic normoxia (i.e., room air), hypercarbic normoxia (i.e., 5% CO2/21% O2/74% N2), and hypercarbic hyperoxia (i.e., carbogen: 5% CO2/95% O2) gas was administered (12 L/minute). Cerebral blood flow and BAT changes were quantified using models that account for macrovascular signal and partial volume effects in all gray matter and regionally in cerebellar, temporal, occipital, frontal, and parietal lobes. Regional reductions in BAT of 4.6% to 7.7% and 3.3% to 6.6% were found in response to hypercarbic normoxia and hypercarbic hyperoxia, respectively. Cerebral blood flow increased by 8.2% to 27.8% and 3.5% to 19.8% for hypercarbic normoxia and hypercarbic hyperoxia, respectively. These findings indicate that changes in BAT values may bias functional ASL data and thus should be considered when choosing appropriate experimental parameters in calibrated functional magnetic resonance imaging or ASL cerebrovascular reactivity experiments that use hypercarbic gas stimuli.

High‐field MRS of the human brain at short TE and TR

In vivo MRS of the human brain at 7 tesla allows identification of a large number of metabolites at higher spatial resolutions than currently possible at lower field strengths. However, several challenges complicate in vivo localization and artifact suppression in MRS at high spatial resolution within a clinically feasible scan time at 7 tesla. Published MRS sequences at 7 tesla suffer from long echo times, inherent signal‐to‐noise ratio (SNR) loss, large chemical shift displacement artifacts or long repetition times because of excessive radiofrequency (RF) power deposition. In the present study a pulse‐acquire sequence was used that does not suffer from these high field drawbacks. A slice selective excitation combined with high resolution chemical shift imaging for in‐plane localization was used to limit chemical shift displacement artifacts. The pulse‐acquire approach resulted in a very short echo time of 1.4 ms. A cost function guided shimming algorithm was developed to constrain frequency offsets in the excited slice, therefore adiabatic frequency selective suppression could be employed to minimize artifacts from high intensity lipids and water signals in the excited slice. The high sensitivity at a TR of 1 s was demonstrated both on a supraventricular slice as well as in an area very close to the skull in the frontal cortex at a nominal spatial resolution of 0.25 cc within a feasible scan time. Copyright

BOLD Consistently Matches Electrophysiology in Human Sensorimotor Cortex at Increasing Movement Rates: A Combined 7T fMRI and ECoG Study on Neurovascular Coupling

Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used to measure human brain function and relies on the assumption that hemodynamic changes mirror the underlying neuronal activity. However, an often reported saturation of the BOLD response at high movement rates has led to the notion of a mismatch in neurovascular coupling. We combined BOLD fMRI at 7T and intracranial electrocorticography (ECoG) to assess the relationship between BOLD and neuronal population activity in human sensorimotor cortex using a motor task with increasing movement rates. Though linear models failed to predict BOLD responses from the task, the measured BOLD and ECoG responses from the same tissue were in good agreement. Electrocorticography explained almost 80% of the mismatch between measured- and model-predicted BOLD responses, indicating that in human sensorimotor cortex, a large portion of the BOLD nonlinearity with respect to behavior (movement rate) is well predicted by electrophysiology. The results further suggest that other reported examples of BOLD mismatch may be related to neuronal processes, rather than to neurovascular uncoupling.

Investigating the non-linearity of the BOLD cerebrovascular reactivity response to targeted hypo/hypercapnia at 7 T

Cerebrovascular reactivity (CVR) is a mechanism responsible for maintaining stable perfusion pressure within the brain via smooth muscle mediated modulations of vascular tone. The amplitude of cerebral blood flow (CBF) change in response to a stimulus has been evaluated using Blood Oxygen Level Dependent (BOLD) MRI, however the relationship between the stimulus and the measured signal remains unclear. CVR measured invasively in animal models and using blood-velocity based measurements in humans has demonstrated a sigmoidal relationship between cerebral blood flow and CO2 partial pressure. Using an ultra-high magnetic field strength (7T) MRI scanner and a computer controlled gas delivery system, we examined the regional and voxel-wise CVR response in relation to a targeted progressively increasing hypo- to hypercapnic stimulus. The aim of this study was to assess the non-linearity/sigmoidal behavior of the CVR response at varying arterial CO2 (PaCO2) levels. We find that a sigmoidal model provides a better description of the BOLD signal response to increasing PaCO2 than a linear model. A distinct whole-brain and gray matter BOLD-CVR signal plateau was observed in both voxel-wise and regional analysis. Furthermore, we demonstrate that a progressively increasing stimulus in combination with a sigmoidal response model can be used to obtain CVR values and provides additional physiologically relevant information (such as linear and non-linear response domains, and maximum response amplitudes) that may be more difficult to obtain from blocked CVR experiments. Considering these results, we propose an alternative way in which to define CVR based on the derivative of the BOLD-CVR response curve, which can potentially be used to differentiate between healthy and diseased vascular states.

BOLD specificity and dynamics evaluated in humans at 7 T: comparing gradient-echo and spin-echo hemodynamic responses.

High-field gradient-echo (GE) BOLD fMRI enables very high resolution imaging, and has great potential for detailed investigations of brain function. However, as spatial resolution increases, confounds due to signal from non-capillary vessels increasingly impact the fidelity of GE BOLD fMRI signals. Here we report on an assessment of the microvascular weighting of the GE BOLD response across the cortical depth in human cortex using spin-echo fMRI which is thought to be dominated by microvasculature (albeit not completely). BOLD responses were measured with a hemodynamic impulse response (HRF) obtained from the spin-echo (SE) and gradient-echo (GE) BOLD contrast using very short stimuli (0.25 s) and a fast event-related functional paradigm. We show that the onset (∼1.25 s) and the rising slope of the GE and SE HRFs are strikingly similar for voxels in deep gray matter presumably containing the most metabolically demanding neurons (layers III–IV). This finding provides a strong indication that the onset of the GE HRF in deep gray matter is predominantly associated with microvasculature.

Examining the regional and cerebral depth-dependent BOLD cerebrovascular reactivity response at 7 T

Changes in cerebral blood flow (CBF) in response to hypercapnia induced changes in vascular tone, known as cerebrovascular reactivity (CVR), can be measured using the Blood Oxygenation Level Dependent (BOLD) MR contrast. We examine regional differences in the BOLD-CVR response to a progressively increasing hypercapnic stimulus as well as regional BOLD characteristics for the return to baseline normocapnia. CVR across 9 subjects was highest in the cerebral lobes and deep gray matter. Peak CVR in these regions was measured at 3.6±1.6mmHg above baseline end-tidal CO2. White matter CVR was generally reduced compared to that of the gray matter (peak white matter CVR was ~48% lower). A positive relationship between the end-tidal CO2 value at which peak CVR was measured and white matter depth is observed. Furthermore, the time required for the BOLD signal to return to baseline after cessation of the hypercapnic stimulus, was also related to white matter depth; the return, expressed as a time constant, was ~25% longer in white matter. To explain the observed differences in regional CVR response, a model is proposed that takes into account the local architecture of the cerebrovascular, which can result in changes in regional blood flow distribution as a function of end-tidal CO2.

Cortical depth dependence of the BOLD initial dip and poststimulus undershoot in human visual cortex at 7 Tesla

Owing to variability in vascular dynamics across cerebral cortex, blood‐oxygenation‐level‐dependent (BOLD) spatial and temporal characteristics should vary as a function of cortical‐depth. Here, the positive response, initial dip (ID), and post‐stimulus undershoot (PSU) of the BOLD response in human visual cortex are investigated as a function of cortical depth and stimulus duration at 7 Tesla (T).