David G. Norris

An Investigation of Functional and Anatomical Connectivity Using Magnetic Resonance Imaging

This article examines functional and anatomical connectivity in healthy human subjects measured with magnetic resonance imaging methods. Anatomical connectivity in white matter is obtained from measurements of the diffusion tensor. A Monte-Carlo simulation determines the probability that a particle diffuses between two points, with the probability of a jump in a particular direction from a given voxel being based on the local value of the diffusion tensor components. Functional connectivity between grey matter pixels is assessed without recourse to a specific activation paradigm, by calculating the correlation coefficient between random fluctuations in the blood oxygenation level-dependent signal time course in different pixels. The methods are used to examine the anatomical and functional connectivities between crowns of adjacent gyri. A high functional connectivity was found between grey matter pixels, with white matter displaying only very low correlation. A comparison of the measurements of anatomical and functional connectivity found that there is no simple correlation between these measures, except that low values of functional connectivity were not found together with high values of anatomical connectivity. Furthermore pairs of regions situated around the central sulcus indicated a dependence of the two connectivity measures on each other. These results are in accordance with an interpretation that regions which are clearly directly linked by white matter fiber tracts should show high functional connectivity, but that the inverse need not be true as functional connectivity may also be indirectly mediated via more distant grey matter regions.

Evolution of regional changes in apparent diffusion coefficient during focal ischemia of rat brain: the relationship of quantitative diffusion NMR imaging to reduction in cerebral blood flow and metabolic disturbances.

Middle cerebral artery occlusion was performed in rats while the animals were inside the nuclear magnetic resonance (NMR) tomograph. Successful occlusion was confirmed by the collapse of amplitude on an electrocorticogram. The ultrafast NMR imaging technique UFLARE was used to measure the apparent diffusion coefficient (ADC) immediately after the induction of cerebral ischemia. ADC values of normal cortex and caudate-putamen were 726 ± 22 × 10−6 mm2/s and 659 ± 17 × 10−6 mm2/s, respectively. Within minutes of occlusion, a large territory with reduced ADC became visible in the ipsilateral hemisphere. Over the 2 h observation period, this area grew continuously. Quantitative analysis of the ADC reduction in this region showed a gradual ADC decrease from the periphery to the core, the lowest ADC value amounting to about 60% of control. Two hours after the onset of occlusion, the regional distribution of ATP and tissue pH were determined with bioluminescence and fluorescence techniques, respectively. There was a depletion of ATP in the core of the ischemic territory (32 ± 20% of the hemisphere) and an area of tissue acidosis (57 ± 19% of the hemisphere) spreading beyond that of ATP depletion. Regional CBF (rCBF) was measured autoradiographically with the iodo[14C]antipyrine method. CBF gradually decreased from the periphery to the ischemic core, where it declined to values as low as 5 ml 100 g−1 min−1. When reductions in CBF and in ADC were matched to the corresponding areas of energy breakdown and of tissue acidosis, the region of energy depletion corresponded to a threshold in rCBF of 18 ± 14 ml 100 g−1 min−1 and to an ADC reduction to 77 ± 3% of control. Tissue acidosis corresponded to a flow value below 31 ± 11 ml 100 g−1 min−1 and to an ADC value below 90 ± 4% of control. Thus, the quantification of ADC in the ischemic territory allows the distinction between a core region with total breakdown of energy metabolism and a corona with normal energy balance but severe tissue acidosis.

Neuronal Dynamics Underlying High- and Low-Frequency EEG Oscillations Contribute Independently to the Human BOLD Signal

Work on animals indicates that BOLD is preferentially sensitive to local field potentials, and that it correlates most strongly with gamma band neuronal synchronization. Here we investigate how the BOLD signal in humans performing a cognitive task is related to neuronal synchronization across different frequency bands. We simultaneously recorded EEG and BOLD while subjects engaged in a visual attention task known to induce sustained changes in neuronal synchronization across a wide range of frequencies. Trial-by-trial BOLD fluctuations correlated positively with trial-by-trial fluctuations in high-EEG gamma power (60-80 Hz) and negatively with alpha and beta power. Gamma power on the one hand, and alpha and beta power on the other hand, independently contributed to explaining BOLD variance. These results indicate that the BOLD-gamma coupling observed in animals can be extrapolated to humans performing a task and that neuronal dynamics underlying high- and low-frequency synchronization contribute independently to the BOLD signal.

Trial-by-trial coupling between EEG and BOLD identifies networks related to alpha and theta EEG power increases during working memory maintenance

PET and fMRI experiments have previously shown that several brain regions in the frontal and parietal lobe are involved in working memory maintenance. MEG and EEG experiments have shown parametric increases with load for oscillatory activity in posterior alpha and frontal theta power. In the current study we investigated whether the areas found with fMRI can be associated with these alpha and theta effects by measuring simultaneous EEG and fMRI during a modified Sternberg task This allowed us to correlate EEG at the single trial level with the fMRI BOLD signal by forming a regressor based on single trial alpha and theta power estimates. We observed a right posterior, parametric alpha power increase, which was functionally related to decreases in BOLD in the primary visual cortex and in the posterior part of the right middle temporal gyrus. We relate this finding to the inhibition of neuronal activity that may interfere with WM maintenance. An observed parametric increase in frontal theta power was correlated to a decrease in BOLD in regions that together form the default mode network. We did not observe correlations between oscillatory EEG phenomena and BOLD in the traditional WM areas. In conclusion, the study shows that simultaneous EEG-fMRI recordings can be successfully used to identify the emergence of functional networks in the brain during the execution of a cognitive task.

Persistent schema-dependent hippocampal-neocortical connectivity during memory encoding and postencoding rest in humans

The hippocampus is thought to promote gradual incorporation of novel information into long-term memory by binding, reactivating, and strengthening distributed cortical-cortical connections. Recent studies implicate a key role in this process for hippocampally driven crosstalk with the (ventro)medial prefrontal cortex (vmPFC), which is proposed to become a central node in such representational networks over time. The existence of a relevant prior associative network, or schema, may moreover facilitate this process. Thus, hippocampal-vmPFC crosstalk may support integration of new memories, particularly in the absence of a relevant prior schema. To address this issue, we used functional magnetic resonance imaging (fMRI) and prior schema manipulation to track hippocampal-vmPFC connectivity during encoding and postencoding rest. We manipulated prior schema knowledge by exposing 30 participants to the first part of a movie that was temporally scrambled for 15 participants. The next day, participants underwent fMRI while encoding the movies final 15 min in original order and, subsequently, while resting. Schema knowledge and item recognition performance show that prior schema was successfully and selectively manipulated. Intersubject synchronization (ISS) and interregional partial correlation analyses furthermore show that stronger prior schema was associated with more vmPFC ISS and less hippocampal-vmPFC interregional connectivity during encoding. Notably, this connectivity pattern persisted during postencoding rest. These findings suggest that additional crosstalk between hippocampus and vmPFC is required to compensate for difficulty integrating novel information during encoding and provide tentative support for the notion that functionally relevant hippocampal-neocortical crosstalk persists during off-line periods after learning.

High field human imaging.

This review article examines the state of knowledge regarding human imaging using MRI at high main magnetic field strengths. The article starts with a summary of the technical issues associated with magnetic field strengths in the range of 3–8 T, including magnet characteristics and the properties of radiofrequency magnetic fields, with special reference to sensitivity, power deposition, and homogeneity. The published data on tissue‐water relaxation times in the brain is tabulated and the implications for contrast and pulse sequence implementation is elucidated. The behavior of the major fast imaging sequences, fast low angle shot (FLASH), rapid acquisition with relaxation enhancement (RARE), and echo planar imaging (EPI), is examined in this context. A number of anatomical images from 3 T systems are presented as examples. Particular attention is given to various forms of vascular imaging, namely, time of flight angiography, venography, and arterial spin labeling. The most complex changes in contrast with main magnetic field strength are in activation studies utilizing the blood oxygen level dependent mechanism, which are examined in detail. Improvements in spatial specificity are emphasized, particularly in conjunction with spin‐echo imaging. The article concludes with a discussion of the current status and the potential impact of technical developments such as parallel imaging. J. Magn. Reson. Imaging 2003;18:519–529.

Reduced power multislice MDEFT imaging

A novel method is presented for acquiring multislice T1‐weighted images. The method utilizes non‐slice‐selective inversion pulses followed by a series of slice‐selective excitations. k‐space is divided into a number of segments equal to the number of slices. Successive segments of k‐space are assigned to successive slice‐selective pulses, and the order in which the slices are excited is manipulated to ensure that images of each slice have identical contrast and point spread function (PSF). This method is applied to the MDEFT experiment, a particular version of the inversion recovery experiment. The implications of this acquisition scheme on the PSF are examined, and it is shown that, provided the k‐space modulation function does not change sign, a good PSF is achieved. For a given maximum number of slices, the total experimental duration depends only on TR and the number of phase‐encoding steps. A method of accelerating the experiment by multiply exciting each slice is described. An experimental demonstration of the proposed sequences is given by imaging the human head at 3 T. J. Magn. Reson. Imaging 2000;11:445–451.

Principles of magnetic resonance assessment of brain function

MRI has advanced to being one of the major tools for the assessment of brain function. This review article examines the basic principles that underpin these measurements. The main emphasis is on the characteristics and detection of blood oxygen level dependent (BOLD) contrast. In the first part of the article the relationship between BOLD, blood flow, blood oxygen, and the rate of metabolic consumption of oxygen is described. The four contrast mechanisms that contribute to the BOLD signal change, namely extravascular static and dynamic dephasing, intravascular T2‐like changes, and the intravascular frequency offset effect are described in terms of their spatial localization and relative contributions to the BOLD signal. The current model of changes in blood flow being an indirect consequence of synaptic input to a region is presented. The second section of the article deals with the imaging characteristics of BOLD in terms of the attainable spatial resolution and linear system characteristics. In the third section, practical BOLD imaging is examined for choice of pulse sequence, resolution, echo time (TE), repetition time (TR), and flip angle. The final section touches on other MRI approaches that are relevant to cognitive neuroimaging, in particular the measurement of blood flow, blood volume, resting state fluctuations in the BOLD signal, and measures of connectivity using diffusion tensor imaging and fiber‐tracking. J. Magn. Reson. Imaging 2006.

Topographical Functional Connectivity Pattern in the Perisylvian Language Networks

We performed a resting-state functional connectivity study to investigate directly the functional correlations within the perisylvian language networks by seeding from 3 subregions of Brocas complex (pars opercularis, pars triangularis, and pars orbitalis) and their right hemisphere homologues. A clear topographical functional connectivity pattern in the left middle frontal, parietal, and temporal areas was revealed for the 3 left seeds. This is the first demonstration that a functional connectivity topology can be observed in the perisylvian language networks. The results support the assumption of the functional division for phonology, syntax, and semantics of Brocas complex as proposed by the memory, unification, and control (MUC) model and indicated a topographical functional organization in the perisylvian language networks, which suggests a possible division of labor for phonological, syntactic, and semantic function in the left frontal, parietal, and temporal areas.

An Investigation of the Value of Spin-Echo-Based fMRI Using a Stroop Color–Word Matching Task and EPI at 3 T

This study examines the value of spin-echo-based fMRI for cognitive studies at the main magnetic field strength of 3 T using a spin-echo EPI (SE-EPI) sequence and a Stroop color-word matching task. SE-EPI has the potential advantage over conventional gradient-echo EPI (GE-EPI) that signal losses caused by dephasing through the slice are not present, and hence although image distortion will be the same as for an equivalent GE-EPI sequence, signal voids will be eliminated. The functional contrast in SE-EPI will be lower than for GE-EPI, as static dephasing effects do not contribute. As an auxiliary experiment interleaved diffusion-weighted and non-diffusion-weighted SE-EPI was performed in the visual cortex to further elucidate the mechanims of functional contrast. In the Stroop experiment activation was detected in all areas previously found using GE-EPI. Additional frontopolar and ventral frontomedian activations were also found, which could not be detected using GE-EPI. The experiments from visual cortex indicated that at 3 T the BOLD signal change has contributions from the extravascular space and larger blood vessels in roughly equal amounts. In comparison with GE-EPI the absence of static dephasing effects would seem to result in a superior intrinsic spatial resolution. In conclusion the sensitivity of SE-EPI at 3 T is sufficient to make it the method of choice for fMR studies that require a high degree of spatial localization or where the requirement is to detect activation in regions affected by strong susceptibility gradients.