T Steudel

Hippocampal–cortical interaction during periods of subcortical silence

Hippocampal ripples, episodic high-frequency field-potential oscillations primarily occurring during sleep and calmness, have been described in mice, rats, rabbits, monkeys and humans, and so far they have been associated with retention of previously acquired awake experience. Although hippocampal ripples have been studied in detail using neurophysiological methods, the global effects of ripples on the entire brain remain elusive, primarily owing to a lack of methodologies permitting concurrent hippocampal recordings and whole-brain activity mapping. By combining electrophysiological recordings in hippocampus with ripple-triggered functional magnetic resonance imaging, here we show that most of the cerebral cortex is selectively activated during the ripples, whereas most diencephalic, midbrain and brainstem regions are strongly and consistently inhibited. Analysis of regional temporal response patterns indicates that thalamic activity suppression precedes the hippocampal population burst, which itself is temporally bounded by massive activations of association and primary cortical areas. These findings suggest that during off-line memory consolidation, synergistic thalamocortical activity may be orchestrating a privileged interaction state between hippocampus and cortex by silencing the output of subcortical centres involved in sensory processing or potentially mediating procedural learning. Such a mechanism would cause minimal interference, enabling consolidation of hippocampus-dependent memory.

Coupling of neural activity and fMRI-BOLD in the motion area MT.

The fMRI-BOLD contrast is widely used to study the neural basis of sensory perception and cognition. This signal, however, reflects neural activity only indirectly, and the detailed mechanisms of neurovascular coupling and the neurophysiological correlates of the BOLD signal remain debated. Here we investigate the coupling of BOLD and electrophysiological signals in the motion area MT of the macaque monkey by simultaneously recording both signals. Our results demonstrate that a prominent neuronal response property of area MT, so-called motion opponency, can be used to induce dissociations of BOLD and neuronal firing. During the presentation of a stimulus optimally driving the local neurons, both field potentials [local field potentials (LFPs)] and spiking activity [multi-unit activity (MUA)] correlated with the BOLD signal. When introducing the motion opponency stimulus, however, correlations of MUA with BOLD were much reduced, and LFPs were a much better predictor of the BOLD signal than MUA. In addition, for a subset of recording sites we found positive BOLD and LFP responses in the presence of decreases in MUA, regardless of the stimulus used. Together, these results demonstrate that correlations between BOLD and MUA are dependent on the particular site and stimulus paradigm, and foster the notion that the fMRI-BOLD signal reflects local dendrosomatic processing and synaptic activity rather than principal neuron spiking responses.

Robust controlled functional MRI in alert monkeys at high magnetic field: Effects of jaw and body movements

The use of functional magnetic resonance imaging (fMRI) in alert non-human primates is of great potential for research in systems neuroscience. It can be combined with invasive techniques and afford better understanding of non-invasively acquired brain imaging signals in humans. However, the difficulties in optimal application of alert monkey fMRI are multi-faceted, especially at high magnetic fields where the effects of motion and of changes in B0 are greatly amplified. To overcome these difficulties, strict behavioral controls and elaborate animal-training are needed. Here, we introduce a number of hardware developments, quantify the effect of movements on fMRI data, and present procedures for animal training and scanning for well-controlled and artifact-reduced alert monkey fMRI at high magnetic field. In particular, we describe systems for monitoring jaw and body movements, and for accurately tracking eye movements. A link between body and jaw movement and MRI image artifacts is established, showing that relying on the immobilization of an animals head is not sufficient for high-quality imaging. Quantitative analysis showed that body and jaw movement events caused large instabilities in fMRI time series. On average, body movement events caused larger instabilities than jaw movement events. Residual baseline brain image position and signal amplitude shifts were observed after the jaw and body movement events ended. Based on these findings, we introduce a novel behavioral paradigm that relies on training the monkeys to stay still during long trials. A corresponding analysis method discards all data that were not obtained during the movement-free periods. The baseline position and amplitude shifts are overcome by motion correction and trial-by-trial signal normalization. The advantages of the presented method over conventional scanning and analysis are demonstrated with data obtained at 7 T. It is anticipated that the techniques presented here will prove useful for alert monkey fMRI at any magnetic field.

Frontoparietal activity with minimal decision and control in the awake macaque at 7 T.

Previous imaging work has identified a frontoparietal network in the human brain involved in many different cognitive functions, as well as in simple updates of attended information. To determine whether a similar network is present in the monkey brain and direct future electrophysiological recordings, we examined the activation of frontoparietal areas during visual stimulation in the awake, fixating monkey. We measured activity with BOLD fMRI in three animals and analyzed the data individually for each animal and at group level. We found reliable activations in lateral prefrontal and parietal areas, even though task-related decision making was minimal, as a response to simple update of visual information. These activations were significant for each individual animal, as well as at group level. Similar to human imaging results the update of visual input was enough to activate an extensive network of frontoparietal cortex in the macaque brain, a network which is normally associated with complex cognitive control processes.

Perfusion-based high-resolution fMRI in the primate brain using a novel vertical large-bore 7 Tesla setup

Tomographic qEEG (qEEGt) has recently been introduced for the 3D in vivo visualization of the sources of abnormal EEG oscillations, including those induced by cerebral ischemia. The cross-spectrum of the EEG is used to estimate source spectra at each voxel by means of Brain Electrical Tomography (BET), a Bayesian EEG inverse solution based on anatomical constraints and a suitable smoothness prior. In turn the source spectra are log transformed and compared to age regressed population means and standard deviations by calculating the z score for each voxel and frequency. These values are then imaged using thresholded SPM procedures to map either excess or defect of oscillations at each frequency with respect to the normative database. qEEGT has been shown to correctly identify the anatomical locus of hyper-acute, acute and chronic stroke. It was also shown that the use of statistical images in BET is mandatory due to a depth bias that is only compensated for by mapping statistics rather than raw values of source spectra. The studies just described however used the MNI probabilistic atlas as an anatomical constraint instead of the subjects own MRI and were not compared to either perfusion weighted (PWI) or diffusion weighted (DWI) images. The present study was designed to explore the feasibility of using the subjects individual anatomy as a basis for qEEGT methods and compares the resulting electrophysiological image to DWI and PWI MRI.Two cases of Cruveilhier-Baumgarten syndrome not clinically evident and without esophageal varices in patients with liver cirrhosis and portal hypertension are presented. The diagnosis was made by real-time ultrasonography, which showed echographic caput medusae with large afferent umbilical veins and efferent inferior superficial epigastric veins. Doppler flowmetry documented high blood flow rates in these collateral portal-systemic circulations, and this explained the absence of large varices at endoscopy. The role of massive spontaneous portal-systemic shunts in preventing the formation of other shunts and particularly esophageal variceal bleeding is discussed.