The Influence of Moderate Hypercapnia on Neural Activity in the Anesthetized Nonhuman Primate

Hypercapnia is often used as vasodilatory challenge in clinical applications and basic research. In functional magnetic resonance imaging (fMRI), elevated CO2 is applied to derive stimulus-induced changes in the cerebral rate of oxygen consumption (CMRO2) by measuring cerebral blood flow and blood-oxygenation-level–dependent (BOLD) signal. Such methods, however, assume that hypercapnia has no direct effect on CMRO2. In this study, we used combined intracortical recordings and fMRI in the visual cortex of anesthetized macaque monkeys to show that spontaneous neuronal activity is in fact significantly reduced by moderate hypercapnia. As expected, measurement of cerebral blood volume using an exogenous contrast agent and of BOLD signal showed that both are increased during hypercapnia. In contrast to this, spontaneous fluctuations of local field potentials in the beta and gamma frequency range as well as multiunit activity are reduced by ∼15% during inhalation of 6% CO2 (pCO2 = 56 mmHg). A strong tendency toward a reduction of neuronal activity was also found at CO2 inhalation of 3% (pCO2 = 45 mmHg). This suggests that CMRO2 might be reduced during hypercapnia and caution must be exercised when hypercapnia is applied to calibrate the BOLD signal

Measurements on the visual system of a proband

Described is an eye monitoring device (300) for inductive orientation measuring on an eye (2) of a proband (1), in particular for use in combination with a magnetic resonance tomography unit (200), wherein said eye monitoring device (300) comprises: a transmitting device (320, 310) which is adapted for generating a magnetic field which changes over time, with which magnetic field an induction voltage can be induced in a receiving device (310, 320); a generator device (330) for generating at least one excitation voltage for the transmitting device (320, 310); and a signal processing device (350) for processing induction voltage signals of the receiving device (310, 320), wherein one of the transmitting or receiving devices comprises an eye coil device (310) with an eye coil (311) which can be connected to the eye (2) and which is movable with said eye (2), while the other one of the transmitting or receiving devices comprises a visual-field coil device (320) with at least one visual-field coil (321, 322) which is smaller than the head (3) of a proband (1) and which is equipped during the process of measuring to be arranged so as to be fixed in front of the eye (2), adjacent to a field of view of said eye (2). Also described is an examination device which comprises an eye monitoring device for inductive eye-orientation measuring, as well as a magnetic resonance tomography unit

Methods and devices for measuring electrical currents

A method of eliminating interfering currents in a measuring system being adapted for simultaneous recording electrophysiological signals and measuring fNMR images, comprises the steps of (a) using an electrode device with a rotational symmetry, (b) using a Sp02-sensor that does not contain any conducting materials, said Sp02-sensor operating with fibre-optic components, (c) using metal wires for grounding infusion solutions, (d) providing ring capacitances for rf shielding on signal lines, (e) providing decoupling resistors for ECG measurements, (f) injecting compensation currents being generated on the basis of detected reference signals, and/or (g) using a current voltage converter being subjected to active interference compensation. Furthermore, methods of measuring and amplifying electrical currents as well as circuits and devices for implementing the above methods are described

Combined neurophysiology and fMRI in the awake monkey

Simultaneous intracortical recordings of neural activity (NA) and BOLD responses in the anaesthetized monkey (Logothetis et al,2001)demonstrated various degrees of correlation between the fMRI data and LFP,MUA and SUA. The present work is a further step in the study of the relationship of BOLD to NA in the behaving monkey in a vertical-bore 7T/60cm scanner equipped with a 38-cm gradient insert (80mT/m,130us, Bruker Inc.). The upright positioning of the animal used in every alert monkey laboratory was also chosen for fMRI to minimize discomfort in the monkeys, expedite their training process, and ensure longer cooperation during psychophysical testing. Here, the monkeys were first trained to perform a fixation task (Wurtz, 1969) using juice as a reward. Stimuli were presented through a fiber-optic system (Silent Vision, FL), and eye movements were measured with the iView eye tracking system (SensorMotoric Inst.,GmbH). During data acquisition suction of juice and body movements were prevented by using a number of pressure and motion sensors and by training the animal to remain relaxed during the observation period. MR-compatible plastic chambers and electrodes made of platinum-iridium coated with glass were used for intracortical recordings. Gradient-induced interference was compensated with custom-made electronics (Patent 01116436.5). Brief pulse stimulation with full-field patterns and small stimuli placed within the receptive field of each recording site was used to elicit cortical responses followed by a BOLD response. The correlation of BOLD to different frequency bands with different spatio-temporal stimulation patterns will be discussed

A novel functional magnetic resonance imaging compatible search-coil eye-tracking system

Measuring eye movements (EMs) using the search-coil eye-tracking technique is superior to video-based infrared methods [Collewijn H, van der Mark F, Jansen TC. Precise recording of human eye movements. Vision Res 1975;15(3):447-50], which suffer from the instability of pupil size, blinking behavior and lower temporal resolution. However, no conventional functional magnetic resonance imaging (fMRI)-compatible search-coil eye tracker exists. The main problems for such a technique are the interaction between the transmitter coils and the magnetic gradients used for imaging as well as the limited amount of space in a scanner. Here we present an approach to overcome these problems and we demonstrate a method to record EMs in an MRI scanner using a search coil. The system described has a spatial resolution of 0.07° (visual angle) and a high temporal resolution (22 kHz). The transmitter coils are integrated into the visual presentation system and the control/analysis unit is portable, which enables us to integrate the eye tracker with an MRI scanner. Our tests demonstrate low noise in the recorded eye traces and scanning with minimal artifact. Furthermore, the induced current in the search coil caused by the RF pulses does not lead to measurable heating. Altogether, this MR-compatible search-coil eye tracker can be used to precisely monitor EMs with high spatial and temporal resolution during fMRI. It can therefore be of great importance for studies requiring accurate fixation of a target, or measurement and study of the subject‘s oculomotor system

Simultaneous recording of neuronal signals and functional NMR imaging

We recently directly examined the relationship between blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals and neural activity by simultaneously acquiring electrophysiological and fMRI data from monkeys in a 4.7-T vertical scanner (Logothetis NK, Pauls J, Augath MA, Trinath T, Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal. Nature 2001;412:150–157). Acquisition of electrical signals in the microvolt range required extensive development of new recording hardware, including electrodes, microdrives, signal conditioning and interference compensation devices. Here, we provide a detailed description of the interference compensation system that can be used to record field and action potentials intracortically within a high-field scanner

In vivo measurement of cortical impedance spectrum in monkeys: implications for signal propagation

Logothetis NK, Kayser C, Oeltermann A. In vivo measurement of cortical impedance spectrum in monkeys: implications for signal propagation. Neuron. 2007;55(5):809-23

Sustained negative BOLD response in the monkey brain

n a previous fMRI study (Shmuel et al., HBM 2001), a robust sustained negative BOLD response (NBR) and blood flow response was detected in the human occipital cortex. Here we report on a sustained (different from the initial dip) NBR in areas V1, V2, and V3 of the macaque. Anesthetized monkeys were presented in 4 cycles with a rotating polar checker pattern (48 s) followed by a blank gray image (48 s). Fifteen axial slices were imaged (GE-EPI, 4.7 T, 0.750.752 mm, TR=.75 s, 6 s/volume). In response to stimulation at 0-10 eccentricity, a positive BOLD response (PBR) and NBR were observed within the central and peripheral visual representation, respectively. The NBR was found preferentially in gray matter and was spatially reproducible across subjects. The time course of the NBR and PBR (mean amplitude ratio 0.5) were similar, suggesting similar mechanisms. Initial results from simultaneous fMRI and electrophysiology demonstrated NBR in 3 regions where no robust changes in electrical activity occurred. We are currently pursuing additional fMRI-electrophysiology experiments. Discussion 1) Robust NBR exists in the monkey brain. 2) Since the activity in the periphery is not expected to increase, the NBR here is the result of a decrease in blood flow rather than increase in oxygen consumption

BOLD responses evoked by electrical stimulation of Locus Coeruleus in rats under anesthesia

We performed a whole-brain fMRI imaging in the rat under urethane anesthesia and studied BOLD responses induced by electrical stimulation of the brain stem noradrenergic nucleus Locus Coeruleus (LC). The rat was implanted with a MRI-compatible custom-made iridium electrode into LC under electrophysiological guidance. A 7T (300 MHz) magnet with a 30-cm horizontal bore (Bruker BioSpec 70/30, Ettlingen, Germany) equipped with a 20cm inner diameter gradient (Bruker BGA-20S Ettlingen, Germany) was used for MRI scanning. The experimental paradigm consisted of 6s baseline sampling, followed by 4s of unilateral LC stimulation and 10s of post-stimulus sampling. Biphasic square pulses (0.05-0.4mA) were delivered to LC at 20-100Hz either continuously for 4s or grouped in 100-500ms trains. These stimulation parameters were efficient in eliciting LC burst firing bilaterally. We also collected BOLD responses induced by peripheral sensory stimulation in the same animal and using the same experimental design (6/4/10s). For visual stimulation we used a luminance flicker presented to both eyes at 16Hz and delivered via fiber optic cables. A mild electrical stimulation (1-5mA) of a forepaw was used as somatosensory stimulation. The fMRI images were collected with spatial resolution of 0.4x0.4x1.0mm and temporal resolution of 1s. BOLD maps were generated by using GLM with standard (HRF-convolved boxcar functions) or neural regressors. We observed a remarkable dichotomy between BOLD responses of cortical and subcortical structures. Specifically, LC stimulation produced positive BOLD responses in the majority of structures belonging to metencephalon, mesencephalon and diencephalon, while negative BOLD responses in the entire neocortex. The robust neuronal activation in thalamic projections of LC was further confirmed by electrophysiological recordings. The cortical inhibition as a result of LC stimulation and associated NE release in cortical targets of LC has been reported in earlier studies. The peripheral sensory stimulation evoked both sensory-specific and non-specific activation/deactivation pattern. Strikingly, the regions of non-specific BOLD responses were common for both sensory modalities and largely overlapped with brain regions that showed responses to LC stimulation. We hypothesize that sensory stimulation activates modality-specific sensory pathways along with LC-NE system; and the LC co-activation produces the observed non-specific BOLD responses