Nociceptive activation in spinal cord and brain persists during deep general anaesthesia.

BACKGROUND: In clinical practice, analgesic drug doses applied during general anaesthesia are considered sufficient when clinical responses (e.g. movement, blood pressure and heart rate elevations) are suppressed during noxious stimulation. We investigated whether absent clinical responses are indicative of suppressed spinal and brain responsiveness to noxious stimulation in anaesthetised subjects. METHODS: Ten healthy volunteers were investigated during deep propofol anaesthesia supplemented with increasing doses of remifentanil in a stepwise manner. Noxious electrical stimuli at an intensity comparable with surgical stimulation were repeatedly administered at each targeted remifentanil concentration. During stimulation, we monitored both clinical responses (blood pressure, heart rate, and movement) and neuronal responses. Neuronal responses were assessed using functional magnetic resonance imaging, spinal reflex responses, and somatosensory evoked potentials. RESULTS: This monitoring combination was able to faithfully detect brain and spinal neuronal responses to the noxious stimulation. Although clinical responses were no longer detected at analgesic dosages similar to those used for general anaesthesia in clinical practice, spinal and brain neuronal responses were consistently observed. Opioid doses that are significantly larger than is usually used in clinical practice only reduced neuronal responses to 41% of their maximal response. CONCLUSIONS: Nociceptive activation persists during deep general anaesthesia despite abolished clinical responses. Absent clinical responses are therefore not indicative of absent nociception-specific activation. Thus, commonly accepted clinical responses might be inadequate surrogate markers to assess anti-nociception during general anaesthesia. Further research is required to investigate whether persistent nociception causes adverse effects on patient outcome.

Estimating the transfer function from neuronal activity to BOLD using simultaneous EEG-fMRI.

Previous studies using combined electrical and hemodynamic measurements of brain activity, such as EEG and (BOLD) fMRI, have yielded discrepant results regarding the relationship between neuronal activity and the associated BOLD response. In particular, some studies suggest that this link, or transfer function, depends on the frequency content of neuronal activity, while others suggest that total neuronal power accounts for the changes in BOLD. Here we explored this dependency by comparing different frequency-dependent and -independent transfer functions, using simultaneous EEG-fMRI. Our results suggest that changes in BOLD are indeed associated with changes in the spectral profile of neuronal activity and that these changes do not arise from one specific spectral band. Instead they result from the dynamics of the various frequency components together, in particular, from the relative power between high and low frequencies. Understanding the nature of the link between neuronal activity and BOLD plays a crucial role in improving the interpretability of BOLD images as well as on the design of more robust and realistic models for the integration of EEG and fMRI.

Robust Bayesian General Linear Models.

We describe a Bayesian learning algorithm for Robust General Linear Models (RGLMs). The noise is modeled as a Mixture of Gaussians rather than the usual single Gaussian. This allows different data points to be associated with different noise levels and effectively provides a robust estimation of regression coefficients. A variational inference framework is used to prevent overfitting and provides a model order selection criterion for noise model order. This allows the RGLM to default to the usual GLM when robustness is not required. The method is compared to other robust regression methods and applied to synthetic data and fMRI.

Dipole source localization and fMRI of simultaneously recorded data applied to somatosensory categorization.

In this study, the feasibility of dipole source localization (DSL) and coregistration with functional magnetic resonance imaging (fMRI) activation patterns on the basis of simultaneously acquired data is demonstrated. Brain activity was mapped during the performance of a somatosensory single reaction and a choice reaction task at high spatiotemporal resolution in six healthy subjects. The choice reaction task required a categorization of two different stimulus intensities, whereas for the single reaction task merely the perception of a tactile stimulus had to be confirmed by the subjects. An offline artifact correction algorithm was applied to 32-channel EEG data that were acquired between subsequent MRI scans. Using a multiple dipole approach, five distinct dipole sources were identified within areas of the somatosensory system. Coregistration of fMRI and DSL showed consistent spatial activation patterns with a mean distance of 9.2 +/- 6.8 mm between dipole sources and fMRI activation maxima. However, since the number of fMRI activation sites exceeded the number of cerebral dipole sources, it was not possible to assign a dipole source to each fMRI activation site. Dipole moment time courses were consistent with previously reported results of similar experiments. A comparison of brain activation patterns during the two tasks with both fMRI and DSL indicated an involvement of the contralateral secondary somatosensory cortex in somatosensory categorization.

Intracerebral pH affects the T2 relaxation time of brain tissue.

Signal changes in activated brain areas are detectable by MRI and MR spectroscopy (MRS). Shifts in pH occur during brain activation. Our aim was to investigate the relationship between changes in pH and T2 relaxation times. T2 was determined in vitro at 24 MHz in various liquids at different pH using a Carr-Purcell-Meiboom-Gill (CPMG) spin-echo sequence. We also studied five Fisher rats were studied at 2.4 tesla with a double-tuneable surface coil. After baseline measurements, potassium cyanide was injected, producing intracerebral acidosis. Alternating series of 1H CPMG spin-echo sequences and 31P spectra were acquired. True T2 relaxation times were calculated from a CPMG multi-echo train. Changes in intracellular pH determined from 31P spectra. In vitro measurements demonstrated a correlation between T2 and pH that could be described by a quadratic fit curve. Depending on the initial pH, changes of 0.2 induced changes in T2 of up to 150 ms. In vivo measurements confirmed these findings. After intraperitoneal injection of a sublethal dose of cyanide, T2 decreased by about 5% in four cases, followed by recovery after 2 h. The in vitro measurements demonstrated that changes in pH can lead to significant signal change on T2- or T2*- weighted images. The dependence of T2 on pH in vitro was confirmed in vivo; it may contribute to signal change in activated brain areas.