Optimized preoperative motor cortex mapping in brain tumors using advanced processing of transcranial magnetic stimulation data.

BACKGROUND AND OBJECTIVE: Transcranial magnetic stimulation (TMS) is a useful technique to help localize motor function prior to neurosurgical procedures. Adequate modelling of the effect of TMS on the brain is a prerequisite to obtain reliable data. METHODS: Twelve patients were included with perirolandic tumors to undergo TMS-based motor mapping. Several models were developed to analyze the mapping data, from a projection to the nearest brain surface to motor evoked potential (MEP) amplitude informed weighted average of the induced electric fields over a multilayer detailed individual head model. The probability maps were compared with direct cortical stimulation (DCS) data in all patients for the hand and in three for the foot. The gold standard was defined as the results of the DCS sampling (with on average 8 DCS-points per surgery) extrapolated over the exposed cortex (of the tailored craniotomy), and the outcome parameters were based on the similarity of the probability maps with this gold standard. RESULTS: All models accurately gauge the location of the motor cortex, with point-cloud based mapping algorithms having an accuracy of 83-86%, with similarly high specificity. To delineate the whole area of the motor cortex representation, the model based on the weighted average of the induced electric fields calculated with a realistic head model performs best. The optimal single threshold to visualize the field based maps is 40% of the maximal value for the anisotropic model and 50% for the isotropic model, but dynamic thresholding adds information for clinical practice. CONCLUSIONS: The method with which TMS mapping data are analyzed clearly affects the predicted area of the primary motor cortex representation. Realistic electric field based modelling is feasible in clinical practice and improves delineation of the motor cortex representation compared to more simple point-cloud based methods.

Large field-of-view movement-compensated intrinsic optical signal imaging for the characterization of the haemodynamic response to spreading depolarizations in large gyrencephalic brains.

Haemodynamic responses to spreading depolarizations (SDs) have an important role during the development of secondary brain damage. Characterization of the haemodynamic responses in larger brains, however, is difficult due to movement artefacts. Intrinsic optical signal (IOS) imaging, laser speckle flowmetry (LSF) and electrocorticography were performed in different configurations in three groups of in total 18 swine. SDs were elicited by topical application of KCl or occurred spontaneously after middle cerebral artery occlusion. Movement artefacts in IOS were compensated by an elastic registration algorithm during post-processing. Using movement-compensated IOS, we were able to differentiate between four components of optical changes, corresponding closely with haemodynamic variations measured by LSF. Compared with ECoG and LSF, our setup provides higher spatial and temporal resolution, as well as a better signal-to-noise ratio. Using IOS alone, we could identify the different zones of infarction in a large gyrencephalic middle cerebral artery occlusion pig model. We strongly suggest movement-compensated IOS for the investigation of the role of haemodynamic responses to SDs during the development of secondary brain damage and in particular to examine the effect of potential therapeutic interventions in gyrencephalic brains.

Regulation of cerebral metabolism during cortical spreading depression.

We analyzed the metabolic response to cortical spreading depression that drastically increases local energy demand to restore ion homeostasis. During single and multiple cortical spreading depressions in the rat cortex, we simultaneously monitored extracellular levels of glucose and lactate using rapid sampling microdialysis and glucose influx using 18 F-fluorodeoxyglucose positron emission tomography while tracking cortical spreading depression using laser speckle imaging. Combining the acquired data with steady-state requirements we developed a mass-conserving compartment model including neurons and glia that was consistent with the observed data. In summary, our findings are: (1) Early breakdown of glial glycogen provides a major source of energy during increased energy demand and leaves 80% of blood-borne glucose to neurons. (2) Lactate is used solely by neurons and only if extracellular lactate levels are >80% above normal. (3) Although the ratio of oxygen and glucose consumption transiently reaches levels <3, the major part (>90%) of the overall energy supply is from oxidative metabolism. (4) During cortical spreading depression, brain release of lactate exceeds its consumption suggesting that lactate is only a circumstantial energy substrate. Our findings provide a general scenario for the metabolic response to increased cerebral energy demand.

Detecting tissue deterioration after brain injury: regional blood flow level versus capacity to raise blood flow.

Regional cerebral blood flow (rCBF) is spatially and temporally adjusted to local energy needs. This coupling involves dilation of vessels both at the site of metabolite exchange and upstream of the activated region. Deficits in upstream blood supply limit the 'capacity to raise rCBF' in response to functional activation and therefore compromise brain function. We here demonstrate in rats that the 'capacity to raise rCBF' can be determined from real-time measurements of rCBF using laser speckle imaging during an energy challenge induced by cortical spreading depolarizations (CSDs). Cortical spreading depolarizations (CSDs) occur with high incidence in stroke and various other brain injuries and cause large metabolic changes. Various conditions of cerebral perfusion were induced, either by modifying microvascular tone, or by altering upstream blood supply independently. The increase in rCBF per unit of time in response to CSD was linearly correlated to the upstream blood supply. In an experimental model of stroke, we found that this marker of the capacity to raise rCBF which, in pathologic tissue may be additionally limited by impaired vasoactive signaling, was a better indicator of the functional status of cerebral tissue than local rCBF levels.

Isoflurane suppresses cortical spreading depolarizations compared to propofol--implications for sedation of neurocritical care patients.

Sedatives in the neurointensive care unit can strongly influence patients' risks of developing secondary brain damage. In particular, isoflurane, a volatile anesthetic, has been recently re-introduced to the neurointensive care unit, and first clinical studies suggest beneficial effects due to elevation of cerebral blood flow and reduction of metabolism. In contrast, propofol is a commonly used intravenous sedative that reduces cerebral blood flow and intra-cranial pressure. We have here studied the influence of these two sedatives on the occurrence of cortical spreading depolarizations (CSDs), which have emerged over the last decade as a major mechanism of delayed brain injury in stroke and brain trauma, constituting a substantial vascular and metabolic threat to peri-infarct tissue and being associated with poor patient outcome. Two experimental models were tested in Wistar rats anesthetized either with isoflurane or with propofol: KCl-evoked CSDs (n=10) and spontaneous CSDs after occlusion of the middle cerebral artery (n=14). Spatiotemporal patterns of CSD waves were observed by real-time laser speckle imaging of regional cerebral blood flow changes associated with the CSDs. During 30 min of cortical KCl application, 5.2±0.7 CSDs were induced under isoflurane compared to 10.2±1.8 CSDs under propofol (p<0.001). After focal ischemia, 2.43±1.0 CSDs/h emerged spontaneously under isoflurane versus 6.83±2.5 CSDs/h under propofol (p<0.001). Furthermore, baseline blood flow and glycemia were much higher under isoflurane compared to propofol, which may set the tissue in better metabolic conditions to recover from the occurrence of CSD waves. We conclude that isoflurane, in comparison to propofol, decreases the occurrence of CSDs and may improve recovery from these metabolically demanding waves. To reduce CSD induced secondary tissue damage, we suggest isoflurane to be favored over propofol to sedate acute stroke and trauma patients in the neurointensive care unit.

Mismatch responses in the awake rat: evidence from epidural recordings of auditory cortical fields.

Detecting sudden environmental changes is crucial for the survival of humans and animals. In the human auditory system the mismatch negativity (MMN), a component of auditory evoked potentials (AEPs), reflects the violation of predictable stimulus regularities, established by the previous auditory sequence. Given the considerable potentiality of the MMN for clinical applications, establishing valid animal models that allow for detailed investigation of its neurophysiological mechanisms is important. Rodent studies, so far almost exclusively under anesthesia, have not provided decisive evidence whether an MMN analogue exists in rats. This may be due to several factors, including the effect of anesthesia. We therefore used epidural recordings in awake black hooded rats, from two auditory cortical areas in both hemispheres, and with bandpass filtered noise stimuli that were optimized in frequency and duration for eliciting MMN in rats. Using a classical oddball paradigm with frequency deviants, we detected mismatch responses at all four electrodes in primary and secondary auditory cortex, with morphological and functional properties similar to those known in humans, i.e., large amplitude biphasic differences that increased in amplitude with decreasing deviant probability. These mismatch responses significantly diminished in a control condition that removed the predictive context while controlling for presentation rate of the deviants. While our present study does not allow for disambiguating precisely the relative contribution of adaptation and prediction error processing to the observed mismatch responses, it demonstrates that MMN-like potentials can be obtained in awake and unrestrained rats.