Spectral modulation of cortical connections measured by EEG coherence in humans.

OBJECTIVE: Description of coherence patterns of cortical EEG. METHODS: EEG recordings were collected from 9 subdural electrode grids implanted in 6 patients undergoing EEG monitoring for refractory epilepsy. RESULTS: Coherence decreased with increasing inter-electrode distance and exhibited considerable variability at the same inter-electrode distances. Analysis of variance demonstrated that both spatial and temporal factors contributed significantly (P < 0.01) to this variability. The spatial factor contributed the largest portion (up to 90%) of the variability, and was modulated by frequency and inter-electrode distance. CONCLUSION: The finding that the mean frequency modulation was consistent over time for the same pair of electrodes and was different between different pairs of electrodes indicated a spatial-spectral pattern of cortical synchrony. The connections (pairs of electrodes) could be accordingly predicted from their spatial-spectral pattern, which suggested that the spatial heterogeneity of neuronal synchrony was expressed not only by the degree of synchrony, but also by distinct spectral channels of synchrony. A model based on neuronal connection and activation is proposed to account for the observations.

Epilepsy and consciousness.

Seizure activity has long been associated with alterations in consciousness. Philosophical and neurologic debates concerning the definition of consciousness have led to confusion regarding an adequate third person assessment of a subjective experience. In order to avoid these controversies, neurologic evaluation of consciousness has focused on operational definitions that permit an objective assessment of behavioral responses that are constituent functions of consciousness. Clinical experience has demonstrated that ictal and post-ictal alterations in consciousness may be associated with loss of selected behavioral responses depending upon the focus and spread of seizure activity. Ictal electrophysiologic studies and brain stimulation has assisted in determining the anatomic structures involved in specific behavioral alterations. Consciousness-dependent mental activity can be modeled as a series of interactive parallel information channels that can be selectively disrupted at any stage of processing giving rise to ictal behavioral patterns. While such modeling falls to grasp the subjective nature of consciousness, it offers the clinical community an objective measure of those responses believed to be dependent on consciousness.

Pathogenesis of spinal cord injury during simulated aneurysm repair in a chronic animal model.

The pathogenesis of paraplegia after repair of thoracic aortic aneurysms is controversial. Using direct spinal cord evoked potential monitoring, critical intercostal arteries (CICA) were identified to evaluate the impact of backbleeding and ligation versus that of preservation during simulated aneurysm repair. Thirty pigs (40 kg) were randomly assigned to one of five groups. In groups 1 through 4, a thoracic segment containing CICA was cross-clamped for 60 minutes and distal aortic perfusion was provided by a centrifugal pump. In groups 1 and 2, the thoracic segment was vented, maintaining segment pressure at 0 mm Hg; CICA were ligated in group 1 and preserved in group 2. Thoracic segment was perfused at 70 mm Hg in groups 3 and 4; CICA were ligated in group 3 and preserved in group 4. Critical intercostal artery ligations were performed at the end of the cross-clamp period. In group 5 simple cross-clamping at the left subclavian artery was performed as a control. The combination of venting and ligation of CICA correlated with impaired neurologic outcome according to Tarlov's score (median, 1.5 in group 1 versus 3 in group 2; p = 0.015), indicated by a significant difference in median values of direct spinal cord evoked potential amplitude (expressed as a fraction of baseline values) at 120 minutes after cross-clamping (0.76 in group 1 versus 0.98 in group 2; p = 0.0082).(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral effects of low-flow cardiopulmonary bypass and hypothermic circulatory arrest.

Although both hypothermic circulatory arrest (HCA) and low-flow cardiopulmonary bypass (CPB) are accepted techniques for the operative management of complex cardiovascular pathology, the potential for neurologic sequelae is still a concern. To assess the relative safety of these techniques, we compared cerebral hemodynamics and clinical outcome in two groups of puppies. Sixteen puppies underwent 45 minutes of either HCA or low-flow CPB (25 mL.kg-1.min-1) after cooling to 13 degrees C. Methodology included radioactive microsphere determination of cerebral blood flow; calculation of cerebral oxygen extraction (arteriovenous oxygen content difference) and consumption; measurement of glucose consumption, and determination of cerebrovascular resistance. Measurements were obtained at baseline (37 degrees C), 13 degrees C, and 30 degrees C and at 2, 4, and 8 hours after HCA or low-flow CPB. No neurologic deficits were observed in any of the survivors (15/16). In both groups, cerebral metabolic rate of oxygen was maintained at baseline or greater levels postoperatively. Cerebrovascular resistance rose slightly in the low-flow CPB group postoperatively in contrast to a marked elevation in the HCA group. During the period of high cerebrovascular resistance after HCA, cerebral metabolic rate of oxygen was maintained by increased oxygen extraction. After low-flow CPB, oxygen extraction was not significantly different from baseline, presumably because of less severe changes in cerebrovascular resistance. Glucose metabolism followed the same trends as oxygen metabolism in both groups. These data suggest that after HCA there is a vulnerable interval, lasting as late as 8 hours postoperatively, in which cerebrovascular resistance remains high and cerebral metabolism is maintained primarily by high oxygen and glucose extraction. Any additional stress during this interval (a decrease in arterial oxygen content or perfusion pressure) could result in cerebral injury.

Effect of blood-brain barrier and blood-tumor barrier modification on central nervous system liposomal uptake.

In this study of 25 central nervous system (CNS) tumor-bearing rats, the CNS biodistribution of intravenously administered, indium-labeled liposomes was investigated. In 16 animals, the blood-brain barrier and blood-tumor barrier were modified using intracarotid administration of etoposide. In control animals, analysis by autoradiography and well-counting experiments demonstrated uptake of liposomes in the tumor-bearing hemisphere (% injected dose/g tissue = 0.135) with minimal uptake in the non-tumor-bearing hemisphere (% injected dose/g tissue = 0.007), p < 0.01. Unilateral intracarotid etoposide administration enhanced liposome uptake in both hemispheres-0.215 and 0.023 (tumor-bearing and nontumor-bearing), respectively. The presence of meningeal tumor involvement in nontumor-implanted hemispheres increased liposomal uptake 10-fold. These findings may have clinical applicability in designing therapeutic protocols for the treatment of CNS tumors.

EEG coherence as a predictor of spike propagation.

The relationship between resting EEG coherence and the propagation of spike activity from an experimental cortical focus was investigated in 6 rats. EEG was collected from an array of 6 epicortical electrodes positioned over the posterior hind limb sensorimotor (HL) and frontal (Fr1, Fr2) cortices. Coherence decreased non-linearly for all frequency bands with increasing interelectrode distance. The greatest decrement in coherence occurred in the region corresponding to the junction between hind limb (HL) and frontal (Fr1) cortices. The decrease in coherence was greatest for the highest frequency band for all interelectrode pairs. A spike focus was induced in all 6 animals following the application of bicuculline at the most posterior electrode of the cortical array. In 5 of the 6 animals spike propagation was delayed at the junction of HL and Fr1 cortices, where the greatest decrease in coherence was observed. In one animal spike activity never advanced across this region. These results demonstrate an association between intracortical coherence and the spatial propagation of spike activity. The function of short and long cortico-cortical pathways as mediators of both EEG coherence and cortical spike propagation are discussed.

The effect of graded spinal cord injury on the extrapyramidal and pyramidal motor evoked potentials of the rat.

This study investigated the differential effects of graded spinal cord injury on the rat extrapyramidal motor evoked potential (exp-MEP) and pyramidal motor evoked potential (pyr-MEP) and the prognostic value of these effects in predicting postinjury motor performance in the rat model. In 20 rats subjected to graded spinal injury (10-100 g-cm), there was a differential injury threshold for ablation of exp-MEP and pyr-MEP. All peaks of the pyr-MEP were extinguished in the animals subjected to impact forces of 50 g-cm and above (n = 12). In contrast, the exp-MEP was completely abolished in only two animals at injuries of 80 g-cm or above. A residual exp-MEP response persisted in the remaining 18 animals. Motor performance was monitored in 16 additional animals for up to 1 week after spinal injury. The pyr-MEP was abolished in 100% of the rats subjected to a 50-g cm injury (n = 7), whereas the exp-MEP persisted up to the highest impact forces (80 g-cm). Hind leg paralysis was present in the five rats where the pyr-MEP was extinguished but with persistence of the exp-MEP. An 80% reduction in the amplitude of the pyr-MEP in four animals resulted in mild ataxia with motor improvement at the end of a week. An increase or a 70% loss in pyr-MEP peak amplitude resulted in no clinical motor deficits (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of spinal gray activation by strychnine on the motor evoked potential in the rat.

Spinal motor evoked potentials were elicited by electrical stimulation of the motor cortex in 14 rats before and after the application of strychnine to the surface of the spinal cord. Strychnine applied to the high cervical cord resulted in the emergence of additional peaks at the site of application and in electrodes positioned distally on the middle and lower thoracic cord. The strychnine-induced peaks occurred earlier and were larger in amplitude (P less than 0.01) in the distal spinal cord. Strychnine applied to the lower thoracic cord resulted in similar peak generation in the lower thoracic cord and in the spinal cord proximal to the application of strychnine. These findings demonstrate that strychnine-induced motor evoked potential changes arise from spinal gray activity induced by efferent pathways activated during transcortical stimulation. The role of the propriospinal tract in mediating the distal effects of strychnine is discussed. In conclusion, the strychnine-induced peaks of the motor evoked potential may be used as a measure of spinal gray integrity in experimental spinal cord injury models.

Brain-stem auditory evoked responses in 56 patients with acoustic neurinoma.

The brain-stem auditory evoked responses (BAER's) recorded from 56 patients with acoustic neurinomas were analyzed. Ten of the patients had intracanalicular tumors and 46 had extracanalicular tumors. It was possible to obtain BAER's following stimulation of the affected side in 28 patients and after stimulation of the unaffected side in all 56. Five patients (11%) had normal BAER's following stimulation of both sides; three of these patients had intracanalicular tumors. Among BAER's obtained following stimulation of the affected ear, the mean interpeak latency (IPL) for peaks I to III associated with extracanalicular tumors was significantly prolonged relative to controls (p less than 0.001), and linear regression analysis revealed a significant positive correlation between tumor size and IPL of peaks I to III (p less than 0.05). Analysis of the 56 BAER's recorded after stimulation of the unaffected side revealed a significant positive correlation between the IPL's of peaks III to V and tumor size (p less than 0.001). This correlation was not strengthened when accounting for the degree of brain-stem compression. Finally, evidence of preserved function within the auditory pathway, even in the presence of partial hearing loss, is presented. This finding suggests that more patients might benefit from surgical procedures that spare the eighth cranial nerve.

CNS activation patterns underlying motor evoked potentials as demonstrated by c-fos immunoreactivity.

Monopolar (n = 5) and bipolar (n = 4) electrical stimulation of the motor cortex associated with spinal motor evoked potentials (MEPs) in rats resulted in central nervous system (CNS) staining for c-fos protein. Staining was demonstrated in the cortex, hippocampus, and caudate-putamen, irrespective of the type of stimulation. C-fos protein was demonstrated in the ventral horn cells in 3 animals and in the superficial layer of the posterior horn in 8 animals. Brainstem staining was more frequent and intense in rats stimulated with monopolar electrodes. In contrast to the diffuse and bilateral cortical staining observed with electrical stimulation, motor cortex stimulation by the local application of bicuculline resulted in c-fos protein staining restricted to the stimulated motor cortex. The cerebellum failed to demonstrate c-fos protein following motor cortex stimulation or direct electrical cerebellum stimulation. The present study demonstrates that c-fos protein can be used as a marker of direct or synaptically activated neurons during electrical and chemical stimulation of the motor cortex. Activation of neural structures outside the motor pathway may reflect physiologic activation or stimulus spread. Increased c-fos protein staining of the brainstem with monopolar stimulation supports previous studies that suggest that components of the MEP following monopolar motor cortex stimulation in the rat may arise from brainstem structures.

Effects of selective spinal cord lesions on the spinal motor evoked potential (MEP) in the rat.

The effects of selective spinal cord lesions on the motor evoked potential (MEP) in 21 rats were investigated. No significant change in peak amplitude was observed following lesions of the pyramidal tract. There was a significant decrease in peaks 1 and 2 with ventral funiculi lesions. All 4 peaks of the MEP were significantly reduced following lesions of the lateral funiculus. The most marked decrease in peak amplitude followed lateral funiculi lesions that involved the lateral grey of the spinal cord. In one animal where the lesion was confined to the grey matter in the cord there was a marked decrease in all peaks of the MEP. In 3 additional animals interruption of the descending tracts of the spinal cord via bilateral hemisections of the spinal cord failed to completely abolish the MEP. Increases in peak latency were also noted following spinal lesions. In some animals the increase in latency occurred in the absence of significant peak amplitude changes. The findings in this study refute the previously held position that the MEP in the rat arises from pyramidal tract activation. The role of the reticulospinal and propriospinal tracts in the generation and propagation of the MEP are discussed.

Systemic biodistribution of radioiodinated interleukin-2 in the rat.

Interleukin-2 (IL-2) is a lymphokine capable of modulating a variety of immune functions. In vitro and in vivo studies have shown promising cytotoxic potential. Despite numerous ongoing clinical trials, however, little is known about the biodistribution of this lymphokine after in vivo administration. In this study using a rat model, the fate of radioiodinated human recombinant IL-2 (RIL-2) was analyzed by camera imaging, autoradiography, and well counting experiments. Camera imaging demonstrated the liver and kidney to be the organs of greatest radioactivity accumulation with peak liver uptake noted at approximately 10 min from onset of infusion, and peak kidney uptake at approximately 20 min. Autoradiographic assessment of selected organs (kidney, adrenal, liver, lung, and brain) revealed marked heterogeneity of uptake in the kidney and adrenal gland with preponderance of RIL-2 in the cortex of these organs. A more homogeneous distribution of RIL-2 uptake was noted in liver, lung, and brain parenchyma. Well counting confirmed the liver and kidney as the organs of greatest RIL-2 accumulation. Knowledge of the biodistribution of IL-2 may be of benefit both in studying mechanisms of toxicity and in designing novel therapeutic approaches.

Three-dimensional data visualization and biomedical applications.

Three-dimensional data visualization is an important tool in several medical, scientific, and engineering areas. Visualization methods are based on a primitive representational element: contour, surface, or volume. Methods often incorporate options to cut open, see around, or see through structures, and form images in multiple windows or with animation. To visualize and interpret two or three related 3D data sets, composite imaging methods are required. The appropriate method depends on the user needs, application area, and available hardware. Visualization of 3D medical data is described for cranium/face, musculoskeletal systems, spine, intracranial structures, cardiovascular system, and radiation therapy.

Brain-stem auditory evoked responses as indicators of early brain insult.

The relationship between cranial ultrasonograms (SONOs) and brain-stem auditory evoked responses (BAERs) was evaluated in 2 independent samples of newborn infants at risk for brain injury (n = 113 and 203). Features of the BAER wave forms subjected to stepwise linear discriminant analysis formed the basis of an algorithm used to detect and follow early brain injury. Using this algorithm, information derived from BAERs reliably predicted SONO abnormalities at least 82.3% of the time in the initial study which was replicated with the second sample (77.3%). The wave I component latency (CL) and the wave III-V inter-peak latency interval (IPL) were independent of each other, and both contributed to a prediction of SONO abnormality. Possible mechanisms for these BAER results include compromise to the cochlear membrane or to the auditory nerve itself as well as prolongation of transmission in the brain-stem due to brain-stem hemorrhage, edema, or compression. Normative BAER values and non-linear regression functions for the wave I, III and V CLs, and the I-III, III-V, and I-V IPLs were calculated across age using data from 109 infants who demonstrated normal BAER patterns and had no history of SONO abnormalities. Our analyses indicate BAER techniques, where a single higher intensity is used to produce the BAER wave form, are both valid and efficient for use in the evaluation of early brain injury.

Noncortical origins of the spinal motor evoked potential in rats.

Motor evoked potentials (MEPs) were recorded from the spinal cord, sciatic nerve, or both during transcortical electrical stimulation in the rat. Four peaks could be consistently identified in the spinal MEP. The latency and amplitude of the peaks varied differentially with intensity and polarity of stimulation. Conduction velocity for Peak 1 of the MEP was 43 m/sec. Bilateral sciatic nerve MEPs were present after unilateral cortical stimulation. The spinal MEP was elicited by stimulation of areas outside the motor cortex, and the response persisted during subcortical stimulation and after motor cortex ablation. We present evidence suggesting that components of the spinal MEP in rats arise from pathways outside the motor cortex.

Effects of etoposide-induced blood-brain barrier disruption on brain water, intracranial pressure, and cerebral vasomotor tone.

This study investigated the effects of hypertension and water loading on etoposide-induced, reversible blood-brain barrier disruption in a rat model. Twenty-nine animals were divided into four groups: group 1--intracarotid (i.c.) injection of saline followed in 1 h by 5 ml i.c. water; group 2--i.c. etoposide followed by i.c. water; group 3--i.c. saline followed by i.v. metaraminol to increase systemic blood pressure; group 4--i.c. etoposide followed by i.v. metaraminol. Systemic blood pressure and intracranial pressure were monitored continuously. Evans blue staining of the brain was used as a monitor of blood-brain barrier disruption. Animals were killed 1 h after either aramine or water infusion, and the brains removed and inspected for the degree of disruption. After dehydration, brain water was calculated for each hemisphere. Two-thirds of the animals infused with etoposide had evidence of barrier disruption, whereas none of the control animals infused with saline were disrupted. Neither control groups 1 or 3 showed significant change in intracranial pressure after water loading or augmentation of systemic blood pressure, respectively. Group 4 animals failed to demonstrate any significant change in intracranial pressure despite marked barrier disruption and acute hypertension (within the limits of normal autoregulation). A small but statistically significant increase in intracranial pressure was noted in group 2 animals with the greatest degree of barrier disruption. A significant increase in brain water was observed ipsilateral to etoposide infusion in only those animals with the most marked barrier disruption. These results indicate that etoposide-induced blood-brain barrier disruption caused significant increases in brain water without significant alteration of cerebral vasomotor tone or increases in intracranial pressure after water loading except in the most severe disruption. The classic untoward consequences of vasogenic edema were not encountered in the present model.

Physiological and electrophysiological consequences of etoposide-induced blood-brain barrier disruption.

The present study investigates the effects of etoposide-induced blood-brain barrier (BBB) disruption on systemic blood pressure (SBP), intracranial pressure (ICP), and electroencephalographic (EEG) activity. A total of 29 rats were divided into two groups. In Group 1, 8 control animals received intracarotid normal saline; in Group 2, 21 animals received intracarotid etoposide. SBP, ICP, and EEG were monitored continuously under general anesthesia and controlled ventilation after tracheostomy. Intravenous Evans blue dye was used for determination of BBB disruption. Although none of the Group 1 animals showed BBB disruption, 57% of the animals in Group 2 showed marked BBB disruption (3+). A slight but statistically significant increase in ICP was noted in the Group 2 animals with 3+ BBB disruption, although lesser degrees of barrier disruption (1+ or 2+) resulted in no significant alteration in ICP. The amplitude and frequency of the EEG decreased significantly ipsilateral to the side of intracarotid infusion in all animals with 3+ barrier disruption with a tendency to return toward normal within 2 hours. The degree of transient EEG change observed correlates well with the degree of barrier disruption, potentially allowing clinical determination of BBB disruption by this method.