Identification of the sensory/motor area and pathologic regions using ECoG coherence.

An electrophysiologic mapping technique which enables identification of the central sulcus and pathologic cortical regions is described. Electrocorticographic recordings of 1 min duration were recorded from 25 patients who were undergoing resection of tumors in the sensory-motor region or being evaluated for temporal lobectomy for epilepsy. Analysis of the patterns of subdural inter-electrode coherence revealed low coherence across the central sulcus for 11/12 cases where its location could be verified with direct cortical stimulation and/or somatosensory evoked potential mapping. Regions of high coherence identified the location of tumors in the sensory-motor region for 10/10 cases. Over the temporal lobe, localized areas of high coherence were evident in 8/9 epilepsy patients, but were not indicative of the location of mesial temporal lobe tumors or inter-ictal spiking, when present. We conclude that analysis of cortical coherence patterns may be helpful for revealing the location of pathologic processes relative to critical cortical areas.

Intra-operative localization of sensorimotor cortex by cortical somatosensory evoked potentials: from analysis of waveforms to dipole source modeling.

Intra-operative localization of sensorimotor cortex is of increasing importance as neurosurgical techniques allow safe and accurate removal of lesions around the central sulcus. Although direct cortical recordings of somatosensory evoked potentials (SEPs) are known to be helpful for cortical localization, source localization models can provide more precise estimates than subjective visual analysis. In addition to intra-operative analysis of waveforms and amplitudes of SEPs to median nerve stimulation in 20 neurosurgical patients, we used a spatiotemporal dipole model to determine the location of the equivalent dipoles consistent with the cortical distribution of the SEPs. The early cortical SEPs were modeled by 2 equivalent dipoles located in the postcentral gyrus. The first dipole was primarily tangentially oriented and explained N20 and P20 peaks. The second dipole was primarily radially oriented and explained P25 activity. We found consistent localization of the first dipole in the postcentral gyrus, which was always located within 8 mm of the central sulcus, with an average distance of 3 mm. This finding provides an objective basis for using the SEP phase reversal method for cortical localization. We conclude that dipole source modeling of the cortical SEPs can be considered as an objective way of localizing the cortical hand sensory area.

Maturation of human visual evoked potentials: 27 weeks conceptional age to 2 years.

Visual evoked potentials to pattern reversal and diffuse flash stimulation were recorded from 520 consecutive pediatric patients and 11 normal infants between the ages of 27 weeks post-conception and 24 months. The latency and peak-to-peak amplitude of the first reproducible positive peak of the binocular pattern visual evoked potential (P100) were measured for five check sizes subtending from 15' to 4 degrees of arc. Three developmental trends were noted: 1) a rapid increase in pattern resolution near term, 2) a subsequent decrease in the latency of P100, and 3) a gradual increase in the amplitude of P100. These three trends reflect the multiplicity of early maturation and are discussed in terms of changes in receptor growth and density, pathway myelination, and cortical synaptivity.

Mechanisms of neurologic deficits and mortality with carotid endarterectomy.

OBJECTIVE: To evaluate the incidence and etiology of perioperative complications of carotid endarterectomy. DESIGN: Retrospective review of carotid endarterectomies performed over 13 years. Risk factors, indications, results of electroencephalographic (EEG) monitoring, and outcomes were evaluated. SETTING: University medical center. PATIENTS: Three hundred sixty-seven consecutive primary carotid endarterectomies were performed on 336 patients. Indications for operation included transient ischemic attack (48.5%), asymptomatic stenosis (24%), stroke (17%), nonlateralizing ischemia (9.5%), and stroke-in-evolution (1%). MAIN OUTCOME MEASURES: Postoperative neurologic deficits (permanent and transient) and deaths were correlated with preoperative symptoms, probable mechanism of the neurologic event, intraoperative EEG changes, and the use of intraoperative shunts. RESULTS: Four new permanent neurologic deficits (1.1%) and one transient postoperative deficit were noted. Of the five deficits, three were related to undiagnosed intraoperative cerebral ischemia and two were related to perioperative emboli. Three perioperative deaths (0.8%) occurred: two of myocardial infarction and one of an intracerebral hemorrhage from a ruptured arteriovenous malformation. Intraoperative EEG tracings for the most recent consecutive 175 procedures were analyzed. Shunts were used in 45 patients (26%), 38 of whom demonstrated significant EEG changes with carotid clamping. CONCLUSIONS: Carotid endarterectomy can be performed with a low risk of stroke (1.1%) and death (0.8%). Stroke was due to cerebral ischemia or embolization. With meticulous surgical technique, death is due to myocardial ischemia and not neurologic events.

Clinical and genetic studies of fatal familial insomnia.

We report a 42-year-old man who, for 8 months, had intermittent motor abnormalities and mild difficulty falling asleep. A diagnosis of fatal familial insomnia (FFI) became evident over the next 6 months when he developed progressive insomnia, myoclonus, sympathetic hyperactivity, and dementia. The amyloid or prion protein (PrP) genotype showed features typically seen in FFI, with a 178Asn mutation and a 129Met polymorphism. There was also a deletion of one octapeptide repeat, suggesting that the association of 178Asn mutation with the 129Met polymorphism is not due to "founder effect." Western immunoblot showed a trace of protease-resistant PrP in the thalamus--which had the most significant neuronal loss and gliosis--a moderate amount of PrP in the fronto-temporal area, and no detectable protein elsewhere in the brain. Endocrine studies showed that a circadian modulation of hormonal levels could be maintained despite a near-total absence of sleep. Administration of gamma-hydroxybutyrate induced a remarkable increase in slow-wave sleep.

Displaying electrocorticographic findings on gyral anatomy.

Human electrocorticographic findings recorded from subdural arrays of electrodes were topographically mapped directly onto magnetic resonance images of gyral anatomy. With this technique gyri involved in generating somatosensory evoked potentials and epileptic phenomena are easily identified. Regions of the cortex which exhibit local spectral changes associated with cognitive tasks can also be visualized. These composite images of structure and function can provide insight regarding the functional organization of human cortex in relation to gyral anatomy and localized pathologic rhythms.

The spatial location of EEG electrodes: locating the best-fitting sphere relative to cortical anatomy.

The location of the international 10-20 system electrode positions and 14 fiducial landmarks are described in cartesian coordinates (+/- 1.4 mm average accuracy). Six replications were obtained on 3 separate days from 4 normal subjects, who were compared to each other with a best-fit sphere algorithm. Test-retest reliability depended on the electrode position: the parasagittal electrodes were associated with greater measurement errors (maximum 7 mm) than midline locations. Location variability due to head shape was greatest in the temporal region, averaging 5 mm from the mean. For each subject's electrode locations a best-fitting sphere was determined (79-87 mm radius, 6% average error). A surface-fitting algorithm was used to transfer the electrode locations and best-fitting sphere to MR images of the brain and scalp. The center of the best-fitting sphere coincided with the floor of the third ventricle 5 mm anterior to the posterior commissure. The melding of EEG electrode location information with brain anatomy provides an empirical basis for associating hypothetical equivalent dipole locations with their anatomical substrates.

Hypoglycemic thresholds for cognitive dysfunction in IDDM.

Fourteen poorly controlled insulin-dependent diabetes mellitus (IDDM) patients (HbA1c 11 +/- 0.5%) with a mean +/- SE duration of disease of 15 +/- 2 yr were studied to evaluate the hypoglycemic threshold for cognitive dysfunction under insulin-induced hypoglycemia. The P300 event-related potential, a measure of cognitive function, and reaction time (RT) in response to visual stimuli under euglycemic conditions and at plasma glucose concentrations of 3.5 and 2.5 mM (63 and 45 mg/dl, respectively) during a constant insulin infusion were recorded. Baseline P300 latency was similar to that of a nondiabetic control group, but baseline RT was greater in the IDDM group. There was no increase in P300 latency or RT under euglycemic clamp conditions or at a plasma glucose level of 3.5 mM (63 mg/dl). However, when plasma glucose was lowered to 2.5 mM (45 mg/dl), there was an increase in P300 latency and a prolongation of RT. As plasma glucose returned to baseline, P300 latency and RT remained prolonged. After administration of intravenous glucose and a meal, P300 latency and RT returned to baseline. P140, an event-related potential reflecting sensory processes, was not altered. Because P300 latency changes paralleled RT changes, hypoglycemia appears to slow decision-making processes in IDDM. This study revealed that 1) baseline P300 latency is not elevated in poorly controlled IDDM patients, suggesting no cumulative cognitive dysfunction.

Tetrahedral recording of 3-D BAEPs: evidence for the centered dipole model.

Three-dimensional brain-stem auditory evoked potentials (3-D BAEPs) were recorded from 12 normal subjects using a new tetrahedral montage, as well as two other bipolar montages previously described for 3-channel Lissajous' trajectories (3-CLTs). Mean responses, as well as between-subject and within-subject variability were described. A mathematical transformation was applied to the recorded trajectories to render them in a common canonical form to test the assumption that the BAEP conforms to a centrally generated dipolar field. Apex, segment, and plane orientations were measured for each trajectory, and discrepancies between montages were evaluated to judge the adequacy of the centered dipole model. For the vector means of apices, segments, and planes, median angles of discrepancy between montages ranged from 10 to 23 degrees. These results support the validity of a centered dipole model for the BAEP and affirm the rationale for employing the 3-channel recording technique. Among the montages studied, the tetrahedron provided maximum economy by using fewer electrodes, avoided certain problematic recording sites, and produced less variable data.

Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep.

To define the roles of circadian rhythmicity (intrinsic effects of time of day independent of the sleep or wake condition) and sleep (intrinsic effects of the sleep condition, irrespective of the time of day) on the 24-h variation in glucose tolerance, eight normal men were studied during constant glucose infusion for a total of 53 h. The period of study included 8 h of nocturnal sleep, 28 h of continuous wakefulness, and 8 h of daytime sleep. Blood samples for the measurement of glucose, insulin, C-peptide, cortisol, and growth hormone were collected at 20-min intervals throughout the entire study. Insulin secretion rates were derived from C-peptide levels by deconvolution. Sleep was polygraphically monitored. During nocturnal sleep, levels of glucose and insulin secretion increased by 31 +/- 5% and 60 +/- 11%, respectively, and returned to baseline in the morning. During sleep deprivation, glucose levels and insulin secretion rose again to reach a maximum at a time corresponding to the beginning of the habitual sleep period. The magnitude of the rise above morning levels averaged 17 +/- 5% for glucose and 49 +/- 8% for calculated insulin secretion. Serum insulin levels did not parallel the circadian variation in insulin secretion, indicating the existence of an approximate 40% increase in insulin clearance during the night. Daytime sleep was associated with a 16 +/- 3% rise in glucose levels, a 55 +/- 7% rise in insulin secretion, and a 39 +/- 5% rise in serum insulin. The diurnal variation in insulin secretion was inversely related to the cortisol rhythm, with a significant correlation of the magnitudes of their morning to evening excursions. Sleep-associated rises in glucose correlated with the amount of concomitant growth hormone secreted. These studies demonstrate previously underappreciated effects of circadian rhythmicity and sleep on glucose levels, insulin secretion, and insulin clearance, and suggest that these effects could be partially mediated by cortisol and growth hormone.

Three-dimensional human pattern visual evoked potentials. I. Normal subjects.

Pattern visual evoked potentials (PVEPs) were obtained from 30 normal adult volunteers, recording from both a conventional horizontal occipital array and three orthogonal bipolar antipodal channels approximating the three dimensions of space. Central and eccentric fixation of 60' checks and central fixation of 30' checks under binocular and monocular viewing conditions was employed. The three antipodal wave forms were displayed as a single 3-D Lissajous trajectory which contained four apices, corresponding to P40 (apex A), N70 (apex B), P100 (apex C) and N125 (apex D). The 3-D evoked potentials depicted the dynamic nature of the human PVEP in terms of changes in the 3-D voltage-voltage-voltage plots of the recordings. The orientation of the A-B, B-C and C-D curvilinear segments reflected the stimulating condition (central fixation vs. right vs. left hemi-field stimulation) for all subjects with more accuracy than did the wave forms from the conventional array. Spherical statistical methods are described for quantifying and evaluating 3-D evoked potential recordings.

Three-dimensional human pattern visual evoked potentials. II. Multiple sclerosis patients.

Pattern visual evoked potentials were obtained from 46 patients with definite relapsing/remitting multiple sclerosis, using both a conventional 5-channel occipital array and a 3-D recording technique consisting of three bipolar derivations approximating the three dimensions of space. These three orthogonal wave forms were displayed as a 3-D Lissajous trajectory for each subject. Two of the 15 patients with completely normal conventional pattern VEPs had abnormalities of the orientation of the B-C curvilinear segment of the 3-D pattern VEPs. Delays in the first major occipital positive component (P100) were evident using both techniques; the correlation between P100 latency and the latency of the corresponding trajectory apex was r = 0.99 (P less than 0.01). Post-chiasmal MRI abnormalities were associated with 3-D VEP orientation abnormalities. Three-dimensional pattern VEPs are moderately more sensitive than conventional pattern VEPs at detecting dysfunction posterior to the optic chiasm in demyelinating disease and do not require the use of eccentric fixation to do so.

Cortical asymmetry of REM sleep EEG following unilateral pontine hemorrhage.

A 24-year-old woman with a left pontine hematoma showed marked asymmetry in the EEG of REM sleep, suggesting that a unilateral pontine lesion is sufficient to disrupt normal REM sleep EEG in the ipsilateral hemisphere. Other REM sleep characteristics (rapid eye movements, muscle atonia) were unaffected by this lesion.

Hypoglycemic thresholds for cognitive dysfunction in humans.

Nineteen healthy adult volunteers were studied to define the nature of and threshold for the cognitive dysfunction that occurs during insulin-induced hypoglycemia. The P300 cerebral event-related potential is an electrophysiological correlate of cognitive decision-making processes that can be measured in response to either an auditory or visual stimulus. P300 and reaction time (RT) were recorded from a visual stimulus under euglycemic conditions and at plasma glucose concentrations of 3.3 and 2.6 mM during insulin infusion in 10 subjects. Reducing plasma glucose levels to 3.3 mM was not associated with an increase in either the latency or amplitude of the P300 component or a change in RT. However, further lowering of plasma glucose to 2.6 mM resulted in an increase in the latency of P300 and a prolongation in RT. Similar changes were seen for the auditory P300 in experiments performed on 9 additional subjects in which both auditory and visual stimuli were presented. The prolongation of P300 did not correct immediately when plasma glucose was raised to basal levels with intravenous glucose but returned to normal 45-75 min later, after ingestion of a carbohydrate-containing meal. Analysis of another event-related potential, P140 (a measure of the sensory processes), showed no change in response to hypoglycemia. Prolongation of RT paralleled the prolongation of P300 latency, suggesting that motor processes were not altered. Therefore, hypoglycemia appears to induce abnormalities in decision-making processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Three-dimensional magnetic resonance images of the brain: application to neurosurgical planning.

Data from single 10-minute magnetic resonance scans were used to create three-dimensional (3-D) views of the surfaces of the brain and skin of 12 patients. In each case, these views were used to make a preoperative assessment of the relationship of lesions to brain surface structures associated with movement, sensation, hearing, and speech. Interactive software was written so that the user could "slice" through the 3-D computer model and inspect cross-sectional images at any level. A surgery simulation program was written so that surgeons were able to "rehearse" craniotomies on 3-D computer models before performing the actual operations. In each case, the qualitative accuracy of the 3-D views was confirmed by intraoperative inspection of the brain surface and by intraoperative electrophysiological mapping, when available.

Electrophysiologic studies on locked-in patients: heterogeneity of findings.

Somatosensory evoked potentials, brain-stem auditory evoked potentials and electroencephalograms were obtained from 9 patients with the diagnosis of 'locked-in' syndrome. No pattern of evoked potential abnormality was specific to this syndrome, with findings ranging from bilaterally normal to unilaterally or bilaterally absent. The evoked potential studies complemented radiographic findings in defining the extent of the lesion and revealed that a portion of the pontine tegmentum was usually involved. Pathology from 2 patients corroborated the findings of the evoked potential studies. The value of evoked potential studies of patients with locked-in syndrome is to provide early objective evidence of brain-stem involvement independent of the clinical examination, EEG and radiographic studies.

Inter- versus intra-subject variance in topographic mapping of the electroencephalogram.

The variability of the normal topographic EEG distribution between a quiet, eyes closed, resting state and the performance of cognitive tasks (listening to a story or music) was studied in 20 normal (10 male) right-handed college students or graduates ages 18-40 yrs. Amplitude changes in the topographic frequency distribution (2.5-7 SD) of alpha frequency band (8-13 Hz) were noted between tasks and resting state in individual subjects. When group data for the resting versus listening states were compared, no statistical differences could be demonstrated. The group variability was 50% of the power of the resting record. Repeat studies in 10 subjects demonstrated a test-retest variance of 10% of the mean individual power. The data suggest that inter-subject differences in the alpha frequency and individual topographic differences will require careful normalization for development of baseline "brain maps" to serve as a standard for investigation of disease states.

Comparison of sympathetic skin response with quantitative sudomotor axon reflex test in diabetic neuropathy.

The sympathetic skin response (SSR), the quantitative sudomotor axon reflex test (Q-SART), and cardiac beat-to-beat variability with respiration as measured by the expiratory/inspiratory ratio (E/I ratio) were studied in 39 patients with diabetic neuropathy of whom 33 also had one or more symptoms of autonomic involvement. In the lower extremities 87% of the patients with an absent SSR had an abnormal Q-SART (P less than 0.001), and 81% of patients with the SSR present had a normal Q-SART (P less than 0.02). The E/I ratio was abnormal in all but one of 23 patients with an absent SSR in the foot, and a normal E/I ratio was present only in those patients (n = 7) with the SSR present in hand and foot, and in an eighth patient who had SSR absent in the foot and present in the hand. A similar correlation was found between the E/I ratio and the Q-SART in the foot, although 4 of 25 patients with an abnormal foot Q-SART had a normal E/I ratio. We conclude that the concordance of results of the SSR and Q-SART supports the combined use of these tests to uncover early distal sympathetic failure in diabetic neuropathy.

Vector analysis of three-dimensional evoked potentials: eccentric dipoles.

The quantitative description of three-dimensional cerebral evoked potentials is extended to include eccentric dipolar sources. Eccentricity-related distortions in dipole orientation and magnitude are assessed. The use of nonstandard montages, the prediction of topographic surface maps, dynamic analysis, and theoretical mechanisms of planar segment formation are discussed.

Hemi-field pattern visual evoked potentials: a comparison of display and analysis techniques.

Three methods for analyzing the spatial organization of visual evoked potentials were compared. Pattern reversal visual evoked potentials were obtained from a single subject under three viewing conditions: stimulation of the left, right, and both visual fields. The scalp distribution of the VEP to 1 deg checks was displayed using three recording and analysis techniques: a conventional horizontal occipital array of electrodes, topographic mapping, and 3-dimensional evoked potentials. All three techniques revealed "paradoxical" lateralization of P100. The relative merits of each technique are discussed.