Jean-Paul Spire

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 subjects 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.

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.

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. This study shows that 1) insulin-induced hypoglycemia results in cognitive dysfunction when plasma glucose is between 3.3 and 2.6 mM on average, 2)decision-making processes rather than sensory or motor processes appear to be predominantly affected, 3)both auditory or visual P300 and RT were affected, 4) recovery of the cortical dysfunction may lag behind the return of plasma glucose to normal by 45–75 min, and 5) individual sensitivity to the adverse effects of hypoglycemia on cortical function appears to exist, but the physiological basis of this finding is not known.

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; 2) the hypoglycemic thresholds for cognitive dysfunction in poorly controlled IDDM are between 2.5 and 3.5 mM (45 and 63 mg/dl, respectively)and are similar to those found in control subjects, suggesting no maladaptive CNS response to hypoglycemia; 3) recovery of cerebral dysfunction, as judged by alterations in P300 latency and RT, lagsbehind the disappearance of hypoglycemia; and 4) there is individual variability to the adverse effects of hypoglycemia on cerebral function.

Noninvasive identification of human central sulcus: a comparison of gyral morphology, functional MRI, dipole localization, and direct cortical mapping.

The locations of the human primary hand cortical somatosensory and motor areas were estimated using structural and functional MRI, scalp-recorded somatosensory-evoked potential dipole localization, expert judgments based on cortical anatomy, and direct cortical stimulation and recording studies. The within-subject reliability of localization (across 3 separate days) was studied for eight normal subjects. Intraoperative validation was obtained from five neurosurgical patients. The mean discrepancy between the different noninvasive functional imaging methods ranged from 6 to 26 mm. Quantitative comparison of the noninvasive methods with direct intraoperative stimulation and recording studies did not reveal a significant mean difference in accuracy. However, the expert judgments of the location of the sensory hand areas were significantly more variable (maximum error, 39 mm) than the dipole or functional MRI techniques. It is concluded that because expert judgments are less reliable for identifying the cortical hand area, consideration of the findings of noninvasive functional MRI and dipole localization studies is desirable for preoperative surgical planning.

Clinical and genetic studies of fatal familial insomnia

Article abstract—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 12gMet polymorphism. There was also a deletion of one octapeptide repeat, suggesting that the association of 178Asn mutation with the 12gMet polymorphism is not due to a “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.

Retrospective fusion of radiographic and MR data for localization of subdural electrodes

Prior to epilepsy surgery, subdural electrodes are often implanted and monitored for a few days to identify the focus of abnormal electrical activity. During the implantation and subsequent brain resection, there may be uncertainty about the exact location of the electrodes with respect to features of brain anatomy such as specific gyral convolutions or lesions. In experiments with a phantom and patients, implanted electrodes were imaged with multiplanar skull radiographs (or CT scans). After retrospective registration with pre-implantation MR data, the electrodes were mapped from these studies onto an MR-derived three-dimensional brain model. The resulting multimodality displays showed the relationship of the electrodes to brain anatomy. In one patient the position of each electrode with respect to a metabolic lesion was also displayed by mapping preimplantation PET data onto the same brain model. This new display of electrode positions may strengthen the interpretation of subdural electrical recordings and thereby reduce uncertainty in planning the resection of epileptic tissue.

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.

Transient inability to distinguish between faces: Electrophysiologic studies

It is not known with certainty at which level of face processing by the cortex the distinction between a familiar and an unfamiliar face is made. Subdural electrodes were implanted under the fusiform gyrus of the right temporal lobe in a patient who developed an unusual inability to distinguish differences between faces as part of the epileptic aura (“all faces looked the same”). A cortical region located posterior to the epileptic focus was identified that exhibited a maximum evoked response to the presentation of facial images (N165), but not to objects, scenes, or character strings. Evoked potentials elicited by a variety of visual images indicated that any perturbation away from novel whole-face stimuli produced submaximal responses from this region of the right temporal lobe. Electrical stimulation of this region resulted in an impairment of face discrimination. It was found that presentation of familiar faces (grandmother, treating physician) produced a different response from that observed for novel faces. These observations demonstrate that within 165 msec of face presentation, and before the conscious precept of face familiarity has formed, this cortical region has already begun to distinguish between a familiar and an unfamiliar face.

Intra-Operative Localization of Sensorimotor Cortex by Cortical Somatosensory Evoked Potentials: From Analysis of Waveforms to Dipole Source Modeling

SummaryIntra-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.