AMPA workshop on challenges faced by investigators conducting Alzheimer's disease clinical trials.

The recruitment and retention of patients are among the greatest challenges currently being faced by researchers who conduct Alzheimer's disease (AD) clinical trials. To discuss these challenges and other major issues associated with clinical research in AD, an international workshop was organized by the Association Monégasque pour la recherche sur la Maladie d'Alzheimer at Monte Carlo, Monaco, in February 2010, with the participation of leading research experts in the field of Alzheimer's. Key topics discussed were as follows: (1) the selection, recruitment, and retention of clinical trial subjects; (2) international co-operation among researchers; and (3) patient rights and informed consent for participants in clinical trials.

ECoG gamma activity during a language task: differentiating expressive and receptive speech areas.

Electrocorticographic (ECoG) spectral patterns obtained during language tasks from 12 epilepsy patients (age: 12-44 years) were analysed in order to identify and characterize cortical language areas. ECoG from 63 subdural electrodes (500 Hz/channel) chronically implanted over frontal, parietal and temporal lobes were examined. Two language tasks were performed.

Mutually suppressive interrelations of symmetric epileptic foci in bitemporal epilepsy and their inhibitory stimulation.

Objectives: The goal of this study is to analyze the suppressive interaction of symmetric temporal lobe epileptic foci, assess some failures of epilepsy surgery, and evaluate the possibility of terminating focal seizures with stimulation of symmetric epileptic foci.

Materials And Methods: One hundred and twenty-nine intractable epilepsy patients (age range 6-53 years) with bitemporal epileptiform abnormalities in multiple scalp EEGs were evaluated with chronically implanted depth and subdural electrodes. Interelectrode coherence and power spectra were studied using internally developed software.

The primary parasomnias. A review for neurologists.

Background: Primary parasomnias are undesirable motor or verbal phenomena which occur during sleep and result in abnormal arousals. They occur out of all sleep stages or during transitions between sleep and awake. Secondary parasomnias are sleep disturbances that are caused by disorders of other organ systems.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.