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. This article highlights some of the challenges faced by investigators when conducting clinical trials in AD, and it also offers some recommendations aimed at overcoming these challenges.

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. During the first language task, patients listened to a series of 50 words preceded by warning tones, and were asked to repeat each word. During a second memory task, subjects heard the 50 words from the first task randomly mixed with 50 new words and were asked to repeat the word only if it was a new word. Increases in ECoG gamma power (70-100 Hz) were observed in response to hearing tones (primary auditory cortex), hearing words (posterior temporal and parietal cortex) and repeating words (lateral frontal and anterior parietal cortex). These findings were compared to direct electrical stimulation and separate analysis of ECoG gamma changes during spontaneous inter-personal conversations. The results indicate that high-frequency ECoG reliably differentiates cortical areas associated with receptive and expressive speech processes for individual patients. Compared to listening to words, greater frontal lobe and decreased temporal lobe gamma activity was observed while speaking. The data support the concept of distributed functionally specific language modules interacting to serve receptive and expressive speech, with frontal lobe 'corollary discharges' suppressing low-level receptive cortical language areas in the temporal lobe during speaking.

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. RESULTS: Bitemporal epileptic foci were found in 85/129 (66%) patients with reciprocal relations between these foci in 57/85 (67%) patients. Temporal lobectomy was performed for 67/85 patients. 12/67 patients became free of seizures (Engel's Class I), 32/67 improved (Classes II and III), and 23/67 did not improve. 14/23 patients demonstrated post-surgical activation of the contralateral temporal lobe epileptic focus. For 8/14 of these patients, the stereotactic cryoamygdalatomy was performed in the temporal lobe contralateral to the first surgery. 5/8 patients became free of seizures. It was found that stimulation of temporal lobe deep epileptic focus may terminate focal seizures in the contralateral symmetric structures. CONCLUSION: A mutually suppressive relationship is one of variants of the interaction of symmetric epileptic foci. Some epilepsy surgery failures may be a result of post-surgical activation of the intact focus. The increase of coherence between both temporal lobes before the seizure onset of the seizure suggests the establishment of functional interrelations between two epileptic foci at an early, "hidden" phase of seizures, and may predict the direction of seizure spread. Mutually suppressive interrelations of symmetric epileptic foci might be employed for chronic therapeutic stimulation.

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. This review addresses only primary parasomnias. Arousal disorders and the parasomnias associated with REM sleep are the primary parasomnias most likely to be seen in a neurology practice. Sleep-wake transition disorders are also discussed with nocturnal leg cramps, probably the most common in this group. REVIEW SUMMARY: The salient clinical features of the primary parasomnias are discussed. Emphasis is placed on the differential diagnosis of the different conditions and the best management strategies. Parasomnias encountered in infancy, such as infant sleep apnea, are not discussed in this review. CONCLUSIONS: Parasomnias are common disturbances of sleep that may significantly affect the patient's quality of life and that of the bed partner. Most parasomnias can be diagnosed with careful history taking and polysomnography, and management is usually safe and effective.

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.

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.