Responses of human somatosensory cortex to stimuli below threshold for conscious sensation.

Averaged evoked responses of somatosensory cortex, recorded subdurally, appeared with stimuli (skin, ventral posterolateral nucleus, cortex) which were subthreshold for sensation. Such responses were deficient in late components. Subthreshold stimuli could elicit sensation with suitable repetition. The primary evoked response was not sufficient for sensation. These facts bear on the problems of neurophysiological correlates of conscious and unconscious experience, and of "subliminal perception."

Stereotactic localization (with computerized tomographic scanning), biopsy, and radiofrequency treatment of deep brain lesions.

In eight patients stereotactic biopsy of deep brain lesions was performed. Adequate tissue was obtained, and the information helped considerably in planning further therapy. No significant complications occurred in these patients. In three of the cases, the stereotactic coordinates were determined from the computerized tomographic (CT) scan. In one patient, after biopsy, stereotactic radiofrequency (RF) lesions in the tumor resulted in temporary improvement.

The on-off effect in Parkinson's disease treated with levodopa with remarks concerning the effect of sleep.

The "On-Off Effect" in levodopa treated Parkinson's disease began in a few patients during the first year of treatment. The number of patients suffering from this phenomenon increased rapidly the first three or four years with some continuing increase throughout the six years of the study. Even those whose disease had worsened would become even more incapacitated during parts of each day. One group of patients experienced their initial "On" effect upon arising at their usual hour of awakening. This would last for 1 to 3 hours and was their best time of day.

EEG findings in heroin addicts during induction and maintenance on methadone.

This study investigated changes in the EEG of addicts initially on heroin as they progressed through the induction and maintenance phases of a methadone program. Spectral analysis of bipolar recordings revealed significant consistent differences only in the eyes-closed resting state. Patients under the influence of heroin showed large sharp peaks at 9-10 c/sec, particularly in the parieto-occipital recording. Methadone induction led either to marked reduction of this peak and widening of alpha band activity or to an increase in frequency of the alpha peak to 12 c/sec. After several months of methadone the alpha peak was still absent unless heroin abuse was present, a theta peak was present in three of four patients, and the alpha bandwidth remained broad. Changes in the theta band were more difficult to interpret.

Stimulation of locus coeruleus in man. Preliminary trials for spasticity and epilepsy.

Stimulating electrodes were chronically implanted unilaterally (in 1975-1977) in the vicinity of the locus coeruleus (LC) in three patients, one with cerebral palsy-spastic quadriplegia, two with epilepsy (one grand mal, one psychomotor). Effective excitation of efferent LC axons was indicated by measuring rises in 3-methoxy-4-hydroxyphenylethyleneglycol in the jugular and systemic venous blood following a 6-min stimulus with discontinuous bursts of pulses. There was a substantial reduction of spasticity during and after stimulation. Improvement was verified by double-blind failures of the stimulator, and the stimulus therapy is still in use after 9 years. There appeared to be a reduction in incidence and severity of both types of epileptic seizures, although this was not rigorously established. The patient with psychomotor epilepsy reported a considerable lengthening of preseizure auras (to 15-30 min), an unusual number of which terminated without a seizure.

Subjective referral of the timing for a conscious sensory experience: a functional role for the somatosensory specific projection system in man.

Subjective experience of a peripherally-induced sensation is found to appear without the substantial delay found for the experience of a cortically-induced sensation. To explain this finding, in relation to the putative delay of up to about 500 ms for achieving the "neuronal adequacy" required to elicit the peripherally-induced experience, a modified hypothesis is proposed: for a peripheral sensory input, (a) the primary evoked response of sensory cortex to the specific projection (lemniscal) input is associated with a process that can serve as a 'time-marker'; and (b), after delayed neuronal adequacy is achieved, there is a subjective referral of the sensory experience backwards in time so as to coincide with this initial 'time-marker'. A crucial prediction of the hypothesis was experimentally tested in human subjects using suitably implanted electrodes, and the results provide specific support for the proposal. In this, the test stimuli to medial lemniscus (LM) and to surface of somatosensory cortex (C) were arranged so that a minimum train duration of 200 ms or more was required to produce any conscious sensory experience in each case. Each such cerebral stimulus could be temporally coupled with a peripheral one (usually skin, S) that required relatively negligible stimulus duration to produce a sensation. The sensory experiences induced by LM stimuli were found to be subjectively timed as if there were no delay relative to those for S, that is, as if the subjective experience for LM was referred to the onset rather than to the end of the required stimulus duration of 200 ms or more. On the other hand, sensory experiences induced by the C stimuli, which did not excite specific projection afferents, appeared to be subjectively timed with a substantial delay relative to those for S, that is, as if the time of the subjective experience coincided roughly with the end of the minimum duration required by the C stimuli. The newly proposed functional role for the specific projection system in temporal referral would be additional to its known role in spatial referral and discrimination. A temporal discrepancy between corresponding mental and physical events, i.e., between the timing of a subjective sensory experience and the time at which the state of 'neuronal adequacy' for giving rise to this experience is achieved, would introduce a novel experimentally-based feature into the concept of psychophysiological parallelism in the mind-brain relationship.

Suppression of an eplieptiform type of electrocortical activity in the rat by stimulation in the vicinity of locus coeruleus.

Stimulation of the locus coeruleus, or in the vicinity of this nucleus or of its ascending tracts, could markedly suppress the appearance of epileptiform-like ECoG bursts. The latter were induced in rats by a subconvulsive dose of pentylenetetrazol. Electrode sites were identified histologically. A unilateral stimulus suppressed bursts bilaterally. An individual burst already in progress could be aborted, stopping within less than 0.5-1 sec after onset of a stimulus train. The antiepileptiform actions occurred with no evidence of any desynchronizing effect of the stimulus on the resting ECoG; they appear to be different in sites of origin and nature from those reported for stimulation of the reticular activating system. It is proposed that stimulation of the ascending noradrenergic system in the brain stem may limit the development and spread of hyperexcitatory, epileptiform states.

Once-daily mometasone furoate dry powder inhaler in the treatment of patients with persistent asthma.

BACKGROUND: Although inhaled glucocorticoids are recommended for all stages of persistent asthma, compliance with long-term therapy is often poor, leading to significant morbidity and mortality. A simplified, once-daily dosing regimen may foster improved compliance. OBJECTIVE: To compare the efficacy and safety of once-daily (AM) administration of mometasone furoate dry powder inhaler (MF DPI) 200 microg and 400 microg with placebo in patients with asthma previously maintained only on short-acting inhaled beta-adrenergic receptor agonists. METHODS: This was a 12-week, double-blind, placebo-controlled, parallel group study. The mean change from baseline to endpoint (last treatment visit) for FEV1 was the primary efficacy variable. RESULTS: At endpoint, both doses of MF DPI were significantly more effective than placebo (P < or = .05) in improving FEV1. Based on morning peak expiratory flow rate, once-daily MF DPI 400 microg was more effective than placebo (P < or = .001) at endpoint. Both active treatments also demonstrated improvement at endpoint in asthma symptom scores, physician-evaluated response to therapy and use of rescue medication. Although both MF DPI dosages were efficacious, MF DPI 400 microg provided additional improvement in some measures of pulmonary function (eg, morning PEFR) when these agents were administered once daily in the morning. Both doses of MF DPI were well tolerated and treatment-related adverse events occurred at a similar incidence among the three treatment groups. CONCLUSIONS: The results of this study indicate that once-daily (AM) MF DPI provides a convenient and effective treatment option for patients with mild or moderate persistent asthma.