1. Activity of up to 10 single units was recorded in parallel from frontal areas of behaving monkeys. 2. Spatiotemporal firing patterns were revealed by a method that detects all excessively repeating patterns regardless of their complexity or single-unit composition. 3. Excess of repeating patterns was found in 30-60% of the cases examined when timing jitter of 1-3 ms was allowed. 4. An independent test refuted the hypothesis that these patterns represented chance events. 5. In a given behavioral condition there were usually many different patterns, each repeating several times, and not one (or a few) pattern repeating many times. 6. In 13 out of 20 cases, when a single unit elevated its firing rate in association with an external event beyond 40/s, most of the spikes within that period were associated with excessively repeating spatiotemporal patterns. 7. Of 157 types of patterns whose excess was most marked, 107 were composed of spikes from one single unit, 45 of the patterns contained spikes from two single units, and only one was composed of spikes from three different single units. 8. These properties suggest that the patterns were generated by reverberations in a synfire mode within self-exciting cell assemblies.

No abstract

Purpose-To report the enlargement rate of geographic atrophy (GA) over time, its relationship to size of atrophy at baseline and to prior enlargement rate, and the implications for designing future treatment trials for GA.Design-Prospective natural history study of GA resulting from age-related macular degeneration.Participants-Two hundred twelve eyes of 131 patients were included in the analysis.Methods-Annual follow-up included stereo color fundus photographs. The areas of GA were identified and measured, and the rate of enlargement of the atrophy was assessed. Sample sizes for clinical trials using systemic treatment and uniocular treatment were determined. Main Outcome Measure-Rate of enlargement of the atrophy.Results-The median overall enlargement rate was 2.1 mm 2 /year (mean, 2.6 mm 2 /year). Eyes with larger areas of atrophy at baseline tended to have larger enlargement rates, but knowledge of prior rates of enlargement was the most significant factor in predicting subsequent enlargement rates. There was high concordance between the enlargement rates in the 2 eyes of patients with bilateral GA (correlation coefficient, 0.76). To detect a 25% reduction in enlargement rate for a systemic treatment (α, 0.05; power, 0.80; losses to follow-up, 15%), 153 patients each in a control and treatment group would be required for a trial with a 2-year follow-up period for each patient. For a uniocular treatment, 38 patients with bilateral GA would be required, with the untreated eye serving as a control for the treated eye. Because GA is a degenerative rather than a neovascular disorder, the possible methods for treatment of this disorder are likely to be different than those for choroidal neovascularization (CNV). To date, there is no definite treatment for GA. Limited information on GA from the Age-Related Eye Disease Study has been published. 12 The findings presented did not attain statistical significance, and there were some contradictory findings, perhaps because of the small numbers. To design future studies of potential therapies for GA, it is important to know the natural history of GA. Conclusions-TreatmentThis article reports our long-term prospective findings of the enlargement of the area of atrophy in GA. We also explore issues important for the design of future treatment trials, including sample size calculations and appropriate eligibility criteria for baseline GA area. Patients and Methods Patients and Annual ExaminationsPatients with GA associated with AMD were enrolled in our National Institutes of Healthfunded prospective natural history study, which ran from 1992 through 2000. Patients were evaluated annually. Eligibility criteria included having an area of GA of at least 500 µm in diameter in the absence of CNV (assessed clinically and by fluorescein angiography) in one or both eyes. At each examination, a battery of visual function tests also was performed, as described previously. 13 Thirty-degree and, when possible, 60° color fundus photographs were obtained at each examination. Fluo...