Linking cognitive integrity to working memory dynamics in the aging human brain.

Aging is accompanied by a decline of working memory, an important cognitive capacity that involves stimulus-selective neural activity that persists after stimulus presentation. Here, we unraveled working memory dynamics in older human adults (male and female) including those diagnosed with mild cognitive impairment (MCI) using a combination of behavioral modeling, neuropsychological assessment, and magnetoencephalographic (MEG) recordings of brain activity. Younger adults (male and female) were studied with behavioral modeling only. Participants performed a visuo-spatial delayed match-to-sample task under systematic manipulation of the delay and distance between sample and test stimuli. Their behavior (match/non-match decisions) was fit with a computational model permitting the dissociation of noise in the internal operations underlying the working memory performance from a strategic decision threshold. Task accuracy decreased with delay duration and sample/test proximity. When sample/test distances were small, older adults committed more false alarms than younger adults. The computational model explained the participants' behavior well. The model parameters reflecting internal noise (not decision threshold) correlated with the precision of stimulus-selective cortical activity measured with MEG during the delay interval. The model uncovered an increase specifically in working memory noise in older compared to younger participants. Furthermore, in the MCI group, but not in the older healthy controls, internal noise correlated with the participants' clinically assessed cognitive integrity. Our results are consistent with the idea that the stability of working memory contents deteriorates in aging, in a manner that is specifically linked to the overall cognitive integrity of individuals diagnosed with MCI.Significance statement Several cognitive functions decline during aging, and this process is aggravated in MCI - a condition constituting a primary risk factor for developing dementia. One function susceptible to age-related cognitive decline is working memory: the ability to maintain information online for the flexible control of behavior, which entails persistent stimulus-selective neural activity in different regions of the cerebral cortex. We used computational modeling of behavioral and neural recordings to show that the stability of working memory contents is reduced in older human subjects and predicts overall cognitive decline in MCI patients. Our findings provide new mechanistic insight into cognitive aging and MCI and highlight working memory stability as an objective marker of the mechanisms underlying cognitive impairment.

Liquid-based cervical-cell collection with brushes and wooden spatulas: a comparison of 100 conventional smears from high-risk women to liquid-fixed cytocentrifuge slides, demonstrating a cost-effective, alternative monolayer slide preparation method.

Our purpose was to demonstrate that 17.5-mm liquid-based cytocentrifuge circle-slides made using a Hettich (Andreas Hettich Co., Tuttlingen, Germany) cytocentrifuge are at least as efficacious as conventional smears for detecting cervical abnormalities. One hundred conventional smears were collected with cytobrushes and wooden spatulas from high-risk women. Both devices were then placed into CytoRich Red (AutoCyte, Inc., Burlington, NC). Cells were concentrated from CytoRich Red by centrifugation and suspended in CytoRich Yellow. Two 17.5-mm circle-slides were produced, compared to each other in order to test reproducibility of diagnoses between slides, and compared to conventional slides. Sixty-five normals, three ASCUS, three LSIL, and two HSIL matched. Overall, cytocentrifugation yielded 27 additional findings among 25 cases. Also, it downgraded one conventional ASCUS to normal (immature metaplasia and chronic inflammation) and one conventional HSIL to normal (transitional cell metaplasia). Cytocentrifugation of 14 conventional normals afforded four ASCUS and 10 LSIL. Cytocentrifugation of 11 conventional ASCUS afforded nine LSIL and two HSIL (one with AIS). One HSIL + AIS was found with a conventional HSIL. Cytobrushes and wooden spatulas can be used to collect material for liquid-based cervico-vaginal cytology if they are placed into CytoRich Red. Hettich cytocentrifuge slides were more reliable than conventional smears in presenting well-dispersed, sharply imaged cells, affording greater diagnostic sensitivity and certainty. Compared to previous split-sample studies, three different outcomes were noted: 1) the endocervical component was consistently well-represented; 2) AIS was seen more often in liquid-based slides; and 3) the liquid-based slide did not underdiagnose its conventional companion. The liquid-based preparations downgraded one ASCUS to normal and one conventional HSIL to transitional-cell metaplasia. Histology correlation of these two cases agreed with the liquid-based cytology diagnoses, which validates their specificity. These improvements are ascribed to differences in fixation and processing. The low cost, ease of operation, and reusable chambers of the Hettich cytocentrifuge make it a cost-effective liquid-based cytology instrument, especially for small to intermediate-size laboratories. The claims that this paper makes must be proven by additional studies, and test implementation needs to be scrutinized by appropriate regulatory agencies whose standards may vary from country to country. Diagn. Cytopathol. 2000;22:86-91.

The prevalence of farmer's lung in an agricultural population.

Four hundred seventy-one persons associated with farming or dairy production were surveyed by means of a questionnaire for evidence of hypersensitivity lung disease due to inhalation of moldy hay or grain (farmer's lung). Of these, 172 were evaluated with spirometry, serologic studies, and chest roentgenographs. A history typical of the farmer's lung syndrome was given by 14 of the 471 subjects (3.9 per cent). Precipitating antibodies to Micropolyspora faeni were identified in sera from 2 of these 14 subjects (14 per cent), and spirograms were abnormal in 4 (28 per cent). The prevalence of farmer's lung in this community (i.e., 3 per cent) is comparable to that found in epidemiologic studies in Britain and Scotland. Farmer's lung disease may be an important occupational illness of dairy and cattlemen in this country, but the diagnosis may be overlooked frequently because of the lack of patient and/or physician awareness.

A comparative study of atropine sulfate and isoproterenol hydrochloride in chronic bronchitis.

Fifteen subjects with chronic bronchitis were treated with inhaled atropine sulfate, isoproterenol hydrochloride, or placebo in a double blind crossover trial. Each drug was inhaled 4 times per day for 3 weeks. Baseline forced expiratory flows, specific airway conductance, airway resistnace, and functional residual capacity were measured weekly. These measurements were repeated 15 min and 60 min after laboratory inhalation of each agent, using a separate double blind protocol. No significant differences were observed among the mean baseline function studies during the 3 treatment periods. There were no significant differences in sputum production, sputum thickness, dyspnea, or mouth dryness among the 3 treatment periods. Side effects were mild; isoproterenol treatment was associated with an increased frequency of palpitations, and atropine treatment was associated with difficulty in voiding. Significant increases in lung function were apparent in the measurements made 15 min and 60 min after inhalation of atropine or isoproterenol. Mean values of flow and specific airway conductance increased, and mean values of airway resistance and functional residual capacity decreased after inhalation of either drug. There was no significant difference between the effects of atropine and isoproterenol on lung function, although both differed significantly from the effects of placebo (P less than 0.001). Inhaled atropine sulfate was as effective a bronchodilator as inhaled isoproterenol hydrochloride, and was well tolerated during the 3-week trial of daily therapy.