Effects of scopolamine on matching to sample paradigm and related tests in human subjects

This was a double-blind placebo-controlled study with a cross-over design to examine the effects of scopolamine on cognitive functions in young healthy subjects. Scopolamine hydrobromide was administered subcutaneously to 12 subjects (mean +/- SD age 23.8 +/- 2.2 years) at doses of 0.3 and 0.6 mg in comparison with two placebo conditions. Scopolamine at both doses produced marked sedation as rated by subjects and an observer. In the continuous performance test, vigilance was impaired by both doses of scopolamine. The span of apprehension test showed differing results (only the high dose of scopolamine showed a performance decrement only in the three-character version of the span of apprehension test). Significant impairment by both doses of scopolamine was seen in immediate and delayed free recall, continuous visual recognition, running word recognition and running picture recognition. While scopolamine caused a significant slowing in average reaction times for simultaneous matching as well as for delayed matching, subjects made more errors under scopolamine compared to placebo only in delayed matching, not in simultaneous matching. Also, the main outcome of matching to sample showed significant effects only in delayed matching, not in simultaneous matching. Notable in this study is the incongruity between the simultaneous matching test and the span of apprehension test on the one hand and the other cognitive tests used on the other. These results demonstrated that scopolamine has a greater effect on memory than on attention. Thus, the scopolamine-induced effects in the present study seem to be more relevant to Alzheimer's disease in an advanced phase than to normal aging. Copyright (C) 2003 S. Karger AG, Basel

Structured Psychosocial Stress and Therapeutic Intervention: Toward a Realistic Biological Medicine

Using generalized 'language of thought' arguments appropriate to interacting cognitive modules, we explore how disease states can interact with medical treatment, including, but not limited to, drug therapy. The feedback between treatment and response creates a kind of idiotypic 'hall of mirrors' generating a pattern of 'efficacy', 'treatment failure', and 'adverse reactions' which will, from a Rate Distortion perspective, embody a distorted image of externally-imposed structured psychosocial stress. This analysis, unlike current pharmacogenetics, does not either reify 'race' or blame the victim by using genetic structure to place the locus-of-control within a group or individual. Rather, it suggests that a comparatively simple series of questions to identify longitudinal and cross-sectional stressors may provide more effective guidance for specification of individual therapy than complicated genotyping strategies of dubious meaning. These latter are likely to be both very expensive and utterly blind to the impact of structured psychosocial stress -- a euphemism for various forms of racism and ethnic cleansing -- which, we contend, is often a principal determinant of treatment outcome at both individual and community levels of organization. We propose, to effectively address 'health disparities' between populations, and in contrast to current biomedical ideology based on a simplistic genetic determinism, a richer program of biological medicine reflecting Lewontin's 'triple helix' of genes, environment, and development, a program more in concert with the realities of a basic human biology marked by hypersociality unusual in vertibrates. Aggressive social, economic, and other policies of affirmative action to redress the persisting burdens of history would be an integral component of any such project

Learning medical alarms whilst performing other tasks.

Two studies are reported which first observe, and then attempt to replicate, the cognitive demands of intensive care unit (ICU) activity whilst concurrently learning audible alarms. The first study, an observational study in an ICU ward, showed that the alarms are very frequent and co-occur with some activities more than others. The three most frequently observed activities observed in the ICU were drugs (calculation, preparation and administration), patient observation and talking. The cognitive demands of these activities were simulated in a second, laboratory-based experiment in which alarms were learned. The results showed that performance in the alarm task generally improved as participants were exposed to more repetitions of those alarms, but that performance decrements were observed in the secondary tasks, particularly when there were two or three of them. Some confusions between the alarms persisted to the end of the study despite prolonged exposure to the alarms, confusions which were likely caused by both acoustic and verbal labelling similarities. PRACTITIONER SUMMARY: The cognitive demands of working in an ICU were observed and simulated whilst alarms were learned. Alarms should generally avoid sharing similar rhythmic (and other) characteristics. The simulation task described here could be used for testing alarm learning without requiring a clinical environment

Do antidepressants cure or create abnormal brain states?

Moncrieff and Cohen argue that psychotropic drugs create abnormal states that may co-incidentally relieve symptoms of mental illness

Cognitive performance in multiple system atrophy

The cognitive performance of a group of patients with multiple system atrophy (MSA) of striato-nigral predominance was compared with that of age and IQ matched control subjects, using three tests sensitive to frontal lobe dysfunction and a battery sensitive to memory and learning deficits in Parkinson's disease and dementia of the Alzheimer type. The MSA group showed significant deficits in all three of the tests previously shown to be sensitive to frontal lobe dysfunction. Thus, a significant proportion of patients from the MSA group failed an attentional set-shifting test, specifically at the stage when an extra-dimensional shift was required. They were also impaired in a subject-ordered test of spatial working memory. The MSA group showed deficits mostly confined to measures of speed of thinking, rather than accuracy, on the Tower of London task. These deficits were seen in the absence of consistent impairments in language or visual perception. Moreover, the MSA group showed no significant deficits in tests of spatial and pattern recognition previously shown to be sensitive to patients early in the course of probable Alzheimer's disease and only a few patients exhibited impairment on the Warrington Recognition Memory Test. There were impairments on other tests of visual memory and learning relative to matched controls, but these could not easily be related to fundamental deficits of memory or learning. Thus, on a matching-to-sample task the patients were impaired at simultaneous but not delayed matching to sample, whereas difficulties in a pattern-location learning task were more evident at its initial, easier stages. The MSA group showed no consistent evidence of intellectual deterioration as assessed from their performance on subtests of the Wechsler Adult Intelligence Scale (WAIS) and the National Adult Reading Test (NART). Consideration of individual cases showed that there was some heterogeneity in the pattern of deficits in the MSA group, with one patient showing no impairment, even in the face of considerable physical disability. The results show a distinctive pattern of cognitive deficits, unlike those previously seen using the same tests in patients with Parkinson's and Alzheimer's diseases, and suggesting a prominent frontal-lobe-like component. The implications for concepts of 'subcortical' dementia and 'fronto-striatal' cognitive dysfunction are considered

The hypocretin/orexin antagonist almorexant promotes sleep without impairment of performance in rats.

The hypocretin receptor (HcrtR) antagonist almorexant (ALM) has potent hypnotic actions but little is known about neurocognitive performance in the presence of ALM. HcrtR antagonists are hypothesized to induce sleep by disfacilitation of wake-promoting systems whereas GABAA receptor modulators such as zolpidem (ZOL) induce sleep through general inhibition of neural activity. To test the hypothesis that less functional impairment results from HcrtR antagonist-induced sleep, we evaluated the performance of rats in the Morris Water Maze in the presence of ALM vs. ZOL. Performance in spatial reference memory (SRM) and spatial working memory (SWM) tasks were assessed during the dark period after equipotent sleep-promoting doses (100 mg/kg, po) following undisturbed and sleep deprivation (SD) conditions. ALM-treated rats were indistinguishable from vehicle (VEH)-treated rats for all SRM performance measures (distance traveled, latency to enter, time within, and number of entries into, the target quadrant) after both the undisturbed and 6 h SD conditions. In contrast, rats administered ZOL showed impairments in all parameters measured compared to VEH or ALM in the undisturbed conditions. Following SD, ZOL-treated rats also showed impairments in all measures. ALM-treated rats were similar to VEH-treated rats for all SWM measures (velocity, time to locate the platform and success rate at finding the platform within 60 s) after both the undisturbed and SD conditions. In contrast, ZOL-treated rats showed impairments in velocity and in the time to locate the platform. Importantly, ZOL rats only completed the task 23-50% of the time while ALM and VEH rats completed the task 79-100% of the time. Thus, following equipotent sleep-promoting doses, ZOL impaired rats in both memory tasks while ALM rats performed at levels comparable to VEH rats. These results are consistent with the hypothesis that less impairment results from HcrtR antagonism than from GABAA-induced inhibition

Effects of ecstasy/polydrug use on memory for associative information

Rationale Associative learning underpins behaviours that are fundamental to the everyday functioning of the individual. Evidence pointing to learning deficits in recreational drug users merits further examination. Objectives A word pair learning task was administered to examine associative learning processes in ecstasy/polydrug users. Methods After assignment to either single or divided attention conditions, 44 ecstasy/polydrug users and 48 non-users were presented with 80 word pairs at encoding. Following this, four types of stimuli were presented at the recognition phase: the words as originally paired (old pairs), previously presented words in different pairings (conjunction pairs), old words paired with new words, and pairs of new words (not presented previously). The task was to identify which of the stimuli were intact old pairs. Results Ecstasy/ploydrug users produced significantly more false-positive responses overall compared to non-users. Increased long-term frequency of ecstasy use was positively associated with the propensity to produce false-positive responses. It was also associated with a more liberal signal detection theory decision criterion value. Measures of long term and recent cannabis use were also associated with these same word pair learning outcome measures. Conjunction word pairs, irrespective of drug use, generated the highest level of false-positive responses and significantly more false-positive responses were made in the divided attention condition compared to the single attention condition. Conclusions Overall, the results suggest that long-term ecstasy exposure may induce a deficit in associative learning and this may be in part a consequence of users adopting a more liberal decision criterion value