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PubMed1998

Cognitive and motor functioning in Parkinson disease: subjects with and without questionable dementia.

BACKGROUND: The nature of cognitive performance in subjects with Parkinson disease (PD) without dementia is controversial, perhaps because of failure to exclude subjects with unrecognized very mild dementia. OBJECTIVE: To compare cognitive and motor functioning in well-characterized subjects with PD without overt dementia with healthy elderly control subjects. DESIGN: Subjects' conditions were evaluated clinically and psychometrically at entry into a longitudinal study of cognitive and motor performance in elderly subjects. Measures included a global dementia staging scale, the Washington University Clinical Dementia Rating; psychometric tests, including Logical Memory, Digit Span, Associate Learning, Information, Block Design, Digit Symbol, Trail-making A, Crossing-off, Boston Naming Test, and Word Fluency; and motor measures, including finger tapping, gait velocity, reaction time, and movement time. SETTING: A university-based research facility. SUBJECTS: There were 3 groups of subjects: healthy elderly control subjects (n=43), subjects with PD without dementia (n=58), and subjects with PD with questionable dementia (n=22), each evaluated at time of entry. RESULTS: As expected, both PD groups were impaired on motor measures (gait velocity, finger tapping, and movement time) compared with the healthy elderly control group. Neither PD group showed slowing in reaction time. The subjects with PD with questionable dementia were more impaired on Logical Memory, Block Design, Digit Symbol, and Trailmaking A compared with the subjects with PD without dementia. Although free of clinically evident cognitive dysfunction (Clinical Dementia Rating score, 0), the PD group without dementia was impaired with respect to the healthy elderly control group on all measures from the psychometric assessment except Digit Span, Associate Learning, and Word Fluency. CONCLUSIONS: The PD group without dementia showed global cognitive impairments in comparison with the healthy elderly control group, possibly because the healthy elderly control subjects represented idealized aging. Although the deficits were of small magnitude, this finding suggests that PD may predispose to subclinical cognitive impairment. Longitudinal follow-up is required to determine whether subjects with PD destined to develop overt dementia can be distinguished from those who do not.

Aged↗

PubMed1985

Modifying the snack food consumption patterns of inner city high school students: the Great Sensations Study.

The Great Sensations Program is a nutrition-education project developed for high school students. It was designed to (a) decrease students' consumption of salty snacks and (b) increase students' consumption of fresh fruit snacks. The overall programs were designed following principles of social learning: informative instruction, participatory classroom activities, personal goal setting, feedback, and reinforcement. The program was delivered in six lessons during regular health-education classes. A parental involvement program consisted of mailers and telephone calls to parents to teach them to encourage changes in student snacking habits. A schoolwide program was designed to provide out-of-class peer support for student modifications in salty snack foods. The program was evaluated in one high school using a 2 X 2 design. A second high school served as a no-treatment control. Program assessments were made at both schools before and after the classes, at the end of the school year, and the following fall the next school year following summer vacation. The schoolwide media program was effective in decreasing consumption of salty snack foods and in increasing consumption of target snack foods. However, only those students receiving classroom instruction maintained those changes until the end of the school year. No changes were maintained across summer vacation. These outcomes suggest that school programs developed using principles of social learning may be effective in facilitating important behavior changes at home and at school.

Adolescent↗

PubMed2000

The environmental genome project: ethical, legal, and social implications.

The National Institute of Environmental Health Sciences is supporting a multiyear research initiative examining genetic influences on environmental response. Proponents of this new initiative, known as the Environmental Genome Project, hope that the information learned will improve our understanding of environmentally associated diseases and allow clinicians and public health officials to target disease-prevention strategies to those who are at increased risk. Despite these potential benefits, the project presents several ethical and social challenges. Of immediate concern is the protection of individual research participants. Other ethical issues relate to the application of research results and how study findings could affect social priorities. Clarifying these emerging areas of concern, many of which have not received adequate attention in the existing bioethics literature, is an important step toward minimizing potential research-related risks and defining research needs.

Environmental Health↗

PubMed2004

The neuroanatomy and neuroendocrinology of fragile X syndrome.

Fragile X syndrome (FXS), caused by a single gene mutation on the X chromosome, offers a unique opportunity for investigation of gene-brain-behavior relationships. Recent advances in molecular genetics, human brain imaging, and behavioral studies have started to unravel the complex pathways leading to the cognitive, psychiatric, and physical features that are unique to this syndrome. In this article, we summarize studies focused on the neuroanatomy and neuroendocrinology of FXS. A review of structural imaging studies of individuals with the full mutation shows that several brain regions are enlarged, including the hippocampus, amygdala, caudate nucleus, and thalamus, even after controlling for overall brain volume. These regions mediate several cognitive and behavioral functions known to be aberrant in FXS such as memory and learning, information and sensory processing, and social and emotional behavior. Two regions, the cerebellar vermis, important for a variety of cognitive tasks and regulation of motor behavior, and the superior temporal gyrus, involved in processing complex auditory stimuli, are reported to be reduced in size relative to controls. Functional imaging, typically limited to females, has emphasized that individuals with FXS do not adequately recruit brain regions that are normally utilized by unaffected individuals to carry out various cognitive tasks, such as arithmetic processing or visual memory tasks. Finally, we review a number of neuroendocrine studies implicating hypothalamic dysfunction in FXS, including abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis. These studies may help to explain the abnormal stress responses, sleep abnormalities, and physical growth patterns commonly seen in affected individuals. In the future, innovative longitudinal studies to investigate development of neurobiologic and behavioral features over time, and ultimately empirical testing of pharmacological, behavioral, and even molecular genetic interventions using MRI are likely to yield significant positive changes in the lives of persons with FXS, as well as increase our understanding of the development of psychiatric and learning problems in the general population.

Adolescent↗

PubMed2003

Enhanced release from proactive interference in nonamnesic alcoholic individuals: implications for impaired associative binding.

Proactive interference (PI) occurs when previously learned information reduces the ability to acquire new, related information. Given that PI is modulated by the cholinergic system in rats (E. De Rosa & M. E. Hasselmo, 2000) and that chronic alcohol dependence disrupts cholinergic function in rats and humans, associative properties of PI in patients with alcoholism were examined. It was hypothesized that normal PI contingencies would be disrupted in alcoholic participants. When tested with a paired-associate simultaneous discrimination paradigm, analogous to that used in the rat model, alcoholic participants showed significantly less PI than controls yet performed comparably on a control response reversal task. The absence of PI in alcoholic participants may reflect impaired configural binding of paired-associate stimuli while sparing the elemental ability to process each stimulus component.

Acetylcholine↗

PubMed1999

Recall readiness in children with autism.

When people are asked to learn information they need to judge when they have encoded the information accurately and will be able to retrieve it correctly. Making such a judgment is an aspect of metacognitive ability, and is referred to as "recall readiness." Previous researchers have not considered recall readiness in children with autism, therefore we asked matched groups of children with autism, children with mental retardation, and normally developing children (mean mental age: 7 years) to study several pictures of objects until they felt ready to recall all the objects without error. Their recall was then tested. The children with autism and the children with mental retardation had impaired recall readiness compared to the normally developing children. We discuss this result with reference to other research into the metacognitive abilities of children with autism.

Adolescent↗

PubMed2001

Evidence that age-induced decline in memory retention is delayed in growth hormone resistant GH-R-KO (Laron) mice.

Although the role of growth hormone (GH) in aging is controversial, the recent production of GH-R-KO mice may provide a means for elucidating its importance. Using the inhibitory avoidance learning task as a measure of cognitive aging, the present study compared learning and retention in young and old GH-R-KO mice and their normal siblings. Results for the old normal animals agreed with the current literature, in that the ability of old animals to retain learned information declined over time. However, retention in the old GH-R-KO mice did not decline between the 24-h, 7-day and 28-day retention tests and did not differ from young animals. To determine whether performance differences seen in the old normal vs. old GH-R-KO groups were due to locomotor behavior or emotionality, both groups were tested in the elevated-plus maze. Results showed that the normal and GH-R-KO mice did not differ in number of open or closed arms entered, time spent in closed or open arms or time taken to first enter an open arm. Thus, it was concluded that inhibitory avoidance performance was not affected by differences of locomotor activity or emotionality, and that the absence of GH signaling may be associated with improved long-term memory in aging mice.

Aging↗

PubMed1998

Who learns preventive health care information from where: cross-channel and repertoire comparisons.

We studied from which information channels individuals reported learning the most information about preventive health care, how those channels correlated with one another, and how well they were predicted by demographics and health orientations. A probability sample of 1,963 adults from 8 midwestern communities were interviewed from late 1994 to early 1995. Respondents reported learning different amounts of preventive health information from different channels, and a mix in levels of learning was found across channels. Television news and information rated unexpectedly high across the population studied. An exploratory factor analysis indicated a clear grouping or repertoire consisting of television channels, and for magazines and newspapers, but also a distinct personal media repertoire involving a mix of health professionals, family and friends, books, educational materials, and computers. Demographics did better at predicting learning from traditional print media, but personal health orientations were more effective predictors of personal media; television was less well predicted by either.

Journal Article↗

PubMed2000

Intelligence: success and fitness.

This chapter presents the consensus among psychometricians regarding the construct of general intelligence ('g') and its measurement. More than any other construct, g illustrates the scientific power of construct validation research. To date, g is carried by more assessment vehicles and saturates more aspects of life than any other dimension of human variation uncovered by psychological science. Phenomena most vital to the core of g's nomological network are reviewed (e.g. abstract learning, information processing, and dealing with novelty). This is followed by coverage of relevant but more peripheral phenomena (e.g. crime, health risk behaviour, and income). Because g constitutes such a ubiquitous aspect of the human condition, its omission in social science research often results in underdetermined causal modelling. Frequently, this constitutes a longstanding error in inductive logic, namely, the Fallacy of the Neglected Aspect. Attending to Carnap's Total Evidence Rule can help to forestall neglected aspects in scientific reasoning.

Child↗

PubMed2004

Posttraumatic stress disorder in callers to the Anxiety Disorders Association of America.

We surveyed callers to the Anxiety Disorders Association of America (ADAA) with posttraumatic stress disorder (PTSD) and subthreshold PTSD (SPTSD). Most subjects heard about ADAA through media referrals and were satisfied with the service given by the association. The most frequent requests were for written information, learning how to cope with anxiety, and access to a local support group. Among callers, rates of PTSD (n=80) and SPTSD (n=111) were 8.0% and 11.1%, respectively. PTSD or SPTSD subjects were more likely to be younger, female, and with lower income than their no-Axis I psychiatric disorder controls (NAC) who had been exposed to trauma. In addition, they presented with more history of trauma, especially violent trauma, psychiatric comorbidity, recent psychotropic use, and side effects. More medical comorbidity, increased health service use, and reduced work productivity were also found among the PTSD and SPTSD subjects. SPTSD subjects were comparable to PTSD subjects on most of the measures with a few exceptions (more likely to be married, to have less psychiatric comorbidity, less medication use for mood and social fear, and fewer sedation and sexual side effects, and to have less health service use and work impairment). In conclusion, callers to ADAA with PTSD were particularly impaired and used the health care system extensively. Although the SPTSD subjects were not as impaired as those with PTSD, they were disadvantaged in many ways.

Adult↗

PubMed2004

MRI morphometric and neuropsychological correlates of long-term memory in survivors of childhood leukemia.

BACKGROUND: Long-term survivors of acute lymphoblastic leukemia (ALL) are reported to have post-treatment neurological changes as well as neuropsychological changes. Few studies have investigated the relationship between magnetic resonance imaging (MRI) volumetric measurements of brain regions of interest and cognitive functioning. This study examined the relationship between hippocampal volumes and long-term memory abilities in survivors of ALL. PROCEDURE: Ten survivors of ALL and ten matched controls underwent MRI acquisition. The participants completed a battery of tests measuring both visual and verbal long-term memory. Volumetric measurements of the hippocampus were obtained by consecutive manual tracing using the NIH Image 1.52 program. Estimates of whole brain volume were also obtained. RESULTS: No significant group differences were found in right or left hippocampi. Nor were there significant differences between the two groups on measures of long-term memory. Correlations between volumetric measurements of the hippocampus and measures of long-term memory were non-significant. CONCLUSIONS: Our hypothesis of deficits in both long-term memory and its neural substrates was not supported. It was concluded that the hippocampus, as an early developing structure, may be less vulnerable to chemotherapy treatment. Children surviving ALL are able to retain and retrieve once learned information comparable with peers.

Adolescent↗

PubMed1997

Triazolam impairs delayed recall but not acquisition of various everyday memory tasks in humans.

A double-blind test battery was administered to 24 human subjects (8 control, 16 drug) to assess the effects of 0.125 mg triazolam (oral) on memory encoding and retention across delay intervals ranging from seconds to 1 week after presentation. Although the drug reduced immediate psychomotor performance, it did not impair recall of previously learned information, nor did it significantly impair encoding of new information. The drug enhanced immediate recall of the location and identity of playing cards, without affecting 4-h delayed recall. The drug treatment impaired correct recall of object names after a delay of 20 min. At 4 h delay, the drug impaired olfactory recognition and free-recall of object names. At both 1 day and 1 week delay, the drug impaired recall of biographical information and correct identification of picture-photographer pair associations. The drug also impaired the daily improvement of the drug group as compared with the control group in a geometric puzzle solving task. The time course of these memory impairments compares well with the known effects of triazolam on long-term potentiation (LTP), a candidate biological mechanism underlying telencephalic memory formation and expression.

Adolescent↗

PubMed2001

Lesions of the entorhinal cortex impair acquisition of hippocampal-dependent trace conditioning.

Rabbits with the electrolytic lesions of bilateral entorhinal cortex (EC) were trained with the hippocampal-dependent trace conditioning of the nictitating membrane response. The multiple-unit activity of the hippocampal CA1 region was recorded during conditioning. The conditioned stimulus was a tone (1 kHz, 85 dB, 200-ms duration), the unconditioned stimulus was a corneal air puff (3 psi, 150-ms duration), and the interstimulus interval was 750 ms. The EC-lesioned animals showed only 30% conditioned response (CR) by the ninth session while the sham-operated animals showed above 80% CR. The lesioned animals did not show learning-related changes in the hippocampal activity. When the training was switched to the 300-ms interstimulus interval trace conditioning, both groups learned above 80% CR. The EC-lesioned animals, however, showed less learning-related activity in the hippocampus than the sham-operated animals. These results suggest that the development of the learning-related activity in the hippocampus depends on the intact EC, and that the EC may provide a possible pathway conveying learning information from the cerebellum or cerebral cortex to the hippocampus during the trace conditioning.

Animals↗

PubMed1992

Acute nicotinic blockade produces cognitive impairment in normal humans.

Single oral doses of the central and peripheral nicotinic antagonist mecamylamine were administered to healthy young normal males in doses of 5, 10, and 20 mg in a placebo-controlled, double-blind study. The 20 mg dose caused a significant increase in errors in the learning condition of the Repeated Acquisition task, producing a slower acquisition curve. The lower doses produced less errors, but more than in the placebo condition. There was no effect of drug on the performance component (retrieval of previously learned information). On the recognition memory task, dose-related increases in false-alarms during the delay period were seen, with little effect on misses or hits. Reaction time measures suggested a dose-related slowing of RT on several tasks. Behavioral effects were minimal and physiologic measures were consistent with dose-related ganglionic blockade. We interpret these results to indicate that acute blockade of nicotinic receptor function can produce measurable and significant cognitive impairment, even in non-smoking normals.

Adult↗

PubMed2005

Communication between anesthesiologists, patients and the anesthesia team: a descriptive study of induction and emergence.

PURPOSE: Although the importance of communication skills in anesthetic practice is increasingly recognized, formal communication skills training has hitherto dealt only with limited aspects of this professional activity. We aimed to document and analyze the informally-learned communication that takes place between anesthesia personnel and patients at induction of and emergence from general anesthesia. METHODS: We adopted an ethnographic approach based principally on observation of anesthesia personnel at work in the operating theatres with subsequent analysis of observation transcripts. RESULTS: We noted three main styles of communication on induction, commonly combined in a single induction. In order of frequency, these were: (1) descriptive, where the anesthesiologists explained to the patient what he/she might expect to feel; (2) functional, which seemed designed to help anesthesiologists maintain physiological stability or assess the changing depth of anesthesia and (3) evocative, which referred to images or metaphors. Although the talk we have described is nominally directed at the patient, it also signifies to other members of the anesthetic team how induction is progressing. The team may also contribute to the communication behaviour depending on the context. Communication on emergence usually focused on establishing that the patient was awake. CONCLUSION: Communication at induction and emergence tends to fall into specific patterns with different emphases but similar functions. This communication work is shared across the anesthetic team. Further work could usefully explore the relationship between communication styles and team performance or indicators of patient safety or well-being.

Anesthesia Recovery Period↗

PubMed2006

The CNS renin-angiotensin system.

The renin-angiotensin system (RAS) is one of the best-studied enzyme-neuropeptide systems in the brain and can serve as a model for the action of peptides on neuronal function in general. It is now well established that the brain has its own intrinsic RAS with all its components present in the central nervous system. The RAS generates a family of bioactive angiotensin peptides with variable biological and neurobiological activities. These include angiotensin-(1-8) [Ang II], angiotensin-(3-8) [Ang IV], and angiotensin-(1-7) [Ang-(1-7)]. These neuroactive forms of angiotensin act through specific receptors. Only Ang II acts through two different high-specific receptors, termed AT1 and AT2. Neuronal AT1 receptors mediate the stimulatory actions of Ang II on blood pressure, water and salt intake, and the secretion of vasopressin. In contrast, neuronal AT2 receptors have been implicated in the stimulation of apoptosis and as being antagonistic to AT1 receptors. Among the many potential effects mediated by stimulation of AT2 are neuronal regeneration after injury and the inhibition of pathological growth. Ang-(1-7) mediates its antihypertensive effects by stimulating the synthesis and release of vasodilator prostaglandins and nitric oxide and by potentiating the hypotensive effects of bradykinin. New data concerning the roles of Ang IV and Ang-(1-7) in cognition also support the existence of complex site-specific interactions between multiple angiotensins and multiple receptors in the mediation of important central functions of the RAS. Thus, the RAS of the brain is involved not only in the regulation of blood pressure, but also in the modulation of multiple additional functions in the brain, including processes of sensory information, learning, and memory, and the regulation of emotional responses.

Angiotensins↗

PubMed2006

Analytical tools and approaches for metabolite identification in early drug discovery.

Determination of the chemical structures of metabolites is a critical part of the early pharmaceutical discovery process. Understanding the structures of metabolites is useful both for optimizing the metabolic stability of a drug as well as rationalizing the drug safety profile. This review describes the current state of the art in this endeavor. The likely outcome of metabolism is first predicted by comparison to the literature. Then metabolites are synthesized in a variety of in vitro systems. The various approaches to LC/UV/MS are applied to learn information about these metabolites and structure hypotheses are made. Structures are confirmed by synthesis or NMR. The special topic of reactive metabolite structure determination is briefly addressed.

Animals↗

PubMed1989

Conditioning experiences and phobias.

A retrospective study was conducted to examine the extent to which phobias are associated with a conditioning pathway to fear. The Phobic Origin Questionnaire (Ost and Hugdahl, Behav. Res. Ther. 19, 439-477, 1981) was administered to a sample of 91 phobic outpatients (patients with panic disorder with agoraphobia, social phobics, simple phobics). Results show clearly that conditioning experiences occur more frequently than either vicarious or informational, learning experiences, which confirms the findings previously reported by Rimm, Janda, Lancaster, Nahl and Dittmar (Behav. Res. Ther. 15, 231-238, 1977) and by Ost and Hugdahl (1981; Behav. Res. Ther. 21, 623-631, 1983). Yet, conditioning experiences consist mainly of panic attacks in confirmed environments. The findings also suggest that a considerable number of phobias are based on a combination of different pathways to fear.

Adult↗