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Biomedical subjects

H Weingartner

Publications and source records attributed to H Weingartner.

At least 19 recordsLinked to original sources

Parallel distributed processing and neuropsychology: a neural network model of Wisconsin Card Sorting and verbal fluency.

Neural networks can be used as a tool in the explanation of neuropsychological data. Using the Hebbian Learning Rule and other such principles as competition and modifiable interlevel feedback, researchers have successfully modeled a widely used neuropsychological test, the Wisconsin Card Sorting Test. One of these models is reviewed here and extended to a qualitative analysis of how verbal fluency might be modeled, which demonstrates the importance of accounting for the attentional components of both tests. Difficulties remain in programming sequential cognitive processes within a parallel distributed processing (PDP) framework and integrating exceedingly complex neuropsychological tests such as Proverbs. PDP neural network methodology offers neuropsychologists co-validation procedures within narrowly defined areas of reliability and validity.

Attention

Measurement and interpretation of changes in memory in response to drug treatments.

Drug-induced changes in cognitive functions such as memory are generally domain specific rather than general effects, that is, only some components of memory are altered. Changes in memory can be secondary to alterations in other cognitive domains such as attention, or non-cognitive domains (mood and arousal), or the direct result of alterations on those neurobiological systems that determine memory functions. The selective memory impairing effects of benzodiazepines are used to illustrate how cognitive neuroscience methods and theory can be useful in assessing the memory changes produced by psychoactive drugs.

Animals

Script generation as an indicator of knowledge representation in patients with Alzheimer's disease.

We examined script and lexical retrieval in patients with probable Dementia-Alzheimer's Type (DAT), Depressed patients, and normal controls. DAT patient breakdown in script production was structurally similar to their impaired lexical retrieval such that script events of low frequency and low centrality value were lost first. DAT patients also produced more events that fell outside the script boundary as well as more event-order errors. Four cases with DAT were identified on the basis of Z scores whose script production was at least 2 SDs greater than their lexical production or vice versa. This finding suggests that it may be possible to dissociate script and lexical knowledge and production processes. The findings lend partial support for a model of knowledge representation that includes parallel and partially redundant memory networks that are distinctly distributed in the brain.

Aged

Automatic memory processes in patients with dementia-Alzheimer's type (DAT).

We examined patients with Dementia-Alzheimer's Type, depression, and matched controls on tasks designed to compare automatic (monitoring frequency and modality) and effortful (free recall) processing of words and pictures. The results demonstrated that depressed patients performed poorly only when conditions required effortful processing, but DAT patients performed poorly under all conditions. There was almost no overlap in scores between DAT and elderly depressed patients on one of the measures of automatic processing suggesting that this measure may be clinically useful. The results suggest that automatic memory processes can be partially dissociated from effortful memory processes, but that both types of operations are impaired in DAT patients.

Aged

Implicit learning in patients with Alzheimer's disease.

We examined implicit memory using priming and procedural learning tasks in patients with probable Dementia-Alzheimer's Type (DAT) to examine whether priming and procedural processes could be dissociated and whether task specificity was a factor in DAT patient performance. Priming was tested using a word recognition paradigm (perceptual priming) and by repeated administrations of a fragmented objects test (long term priming). Procedural learning was tested using repeated and random sequences on a choice serial reaction time task and by repeated administration of a puzzle map of the United States. DAT patients were compared to hospitalized depressed patients, patients suffering from Progressive Supranuclear Palsy (PSP), and normal controls. We found that DAT patients demonstrated marginal but significant implicit learning on both procedural learning and perceptual priming tasks. DAT patients performed relatively better on the procedural learning task than a perceptual priming task compared to PSP patients, suggesting that priming of meaningful stimuli is subserved by cortical structures whereas procedural motor responses to simple serial visual stimulus patterns can be maintained by subcortical systems. Furthermore, our findings suggest that priming and procedural processes can be dissociated and that task specificity is a factor in interpreting the results of implicit learning paradigms in DAT patients. The implications of these results for models of knowledge representation and memory processes as well as the way they can serve as models for testing nootropic drug effects are discussed.

Aged

Cognitive effects of corticosteroids.

In three independent studies with different designs and groups of subjects, the authors found that 1) depressed patients who did not suppress cortisol when given dexamethasone (compared to suppressors and normal control subjects), 2) healthy volunteers given a single 1-mg dose of dexamethasone (compared to those given placebo), and 3) healthy volunteers given 80 mg/day of prednisone for 5 days (compared to those given placebo) all made significantly more errors of commission in verbal memory tasks, with no significant change in their rates of errors of omission. These findings raise the possibility of specific corticosteroid-related cognitive impairments.

Adrenal Cortex Hormones

Low-dose oral lorazepam administration in Alzheimer subjects and age-matched controls.

Ten patients with Alzheimer's disease and ten age-matched normal controls were studied in a double-blind, placebo-controlled acute trial of 1 mg PO lorazepam to test the effects of low-dose benzodiazepine on memory and behavior in a mostly older population. Cognitive effects differed somewhat between Alzheimer patients and normal controls, with Alzheimer patients revealing predominantly "attentional" impairments and age-matched controls showing possible "disinhibition." Specifically, Alzheimer patients made more omission errors on a continuous performance task, whereas controls made more commission and intrusion errors with lorazepam versus placebo. This low dose of lorazepam (1 mg), which was associated with mild but statistically significant sedation in both groups, also produced no significant decrease in recent memory or in access to semantic memory. These cognitive findings contrast markedly to the reported effects of scopolamine on recent memory; therefore, supporting the idea that cholinergic interruption has a more specific effect on human memory and on learning than that of low-dose benzodiazepines. Further studies with a wider dose range of benzodiazepines are necessary to evaluate the possibility of differential sensitivity between Alzheimer patients and normal elderly controls.

Administration, Oral

Multiple-dose arecoline infusions in Alzheimer's disease.

Twelve patients with dementia of the Alzheimer type received two-hour infusions of placebo and the muscarinic cholinergic agonist arecoline hydrobromide at rates of 1, 2, and 4 mg/h in a double-blind, randomized fashion. These infusions resulted in dose-dependent physiologic and neuroendocrine effects consistent with central cholinergic stimulation. Infusions were generally well tolerated. No statistically significant improvement in performance on most cognitive tasks assessing knowledge memory and episodic learning and memory was observed at any dose, although marginal improvement in picture recognition ability and in ratings of word-finding were observed at the lower doses. Psychomotor activation and slightly improved affect were reliably observed at the lower doses, whereas increasing psychomotor retardation was observed at the highest dose. The data support a role for central cholinergic modulation of some aspects of cognition, behavior, and affect in this population. The apparent greater behavioral sensitivity of patients with Alzheimer's disease in comparison with subject populations previously studied, as well as the altered dose responsiveness, merit further study in relationship to normal aging.

Aged

The effects of acute scopolamine in geriatric depression.

In an intensive multidrug, multidose study, nine elderly depressed patients were administered 0.1, 0.25, and 0.5 mg of scopolamine hydrobromide, 1 mg of oral lorazepam, and placebo in a double-blind investigation aimed at assessing the status of the central cholinergic nervous system in geriatric depression. Significant cognitive and behavioral effects of scopolamine were observed only at the high dose (0.5 mg), while lower doses and lorazepam showed no significant differences from placebo. Cognitive deficits caused by scopolamine were in the areas of new learning, access to semantic memory, vigilance, and continuous performance. Behavioral effects consisted of activation, restlessness, and anxiety, but there was no significant effect on depressed mood. These results suggest that elderly depressed patients with mild to moderate cognitive impairment seem to be more similar to previously studied elderly controls rather than to patients with Alzheimer's disease in their reaction to short-term cholinergic blockade, and suggest that the cognitive and mood changes often seen in geriatric depression may involve factors other than disturbed muscarinic cholinergic mechanisms.

Aged

Clinical relevance of effects of benzodiazepines on learning and memory.

The effects of benzodiazepines on learning and memory are examined in the various clinical situations in which these drugs are used. Alterations in performance arising from the conditions for which benzodiazepines are prescribed are also considered. Current evidence indicates that, in anxious patients, as in normal volunteers, benzodiazepines impair the acquisition of new information (episodic memory). Although some tolerance may develop to these impairments, deficits are observed even after patients have been taking their medication chronically. Like amnesic patients, benzodiazepine-treated subjects may be unaware of their impaired ability to learn. The effects of the impairments on behavioral psychotherapies are considered.

Anti-Anxiety Agents

Intravenous nicotine in Alzheimer's disease: a pilot study.

In the first study to examine direct nicotinic augmentation of central cholinergic functioning in Alzheimer's disease, six patients were studied in an intensive pilot study with three doses (0.125, 0.25, and 0.5 microgram/kg/min) of intravenous nicotine and placebo. Cognitive tests showed a decrease in intrusion errors on the middle (0.25 microgram) dose. Prominent behavioral effects were noted, with significant dose-related increases in anxiety and depressive affect. These results suggest that central nicotinic cholinergic stimulation deserves further investigation as a treatment in Alzheimer's disease and that nicotine may also be a useful investigative tool in other populations as a probe of central cholinergic function, especially in regard to the modulation of affect.

Aged

Automatic and effortful processing in attention deficit/hyperactivity disorder.

Twenty-five boys with Attention Deficit/Hyperactivity Disorder and 23 age-matched controls were compared on verbal memory tasks differentiating automatic versus effortful information processing. Automatic processing tasks included the recognition of new or old words in a list and the recognition of frequency of occurrence of words in a list. Effortful tasks included free recall of lists of both related and unrelated words. Hyperactive boys did not differ from controls in automatic processing capabilities but demonstrated significantly poorer effortful processing. Intercorrelations of the variables revealed high correlations between scores on effortful measures and also raise questions about the purity of automaticity in some tasks employed. Stepwise discriminant analysis demonstrated that free recall of related words (an effortful task) best discriminated between groups. Effort-related processing in hyperactive and normal children is discussed in relation to variables of motivation, affect, arousal, and other higher-order cognitive processes.

Arousal

Intellectual function following penetrating head injury in Vietnam veterans.

The extent to which intellectual processes are preserved as a function of preinjury 'intelligence' and of size and location of the brain lesions was evaluated in Vietnam war veterans who survived penetrating missile wounds. With regard to an overall postinjury intelligence test score, preinjury intelligence was most predictive, size of lesion was next most predictive and lesion location was least important. For subtest scores from the same intelligence test, lesion location assumed much greater predictive value. Specifically, left temporal and occipital lesions impaired performance on subtests assessing vocabulary and object-function matching ability.

Adult

High-dose naloxone in older normal subjects: implications for Alzheimer's disease.

The behavioral and cognitive effects of naloxone HCl, in doses of 5 micrograms/kg, 0.1 mg/kg, and 2.0 mg/kg administered as an IV bolus, were assessed in a double-blind, placebo-controlled, randomized study of eight normal subjects ranging in age from 44 to 74 years (mean 63). Naloxone produced mild behavioral effects with slight cognitive impairment after the 2.0 mg/kg dose only. The threshold, dose dependency, characteristics, and magnitude of these behavioral effects were similar to what has previously been reported in young normal subjects, but markedly different from those observed in patients with dementia of the Alzheimer type (DAT) matched in age to the current study sample. These data suggest that the metabolic fate of naloxone is not substantially affected by age within the range studied. The findings of this study provide further support for a role for endogenous opiate systems in the modulation of behavior and cognition, and suggest that the unusual behavioral sensitivity of patients with DAT to naloxone cannot be accounted for by the effect of age.

Adult

L-deprenyl in Alzheimer's disease. Preliminary evidence for behavioral change with monoamine oxidase B inhibition.

Since monoamine neurotransmitter disturbances exist in some cases of dementia of the Alzheimer's type (DAT), monoamine-enhancing drugs may ameliorate some symptoms of DAT. L-Deprenyl is a monoamine oxidase (MAO) inhibitor that is generally free of undesired effects. At low doses (10 mg/d) it selectively inhibits MAO-B, an enzyme whose level is elevated in the brains of patients with DAT who are studied post mortem. At higher doses it has more complex effects, including inhibition of MAO-A plus MAO-B. We administered 10 mg/d and 40 mg/d of L-deprenyl to 17 patients with DAT in a double-blind, placebo-controlled, serial treatment. Total Brief Psychiatric Rating Scale scores decreased significantly during 10-mg/d treatment, with decreases in measures of anxiety/depression, tension, and excitement. Approximately one half of the patients' conditions were judged to be improved clinically, with evidence of increased activity and social interaction along with reduced tension and retardation. Similar but smaller changes were observed during 40-mg/d treatment. The behavioral changes were associated with improvement in performance on a complex cognitive task requiring sustained effort. There were minimal physiologic and side effects. The greater effect of low-dose L-deprenyl therapy suggests that it is the inhibition of MAO-B, and not MAO-A, that may be important in the behavioral effects of L-deprenyl administration to patients with DAT.

Adult

Cognitive effects of L-deprenyl in Alzheimer's disease.

Monoamine neurotransmitter systems, along with cholinergic systems, are known to play important roles in cognition, and are disrupted in at least some patients with dementia of the Alzheimer type (DAT). This suggests that monoamine-enhancing drugs might ameliorate cognitive symptoms in certain patients with DAT. L-Deprenyl is a monoamine oxidase (MAO) inhibitor which may selectively inhibit MAO-B at low doses, while at high doses it nonselectively inhibits MAO-A as well as MAO-B. We studied its effects on several types of cognitive function in 17 patients with DAT. Two doses of L-deprenyl (10 mg/day and 40 mg/day) and placebo were compared in a double-blind, serial treatment design. Episodic learning and memory, knowledge memory, attention, recognition, and performance on a continuous performance task were assessed at baseline and under these drug and placebo conditions. Statistically significant improvement was noted in performance on an episodic memory and learning task requiring complex information processing and sustained conscious effort during treatment with L-deprenyl 10 mg/day. Knowledge memory, intrusions, and other cognitive functions relevant to DAT were not altered by L-deprenyl at either dose.

Adult