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Biomedical subjects

J O'Keefe

Publications and source records attributed to J O'Keefe.

At least 19 recordsLinked to original sources
PubMed2001

Transmyocardial CO(2) laser revascularization improves symptoms, function, and quality of life: 12-month results from a randomized controlled trial.

PURPOSE: To describe differences in health status (symptoms, physical function, and quality of life) between continued medical management and transmyocardial revascularization with a carbon dioxide laser in patients with severe, symptomatic, inoperable coronary artery disease. SUBJECTS AND METHODS: This prospective, multicenter trial randomized 98 patients to transmyocardial revascularization and 99 to continued medical therapy. Health status was assessed with the Seattle Angina Questionnaire and the Short Form-36 at baseline and at 3, 6, and 12 months. A new analytic technique, the benefit statistic, was developed to facilitate interpretability of disease-specific health status assessments over time. RESULTS: Of the 99 patients assigned to medical therapy, 59 (60%) subsequently underwent transmyocardial revascularization. By an intention-to-treat analysis, patients initially randomized to transmyocardial revascularization had 44% of their angina eliminated versus 21% for the medical treatment group (difference = 23%; 95% confidence interval [CI], 11% to 34%). Differences in the benefits of transmyocardial revascularization on physical limitations (33% vs 11% in the medical arm [difference = 23%; 95% CI, 15% to 31%]) and quality of life (47% vs 20% in the medical arm [difference = 26%; 95% CI, 18% to 35%]) were similarly large. These benefits were apparent at 3 months and sustained throughout the 1 year of follow-up. An efficacy analysis that excluded patients who crossed over from the medical treatment to transmyocardial revascularization arm suggested greater treatment benefits. CONCLUSIONS: Transmyocardial revascularization may offer a valuable palliative alternative to patients with severe limitations in health status for whom no standard revascularization options exist.

Angina Pectoris↗
PubMed2001

Memory for events and their spatial context: models and experiments.

The computational role of the hippocampus in memory has been characterized as: (i) an index to disparate neocortical storage sites; (ii) a time-limited store supporting neocortical long-term memory; and (iii) a content-addressable associative memory. These ideas are reviewed and related to several general aspects of episodic memory, including the differences between episodic, recognition and semantic memory, and whether hippocampal lesions differentially affect recent or remote memories. Some outstanding questions remain, such as: what characterizes episodic retrieval as opposed to other forms of read-out from memory; what triggers the storage of an event memory; and what are the neural mechanisms involved? To address these questions a neural-level model of the medial temporal and parietal roles in retrieval of the spatial context of an event is presented. This model combines the idea that retrieval of the rich context of real-life events is a central characteristic of episodic memory, and the idea that medial temporal allocentric representations are used in long-term storage while parietal egocentric representations are used to imagine, manipulate and re-experience the products of retrieval. The model is consistent with the known neural representation of spatial information in the brain, and provides an explanation for the involvement of Papez's circuit in both the representation of heading direction and in the recollection of episodic information. Two experiments relating to the model are briefly described. A functional neuroimaging study of memory for the spatial context of life-like events in virtual reality provides support for the model's functional localization. A neuropsychological experiment suggests that the hippocampus does store an allocentric representation of spatial locations.

Animals↗
PubMed2001

Bilateral hippocampal pathology impairs topographical and episodic memory but not visual pattern matching.

A virtual reality environment was used to test memory performance for simulated "real-world" spatial and episodic information in a 22-year-old male, Jon, who has selective bilateral hippocampal pathology caused by perinatal anoxia. He was allowed to explore a large-scale virtual reality town and was then tested on his memory for spatial layout and for episodes experienced. Topographical memory was tested by assessing his ability to navigate, recognize previously visited locations, and draw maps of the town. Episodic memory was assessed by testing the retrieval of simulated events which consisted of collecting objects from characters while following a route through the virtual town. Memory for the identity of objects, as well as for where they were collected, from whom, and in what order, was also tested. While the first task tapped simple recognition memory, the latter three tested memory for context. Jon was impaired on all topographical tasks and on his recall of the context-dependent questions. However, his recognition of objects from the virtual town, and of "topographical" scenes (as evaluated by standard neuropsychological tests), was not impaired. These findings are consistent with the view that the hippocampus is involved in navigation, recall of long term allocentric spatial information and context-dependent episodic memory, but not visual pattern matching.

Adult↗
PubMed2001

A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events.

Virtual reality (VR) and event-related functional magnetic resonance imaging were used to study memory for the spatial context of controlled but lifelike events. Subjects received a set of objects from two different people in two different places within a VR environment. Memory for the objects, and for where and from whom they were received was tested by putting the subject back into a place in the company of a person and giving a paired forced choice of objects. In four conditions objects had to be chosen according to different criteria: which was received in that place, which was received from that person, which object was recognized, and which object was widest. Event-related functional magnetic resonance imaging was performed during testing to identify areas involved in retrieval of the spatial context of an event. A network of areas was identified consisting of a temporoparietal pathway running between the precuneus and parahippocampi via retrosplenial cortex and the parieto-occipital sulcus, left hippocampus, bilateral posterior parietal, dorsolateral, ventrolateral and anterior prefrontal cortices, and the anterior cingulate. Of these areas the parahippocampal, right posterior parietal, and posteriodorsal medial parietal areas were specifically involved in retrieval of spatial context compared to retrieval of nonspatial context. The posterior activations are consistent with a model of long-term storage of allocentric representations in medial temporal regions with translation to body-centered and head-centered representations computed in right posterior parietal cortex and buffered in the temporoparietal pathway so as to provide an imageable representation in the precuneus. Prefrontal activations are consistent with strategic retrieval processes, including those required to overcome the interference between the highly similar events.

Adult↗
PubMed2001

Unilateral temporal lobectomy patients show lateralized topographical and episodic memory deficits in a virtual town.

A large-scale virtual reality town was used to test the topographical and episodic memory of patients with unilateral temporal lobe damage. Seventeen right and 13 left temporal lobectomy patients were compared with 16 healthy matched control subjects. After they had explored the town, subjects' topographical memory was tested by requiring them to navigate to specific locations in the town. The ability to recognize scenes from and draw maps of the virtual town was also assessed. Following the topographical memory tests, subjects followed a route around the same town but now collected objects from two different characters in two different locations. Episodic memory for various aspects of these events was then assessed by paired forced-choice recognition tests. The results showed an interaction between laterality and test type such that the right temporal lobectomy (RTL) patients were worse on tests of topographical memory, and the left temporal lobectomy (LTL) patients worse on tests of context-dependent episodic memory. Specifically, the RTL group was impaired on navigation, scene recognition and map drawing relative to control subjects. They were also impaired on recognition of objects in the episodic memory task. The LTL group was impaired relative to control subjects on their memory for contextual aspects of the events, such as who gave them the objects, the order in which objects were received and the locations in which they received them. They were also mildly impaired on topographical memory, but less so than the RTL group. These results suggest that topographical memory is predominately mediated by structures in the right medial temporal lobe, whereas the context-dependent aspects of episodic memory in this non-verbal test are more dependent on the left medial temporal lobe.

Adult↗
PubMed2001

Balance and mobility following stroke: effects of physical therapy interventions with and without biofeedback/forceplate training.

BACKGROUND AND PURPOSE: Visual biofeedback/forceplate systems are often used for treatment of balance disorders. In this study, the researchers investigated whether the addition of visual biofeedback/forceplate training could enhance the effects of other physical therapy interventions on balance and mobility following stroke. SUBJECTS: The study included a sample of convenience of 13 outpatients with hemiplegia who ranged in age from 30 to 77 years (mean=60.4, SD=15.4) and were 15 to 538 days poststroke. METHODS: Subjects were assigned randomly to either an experimental group or a control group when the study began, and their cognitive and visual-perceptual skills were tested by a psychologist. Subjects were also assessed using the Berg Balance Scale and the Timed "Up & Go" Test before and after 4 weeks of physical therapy. Both groups received physical therapy interventions designed to improve balance and mobility 2 to 3 times per week. The experimental group trained on the NeuroCom Balance Master for 15 minutes of each 50-minute treatment session. The control group received other physical therapy for 50 minutes. RESULTS: Following intervention, both groups scored higher on the Berg Balance Scale and required less time to perform the Timed "Up & Go" Test. These improvements corresponded to increased independence of balance and mobility in the study population. However, a comparison of mean changes revealed no differences between groups. DISCUSSION AND CONCLUSION: Although both groups demonstrated improvement following 4 weeks of physical therapy interventions, no additional effects were found in the group that received visual biofeedback/forceplate training combined with other physical therapy.

Accidental Falls↗
PubMed2000

Combined lesions of hippocampus and subiculum Do not produce deficits in a nonspatial social olfactory memory task.

Rats transmit information to each other about which foods are safe to eat. If a rat smells a food odor on the breath of another rat, it is subsequently more likely to eat that food than an alternative. Work by Galef et al. (1988) has shown that the observer rat forms an association between two olfactory stimuli on the breath of the demonstrator rat that has eaten the food, the food odor and carbon disulphide, which is normally present in the rat breath. Bunsey and Eichenbaum (1995) claimed that the hippocampus/subicular region is required for the long-term retention of this nonspatial form of associative memory on the basis that combined lesions of the hippocampus and subiculum produced a deficit, but lesions of either structure alone did not. We report here a failure to repeat this finding. Rats with either combined lesions of the hippocampus and subiculum or with amygdala lesions were tested on their ability to remember this association either immediately (testing short-term memory) or after a 24 hr delay (testing long-term memory). Neither lesion group exhibited significant memory deficits on this nonspatial associative task at either test interval. In contrast, a deficit was observed on a spatial memory task (forced-choice alternation t-maze) for animals with combined lesions of the hippocampus and subiculum. These results contradict the findings of Bunsey and Eichenbaum (1995) and support the idea that the hippocampus/subicular region is not required for this nonspatial associative memory.

Amygdala↗
PubMed2000

Modeling place fields in terms of the cortical inputs to the hippocampus.

A model of place-cell firing is presented that makes quantitative predictions about specific place cells' spatial receptive fields following changes to the rat's environment. A place cell's firing rate is modeled as a function of the rat's location by the thresholded sum of the firing rates of a number of putative cortical inputs. These inputs are tuned to respond whenever an environmental boundary is at a particular distance and allocentric direction from the rat. The initial behavior of a place cell in any environment is simply determined by its set of inputs and its threshold; learning is not necessary. The model is shown to produce a good fit to the firing of individual place cells, and populations of place cells across environments of differing shape. The cells' behavior can be predicted for novel environments of arbitrary size and shape, or for manipulations such as introducing a barrier. The model can be extended to make behavioral predictions regarding spatial memory.

Afferent Pathways↗
PubMed2000

Predictions derived from modelling the hippocampal role in navigation.

A computational model of the lesion and single unit data from navigation in rats is reviewed. The model uses external (visual) and internal (odometric) information from the environment to drive the firing of simulated hippocampal place cells. Constraints on the functional form of these inputs are drawn from experiments using an environment of modifiable shape. The place cell representation is used to guide navigation via the creation of a representation of goal location via Hebbian modification of synaptic strengths. The model includes consideration of the phase of firing of place cells with respect to the theta rhythm of hippocampal EEG. A series of predictions for behavioural and single-unit data in rats are derived from the input and output representations of the model.

Animals↗
PubMed2000

Caveat emptor.

Explore the source record for details and available documents.

Conflict of Interest↗
PubMed1999

Do hippocampal pyramidal cells signal non-spatial as well as spatial information?

It is generally agreed that the rat hippocampus is involved in spatial memory. Whether this is its sole or primary function, or merely one component of a broader function, is still debated. It has been suggested, for example, that the hippocampus stores information about flexible relations between stimuli, both spatial and non-spatial. In this paper, I reiterate the basic tenet of the cognitive map theory that the processing and storage of spatial information is the primary and perhaps the exclusive role of the hippocampus in the rat, and that data that appear to contradict this have been misinterpreted. These data are found in reports of non-spatial correlates of unit activity recorded in the awake animals and reports of deficits on non-spatial tasks following hippocampal lesions. In this paper, I examine both claims and suggest alternative explanations of the data. The first part of the paper contains a review of some of the properties of hippocampal place cells, which might be misinterpreted as non-spatial in "non-spatial" tasks. For example, if an animal is trained to carry out a sequence of stereotyped actions in different parts of an environment, there will be a strong correlation between the performance of each behaviour and the animal's location, and it is necessary to rule out the locational correlate as the cause of the firing pattern. The second part of the paper looks at the results of experiments on conditioning and non-spatial discrimination tasks and concludes that the results are less supportive of a more general relational theory of hippocampal function than has been suggested. Furthermore, there is often a discrepancy between the correlates of unit firing in non-spatial tasks and the absence of an effect of hippocampal damage on these same or similar tasks. It is concluded that, contrary to the claims of its detractors, the cognitive map theory is still the theory of hippocampal function that is most clearly specified, makes the most testable predictions, and for which there is the strongest experimental support.

Animals↗
PubMed1999

Long-term outcome after primary angioplasty: report from the primary angioplasty in myocardial infarction (PAMI-I) trial.

OBJECTIVES: This study sought to compare the two-year outcome after primary percutaneous coronary angioplasty or thrombolytic therapy for acute myocardial infarction. BACKGROUND: Primary angioplasty, that is, angioplasty without antecedent thrombolytic therapy, has been shown to be an effective reperfusion modality for patients suffering an acute myocardial infarction. This report reviews the two-year clinical outcome of patients randomized in the Primary Angioplasty in Myocardial Infarction trial. METHODS: At 12 clinical centers, 395 patients who presented within 12 h of the onset of myocardial infarction were randomized to undergo primary angioplasty (195 patients) or to receive tissue-type plasminogen activator (t-PA) (200 patients) followed by conservative care. Patients were followed by physician visits, phone call, letter and review of hospital records for any hospital admission at one month, six months, one year and two years. RESULTS: At two years, patients undergoing primary angioplasty had less recurrent ischemia (36.4% vs. 48% for t-PA, p = 0.026), lower reintervention rates (27.2% vs. 46.5% for t-PA, p < 0.0001) and reduced hospital readmission rates (58.5% vs. 69.0% for t-PA, p = 0.035). The combined end point of death or reinfarction was 14.9% for angioplasty versus 23% for t-PA, p = 0.034. Multivariate analysis found angioplasty to be independently predictive of a reduction in death, reinfarction or target vessel revascularization (p = 0.0001). CONCLUSIONS: The initial benefit of primary angioplasty performed by experienced operators is maintained over a two-year follow-up period with improved infarct-free survival and reduced rate of reintervention.

Angioplasty, Balloon, Coronary↗