Success or failure of dipyridamole in migraine.
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Biomedical subjects
Publications and source records attributed to H Damasio.
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Among 296 patients with thrombocytopenia, 14 had frequent migraine-like headaches, 6 of them having definite migraine. Only 1 of the 6 patients had had migraine before the onset of the blood disorder, and all 6 had migraine attacks during periods of bruising tendency and low platelet count. Control of thrombocytopenia with splenectomy or steroids was accompanied by dramatic improvement in migraine. It is suggested that migraine attacks are caused by abnormal platelet activity and abnormal serotonin metabolism. It is suggested that the immediate factor producing the abnormal platelet activity in our patients was immunological and that other cases of migraine may have an immunological cause.
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Following damage to the ventromedial prefrontal cortex, humans develop a defect in real-life decision-making, which contrasts with otherwise normal intellectual functions. Currently, there is no neuropsychological probe to detect in the laboratory, and the cognitive and neural mechanisms responsible for this defect have resisted explanation. Here, using a novel task which simulates real-life decision-making in the way it factors uncertainty of premises and outcomes, as well as reward and punishment, we find that prefrontal patients, unlike controls, are oblivious to the future consequences of their actions, and seem to be guided by immediate prospects only. This finding offers, for the first time, the possibility of detecting these patients' elusive impairment in the laboratory, measuring it, and investigating its possible causes.
Using both the lesion method and functional imaging (positron emission tomography) in large cohorts of subjects investigated with the same experimental tasks, we tested the following hypotheses: (A) that the retrieval of words which denote concrete entities belonging to distinct conceptual categories depends upon partially segregated regions in higher-order cortices of the left temporal lobe; and (B) that the retrieval of conceptual knowledge pertaining to the same concrete entities also depends on partially segregated regions; however, those regions will be different from those postulated in hypothesis A, and located predominantly in the right hemisphere (the second hypothesis tested only with the lesion method). The analyses provide support for hypothesis A in that several regions outside the classical Broca and Wernicke language areas are involved in name retrieval of concrete entities, and that there is a partial segregation in the temporal lobe with respect to the conceptual category to which the entities belong, and partial support for hypothesis B in that retrieval of conceptual knowledge is partially segregated from name retrieval in the lesion study. Those regions identified here are seen as parts of flexible, multi-component systems serving concept and word retrieval for concrete entities belonging to different conceptual categories. By comparing different approaches the article also addresses a number of method issues that have surfaced in recent studies in this field.
Although it has been established that the left cerebral hemisphere subserves spoken language, the nature of brain organization for sign language remains relatively unexplored. The issue is especially important because sign language displays the complex linguistic structure of spoken languages, but conveys it through manipulation of visuo-spatial relations, thereby exhibiting properties for which the hemispheres of hearing individuals show opposing specializations. We had the unique opportunity to study a hearing signer proficient in American sign language (ASL), during the left intracarotid injection of a barbiturate (the Wada test), and before and after a right temporal lobectomy. The subject was a strong right-hander. Neuropsychological and anatomical asymmetries suggested left cerebral dominance for auditory-based language. Emission tomography revealed lateralized activity of left Broca's and Wernicke's regions for spoken language. The Wada test, during which all left language areas were rendered inoperative, caused a marked aphasia in both English and ASL. After partial ablation of the right temporal lobe, the abilities to sign and understand signing were unchanged. These data add further support to the notion that anatomical structures of the left cerebral hemisphere subserve language in a visuo-spatial as well as an auditory mode.
Current neuroimaging methodologies have lacked the resolution needed to visualize cortical organization at the microscopic level. As a consequence, when neurological diseases disrupt the internal structure of the cerebral cortex, the changes can only be visualized postmortem, by histological examination. This imposes severe limitations in the in vivo diagnosis and investigation of those conditions. Here, we report on a magnetic resonance technique that permitted the visualization of some features of cerebral cortex in 14 living human subjects and in 2 fixed brains. The key finding was a periodic pattern of low- and high-signal slabs, oriented perpendicularly to the pial surface, that seem to correspond, respectively, to columnar modules and myelin septa. The key parameters of the new protocol included modifications in pulse sequence, field of view, number of repetitions, and plane of sectioning.
Following damage to specific sectors of the prefrontal cortex, humans develop a defect in real-life decision making, in spite of otherwise normal intellectual performance. The patients so affected may even realize the consequences of their actions but fail to act accordingly, thus appearing oblivious to the future. The neural basis of this defect has resisted explanation. Here we identify a physiological correlate for the defect and discuss its possible significance. We measured the skin conductance responses (SCRs) of 7 patients with prefrontal damage, and 12 normal controls, during the performance of a novel task, a card game that simulates real-life decision making in the way it factors uncertainty, rewards, and penalties. Both patients and controls generated SCRs after selecting cards that were followed by penalties or by reward. However, after a number of trials, controls also began to generate SCRs prior to their selection of a card, while they pondered from which deck to choose, but no patients showed such anticipatory SCRs. The absence of anticipatory SCRs in patients with prefrontal damage is a correlate of their insensitivity to future outcomes. It is compatible with the idea that these patients fail to activate biasing signals that would serve as value markers in the distinction between choices with good or bad future outcomes; that these signals also participate in the enhancement of attention and working memory relative to representations pertinent to the decision process; and that the signals hail from the bioregulatory machinery that sustains somatic homeostasis and can be expressed in emotion and feeling.
A dose-escalation study was performed in 27 patients to determine the highest safe and potentially optimal dose of naloxone for treatment of acute cerebral ischemia. All patients received a bolus of naloxone followed by a continuous 24 hour infusion at an hourly rate 50% of the bolus. Loading doses ranged from 2.5 to 200 mg/m2. Total patient doses ranged from 52.3 to 4978 mg. No major dose-related side effects occurred. This study was not designed to determine naloxone's efficacy in stroke, but transient or sustained improvement was observed in 13 patients. Three patients' neurological condition worsened within three hours after the naloxone was discontinued. Our experience suggests that further therapeutic trials of naloxone are worthwhile.
We investigated sensorimotor skill learning, a form of nondeclarative (implicit) memory, in 28 subjects with declarative (explicit) memory defects caused by either mesial temporal (n = 15) or basal forebrain (n = 13) damage and in 66 normal control subjects. All 28 amnesics had normal learning of a rotor pursuit task. We also studied in detail the sensorimotor skill learning of patient Boswell. As a result of bilateral damage to both mesial and lateral aspects of the temporal lobes and to the basal forebrain, Boswell has one of the most severe impairments ever reported for learning of all types of declarative knowledge. Compared to matched controls, Boswell acquired and retained normally the skills associated with performing motor tasks. We conducted a long-term (2-year) followup study of Boswell's retention of the rotor pursuit task, and we found that he retained the skill as well as normal controls. Our study builds on previous work in the following respects: (1) It provides evidence, for the first time, that skill learning is normal in basal forebrain amnesics; (2) it shows that patient Boswell has normal learning and long-term retention of sensorimotor skills, in spite of his extensive damage; and (3) it offers additional evidence that mesial temporal lobe damage spares skill learning. These findings demonstrate unequivocally that sensorimotor skill learning does not require structures in mesial and lateral temporal regions nor in basal forebrain.