Biomedical subjects
A Damasio
Publications and source records attributed to A Damasio.
The selective vulnerability of brainstem nuclei to Alzheimer's disease.
In a study of thioflavin S-stained serial sections from the entire brainstem, we found that the inferior and superior colliculi and the autonomic, monoaminergic, cholinergic, and classical reticular nuclei were affected with varying degrees of severity and frequencies in 32 patients with Alzheimer's disease, whereas no changes were seen in the brainstems of 26 control subjects. The majority of the affected nuclei in patients with Alzheimer's disease exhibit either neurofibrillary tangles or senile plaques, and only a few display both. However, when sections were immunostained with the antibodies 10D5 and AT8 or ALZ50, both beta-amyloid and hyperphosphorylated epitopes of tau protein were found to be present in various concentrations in all the affected nuclei. Our findings suggest that each brainstem nucleus has a distinct vulnerability to Alzheimer's disease-related pathological changes. Given that each nucleus has idiosyncratic neuroanatomical connections and prevailing neurochemical characteristics, the heterogeneous collection of brainstem nuclei can be considered a suitable anatomical ground for further investigation of selective vulnerability in Alzheimer's disease. The finding of severe pathological changes in some brainstem nuclei also raises the possibility that the dysfunction of these nuclei may contribute to the cognitive defects and increased rates of morbidity and mortality in patients with Alzheimer's disease.
Consciousness and the brainstem.
In the first part of this article we summarize a theoretical framework and a set of hypotheses aimed at accounting for consciousness in neurobiological terms. The basic form of consciousness, core consciousness is placed in the context of life regulation; it is seen as yet another level of biological processing aimed at ensuring the homeostatic balance of a living organism; and the representation of the current organism state within somato-sensing structures is seen as critical to its development. Core consciousness is conceived as the imaged relationship of the interaction between an object and the changed organism state it causes. In the second part of the article we discuss the functional neuroanatomy of nuclei in the brainstem reticular formation because they constitute the basic set of somato-sensing structures necessary for core consciousness and its core self to emerge. The close relationship between the mechanisms underlying cortical activation and the bioregulatory mechanisms outlined here is entirely compatible with the classical idea that the reticular formation modulates the electrophysiological activity of the cerebral cortex. However, in the perspective presented here, that modulation is placed in the setting of the organism's homeostatic regulation.
Selective pathological changes of the periaqueductal gray matter in Alzheimer's disease.
The periaqueductal gray matter (PAG) is a major neuroanatomical component of the brainstem and has pivotal roles in autonomic functions, behavior, and cognition, most notably in the processing of emotions and feelings. In a study of 32 brains obtained from patients with Alzheimer's disease (AD), thioflavin S-stained sections from the PAG contained major pathological changes in 81% of cases. These changes were absent in all 26 control brains (13 from normal subjects and 13 from non-AD patients). In the AD cases, both sides of the PAG were affected symmetrically; in 72%, there were only senile plaques, but there were both senile plaques and neurofibrillary tangles in 9%. Using immunohistochemical methods with 10D5, ALZ-50, and AT8 antibodies, we also established the presence of beta-amyloid peptide and abnormally phosphorylated tau protein in the PAG. Furthermore, we found that the type and density of pathological changes were expressed differently in different PAG regions and correlated with gender and the duration of dementia. These findings constitute a first step in documenting the selective changes of PAG in AD. The compartmentalized pattern of AD changes in PAG also reveals for the first time the columnar organization of PAG in human subjects.
Severe pathological changes of parabrachial nucleus in Alzheimer's disease.
In the first of a series of studies aimed at mapping brain stem pathological changes in patients with Alzheimer's disease (AD), we report a new finding regarding the parabrachial nucleus (PBN), a unit of paramount importance in the relay and integration of visceral and nociceptive information as well as in homeostatic control. The brains of 20 patients with AD were surveyed. The PBN contained pervasive neuropathological changes in 100% of the brains from those with early-onset dementia and in 80% from those with late-onset dementia. These changes were entirely absent in all 10 normal controls. The pathological changes of PBN, would cause autonomic dysfunction in patients with AD and perhaps contribute to the disproportionate mortality encountered in these patients.
Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala.
Studies in animals have shown that the amygdala receives highly processed visual input, contains neurons that respond selectively to faces, and that it participates in emotion and social behaviour. Although studies in epileptic patients support its role in emotion, determination of the amygdala's function in humans has been hampered by the rarity of patients with selective amygdala lesions. Here, with the help of one such rare patient, we report findings that suggest the human amygdala may be indispensable to: (1) recognize fear in facial expressions; (2) recognize multiple emotions in a single facial expression; but (3) is not required to recognize personal identity from faces. These results suggest that damage restricted to the amygdala causes very specific recognition impairments, and thus constrains the broad notion that the amygdala is involved in emotion.
A human visual disorder resembling area V4 dysfunction in the monkey.
We surveyed a broad range of visual functions in a man who complained of abnormal color experience and inability to recognize faces following bilateral damage in the visual cortex. A lesion in his right visual cortex caused complete left visual field loss. A lesion in his left visual cortex, located entirely below the calcarine fissure, affected the vision in his remaining hemifield, the right one. Psychophysical testing showed severely defective color vision and pattern processing, but relatively normal luminance contrast detection thresholds. The finding of normal spatial contrast sensitivity and static stereopsis did not resemble a parvocellular defect of the type described in the monkey. The abilities to detect global coherent motion among noise, structure from motion and dynamic stereopsis, and to pursue moving targets showed normal motion processing at several levels. Together with normal flicker perception, these results excluded magnocellular or MT-like defects. Altogether, the findings mimic area V4 dysfunction.
University of Iowa plays crucial role in Alzheimer's research.
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Central achromatopsia: behavioral, anatomic, and physiologic aspects.
The neuropsychologic, neuroanatomic, and neurophysiologic correlates of achromatopsia were studied in two patients. Prosopagnosia accompanied the color perception defect in the bilateral case but not in the unilateral one. No other neuropsychologic disturbance was present in either case. The lesions compromised the ventromedial sector of the occipital lobe in both cases. Cerebral evoked responses produced by pattern shift stimulation were normal for black and white but abnormal for red and green, when stimulation was given in the achromatopsic field.
Electroencephalographic absence status with minimal behavior change.
Difficulty in correlating EEG abnormalities with clinical seizures is emphasized in this case report of an epileptic patient with electrical status epilepticus and normal behavior. In addition, the usefulness of dichotic listening tests in the identification of subtle perceptive and expressive impairments is illustrated in this same patient at a time of noncompliance with anticonvulsant therapy.
Is idiopathic dementia a regional vitamin deficiency state?
We hypothesize that some cases of idiopathic dementia are due to a gradual undernourishment of the brain with water-soluble vitamins. This occurs because the choroid plexus and possibly other transport loci in the central nervous system become unable to transport water-soluble vitamins from blood into the central nervous system in adequate amounts. If this testable hypothesis is correct, direct injections of vitamins into the ventricular cerebrospinal fluid should ameliorate the development of dementia.
"Paradoxic" ear extinction in dichotic listening: possible anatomic significance.
"Paradoxic" extinction in dichotic listening tasks has been attributed to lesions in the interhemispheric auditory pathways, the anatomic courses of which are unknown. The localization of cerebral lesions related to abnormal patterns of dichotic listening was studied in computerized tomographic (CT) scans with a method of anatomic templates. Paradoxic extinction was found consistently with lesions near the lateral wall of the lateral ventricles at the level of the trigone in both left and right hemispheres. On the basis of these findings, we propose that the pathway leaves the auditory cortex traveling backward and upward to arch around the lateral ventricles and join the callosum in its posterior region.
Neural systems behind word and concept retrieval.
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.
Sign language aphasia during left-hemisphere Amytal injection.
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.