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M M Mesulam

Publications and source records attributed to M M Mesulam.

At least 91 records · Page 5Linked to original sources

Differential cholinergic innervation within functional subdivisions of the human cerebral cortex: a choline acetyltransferase study.

The distribution of cholinergic fibers in the human brain was investigated with choline acetyltransferase immunocytochemistry in 35 cytoarchitectonic subdivisions of the cerebral cortex. All cortical areas and all cell layers contained cholinergic axons. These fibers displayed numerous varicosities and, on occasion, complex preterminal profiles arranged in the form of dense clusters. The density of cholinergic axons tended to be higher in the more superficial layers of the cerebral cortex. Several distinct patterns of lamination were identified. There were also major differences in the overall density of cholinergic axons from one cytoarchitectonic area to another. The cholinergic innervation of primary sensory, unimodal, and heteromodal association areas was lighter than that of paralimbic and limbic areas. Within unimodal association areas, the density of cholinergic axons and varicosities was significantly lower in the upstream (parasensory) sectors than in the downstream sectors. Within paralimbic regions, the non-isocortical sectors had a higher density of cholinergic innervation than the isocortical sectors. The highest density of cholinergic axons was encountered in core limbic structures such as the hippocampus and amygdala. These observations show that the cholinergic innervation of the human cerebral cortex displays regional variations that closely follow the organization of information processing systems.

Adult↗

Overlap between acetylcholinesterase-rich and choline acetyltransferase-positive (cholinergic) axons in human cerebral cortex.

The distribution of acetylcholinesterase-rich axons was compared to that of choline acetyltransferase-positive (cholinergic) axons in 28 major cytoarchitectonic divisions of the adult human cerebral cortex. Acetylcholinesterase-rich as well as choline acetyltransferase-positive cortical axons contained multiple varicosities. Each type of axon was more densely distributed in limbic-paralimbic regions of the brain. In all the cortical areas that were examined, the two markers displayed laminar and regional distribution patterns that were indistinguishable from each other. A method that allowed the concurrent visualization of both reaction products demonstrated that acetylcholinesterase and choline acetyltransferase were colocalized in the same axon. These observations show that there is probably a complete correspondence between choline acetyltransferase-positive and acetylcholinesterase-rich axons and that the acetylcholinesterase reaction can be used as a specific marker for cortical cholinergic axons in the adult human brain.

Acetylcholine↗

A one-step cobalt-ferrocyanide method for histochemical demonstration of acetylcholinesterase activity in central nervous system tissue.

We introduce a one-step histochemical method with cobalt as the precipitating agent for ferrocyanide for the light microscopic demonstration of acetylcholinesterase activity. This method was used to demonstrate acetylcholinesterase in normal cortical fibers and neurons, as well as pathological elements such as plaques and tangles. This procedure can also be easily combined with immunohistochemical methods that use diaminobenzidine as a chromogen.

Acetylcholinesterase↗

Diminished curiosity in patients with probable Alzheimer's disease as measured by exploratory eye movements.

Clinical accounts of Alzheimer's disease (AD) suggest that some patients exhibit markedly diminished curiosity and initiative early in the course of their illness. Such behavioral changes are extremely difficult to measure experimentally. We studied one aspect of curiosity by measuring exploratory eye movements in response to provocative visual stimuli in 12 patients with probable AD and 10 matched controls. Subjects viewed slides, each of which contained an incongruous or irregular figure paired with a congruous or regular one. Unlike controls, who spent significantly more time viewing the incongruous stimuli, AD patients distributed their viewing time equally and spent significantly less time than controls looking at the novel stimuli. Additionally, when presented with picture slides containing an unexpected element, AD patients exhibited diminished visual exploration overall and decreased attention to the incongruous part. Further analyses suggest that the results cannot be adequately explained by a general decline in cognition or by problems with ocular motility or directing visual attention. We conclude that AD patients exhibit diminished curiosity which can be measured by the study of exploratory eye movements.

Aged↗

Neuropsychological aspects of dementia of motor neuron disease: a report of two cases.

We describe the neuropsychological data from two cases of dementia of motor neuron disease. In both cases, a gradually progressive presenile dementia began prior to the development of motor neuron disease involving predominantly bulbar musculature. These data, along with the neuropathologic findings available in one case, suggest that dementia of motor neuron disease differs from that of Alzheimer's disease (AD). Both patients displayed major alterations of personality and comportment. Neuropsychological test results revealed marked attention deficits, particularly on tasks requiring sustained effort and on those requiring ability to shift from one line of thinking to another. Confrontation naming, verbal fluency, insight, and judgment also showed extensive impairment. By contrast, verbal and nonverbal memory remained intact after several years of illness. This pattern is quite different from that seen in AD, where memory deficits are salient.

Aged↗

Acetylcholinesterase-rich neurons of the human cerebral cortex: cytoarchitectonic and ontogenetic patterns of distribution.

Layers 3 and 5 of the adult human cerebral cortex contain a very large number of pyramidal neurons that express intense acetylcholinesterase (AChE) enzymatic activity and AChE-like immunoreactivity. The density of these neurons is high in motor, premotor, and neocortical association areas but quite low in paralimbic cortex. These AChE-rich neurons are located predominantly within layer 3 in the premotor and association cortex, within layer 5 in the non-isocortical components of the paralimbic cortex, and are equally prominent in layers 3 and 5 in the motor cortex. Almost all Betz cells in the motor cortex and up to 80% of layer 3 pyramidal neurons in some parts of the association neocortex yield an AChE-rich staining pattern. The existence of a specific laminar and cytoarchitectonic distribution suggests that the AChE-rich enzymatic pattern of these neurons is selectively regulated. The AChE-rich enzymatic reactivity of the layer 3 and layer 5 neurons is not detectable during early childhood, becomes fully established during adulthood, and does not show signs of decline during advanced senescence in mentally intact individuals. The AChE activity (or enzyme synthesis) in these neurons is therefore held in check for several years during infancy and childhood and begins to be expressed at a time when the more advanced motor and cognitive skills are also being acquired. The absence of immunostaining with an antibody to choline acetyltransferase suggests that these AChE-rich neurons are not cholinergic. The regional distribution of these AChE-rich neurons does not parallel the regional variations of cortical cholinergic innervation. Whereas the AChE-rich pyramidal neurons of layers 3 and 5 almost certainly represent one subgroup of cholinoceptive cortical neurons, their AChE-rich enzymatic pattern is probably also related to a host of non-cholinergic processes that may include maturational changes and plasticity in the adult brain.

Acetylcholinesterase↗

Electron microscopic localization of cholinesterase activity in Alzheimer brain tissue.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity was localized by electron microscopic enzyme cytochemistry in cortex from Alzheimer brains and brains from non-demented cases. In the tangle-rich medial temporal cortex of the Alzheimer brain, most of the neuronal AChE was associated with neurofibrillary tangles. These structures also contained BChE activity. In normal neurons AChE activity was found in the rough endoplasmic reticulum, nuclear envelope and Golgi apparatus. Little BChE activity was noted in normal cortex. In neuritic plaques, AChE and BChE activity was associated mostly with the amyloid, but also with the neuritic component.

Acetylcholinesterase↗

Immunocytochemical demonstration of axonal and perikaryal acetylcholinesterase in human cerebral cortex.

The adult human neocortex contains a dense net of axons and perikarya which yield an acetylcholinesterase-rich enzymatic reaction pattern in histochemical experiments. We employed a monoclonal antibody to human acetylcholinesterase and a method for the concurrent visualization of histochemical and immunohistochemical reaction-products to explore the relationship between immunological and enzymatic markers of acetylcholinesterase. We observed that the cortical axons and perikarya with a histochemically determined acetylcholinesterase-rich enzymatic activity also contain acetylcholinesterase-like immunoreactivity. This was especially informative for the intracortical acetylcholinesterase-rich perikarya of layers III and V since these neurons require prolonged incubations for histochemical detection and since they are not conspicuous in other animal species. The availability of a reliable immunohistochemical method makes it possible to investigate the distribution of the acetylcholinesterase enzyme molecule independent of its enzymatic activity.

Acetylcholinesterase↗

Broca's aphasia following damage to Wernicke's area. For or against traditional aphasiology?

Classic aphasiology has been challenged by studies that have employed cranial computed tomography to test predicted anatomic-behavioral correlations. We treated a patient who developed a classic Broca's aphasia but whose computed tomographic scan revealed damage to Wernicke's area, thus seeming to contradict the principles of traditional aphasiology. However, subsequent information obtained by magnetic resonance imaging, intracarotid amobarbital (Amytal) testing, and electrophysiologic studies, including cortical stimulation, demonstrated that the brain-behavior correlations in this patient can be understood in terms of the formulations of traditional aphasiology.

Adult↗

Frontal lobe dysfunction following infarction of the left-sided medial thalamus.

We treated a 62-year-old woman who developed a dramatic change in personality and behavior following a discrete left-sided medial thalamic infarction involving the dorsomedial nucleus. Neuropsychological testing demonstrated severe impairment of complex executive behaviors that are usually associated with frontal lobe function. Electroencephalography and single-photon emission computed tomography strongly implicated dysfunction of the ipsilateral frontal lobe. This case further supports a functional and physiologic thalamofrontal linkage as part of a broader cerebral network modulating complex human behavior.

Brain Diseases↗

Right hemisphere advantage for evaluating emotional facial expressions.

The ability to evaluate the intensity of emotional facial expressions was investigated in patients undergoing the intracarotid sodium amytal procedure. It was found that when the hemisphere non-dominant for language (usually right) was anesthetized, the patients' ratings of the intensity of emotional expressions in photographs were lower than baseline ratings of these expressions. Such an effect was not seen with anesthetization of the hemisphere dominant for language (usually left). Ratings of shades of gray (which served as control stimuli) showed no such effect. The findings are interpreted in terms of a right hemisphere superiority in the perception and evaluation of emotional expression.

Adolescent↗

Human striatal cholinergic neurons in development, aging and Alzheimer's disease.

The cross-sectional area of cholinergic neurons stained immunohistochemically for choline acetyltransferase were measured in the striatum of infants, young adults, aged individuals and patients with Alzheimer's disease. Cholinergic neurons were distributed throughout the caudate nucleus and the putamen and displayed no significant variations in size across the two structures. The cross-sectional area of striatal cholinergic neurons was smaller in infants as compared with all other groups examined. No significant changes were observed in the size of these neurons as a consequence of aging or Alzheimer's disease.

Adult↗

Primary progressive aphasia. Longitudinal course, neuropsychological profile, and language features.

Four patients with the clinical syndrome of primary progressive aphasia and a nonfluent aphasia profile were followed up over a period of 3 to 5 years. Extensive neuropsychological data for three patients revealed a progressive, quantitative decline of language with relative stability of memory, visuospatial skills, and reasoning. Comportment and most activities of daily living were preserved even when speech was unintelligible. Although several aphasia types may be associated with primary progressive aphasia, a nonfluent aphasia profile and phonemic paraphasic errors are most useful in differentiating it from the much more common clinical syndrome, "probable Alzheimer's disease." The clinicopathological correlates of probable Alzheimer's disease differ from those associated with primary progressive aphasia. Therefore, the clinical distinction between the two syndromes may be important for predicting the underlying pathophysiologic changes during the life of the patient.

Adult↗

Dissociated neglect behavior following sequential strokes in the right hemisphere.

A 42-year-old woman suffered two focal right hemisphere strokes, sequentially damaging different components of a proposed cerebral network for the spatial distribution of attention. Her first stroke was centered in the right frontal lobe and resulted in left hemi-spatial neglect but only for tasks that emphasize exploratory-motor components of directed attention. A second stroke occurred 20 days later in the parietal lobe and led to the emergence of perceptual-sensory aspects of neglect. This case strongly supports the existence of a distributed anatomic-functional network subserving directed attention.

Adult↗

Large-scale neurocognitive networks and distributed processing for attention, language, and memory.

Cognition and comportment are subserved by interconnected neural networks that allow high-level computational architectures including parallel distributed processing. Cognitive problems are not resolved by a sequential and hierarchical progression toward predetermined goals but instead by a simultaneous and interactive consideration of multiple possibilities and constraints until a satisfactory fit is achieved. The resultant texture of mental activity is characterized by almost infinite richness and flexibility. According to this model, complex behavior is mapped at the level of multifocal neural systems rather than specific anatomical sites, giving rise to brain-behavior relationships that are both localized and distributed. Each network contains anatomically addressed channels for transferring information content and chemically addressed pathways for modulating behavioral tone. This approach provides a blueprint for reexploring the neurological foundations of attention, language, memory, and frontal lobe function.

Animals↗