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M M Mesulam

Publications and source records attributed to M M Mesulam.

At least 109 records · Page 6Linked to original sources
PubMed1990

The comportmental learning disabilities of early frontal lobe damage.

Two adult patients are described who suffered bilateral prefrontal damage early in life and who subsequently came to psychiatric attention because of severely aberrant behaviour. A battery of developmental psychology paradigms (not previously used to assess neurologically impaired individuals) showed that social and moral development of these 2 patients was arrested at an immature stage. In comparison with other types of brain damage which disrupt cognitive development, frontal damage acquired early in life appears to provide the neurological substrate for a special type of learning disability in the realms of insight, foresight, social judgement, empathy, and complex reasoning.

Adult↗
PubMed1990

Visual neglect during intracarotid amobarbital testing.

The unilateral suppression of hemispheric function by sodium amobarbital may result in hemispatial visual neglect, as measured by performance on a random letter cancellation task. Our study not only investigates this hypothesis but also attempts to identify more precisely the anatomic locus of control for directed attention to extrapersonal space by correlating scanning performance with EEG activity. Forty-eight consecutive patients with epilepsy underwent preoperative intracarotid amobarbital tests. The results indicated that disruption of scanning and contralateral neglect occurred only after right-hemisphere suppression and seemed specifically related to changes in right frontal lobe EEG activity. This pattern of performance held not only for right-handed subjects, but also for those who were left-handed, and even for those who had right-hemisphere language dominance.

Adolescent↗
PubMed1989

Human reticular formation: cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei and some cytochemical comparisons to forebrain cholinergic neurons.

Choline acetyltransferase immunohistochemistry showed that the human rostral brainstem contained cholinergic neurons in the oculomotor, trochlear, and parabigeminal nuclei as well as within the reticular formation. The cholinergic neurons of the reticular formation were the most numerous and formed two intersecting constellations. One of these, designated Ch5, reached its peak density within the compact pedunculopontine nucleus but also extended into the regions through which the superior cerebellar peduncle and central tegmental tract course. The second constellation, designated Ch6, was centered around the laterodorsal tegmental nucleus and spread into the central gray and medial longitudinal fasciculus. There was considerable transmitter-related heterogeneity within the regions containing Ch5 and Ch6. In particular, Ch6 neurons were intermingled with catecholaminergic neurons belonging to the locus coeruleus complex. The lack of confinement within specifiable cytoarchitectonic boundaries and the transmitter heterogeneity justified the transmitter-specific Ch5 and Ch6 nomenclature for these two groups of cholinergic neurons. The cholinergic neurons in the nucleus basalis (Ch4) and those of the Ch5-Ch6 complex were both characterized by perikaryal heteromorphism and isodendritic arborizations. In addition to choline acetyltransferase, the cell bodies in both complexes also had high levels of acetylcholinesterase activity and nonphosphorylated neurofilament protein. However, there were also marked differences in cytochemical signature. For example, the Ch5-Ch6 neurons had high levels of NADPHd activity, whereas Ch4 neurons did not. On the other hand, the Ch4 neurons had high levels of NGF receptor protein, whereas those of Ch5-Ch6 did not. On the basis of animal experiments, it can be assumed that the Ch5 and Ch6 neurons provide the major cholinergic innervation of the human thalamus and that they participate in the neural circuitry of the reticular activating, limbic, and perhaps also extrapyramidal systems.

Adult↗
PubMed1989

Alterations of hippocampal acetylcholinesterase in human temporal lobe epilepsy.

Hippocampal sclerosis is the most common pathological finding associated with human temporal lobe epilepsy. Histochemical study with acetylcholinesterase (AChE) staining was used to investigate 7 surgically resected temporal lobes with hippocampal sclerosis from patients with temporal lobe epilepsy. In all 7 specimens, an abnormal but consistent pattern of staining was noted. In the hilum of the dentate gyrus, AChE-rich polymorphic cells were relatively preserved in comparison to the pyramidal neurons. In Ammon's horn, AChE fibers were lost in regions corresponding to the pyramidal cell dropout. AChE fibers were also lost along the inner portion of the molecular layer of the dentate gyrus, yet they were preserved within the outer portions of the molecular layer. These findings provide additional evidence for the relative selectivity of hippocampal pathology in human temporal lobe epilepsy.

Acetylcholinesterase↗
PubMed1989

Protease nexin I immunostaining in Alzheimer's disease.

Immunohistochemical experiments showed that a small subset of neuritic plaques in brains affected by Alzheimer's disease stain positively with an antibody to the protease inhibitor protease nexin I. Nearly all plaques and tangles throughout the brain also showed a heightened avidity for a protease nexin I antibody-antigen aggregate, suggesting that plaques and tangles may have a particularly high density of protease nexin I-binding sites. These observations provide further evidence for a potential disruption of protein processing in the brains of patients with Alzheimer's disease.

Aged↗
PubMed1989

Cortical cholinergic fibers in aging and Alzheimer's disease: a morphometric study.

A histochemical method for acetylcholinesterase was used to assess the regional density of acetylcholinesterase-rich (putatively cholinergic) axons in the cerebral cortex. A dense plexus of these fibers was observed in all cortical areas. The entorhinal, cingulate and inferotemporal regions were used for quantitative analysis. The paralimbic cortical areas (entorhinal and cingulate) contained a higher density of acetylcholinesterase-rich fibers than the association cortex of inferotemporal area TE. The more superficial layers in all three regions contained a denser net of these fibers than did the deep layers. Aging was accompanied by a modest loss in the density of acetylcholinesterase-positive fibers in the entorhinal and inferotemporal cortex but not in the cingulate area. In brains from patients with Alzheimer's disease, a dramatic loss of these fibers was observed in all three areas examined but the loss was relatively less pronounced in the cingulate area. The results demonstrate that the cholinergic innervation of the cerebral cortex in the human brain displays considerable regional and laminar variations. Regional variations were also observed in the alterations that the cortical cholinergic fibers displayed as a result of normal aging and Alzheimer's disease. The age-related reduction observed in the density of cholinergic fibers in the cerebral cortex was quite modest when compared with the dramatic loss in Alzheimer's disease.

Acetylcholinesterase↗
PubMed1988

Distribution of muscarinic receptor subtypes within architectonic subregions of the primate cerebral cortex.

The regional distributions of muscarinic receptor subtypes (M1 and M2) in the macaque brain were investigated by in vitro receptor autoradiography. Putative muscarinic receptor subtypes were distinguished by their differential affinities for pirenzepine and carbachol in competition with [3H]-quinuclidinyl benzilate. Autoradiographic visualization of muscarinic receptor subtypes demonstrated marked regional and laminar variations that respected architectonic boundaries. The M1 receptor subtype was widely distributed throughout most cortical areas and was most intense over the superficial layers. Almost all limbic and paralimbic regions including the amygdala, hippocampus, orbitofrontal, temporopolar, parahippocampal, cingulate, and parolfactory areas displayed peak densities of the M1 receptor subtype. The M2 receptor subtype was selectively elevated in the primary sensory areas of all five sensory modalities, including the visual (area 17, V1), auditory (A1), and somatosensory (3b, S1) koniocortices, the anterior olfactory nucleus, and the gustatory area. The primary motor area also displayed a relative peak of M2 receptor subtype labeling. In the hippocampal formation, M1, M2, and nicotine receptors were distributed differentially, with each subdivision having a specific complement of cholinergic receptor subtype. The M1 receptor subtype was prevalent in the dentate gyrus, the CA4-CA3 region, and the CA1 ammonic sector. The M2 receptor subtype was concentrated in the CA2 sector, the subiculum, the rhinal cortices, and the parasubiculum. Putative neural nicotinic receptors, tagged with L-[3H]-nicotine, were most concentrated within the presubiculum.

Animals↗
PubMed1988

Nucleus basalis (Ch4) and cortical cholinergic innervation in the human brain: observations based on the distribution of acetylcholinesterase and choline acetyltransferase.

The nucleus basalis (NB) of the human brain is a large, complex, and highly differentiated structure. Many of its neurons are magnocellular, hyperchromic, isodendritic, acetylcholinesterase-rich, and choline-acetyltransferase-positive. Concurrent histochemical and immunological staining demonstrated that all choline-acetyltransferase-positive NB neurons in the human brain also contain acetylcholinesterase enzyme activity. Only a small minority of acetylcholinesterase-rich magnocellular cell bodies in the NB failed to show choline acetyltransferase immunoreactivity. Sections that were counterstained for Nissl substance showed that 80-90% of all magnocellular neurons in the NB were choline-acetyltransferase-positive and therefore cholinergic. These characteristics, which are very similar to those of the NB in the monkey brain, justified the designation of these cholinergic neurons in the human brain as the Ch4 (or NB-Ch4) complex. On morphological grounds, the compact parts of the human NB-Ch4 complex were divided into distinct sectors which appeared to show a greater level of differentiation than in the monkey brain. In addition to the compact sectors, interstitial elements of NB Ch4 were embedded within adjacent fiber bundles. The putative cortical projections from NB-Ch4 were identified in the form of acetylcholinesterase-rich fibers. These fibers formed a dense plexus in all cortical regions but also displayed laminar and regional variations. Limbic and paralimbic areas had higher concentrations of these fibers than the immediately adjacent neocortical association areas. Alzheimer's disease was associated with a marked depletion of cortical acetylcholinesterase. Two cases of Alzheimer's disease with relatively selective NB-Ch4 cell loss supported the hypothesis that the corticopetal cholinergic pathways in the human brain may have a topographical organization similar to that in the monkey brain.

Acetylcholine↗
PubMed1988

Acetylcholinesterase fiber staining in the human hippocampus and parahippocampal gyrus.

The AChE fiber distribution within the human hippocampus and parahippocampal gyrus was studied in order to provide normative data for the examination of cholinergic fiberarchitecture in human pathology and to clarify the cytoarchitectonic organization of these structures. A modification of the Koelle method was used to stain temporal lobe serial sections from 6 neurologically normal human brains collected at autopsy. The hippocampal formation contains some of the densest staining of any cortical area. Regions with the heaviest concentrations of AChE fibers include a thin band along the inner edge of the molecular layer of the dentate gyrus (ml-DG) and parts of the CA2, CA3, and CA4 sectors of Ammon's horn. Staining is of intermediate intensity in the CA1 region. The subiculum (S) is more lightly stained than the CA fields. Staining in the parahippocampal gyrus is generally less dense than in the hippocampal formation. The most conspicuous feature of the human entorhinal cortex (EC) is the AChE-rich fiber patches seen overlapping the stellate cell islands in layer II. An additional band of relatively dense AChE staining is identified in layers IV-V. Prominent AChE-rich polymorphic neurons are present within the hilum of the dentate gyrus. The CA1/subiculum transition in Nissl preparation is characterized by an oblique interdigitation of CA1 cells. The transition from EC to prorhinal cortex occurs along the medial bank of the rhinal sulcus and is characterized by a band of AChE staining, which slopes obliquely away from layer II until it joins an intermediate pyramidal cell layer. Some comparisons with AChE staining in the monkey were made. The monkey has a similar pattern except in DG, where the intensely AChE staining band along the inner ml-DG is thicker and much more prominent. In comparison to the human, the monkey has more conspicuous AChE staining in the parasubicular region.

Acetylcholinesterase↗
PubMed1988

Immunohistochemical evidence for a possible somatostatin-containing amygdalostriatal pathway in normal and Alzheimer's disease brain.

Somatostatin (SOM) immunohistochemistry was used to map SOM-containing fibers, perikarya and terminal-like structures in the human forebrain of 8 control and 8 Alzheimer's diseased patients. Immunohistochemically processed tissue revealed a somatostatin-immunoreactive amygdalostriatal fiber pathway apparently originating from SOM-positive neurons of the central amygdaloid nucleus. This pathway coursed dorsomedially between the optic tract and the internal segment of the globus pallidus within the ansa peduncularis-ventral amygdalofugal fiber system en route to the substantia innominata-nucleus basalis complex, the bed nucleus of the stria terminalis, the medial preoptic hypothalamic area, the nucleus accumbens and the olfactory tubercle. Somatostatin fibers associated with this pathway appeared as coarse heavily stained 'wooly fibers'. At the light microscopic level, there was no apparent difference in this somatostatin containing amygdalostriatal pathway between neurologically normal and Alzheimer's diseased brains.

Adolescent↗
PubMed1988

Acetylcholinesterase-rich pyramidal neurons in the human neocortex and hippocampus: absence at birth, development during the life span, and dissolution in Alzheimer's disease.

Acetylcholinesterase-rich pyramidal neurons in the human association neocortex and hippocampal formation are virtually absent early in life, become established by adolescence, and appear to increase in density during adulthood and perhaps even senescence. Analogous neurons are not detectable in the adult monkey brain. This novel class of neurons may represent a uniquely human adaptation in primate evolution and may provide a neuroanatomical substrate for the mental development that occurs during the adult stages of life. These phylogenetically and ontogenetically progressive neurons are also markedly vulnerable to degeneration in Alzheimer's disease.

Acetylcholinesterase↗
PubMed1988

Visual hemispatial inattention: stimulus parameters and exploratory strategies.

Patients with unilateral hemispheric lesions were given visual target cancellation tasks. As expected, marked contralateral and less severe ipsilateral visual inattention were observed in patients with right-sided cerebral lesions whereas those with left-sided lesions showed only mild contralateral neglect. Stimulus material (shapes vs letters) and array (random vs structured) interacted in a complex manner to influence target detection only in patients with right-sided lesions. Furthermore, the search strategy of these patients tended to be erratic, particularly when the stimuli were in an unstructured array. A structured array prompted a more systematic and efficient search. It appears, therefore, that stimulus content and spatial array affect neglect behaviour in patients with right-sided lesions and that a lack of systematic visual exploration within the extrapersonal space is one factor that contributes to visual hemispatial inattention.

Aged↗
PubMed1987

Cortical effects of neurotoxic damage to the nucleus basalis in rats: persistent loss of extrinsic cholinergic input and lack of transsynaptic effect upon the number of somatostatin-containing, cholinesterase-positive, and cholinergic cortical neurons.

Ibotenic acid injections into the nucleus basalis (Ch4) resulted in a near-total loss of cortical cholinesterase fibers. This loss of cholinergic input is irreversible for at least 6 months. The degeneration of cholinergic input has no transsynaptic effect upon the number of cortical somatostatinergic, cholinergic and cholinesterase-positive (cholinoceptive) neurons.

Acetylcholinesterase↗