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M M Mesulam

Publications and source records attributed to M M Mesulam.

At least 55 records · Page 3Linked to original sources
PubMed1997

Apolipoprotein E genotypes in primary progressive aphasia.

We obtained apolipoprotein E genotyping in a population of 12 consecutive patients who fulfilled rigorous criteria for the clinical diagnosis of primary progressive aphasia (PPA). The allele frequencies were 4% for E2, 83% for E3, and 13% for E4. This pattern of allele distribution was significantly different from the pattern seen in groups of patients either with the clinical diagnosis of probable Alzheimer's disease (PRAD) or the histopathologic diagnosis of Alzheimer's disease (AD). The E4 allele frequency in the group of patients with PPA was in the range seen in control populations and was much lower than the one reported in populations of patients with PRAD or AD. The E4 allele is therefore not a significant risk factor for developing PPA. These results provide neurobiological support for the syndromic distinction of PPA from PRAD and are in keeping with neuropathologic evidence showing that the vast majority of patients with PPA do not have the histopathology of AD. Although we do not yet have neuropathologic information on our patients, these results indicate that the clinical diagnosis of PPA has biological validity in that it identifies a population that is genetically different from the population of patients with a clinical diagnosis of PRAD.

Adult↗
PubMed1997

Neurophysiologic correlates of implicit face memory in intracranial visual evoked potentials.

Visual evoked potentials were recorded in the amygdala, hippocampus, mid- and inferotemporal cortex, orbitofrontal cortex, and lateral frontal cortex of seven epileptic patients while they were engaged in a difficult task requiring the discrimination between repeated and nonrepeated faces. The explicit recognition of previously seen faces was at chance levels, as measured by the accuracy of push-button responses. Nevertheless, all subjects showed clear-cut differential evoked responses to repeated versus nonrepeated faces, indicating implicit encoding of the distinction between the two types of stimuli. Differential responses were more frequent in neocortical recording sites (especially in the mid- and inferotemporal leads) than in limbic recording sites such as the amygdala and hippocampus. The authors conclude that implicit encoding processes are modulated by neocortical visual association areas of the temporal lobes.

Adult↗
PubMed1996

Functional imaging of human right hemispheric activation for exploratory movements.

We employed positron emission tomography to examine the functional anatomy of the exploratory-motor aspect of spatial attention. Subjects moved their right hand under nonexploratory (control) versus exploratory (active) conditions. Movement architecture and eye movements were matched across conditions. Statistical parametric maps of the exploratory (active) minus nonexploratory (control) tasks in subjects using their right hand in the right hemispace demonstrated activation in right cingulate, premotor and posterior parietal areas. The net activation of multiple right hemisphere cortical areas ipsilateral to the active limb and hemispace strongly supports the predicted, distributed network anatomy and is consistent with possible right hemispheric dominance for exploratory attentional movements.

Adult↗
PubMed1996

Cortical activation in the human brain during lateral saccades using EPISTAR functional magnetic resonance imaging.

The location of the human cortical substrate underlying simple horizontal saccadic eye movements was investigated using echoplanar functional magnetic resonance imaging (fMRI) in young healthy volunteers. Echoplanar imaging with signal targeting and alternating radiofrequency (EPISTAR), a novel perfusion technique, measured signal intensity changes in one to four contiguous 10-mm slices centered to include both striate cortex and putative frontal eye fields during horizontal saccade and fixation conditions. Subtraction images of self-paced visually guided saccadic versus fixation conditions showed bilateral marked and statistically significant localized signal increases in the precentral region (Brodmann areas 4, 6) and peristriate cortex (areas 17, 18, 19) and qualitative increases in the superior medial frontal region, as identified by a Talairach-Tournoux generalized template in the brain slices that were scanned. Additional parietal activation occurred during a target-guided saccade task. Our data (i) support the localization of the human FEF, as identified by simple, nonexploratory saccadic eye movements, in the precentral motor strip and premotor cortex, (ii) show individual variability in the exact anatomical location of saccade-related activations, and (iii) confirm that the EPISTAR technique can demonstrate localized signal increases during a behavioral task.

Adult↗
PubMed1996

Right sided hemispatial neglect and bilateral cerebral lesions.

This study compared the frequency with which unilateral and bilateral cerebral disease gives rise to right sided visual hemispatial inattention. A retrospective survey identified brain injured patients for whom target omissions on visual target cancellation tasks significantly exceeded control values. Subjects consisted of 40 right handed patients referred for clinical evaluation or research study of hemispatial inattention. Right sided visual hemispatial inattention occurred with greater frequency and severity in patients with bilateral lesions than in patients with unilateral left sided or right sided lesions. All eight patients with bilateral lesions manifested right sided hemispatial inattention and failed to detect more targets overall than patients in the other two groups. Of the 13 patients with left sided lesion, seven ignored more targets on the right and six ignored more targets on the left. All but one of the 19 patients with right sided lesions ignored more targets on the left. The association of severe right sided visual hemispatial inattention with bilateral cerebral disease extends previous findings and showed that, in this sample, the most common setting for right sided hemispatial neglect occurred in patients with bilateral cerebral lesions.

Aged↗
PubMed1996

Location of the central sulcus via cortical thickness of the precentral and postcentral gyri on MR.

PURPOSE: To determine whether relative cortical thickness measurements of the precentral and postcentral gyri can be used to differentiate the central sulcus from adjacent cortical sulci. METHODS: Turbo inversion-recovery MR imaging of the entire brain was done with scans parallel to the anterior commissure-posterior commissure line. Cortical thickness was measured in each hemisphere with a jeweler's eyepiece with 0.1-mm gradations. Three measurements were obtained perpendicular to the central, precentral, and superior frontal sulci, as determined by means of established anatomic methods. The ratios of cortical thickness on both sides of the central, precentral, and superior frontal sulci were calculated and compared. RESULTS: The mean ratio of precentral/postcentral gyri was 1.64 for the right hemisphere and 1.53 for the left hemisphere. The mean cortical thickness ratios were as follows: 1.01 for the right hemisphere and 3.01 for the left hemisphere across the precentral sulcus, and 1.03 for the right hemisphere and 0.99 for the left hemisphere across the superior frontal sulcus. CONCLUSION: Cortical thickness measurements across the central sulcus provide a method for locating the primary motor (precentral gyri) and primary somatosensory (postcentral gyri) cortices. The higher mean cortical thickness ratio across the central sulcus corresponds with known cytoarchitectonic relationships.

Adult↗
PubMed1995

Selectively distributed processing of visual object recognition in the temporal and frontal lobes of the human brain.

Evoked potentials to visually driven cognitive tasks were recorded through depth electrodes placed bilaterally within the amygdala, hippocampus, midtemporal and inferotemporal cortex, and lateral frontal cortex of 6 epileptic patients. Task-related differential response patterns were used to identify the recording sites engaged by specific aspects of visual encoding. In this group of 6 patients, the amygdala was most frequently engaged in encoding the familiarity of faces; midtemporal and inferotemporal cortex, in encoding perceptual identity and object categorization; and lateral frontal cortex, in holding visual object information in working memory. The two aspects of encoding that most frequently engaged the hippocampal region were related to working memory and object categorization. The processing of complex visual knowledge is thus anatomically distributed but regionally specialized. These experiments also showed that identical input and output parameters can engage different areas of the brain depending on the nature of the instructional set.

Adult↗
PubMed1995

Postnatal development of cortical acetylcholinesterase-rich neurons in the rat brain: permanent and transient patterns.

The development of acetylcholinesterase (AChE) activity within cortical neurons of the rat brain was investigated using a histochemical method. The fate of these neurons in later stages of development was studied in animals in which AChE within cortical axons (mostly cholinergic) had been depleted by lesions of the cholinergic neurons of the basal forebrain or by injections of diisopropyl fluorophosphate. We designated neurons with medium to high intensity of reaction product as AChEH and neurons with a low intensity of reaction product as AChEL. Four groups of AChEH cortical neurons were detected: (1) AChEH Cajal-Retzius cells were present in layer I at birth (P0) and decreased steadily in number until none could be detected at P17 or thereafter. (2) AChEH neurons within layer VI and underlying white matter were present at P0, peaked in number and staining intensity at P8-P9, showed a moderate decrease in number at P11-P13 and a further decrease into adulthood. (3) AChEH polymorphic intracortical neurons appeared at P3-P4 in deep cortical layers and by P9 were present in layers II-VI. They continued to increase in number through P11-P14 at which time they displayed the adult pattern and were found in all cortical areas. (4) A large population of AChEH pyramidal neurons appeared at P1-P4, peaked at P8-P10 and was no longer visible at P21. In the adult cerebral cortex, few pyramidal neurons displayed AChE activity and these were almost always of the AChEL type. These results indicate that the AChE within cortical neurons is developmentally regulated and that the content of this enzyme helps to differentiate cortical neurons into distinct populations. The transient expression of AChE activity within cortical neurons suggests a role for this enzyme in the development of the cerebral cortex.

Acetylcholinesterase↗
PubMed1995

Cholinesterases and the pathology of Alzheimer disease.

Alzheimer disease (AD) is accompanied by a marked loss of acetylcholinesterase (AChE) activity associated with cortical cholinergic axons and cholinoceptive neurons. Simultaneous with this loss, cholinesterase (ChE) activity emerges in AD cortex in the form of AChE and butyrylcholinesterase activity associated with plaques, tangles, and amyloid angiopathy. Our observations have shown that the ChEs associated with the pathological lesions of AD (ADChEs) possess different enzymatic properties and quite possibly are of a different source as compared with the ChEs associated with normal neurons and axons. The ADChEs most likely have noncholinergic functions involved in the pathogenesis of AD. The postulated functions include acting as proteases/peptidases, participating directly in the amyloidogenic processing of the amyloid precursor protein, and causing aberrant growth of neuronal processes. The therapeutic and diagnostic implications of ADChEs are discussed.

Acetylcholinesterase↗
PubMed1994

Human striatum: the distribution of neurofibrillary tangles in Alzheimer's disease.

The distribution of neurofibrillary tangles and senile plaques was surveyed in the striatum of Alzheimer's disease cases. Neurofibrillary tangles were present throughout the striatum, but displayed significantly higher densities in the nucleus accumbens, olfactory tubercle and tail of the caudate nucleus. Senile plaques with dense amyloid cores showed a similar pattern of distribution. By contrast, non-cored senile plaques were homogeneously distributed in all striatal territories. No tangles and few plaques were observed in the striatum of control cases. These findings suggest that the 'limbic' striatum is preferentially vulnerable to pathology in Alzheimer's disease.

Adult↗
PubMed1994

Cholinesterase activity in the plaques, tangles and angiopathy of Alzheimer's disease does not emanate from amyloid.

Previous histochemical observations in our laboratory have demonstrated the presence of butyrylcholinesterase and an enzymatically altered form of acetylcholinesterase activity in the plaques, tangles and amyloid-containing vessels of Alzheimer's disease. These findings suggested possible interactions between amyloid and cholinesterases. In this study we employed a cholinesterase biochemical assay to determine whether the amyloid precursor protein either had cholinesterase activity itself or influenced the enzymatic activity of cholinesterases. None of the three amyloid precursor sequences used (695, 751, 770, up to 16 micrograms/ml) exhibited any acetylcholinesterase or butyrylcholinesterase activity that could be detected by our method. In addition, none of the amyloid precursor proteins influenced the enzymatic activity of purified acetylcholinesterase or butyrylcholinesterase in a specific manner. It is therefore quite unlikely that amyloid can, by itself, account for the intense cholinesterase activity associated with the pathological lesions of AD.

Alzheimer Disease↗
PubMed1994

The impact of aging on curiosity as measured by exploratory eye movements.

OBJECTIVE: To investigate changes in novelty-seeking behavior (curiosity) associated with normal aging. BACKGROUND: Recently, we demonstrated that patients with a diagnosis of probable Alzheimer's disease display diminished novelty-seeking behavior as measured by exploratory eye movements. Nondemented, elderly individuals are often depicted in clinical descriptions as exhibiting diminished curiosity and increased disengagement from their surroundings. However, this behavior has not been systematically investigated as a function of normal aging. SETTING: University hospital center studying aging and dementia. SUBJECTS: Fourteen active, healthy elderly subjects (mean age, 72 years) and 16 middle-aged subjects (mean age, 42 years) matched for education and estimated IQ. MEASURES: Exploratory eye movements were recorded in response to visual stimuli that varied in novelty, complexity, and incongruity. RESULTS: Both older and middle-aged subjects (1) spent significantly more time exploring the more irregular or incongruous of two simultaneously presented stimuli, (2) spent increasingly less time looking at a repeating visual stimulus paired with a stimulus that changed with each trial, and (3) exhibited the same degree of overall exploration of a visual scene and devoted an approximately equal amount of attention to an unexpected element within it. As a group, older subjects spent slightly less time than middle-aged subjects examining incongruous stimuli. However, 71% (10/14) of older subjects performed within 1 SD of the mean of middle-aged subjects and 21% (3/14) performed as well as the top 50% (8/16) of middle-aged controls. CONCLUSIONS: The drive for curiosity, as measured by exploratory eye movements, can be well preserved in older individuals. Further research is needed to determine if the integrity of this drive can serve as a marker of "successful aging" and to identify which physiological and psychological factors influence its preservation through the life cycle.

Adult↗
PubMed1994

Impairment of spatially directed attention in patients with probable Alzheimer's disease as measured by eye movements.

OBJECTIVE: To investigate changes in spatially directed attention in patients with a diagnosis of probable Alzheimer's disease (AD). BACKGROUND: Impaired attention in patients with probable AD has not been the subject of extensive research. Yet recent reports suggest that attentional deficits may be an important early feature of the disease in a subset of patients. SETTING: University hospital center studying dementia and aging. SUBJECTS: Ten mild to moderately impaired patients diagnosed as having probable AD, by National Institute of Neurologic and Communicative Diseases and Stroke criteria, and 11 healthy age- and education-matched controls. MEASURES: Eye movements were recorded as subjects participated in two experiments designed to measure spatially directed attention. Subjects were instructed to (1) attend to and fixate a target appearing randomly to the right or left of a central marker and (2) direct attention to and fixate a target appearing randomly in one of four peripheral locations. RESULTS: Patients with probable AD exhibited fewer accurate trials and longer saccade latencies in both tasks. As a group, patients performed worse in the second task that placed increased demands on attention. However, the performance of patients in this second experiment varied. Four patients performed significantly worse than all other patients, while three patients performed as well as controls. Errors in the second task were reviewed to identify specific types of attentional deficits. Six empirically derived error patterns were classified into one of two major categories: perseveration and impersistence. Seven of 10 patients made greater than 50% errors of perseveration, and three of 10 made greater than 50% errors of impersistence. CONCLUSIONS: Impairment of attention may be an early feature of AD and a prominent clinical characteristic of some patients. The differences observed in error types made by patients may reflect the varied distribution of neuropathologic changes affecting structures that mediate aspects of attention. The architecture of eye movements can be used as a physiologic measure that should provide useful information for the diagnosis and clinicopathologic subtyping of patients with AD.

Aged↗
PubMed1994

Butyrylcholinesterase reactivity differentiates the amyloid plaques of aging from those of dementia.

In a sample of consecutively received, 4 demented and 4 age-matched nondemented brains, the total cortical area covered by plaque-like A beta amyloid and butyrylcholinesterase deposits was measured at two regions of the temporal cortex with the help of computed densitometry. Demented as well as age-matched nondemented brains contained A beta and butyrylcholinesterase-positive plaques. The total cortical area covered by the A beta precipitates was higher in demented individuals but there was overlap with the values seen in the specimens from nondemented individuals. The proportional plaque area displaying butyrylcholinesterase reactivity was very significantly and five fold to sixfold higher in the demented than in the nondemented group and there was no overlap between the two populations. Diffuse A beta deposits in nondemented elderly brains may represent a benign or preclinical stage of plaque deposition with relatively little pathological effect on brain tissue and mental function. Our results suggest that the progressively more extensive butyrylcholinesterase reactivity of plaques may participate in their transformation from a relatively benign form to pathogenic structures associated with neuritic degeneration and dementia.

Aged↗
PubMed1994

Two types of cholinergic projections to the rat amygdala.

The cholinergic innervation of the rat amygdala was studied immunohistochemically with antibodies against choline acetyltransferase and the low affinity p75 nerve growth factor receptor in normal rats and in rats lesioned with an immunotoxin, 192 IgG-saporin, directed against the p75 nerve growth factor receptor. The density of choline acetyltransferase-positive fibers was high in the nucleus of the lateral olfactory tract, the basolateral nucleus, and the amygdalohippocampal area; medium in the lateral nucleus, the cortical nucleus, the accessory basal nucleus, the periamygdaloid cortex, and the anterior amygdaloid area; and low in the medial and central nuclei. Nerve growth factor receptor-positive fibers were of medium density in the lateral nucleus, the accessory basal nucleus, the cortical nucleus, the anterior amygdaloid area, the periamygdaloid cortex, and the amygdalohippocampal area. The medial nucleus and the central nucleus displayed a low density of nerve growth factor receptor-positive fibers. The basolateral nucleus and the nucleus of the lateral olfactory tract also contained a low density of nerve growth factor receptor-positive fibers even though the two nuclei displayed the highest density of choline acetyltransferase-positive fibers in the amygdala. Injections of 192 IgG-saporin induced a complete loss of cholinergic nerve growth factor receptor-positive neurons in the basal forebrain but spared a subpopulation of nerve growth factor receptor-negative cholinergic neurons in the nucleus basalis-substantia innominata complex. Following 192 IgG-saporin injections, choline acetyltransferase-positive and acetylcholinesterase-positive fibers were essentially unchanged in the nucleus of the lateral olfactory tract and the basolateral nucleus and showed a partial reduction in the remaining nuclei of the amygdaloid complex. Cholinergic fibers emanating from cholinergic cell group 4 neurons reached the amygdala via the stria terminalis and the ventral amygdalofugal pathway. These observations indicate that two amygdaloid nuclei, the nucleus of the lateral olfactory tract and the basolateral nucleus, receive their cholinergic projections predominantly, if not exclusively, from nerve growth factor receptor-negative cholinergic neurons whereas all remaining amygdaloid regions receive fibers from nerve growth factor receptor-negative as well as nerve growth factor receptor-positive cholinergic neurons.

Amygdala↗
PubMed1994

Human striatum: chemoarchitecture of the caudate nucleus, putamen and ventral striatum in health and Alzheimer's disease.

The morphology and distribution of perikarya positive for choline acetyltransferase, somatostatin, calcium binding protein (calbindin D28K) and nicotinamide adenine dinucleotide phosphate diaphorase were surveyed in the human striatum. Choline acetyltransferase and somatostatin antibodies labeled separate populations of large striatal interneurons. Somatostatin immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (nitric oxide synthase) activity were completely co-localized. Calbindin antibody identified two distinct groups of striatal neurons: (1) numerous medium-sized, lightly stained neurons, probably analogous to striatopallidal projection neurons in the rat, and (2) much less numerous, large, darkly stained neurons. Half of the latter group, but none of the former, were also nicotinamide adenine dinucleotide phosphate diaphorase-positive. Somatostatin-positive and medium-sized, calbindin-positive neurons were more numerous in the caudate nucleus than in the putamen or ventral striatum. By contrast, large calbindin-immunoreactive neurons were more frequently encountered in the putamen. Choline acetyltransferase-positive neurons were evenly distributed across striatal components. In aged control subjects, the size of large, darkly stained calbindin-positive neurons was reduced relative to young subjects. Aging had no effect on somatostatin-, medium-sized calbindin-, or choline acetyltransferase-positive neurons. However, in histologically confirmed cases of Alzheimer's disease, there was a selective, 75% loss of choline acetyltransferase-immunoreactive perikarya from the ventral striatum, but not from the dorsal striatum, compared to aged controls. Furthermore, the remaining cholinergic neurons in the ventral striatum of Alzheimer's disease cases were significantly smaller than similar neurons in controls. These results indicate that various striatal components which have been shown to differ in their anatomical connectivity and functional specialization, also differ in their neurochemical signatures. The specific and marked loss of choline acetyltransferase-positive neurons from the ventral striatum in Alzheimer's disease is consistent with the characteristic cholinergic and 'limbic' pathology in this disease.

Adult↗