Biomedical subjects

G E Alexander

Publications and source records attributed to G E Alexander.

At least 37 records · Page 2Linked to original sources

PubMed1999

Cerebral blood flow patterns underlying the differential impairment in category vs letter fluency in Alzheimer's disease.

Verbal fluency tasks are used to assess language functioning in Alzheimer's disease (AD), and performance typically declines as the disease progresses. However, several studies have shown that Category Fluency performance (produce words from a category) declines faster than Letter Fluency performance (produce words beginning with a certain letter), which is not the case for other dementias. The purpose of this study was to determine if each of these two types of fluency tasks was associated with different patterns of cerebral blood flow abnormality in AD. A resting, Xenon-inhalation regional cerebral blood flow measurement (133Xe rCBF) and neuropsychological evaluation was administered to 25 patients with probable AD and 24 healthy elderly controls. Stepwise regression using rCBF measures as predictor variables was used to predict Category and Letter Fluency performance, in both a combined group of patients and controls, and in the patient group alone. Correlations were also computed between rCBF variables and the difference between normatively corrected scores on each task for each subject, which characterized the extent of the discrepancy between them. In full sample regressions, both Category and Letter Fluency were predicted by education and the decline in left inferior parietal flow, a focal AD-related deficit. Additional variance in Category fluency, however, was predicted by global mean flow, while additional variance in Letter Fluency was predicted by frontal flow. Within the patient sample, in turn, the primary predictor of Category Fluency was mean flow; the primary predictor of Letter Fluency was left-sided frontal flow. Analysis of the fluency difference score revealed that relatively greater impairment of Category Fluency was associated with more typical, AD-related deficits in posterior temporal and parietal perfusion. When the two were equivalently impaired, typical AD-related deficits were accompanied by marked deficits in frontal perfusion. These findings are consistent with the underlying neuropsychology of these tasks, and suggest that Category Fluency's stronger association to the most typical CBF deficits of AD account for its greater sensitivity to this disease. Letter Fluency deficits, on the other hand, carry significant information about the degree to which perfusion deficits have spread to frontal cortex.

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PubMed1999

Role of the posterior parietal cortex in updating reaching movements to a visual target.

The exact role of posterior parietal cortex (PPC) in visually directed reaching is unknown. We propose that, by building an internal representation of instantaneous hand location, PPC computes a dynamic motor error used by motor centers to correct the ongoing trajectory. With unseen right hands, five subjects pointed to visual targets that either remained stationary or moved during saccadic eye movements. Transcranial magnetic stimulation (TMS) was applied over the left PPC during target presentation. Stimulation disrupted path corrections that normally occur in response to target jumps, but had no effect on those directed at stationary targets. Furthermore, left-hand movement corrections were not blocked, ruling out visual or oculomotor effects of stimulation.

Humans↗

PubMed1999

High brain myo-inositol levels in the predementia phase of Alzheimer's disease in adults with Down's syndrome: a 1H MRS study.

OBJECTIVE: An extra portion of chromosome 21 in Down's syndrome leads to a dementia in later life that is phenotypically similar to Alzheimer's disease. Down's syndrome therefore represents a model for studying preclinical stages of Alzheimer's disease. Markers that have been investigated in symptomatic Alzheimer's disease are myoinositol and N-acetyl-aspartate. The authors investigated whether abnormal brain levels of myo-inositol and other metabolites occur in the preclinical stages of Alzheimer's disease associated with Down's syndrome. METHOD: The authors used 1H magnetic resonance spectroscopy (MRS) with external standards to measure absolute brain metabolite concentrations in 19 nondemented adults with Down's syndrome and 17 age- and sex-matched healthy comparison subjects. RESULTS: Concentrations of myoinositol and choline-containing compounds were significantly higher in the occipital and parietal regions of the adults with Down's syndrome than in the comparison subjects. Within the Down's syndrome group, older subjects (42-62 years, N = 11) had higher myo-inositol levels than younger subjects (28-39 years, N = 8). Older subjects in both groups had lower N-acetylaspartate levels than the respective younger subjects, although this old-young difference was not greater in the Down's syndrome group. CONCLUSIONS: The approximately 50% higher level of myo-inositol in Down's syndrome suggests a gene dose effect of the extra chromosome 21, where the human osmoregulatory sodium/myo-inositol cotransporter gene is located. The even higher myoinositol level in older adults with Down's syndrome extends to the predementia phase earlier findings of high myoinositol levels in symptomatic Alzheimer's disease.

Adult↗

PubMed1999

Association between brain functional failure and dementia severity in Alzheimer's disease: resting versus stimulation PET study.

OBJECTIVE: This study tested the hypothesis that regional cerebral glucose metabolism during neuronal activation is a more sensitive index of neuronal dysfunction and clinical severity in Alzheimer's disease than is glucose metabolism at rest. METHOD: The subjects were 15 Alzheimer's disease patients with a wide range of Mattis Dementia Rating Scale scores (23-128). By using positron emission tomography, absolute glucose metabolism was measured in the parietal, occipital (visual areas), and temporal (auditory areas) cortical regions during rest (eyes/ears covered) and audiovisual stimulation. RESULTS: In the parietal cortex, glucose metabolism correlated with dementia severity in both conditions. In contrast, in the relatively preserved visual and auditory cortical regions, glucose metabolism predicted dementia severity during stimulation but not at rest. CONCLUSIONS: These findings suggest that regional cerebral glucose metabolism during stimulation is a more sensitive index of the functional/metabolic failure of neuronal systems than is metabolism at rest.

Acoustic Stimulation↗

PubMed1998

Volumes of medial temporal lobe structures in patients with Alzheimer's disease and mild cognitive impairment (and in healthy controls).

BACKGROUND: The clinical diagnosis of Alzheimer's disease (AD) can be difficult to make in early stages of disease. Structural neuroimaging offers a potential tool in the clinical diagnosis of AD with mild cognitive impairment. Postmortem studies indicate that early neuropathology in AD occurs in medial temporal lobe limbic structures. Magnetic resonance imaging (MRI) studies that assessed these volumes in mildly impaired AD patients remain inconclusive. METHODS: Using MRI, we measured volumes of left and right hippocampus, amygdala, and anterior and posterior parahippocampal gyrus (PHG) in 13 AD patients with mild cognitive impairment, defined as > or = 20 on the Mini-Mental State Exam, and in 21 healthy age- and sex-matched controls. RESULTS: The AD patients had smaller medial temporal lobe volumes, except for the right anterior PHG. Discriminant function analysis using MRI volumes produced 94% correct group classification. CONCLUSIONS: These results show that in mildly impaired AD patients atrophy is present in medial temporal lobe structures; that MRI volumes of the anterior PHG, which contains entorhinal cortex, are reduced, but the amygdala and hippocampal volumes show greater reduction; and that discriminant function analysis using all volumes as predictors can correctly classify a high proportion of individuals.

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PubMed1998

Corpus callosum atrophy is a possible indicator of region- and cell type-specific neuronal degeneration in Alzheimer disease: a magnetic resonance imaging analysis.

BACKGROUND: Pathological studies in Alzheimer disease indicate the specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long corticocortical connections within and between the cerebral hemispheres. OBJECTIVE: To evaluate the corpus callosum as an in vivo marker for cortical neuronal loss. METHOD: Using a new imaging technique, we measured region-specific corpus callosum atrophy in patients with Alzheimer disease and correlated the changes with neuropsychological functioning. Total cross-sectional area of the corpus callosum and areas of 5 callosal subregions were measured on midsagittal magnetic resonance imaging scans of 14 patients with Alzheimer disease (mean age, 64.4 years; Mini-Mental State Examination score, 11.4) and 22 healthy age- and sex-matched control subjects (mean age, 66.6 years; Mini-Mental State Examination score, 29.8). All subjects had minimal white matter changes. RESULTS: The total callosal area was significantly reduced in the patients with Alzheimer disease, with the greatest changes in the rostrum and splenium and relative sparing of the callosal body. Regional callosal atrophy correlated significantly with cognitive impairment in the patients with Alzheimer disease, but not with age or the white matter hyperintensities score. CONCLUSIONS: Callosal atrophy in patients with Alzheimer disease with only minimal white matter changes may indicate loss of callosal efferent neurons in corresponding regions of the cortex. Because these neurons are a subset of corticocortical projecting neurons, region-specific callosal atrophy may serve as a marker of progressive neocortical disconnection in Alzheimer disease.

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PubMed1998

Functional anatomy of saccadic adaptation in humans.

Positron emission tomography (PET) was used to investigate the neurophysiological substrate of human saccadic adaptation. Subjects made saccadic eye movements toward a visual target that was displaced during the course of the initial saccade, a time when visual perception is suppressed. In one condition, displacement was random from trial to trial, precluding any systematic modification of the initial saccade amplitude. In the second condition, the direction and magnitude of displacement were consistent, causing adaptative modification of the initial saccade amplitude. PET difference images reflecting metabolic changes attributable to the process of saccadic adaptation showed selective activation of the medioposterior cerebellar cortex. This localization is consistent with neurophysiological findings in monkeys and brain-lesioned humans.

Adaptation, Physiological↗

PubMed1998

Movement sequence-related activity reflecting numerical order of components in supplementary and presupplementary motor areas.

The supplementary motor area (SMA) and presupplementary motor areas (pre-SMA) have been implicated in movement sequencing, and neurons in SMA have been shown to encode what might be termed the relational order among sequence components (e.g., movement X followed by movement Y). To determine whether other aspects of movement sequencing might also be encoded by SMA or pre-SMA neurons, we analyzed task-related activity recorded from both areas in conjunction with a sequencing task that dissociated the numerical order of components (e.g., movement X as the 2nd component, irrespective of which movements precede or follow X). Sequences were constructed from eight component movements, each characterized by three spatial variables (origin, direction, and endpoint). Task-related activity recorded from 56 SMA and 63 pre-SMA neurons was categorized according to both the epoch (delay, reaction time, and movement time) and the spatial variable or component movement with which it was associated. All but one instance of task-related activity was selective for one of the spatial variables (SV-selective) rather than for any of the component movements themselves. Of 110 instances of SV-selective activity in SMA, 43 (39%) showed significant effects of numerical order. The corresponding incidence in pre-SMA, 82 (71%) of 116, was substantially higher (P < 0.00001). No effects of numerical order were evident among the hand paths, movement times, or electromyographic activity associated with task performance. We concluded that neurons in SMA and pre-SMA may encode the numerical order of components, at least for sequences that are distinguished mainly by that aspect of component ordering.

Animals↗

PubMed1998

Increasing required neural response to expose abnormal brain function in mild versus moderate or severe Alzheimer's disease: PET study using parametric visual stimulation.

OBJECTIVE: The authors examined the interaction of Alzheimer's disease severity and visual stimulus complexity in relation to regional brain function. METHOD: Each subject had five positron emission tomography [15]H2O scans while wearing goggles containing a grid of red lights embedded into each lens. Regional cerebral blood flow (CBF) was measured at 0 Hz and while lights were flashed alternately into the two eyes at 1, 4, 7, and 14 Hz. Changes in regional CBF from the 0-Hz baseline were measured at each frequency in 19 healthy subjects (mean age = 65 years, SD = 11), 10 patients with mild Alzheimer's disease (mean age = 69, SD = 5; Mini-Mental State score > or = 20), and 11 patients with moderate to severe Alzheimer's disease (mean age = 73, SD = 12; Mini-Mental State score < or = 19). RESULTS: As pattern-flash frequency increased, CBF responses in the comparison group included biphasic rising then falling in the striate cortex, linear increase in visual association areas, linear decrease in many anterior areas, and a peak at 1 Hz in V5/MT. Despite equivalent resting CBF and CBF responses to low frequencies among all groups, the groups with Alzheimer's disease had significantly smaller CBF responses than the comparison group at the frequency producing the largest response in the comparison group in many brain regions. Also, patients with moderate/severe dementia had smaller responses at frequencies producing intermediate responses in comparison subjects. CONCLUSIONS: Functional failure was demonstrated in patients with mild dementia when large neural responses were required and in patients with moderate/severe dementia when large and intermediate responses were required.

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PubMed1998

Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer's disease.

OBJECTIVE: To determine whether the hypometabolism observed in PET images of patients with Alzheimer's disease (AD) is due entirely to brain atrophy. BACKGROUND: Reduced brain glucose metabolism in AD patients measured using PET has been reported by numerous authors. Actual glucose metabolic values in AD may be reduced artificially because of brain atrophy, which accentuates the partial volume effect (PVE) on data collected by PET. METHODS: Using segmented MR images, we corrected regional cerebral metabolic rates for glucose for PVEs to evaluate the effect of atrophy on uncorrected values for brain metabolism in AD patients and healthy control subjects. RESULTS: Global glucose metabolism was reduced significantly before and after correction in AD patients compared with controls. Before PVE correction, glucose metabolic values in patients were lower than in control subjects in the inferior parietal, frontal, and lateral temporal cortex; in the posterior cingulate; and in the precuneus. These reductions remained significantly lower after PVE correction, although in the posterior cingulate the difference in metabolism between AD patients and control subjects lessened. Regional glucose metabolism of these areas with PVE correction was lower in moderately-severely demented patients than in mildly demented patients. CONCLUSION: Reduced glucose metabolism measured by PET in AD is not simply an artifact due to an increase in CSF space induced by atrophy, but reflects a true metabolic reduction per gram of tissue.

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PubMed1998

Dissociation between corpus callosum atrophy and white matter pathology in Alzheimer's disease.

OBJECTIVE: To determine whether the size of the corpus callosum is related to the extent of white matter pathology in patients with AD and age-matched healthy control subjects. METHODS: White matter hyperintensity load and corpus callosum size were compared between 20 clinically diagnosed AD patients and 21 age-matched healthy control subjects. We investigated the effect of age and disease severity on corpus callosum size and white matter hyperintensity, in addition to the relation between corpus callosum areas and white matter hyperintensity load. RESULTS: We found significant regional atrophy of the corpus callosum in AD when compared with control subjects, although the groups did not differ in their white matter hyperintensity load. We further showed a region-specific correlation between corpus callosum size and white matter hyperintensity in the control group but not in AD patients. In the AD group, corpus callosum size correlated with age and dementia severity, whereas white matter hyperintensity correlated only with age. CONCLUSION: Corpus callosum atrophy in AD can occur independent of white matter degeneration, likely reflecting specific AD pathology in projecting neurons.

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PubMed1997

Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory.

Modulation of the cholinergic neurotransmitter system results in changes in memory performance, including working memory (WM), in animals and in patients with Alzheimer disease. To identify associated changes in the functional brain response, we studied performance measures and regional cerebral blood flow (rCBF) using positron emission tomography (PET) in healthy subjects during performance of a WM task. Eight control subjects received an infusion of saline throughout the study and 13 experimental subjects received a saline infusion for the first 2 scans followed by a continuous infusion of physostigmine, an acetylcholinesterase inhibitor, for the subsequent 8 scans. rCBF was measured using H215O and PET in a sequence of 10 PET scans that alternated between rest and task scans. During task scans, subjects performed the WM task for faces. Physostigmine both improved WM efficiency, as indicated by faster reaction times, and reduced WM task-related activity in anterior and posterior regions of right midfrontal gyrus, a region shown previously to be associated with WM. Furthermore, the magnitudes of physostigmine-induced change in reaction time and right midfrontal rCBF correlated. These results suggest that enhancement of cholinergic function can improve processing efficiency and thus reduce the effort required to perform a WM task, and that activation of right prefrontal cortex is associated with task effort.

Adult↗

PubMed1997

Relation of age and apolipoprotein E to cognitive function in Down syndrome adults.

To test the cognitive effects of aging and apolipoprotein E (APOE) in individuals at high risk for Alzheimer's disease (AD), we assessed APOE genotypes and performance on a battery of neuropsychological tests in 41 non-demented, Down syndrome (DS) adults. Old DS subjects (ages 41-61 years) showed poorer memory and orientation scores than young DS adults (ages 22-38 years), but the groups did not differ in other measures after we controlled for intellectual function. Language ability was inversely related to APOE genotype, even after age was controlled for, with the presence of the epsilon 2 allele corresponding to better language skills than epsilon 4. Age-related cognitive changes in non-demented DS adults are consistent with the early effects of AD. The relationship between basic linguistic skills and APOE genotype supports this genetic factor in influencing the development of dementia and AD neuropathology in DS.

Adult↗

PubMed1997

Frequency variation of a pattern-flash visual stimulus during PET differentially activates brain from striate through frontal cortex.

We evaluate regional cerebral blood flow (rCBF) in 19 healthy elderly subjects, mean age 64 +/- 11 (SD, years), during a passive visual stimulus in which pattern-flash frequency was parametrically manipulated. Using goggles with a grid of red lights imbedded into each lens, we performed five positron emission tomography (PET) H2(15)O water scans on each subject at alternating (left to right eye) flash frequencies of 0, 1, 4, 7, and 14 Hz. We found a biphasic rising and falling rCBF response in the striate cortex (7 Hz peak) and left anterior cingulate (4 Hz peak), 1 Hz activation in left middle temporal gyrus (V5), monotonically increasing rCBF in posterior areas (lateral and inferior visual association areas, Brodmann 18 and 19), and monotonically decreasing rCBF in anterior areas (frontal, cingulate, and superior temporal) predominantly in right hemisphere. We suggest the striate rCBF changes at all frequencies primarily reflect lateral geniculate input, the middle temporal activation at 1 Hz reflects perception of apparent motion, and the posterior extrastriate rCBF monotonic increase represents a neural response to increasing luminance intensity and form and color complexity that occur as pattern-flash frequency increases. The anterior monotonic rCBF decrease may represent active cross-modal functional suppression of brain areas irrelevant for processing the passive visual stimulus. Pattern-flash rCBF responses were highly reproducible (no series effect), more so in posterior than in anterior brain regions. The reproducibility and systematically changing rCBF responses to this passive stimulus suggest that it could be successfully used as a disease probe to evaluate neural function and drug effects in cognitively impaired patients.

Aged↗

PubMed1997

Controlling the focus of spatial attention during visual search: effects of advanced aging and Alzheimer disease.

It was hypothesized that slowed visual search in healthy adult aging arises from reduced ability to adjust the size of the attentional focus. A novel, cued-visual search task manipulated the scale of spatial attention in a complex field in healthy elderly individuals and patients with dementia of the Alzheimer type (DAT). Precues indicated with varying validity the size and location of the area to be searched. Location precues exerted the strongest effects on conjunction search and the weakest effects on feature search. As the size of valid location cues decreased, conjunction search was facilitated. These effects declined progressively with advanced age and the onset of DAT. As the size of invalid cues increased, conjunction search was first facilitated, then slowed, but neither age nor DAT altered this effect. These results indicate that both Alzheimer's disease and, to a lesser degree, advanced aging, reduce control of the spatial focus of attention.

Aged↗

PubMed1997

Neural correlates of a spatial sensory-to-motor transformation in primary motor cortex.

Primary motor cortex (MC) has been strongly implicated in motor processing, but there have been relatively few attempts to determine whether MC may also play a role in either sensory or context-dependent processing. In the present study, neuronal activity in MC was characterized in relation to the planning and execution of visually instructed limb movements whose trajectories were dissociated from their spatial targets. This design permitted the dissociation of neuronal activity related to motor processing from activity related to sensory or context-dependent processing. Two macaque monkeys were trained to perform a visually instructed, delayed reaching paradigm with indirect visual feedback. Subjects used the right forelimb to capture targets presented on a video display by moving a two-dimensional joystick whose position was reflected by a cursor. The target to be capture on each trial was indicated by a visual instruction stimulus (IS), which was separated from a movement-triggering stimulus (TS) by a variable delay. The direction of forelimb movement was dissociated from the location of the target by varying the spatial mappings between joystick and cursor across two conditions, unrotated (0 degrees offset between cursor and limb direction) and rotated (90 degrees offset). Task-related activity was recorded from a total of 180 MC neurons. The focus of this study was on directionally tuned neuronal activity that included phasic, stimulus-related activity following the IS; tonic, set-related activity between IS and TS; and phasic, movement-related activity following the TS. Of the entire sample of MC neurons with directionally tuned activity, 119 cells were tested both under rotation conditions, permitting dissociation of directional responses that depended on target locations from those that depended on limb trajectory. Task-related neuronal activity was classified as target dependent if it covaried exclusively with target location across both conditions, and as limb dependent if it covaried exclusively with limb trajectory. Directional activity that did not fulfill criteria for either target or limb dependence, because of changes across rotation conditions, was classified as complex. Approximately one quarter of MC neurons showed weak, but consistent, stimulus-related activity that was directionally tuned (24%, 29 of 119). Nearly all of the directionally classifiable stimulus-related activity was target dependent (94%, 15 of 16 responses), with the exception of a single limb-dependent response (6%, 1 of 16). A majority of MC neurons showed set-related activity that was directionally tuned (61%, 72 of 119). Of the directionally classifiable set-related activity, there were comparable numbers of target-dependent (37%, 16 of 43) and limb-dependent responses (35%, 15 of 43), with the remainder being complex (27%, 12 of 43). Movement-related activity following the TS was considered to be early or late, depending on whether it preceded or followed the onset of movement. The large majority of MC neurons showed early movement-related activity that was directionally tuned (86%, 102 of 119): among those whose neurons early activity was directionally classifiable, there were only one third as many target-dependent responses (14%, 11 of 79) as limb-dependent responses (43%, 34 of 79), with the remainder being complex (43%, 34 of 79). There was also a large majority of MC neurons that showed late movement-related activity that was directionally tuned (84%, 100 of 119): among those whose late activity was directionally classifiable, there were only one ninth as many target-dependent responses (5%, 4 of 88) as there were limb-dependent responses (41%, 36 of 88), with the remainder being complex (55%, 48 of 88). The instructed delay task employed in this study required a sensory-to-motor transformation through which the instructed target location was associated with a limb movement of the appropriate direction. (ABSTRACT TRUNCATED)

Action Potentials↗

PubMed1997

Preferential representation of instructed target location versus limb trajectory in dorsal premotor area.

The dorsal premotor area (PMd) of monkeys has been implicated in processes relating to movement preparation and movement selection. In the present study, we sought to determine whether PMd neurons that are activated during a delayed reaching task have directional responses that reflect either the target (i.e., the goal) of an intended movement or the physical properties of the movement itself. Two macaque monkeys were trained to perform a visually instructed, delayed reaching task with indirect visual feedback. The subjects and methods were identical to those described in the preceding paper. In the behavioral task, each subject moved a two-dimensional joystick with the right forelimb to align a cursor with targets presented on a video display. The paradigm dissociated the direction of forelimb movement from the spatial location of the target. This was accomplished by varying the spatial mappings between joystick and cursor. A variable delay separated the visual stimulus that instructed the target location (IS) from the visual stimulus that triggered the instructed movement (TS). Task-related activity was recorded from a total of 181 PMd neurons. The focus of this study was on directionally tuned neuronal responses that included 1) stimulus-related activity (phasic, following IS); 2) set-related activity (phasic, following IS and TS); and 3) movement-related activity (phasic, following TS). Of the entire sample of PMd neurons with directionally tuned activity, 114 were tested with two joystick/cursor mappings, permitting dissociation of directional responses that depended on limb trajectory from those that depended on target location. Task-related neuronal activity was classified as target-dependent if it covaried exclusively with target location across both conditions, and as limb-dependent if it covaried exclusively with limb trajectory. Directional activity that changed significantly across rotation conditions was classified as complex. Approximately one half of the sample of PMd neurons showed stimulus-related activity that was directionally tuned (56%, 64 of 114). Nearly all of the directionally classifiable stimulus-related activity was target dependent (94%, 44 of 47 responses), and none was limb dependent. A small proportion was classified as complex (6%, 3 of 47 responses). More than two thirds of the PMd neurons showed set-related activity that was directionally tuned (69%, 79 of 114). Among cells with set-related activity that was directionally classifiable, there were approximately 9 times as many target-dependent responses (76%, 48 of 63) as there were limb-dependent responses (8%, 5 of 63), with the remainder being complex (16%, 10 of 63). Approximately three quarters of the sample of PMd neurons showed early movement-related activity (before movement onset) that was directionally tuned (78%, 89 of 114). Among those cells whose early movement-related activity was directionally classifiable, there were > 3 times as many target-dependent responses ((51%, 34 of 66) as limb-dependent responses (14%, 9 of 66), with the remainder being complex (35%, 23 of 66). Approximately two thirds of the sample showed late movement-related responses (after movement onset) that were directionally tuned (68%, 78 of 114). Among those cells whose late movement-related activity was directionally classifiable, there were comparable numbers of target-dependent (25%, 15 of 61) and limb-dependent responses (28%, 17 of 61), with the remainder being complex (47%, 29 of 61). These results indicate a preferential representation of target location rather than limb trajectory among PMd neurons. Over the extended interval from IS to motor response, there was a gradual decline in the frequency of target-dependent activity and corresponding increases in the frequencies of both limb-dependent and complex activity. These findings suggest that PMd neurons may participate in mediating the sensory-to-motor transformation required by the delayed reaching

Animals↗

PubMed1997

Interactive effects of age and hypertension on volumes of brain structures.

BACKGROUND AND PURPOSE: Advanced age and hypertension have each been associated with changes in brain morphology and cognitive function. To investigate the interaction of age and hypertension with structural brain changes and neuropsychological performance in otherwise healthy patients with essential hypertension, we compared young-old (ages 56 to 69 years) and old-old (ages 70 to 84 years) hypertensive patients (n = 27) with 20 age-matched normotensive healthy control subjects, using quantitative volumetric MRI and a battery of neuropsychological tests. METHODS: Quantitative regions of interest and segmentation analyses were applied to MRI scans of brain to measure volumes of different brain structures and of cerebrospinal fluid (CSF). Severity of white matter hyperintensities (WMHs) was qualitatively rated in the MRI scans. A battery of neuropsychological tests was administered to each subject. RESULTS: The combined hypertensive group (young-old and old-old) had smaller volumes of thalamic nuclei and larger volumes of CSF in the cerebellum and temporal lobes and showed poorer performance in memory and language tests than did the control subjects. Main effects for age were significant in multiple brain regions of interest. The old-old hypertensive patients and age-matched control subjects demonstrated volume reductions in brain structures and increases in ventricular and peripheral CSF volumes compared with the younger subjects. There was a significant group x age-group interaction in temporal and occipital CSF, not related to WMH, with the old-old hypertensive patients having significantly larger CSF volumes in these regions than the young-old hypertensives and both healthy control groups. CONCLUSIONS: Hypertension exacerbates the morphological changes accompanying advanced age. Temporal and occipital regions appear most vulnerable to brain atrophy due to the interactive effects of age and hypertension.

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