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D R Gitelman

Publications and source records attributed to D R Gitelman.

32 records · Page 2Linked to original sources

The large-scale neural network for spatial attention displays multifunctional overlap but differential asymmetry.

Functional magnetic resonance imaging (fMRI) was used to determine the brain regions activated by two types of covert visuospatial attentional shifts: one based on exogenous spatial priming and the other on foveally presented cues which endogenously regulated the direction of spatial expectancy. Activations were seen in the cortical and subcortical components of a previously characterized attentional network, namely, the frontal eye fields, posterior parietal cortex, the cingulate gyrus, the putamen, and the thalamus. Additional activations occurred in the anterior insula, dorsolateral prefrontal cortex, temporo-occipital cortex in the middle and inferior temporal gyri, the supplementary motor area, and the cerebellum. Direct comparisons showed a nearly complete overlap in the location of activations resulting from the two tasks. However, the spatial priming task displayed a more pronounced rightward asymmetry of parietal activation, and a conjunction analysis showed that the area of posterior parietal cortex jointly activated by both tasks was more extensive in the right hemisphere. Furthermore, the posterior parietal and temporo-occipital activations were more pronounced in the task of endogenous attentional shifts. The results show that both exogenous (based on spatial priming) and endogenous (based on expectancy cueing) shifts of attention are subserved by a common network of cortical and subcortical regions. However, the differences between the two tasks, especially in the degree of rightward asymmetry, suggests that the pattern of activation within this network may show variations that reflect the specific attributes of the attentional task.

Adult↗

Neuroanatomic overlap of working memory and spatial attention networks: a functional MRI comparison within subjects.

Frontal and posterior parietal activations have been reported in numerous studies of working memory and visuospatial attention. To directly compare the brain regions engaged by these two cognitive functions, the same set of subjects consecutively participated in tasks of working memory and spatial attention while undergoing functional MRI (fMRI). The working memory task required the subject to maintain an on-line representation of foveally displayed letters against a background of distracters. The spatial attention task required the subject to shift visual attention covertly in response to a centrally presented directional cue. The spatial attention task had no working memory requirement, and the working memory task had no covert spatial attention requirement. Subjects' ability to maintain central fixation was confirmed outside the MRI scanner using infrared oculography. According to cognitive conjunction analysis, the set of activations common to both tasks included the intraparietal sulcus, ventral precentral sulcus, supplementary motor area, frontal eye fields, thalamus, cerebellum, left temporal neocortex, and right insula. Double-subtraction analyses yielded additional activations attributable to verbal working memory in premotor cortex, left inferior prefrontal cortex, right inferior parietal lobule, precuneus, and right cerebellum. Additional activations attributable to covert spatial attention included the occipitotemporal junction and extrastriate cortex. The use of two different tasks in the same set of subjects allowed us to provide an unequivocal demonstration that the neural networks subserving spatial attention and working memory intersect at several frontoparietal sites. These findings support the view that major cognitive domains are represented by partially overlapping large-scale neural networks. The presence of this overlap also suggests that spatial attention and working memory share common cognitive features related to the dynamic shifting of attentional resources.

Adult↗

A large-scale distributed network for covert spatial attention: further anatomical delineation based on stringent behavioural and cognitive controls.

Functional MRI was used to examine cerebral activations in 12 subjects while they performed a spatial attention task. This study applied more stringent behavioural and cognitive controls than previously used for similar experiments: (i) subjects were included only if they showed evidence of attentional shifts while performing the task in the magnet; (ii) the experimental task and baseline condition were designed to eliminate the contributions of motor output, visual fixation, inhibition of eye movements, working memory and the conditional (no-go) component of responding. Activations were seen in all three hypothesized cortical epicentres forming a network for spatial attention: the lateral premotor cortex (frontal eye fields), the posterior parietal cortex and the cingulate cortex. Subcortical activations were seen in the basal ganglia and the thalamus. Although the task required attention to be equally shifted to the left and to the right, eight of 10 subjects showed a greater area of activation in the right parietal cortex, consistent with the specialization of the right hemisphere for spatial attention. Other areas of significant activation included the posterior temporo-occipital cortex and the anterior insula. The temporo-occipital activation was within a region broadly defined as MT+ (where MT is the middle temporal area) which contains the human equivalent of area MT in the macaque monkey. This temporo-occipital area appears to constitute a major component of the functional network activated by this spatial attention task. Its activation may reflect the 'inferred' shift of the attentional focus across the visual scene.

Adult↗

Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain.

All sectors of the human cerebral cortex receive dense cholinergic input. The origin of this projection is located in the Ch4 cell group of the nucleus basalis of Meynert. However, very little is known about the location of the pathways which link the cholinergic neurons of the nucleus basalis to the human cerebral cortex. This question was addressed in whole-hemisphere sections processed for the visualization of multiple cholinergic markers. Two highly organized and discrete bundles of cholinergic fibres extended from the nucleus basalis to the cerebral cortex and amygdala and were designated as the medial and lateral cholinergic pathways. These bundles contained acetylcholinesterase, choline acetyltransferase and nerve growth factor receptors, confirming their cholinergic nature and origin within the basal forebrain. The medial pathway joined the white matter of the gyrus rectus, curved around the rostrum of the corpus callosum to enter the cingulum and merged with fibres of the lateral pathway within the occipital lobe. It supplied the parolfactory, cingulate, pericingulate and retrosplenial cortices. The lateral pathway was subdivided into a capsular division travelling in the white matter of the external capsule and uncinate fasciculus and a perisylvian division travelling within the claustrum. Branches of the perisylvian division supplied the frontoparietal operculum, insula and superior temporal gyrus. Branches of the capsular division innervated the remaining parts of the frontal, parietal and temporal neocortex. Representation of these cholinergic pathways within a 3D MRI volume helped to identify white matter lesion sites that could interfere with the corticopetal flow of cholinergic pathways.

Adult↗

Dopamine agonists reorient visual exploration away from the neglected hemispace.

OBJECTIVE: To study the effects of bromocriptine, a dopamine agonist, on visual search. BACKGROUND: The anatomic substrate of spatial attention takes the form of a distributed network with interconnected cortical (frontal, parietal, and cingulate) and subcortical (striatal and thalamic) components. Dopamine appears to exert a modulatory effect on the function of this network. METHODS: Seven consecutive right-handed subjects with right-sided cerebral lesions were studied using a computerized target search paradigm. Eye movements were recorded. RESULTS: Bromocriptine caused the subjects to spend more time exploring the ipsilesional hemispace and therefore increased the relative neglect of the contralesional left hemispace. However, target detection accuracy did not change. Bromocriptine thus had a differential impact on the exploratory-motor versus sensory-perceptual components of directed attention. CONCLUSIONS: Our results show that bromocriptine may worsen some aspects of hemispatial neglect in patients with lesions that include the postsynaptic components of ascending dopaminergic pathways.

Adult↗

Functional localization of the system for visuospatial attention using positron emission tomography.

PET was used to image the neural system underlying visuospatial attention. Analysis of data at both the group and individual-subject level provided anatomical resolution superior to that described to date. Six right-handed male subjects were selected from a pilot behavioural study in which behavioural responses and eye movements were recorded. The attention tasks involved covert shifts of attention, where peripheral cues indicated the location of subsequent target stimuli to be discriminated. One attention condition emphasized reflexive aspects of spatial orientation, while the other required controlled shifts of attention. PET activations agreed closely with the cortical regions recently proposed to form the core of a neural network for spatial attention. The two attention tasks evoked largely overlapping patterns of neural activation, supporting the existence of a general neural system for visuospatial attention with regional functional specialization. Specifically, neocortical activations were observed in the right anterior cingulate gyrus (Brodmann area 24), in the intraparietal sulcus of right posterior parietal cortex, and in the mesial and lateral premotor cortices (Brodmann area 6).

Attention↗

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↗

Safety of hypercapnic challenge: cardiovascular and neurologic considerations.

The hemodynamic, cerebrovascular, and neurologic effects of hypercapnia with 4% and 6% CO2 were retrospectively reviewed in 217 patients referred for regional CBF (rCBF) procedures. Inhalation of CO2 significantly increased rCBF, blood pressure, and pulse from baseline. The findings suggest a higher incidence of side effects with 6% CO2 concentration and an equivalent vasoreactivity to 4%. We recommend the use of 4% CO2 for hypercapnic stimulation, and present safety guidelines for its use.

Administration, Inhalation↗

Perfusion insufficiency in limb-shaking transient ischemic attacks.

We describe a 63-year-old man with severe bilateral internal carotid artery disease who presented with repeated, brief attacks of left limb shaking precipitated by his standing up. Cerebral blood flow measured by xenon-133 inhalation showed reduced resting flows and a focal perfusion deficit in the right dorsofrontal and upper rolandic regions. Blood flow velocity and pulsatility index of the right middle cerebral artery measured by transcranial Doppler ultrasonography were also reduced. With hypercapnic challenge, both hemispheric tissue perfusion and blood flow velocity showed impaired reactivity. With induced hypotension, the focal perfusion deficit in the right dorsofrontal region was accentuated. Following right internal carotid endartectomy, resting cerebral blood flow and blood flow velocity improved, as did hypercapnic vasoreactivity. These reversible deficits in cerebral blood flow and vasoregulation, which were maximal in the dorsofrontal region, are consistent with low perfusion in the border zone territory or the distal fields and demonstrate that hemodynamic failure is the likely mechanism for limb-shaking transient ischemic attacks from severe carotid artery disease.

Biomechanical Phenomena↗

A mathematical model and image analysis technique for calculating regional cerebral blood flow.

This paper discusses the theory and implementation of a modular data analysis system for the calculation and imaging of regional cerebral blood flow. The program may be generalized to any system requiring instantaneous and controllable visual data display, and we have set it up for compartmental analysis as described by the Fick equation with certain correction factors. We have included flow charts of the program source code and data paths for the various modules. We also describe the functional hardware components necessary for the execution of these algorithms. Finally, analyzed data are represented from a set of experiments employing differential visual stimulation. The results obtained using our methods are comparable to those in the existing literature; they are more accurately and easily obtained, and have the added power of manipulable digitization of the original image without loss of data.

Animals↗

Decay of RNA in RNA processing mutants of Escherichia coli.

Stability of RNA was tested in strains of Escherichia coli carrying single, double, or triple mutations in the RNA processing enzymes RNase III, RNase E and RNase P. Tests were carried out for total pulse labeled RNA, beta-galactosidase mRNA and for the decay of preexisting RNA during carbon starvation. Decay of RNA was measured at permissive and nonpermissive temperatures, and in no case were significant differences between mutants and non-mutant strains found. Therefore, we conclude that the three processing enzymes; RNase III, E and P do not contribute significantly to turnover of RNA IN Escherichia coli.

Escherichia coli↗

Muscarinic and nicotinic contributions to cognitive function and cortical blood flow.

Muscarinic receptor blockade in humans induces a transient memory deficit claimed to mimic aspects of Alzheimer's disease (AD). AD is also strongly associated with a specific blood flow abnormality in parietotemporal cortex; we previously showed that, despite induction of a dementia-like state, scopolamine does not produce these blood flow changes. In the present study, we administered both muscarinic and nicotinic receptor blockade (using scopolamine and mecamylamine) to seven elderly healthy subjects and measured subsequent changes in cognition and cortical perfusion, using the 133Xe inhalation method to quantify regional cerebral blood flow (rCBF). Results confirmed earlier findings of scopolamine-induced memory deficit and frontal cortex flow reduction. Only mecamylamine, however, produced a perfusion deficit in parietotemporal cortex. All effects were transient and dose-dependent. These findings demonstrate the safety and feasibility of differential and combined blockade of nicotinic and muscarinic cholinergic blockade in human subjects. Furthermore, the nicotinic antagonist mecamylamine yields rCBF changes similar to those seen in AD, despite producing only minimal cognitive effects on its own. The rCBF and behavioral manifestations in AD may therefore reflect the functional loss of nicotinic receptors in addition to alterations in other receptor systems.

Aged↗