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Biomedical subjects

J C Mazziotta

Publications and source records attributed to J C Mazziotta.

At least 19 recordsLinked to original sources
PubMed2000

Patterns of brain activation in people at risk for Alzheimer's disease.

BACKGROUND: The epsilon4 allele of the apolipoprotein E gene (APOE) is the chief known genetic risk factor for Alzheimer's disease, the most common cause of dementia late in life. To determine the relation between brain responses to tasks requiring memory and the genetic risk of Alzheimer's disease, we performed APOE genotyping and functional magnetic resonance imaging (MRI) of the brain in older persons with intact cognition. METHODS: We studied 30 subjects (age, 47 to 82 years) who were neurologically normal, of whom 16 were carriers of the APOE epsilon4 allele and 14 were homozygous for the APOE epsilon3 allele. The mean age and level of education were similar in the two groups. Patterns of brain activation during functional MRI scanning were determined while subjects memorized and recalled unrelated pairs of words and while subjects rested between such periods. Memory was reassessed in 14 subjects two years later. RESULTS: Both the magnitude and the extent of brain activation during memory-activation tasks in regions affected by Alzheimer's disease, including the left hippocampal, parietal, and prefrontal regions, were greater among the carriers of the APOE epsilon4 allele than among the carriers of the APOE epsilon3 allele. During periods of recall, the carriers of the APOE epsilon4 allele had a greater average increase in signal intensity in the hippocampal region (1.03 percent vs. 0.62 percent, P<0.001) and a greater mean (+/-SD) number of activated regions throughout the brain (15.9+/-6.2 vs. 9.4+/-5.5, P=0.005) than did carriers of the APOE epsilon3 allele. Longitudinal assessment after two years indicated that the degree of base-line brain activation correlated with degree of decline in memory. CONCLUSIONS: Patterns of brain activation during tasks requiring memory differ depending on the genetic risk of Alzheimer's disease and may predict a subsequent decline in memory.

Aged↗
PubMed2000

Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease.

The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments.

Aged↗
PubMed2000

Modulating emotional responses: effects of a neocortical network on the limbic system.

Humans share with animals a primitive neural system for processing emotions such as fear and anger. Unlike other animals, humans have the unique ability to control and modulate instinctive emotional reactions through intellectual processes such as reasoning, rationalizing, and labeling our experiences. This study used functional MRI to identify the neural networks underlying this ability. Subjects either matched the affect of one of two faces to that of a simultaneously presented target face (a perceptual task) or identified the affect of a target face by choosing one of two simultaneously presented linguistic labels (an intellectual task). Matching angry or frightened expressions was associated with increased regional cerebral blood flow (rCBF) in the left and right amygdala, the brain's primary fear centers. Labeling these same expressions was associated with a diminished rCBF response in the amygdalae. This decrease correlated with a simultaneous increase in rCBF in the right prefrontal cortex, a neocortical region implicated in regulating emotional responses. These results provide evidence for a network in which higher regions attenuate emotional responses at the most fundamental levels in the brain and suggest a neural basis for modulating emotional experience through interpretation and labeling.

Adult↗
PubMed1999

Cortical mechanisms of human imitation.

How does imitation occur? How can the motor plans necessary for imitating an action derive from the observation of that action? Imitation may be based on a mechanism directly matching the observed action onto an internal motor representation of that action ("direct matching hypothesis"). To test this hypothesis, normal human participants were asked to observe and imitate a finger movement and to perform the same movement after spatial or symbolic cues. Brain activity was measured with functional magnetic resonance imaging. If the direct matching hypothesis is correct, there should be areas that become active during finger movement, regardless of how it is evoked, and their activation should increase when the same movement is elicited by the observation of an identical movement made by another individual. Two areas with these properties were found in the left inferior frontal cortex (opercular region) and the rostral-most region of the right superior parietal lobule.

Adult↗
PubMed1999

Mapping biochemistry to metabolism: FDG-PET and amyloid burden in Alzheimer's disease.

We evaluated the relationship between amyloid-beta protein (A beta) concentration and the metabolic abnormality in an Alzheimer's disease (AD) patient as measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). Across most regions there were significant inverse correlations among FDG-PET intensity values and both insoluble. The temporal lobe samples showed no significant correlation between FDG-PET values and A beta deposition. Findings support A beta as contributing to the hypometabolism in regions of the AD brain that are still relatively viable metabolically; those regions with chronic pathologic damage, such as temporal cortex, may have other factors that contribute to metabolic deficits.

Aged↗
PubMed1999

Beneficial effect of siphoning in treatment of adult hydrocephalus.

OBJECTIVE: To increase awareness about the treatment of adult patients with shunt-nonresponsive hydrocephalus--a state characterized by marked ventriculomegaly, low intracranial pressure, and a patent cerebrospinal fluid diversionary shunt. DESIGN: Retrospective analysis of hospital and outpatient records. PATIENTS: Four patients with symptomatic ventriculomegaly and patent ventriculoperitoneal shunts treated with a protocol of progressive ventricular hypotension induced by external cerebrospinal fluid drainage. RESULTS: Severe clinical manifestations exhibited by the patients, including parkinsonian features, Parinaud syndrome, and extensor posturing, completely reversed once a normalization of ventricular size was achieved. External ventricular drainage pressures as low as -30 cm H2O were required to reduce ventricular size. All patients finally received a shunt incorporating a standard medium differential pressure valve with no antisiphon device. CONCLUSIONS: Shunt siphoning may be an essential mechanism by which cerebrospinal fluid shunting is effective in many patients with adult hydrocephalus. Cerebrospinal fluid shunts that contain an antisiphon device are ineffective in these patients, despite the attainment of "physiologic" intracranial pressures. Based on reported experimental and clinical evidence, it seems that the cause of this condition may be related to abnormally high intracranial compliance.

Adult↗
PubMed1999

Emission tomography contribution to clinical neurology.

The role of functional neuroimaging techniques in furthering the understanding of pathophysiological mechanisms of neurological diseases and in the assessment of neurological patients is increasingly important. Here, we review data mainly from emission tomography techniques, namely positron emission tomography (PET) and single photon emission computerized tomography (SPECT), that have helped elucidate the pathophysiology of a number of neurological diseases and have suggested strategies in the treatment of neurological patients. We also suggest possible future developments of functional neuroimaging applied to clinical populations and briefly touch on the emerging role of functional magnetic resonance imaging (fMRI) in clinical neurology and neurosurgery.

Brain↗
PubMed1999

Creation and use of a Talairach-compatible atlas for accurate, automated, nonlinear intersubject registration, and analysis of functional imaging data.

Spatial normalization in functional imaging can encompass various processes, including nonlinear warping to correct for intersubject differences, linear transformations to correct for identifiable head movements, and data detrending to remove residual motion correlated artifacts. We describe the use of AIR to create a custom, site-specific, normal averaged brain atlas that can be used to map T2 weighted echo-planar images and coplanar functional images directly into a Talairach-compatible space. We also discuss extraction of characteristic descriptors from sets of linear transformation matrices describing head movements in a functional imaging series. Scores for these descriptors, derived using principal components analysis with singular value decomposition, can be treated as confounds associated with each individual image in the series and systematically removed prior to voxel-by-voxel statistical analysis.

Anatomy, Artistic↗
PubMed1998

Bimodal (auditory and visual) left frontoparietal circuitry for sensorimotor integration and sensorimotor learning.

We used PET to test whether human premotor and posterior parietal areas can subserve basic sensorimotor integration and sensorimotor learning equivalently in response to auditory and visual stimuli, as has been shown in frontoparietal neurons in non-human primates. Normal subjects were studied while they performed a spatial compatibility task. They were instructed to respond to lateralized auditory and visual stimuli with the ipsilateral hand (compatible condition) or with the contralateral hand (incompatible condition). Reaction times were faster in the compatible than in the incompatible condition, for both auditory and visual stimuli. Left rostral dorsal premotor and posterior parietal blood-flow increases were observed in the incompatible condition, compared with the compatible condition, for both auditory and visual modalities. Blood-flow increases, which were correlated with the reaction-time learning curves, were observed in both auditory and visual modalities in the left caudal dorsal premotor cortex. These data suggest that, as in non-human primates, human frontoparietal areas can subserve basic sensorimotor transformations equivalently in the auditory and visual modality. Further, they reveal a functional rostrocaudal fractionation of human dorsal premotor cortex that resembles the rostrocaudal anatomical and physiological fractionation observed in non-human primates.

Acoustic Stimulation↗
PubMed1997

Oral 18F-fluoro-2-deoxyglucose for primate PET studies without behavioral restraint: demonstration of principle.

We describe a method of orally administering 18F-fluoro-2-deoxyglucose (FDG) for positron emission tomography (PET) scans to determine local cerebral metabolic rates for glucose (LCMRGlc), normalized to that of whole brain, in fully conscious, non-restrained primates. Oral FDG-PET studies were performed in both non-restrained and chaired monkeys, and in one human where results could be compared with traditional intravenous FDG administration. The oral route of FDG administration gave images and whole brain-normalized PET LCMRGlc results comparable to those obtained by the intravenous route. This oral FDG-PET method may provide a useful means by which to obtain measures of LCMRGlcs for brain structures, relative to each other, in non-restrained, non-drugged primates in field and laboratory studies. This method might also have clinical applications for PET studies of children.

Administration, Oral↗
PubMed1997

Positron-emission tomographic study of human amblyopia with use of defined visual stimuli.

PURPOSE: The purpose of this study was to use positron emission tomography (PET) to evaluate effects of amblyopia on cerebral blood flow and glucose metabolism in humans viewing defined visual stimuli and to correlate these effects with specific behavioral and electrophysiologic measures of visual function. METHODS: One subject with normal vision and five patients with amblyopia were prospectively studied. During monocular viewing of a checkerboard reversal stimulus by each subject, we performed PET imaging of relative cerebral glucose metabolism with use of [18F]fluorodeoxyglucose, PET imaging of relative cerebral blood flow with use of H2(15)O, and visual evoked potentials. Control studies were also performed with use of binocular occlusion and during presentation of stationary and horizontally drifting checkerboards. These data were correlated with letter acuities and contrast sensitivity functions for each eye. RESULTS: Although spatial resolution was superior for glucose metabolic imaging, PET readily demonstrated activation of calcarine cortex with use of both metabolic and blood flow tracers. Even in patients with mild amblyopia, functional activation of calcarine cortex was reduced in amblyopic eyes compared with sound eyes to a degree more closely correlated with visual acuity than were visual evoked potential amplitudes to the same stimulus. When responses to drifting versus stationary stimuli were compared, a putative motion processing center was identified in the right temporoparietal region. Activity in this motion center was relatively preserved during viewing of drifting stimuli by the affected eye of an anisometropic amblyopic subject, but was attenuated during viewing of the same stimulus by the affected eye of a strabismic amblyopic subject. CONCLUSIONS: PET imaging of blood flow and metabolism can quantitatively evaluate functional deficits resulting from amblyopia in striate as well as extrastriate visual areas. Calcarine cortical function correlates closely with severity of amblyopia, but function in a putative motion processing area may vary according to the type of amblyopia present.

Adult↗
PubMed1997

Merging of oculomotor and somatomotor space coding in the human right precentral gyrus.

Using PET and H215O, we investigated the cortical areas that merge two different ways of coding space in the cerebral cortex, those concerned with the oculomotor and the somatomotor space. Normal subjects performed a visuomotor task that required the spatial coding of visual stimuli in oculomotor space and of motor responses in somatomotor space. We manipulated the mapping of oculomotor and somatomotor space by instructing subjects to respond in half of the PET scans with uncrossed hands, i.e. each hand was in the homonymous hemispace (standard oculomotor-somatomotor mapping), and in the other half with crossed hands, i.e. with the left hand in the right hemispace and the right hand in the left hemispace (nonstandard oculomotor-somatomotor mapping). Reaction times were slower for crossed hands than uncrossed hands. Crossed hands produced increases in blood flow in the precentral and postcentral gyri of the right hemisphere. Increases in blood flow in the precentral gyrus were correlated with increases in reaction time comparing the crossed-hand task with the uncrossed one, whereas the increases in blood flow in the postcentral gyrus were not. These findings suggest that the right precentral gyrus merges oculomotor and somatomotor space coding in the human brain.

Adult↗
PubMed1996

Early detection of Alzheimer's disease by combining apolipoprotein E and neuroimaging.

New treatments for Alzheimer's disease (AD) are more likely to slow or halt disease progression rather than to reverse existing neuronal damage. Identifying persons with mild cognitive complaints who are at risk for AD will allow investigators to apply anti-dementia treatments before extensive brain damage develops. The discovery of the apolipoprotein E epsilon 4 allele (APOE epsilon 4) as a major risk factor for AD offers promise of assisting in early detection and prediction of Alzheimer's disease, particularly when genetic assessments are combined with other biomarkers such as neuroimaging. Studies of relatives at risk for familial AD using neuroimaging (positron emission tomography [PET]) and genetic assessments of APOE suggest that at-risk relatives with APOE epsilon 4 have lower parietal metabolism than those without APOE epsilon 4. Additional techniques that might increase sensitivity and specificity include longitudinal assessment of clinical and brain functional change, pharmacological challenges of short-acting anticholinergic agents, and memory activation paradigms during functional scanning. Such strategies should eventually assist in early detection of AD and in vivo therapeutic monitoring of brain function during experimental anti-dementia treatment trials.

Adult↗