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Biomedical subjects

J M Hoffman

Publications and source records attributed to J M Hoffman.

At least 19 recordsLinked to original sources
PubMed1999

Acute blood flow changes and efficacy of vagus nerve stimulation in partial epilepsy.

OBJECTIVE: To determine possible sites of therapeutic action of vagus nerve stimulation (VNS), by correlating acute VNS-induced regional cerebral blood flow (rCBF) alterations and chronic therapeutic responses. BACKGROUND: We previously found that VNS acutely induces rCBF alterations at sites that receive vagal afferents and higher-order projections, including dorsal medulla, somatosensory cortex (contralateral to stimulation), thalamus and cerebellum bilaterally, and several limbic structures (including hippocampus and amygdala bilaterally). METHODS: VNS-induced rCBF changes were measured by subtracting resting rCBF from rCBF during VNS, using [O-15]water and PET, immediately before ongoing VNS began, in 11 partial epilepsy patients. T-statistical mapping established relative rCBF increases and decreases for each patient. Percent changes in frequency of complex partial seizures (with or without secondary generalization) during three months of VNS compared with pre-VNS baseline, and T-thresholded rCBF changes (for each of the 25 regions of previously observed significant CBF change), were rank ordered across patients. Spearman rank correlation coefficients assessed associations of seizure-frequency change and t-thresholded rCBF change. RESULTS: Seizure-frequency changes ranged from 71% decrease to 12% increase during VNS. Only the right and left thalami showed significant associations of rCBF change with seizure-frequency change. Increased right and left thalamic CBF correlated with decreased seizures (p < 0.001). CONCLUSIONS: Increased thalamic synaptic activities probably mediate some antiseizure effects of VNS. Future studies should examine neurotransmitter-receptor alterations in reticular and specific thalamic nuclei during VNS.

Adult↗
PubMed1999

Neural evidence linking visual object enumeration and attention.

Visual object enumeration is rapid and accurate for four or fewer items but slow and error-prone for over four items. This dichotomy has recently been linked to visual attentional phenomena by findings suggesting that 'subitizing' of small sets of objects is preattentive whereas 'counting' of over four items demands spatial shifts of attention. We evaluated this link at a neural level, using H2 15-O positron emission tomography to measure changes in regional cerebral blood flow while subjects enumerated the number of target vertical bars that 'popped out' of a 16-bar visual display consisting of both horizontal and vertical bars. Relative to a condition with a single target, subitizing (one to four targets) activated foci in the occipital extrastriate cortex, consistent with involvement of early, preattentive visual processes. Relative to subitizing, counting (five to eight targets) activated a widespread network of brain regions, including multiple foci implicated in shifting visual attention-large regions of the superior parietal cortex bilaterally and a focus in the right inferior frontal cortex. These results offer the first direct neural support for mapping the subitizing-counting dichotomy onto separable processes mediating preattentive vision and shifts of visual attention.

Adolescent↗
PubMed1999

Synthesis and evaluation of [18F]1-amino-3-fluorocyclobutane-1-carboxylic acid to image brain tumors.

UNLABELLED: We have developed a new tumor-avid amino acid, 1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC), labeled with 18F for nuclear medicine imaging. METHODS: [18F]FACBC was prepared with high specific activity (no carrier added [NCA]) and was evaluated for its potential in tumor localization. A comparative study was performed for [18F]FACBC and [18F]2-fluorodeoxyglucose (FDG) in which the uptake of each agent in 9L gliosarcoma (implanted intracerebrally in Fisher 344 rats) was measured. In addition, the first human PET study of [18F]FACBC was performed on a patient with residual glioblastoma multiforme. Quantitative brain images of the patient were obtained by using a Siemens 921 47-slice PET imaging system. RESULTS: In the rat brain, the initial level of radioactivity accumulation after injection of [18F]FACBC was low (0.11 percentage injected dose per gram [%ID/g]) at 5 min and increased slightly to 0.26 %ID/g at 60 min. The tumor uptake exhibited a maximum at 60 min (1.72 %ID/g), resulting in a tumor-to-brain ratio increase of 5.58 at 5 min to 6.61 at 60 min. In the patient, the uptake of [18F]FACBC in the tumor exhibited a maximum concentration of 146 nCi/mL at 35 min after injection. The uptake of radioactivity in the normal brain tissue was low, 21 nCi/mL at 15 min after injection, and gradually increased to 29 nCi/mL at 60 min after injection. The ratio of tumor to normal tissue was 6 at 20 min after injection. The [18F]FACBC PET scan showed intense uptake in the left frontal region of the brain. CONCLUSION: The amino acid FACBC can be radiofluorinated for clinical use. [18F]FACBC is a potential PET tracer for tumor imaging.

Animals↗
PubMed1998

An examination of individual differences in the relationship between interpersonal stress and disease activity among women with rheumatoid arthritis.

OBJECTIVE: The effects of interpersonal stress on disease activity were examined for married women with rheumatoid arthritis (RA) who differ in the quality of their relationships with their spouses. METHODS: Measures of interpersonal events were collected weekly for 12 weeks and related to disease activity through a comparison of clinician ratings and immune markers taken at baseline and during a highly stressful week for 20 RA patients. Individual differences in marital relationship variables and illness characteristics were used to predict group differences in how stress affected disease activity. RESULTS: Significant elevations in total T cell activation (DR + CD3 cells), soluble interleukin-2 receptor (sIL-2R), and clinician's global ratings of disease activity were found during a week of significant interpersonal stress. However, women with better spousal relationships did not show increases in disease activity following an episode of interpersonal stress. In addition, patients taking low-dose prednisone showed greater reactivity to stress than patients not currently using glucocorticoid treatment. CONCLUSION: The results are consistent with the hypothesis that disease activity in RA increases following increases in interpersonal stress and that women with stronger marital relationships were less vulnerable to those stressors.

Adult↗
PubMed1998

Compensatory recruitment of neural resources during overt rehearsal of word lists in Alzheimer's disease.

Functional neuroanatomical correlates subserving maintenance rehearsal relative to a reading control task were investigated with positron emission tomography imaging of cerebral blood flow in 6 healthy older participants and 6 patients with mild Alzheimer's disease (AD). Rehearsal and reading rates and number of unique words rehearsed did not differ significantly for the 2 groups. The right dorsolateral prefrontal cortex was activated in both groups during rehearsal, highlighting this region's role in short-term maintenance of verbal information. A shift in cortical processing resources to more anterior brain regions with increased rehearsal list length was seen, likely reflecting greater demands on frontal cortex as cognitive load grows. Whereas controls showed unilateral right frontal activation during rehearsal, AD patients demonstrated bilateral frontal activation, possibly reflecting compensatory recruitment of neural resources.

Adaptation, Physiological↗
PubMed1998

Brain blood flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: I. Acute effects at high and low levels of stimulation.

PURPOSE: Left cervical vagus nerve stimulation (VNS) decreases complex partial seizures (CPS) by unknown mechanisms of action. We hypothesized that therapeutic VNS alters synaptic activities at vagal afferent terminations and in sites that receive polysynaptic projections from these medullary nuclei. METHODS: Ten patients with partial epilepsy underwent positron emission tomographic (PET) measurements of cerebral blood flow (BF) three times before and three times during VNS. Parameters for VNS were at high levels for 5 patients and at low levels for 5. Resting BF measurements were subtracted from measurements during VNS in each subject. Subtraction data were averaged in each of 2 groups of 5 patients. t Tests were applied to BF changes in brain regions that receive vagal afferents and projections (significant at p < 0.05, corrected for repeated measures). RESULTS: In both the low- and high-stimulation groups during VNS, brain BF was (a) increased in the rostral, dorsal-central medulla; (b) increased in the right postcentral gyrus, (c) increased bilaterally in the hypothalami, thalami, and insular cortices, and in cerebellar hemispheres inferiorly; and (d) decreased bilaterally in hippocampus, amygdala, and posterior cingulate gyri. The high-stimulation group had greater volumes of activation and deactivation sites. CONCLUSIONS: Our findings suggest that left cervical VNS acutely increases synaptic activity in structures directly innervated by central vagal structures and areas that process left-sided somatosensory information, but VNS also acutely alters synaptic activity in multiple limbic system structures bilaterally. These findings may reflect sites of therapeutic actions of VNS.

Adult↗
PubMed1998

Motor subcircuits mediating the control of movement velocity: a PET study.

The influence of changes in the mean velocity of movement on regional cerebral blood flow (rCBF) was studied using positron emission tomography (PET) in nine healthy right-handed adults while they performed a smooth pursuit visuomanual tracking task. Images of relative rCBF were obtained while subjects moved a hand-held joystick to track the movement of a target at three different rates of a sinusoidal displacement (0.1, 0.4, and 0.7 Hz). Significant changes in rCBF between task conditions were detected using analysis of variance and weighted linear contrasts. The kinematics of arm and eye movements indicated that subjects performed tasks in a similar manner, particularly during the faster two tracking conditions. Significant increases in rCBF during arm movement (relative to an eye tracking only control condition) were detected in a widespread network of areas known for their involvement in motor control. The activated areas included primary sensorimotor (M1S1), dorsal and mesial premotor, and dorsal parietal cortices in the left hemisphere and to a lesser extent the sensorimotor and superior parietal cortices in the right hemisphere. Subcortically, activations were found in the left putamen, globus pallidus (GP), and thalamus, in the right basal ganglia, and in the right anterior cerebellum. Within the cerebral volume activated with movement, three areas had changes in rCBF that correlated positively with the rate of movement: left M1S1, left GP, and right anterior cerebellum. No movement-related sites had rCBF that correlated negatively with the rate of movement. Regressions of mean percent change (MPC) in rCBF onto mean hand velocity yielded two nonoverlapping subpopulations of movement-related loci, the three sites with significant rate effects and regression slopes steeper than 0.17 MPC.cm-1.s-1 and all other sites with nonsignificant rate effects and regression slopes below 0.1 MPC.cm-1. s-1. Moreover, the effects of movement per se and of movement velocity varied in magnitude independently. These results confirm previous reports that movement-related activations of M1S1 and cerebellum are sensitive to movement frequency or some covarying parameter of movement. The activation of GP with increasing movement velocity, not described in previous functional-imaging studies, supports the hypothesis that the basal ganglia motor circuit may be involved preferentially in controlling or monitoring the scale and/or dynamics of arm movements. The remaining areas that were activated equally for all movement rates may be involved in controlling higher level aspects of motor control that are independent of movement dynamics.

Aged↗
PubMed1997

Feeling with the mind's eye.

Mental imagery is thought to play a key role in certain aspects of visual perception and to depend on neural activity in visual cortex. We asked whether tactile discrimination of grating orientation, which appears to involve visual mental imagery, recruits visual cortical areas. H215O positron emission tomography was performed in humans during presentation of gratings to the right index fingerpad. Selective attention to grating orientation significantly increased regional cerebral blood flow, relative to a control task involving selective attention to grating dimensions, in a region located in left parieto-occipital cortex. We propose that this activation reflects the use of imagery-related visuo-spatial processes to enable the tactile discrimination of orientation.

Adult↗
PubMed1997

Sex differences in the relationship of body fat distribution with psychosocial variables.

OBJECTIVE: This study tested the hypothesis that the relationship of psychosocial variables to body fat distribution would differ in men and women and would vary according to gender differences in natural patterns of fat distribution. METHOD: Body fat distribution and psychological functioning were examined in 5,930 male and 7,598 female dieters. RESULTS: Upper body size and shape were more strongly related to psychological functioning in men and lower body size and shape were more important in women. DISCUSSION: To better understand the association of weight with psychosocial status, patterns of body fat distribution should be considered.

Adipose Tissue↗
PubMed1997

Pulmonary abnormalities and PET data analysis: a retrospective study.

PURPOSE: To assess methods of standard uptake ratio (SUR) calculation with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) positron emission tomography (PET) in indeterminate focal pulmonary abnormalities. MATERIALS AND METHODS: One hundred ninety-seven adult patients with indeterminate pulmonary abnormalities had complete FDG PET data, consistent methods of data acquisition, and definitive diagnosis with tissue biopsy or negative 2-year follow-up findings. PET studies were evaluated by using SURs calculated with the average or maximum region-of-interest pixel value in the numerator and with weight, lean body mass, or body surface area in the denominator. RESULTS: One hundred twenty malignant lesions and 77 benign processes were identified. Receiver operating characteristic (ROC) curve areas were statistically significantly larger with the average rather than the maximum pixel value in the calculation of the SUR for any of the three denominators (P < or = .05). SURs calculated with weight versus lean body mass versus body surface area in the denominator showed no statistically significant difference in ROC curve areas. CONCLUSION: SURs determined by using average pixel values provide statistically significant improvement in ROC curve areas over those determined by using maximum pixel values. Weight, lean body mass, and body surface area in the denominator of the SUR calculation provide equivalent ROC curve areas and are therefore equivalent in accuracy in this population.

Adult↗
PubMed1997

Fluorine-18-FPCT: a PET radiotracer for imaging dopamine transporters.

UNLABELLED: Fluorine-18-labeled 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3-fluoropropyl) nortropane (FPCT) has been synthesized as a new dopamine transporter imaging agent. METHODS: Fluorine-18 was introduced into 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3-fluoropropyl) nortropane by preparation of 1-[18F]fluoro-3-iodopropane followed by alkylation of 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)nortropane. RESULTS: Tissue distribution studies in rats with [18F]FPCT showed high striatal uptake (0.70% dose/g at 60 min; 0.38% dose/g at 120 min) and good striatal-to-cerebellum ratios (5.5 at 60 min; 6.2 at 120 min). Imaging studies in rhesus monkeys (n = 2) with [18F]FPCT showed high uptake and retention in the putamen (P) (P = 0.03%-0.12% dose/g; at 115 min) and good putamen-to-cerebellum ratios of 3.40-3.43 at 115 min. Plasma metabolites were analyzed in rhesus monkeys (n = 2) by ether extraction and HPLC. The radioactivity in the ether-extractable fraction displayed a single peak that corresponded on HPLC to unmetabolized authentic FPCT. CONCLUSION: These results suggest that [18F]FPCT is an excellent candidate for PET imaging of dopamine transporters.

Animals↗
PubMed1996

Role of posterior parietal cortex in the recalibration of visually guided reaching.

Visually guided reaching requires complex neural transformations to link visual and proprioceptive inputs with appropriate motor outputs. Despite the complexity of these transformations, hand-eye coordination in humans is remarkably flexible, as demonstrated by the ease with which reaching can be adapted to distortions in visual feedback. If subjects attempt to reach to visual targets while wearing displacing prisms, they initially misreach in the direction of visual displacement. Given feedback about their reaching errors, however, they quickly adapt to the visual distortion. This is shown by the gradual resumption of accurate reaching while the prisms remain in place, and by the immediate onset of reaching errors in the opposite direction after the prisms have been removed. Despite an abundance of psychophysical data on adaptation to prisms, the functional localization of this form of sensorimotor adaptation is uncertain. Here we use positron emission tomography (PET) to localize changes in regional cerebral blood flow (rCBF) in subjects who performed a prism-adaptation task as well as a task that controlled for the sensory, motor and cognitive conditions of the adaptation experiment. Difference images that reflected the net effects of the adaptation process showed selective activation of posterior parietal cortex contralateral to the reaching limb.

Adaptation, Physiological↗
PubMed1996

Adult age differences in regional cerebral blood flow during visual world identification: evidence from H215O PET.

We used H215O PET to investigate adult age differences in regional cerebral blood flow (rCBF) during the performance of a visual word identification task. The study participants were 20 healthy, right-handed men: 10 young adults between 18 and 27 years of age, and 10 older adults between 63 and 75 years of age. The word identification task comprised six blocks of test trials representing four task conditions; subjects responded manually. The task conditions varied with regard to whether semantic retrieval was required (e.g., word/nonword discrimination vs simple response to each stimulus) and with regard to the difficulty of visual encoding (e.g., words presented normally vs words with asterisks inserted between adjacent letters). Each subject performed all six trial blocks, concurrently with each of six H215O PET scans. Analyses of quantitative CBF data obtained from the arterial time-activity curve demonstrated a significant age-related decline in global CBF rate. Analyses of the changes in rCBF between task conditions indicated that retrieval of semantic information sufficient to distinguish words from nonwords is mediated by a ventral occipitotemporal cortical pathway. Specific areas within this pathway were also associated with visual encoding processes. Several rCBF activations were significantly greater for young adults than for older adults, indicating an age-related decline in processing efficiency within this ventral occipitotemporal pathway. Although the performance data demonstrated a greater age-related slowing for visual encoding than for semantic retrieval, these age-related performance changes were not associated with corresponding changes in rCBF activation.

Adolescent↗
PubMed1996

Positron emission tomography in the pretreatment evaluation and follow-up of non-small cell lung cancer patients treated with radiotherapy: preliminary findings.

The purpose of this study was to prospectively evaluate positron emission tomography (PET) for delineating lung cancers preradiotherapy and to assess PET's ability to distinguish residual tumor from scarring following radiotherapy. Between April 1991 and October 1992, 20 patients underwent 18fluoro-2-deoxyglucose (18FDG) PET scanning of the chest prior to radiotherapy for lung cancer. Tumor volumes on chest x-ray (CXR) and computerized tomography (CT) scan were correlated with abnormalities on PET scans. Follow-up PET studies were compared to postradiotherapy chest x-ray and/or CT scans, and correlated with clinical outcome. Six of seven well-demarcated tumors showed increased uptake of 18FDG correlating with the CT/CXR tumor volume. Twelve poorly demarcated tumors demonstrated increased 18FDG uptake. In seven of 12, the CT/CXR abnormality correlated with changes on PET scan. In three of 12, CT/CXR abnormalities were larger than on PET, whereas in two of 12, abnormalities on PET extended outside the region of CT/CXR changes. The 13th patient in the poorly demarcated category had diffuse carcinoma in situ at the surgical margin that demonstrates increased 18FDG uptake, but was not visible by CT/CXR. Of 12 patients with follow-up studies, all had changes on CXR and/or CT that made it difficult to assess response. Four of 12 had a complete response by PET; all remain locally controlled. The remaining eight patients had either a partial response (n = 6) or no response (n = 2) by PET. Four of these eight patients remain alive and well 11-24 months after therapy. 18FDG PET may be useful for delineation of lung cancer volumes that are poorly defined by CXR and/or CT scan. The value of PET in differentiating tumor from fibrosis after radiotherapy for lung cancer remains to be established.

Carcinoma in Situ↗
PubMed1996

Interpretation variability of 18FDG-positron emission tomography studies in dementia.

RATIONALE AND OBJECTIVES: Functional imaging studies such as 18F-fluoro-18-labeled-deoxyglucose-positron emission tomography (18FDG-PET) are being used increasingly in the evaluation of patients with dementia. The authors evaluate inter- and intraobserver interpretation agreement in a diverse group of patients with clinically diagnosed dementia and subjective memory complaints, as well as two healthy control subjects. METHODS: Ninety-six patients with clinical diagnoses of probable Alzheimer's disease (n = 18), possible Alzheimer's disease (n = 33), dementia (n = 26), and mild memory impairment (n = 17), as well as two healthy control subjects were studied using 18FDG-PET. Three observers graded all studies for regional 18FDG uptake in the temporal, parietal, and frontal regions bilaterally. The studies also were interpreted for the presence of bilateral temporoparietal hypometabolism, which typically is present in Alzheimer's disease. The kappa statistic was used to determine intra- and interobserver agreement for regional 18FDG uptake and bilateral temporoparietal hypometabolism. RESULTS: There was excellent intraobserver (kappa = .56, P < 0.0005) and interobserver (kappa = .51, P < 0.0005) interpretation agreement for bilateral temporoparietal hypometabolism. There also was excellent intraobserver (kappa = .61, P < 0.000) and interobserver (kappa = .55, P < 0.000) interpretation agreement of regional 18FDG uptake. Interobserver agreement was extremely high in those patients who were considered clinically to have possible (kappa = .42, P < 0.001) or probable (kappa = .42, P < 0.01) Alzheimer's disease. CONCLUSIONS: Results confirm that bilateral temporoparietal hypometabolism is the metabolic abnormality associated with the diagnosis of probable Alzheimer's disease. Furthermore, intra- and interobserver agreement of visual interpretation of 18FDG-PET images indicates that 18FDG-PET is acceptable as an imaging technique in the clinical evaluation of the dementia patient.

Adult↗
PubMed1996

PGY1.

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Curriculum↗
PubMed1995

Differential recovery of volitional motor function, lateralized cognitive function, dopamine agonist-induced rotation and dopaminergic parameters in monkeys made hemi-parkinsonian by intracarotid MPTP infusion.

There is still controversy regarding the frequency and extent of spontaneous functional recovery in primate models of parkinsonism, perhaps in part stemming from the variety of ways in which recovery has been assessed. The present study examined functional recovery in monkeys made unilaterally parkinsonian by intracarotid infusion of MPTP. Monkeys were evaluated prior to lesioning and for at least 1 year after lesioning on a battery of tests including a rating of spontaneous behaviors, a learned reaction time/movement time task, tests of lateralized neglect or inattention (i.e. lateralized reward retrieval task, extinction with double simultaneous stimulation, and response to a target moving from one hemispace to the other), and rotational asymmetry in response to a dopamine agonist. Some animals also received 6-[18F]Fluoro-L-Dopa (F-DOPA) position emission tomography (PET) scans before MPTP, when symptomatic, and when showing signs of functional recovery. These animals were sacrificed for post mortem neurochemical assessment following the last PET scan. Results showed that estimates of functional recovery in hemi-parkinsonian monkeys may depend upon the behavioral assay used. Even in behavioral tasks that were sensitive to recovery effects, the degree of functional recovery shown by an animal on one such task did not predict recovery on another. This may in part be due to the inherent difficulty in designing behavioral tests to assess basal ganglia functioning, when there is no consensus concerning which aspects of behavior the normal basal ganglia actually control.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗