The role of area 17 in visual imagery: convergent evidence from PET and rTMS.

Visual imagery is used in a wide range of mental activities, ranging from memory to reasoning, and also plays a role in perception proper. The contribution of early visual cortex, specifically Area 17, to visual mental imagery was examined by the use of two convergent techniques. In one, subjects closed their eyes during positron emission tomography (PET) while they visualized and compared properties (for example, relative length) of sets of stripes. The results showed that when people perform this task, Area 17 is activated. In the other, repetitive transcranial magnetic stimulation (rTMS) was applied to medial occipital cortex before presentation of the same task. Performance was impaired after rTMS compared with a sham control condition; similar results were obtained when the subjects performed the task by actually looking at the stimuli. In sum, the PET results showed that when patterns of stripes are visualized, Area 17 is activated, and the rTMS results showed that such activation underlies information processing.

Visual imagery and perception in posttraumatic stress disorder. A positron emission tomographic investigation.

BACKGROUND: Relative regional cerebral blood flow (rCBF) changes were measured in Vietnam combat veterans with and without posttraumatic stress disorder (PTSD) during exposure to combat-related stimuli. METHODS: Positron emission tomography was used to measure rCBF in 7 combat veterans with PTSD (PTSD group) and 7 healthy combat veterans (control group) who viewed and generated visual mental images of neutral, negative, and combat-related pictures. RESULTS: Unlike control subjects, subjects with PTSD had increased rCBF in ventral anterior cingulate gyrus and right amygdala when generating mental images of combat-related pictures; when viewing combat pictures, subjects with PTSD showed decreased rCBF in Broca's area. CONCLUSIONS: Results suggest that ventral anterior cingulate gyrus and right amygdala play a role in the response of combat veterans with PTSD to mental images of combat-related scenes. Reexperiencing phenomena of PTSD, which often involve emotional visual mental imagery, may be likewise associated with increased rCBF in these regions.

Management of alcohol withdrawal syndromes.

Withdrawal from alcohol (ethanol, ethyl alcohol) or other general sedatives leads to progressive hyperactivity that progresses from tremulousness, sleep disturbance, and hallucinosis, to the more serious rum fits and delirium tremens (DTs). Withdrawal can be prevented and, in most cases, arrested by prompt replacement of alcohol with paraldehyde, benzodiazepines or other general sedatives. Diazepam is appropriate replacement therapy for most patients. When delirium is manifest, the chance is greater than 15% that the patient will die, and this reaction cannot be aborted. The patient with DTs must be calmed with a general sedative that has a rapid onset of maximal effect to prevent overdosage. Diazepam, 5 mg intravenously every five minutes, permits evaluation of the maximal effect of each dose before the next dose is administered. Although some patients have advance sedative or alcohol withdrawal, great care must be taken to elicit the proper history of alcohol abuse so that sedative replacement therapy will prevent or abort early withdrawal, thus sparing the patient a mortality equivalent to that of acute myocardial infarction or Russian roulette.

Shock. Diagnosis and management.

Recent investigations have underscored the great diversity in both the causes and manifestations of clinical shock. The emphasis has shifted toward more specific therapy when that has been possible. Pure vasoconstrictors have assumed a secondary therapeutic role, as volume replacement or expansion has become the initial management of shock. Agents, such as naloxone hydrochloride, corticosteroids, fructose diphosphate, amrinone and milrinone , and nonsteroidal antiinflammatory agents, while still experimental, offer improved understanding and management of the shock syndrome.

A protein from polymorphonuclear leukocytes (LEM) which affects the rate of hepatic amino acid transport and synthesis of acute-phase globulins.

A proteinaceous secretion from phagocytizing polymorphonuclear leukocytes, termed "leukocytic endogenous mediator" (LEM), has been shown to have marked effects on hepatic amino acid transport and RNA and protein synthesis. A single injection of LEM results in a marked accumulation of labeled nonmetabolizable model amino acids in the liver of normal rats. The LEM-stimulated uptake of amino acids by liver was observed in adrenalectomized, hypophysectomized, thyroidectomized, or diabetic rats and could not be duplicated by pharmacological doses of a large variety of hormones. In addition, LEM stimulated an increased uptake of alpha-aminoisobutyric acid by isolated livers during their perfusion in vitro. LEM also stimulated an increased incorporation of orotic acid into hepatic RNA of intact rats, especially into the bound ribosomal fraction. This increased synthesis of RNA preceded an enhanced hepatic production of a number of the acute-phase plasma globulins. LEM did not stimulate the adenylate cyclase-cAMP system in liver and was not found to utilize this system as a second messenger. Thus, the effects of LEM in stimulating hepatic amino acid transport appear to be direct, without mediation by other hormones, and to be independent of cAMP. On the other hand, the ability of LEM to stimulate RNA and acute phase globulin synthesis in liver may require the presence of physiological quantities of hormones such as adrenal corticoids.

Vasodilator monotherapy in the treatment of hypertension: comparative efficacy and safety of pinacidil, a potassium channel opener, and prazosin.

We compared antihypertensive effects of monotherapy with pinacidil (N = 197) or prazosin (N = 204) in a randomized, parallel, double-blind dose-titration study in which hydrochlorothiazide or propranolol could be added for adverse events or lack of efficacy. Pinacidil (12.5 to 75 mg b.i.d.) was a more potent vasodilator, producing a mean decrease in supine diastolic blood pressure (baseline = 102 to 103 +/- 9 mm Hg) of 18.8 +/- 10.0 (SD) mm Hg compared with 15.5 +/- 9.2 mm Hg with prazosin (1 to 10 mg b.i.d.; p less than 0.001). Patients responding to each drug had similar average blood pressure levels during 12-hour monitoring (137/85 mm Hg). More patients taking pinacidil required hydrochlorothiazide for edema (p = 0.008) and more taking prazosin required hydrochlorothiazide and propranolol for lack of efficacy (p less than 0.001). Tachycardia (15% to 20%) and palpitation (13% to 15%) were frequent events with both drugs. Edema (38.2% vs 22.3%) was more frequent with pinacidil (p less than 0.001) and postural hypotension (4.7% vs 1.0%) and asthenia (20.2% vs 13.2%) were more frequent with prazosin (p = 0.025; 0.062). No significant laboratory toxicity was noted. In conclusion, both pinacidil and prazosin are effective as monotherapy for hypertension. Monotherapy with pinacidil is limited by adverse events related to vasodilatation and monotherapy with prazosin is limited by lack of efficacy.

Hypnotic visual illusion alters color processing in the brain.

OBJECTIVE: This study was designed to determine whether hypnosis can modulate color perception. Such evidence would provide insight into the nature of hypnosis and its underlying mechanisms. METHOD: Eight highly hypnotizable subjects were asked to see a color pattern in color, a similar gray-scale pattern in color, the color pattern as gray scale, and the gray-scale pattern as gray scale during positron emission tomography scanning by means of [(15)O]CO(2). The classic color area in the fusiform or lingual region of the brain was first identified by analyzing the results when subjects were asked to perceive color as color versus when they were asked to perceive gray scale as gray scale. RESULTS: When subjects were hypnotized, color areas of the left and right hemispheres were activated when they were asked to perceive color, whether they were actually shown the color or the gray-scale stimulus. These brain regions had decreased activation when subjects were told to see gray scale, whether they were actually shown the color or gray-scale stimuli. These results were obtained only during hypnosis in the left hemisphere, whereas blood flow changes reflected instructions to perceive color versus gray scale in the right hemisphere, whether or not subjects had been hypnotized. CONCLUSIONS: Among highly hypnotizable subjects, observed changes in subjective experience achieved during hypnosis were reflected by changes in brain function similar to those that occur in perception. These findings support the claim that hypnosis is a psychological state with distinct neural correlates and is not just the result of adopting a role.

Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: A PET investigation.

OBJECTIVE: The purpose of this study was to determine whether anterior limbic and paralimbic regions of the brain are differentially activated during the recollection and imagery of traumatic events in trauma-exposed individuals with and without posttraumatic stress disorder (PTSD). METHOD: Positron emission tomography (PET) was used to measure normalized regional cerebral blood flow (CBF) in 16 women with histories of childhood sexual abuse: eight with current PTSD and eight without current PTSD. In separate script-driven imagery conditions, participants recalled and imagined traumatic and neutral autobiographical events. Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. RESULTS: In the traumatic condition versus the neutral control conditions, both groups exhibited regional CBF increases in orbitofrontal cortex and anterior temporal poles; however, these increases were greater in the PTSD group than in the comparison group. The comparison group exhibited regional CBF increases in insular cortex and anterior cingulate gyrus; increases in anterior cingulate gyrus were greater in the comparison group than in the PTSD group. Regional CBF decreases in bilateral anterior frontal regions were greater in the PTSD group than in the comparison group, and only the PTSD group exhibited regional CBF decreases in left inferior frontal gyrus. CONCLUSIONS: The recollection and imagery of traumatic events versus neutral events was accompanied by regional CBF increases in anterior paralimbic regions of the brain in trauma-exposed individuals with and without PTSD. However, the PTSD group had greater increases in orbitofrontal cortex and anterior temporal pole, whereas the comparison group had greater increases in anterior cingulate gyrus.

Encoding words and pictures: a positron emission tomography study.

Subjects viewed words, pictures, crosshairs, or a large X flanked by two smaller xs on either side while their brain activity was monitored using positron emission tomography (PET). When activation from the pictures, crosshairs, or Xs condition was subtracted from activation in the words condition, the left angular gyrus and Broca's area were found to be activated. In the comparison of words and pictures, additional language areas were activated. These results provide support for the classical neurological model of reading. The results also suggest that a "word form area" is near the margin of the left angular gyrus.

Two types of image generation: evidence for left and right hemisphere processes.

The results from seven experiments provide evidence that visual mental images can be generated by either the left or right cerebral hemisphere, but in different ways. Subjects were cued to form images within a grid or within a set of four corner brackets; a single X mark was enclosed within each stimulus, and the subjects were to determine whether the X mark was enclosed within each stimulus, and the subjects were to determine whether the X mark would have fallen on an imaged pattern. When subjects memorized descriptions of how parts were arranged, they could later form images of the composite pattern when cued in the right visual field (left hemisphere) more accurately than when they were cued in the left visual field (right hemisphere). In contrast, when subjects memorized individual segments on a screen, and 'mentally glued' them into a single pattern, they later could form images more accurately, at least in some circumstances, when cued in the left visual field. These results were predicted by the theory that images are built up by arranging parts, and that two different processes can be used to arrange them. One process uses stored descriptions to arrange parts, and is more effective in the left cerebral hemisphere; the other process uses stored memories of metric positions to arrange parts, and is more effective in the right cerebral hemisphere. Convergent evidence was obtained by having subjects memorize letters in grids (which are easily encoded using descriptions of the positions of segments) or within a space delineated by four brackets (which require memorizing the precise positions of the segments). Subjects were relatively more accurate when cued in the left visual field with bracket stimuli, but tended to be relatively more accurate when cued in the right visual field with grids stimuli. Control experiments showed that this finding was not due to hemispheric differences in the ease of forming images at different sizes or differences in the ease of perceptually encoding the probes.

Bone mineral content determined by functional imaging.

Quantitation of bone mineral by photon absorptiometry is a simple and accurate method for determining changes in bone volume and mineral content in serial studies. An extension of the scintillation camera method for studying such changes in the calcaneous is described. This technique is applicable to large areas of bone, thereby minimizing the effect of repositioning errors. Using a 40-mCi 241Am sheet source, a 2.1% reproducibility in bone phantoms and a 2.4% reproducibility in normal patients was achieved. Several case studies are presented to illustrate sensitivity and clinical application of the method. Although bone mineral determinations are now performed in a limited number of health care facilities, the scintillation camera method described in this report could increase the availability of these determinations significantly.

Radionuclide computed tomography of the body using routine radiopharmaceuticals. I. System characterization.

A whole-body computed tomography system for single-photon emitters was evaluated from the standpoint of spatial resolution, sensitivity, and thresholds for count densities with reference to standard doses of currently used radiopharmaceuticals in patients. In air and tissue equivalents, spatial resolution was relatively constant throughout the field of view and attentuation correction algorithms returned uniformity of response to within 10%. In a phantom of the human abdomen 1.5-cm spherical "cold" lesions and 1-cm "hot" lesions could be resolved. Aspects of the partial-volume effect were observed and investigated. To detect 1.5 cm-cold lesions in an abdominal phantom, five million events were required.

Automated patient report-generation in nuclear medicine.

The proliferation of computer-based office-management systems in the past few years has involved the private physician's office as well as the hospital laboratory. Many radiology departments have already adopted this approach for patient report generation and data storage. Due to the absence of commercially available software, some nuclear medicine departments will be interested in writing their own, but may not have enough experience in nonimaging computer applications to determine the performance needed for a practical system. A report-generation system for scintigraphic studies has been developed in our department over the past 2 yr. During this time an essential hardware/software performance level was established. Ideas for design of program flow that enhance staff acceptance of this concept are presented. Significant reduction of errors in report transcription and billing, together with reduced requirements for secretarial and clerical staff, make a general system like this cost effective.

Integration of database capabilities into a patient reporting system.

A database design is described which automatically archives computer-generated patient imaging and radioassay reports. Selected phrases are condensed so that data storage will be efficient without sacrificing a prose style of report. An indexed file structure has been used to facilitate rapid record retrieval even when several hundred thousand records are stored. Personnel time is considerably reduced for recalling patient records, preparing periodic summaries of studies completed, and performing administrative functions such as billing and keeping track of checked out images. Complex queries, such as "list all the patients between the ages of 50 and 60 on digitalis referred for a stress cardiac study, with left ventricular ejection fraction less than 40% and apical dyskinesis," become feasible. A system for data backup is described to protect against catastrophic data loss.

Clinical utility of a two-site immunoradiometric assay for creatine kinase-MB in the detection of perioperative myocardial infarction.

In 144 patients, creatine kinase MB was measured serially at 0, 8, 16, 24, 48, and 72 hr using a two-site immunoradiometric assay (IRMA). Cardiac enzymes were also measured, including SGOT, LDH, total CPK, and CK-MB by electrophoresis. The presence of perioperative myocardial infarction (poMI) was established in 24 patients by the appearance of new electrocardiographic Q waves and/or new wall motion abnormalities detected by radionuclide ventriculography. In patients without poMI, CK-MB (IRMA) was elevated (6.4 +/- 4.9 equivalent units per liter) at 0-8 hr but decreased to 3.4 +/- 1.3 EU/l by 16 hr. In patients with poMI, peak values occurred at 16-24 hr (21.0 +/- 19.8 EU/l). Using a threshold value of 8.5 EU/l, patients with poMI could be distinguished from those without with 97% accuracy (sensitivity = 88%, specificity = 99%). The CK-MB (IRMA) was more reliable than the other enzyme assays, for which we used both empirically elevated threshold values based upon previous experience, and also threshold values retrospectively optimized for the study population. We conclude that the CK-MB (IRMA) can serve as a valuable postoperative screening test for poMI.

Drug-induced electrolyte abnormalities.

Drugs can interfere with the normal intake, elimination, regulation and total body distribution of electrolytes. These drug-induced abnormalities may be dramatic and life threatening, posing diagnostic and management problems to the physician who is not familiar with them. Serum potassium concentrations can be altered as potassium shifts between the tissue and plasma compartments secondary to drug actions. In addition, drugs have been shown to interfere with the normal physiological functioning of the kidney with respect to potassium homeostasis, as well as the renin-aldosterone axis. The regulation of serum sodium levels is integrally related to the regulation of total body water. Thus, drugs that alter the regulation of antidiuretic hormone secretion and its action on the kidney can result in large changes in serum sodium concentrations. Abnormal losses or intake of sodium related to drug use can also have profound effects in the plasma compartment. The normally fine regulation of serum calcium concentrations can be easily upset by pharmacological therapy at the level of parathyroid hormone secretion and action, bone metabolism or renal calcium excretion. Through awareness of these drug-induced changes in electrolytes and the mechanisms involved, subtle and often dangerous problems in clinical management can be handled rationally.

Imagining rotation by endogenous versus exogenous forces: distinct neural mechanisms.

Previous neuroimaging studies of mental image transformations have sometimes implicated motor processes and sometimes not. In this study, prior to neuroimaging the subjects either viewed an electric motor rotating an angular object, or they rotated the object manually. Following this, they performed the identical mental rotation task in which they compared members of pairs of such figures, but were asked to imagine the figures rotating as they had just seen the model rotate. When results from the two rotation conditions were directly compared, motor cortex (including area M1) was found to be activated only when subjects imagined the rotations as a consequence of manual activity. Thus, there are at least two, qualitatively distinct, ways to imagine objects rotating in images, and these different strategies can be adopted voluntarily.

Neural effects of visualizing and perceiving aversive stimuli: a PET investigation.

Cerebral blood flow was recorded (using positron emission tomography) while middle-aged subjects viewed or visualized pictures of neutral or aversive stimuli, and then determined whether auditorily presented statements correctly described the stimuli. Visualizing aversive stimuli enhanced cerebral blood flow, relative to visualizing neutral stimuli, in areas 17 (right) and 18 (bilateral), as well as the anterior insula (bilateral) and middle frontal cortex (left). Areas 17 and 18 have been identified as supporting the representations that underlie the experience of imagery, and the anterior insula is a major cortical recipient of input from the autonomic nervous system. Perceiving aversive stimuli enhanced cerebral blood flow, relative to neutral stimuli, in area 46, the angular gyrus and area 19, area 47, and the middle temporal gyrus (all in the left hemisphere). All of these areas have previously been implicated in visual object identification. It is striking that negative emotion did not modulate activation in any areas in the same way during imagery and perception.

Brain mechanisms in human classical conditioning: a PET blood flow study.

Five healthy male subjects participated in a classical conditioning experiment, and positron emission tomography (PET) was used to compare regional cerebral blood flow before and after conditioning. The subjects participated in three different experimental phases. In the first (habituation) phase they listened to 24 repetitions of a tone with random intervals. In the second (acquisition) phase, the tone was paired with a brief shock to the wrist. In the third (extinction) phase, the tone was presented alone again. 15OPET scans were taken during the habituation and extinction phases. Because the habituation and extinction phases were similar, any difference in blood flow to the tones presented during extinction probably reflected conditioning that occurred during the acquisition phase. Statistical parametric mapping (SPM) analysis of the PET data showed significantly increased activation in the right hemisphere in the orbito-frontal cortex, dorsolateral prefrontal cortex, inferior and superior frontal cortices, and inferior and middle temporal corticies. The only activated areas in the left hemisphere were area 19 and the superior frontal cortex. The results are interpreted as evidence for the involvement of cortical areas in human classical conditioning.

Clinical pharmacokinetics of pinacidil, a potassium channel opener, in hypertension.

Pinacidil is a potassium channel opener that decreases blood pressure by reducing peripheral arterial resistance. In two multicenter trials, we studied the concentrations and apparent clearance of pinacidil (406 patients) and concentrations of its pyridyl-N-oxide metabolite (147 patients). Responding patients had plasma samples collected hourly for 12 hours on 2 occasions after weeks to months of treatment. Pinacidil dose was titrated from 12.5 to 75 mg b.i.d. The peak concentration of pinacidil and N-oxide and the area under the concentration-time curve (AUC) were proportional to the dose of pinacidil, with an average pinacidil concentration of 268 micrograms/L (1.02 microM) and N-oxide concentration of 172 micrograms/L (0.65 microM) for every 1 mg/kg pinacidil administered. Clearance of pinacidil (Clp = Dose/AUC) was 31 L/hr in patients younger than 45 years and 27 L/hr in those older than 60. Clp was significantly smaller in white patients compared with other races (Clp = 28 vs. 34 L/hr). Clp was significantly less in patients taking hydrochlorothiazide (27 vs. 31 L/hr) and greater in smokers (33 vs. 29 L/hr). Concomitant propranolol use did not influence Clp.