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Biomedical subjects

G L Watkins

Publications and source records attributed to G L Watkins.

At least 37 records · Page 2Linked to original sources
PubMed1996

Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry.

Patients suffering from schizophrenia display subtle cognitive abnormalities that may reflect a difficulty in rapidly coordinating the steps that occur in a variety of mental activities. Working interactively with the prefrontal cortex, the cerebellum may play a role in coordinating both motor and cognitive performance. This positron-emission tomography study suggests the presence of a prefrontal-thalamic-cerebellar network that is activated when normal subjects recall complex narrative material, but is dysfunctional in schizophrenic patients when they perform the same task. These results support a role for the cerebellum in cognitive functions and suggest that patients with schizophrenia may suffer from a "cognitive dysmetria" due to dysfunctional prefrontal-thalamic-cerebellar circuitry.

Adult↗
PubMed1996

Auditory attentional deficits in patients with schizophrenia. A positron emission tomography study.

BACKGROUND: Patients with schizophrenia have frequently been found to perform poorly on tasks requiring selective attention, defined as the ability to focus attention on relevant information while simultaneously ignoring irrelevant stimuli. This study explores the brain mechanisms mediating attentional processing in patients with schizophrenia by measuring their regional cerebral blood flow (rCBF) with positron emission tomography using [15O] water as they performed tasks that differed systematically in attentional demand. METHODS: Ten schizophrenic patients (either neurolepticnaive or withdrawn from medication) (patient group) and 10 normal volunteers (control group) performed auditory target detection tasks. Different types of auditory stimuli (environmental sounds, meaningless speech sounds, and words) were presented either binaurally (ie, same sounds in both ears) or dichotically (simultaneous and different sounds in the 2 ears). In dichotic conditions, subjects were instructed to focus on either their left or right ear. RESULTS: Initial subtraction-based image analyses sought significant rCBF changes anywhere in the brain. Patients consistently had less significant activation than controls in right superotemporal gyrus (STG). Follow-up analyses used regions of interest traced on individual magnetic resonance images to precisely measure rCBF in STG. Unlike controls, patients had higher rCBF in the left STG during all activation conditions. CONCLUSIONS: The abnormal task-related rCBF asymmetry in STG of schizophrenic patients may indicate an isolated temporal lobe deficit, but it may also indicate abnormality in the thalamocortical circuitry mediating selective attention and/or in the brain systems that integrate auditory processing in the 2 hemispheres.

Adult↗
PubMed1996

A positron emission tomography study of binaurally and dichotically presented stimuli: effects of level of language and directed attention.

Regional cerebral blood flow (rCBF) was measured using positron emission tomography with oxygen- 15 labeled water as 10 normal subjects listened to three types of auditory stimuli (environmental sounds, meaningless speech, and words) presented binaurally or dichotically. Binaurally presented environmental sounds and words caused similar bilateral rCBF increases in left and right superior temporal gyri. Dichotically presented stimuli (subjects attended to left or right ears) caused asymmetric activation in the temporal lobes, resulting from increased rCBF in temporal lobe regions contralateral to the attended ear and decreased rCBF in the opposite hemisphere. The results indicate that auditorily presented language and non-language stimuli activate similar temporal regions, that dichotic stimulation dramatically changes rCBF in temporal lobes, and that the change is due both to attentional mechanisms and to hemispheric specialization.

Adult↗
PubMed1996

Sample size and statistical power in [15O]H2O studies of human cognition.

Determining the appropriate sample size is a crucial component of positron emission tomography (PET) studies. Power calculations, the traditional method for determining sample size, were developed for hypothesis-testing approaches to data analysis. This method for determining sample size is challenged by the complexities of PET data analysis: use of exploratory analysis strategies, search for multiple correlated nodes on interlinked networks, and analysis of large numbers of pixels that may have correlated values due to both anatomical and functional dependence. We examine the effects of variable sample size in a study of human memory, comparing large (n = 33), medium (n = 16,17), small (n = 11, 11, 11), and very small (n = 6,6,7,7,7) samples. Results from the large sample are assumed to be the "gold standard." The primary criterion for assessing sample size is replicability. This is evaluated using a hierarchically ordered group of parameters: pattern of peaks, location of peaks, number of peaks, size (volume) of peaks, and intensity of the associated t (or z) statistic. As sample size decreases, false negatives begin to appear, with some loss of pattern and peak detection; there is no corresponding increase in false positives. The results suggest that good replicability occurs with a sample size of 10-20 subjects in studies of human cognition that use paired subtraction comparisons of single experimental/baseline conditions with blood flow differences ranging from 4 to 13%.

Adult↗
PubMed1996

Dosimetry of [15O]water: a physiologic approach.

Earlier dosimetry estimates for [15O]water assumed its instantaneous equilibrium with total body water. This assumption leads to an underestimation of the absorbed doses to organs with high blood flows, since the biodistribution of this short-lived radiopharmaceutical is dependent upon blood flow to organs. We have developed a physiologically based whole body blood flow model (WBBFM) using a commercially available icon-driven mathematical simulation software package and applied it to the reevaluation of [15O]water dosimetry in humans. The WBBFM uses multiple parallel compartments to represent organs, heart chambers, the injection site for [15O]water, and blood sampling sites (arterial and venous). Input values to the WBBFM include organ blood flows, organ masses, organ water volumes, organ:blood partition coefficients, injected activity and S-values of [15O]. The WBBFM is based on the same assumptions that are used in calculating regional blood flow using [15O]water and simulates the human body closely in its physiologic response. The activity in each organ is derived from the simulation and is used to calculate absorbed doses. The WBBFM calculated absorbed doses in microGy/MBq (mrad/mCi) to various organs are as follows: heart--2.66 (9.84), kidneys--2.20 (8.15), thyroid--1.83 (6.78), brain--1.66 (6.13), ovaries--1.25 (4.61), breast--1.24 (4.59), and small intestine--1.03 (3.83). These values are approximately two- to threefold higher than the earlier estimates of Kearfott [J. Nucl. Med. 23, 1031-1037 (1982)] and similar to the recent findings of Herscovitch et al. [J. Nucl. Med. 34, 155P (1983)]. We believe this approach yields more realistic dosimetry estimates for [15O]water. Accordingly, we have revised the amount of [15O]water administered during regional blood flow studies at our institution. The relative ease and accuracy of this approach suggests its usefulness in dosimetry estimation for other freely diffusible radiopharmaceuticals.

Biophysical Phenomena↗
PubMed1996

Neural substrates of facial recognition.

Seventeen healthy normal volunteers performed three facial recognition tasks while their cerebral blood flow was measured with PET: categorizing faces according to gender, recognizing new faces, and recognizing familiar faces. These tasks activated three different pathways: respectively, the left inferior temporal lobe and left frontal cortex; a predominantly right frontal-right parietal-left cerebellar network; and left lingual and left and right fusiform gyri. These results suggest that humans use different brain regions in performing these three routine daily activities. The results are consistent with previous observations concerning organization of extrastriate visual cortex in human and nonhuman primate lesion studies, including studies of the unusual syndrome of prosopagnosia (loss of the ability to recognize familiar faces with intact ability to recognize a face as a face).

Adult↗
PubMed1995

Short-term and long-term verbal memory: a positron emission tomography study.

Short-term and long-term retention of experimentally presented words were compared in a sample of 33 healthy normal volunteers by the [15O]H2O method with positron emission tomography (PET). The design included three conditions. For the long-term condition, subjects thoroughly studied 18 words 1 week before the PET study. For the short-term condition, subjects were shown another set of 18 words 60 sec before imaging, with instructions to remember them. For the baseline condition, subtracted from the two memory conditions, subjects read a third set of words that they had not previously seen in the experiment. Similar regions were activated in both short-term and long-term conditions: large right frontal areas, biparietal areas, and the left cerebellum. In addition, the short-term condition also activated a relatively large region in the left prefrontal region. These complex distributed circuits appear to represent the neural substrates for aspects of memory such as encoding, retrieval, and storage. They indicate that circuitry involved in episodic memory has much larger cortical and cerebellar components than has been emphasized in earlier lesion studies.

Adult↗
PubMed1995

I. PET studies of memory: novel and practiced free recall of complex narratives.

Positron Emission Tomography (PET) with the tracer H215O was used to measure regional cerebral blood flow in 13 healthy volunteers during two experimental memory tasks, one of which was well-practiced and the other of which was novel. The materials used for the memory tasks consisted of two complex narratives (Story A and Story B from the Wechsler Memory Scale). Natural language materials were chosen because they similate experimentally the natural learning situation and permit study of the neural mechanisms by which recall memory becomes more fluid, automatic, or "rote." One week before the PET study, subjects were trained to perfect recall of Story A, while they were exposed to Story B only 60 s prior to PET data acquisition. Despite the substantial differences in level of familiarity (and in free recall performance), patterns of activation were quite similar; activations presumed to reflect recall in both tasks included frontal, inferior temporal, thalamic, anterior cingulate, and cerebellar regions. Many regions were smaller during recall of the familiar story, however, presumably reflecting greater neural efficiency due to practice. In addition, the novel task activated an additional left frontal region that is presumed to reflect more active encoding. The similarity and multiplicity of the activations in the two tasks suggest that the brain uses a multinodal general network for memory tasks such as free recall, while the differences suggest that some nodes in the network may be used for specific components of memory such as encoding and retrieval.

Adult↗
PubMed1995

II. PET studies of memory: novel versus practiced free recall of word lists.

Positron emission tomography (PET) with the tracer H215O was used to measure regional cerebral blood flow in 13 healthy volunteers while they engaged in free recall of 15-item word lists from the Rey Auditory Verbal Learning task. The study was designed so that recall of well-practiced versus novel material could be compared. One week before the PET study, subjects were trained to perfect recall of List A, while they were exposed to list B only 60 s prior to PET data acquisition. As in the companion study of free recall of complex narratives, we observed that practice tended to decrease the size of activations in regions involved in the memory component of the task; we also observed that the novel recall task produced greater activation in left frontal regions, probably due to active encoding. A commonality of other regions observed in this pair of studies, as well as other studies of memory in the literature, suggests that the human brain may contain a distributed multinodal general memory system. Nodes on this network include the frontal, parietal, and temporal cortices, the thalamus, the anterior and posterior cingulate, the precuneus, and the cerebellum. There appears to be a commonality of components across tasks (e.g., retrieval, encoding) that is independent of content, as well as differentiation of some components that may be content-specific or tasks-specific. In addition, these results support a significant role for the cerebellum in cognitive functions such as memory.

Adult↗
PubMed1995

Remembering the past: two facets of episodic memory explored with positron emission tomography.

OBJECTIVE: This study used positron emission tomography to examine two kinds of personal memory that are used in psychiatric evaluation: focused episodic memory (recall of past experience, employed in "taking a history") and random episodic memory (uncensored thinking about experience, examined during analytic therapy using free association). For comparison, a third memory task was used to tap impersonal memory that represents general information about the world ("semantic memory"). METHOD: Thirteen subjects were studied using the [15O]H2O method to obtain quantitative measurements of cerebral blood flow. The three conditions were subtracted and their relative relationships examined. RESULTS: The random episodic condition produced activations in widely distributed association cortex (right and left frontal, parietal, angular/supramarginal, and posterior inferior temporal regions). Focused episodic memory engaged a network that included the medial inferior frontal regions, precuneus/retrosplenial cingulate, anterior cingulate, thalamus, and cerebellum. The use of medial frontal regions and the precuneus/retrosplenial cingulate was common to both focused and random episodic memory. The major difference between semantic and episodic memory was activation of Broca's area and the left frontal operculum by semantic memory. CONCLUSIONS: These results indicate that free-ranging mental activity (random episodic memory) produces large activations in association cortex and may reflect both active retrieval of past experiences and planning of future experiences. Focused episodic memory shares some components of this circuit (inferior frontal and precuneus), which may reflect the time-linked components of both aspects of episodic memory, and which permit human beings to experience personal identity, consciousness, and self-awareness.

Adult↗
PubMed1995

A comparison of approaches to the statistical analysis of [15O]H2O PET cognitive activation studies.

This study compares two of the most widely used statistical techniques for analyzing data obtained from [15O]H2O PET studies of brain function. The Friston method (SPM94) and the Worsley (Montreal) method were applied to a single data set of 33 subjects who were studied in a paradigm designed to evaluate memory for word lists. Neither of these methods emerged as either strikingly different or strikingly preferable, although the occasional differences may be important in some experiments. In general, the two methods were found to produce similar results in identifying brain regions active during long-term memory: frontal, parietal, cingulate, and cerebellar. Underlying assumptions of the two methods, as well as their strengths and weaknesses, are discussed.

Arousal↗
PubMed1994

Positron emission tomographic measurement of bone marrow blood flow to the pelvis and lumbar vertebrae in young normal adults.

Ten young normal adults had pelvic and lumbar vertebral body bone marrow blood flow examined using [15O]water and positron emission tomography (PET) in a study designed to assess the feasibility and reproducibility of the PET technique for measuring marrow blood flow to various marrow regions. The procedure was well tolerated. Repeated blood flow measurements obtained from two consecutive [15O]water exams on each individual subject were highly reproducible. In addition, there was minimal variation in marrow blood flow from individual to individual and no gender differences were noted. In contrast, mean +/- SD bone marrow blood flows (expressed as milliliters per minute per 100 g) at selected anatomical sites were significantly different and were as follows: lower lumbar vertebral bodies, 17.6 +/- 3.1; most posterior and superior pelvis (conventional site of percutaneous bone marrow biopsy), 14.3 +/- 3.1; and total superior pelvis, 11.1 +/- 2.0. We conclude that PET is a relatively noninvasive, simple, and reproducible technique for measuring bone marrow blood flow. Marrow blood flow is consistent between normal young subjects, but varies significantly between different anatomic regions of the marrow.

Adult↗
PubMed1994

Effects of timing and duration of cognitive activation in [15O]water PET studies.

The multiple injection [15O]water method offers unique opportunities for studying cognitive processing by the human brain. The influence of the duration and temporal placement of an activation task, in relation to the arrival of the radiotracer in the brain, is a fundamental methodologic question for cognitive activation studies. A quantitative positron emission tomography (PET) study of five normal volunteers was performed in which the stimulation consisted of a visual activation task (alternating checkerboard pattern) superimposed on an auditory baseline task (syllable monitoring). Ten injection conditions, with varying duration and timing of the visual activation, were used. Regional CBF (rCBF) in visual cortex was measured quantitatively using the autoradiographic method. A 20-s stimulation, centered on the bolus arrival in the brain, produced significant changes in rCBF. Because varying the duration and timing of the activation task technically violates the temporal homogeneity assumption of the autoradiographic model, a mathematical simulation was formulated to evaluate the potential influence of these variations. Results of the simulation are consistent with the PET data and suggest that activation can be limited to a narrow temporal window centered on the radiotracer uptake. The ability to observe significant changes in rCBF with short stimulation intervals is of particular interest in the use of [15O]water PET for studies of cognitive processes with a short time course.

Adult↗
PubMed1993

Control of early postoperative pain with bupivacaine in adult local tonsillectomy.

Early postoperative pain following tonsillectomy remains a significant obstacle to speedy recovery and smooth convalescence. Inadequate analgesia causes poor oral intake and occasionally requires overnight hospitalization in same-day surgery practices. Although several otolaryngologists anecdotally support intraoperative infiltration with long-acting anesthetic agents for postoperative pain control, to our knowledge, no previous study confirms this claim. In a prior investigation, we found no difference between bupivacaine hydrochloride and saline placebo in pediatric patients undergoing tonsillectomy. In this trial, we performed a similar study in an adult population. Fifty-one patients undergoing tonsillectomy with local anesthesia were randomized into bupivacaine or saline placebo groups. Patients provided the following data: (1) pain level; (2) oral intake; (3) number of pain medication doses; and (4) level of pain on jaw opening, all at 10 hours postoperatively. Bupivacaine administration resulted in no adverse effects. No difference was noted in pain level, amount of oral intake, or pain on full jaw opening. Bupivacaine group patients received fewer though not statistically significant doses of pain medication than placebo group patients. We conclude that bupivacaine is a safe medication but offers no advantage in the control of early postoperative pain in adult patients undergoing local tonsillectomy.

Adult↗
PubMed1993

Control of early postoperative pain with bupivacaine in pediatric tonsillectomy.

Early postoperative pain following pediatric tonsillectomy remains a significant obstacle to speedy recovery and smooth convalescence. Inadequate analgesia causes poor oral intake and occasionally requires overnight hospitalization in same day surgery practices. Several otolaryngologists anecdotally support intraoperative infiltration with a long-acting amide anesthetic, bupivacaine hydrochloride, for postoperative pain control. However, no previous study supports these claims. At the National Naval Medical Center, a prospective, randomized, double-blinded study was undertaken in fifty patients, ages 3 to 16 years old. After tonsil resection, either 0.5% bupivacaine or saline was injected into each fossa. We asked the parents three questions. First, what was the level of pain at 2, 6 and 10 hours postoperatively? Second, what was the amount of oral intake during the first 10 hours after surgery? And third, how many doses of oral acetaminophen elixir were administered over the first 10 postoperative hours? Bupivacaine administration caused no adverse effects. There was no difference in perceived pain level between bupivacaine and saline groups at 2, 6 and 10 hours. Oral intake levels over the first 10 hours were similar. Although bupivacaine group patients received fewer doses of oral acetaminophen, the difference between groups was not statistically significant. We conclude that bupivacaine is a safe medication for infiltration, but offers no advantage over saline in the control of early postoperative pain in pediatric tonsillectomy.

Bupivacaine↗