Biomedical subjects

S Houle

Publications and source records attributed to S Houle.

At least 91 records · Page 5Linked to original sources

PubMed1996

High levels of dopamine D2 receptor occupancy with low-dose haloperidol treatment: a PET study.

OBJECTIVE: The purpose of this study was to determine the dopamine D2 receptor occupancy induced by low-dose haloperidol treatment in a prospective trial. METHOD: Seven patients with schizophrenia were treated with 2 mg/day of haloperidol for 2 weeks, and D2 receptor occupancy was measured by [11C]raclopride and positron emission tomography. RESULTS: The patients showed high levels of D2 occupancy (53%-74%); five of them showed substantial clinical improvement, and none showed important side effects. CONCLUSIONS: The findings demonstrate that low doses of haloperidol induce D2 receptor occupancies that are in the putative therapeutic range. In combination with recent empirical trials, these findings should encourage clinicians to initiate treatment of psychotic episodes with low (2-4 mg haloperidol equivalent) doses of typical neuroleptics, particularly for first-episode patients.

Adult↗

PubMed1995

Functional brain maps of retrieval mode and recovery of episodic information.

Positron emission tomography (PET) was used to identify brain regions associated with two component processes of episodic retrieval; those related to thinking back in subjective time (retrieval mode) and those related to actual recovery of stored information (ecphory). Healthy young subjects recognized words that had been encoded with respect to meaning or the speaker's voice. Regardless of how the information had been encoded, recognition was associated with increased activation in regions in right prefrontal cortex, left anterior cingulate, and cerebellum. These activations reflect retrieval mode. Recognition following meaning encoding was specifically associated with increased activation in left temporal cortex, and recognition following voice encoding involved regions in right orbital frontal and parahippocampal cortex. These activations reflect ecphory of differentially encoded information.

Adult↗

PubMed1995

Dissociation of pathways for object and spatial vision: a PET study in humans.

A positron emission tomography (PET) study was conducted to determine which brain regions are differentially involved in visual object identification and object localization. Subjects engaged in a spatial task in which they matched the location of common objects, and an object task in which they matched the identity of common objects. In both tasks the stimulus arrangements used were of the same kind. Regional cerebral blood flow data showed that a right-sided region in the inferior parietal lobule was more activated during spatial than during object matching. In contrast, bilateral occipitotemporal regions, with the left more predominant, were more activated during object than spatial matching. These results provide support for Ungerleider and Mishkin's dual pathway model of vision and indicate important patterns of lateralization in the human visual system.

Brain↗

PubMed1995

Functional role of the prefrontal cortex in retrieval of memories: a PET study.

Retrieval of information from episodic memory involves the processes invoked by the attempt to remember (retrieval attempt) as well as processes associated with the successful retrieval of stored information (ecphory). Previous PET studies of memory have shown an activation of the prefrontal cortex in memory retrieval tasks, and we hypothesised that this activation represents retrieval attempt, not ecphory. This hypothesis was directly directed using [15O]H2 PET imaging in 19 healthy subjects who performed three matched tasks which involved different levels of retrieval attempt and ecphory. The results showed that retrieval attempt was associated with activation of the prefrontal cortex, right greater than left, while ecphory involved the posterior cortical regions. These findings illuminate the functional role of the different neuroanatomical regions involved in episodic remembering.

Adult↗

PubMed1995

Distinct neural correlates of visual long-term memory for spatial location and object identity: a positron emission tomography study in humans.

The purpose of the present study was to investigate by using positron emission tomography (PET) whether the cortical pathways that are involved in visual perception of spatial location and object identity are also differentially implicated in retrieval of these types of information from episodic long-term memory. Subjects studied a set of displays consisting of three unique representational line drawings arranged in different spatial configurations. Later, while undergoing PET scanning, subjects' memory for spatial location and identity of the objects in the displays was tested and compared to a perceptual baseline task involving the same displays. In comparison to the baseline task, each of the memory tasks activated both the dorsal and the ventral pathways in the right hemisphere but not to an equal extent. There was also activation of the right prefrontal cortex. When PET scans of the memory tasks were compared to each other, areas of activation were very circumscribed and restricted to the right hemisphere: For retrieval of object identity, the area was in the inferior temporal cortex in the region of the fusiform gyrus (area 37), whereas for retrieval of spatial location, it was in the inferior parietal lobule in the region of the supramarginal gyrus (area 40). Thus, our study shows that distinct neural pathways are activated during retrieval of information about spatial location and object identity from long-term memory.

Adult↗

PubMed1995

The D2 dopamine receptor occupancy of risperidone and its relationship to extrapyramidal symptoms: a PET study.

Risperidone is a recently introduced neuroleptic distinguished by a decreased incidence of extrapyramidal side effects (EPS). The mechanism of its low EPS is unclear. Since it has been shown that EPS is related to the level of D2 receptor occupancy, we studied nine patients receiving 2-6 mg/day of risperidone using [11C]-raclopride PET scans in order to determine the in vivo D2 receptor binding characteristics of risperidone. The mean level of receptor occupancy was 66% at 2 mg; 73% at 4 mg; and 79% at 6 mg. Three patients, those with the highest receptor occupancies, exhibited mild EPS, though none required anitparkinsonian medications. Our results suggest that at doses of 4-6 mg the in vivo D2 receptor occupancy of risperidone is similar to that of typical neuroleptics and higher than that of clozapine. This would suggest that the EPS benefits of risperidone cannot be explained by a low D2 binding but may be related to its high 5-HT2 affinity. However, the emergence of EPS at higher levels of D2 receptor occupancy, in this study and in previous clinical trials, would suggest that risperidone's high 5-HT2 affinity provides only a relative protection from EPS. And once the D2 occupancy exceeds a certain threshold this 'relative' 5-HT2-mediated protection from EPS may be lost.

Adult↗

PubMed1995

Synthesis of two radiofluorinated cocaine analogues using distilled 2-[18F]fluoroethyl bromide.

Two fluorinated congeners of cocaine, 2'-fluoroethyl (1R-2-exo-3-exo)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane- 2-carboxylate (FETT) and its 4-chlorophenyl analogue (FECT) were synthesized. Radiolabelling with 18F was achieved by O-[18F]fluoroalkylation of the corresponding carboxylic acid salts with distilled 2-[18F]fluoroethyl bromide in DMF. After HPLC purification, yields of radiochemically pure, formulated products were 22-30% (not corrected for decay) in a synthesis time of 60-70 min. The use of distilled 2-[18F]fluoroethyl bromide was indispensable for the reliable production of pure products.

Biological Transport↗

PubMed1995

The statistical power of [15O]-water PET activation studies of cognitive processes.

[15O]-Water positron emission tomography (PET) scanning is an important means of investigating the neural correlates of cognitive processes. This study analyses the statistical power of these experiments under usual experimental conditions. Eleven subjects were scanned repeatedly while they undertook an active-baseline task. Using an empirically derived estimate of variance, the statistical power to detect task-induced increases in regional cerebral blood flow was calculated for different values of magnitude of change, number of subjects and probability of Type I error. The results (a) provide an empirical basis for selecting the number of subjects for cognitive studies using [15O]-water PET; (b) illustrate the importance of considering the statistical power of the test, while making a physiological interpretation of the results; and (c) highlight the problems in concluding the non-involvement of a given brain region in a cognitive task, based solely on the results of a PET study.

Adult↗

PubMed1994

Novelty encoding networks in the human brain: positron emission tomography data.

Data from positron emission tomography (PET) studies showed novelty activations--higher regional cerebral blood flow associated with perceiving novel rather than familiar stimuli. Regions in the right 'expanded' limbic system--hippocampal formation, parahippocampal gyrus, retrosplenial cortex, thalamus, subcallosal area, the border between cortical areas 32 and 10, anterior and inferior cingulate cortex, putamen, and medial prefrontal cortex--showed such activations for complex pictures. Because novel information is usually encoded for storage in memory, these regions can be seen as constituting components of a visual/spatial novelty encoding network. Insular, opercular and temporal regions (e.g. area 37) showed novelty activations not only for visual pictures but also for auditorily presented sentences, and can be thought of as components of a transmodal novelty encoding network.

Auditory Pathways↗

PubMed1994

The role of the left prefrontal cortex in verbal processing: semantic processing or willed action?

This study was designed to test the various proposed explanations (semantic processing, willed action, production of a spoken response) for the unilateral activation of the left prefrontal cortex noted in PET studies of verbal processing. Twenty subjects underwent 15O-water PET scans while undertaking a lexical task (detecting the letter 'a' in visually presented words) and a semantic task (categorizing nouns into living/non-living). The semantic task resulted in a significant unilateral left dorsolateral prefrontal activation. This finding suggests that the left inferior prefrontal cortex is the anatomical region involved in 'working with meaning', and that the activation does not reflect willed action, is not task-specific and is not attributable to the requirements of a spoken response.

Adult↗

PubMed1994

Activation of specific cortical regions by apomorphine: an [15O]H2O PET study in humans.

The purpose of this study was to investigate the functional effects of apomorphine, a non-selective dopamine agonist, on regional neuronal activity using regional cerebral blood flow, measured using [15O]H2O and positron emission tomography (PET), as an index. Eight normal volunteers were scanned twice before and twice after receiving 10 micrograms/kg subcutaneous apomorphine. Apomorphine produced the expected side-effects and endocrine response. Analysis of the PET scans revealed that apomorphine increased regional cerebral blood flow (rCBF), presumably reflecting a change in neuronal activity, in the anterior cingulate, ventral motor cortex and the dorsolateral prefrontal cortex along with a decrease in rCBF in the retrosplenial cingulate region. These regions form a functional network of brain regions modulated by the dopaminergic system.

Adult↗

PubMed1994

Modulation of cortical neuronal activity by a serotonergic agent: a PET study in humans.

This study investigates the effect of a serotonergic agent, fenfluramine, on neuronal activity, as measured using [18F]fluorodeoxyglucose (FDG) uptake with positron emission tomography (PET) in humans. Eleven subjects each received oral fenfluramine and placebo, on two different occasions, followed by FDG PET scans. Our study shows that fenfluramine modulates ongoing neuronal activity in a regionally specific fashion with a relative increase in metabolism in the prefrontal cortex and a relative decrease in the occipital-temporal regions.

Adult↗

PubMed1994

Neuroanatomical correlates of encoding in episodic memory: levels of processing effect.

Cognitive studies of memory processes demonstrate that memory for stimuli is a function of how they are encoded; stimuli processed semantically are better remembered than those processed in a perceptual or shallow fashion. This study investigates the neural correlates of this cognitive phenomenon. Twelve subjects performed two different cognitive tasks on a series of visually presented nouns. In one task, subjects detected the presence or absence of the letter a; in the other, subjects categorized each noun as living or nonliving. Positron emission tomography (PET) scans using 15O-labeled water were obtained during both tasks. Subjects showed substantially better recognition memory for nouns seen in the living/nonliving task, compared to nouns seen in the a-checking task. Comparison of the PET images between the two cognitive tasks revealed a significant activation in the left inferior prefrontal cortex (Brodmann's areas 45, 46, 47, and 10) in the semantic task as compared to the perceptual task. We propose that memory processes are subserved by a wide neurocognitive network and that encoding processes involve preferential activation of the structures in the left inferior prefrontal cortex.

Adult↗

PubMed1994

Neuroanatomical correlates of retrieval in episodic memory: auditory sentence recognition.

This study used positron emission tomography (PET) to investigate the neuroanatomical correlates of remembering previously experienced events. Twelve young healthy adults listened to "old" meaningful sentences which they had studied 24 hr previously. As a control task the subjects listened to comparable "new" sentences that they had never heard before. Regional cerebral blood flow associated with each task was measured by PET scans using 15O-labeled water. Comparison (old-sentence task minus new-sentence task) of the PET images revealed an extended strip of increased blood flow in the right dorsolateral prefrontal cortex (Brodmann's areas 10, 46, and 9) and the anterior portion of area 6. Other principal regions of increased blood flow were situated around the left anterior cingulate sulcus and bilaterally in the parietal lobes (areas 7 and 40). Major decreases in blood flow were situated bilaterally in the temporal lobes (areas 21, 22, 41, and 42). A high proportion of activity changes seemed to be located in the depths of cortical sulci. Increases in blood flow are seen as reflecting the operations of a widely distributed neuronal network involving prefrontal and parietal cortical regions that subserves the conscious recollection of previously experienced events. Decreases in blood flow in the temporal auditory areas are interpreted as reflecting auditory priming. The prevalence of sulcal blood-flow changes may reflect extensive cortical gyrification; it may also indicate that memory-related processes rely on the densely packed neuropil of sulcal regions.

Adult↗

PubMed1994

Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings.

Data are reviewed from positron emission tomography studies of encoding and retrieval processes in episodic memory. These data suggest a hemispheric encoding/retrieval asymmetry model of prefrontal involvement in encoding and retrieval of episodic memory. According to this model, the left and right prefrontal lobes are part of an extensive neuronal network that subserves episodic remembering, but the two prefrontal hemispheres play different roles. Left prefrontal cortical regions are differentially more involved in retrieval of information from semantic memory and in simultaneously encoding novel aspects of the retrieved information into episodic memory. Right prefrontal cortical regions, on the other hand, are differentially more involved in episodic memory retrieval.

Brain↗

PubMed1994

Absence of residual effects after physiological stimulation of the visual and motor cortex: an [15O]-H2O PET study in humans.

Cognitive experiments using positron emission tomography (PET) with [15O]-H2O require multiple scans done at 10 to 12 min intervals. Momose and colleagues reported that regional cerebral blood flow changes in response to visual stimulation do not return to baseline even 15 min after the stimulation. If confirmed, this fact would have important implications for the design and interpretation of PET cognitive studies. The purpose of this study was to determine the temporal course of residual effects following visual and motor stimulation. Six healthy volunteers undertook six scans each. Two scans were done to establish a baseline, one to observe the task induced activation, and three scans to investigate the residual effects at varying intervals after the task. The data were analysed using both statistical parametric mapping and a region of interest analysis. The visual and motor task produced robust activations bilaterally in the occipital cortex and in the contralateral primary motor cortex. There was no evidence for a statistically significant residue effect at any of the three intervals studied (30 s, 3 and 6 min). Our results refute the findings of Momose and colleagues and suggest that the 10-min interscan interval is more than adequate to re-establish a resting baseline.

Adult↗

PubMed1993

Compartmental analysis of the pharmacokinetics of radioiodinated monoclonal antibody B72.3 in colon cancer patients.

Sixteen patients with colorectal cancer were administered 37-74 MBq (1 mg) of radioiodinated B72.3 monoclonal antibody. Pharmacokinetic analysis was carried out on plasma and urine samples. Elimination from the plasma was biexponential with a mean T1/2 alpha of 3.7 h and T1/2 beta of 62.4 h. The plasma clearance was fit to a two-compartmental model. This was combined with a previously reported model for radioiodine to construct a composite model. There was a good correlation (r = 0.952) between the model-predicted and observed excretion of radioiodine suggesting that the composite model is compatible with the pharmacokinetics of the radiolabelled antibody.

Adult↗

PubMed1992

A phase I dose escalation trial of yttrium-90 microspheres in the treatment of primary hepatocellular carcinoma.

METHODS: Ten patients with primary hepatocellular carcinoma were treated with intraarterial instillation of yttrium-90 (Y-90) microspheres, including eight men and two women (median age, 52 years; range, 29-69 years). Four patients were treated at a targeted hepatic dose of 50 Gy, two at 75 Gy, and four at 100 Gy. RESULTS: In 8 of the 10 patients, there was a significant concentration of Y-90 in localized tumor masses with tumor-to-liver perfusion ratios from 1.0:1-10.0:1. No patient had a complete or partial response, but 10 patients had stable disease (median duration, 10 weeks; range, 5-64 weeks). The median survival was 18 weeks (range, 2-150 weeks), and three patients lived longer than 1 year. Significant bone marrow or hepatic toxicity was not seen. One patient had a radiation-induced duodenal ulcer that required surgical management. CONCLUSIONS: Intraarterial instillation of Y-90 microspheres appears to be safe and deserves additional evaluation to determine whether there is meaningful activity in patients with primary hepatocellular carcinoma.

Adult↗