Showing papers by "Raymond J. Dolan published in 1991"

The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography.

Abstract: We have studied regional cerebral blood flow changes in 6 patients after their recovery from a first hemiplegic stroke. All had a single well-defined hemispheric lesion and at least a brachial monoparesis that subsequently recovered. Each patient had 6 measurements of cerebral blood flow by positron tomography with 2 scans at rest, 2 during movement of fingers of the recovered hand, and 2 during movement of fingers of the normal hand. When the normal fingers were moved, regional cerebral blood flow increased significantly in contralateral primary sensorimotor cortex and in the ipsilateral cerebellar hemisphere. When the fingers of the recovered hand were moved, significant regional cerebral blood flow increases were observed in both contralateral and ipsilateral primary sensorimotor cortex and in both cerebellar hemispheres. Other regions, namely, insula, inferior parietal, and premotor cortex, were also bilaterally activated with movement of the recovered hand. We have also demonstrated, by using a new technique of image analysis, different functional connections between the thalamic nuclei and specific cortical and cerebellar regions during these movements. Our results suggest that ipsilateral motor pathways may play a role in the recovery of motor function after ischemic stroke.

Predictors of post-traumatic stress disorder following physical trauma: an examination of the stressor criterion.

Abstract: A prospective study documenting psychopathology was undertaken in 48 subjects exposed to a range of physical trauma, but whose injuries were of similar severity. No support was found for the DSM-III-R view correlating the severity of the stressor with the development of post-traumatic stress disorder (PTSD). Distress post injury (high scores on the impact of event scale), indicative of difficulty with cognitive assimilation of the traumatic event, was found to be highly predictive of psychiatric morbidity and PTSD at 6 months.

Measurement of human cerebral monoamine oxidase type B (MAO-B) activity with positron emission tomography (PET): a dose ranging study with the reversible inhibitor Ro 19-6327.

Abstract: Eight normal subjects (3 females and 5 males) were studied using intravenous L-11C] deprenyl and positron emission tomography. In a single blind study one subject received tracer alone, one subject received an oral pre-dose of 20 mg of L-deprenyl and 6 subjects received oral pre-doses of 10 to 50 mg of a novel reversible MAO-B inhibitor (Ro 19-6327). Dynamic PET scans beginning 12 h after the oral dose were collected over 90 min and arterial blood was continuously sampled. Data analysis was modelled for two tissue compartments and using an iterative curve fitting technique the value of the rate constant for irreversible binding of L-[11C] deprenyl to MAO-B (k3) in whole brain was obtained for each subject. The dose response curves obtained indicated that a dose of at least 0.48 mg·kg−1 of Ro 19-6327 was necessary for >90% decrease in whole brain k3. Inhibition of MAO-B in platelets isolated from blood samples taken at the time of scanning correlated strongly with decrease in whole brain k3 (r=0.949). The results indicate that PET can be used to determine the dose of Ro 19-6327 necessary to inhibit >90% of brain MAO-B. This technique is an attractive alternative to traditional large scale patient-based dose-finding studies. Moreover it is shown that inhibition of platelet MAO-B can be used as a marker for central MAO-B inhibition with Ro 19-6327.

The neurotransmitter basis of cognition: psychopharmacological activation studies using positron emission tomography.

Abstract: The neuromodulatory effect of manipulating monoaminergic receptor function was assessed by combining a psychological and a pharmacological activation during repeated positron emission tomographic (PET) scans. The effects of buspirone (a 5-HT1A receptor partial agonist) on changes in regional cerebral blood flow (rCBF) associated with free word recall were examined. A factorial design was used to demonstrate a significant interaction (changes in rCBF brought about by psychological activation which depend on drug administration) in the left parahippocampal region. This interaction was an attenuation of increases in local neuronal activity (rCBF) related to memory function. Buspirone-induced decreases in rCBF, independent of the memory effect, were seen in the left prefrontal and parietal cortices. We suggest that combined psychological and pharmacological activation is a way of measuring direct (main) drug effects and modulatory effects on neurotransmission associated with cognitive functions (interaction).

Positron emission tomography as a research tool in the investigation of psychiatric and psychological disorders.

Abstract: Summary The principles of positron emission tomography (PET) are described, and illustrations of how these can be applied to clinical psychiatric questions relating to schizophrenia and depression are delineated. The metabolic changes in the frontal lobes which have been described in both depression and schizophrenia and depression are reviewed and discussed. More recent PET techniques allow several serial measurements of changes in regional blood flow in response to either a pharmacological challenge or a specific psychological task. This method provides a promising new approach to the study of the dopaminergic system in schizophrenia. New tracer methods of quantitating changes in in vivo concentrations of opioid receptors allow direct pharmacological access to the endogenous opioid system in the brain. Observations of regional cortical differences in opioid receptor concentration in relation to the medial and lateral pain systems are described. In addition, changes in receptor occupancy during sleep using [ 11 C]diprenorphine and changes in the μ-specific tracer [ 11 C]carfentanil in temporal lobe epilepsy are discussed.

In vivo Distribution of Radiolabelled Citalopram in Brain as a Marker of 5-HT Uptake Sites for PET

Abstract: In rat brain, the biologically active isomer (+)-[ N - methyl - 11 C]citalopram can be used to label 5-HT uptake sites in vivo , giving ratios of uptake in selected regions of interest relative to cerebellum of approximately 2: 1. In human brain, however, the non-specific carbon-11 label is retained over a 90 min scanning period. Both (+)- and (-)-isomers gave similar summed images and similarly shaped time-activity curves for all regions analysed (including cerebellum). The reasons for the species difference in retention of non-specific label are not clear.