Sites of action of morphine in the brain.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
R S Frackowiak
Publications and source records attributed to R S Frackowiak.
Willed action and the prefrontal cortex in man: a study with PET.
We used positron emission tomography to contrast changes in cerebral blood flow associated with willed and routine acts. In the six tasks used, volunteers had to make a series of responses to a sequence of stimuli. For the routine acts, each response was completely specified by the stimulus. For the willed acts, the response was open-ended and therefore volunteers had to make a deliberate choice. Willed acts in the two response modalities studied (speaking a word, or lifting a finger) were associated with increased blood flow in the dorsolateral prefrontal cortex (Brodmann area 46). Willed acts were also associated with decreases in blood flow, but the location of these decreases was modality dependent.
Acoustic Stimulation↗
Investigating a network model of word generation with positron emission tomography.
By using positron emission tomography (PET) we examined the biological validity of a network model describing changes in cerebral activity associated with intrinsic and extrinsic word generation. The production of words not specified by an extrinsic stimulus constitutes willed or intrinsic generation. Perceiving a heard word is an example of extrinsic generation. The model incorporates three neuronal systems: a pool that stores word representations in a distributed fashion, an afferent system conveying sensory input to the pool and a modulating system that alters the responsivity of neurons in the pool. Simulations based on the model suggested that intrinsic generation would be associated with low activity in the pool, consequent on reduced modulation, and extrinsic generation with high activity. We measured cerebral activity with PET during intrinsic (verbal fluency) and extrinsic (responding to heard words) word generation and found this pattern of changes in the left superior temporal region. We were able to designate this region the site of the distributed word store and implicate the left dorsolateral prefrontal cortex (DLPFC) as the source of modulation. The relation between the superior temporal gyrus and DLPFC was shown by examining the correlation between the two regions in terms of cerebral activity. We conclude that the left DLPFC is responsible for modulating the responsivity of a neural system in the superior temporal gyrus and is the probable mediator of changes in attentional and intentional states that underlies the intrinsic generation of words.
Animals↗
Cortical and subcortical localization of response to pain in man using positron emission tomography.
A quantitative study of the regional cerebral responses to non-painful and painful thermal stimuli in six normal volunteers has been done by monitoring serial measurements of regional blood flow measured by positron emission tomography (PET). In comparison to a baseline of warm stimulation no statistically significant changes in blood flow were seen in relation to increasing non-painful heat. However, highly significant increases in blood flow were seen in response to painful heat in comparison to non-painful heat. These changes were in the contralateral cingulate cortex, thalamus and lenticular nucleus. These findings are discussed in relation to previous physiological observations of responses to nociceptive stimuli in man and primates.
Adult↗
The functional anatomy of recovery from brain injury.
The functional neuroanatomical basis for recovery from ischaemic brain injury is not known. We have used positron emission tomography (PET) to study changes in the functional organization of the brain in patients recovering from striatocapsular motor strokes. Significant changes in regional cerebral blood flow (rCBF) were found during repetitive sequential opposition movements of the fingers in normal subjects and in patients with recovery from motor deficits. There was a difference in the pattern of cerebral activation when patients performed the motor task with the unaffected hand (when the activation was lateralized to contralateral sensorimotor and premotor cortex and ipsilateral cerebellum) and when the task was performed with the recovered, previously plegic hand (when the activation was bilateral and involved novel areas of cortex, especially area 40). Comparisons of rCBF maps at rest in the patient group and in normal subjects showed areas with significantly decreased rCBF in the patients (contralateral to the plegic hand in the basal ganglia, thalamus, insular cortex, brainstem and ipsilateral cerebellum), which reflected the distribution of dysfunction caused by the ischaemic lesions. A significantly increased activation over and above that in normal subjects was found in patients during movement of the recovered fingers in ipsilateral premotor cortex and bilateral frontal opercular/insular regions and area 40, the ipsilateral basal ganglia (the ischaemic lesion lying contralaterally) and the contralateral cerebellum. We postulate that these findings may be explained by the generation of movements by pathways that are different from those that normal subjects use to perform what are ordinarily fairly simple, automated tasks. We suggest that this is a direct demonstration of cerebral plasticity resulting in the resolution of acquired motor deficits.
Brain Ischemia↗
The neurotransmitter basis of cognition: psychopharmacological activation studies using positron emission tomography.
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).
Adult↗
The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography.
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.
Adult↗
Dopa-responsive dystonia: [18F]dopa positron emission tomography.
The syndrome of dopa-responsive dystonia comprises a minority of patients with dystonia, yet it is of considerable diagnostic importance because patients respond dramatically to L-dopa therapy. Benefits from this treatment are lasting, and the problems associated with long-term L-dopa therapy in patients with Parkinson's disease are generally absent. It has been suggested that this condition is due to a defect in the dopamine synthetic pathway, which is bypassed when patients are treated with L-dopa. We have studied [18F]dopa uptake in 6 patients with classic dopa-responsive dystonia (5 familial patients and 1 sporadic patient), aged 18 to 66 years. Data have been analyzed according to a graphic approach, calculating an influx constant for each region studied. We have also studied a seventh, clinically atypical, patient with juvenile dystonia-parkinsonism. Similar data have been calculated for a group of 10 healthy control subjects and 10 patients with Parkinson's disease. The 6 patients with typical dopa-responsive dystonia had a modest but significant reduction in the uptake of tracer into both caudate and putamen, which indicates a defect in the decarboxylation, vesicular uptake, and storage of [18F]dopa. This argues against the proposition that dopa-responsive dystonia is due to an inherited defect of tyrosine hydroxylase alone. In the atypical patient, however, we found a greater reduction of [18F]dopa uptake into both caudate and putamen, comparable with that in patients with Parkinson's disease.
Adolescent↗
Cortical areas and the selection of movement: a study with positron emission tomography.
Regional cerebral blood flow was measured in normal subjects with positron emission tomography (PET) while they performed five different motor tasks. In all tasks they had to moved a joystick on hearing a tone. In the control task they always pushed it forwards (fixed condition), and in four other experimental tasks the subjects had to select between four possible directions of movement. These four tasks differed in the basis for movement selection. A comparison was made between the regional blood flow for the four tasks involving movement selection and the fixed condition in which no selection was required. When selection of a movement was made, significant increases in regional cerebral blood flow were found in the premotor cortex, supplementary motor cortex, and superior parietal association cortex. A comparison was also made between the blood flow maps generated when subjects performed tasks based on internal or external cues. In the tasks with internal cues the subjects could prepare their movement before the trigger stimulus, whereas in the tasks with external cues they could not. There was greater activation in the supplementary motor cortex for the tasks with internal cues. Finally a comparison was made between each of the selection conditions and the fixed condition; the greatest and most widespread changes in regional activity were generated by the task on which the subjects themselves made a random selection between the four movements.
Adult↗
A PET study of word finding.
We have used PET in conjunction with psychological activations to identify cortical areas involved in the intrinsic activation of word representations. In four normal subjects intrinsic generation of a word (verbal fluency) was associated with an increase in left dorsolateral prefrontal cortical activity (BA 46) and a bilateral decrease in activity in auditory and superior temporal cortices. Conversely, when subjects made lexical decisions about words that were heard, there was an increase in superior temporal activity with no change in area 46. We suggest that the superior temporal regions are the site of stored word representations and that inhibitory modulation of these areas by the left prefrontal cortex is the basis of intrinsic word generation.
Adult↗
PET and plasma pharmacokinetic studies after bolus intravenous administration of [11C]melatonin in humans.
A human PET study was performed with carbon-11 labelled melatonin in a healthy volunteer. Plasma pharmacokinetics of melatonin and 6-sulfatoxymelatonin were simultaneously determined using radioimmunoassay. Analysis of tracer kinetics showed maximum activity in the brain 8.5 min following injection, which was different from the curve observed for the plasma radioactivity (maximum at 3.5 min). The results confirmed that melatonin readily crosses the blood-brain barrier and that 6-sulfatoxymelatonin is the main plasma metabolite. The distribution of tracer as a function of time in this study failed to reveal any specific binding.
Adult↗
Measurement of cerebral monoamine oxidase B activity using L-[11C]deprenyl and dynamic positron emission tomography.
A tracer kinetic procedure was developed for the measurement of monoamine oxidase type B (MAO-B) activity using L-[11C]deprenyl and positron emission tomography (PET). The kinetic model consisted of two tissue compartments with irreversible binding to the second compartment (three rate constants). In addition, a blood volume component was included. Special attention was given to the accurate measurement of the plasma and whole blood input functions. The method was applied to the measurement of the dose-response curve of a reversible MAO-B inhibitor (Ro 19-6327). From the results, it followed that the rate constant for irreversible binding (k3) appeared to be a better index of MAO-B activity than the net influx constant Ki. Furthermore, regional analysis demonstrated that Ki, but not k3, was flow dependent. This implies that full kinetic analysis is required for an accurate assessment of MAO-B activity.
Aged↗
Decreases in regional cerebral blood flow with normal aging.
Positron emission tomographic (PET) images of regional cerebral blood flow (rCBF) from 30 normal, resting volunteers aged 30 to 85 years were analysed to identify areas where rCBF fell with age. Images were anatomically normalised, and a pixel-by-pixel linear regression was performed to remove differences in global CBF between subjects. Pixels at which rCBF then showed a significant (p less than 0.01) negative correlation with age were identified. They were displayed as a statistical parametric map (SPM) of correlations. We demonstrate an age-related decrease in adjusted rCBF in the cingulate, parahippocampal, superior temporal, medial frontal, and posterior parietal cortices bilaterally, and in the left insular and left posterior prefrontal cortices (omnibus significance, chi 2 = 2,291, p less than 0.0001, df = 1). Decreases in rCBF suggest a regionally specific loss of cerebral function with age. The affected areas were all limbic, or association, cortices. Therefore, these decreases may constitute the cerebral substrate of the cognitive changes that occur during normal aging.
Adult↗
Comparing functional (PET) images: the assessment of significant change.
Statistical parametric maps (SPMs) are potentially powerful ways of localizing differences in regional cerebral activity. This potential is limited by uncertainties in assessing the significance of these maps. In this report, we describe an approach that may partially resolve this issue. A distinction is made between using SPMs as images of change significance and using them to identify foci of significant change. In the first case, the SPM can be reported nonselectively as a single mathematical object with its omnibus significance. Alternatively, the SPM constitutes a large number of repeated measures over the brain. To reject the null hypothesis, that no change has occurred at a specific location, a threshold adjustment must be made that accounts for the large number of comparisons made. This adjustment is shown to depend on the SPM's smoothness. Smoothness can be determined empirically and be used to calculate a threshold required to identify significant foci. The approach models the SPM as a stationary stochastic process. The theory and applications are illustrated using uniform phantom images and data from a verbal fluency activation study of four normal subjects.
Adult↗
Macrophage and astrocyte populations in relation to [3H]PK 11195 binding in rat cerebral cortex following a local ischaemic lesion.
PK 11195 is a selective and specific ligand for the peripheral-type benzodiazepine binding site. Its potential for in vivo visualisation of lesioned human brain using positron emission tomography (PET) is currently being assessed. The present study examines the relationship between the temporal development of a local ischaemic lesion with its associated cell populations and the binding of [3H]PK 11195 in rat brain. Unilateral cortical infarcts were induced using the photosensitive dye Rose Bengal. At time intervals from 1 to 7 days after lesioning, the localisation of [3H]PK 11195 binding was determined using in vivo and in vitro autoradiography. Sections adjacent to those used for autoradiography were processed for immunohistochemistry using glial fibrillary acidic protein for astrocytes and ED-1 for macrophages. The results show that the binding of [3H]PK 11195 correlates in both time and spatial localisation with the appearance of macrophages around the lesion. Reactive astrocytes, although present, occupy a separate region in the tissue surrounding the lesion and lie outside the region defined by the [3H]PK 11195 binding. We conclude that the [3H]PK 11195 signal associated with this ischaemic lesion originates primarily from binding to macrophages and that [11C]PK 11195 could be used for imaging acute inflammatory response in human brain using PET.
Animals↗
Corticobasal degeneration. A unique pattern of regional cortical oxygen hypometabolism and striatal fluorodopa uptake demonstrated by positron emission tomography.
Corticobasal degeneration presents with an asymmetric akinetic-rigid syndrome, apraxia and combinations of supranuclear gaze palsy, myoclonus, and an alien limb. Six patients aged 59-77 yrs, diagnosed on clinical criteria as having corticobasal degeneration, have been studied with positron emission tomography using tracers of dopamine storage capacity and oxygen metabolism. Striatal 18F-6-fluorodopa uptake was reduced in an asymmetric pattern, caudate and putamen being involved in all cases. Uptake into medial frontal cortex was also impaired. Regional cortical oxygen metabolism was most significantly depressed in the superior and posterior temporal, inferior parietal, and occipital associated cortices. Within the frontal lobe, the hypometabolism was chiefly posterior. This unique combination of regional hypometabolism and disruption of the nigrostriatal system is discussed in relation to the clinical features of the disease and is compared with reported findings in other disorders of cognition and movement.
Aged↗
Obsessional slowness. Functional studies with positron emission tomography.
Patients with Obsessional Slowness (OS) exhibit extreme slowness in the execution of some everyday tasks, such as washing and eating. This may be due to time-consuming rituals, checking behaviour and compulsions. On examination some have neurological signs such as a glabellar tap reflex, cogwheel rigidity or abnormal postures. The purpose of this study was to establish a functional explanation for slowness in this patient group. We have studied 6 OS patients using positron emission tomography (PET) with (15)Oxygen to measure regional cerebral oxygen metabolism and [18F]-6-Fluorodopoa (18F-dopa) to assess the integrity of the presynaptic nigrostriatal system. The findings were of focal hypermetabolism in orbital frontal, premotor and midfrontal cortex, whilst dopa uptake into caudate, putamen and medial frontal cortex was normal. The relationship of these findings to the patients' slowness is discussed.
Adult↗