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R S Frackowiak

Publications and source records attributed to R S Frackowiak.

303 records · Page 17Linked to original sources

Positron emission tomography: state of the art in neurology.

The initial clinical application of PET has demonstrated intriguing aspects in ischaemic cerebrovascular disease and epilepsy. A few observations on migraine have also been published, and studies on extrapyramidal disorders are currently underway at the UCLA and the Hammersmith Hospital. The development of PET centres in the USA and Europe will result in larger clinical studies. The capacity for accurate and reliable quantitation of physiological parameters now opens the door to serial measurements in individual patients. Quantitation in absolute units of flow or consumption of a metabolite means that correlations and comparisons can be made between patients, and between studies in individual patients. This means that the natural history of cerebral disease in pathophysiological terms is open to study and, in turn, the effects of therapeutic interventions can be monitored. In this way, with the formulation of appropriate clinical research questions, significant advances in the understanding of cerebral disease and its treatment can be expected. Though the clinical results from PET studies are as yet scanty or preliminary, sufficient data exists to indicate that PET is the most promising tool for the exploration of functional and metabolic processes in the central nervous system in vivo.

Brain Diseases↗

Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using 15O and positron emission tomography: theory, procedure, and normal values.

A method is described for quantifying regional cerebral blood flow (rCBF), oxygen extraction (rOER), and oxygen utilization (rCMRO2) in man non-invasively, using inhaled 15O-labeled CO2 and O2 and positron emission tomography. The theoretical considerations and practical aspects are described. The results of rCBF, rCMRO2, and rOER for gray and white matter in normal volunteers are presented. The significance and limitations of the results are discussed. The method appears suitable for the study of human cerebral aerobic metabolism and blood flow under differing physiological conditions and in a wide variety of neurological disorders.

Adult↗

Regional cerebral oxygen utilization and blood flow in normal man using oxygen-15 and positron emission tomography.

Quantitative determination of regional cerebral blood flow (rCBF), regional cerebral oxygen utilization (rCMRO2) and regional oxygen extraction ratio (rOER) was performed in 11 normal volunteers by an oxygen 15 inhalation method and positron emission tomography. Regional values comparable with figures from the literature have been obtained. This non-invasive approach offers the possibility of a simultaneous quantitative evaluation of these physiological parameters in health and disease.

Adult↗

Entropy and cortical activity: information theory and PET findings.

Functional segregation requires convergence and divergence of neuroanatomical connections. Furthermore, the nature of functional segregation suggests that (1) signals in convergent afferents are correlated and (2) signals in divergent efferents are uncorrelated. The aim of this article is to show that this arrangement can be predicted mathematically, using information theory and an idealized model of cortical processing. In theory, the existence of bifurcating axons limits the number of independent output channels from any small cortical region, relative to the number of inputs. An information theoretic analysis of this special (high input:output ratio) constraint indicates that the maximal transfer of information between inputs, to a cortical region, and its outputs will occur when (1) extrinsic connectivity to the area is organized such that the entropy of neural activity in afferents is optimally low and (2) connectivity intrinsic to the region is arranged to maximize the entropy measured at the initial segments of projection neurons. Under the constraints of the model, a low entropy is synonymous with high correlations between axonal firing rates (and vice versa). Consequently this antisymmetric arrangement of functional activity in convergent and divergent connections underlying functional segregation is exactly that predicted by the principle of maximum preservation of information, considered in the context of axonal bifurcation. The hypothesis that firing in convergent afferents is correlated (has low entropy) and spatially coherent was tested using positron emission tomographic measurements of cortical synaptic function in man. This hypothesis was confirmed.

Afferent Pathways↗

Area V5 of the human brain: evidence from a combined study using positron emission tomography and magnetic resonance imaging.

In pursuing our work on the organization of human visual cortex, we wanted to specify more accurately the position of the visual motion area (area V5) in relation to the sulcal and gyral pattern of the cerebral cortex. We also wanted to determine the intersubject variation of area V5 in terms of position and extent of blood flow change in it, in response to the same task. We therefore used positron emission tomography (PET) to determine the foci of relative cerebral blood flow increases produced when subjects viewed a moving checkerboard pattern, compared to viewing the same pattern when it was stationary. We coregistered the PET images from each subject with images of the same brain obtained by magnetic resonance imaging, thus relating the position of V5 in all 24 hemispheres examined to the individual gyral configuration of the same brains. This approach also enabled us to examine the extent to which results obtained by pooling the PET data from a small group of individuals (e.g., six), chosen at random, would be representative of a much larger sample in determining the mean location of V5 after transformation into Talairach coordinates. After stereotaxic transformation of each individual brain, we found that the position of area V5 can vary by as much as 27 mm in the left hemisphere and 18 mm in the right for the pixel with the highest significance for blood flow change. There is also an intersubject variability in blood flow change within it in response to the same visual task. V5 nevertheless bears a consistent relationship, within each brain, to the sulcal pattern of the occipital lobe. It is situated ventrolaterally, just posterior to the meeting point of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus. In position it corresponds almost precisely with Flechsig's Feld 16, one of the areas that he found to be myelinated at birth.

Adult↗

Demonstrating the implicit processing of visually presented words and pseudowords.

This study demonstrates that even when subjects are instructed to perform a nonlinguistic visual feature detection task, the mere presence of words or pseudowords in the visual field activates a widespread neuronal network that is congruent with classical language areas. The implication of this result is that subjects will process words beyond the functional demands of the task. Therefore, contrasting brain activity in a word task that explicitly requires a cognitive function with a word task in which the function is activated implicitly will not necessarily isolate the brain area of interest. Furthermore, in most brain regions, we found that pseudowords, which have unfamiliar phonological associations and no associated semantic association, produce greater activation than words. Greater brain activity associated with pseudowords illustrates that unfamiliar stimuli that are unable to access word associations may activate the neuronal network more strongly than familiar words for which access occurs with ease.

Brain↗

Functional topography: multidimensional scaling and functional connectivity in the brain.

In neuroimaging, functional mapping usually implies mapping function into an anatomical space, for example, using statistical parametric mapping to identify activation foci, or the characterization of distributed changes with spatial modes (eigenimages or principal components) (Friston et al., 1993a). This article is about a complementary approach, namely, mapping anatomy into a functional space. We describe a simple variant of multidimensional scaling (principal coordinates analysis; Gower, 1966) that uses functional connectivity as its metric. The scaling transformation maps anatomy into a functional space. The topography, or proximity relationships, in this space embody the functional connectivity among brain regions. The higher the functional connectivity, the closer the regions. Functional connectivity is defined here as the correlation between remote neurophysiological events. The technique represents a descriptive characterization of anatomically distributed changes in the brain that reveals the structure of corticocortical interactions in terms of functional correlations. To illustrate the approach we have analyzed data from normal subjects and schizophrenic patients obtained with PET during the performance of word generation tasks. In particular, we focus on prefrontotemporal integration in normal subjects and show that, in schizophrenia, the left temporal regions and prefrontal cortex evidence abnormal functional connectivity.

Brain↗

Active representation of shape and spatial location in man.

Neural activity during the delay period of spatial delayed response (DR) and delayed matching (DM) tasks was investigated by positron emission tomography. A distributed cortical system was activated in each condition. The bilateral dorsolateral prefrontal cortex (DLPFC) was activated in the delay period of both tasks; activation was of higher significance on the right in the DR task and the left in the DM task, and extended to the anterolateral prefrontal cortex in the DM condition. Active representation of spatial location in the DR task was associated with co-activation of the medial and lateral parietal cortex and the extrastriate visual cortex. Active representation of shape in the DM task was associated with co-activation of medial and lateral parietal cortex and the inferior temporal cortex. Response-related activity was observed in both tasks. Activation of anterior cingulate, inferior frontal, lateral promotor and rostral inferior parietal cortex was observed in the DR condition, a task characterized by preparation of a movement to a predetermined location. In contrast, preparation to move to an undetermined location in the DM task was associated with activation predominantly in rostral SMA.

Adolescent↗

Plastic transformation of PET images.

A theory and technique are presented that allow nonlinear resampling of positron emission tomography data to remove nonlinear differences in brain shape. The resampling is determined empirically by a function relating the observed image and a desired template. The validity, reliability, and precision of the plastic transformation are compared with linear rescaling alone, within, and between subjects.

Brain↗

Estimating smoothness in statistical parametric maps: variability of p values.

OBJECTIVE: The smoothness parameter that characterises the spatial dependence of pixel values in functional brain images is usually estimated empirically from the data. Since this parameter is essential for the assessment of significant changes in brain activity, it is important to know (a) the variance of its estimator and (b) how this variability affects the results of the ensuing statistical analysis. MATERIALS AND METHODS: In this article, we derive an approximate expression for the variance of the smoothness estimator and investigate the effects of this variability on assessing the significance of cerebral activation in statistical parametric maps using a verbal fluency PET activation experiment. RESULTS: Our results suggest that, for p values around 0.05, the variability in the p value (due to smoothness estimation) is approximately 20%. CONCLUSION: The effect of the assessment of the spatial dependency of the data is far from being negligible, and this suggests a more comprehensive methodology for functional imaging than the one used so far. This work provides a simple tool for taking into account this effect.

Algorithms↗

Studies on cerebral blood flow and oxygen metabolism in patients with established cerebral infarcts undergoing omental transposition.

Regional cerebral blood flow, blood volume, fractional oxygen extraction, and oxygen consumption were measured by positron emission tomography in 4 stroke patients prior to and 6 months following omental transposition surgery. Preoperatively, 3 patients showed the typical picture of established infarction with a matched reduction in flow and oxygen metabolism and a normal oxygen extraction fraction in the symptomatic hemisphere. One patient showed a chronically impaired perfusion reserve with a proportionally greater reduction in flow than oxygen metabolism and a compensatory rise in oxygen extraction ratio. No change in the physiological parameters was demonstrated in the postoperative studies.

Cerebral Infarction↗

Forthergillian Lecture. Imaging human brain function.

The non-invasive brain scanning techniques introduced a quarter of a century ago have become crucial for diagnosis in clinical neurology. They have also been used to investigate brain function and have provided information about normal activity and pathogenesis. They have been used to investigate functional specialization in the brain and how specialized areas communicate to generate complex integrated functions such as speech, memory, the emotions and so on. The phenomenon of brain plasticity is poorly understood and yet clinical neurologists are aware, from everyday observations, that spontaneous recovery from brain lesions is common. An improved understanding of the mechanisms of recovery may generate new therapeutic strategies and indicate ways of modulating mechanisms that promote plastic compensation for loss of function. The main methods used to investigate these issues are positron emission tomography and magnetic resonance imaging (M.R.I.). M.R.I. is also used to map brain structure. The techniques of functional brain mapping and computational morphometrics depend on high performance scanners and a validated set of analytic statistical procedures that generate reproducible data and meaningful inferences from brain scanning data. The motor system presents a good paradigm to illustrate advances made by scanning towards an understanding of plasticity at the level of brain areas. The normal motor system is organized in a nested hierarchy. Recovery from paralysis caused by internal capsule strokes involves functional reorganization manifesting itself as changed patterns of activity in the component brain areas of the normal motor system. The pattern of plastic modification depends in part on patterns of residual or disturbed connectivity after brain injury. Therapeutic manipulations in patients with Parkinson's disease using deep brain stimulation, dopaminergic agents or fetal mesencephalic transplantation provide a means to examine mechanisms underpinning plastic change. Other models of plastic change, such as normal visuospatial learning or re-establishing speech comprehension after cochlear implantation in the deaf illustrate how patterns of brain function adapt over time. Limitations of the scanning techniques and prospects for the future are discussed in relation to new developments in the neuroimaging field.

Brain↗