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Biomedical subjects

R S Frackowiak

Publications and source records attributed to R S Frackowiak.

At least 109 records · Page 6Linked to original sources
PubMed1996

Differential activation of the prefrontal cortex in successful and unsuccessful memory retrieval.

Six subjects underwent PET scans while they performed three versions of a recognition memory test for words and three versions of a control task. In each memory condition, the subjects discriminated between words presented in a prescan study list and words new to the experiment. During the 30 s scanning interval, the ratio of old and new words was 0:20, 4:16 or 16:4, depending on the experimental condition. Outside this interval, the ratio was 50:50 in all three conditions. The requirement in the control task was to discriminate between two character strings, the ratios of which were also manipulated during the 30 s scanning interval. Employing the control task as a covariate, analysis with statistical parametric mapping revealed that regional cerebral blood flow (rCBF) covaried with increasing density of old items in three regions of prefrontal cortex: right dorsolateral [Brodmann area (BA) 9/46], right medial (BA 32/8) and bilateral frontopolar cortex (BA 10). It is concluded that the prefrontal cortex, especially in the right hemisphere, is more active when a retrieval attempt succeeds than when it fails. This finding is consistent with the idea that the prefrontal cortex supports processes that operate selectively on the products of memory retrieval.

Adult↗
PubMed1996

Comparison of methods for analysis of clinical [11C]raclopride studies.

Five different methods for the estimation of the binding potential, a measure of Bmax/Kd, of [11C]raclopride in human striatum were compared using data from a dose ranging study of the neuroleptic CP-88,059-01. Binding potential was estimated indirectly, from distribution volumes in striatum and cerebellum, using both single- and two-tissue compartment models with a metabolite-corrected plasma curve as input function. The two-tissue compartment model was also used for a direct estimate of the binding potential. In addition, a direct estimate was obtained from the reference tissue compartment model using the cerebellum as indirect input function. Finally, an estimate of binding potential was calculated from the ratio of striatum over cerebellum counts at late times after injection. The estimates of striatum binding potential from all methods, except the direct determination using a two-tissue compartment model with metabolite-corrected plasma input function, correlated with each other. Use of an average metabolite correction resulted in only a small reduction in accuracy in this series of normal subjects. The reference tissue model provided estimates of the binding potential with the same sensitivity for detecting changes as those methods that required a metabolite-corrected plasma input function. This indicates that for routine analysis of clinical [11C]raclopride studies, no arterial cannulation is required. The range of normal values was significantly less variable with the reference tissue method than when simple striatum-to-cerebellum ratios were used.

Adult↗
PubMed1996

A critique of a new analysis proposed for functional neuroimaging.

Methods for analysing functional imaging data have evolved rapidly over the last ten years. Standardized techniques based on formal mathematical and statistical theory and rigorous empirical validation have been proposed to facilitate comparisons of biological results between laboratories. This paper examines an image analysis technique that appears to identify unexpectedly large numbers of activated brain areas for the data collected. It concludes that the method may not adequately control for false positives, rendering interpretation of the functional anatomy difficult.

Brain↗
PubMed1996

Comparison of regional cerebral blood flow with transcranial magnetic stimulation at different forces.

This study's objective was to investigate regional cerebral blood flow (rCBF) within the primary motor cortex (M1) and to compare it with thresholds of transcranial magnetic stimulation (TMS) and electromyographic recordings during exertion of different force levels with the right index finger. Quantitative electromyographic recordings, TMS, and positron emission tomography scans were performed while five and six volunteers, respectively, pressed a Morse key repetitively or with constant force with the right hand at five different force levels: 5, 10, 20, 40, and 60% of the individual's maximum voluntary contraction (MVC). Although at 5% MVC muscle activity was restricted to the first dorsal interosseus muscle, superficial finger flexors, and extensors, there was progressive involvement of proximal muscles during finger flexion with increasing force. rCBF increased logarithmically in the contralateral M1 with increasing force. In ipsilateral M1, rCBF decreased at 5% MVC and then increased logarithmically at higher force levels. TMS thresholds in the contralateral hemisphere declined logarithmically to reach a plateau at high force levels. The threshold in the ipsilateral hemisphere decreased slightly at high force levels. The logarithmic increase of rCBF and decrease of TMS thresholds in the contralateral hemisphere suggest related underlying physiological phenomena; increased cortical synaptic activity and increased excitability. It suggested that the pronounced ipsilateral rCBF alterations reflect transcallosal inhibition and are more prominent during repetitive movements (as used in the positron emission tomography study) than during the generation of a constant force (as exerted during TMS).

Adult↗
PubMed1996

Human cerebral activity with increasing inspiratory force: a study using positron emission tomography.

Human cerebral activity with increasing inspiratory force: a study using positron emission tomography. J. Appl. Physiol. 81(3): 1295-1305, 1996.--The major aim of this study was to use positron emission tomography (PET) to assess dose-dependent effects of inspiratory loads on relative regional cerebral blood flow as an indication of neuronal activation and recruitment. Six normal men underwent H2 15O-PET scanning during unloaded breathing and with external inspiratory loads (generating mouth pressures of -5, -10, and -15 cmH2O); positive-pressure ventilation against relaxed respiratory muscles acted as control. During unloaded breathing, the supplementary motor area was significantly activated. With the addition of the smallest load, activations also occurred in the right premotor area and bilaterally in the superolateral motor cortex (MI) in areas previously shown to be activated with deeper breathing. There was little further change in these areas with greater loads. Additional force-related activations occurred in the inferolateral sensorimotor cortex, parietal cortex, and midbrain/hypothalamus. The results suggest that volitionally induced increases in inspiratory muscle force are achieved via a complex integration of neuronal activations in cortical and subcortical regions associated with motor control.

Adult↗
PubMed1996

The neural correlates of inner speech and auditory verbal imagery in schizophrenia: relationship to auditory verbal hallucinations.

BACKGROUND: Auditory verbal hallucinations are thought to arise from the disordered monitoring of inner speech (thinking in words). We tested the hypothesis that a predisposition to verbal auditory hallucinations would be associated with an abnormal pattern of brain activation during tasks which involved the generation and monitoring of inner speech. METHOD: The neural correlates of tasks which engaged inner speech and auditory verbal imagery were examined using positron emission tomography in (a) schizophrenic patients with a strong predisposition to auditory verbal hallucinations (hallucinators), (b) schizophrenic patients with no history of hallucinations (nonhallucinators), and (c) normal controls. RESULTS: There were few between-group differences in activation during the inner speech task. However, when imagining sentences spoken in another person's voice, which entails the monitoring of inner speech, hallucinators showed reduced activation in the left middle temporal gyrus and the rostral supplementary motor area, regions which were strongly activated by both normal subjects and nonhallucinators (P < 0.001). Conversely, when nonhallucinators imagined speech, they differed from both hallucinators and controls in showing reduced activation in the right parietal operculum. CONCLUSIONS: A predisposition to verbal hallucinations in schizophrenia is associated with a failure to activate areas implicated in the normal monitoring of inner speech, whereas the absence of a history of hallucinations may be linked to reduced activation in an area concerned with verbal prosody.

Adult↗
PubMed1995

Hyperpnoea during and immediately after exercise in man: evidence of motor cortical involvement.

1. The neurophysiological basis for the increase in breathing associated with exercise remains obscure. The present study uses positron emission tomography (PET) to measure relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during and immediately following exercise. 2. Male volunteers underwent H2(15)O PET scanning during two complementary studies. Firstly, six subjects performed right leg exercise, adequate to increase oxygen uptake 2.5-fold. Secondly, five different subjects were scanned immediately following bicycle exercise (adequate to increase oxygen uptake 5-fold) while breathing was still increased. In each study, as a control, scanning was also performed during matched passive isocapnic positive pressure ventilation; additionally, in the first study, passive right leg movement was performed. 3. Increases in relative rCBF were obtained in each individual and co-registered with their magnetic resonance image of the brain defining individual gyral morphology. 4. During exercise, individual and group analysis revealed significant relative rCBF increases in the left and right superomedial primary motor cortex (the motor cortical 'leg' areas) and also in the left and right superolateral primary motor cortex in areas previously shown to be associated with volitional breathing. After exercise, there was no significant increase in relative rCBF in the superomedial areas but such increases were still present bilaterally in the superolateral areas which had been activated during the exercise. Other relative rCBF increases were also found, both during and after exercise, in cortical and subcortical areas known to be involved in motor control. 5. The results from PET scans during and after exercise, taken together, provide evidence for motor cortical involvement in the exercise-related hyperpnoea in man.

Adult↗
PubMed1995

Dopaminergic modulation of impaired cognitive activation in the anterior cingulate cortex in schizophrenia.

Dopaminergic dysregulation remains an empirical cornerstone for theories concerning the causation of schizophrenia. Evidence for a dopamine system dysfunction in schizophrenia includes the psychosis-inducing effects of dopaminergic agonists and the antipsychotic potency of dopaminergic antagonists. Here we use positron emission tomography (PET) to examine the regulatory role of dopamine on cortical function in normal subjects and unmedicated schizophrenic patients. Using a factorial experimental design, we compared the effect of dopaminergic manipulation with apomorphine on a neural response to a cognitive task. In the schizophrenic patients, relative to controls, an impaired cognitive activation of the anterior cingulate cortex was significantly modulated by a manipulation of dopaminergic neurotransmission. Thus, after apomorphine, the schizophrenic subjects displayed a significantly enhanced cognitive activation of the anterior cingulate cortex relative to the controls. These data provide in vivo evidence that an impaired cognitive-task-induced activation of the anterior cingulate cortex in schizophrenic patients can be significantly modulated by a dopaminergic manipulation.

Adult↗
PubMed1995

Evidence for limbic system activation during CO2-stimulated breathing in man.

1. The role of supra-brainstem structures in the ventilatory response to inhaled CO2 is unknown. The present study uses positron emission tomography (PET), with infusion of H2(15)O, to measure changes in relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during CO2-stimulated breathing (CO2-SB) in awake man. 2. Five male volunteers were scanned during CO2-SB (mean +/- S.E.M.; end-tidal PCO2, 50.3 +/- 1.7 mmHg; respiratory frequency, 16.4 +/- 2.7 min-1; tidal volume, 1.8 +/- 0.2 l). As control, scans were performed during 'passive' isocapnic (elevated fraction of inspired CO2) positive pressure ventilation (end-tidal PCO2, 38.4 +/- 1.0 mmHg; respiratory frequency, 15.5 +/- 2.2 min-1; tidal volume, 1.6 +/- 0.2 l). With CO2-SB, all subjects reported dyspnoea. 3. The anatomical locations of the increases in relative rCBF (CO2-SB versus control) were obtained using magnetic resonance imaging. 4. Group analysis identified neuronal activation within the upper brainstem, midbrain and hypothalamus, thalamus, hippocampus and parahippocampus, fusiform gyrus, cingulate area, insula, frontal cortex, temporo-occipital cortex and parietal cortex. No neuronal activation was seen within the primary motor cortex (at sites previously shown to be associated with volitional breathing). 5. These results suggest neuronal activation within the limbic system; this activation may be important in the sensory and/or motor respiratory responses to hypercapnia in awake man.

Adult↗
PubMed1995

Abnormal monitoring of inner speech: a physiological basis for auditory hallucinations.

Auditory verbal hallucinations ("voices") are thought to arise from a disorder of inner speech (thinking in words). We examined the neural correlates of tasks which involve inner speech in subjects with schizophrenia who hear voices (hallucinators), subjects with schizophrenia who do not (nonhallucinators), and normal controls. There were no differences between hallucinators and controls in regional cerebral blood flow during thinking in sentences. However, when imagining sentences being spoken in another person's voice--which entails both the generation and monitoring of inner speech--hallucinators had a normal left frontal response, but reduced activation in the left middle temporal gyrus and the rostral supplementary motor area, regions which were activated by both normal subjects and nonhallucinators (p < 0.001). These findings suggest that a predisposition to verbal hallucinations is associated with a failure to activate areas concerned with the monitoring of inner speech.

Adult↗
PubMed1995

Modulation of conscious experience by peripheral sensory stimuli.

Lack of awareness of touch associated with brain damage may transiently recover after stimulation of the vestibular system. We used positron emission tomographic regional cerebral blood flow measurements to study the neurophysiological effect of vestibular stimulation on touch imperception in a subject with a right brain lesion. We tested the hypothesis that the vestibular system aids conscious tactile perception by introducing a bias in the neural system subserving body representation. We show that in normal subjects touch and vestibular signals share projections to the putamen, insula, somatosensory area II, premotor cortex and supramarginal gyrus. In our patient a subset of these regions (right putamen and insula) was spared by the lesion and was maximally active when touch and vestibular stimulations were combined. These results support the suggestion that our phenomenological consciousness is associated with activation in circumscribed brain areas specific to the particular sensation of which we are aware.

Adult↗
PubMed1995

Deficits in cerebral glucose metabolism demonstrated by positron emission tomography in individuals at risk of familial Alzheimer's disease.

In order to establish whether positron emission tomography (PET) can identify metabolic changes in Alzheimer's disease at a presymptomatic stage, we have examined 24 asymptomatic at risk individuals from families with Alzheimer's disease. A significant reduction in global cerebral metabolic rate for glucose was found when compared with 16 age-matched controls. There was also a focal, parieto-temporal deficit similar to, although less extensive than, that found in 18 symptomatic individuals from familial Alzheimer's disease (FAD) pedigrees. Follow up of this cohort will establish whether these metabolic changes relate to a presymptomatic stage of the disease.

Adult↗
PubMed1995

Analysis of fMRI time-series revisited.

This paper presents a general approach to the analysis of functional MRI time-series from one or more subjects. The approach is predicated on an extension of the general linear model that allows for correlations between error terms due to physiological noise or correlations that ensue after temporal smoothing. This extension uses the effective degrees of freedom associated with the error term. The effective degrees of freedom are a simple function of the number of scans and the temporal auto correlation function. A specific form for the latter can be assumed if the data are smoothed, in time, to accentuate hemodynamic responses with a neural basis. This assumption leads to an expedient implementation of a flexible statistical framework. The importance of this small extension is that, in contradistinction to our previous approach, any parametric statistical analysis can be implemented. We demonstrate this point using a multiple regression analysis that tests for effects of interest (activations due to word generation), while taking explicit account of some obvious confounds.

Arousal↗
PubMed1995

Retinotopic maps in human prestriate visual cortex: the demarcation of areas V2 and V3.

We have used PET (positron emission tomography) to chart the mapping of the retina in human occipital visual cortex and hence to locate the secondary and tertiary visual areas, V2 and V3. A group of four non-selected male volunteers was presented with dynamic stimuli that were aligned with either the vertical or the right horizontal meridians (VM or HM) from 0 degree to 29 degrees eccentricity; the vertical stimuli were restricted to either the inferior or the superior hemifields. PET scans were performed using intravenous infusion of H215O and a Siemens-CTI 953B PET scanner with 3D data acquisition. Subjects received 18 scans, divided equally among the right HM, the superior VM, and the inferior VM. Data were analyzed with SPM software. The group average result confirmed our experimental hypothesis that human occipital visual cortex has retinotopic maps similar to those of the macaque monkey. Thus human areas V2 and V3 can be defined on the basis that the border between them is formed by the HM and that the outer border of V3 is demarcated by a second representation of the VM that runs approximately parallel to the primary representation of the VM at the V1/V2 border. Furthermore, as in many mammals, the extrastriate representation of the HM is "split", such that the superior contralateral quadrant is mapped in lower V2 and V3, occupying the ventral surface of human cortex, and the inferior contralateral quadrant is mapped in upper V2 and V3, which extend over the lateral and medial surfaces of each hemisphere. After stereotaxic normalization, the position of V3 defined by retinal topography was found to correspond to that surmised from our previous PET studies employing moving stimuli.

Adult↗
PubMed1995

Characterizing evoked hemodynamics with fMRI.

We describe an implementation of the general linear model that facilitates the characterization of evoked hemodynamic responses to sensorimotor or cognitive processing, when the exact form of these responses is not known. The importance of this approach is that one can test for differential responses among tasks that may elude more conventional analyses. In particular, we suppose that an evoked response has early and late components and that a differential response may involve (i) both components to the same degree, as in a conventional "activation" or (ii) differential expression of the early and late components in two tasks, as might be seen in differential adaptation, or differences associated with the tasks (e.g., requiring and not requiring sustained attention). Using this approach we were able to demonstrate that the anterior cingulate differentiates, in terms of its response, between two motor tasks that did and did not require sustained attention. This differential response was observed even though there was no classical "activation" (i.e., there was no difference in the mean activity associated with the two conditions). It is suggested that these demonstration results point to the possibility of making greater use of the temporal resolution afforded by fast fMRI techniques.

Arousal↗
PubMed1995

Characterizing dynamic brain responses with fMRI: a multivariate approach.

In this paper we present a multivariate analysis of evoked hemodynamic responses and their spatiotemporal dynamics as measured with fast fMRI. This analysis uses standard multivariate statistics (MANCOVA) and the general linear model to make inferences about effects of interest and canonical variates analysis (CVA) to describe the important features of these effects. We have used these techniques to characterize the form of hemodynamic transients that are evoked during a cognitive or sensorimotor task. In particular we do not assume that the neural or hemodynamic response reaches some "steady state" but acknowledge that these physiological changes could show profound task-dependent adaptation and time-dependent changes during the task. To address this issue we have modeled hemodynamic responses using appropriate temporal basis functions and estimated their exact form within the general linear model using MANCOVA. We do not propose that this analysis is a particularly powerful way to make inferences about functional specialization (or more generally functional anatomy) because it only provides statistical inferences about the distributed (whole brain) responses evoked by different conditions. However, its application to characterizing the temporal aspects of evoked hemodynamic responses reveals some compelling and somewhat unexpected perspectives on transient but stereotyped responses to changes in cognitive or sensorimotor processing. The most remarkable observation is that these responses can be biphasic and show profound differences in their form depending on the extant task or condition. Furthermore these differences can be seen in the absence of changes in mean signal.

Arousal↗
PubMed1995

The mind's eye--precuneus activation in memory-related imagery.

We examined brain activity associated with visual imagery at episodic memory retrieval using positron emission tomography (PET). Twelve measurements of regional cerebral blood flow (rCBF) were taken in six right-handed, healthy, male volunteers. During six measurements, they were engaged in the cued recall of imageable verbal paired associates. During the other six measurements, they recalled nonimageable paired associates. Memory performance was equalized across all word lists. The subjects' use of an increased degree of visual imagery during the recall of imageable paired associates was confirmed using subjective rating scales after each scan. Memory-related imagery was associated with significant activation of a medial parietal area, the precuneus. This finding confirms a previously stated hypothesis about the precuneus and provides strong evidence that it is a key part of the neural substate of visual imagery occurring in conscious memory recall.

Adult↗