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Biomedical subjects

K J Friston

Publications and source records attributed to K J Friston.

At least 19 recordsLinked to original sources
PubMed1997

Neural responses to salient visual stimuli.

The neural mechanisms involved in the selective processing of salient or behaviourally important stimuli are uncertain. We used an aversive conditioning paradigm in human volunteer subjects to manipulate the salience of visual stimuli (emotionally expressive faces) presented during positron emission tomography (PET) neuroimaging. Increases in salience, and conflicts between the innate and acquired value of the stimuli, produced augmented activation of the pulvinar nucleus of the right thalamus. Furthermore, this pulvinar activity correlated positively with responses in structures hypothesized to mediate value in the brain right amygdala and basal forebrain (including the cholinergic nucleus basalis of Meynert). The results provide evidence that the pulvinar nucleus of the thalamus plays a crucial modulatory role in selective visual processing, and that changes in perceptual salience are mediated by value-dependent plasticity in pulvinar responses.

Adult↗
PubMed1997

Analysis of dynamic radioligand displacement or "activation" studies.

We present a simple way of assessing dynamic or time-dependent changes in displacement during single-subject radioligand positron emission tomography (PET) activation studies. The approach is designed to facilitate dynamic activation studies using selective radioligands. These studies are, in principle, capable of characterising functional neurochemistry by analogy with the study of functional neuroanatomy using rCBF activation studies. The proposed approach combines time-dependent compartmental models of tracer kinetics and the general linear model used in statistical parametric mapping. This provides for a comprehensive, voxel-based and data-led assessment of regionally specific effects. The statistical model proposed in this paper is predicated on a single-compartment model extended to allow for time-dependent changes in kinetics. We have addressed the sensitivity and specificity of the analysis, as it would be used operationally, by applying the analysis to 11C-Flumazenil dynamic displacement studies. The activation used in this demonstration study was a pharmacological (i.v. midazolam) challenge, 30 min after administration of the tracer. We were able to demonstrate, and make statistical inferences about, regional increases in k2 (or decreases in the volume of distribution) in prefrontal and other cortical areas.

Activation Analysis↗
PubMed1997

Neuroanatomical correlates of externally and internally generated human emotion.

OBJECTIVE: Positron emission tomography was used to investigate the neural substrates of normal human emotional and their dependence on the types of emotional stimulus. METHOD: Twelve healthy female subjects underwent 12 measurements of regional brain activity following the intravenous bolus administration of [15O]H2O as they alternated between emotion-generating and control film and recall tasks. Automated image analysis techniques were used to characterize and compare the increases in regional brain activity associated with the emotional response to complex visual (film) and cognitive (recall) stimuli. RESULTS: Film- and recall-generated emotion were each associated with significantly increased activity in the vicinity of the medial prefrontal cortex and thalamus, suggesting that these regions participate in aspects of emotion that do not depend on the nature of the emotional stimulus. Film-generated emotion was associated with significantly greater increases in activity bilaterally in the occipitotemporparietal cortex, lateral cerebellum, hypothalamus, and a region that includes the anterior temporal cortex, amygdala, and hippocampal formation, suggesting that these regions participate in the emotional response to certain exteroceptive sensory stimuli. Recall-generated sadness was associated with significantly greater increases in activity in the vicinity of the anterior insular cortex, suggesting that this region participates in the emotional response to potentially distressing cognitive or interoceptive sensory stimuli. CONCLUSIONS: While this study should be considered preliminary, it identified brain regions that participate in externally and internally generated human emotion.

Adult↗
PubMed1996

The neural regions sustaining object recognition and naming.

This positron emission tomography study dissociates the neural correlates of object recognition and naming. Stimuli comprised coloured outline drawings of objects and coloured nonsense shapes. Subjects either viewed or explicitly named objects, similarly they viewed or named the colour of the shapes. Activations common to object and colour naming were identified by contrasting the explicit naming conditions (objects and colours) with the control (viewing) conditions. Activations associated with object recognition were identified by contrasting both object conditions (naming and viewing) with both shape conditions and activations specific to object or colour naming were identified by contrasting object naming (relative to object viewing) with colour naming (relative to shape viewing). The results associate: (i) object recognition with left middle occipital and bilateral anterior temporal cortices; (ii) modality independent naming with left posterior basal temporal lobe and the left prefrontal cortex; (iii) areas specific to object naming with left temporal extrasylvian regions, left anterior insula and right cerebellum; and (iv) areas specific to colour naming with left posterior lingual and fusiform gyri and midline cerebellum. These results are discussed in relation to previous neuroimaging and neuropsychological findings.

Adult↗
PubMed1996

Local and distributed effects of apomorphine on fronto-temporal function in acute unmedicated schizophrenia.

We used positron emission tomography (PET) to measure brain activity in healthy control subjects and unmedicated patients with schizophrenia. Subjects were scanned in the context of a combined psychological and pharmacological challenge, and we examined the effects of apomorphine, a drug acting on dopamine receptors, on brain systems engaged by a paced verbal fluency task. This factorial design enabled comparison of control subjects and schizophrenics in terms of the activations engendered by the cognitive task and the pharmacological challenge and the interaction of the two. We report a failure of cognitive task-related activation in anterior cingulate cortex and of task-related deactivation in the left superior temporal gyrus in the schizophrenic subjects. Compared with controls, the impaired cingulate activation was significantly reversed by apomorphine. Additionally, there was a trend for the abnormal fronto-temporal pattern of activation in schizophrenic subjects to be normalized by the drug. Overall, in schizophrenic subjects the effect of apomorphine, which we interpret in terms of a net dopaminergic antagonism, was to modify the brain activity, making the pattern more akin to that seen in control subjects. The results indicate both a regionally specific abnormality of brain function in schizophrenia and an abnormal pattern of fronto-temporal interactions.

Acute Disease↗
PubMed1996

Movement-related effects in fMRI time-series.

This paper concerns the spatial and intensity transformations that are required to adjust for the confounding effects of subject movement during functional MRI (fMRI) activation studies. An approach is presented that models, and removes, movement-related artifacts from fMRI time-series. This approach is predicated on the observation that movement-related effects are extant even after perfect realignment. Movement-related effects can be divided into those that are a function of position of the object in the frame of reference of the scanner and those that are due to movement in previous scans. This second component depends on the history of excitation experienced by spins in a small volume and consequent differences in local saturation. The spin excitation history thus will itself be a function of previous positions, suggesting an autoregression-moving average model for the effects of previous displacements on the current signal. A model is described as well as the adjustments for movement-related components that ensue. The empirical analyses suggest that (in extreme situations) over 90% of fMRI signal can be attributed to movement, and that this artifactual component can be successfully removed.

Artifacts↗
PubMed1996

Hearing and saying. The functional neuro-anatomy of auditory word processing.

The neural systems involved in hearing and repeating single words were investigated in a series of experiments using PET. Neuropsychological and psycholinguistic studies implicate the involvement of posterior and anterior left perisylvian regions (Wernicke's and Broca's areas). Although previous functional neuroimaging studies have consistently shown activation of Wernicke's area, there has been only variable implication of Broca's area. This study demonstrates that Broca's area is involved in both auditory word perception and repetition but activation is dependent on task (greater during repetition than hearing) and stimulus presentation (greater when hearing words at a slow rate). The peak of frontal activation in response to hearing words is anterior to that associated with repeating words; the former is probably located in Brodmann's area 45, the latter in Brodmann's area 44 and the adjacent precentral sulcus. As Broca's area activation is more subtle and complex than that in Wernicke's area during these tasks, the likelihood of observing it is influenced by both the study design and the image analysis technique employed. As a secondary outcome from the study, the response of bilateral auditory association cortex to 'own voice' during repetition was shown to be the same as when listening to "other voice' from a prerecorded tape.

Auditory Perception↗
PubMed1996

Cerebral benzodiazepine receptors in hippocampal sclerosis. An objective in vivo analysis.

We objectively delineated the extent of abnormalities in central benzodiazepine receptor (cBZR) binding using [11C]flumazenil (FMZ)-PET and high resolution volumetric MRI in 12 patients with mesial temporal lobe epilepsy (mTLE) associated with unilateral hippocampal sclerosis, who underwent presurgical evaluation and subsequent temporal lobe surgery. We compared parametric 3D-images of regional cerebral [11C]FMZ volume of distribution (Vd) obtained from individuals and groups of patients with [11C]FMZ-Vd from a group of 17 healthy controls using statistical parametric mapping (SPM). The [12C]FMZ-Vd was significantly reduced (P < 0.001) in the affected hippocampus in the group of 12 patients with unilateral hippocampal sclerosis. Analysis of individual patients reflected the group finding and there was no significant abnormality of cBZR binding outside the hippocampus in any patient. We conclude that SPM is an useful objective method for detecting changes in regional cerebral [11C]FMZ binding and that in patients with mTLE and unilateral hippocampal sclerosis reduction of cBZR binding is restricted to the area of hippocampal sclerosis with no abnormalities being detected in the temporal neocortex or elsewhere in the neocortex.

Adult↗
PubMed1996

Theoretical neurobiology and schizophrenia.

This chapter addresses the idea that schizophrenia is a 'disconnection syndrome' from a theoretical and computational perspective. The distinction between anatomical and functional connectivity is reviewed and used as a framework to introduce empirical and computational evidence that schizophrenia involves, at some level, a disintegration of neuronal interactions. The chapter concludes with an example of computational neuroscience that relates observations on the dimensional complexity of neuronal dynamics in schizophrenia to the disconnection hypothesis.

Brain↗
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↗
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

Neuronal transients.

A recent letter to Nature (Vaadia et al. Nature, Lond. 373, 515-518 (1995)) presented compelling results concerning neuronal interactions in monkey cortex. Vaadia et al. made two fundamental points: (i) it is possible that cortical function is mediated by dynamic modulation of coherent firing among neurons; and (ii) these time-dependent changes in correlations can emerge without modulation of firing rates. These observations have severe implications for models of neural coding and empirical approaches that are based on firing rates (e.g. neuroimaging). This communication presents a simpler explanation for the results presented in Vaadia et al., by noting they are consistent with the correlated expression of stereotyped neuronal transients following (or preceding) a salient event. This re-formulation is important because: (i) correlations measured in terms of transients are not time-dependent, allowing prevailing models of neural coding to be 'reinstated'; and (ii) it suggests a powerful analysis based on singular value decomposition of firing rates.

Animals↗
PubMed1995

The effect of the muscarinic antagonist scopolamine on regional cerebral blood flow during the performance of a memory task.

Scopolamine, a muscarinic antagonist, impairs memory performance in both humans and animals. In this study, repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers whilst performing auditory verbal memory tasks, before and after the administration of scopolamine (0.4 mg s.c.) or placebo. Compared to placebo, scopolamine increased blood flow in the lateral occipital cortex bilaterally and the left orbitofrontal region. Scopolamine decreased rCBF in the region of the right thalamus, the precuneus and the right and left lateral premotor areas. Scopolamine attenuated memory-task-induced increases of rCBF in the left and right prefrontal cortex and the right anterior cingulate region. These data suggest that acute blockade of cholinergic neurotransmission affects diverse brain areas, including components of the visual and motor systems, and, in addition, modulates memory task activations at distinct points in a distributed network for memory function.

Adult↗
PubMed1995

Activation of human hippocampal formation during memory for faces: a PET study.

Using positron emission tomography, we examined cerebral blood flow changes in human subjects whilst engaged in the visual processing of face stimuli. A task requiring anterograde memory of faces was compared with a control task involving simple gender classification--considered an automatic process that did not require any significant memory component. A second task requiring recognition of famous politicians' faces, and therefore involving long-term "semantic" memory, was also contrasted with the control task. To identify brain regions associated with primary visual processing of the face we compared all tasks against a control population scanned with eyes closed. Our results indicate--(1) The involvement of bilateral lingual/fusiform gyri and the right parahippocampal gyrus in addition to striate cortex in primary visual processing of the face; (2) the involvement of the left hippocampal gyrus in both types of memory; (3) a relative decrease in local cerebral blood flow in the inferior parietal lobules in long-term "semantic" memory. In addition, both memory tasks resulted in a suppression of cerebral blood flow in the left superior temporal cortex. We conclude that right hippocampal regions are involved in a largely automatic, primary processing of faces, while left hippocampal regions are additionally involved when explicit memory for faces is required.

Adult↗
PubMed1995

Regional brain activity in chronic schizophrenic patients during the performance of a verbal fluency task.

BACKGROUND: This study examined the pattern of cerebral blood flow observed in chronic schizophrenic patients while they performed a paced verbal fluency task. Such tasks engage a distributed brain system associated with willed action. Since willed action is impaired in many chronic schizophrenic patients we hypothesised that task performance would be associated with an abnormal pattern of blood flow. METHOD: Positron emission tomography (PET) was applied to 18 chronic schizophrenic patients stratified into three groups on the basis of verbal fluency performance and current symptoms. Regional cerebral blood flow (rCBF) was measured while the patients performed (a) verbal fluency, (b) word categorisation, and (c) word repetition. Results were compared with six normal controls matched for age, sex and premorbid IQ. Analysis was restricted to six brain regions previously identified in studies of normal volunteers. RESULTS: In five brain areas, including the left dorsolateral prefrontal cortex, the patients showed the same pattern of activation as control subjects. However, in the left superior temporal cortex, all patient groups failed to show the normal decrease in blood flow when verbal fluency was compared with word repetition. CONCLUSION: These observations suggest that (a) chronic schizophrenic patients can show a normal magnitude of frontal activation when matched for performance with controls, and (b) they fail to show the expected reductions of activity in the superior temporal cortex. This latter result may reflect abnormal functional connectivity between frontal and temporal cortex.

Adult↗
PubMed1995

Schizophrenia: a disconnection syndrome?

We review the evidence of pathophysiological changes in the prefrontal and temporal cortices of schizophrenic subjects and of abnormal integration of the physiological dynamics in these two regions. The argument we develop is that some schizophrenic phenomena are best understood in terms of abnormal interactions between different areas, not only at the levels of physiology and functional anatomy, but at the level of cognitive and sensorimotor functioning. We discuss recent functional imaging evidence suggesting abnormal prefronto-temporal interactions in relation to a psychological analysis of experiential symptoms in schizophrenia. Cortico-cortical interactions have been assessed in terms of functional connectivity and eigenimages, using time series of neurophysiological data obtained with positron emission tomography. The results of these analyses suggest that there is a profound disruption of large-scale prefronto-temporal interactions in schizophrenia. These disruptions are particularly relevant if one considers that many positive symptoms of schizophrenia reflect a failure to integrate intrinsically generated behaviour and concurrent perception.

Brain Mapping↗
PubMed1995

Functional MR imaging correlations with positron emission tomography. Initial experience using a cognitive activation paradigm on verbal working memory.

The most established functional MR imaging technique for activation studies relies on a T2*-weighted contrast. This signal arises primarily from a blood oxygen level dependent contrast generated by an imbalance between the increase in regional cerebral blood flow and oxygen metabolism in the brain during activation. As predicted by theory, the percentage signal changes observed in functional MR imaging experiments are considerably smaller than those detected by positron emission tomography, which directly measures regional cerebral blood flow as an index of neuronal activity. Cross-validation of functional MR imaging with an established technique such as positron emission tomography would be extremely valuable for determining the correlation between functional MR image signal change and regional cerebral blood flow change and for assessing the sensitivity of the functional MR imaging technique. The authors report on such cross-validation experiments in three subjects challenged with a verbal working memory task and show that satisfactory replication of positron emission tomography results with functional MR imaging was achieved in two subjects. Limitations owing to magnetic field strength used and single-slice sampling may have contributed to the lack of signal detection in the case where no reliable activation pattern was detected with functional MR imaging.

Adult↗