Biomedical subjects

C D Frith

Publications and source records attributed to C D Frith.

At least 145 records · Page 8Linked to original sources

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

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↗

PubMed1995

A voxel-based method for the statistical analysis of gray and white matter density applied to schizophrenia.

We describe a novel technique for characterizing regional cerebral gray and white matter differences in structural magnetic resonance images by the application of methods derived from functional imaging. The technique involves automatic scalp-editing of images followed by segmentation, smoothing, and spatial normalization to a symmetrical template brain in stereotactic Talairach space. The basic idea is (i) to convert structural magnetic resonance image data into spatially normalized images of gray (or white) matter density, effected by segmenting the images and smoothing, and then (ii) to use Statistical Parametric Mapping to make inferences about the relationship between gray (or white) matter density and symptoms (or other pathophysiological measures) in a regionally specific fashion. Because the whole brain sum of gray (or white) matter indices is treated as a confound, the analysis reduces to a characterization of relative gray (or white) matter density on a voxel by voxel basis. We suggest that this is a powerful approach to voxel-based statistical anatomy. Using the technique, we constructed maps of the regional cerebral gray and white matter density correlates of syndrome scores (distinct psychotic symptoms) in a group of 15 schizophrenic patients. There was a negative correlation between the score for the reality distortion syndrome and regional gray matter density in the left superior temporal lobe (P = 0.01) and regional white matter density in the corpus callosum (P < 0.001). These abnormalities may be associated with functional changes predisposing to auditory hallucinations and delusions. This method permits the detection of structural differences within the entire brain (as opposed to selected regions of interest) and may be of value in the investigation of structural gray and white matter abnormalities in a variety of brain diseases.

Adult↗

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

Other minds in the brain: a functional imaging study of "theory of mind" in story comprehension.

The ability of normal children and adults to attribute independent mental states to self and others in order to explain and predict behaviour ("theory of mind") has been a focus of much recent research. Autism is a biologically based disorder which appears to be characterised by a specific impairment in this "mentalising" process. The present paper reports a functional neuroimaging study with positron emission tomography in which we studied brain activity in normal volunteers while they performed story comprehension tasks necessitating the attribution of mental states. The resultant brain activity was compared with that measured in two control tasks: "physical" stories which did not require this mental attribution, and passages of unlinked sentences. Both story conditions, when compared to the unlinked sentences, showed significantly increased regional cerebral blood flow in the following regions: the temporal poles bilaterally, the left superior temporal gyrus and the posterior cingulate cortex. Comparison of the "theory of mind" stories with "physical" stores revealed a specific pattern of activation associated with mental state attribution: it was only this task which produced activation in the medial frontal gyrus on the left (Brodmann's area 8). This comparison also showed significant activation in the posterior cingulate cortex. These surprisingly clear-cut findings are discussed in relation to previous studies of brain activation during story comprehension. The localisation of brain regions involved in normal attribution of mental states and contextual problem solving is feasible and may have implication for the neural basis of autism.

Adolescent↗

PubMed1995

Schizophrenia, symptomatology and social inference: investigating "theory of mind" in people with schizophrenia.

It has been proposed that certain psychotic symptoms associated with schizophrenia reflect a deficit in the ability to appreciate other people's mental states (Frith, 1992). This notion is tested using a newly devised task examining the capacity to infer intentions behind indirect speech. The findings support the notion that some patients with schizophrenia have difficulties with tasks requiring 'theory of mind' skills and that this deficiency is symptom specific. The findings are discussed with reference to the cognitive skills which may be involved in the performance of tasks requiring social inferences.

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

Brain systems for encoding and retrieval of auditory-verbal memory. An in vivo study in humans.

Long-term auditory-verbal memory comprises, at a neuropsychological level, a number of distinct cognitive processes. In the present study we determined the brain systems engaged during encoding (experiment 1) and retrieval (experiment 2) of episodic auditory-verbal material. In the separate experiments, PET measurements of regional cerebral blood flow (rCBF), an index of neural activity, were performed in normal volunteers during either the encoding or the retrieval of paired word associates. In experiment 1, a dual task interference paradigm was used to isolate areas involved in episodic encoding from those which would be concurrently activated by other cognitive processes associated with the presentation of paired associates, notably priming. In experiment 2, we used the cued retrieval of paired associates from episodic or from semantic memory in order to isolate the neural correlates of episodic memories. Encoding of episodic memory was associated with activation of the left prefrontal cortex and the retrosplenial area of the cingulate cortex, while retrieval from episodic memory was associated with activation of the precuneus bilaterally and of the right prefrontal cortex. These results are compatible with the patterns of activation reported in a previous PET memory experiment in which encoding and retrieval were studied concurrently. They also indicate that separate brain systems are engaged during the encoding and retrieval phases of episodic auditory-verbal memory. Retrieval from episodic memory engages a different, but overlapping, system to that engaged by retrieval from semantic memory, a finding that lends functional anatomical support to this neuropsychological distinction.

Adult↗

PubMed1995

The physiology of coloured hearing. A PET activation study of colour-word synaesthesia.

In a small proportion of the normal population, stimulation in one modality can lead to perceptual experience in another, a phenomenon known as synaesthesia. In the most common form of synaesthesia, hearing a word can result in the experience of colour. We have used the technique of PET, which detects brain activity as changes of regional cerebral blood flow (rCBF), to study the physiology of colour-word synaesthesia in a group of six synaesthete women. During rCBF measurements synaesthetes and six controls were blindfolded and were presented with spoken words or pure tones. Auditory word, but not tone, stimulation triggered synaesthesia in synaesthetes. In both groups word stimulation compared with tone stimulation activated the classical language areas of the perisylvian regions. In synaesthetes, a number of additional visual associative areas, including the posterior inferior temporal cortex and the parieto-occipital junctions, were activated. The former has been implicated in the integration of colour with shape and in verbal tasks which require attention to visual features of objects to which words refer. Synaesthetes also showed activations in the right prefrontal cortex, insula and superior temporal gyrus. By contrast, no significant activity was detected in relatively lower visual areas, including areas V1, V2 and V4. These results suggest that colour-word synaesthesia may result from the activity of brain areas concerned with language and visual feature integration. In the case of colour-word synaesthesia, conscious visual experience appears to occur without activation of the primary visual cortex.

Adult↗

PubMed1995

Functional anatomy of the mental representation of upper extremity movements in healthy subjects.

1. Differences in the distribution of relative regional cerebral blood flow during motor imagery and execution of a joy-stick movement were investigated in six healthy volunteers with the use of positron emission tomography (PET). Both tasks were compared with a common baseline condition, motor preparation, and with each other. Data were analyzed for individual subjects and for the group, and areas of significant flow differences were related to anatomy by magnetic resonance imaging (MRI). 2. Imagining movements activated a number of frontal and parietal regions: medial and lateral premotor areas, anterior cingulate areas, ventral opercular premotor areas, and parts of superior and inferior parietal areas were all activated bilaterally when compared with preparation to move. 3. Execution of movements compared with imagining movements led to additional activations of the left primary sensorimotor cortex and adjacent areas: dorsal parts of the medial and lateral premotor cortex; adjacent cingulate areas; and rostral parts of the left superior parietal cortex. 4. Functionally distinct rostral and caudal parts of the posterior supplementary motor area (operationally defined as the SMA behind the coronal plane at the level of the anterior commissure) were identified. In the group, the rostral part of posterior SMA was activated by imagining movements, and a more caudoventral part was additionally activated during their execution. A similar dissociation was observed in the cingulate areas. Individual subjects showed that the precise site of these activations varied with the individual anatomy; however, a constant pattern of preferential activation within separate but adjacent gyri of the left hemisphere was preserved. 5. Functionally distinct regions were also observed in the parietal lobe: the caudal part of the superior parietal cortex [medial Brodmann area (BA) 7] was activated by imagining movements compared with preparing to execute them, whereas the more rostral parts of the superior parietal lobe (BA 5), mainly on the left, were additionally activated by execution of the movements. 6. Within the operculum, three functionally distinct areas were observed: rostrally, prefrontal areas (BA 44 and 45) were more active during imagined than executed movements; a ventral premotor area (BA 6) was activated during both imagined and executed movements; and more caudally in the parietal lobe, an area was found that was mainly activated by execution presumably SII. 7. These data suggest that imagined movements can be viewed as a special form of "motor behavior' that, when compared with preparing to move, activate areas associated heretofore with selection of actions and multisensory integration.(ABSTRACT TRUNCATED AT 400 WORDS)

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

Determinants of the extremes of outcome in schizophrenia.

BACKGROUND: Although poor prognosis has been considered a defining characteristic of schizophrenia, long-term studies show marked heterogeneity of outcome. METHOD: Assessments of positive and negative symptoms, premorbid and current IQ, and months of in-patient care made in an outcome study of 342 schizophrenic patients were categorised by severity. Determinants of these categorisations were sought from the historical variables available, using analysis of variance. Vignettes of patients with the best and worst symptomatic outcomes were then compared. RESULTS: Negative symptoms were associated with early onset, male sex and poor academic record. Positive symptoms were associated with occupational decline. Cognitive decline was associated with occupational variables, and in-patient care with academic and occupational variables. The vignettes showed that good outcome was associated with family psychiatric history and poor outcome with unavailability of family history. CONCLUSIONS: The findings support the view that the most malignant form of schizophrenia is neurodevelopmental, but poor outcome was clearly associated with family fragmentation.

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↗

PubMed1995

The cognitive abnormalities underlying the symptomatology and the disability of patients with schizophrenia.

A variety of cognitive impairments can be observed in patients with schizophrenia, including substantial reductions in the intelligence quotient (IQ). I propose that these impairments can be best understood in terms of the abnormal processes underlying the signs and symptoms manifested by the patient at the time of the cognitive assessment. Negative signs such as poverty of speech are associated with defects of willed action, while positive symptoms such as hallucinations are associated with defects of self-monitoring. Hypotheses about the brain systems underlying these processes can be examined using functional brain imaging.

Cognition↗