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C D Frith

Publications and source records attributed to C D Frith.

At least 127 records · Page 7Linked to original sources
PubMed1996

Detecting activations in PET and fMRI: levels of inference and power.

This paper is about detecting activations in statistical parametric maps and considers the relative sensitivity of a nested hierarchy of tests that we have framed in terms of the level of inference (voxel level, cluster level, and set level). These tests are based on the probability of obtaining c, or more, clusters with k, or more, voxels, above a threshold u. This probability has a reasonably simple form and is derived using distributional approximations from the theory of Gaussian fields. The most important contribution of this work is the notion of set-level inference. Set-level inference refers to the statistical inference that the number of clusters comprising an observed activation profile is highly unlikely to have occurred by chance. This inference pertains to the set of activations reaching criteria and represents a new way of assigning P values to distributed effects. Cluster-level inferences are a special case of set-level inferences, which obtain when the number of clusters c = 1. Similarly voxel-level inferences are special cases of cluster-level inferences that result when the cluster can be very small (i.e., k = 0). Using a theoretical power analysis of distributed activations, we observed that set-level inferences are generally more powerful than cluster-level inferences and that cluster-level inferences are generally more powerful than voxel-level inferences. The price paid for this increased sensitivity is reduced localizing power: Voxel-level tests permit individual voxels to be identified as significant, whereas cluster-and set-level inferences only allow clusters or sets of clusters to be so identified. For all levels of inference the spatial size of the underlying signal f (relative to resolution) determines the most powerful thresholds to adopt. For set-level inferences if f is large (e.g., fMRI) then the optimum extent threshold should be greater than the expected number of voxels for each cluster. If f is small (e.g., PET) the extent threshold should be small. We envisage that set-level inferences will find a role in making statistical inferences about distributed activations, particularly in fMRI.

Brain↗
PubMed1996

Neural systems engaged by planning: a PET study of the Tower of London task.

The functional anatomy of planning was investigated using the Tower of London task. Activation was observed in a distributed network of cortical areas incorporating prefrontal, cingulate, premotor, parietal and occipital cortices. Activation in corresponding areas has been observed in visuospatial working memory tasks with the exception of the rostral prefrontal cortex. This area may be identified with the executive components of planning comprising response selection and evaluation. Enhanced neural activity in both this rostral prefrontal area and the visuospatial working memory system was associated with increased task difficulty.

Adolescent↗
PubMed1996

A fronto-parietal network for rapid visual information processing: a PET study of sustained attention and working memory.

The rapid visual information processing (RVIP) task, a test of sustained attention which also requires working memory for its successful execution, has been used in a number of human psychopharmacological studies. Single digits are presented in quick succession (100 or 200 digits/min) on a computer screen, and target sequences of numbers must be detected with a button press. Although previous neuroimaging studies have implicated the frontal and parietal cortices in performance of simple sustained attention tasks, the neuroanatomical substrates of RVIP performance are not yet known. This information would prove invaluable in the interpretation of drug effects on this task, possibly delineating a neuronal network for neurotransmitter action. Therefore, this study investigated the functional anatomy of the RVIP task using positron emission tomography (PET) derived measures of regional cerebral blood flow (rCBF) in eight healthy volunteers. Subjects were required to perform variants of the RVIP task which manipulated both the level of working memory load and the speed of stimulus presentation. Compared with a rest condition (eyes closed), the RVIP task increased rCBF bilaterally in the inferior frontal gyri, parietal cortex and fusiform gyrus, and also in the right frontal superior gyrus rostrally. In comparison with a simple sustained attention control condition, the aforementioned right frontal activations were no longer apparent. We suggest that these data are consistent with the existence of a right fronto-parietal network for sustained, and possibly selective, attention, and a left fronto-parietal network for the phonological loop component of working memory.

Adult↗
PubMed1996

Functional anatomy of inner speech and auditory verbal imagery.

The neural correlates of inner speech and of auditory verbal imagery were examined in normal volunteers, using positron emission tomography (PET). Subjects were shown single words which they used to generate short, stereotyped sentences without speaking. In an inner speech task, sentences were silently articulated, while in an auditory verbal imagery condition, subjects imagined sentences being spoken to them in an another person's voice. Inner speech was associated with increased activity in the left inferior frontal gyrus. Auditory verbal imagery was associated with increases in the same region, and in the left premotor cortex, the supplementary motor area and the left temporal cortex. The data suggest that the silent articulation of sentences involves activity in an area concerned with speech generation, while imagining speech is associated with additional activity in regions associated with speech perception.

Adult↗
PubMed1996

The nature of 'transient' and 'partial' psychoses: findings from the Northwick Park 'Functional' Psychosis Study.

Three hundred and twenty-six consecutively admitted patients with definite or possible functional psychotic illnesses to which no diagnostic classification had been applied were followed up after 2.5 years. In 86 cases symptomatology had been inadequate for the patients to enter the functional psychosis study, and in 75 cases this was because the symptoms were partial or transient. These patients were compared at follow-up with those who fulfilled operational criteria for schizophrenic, affective or schizoaffective psychoses. Differences between the 'partial' cases and those fulfilling specific diagnostic criteria were few, but the transient cases fared significantly better. Although the transient illnesses were recurrent, at follow-up at 2.5 years they appeared to have a good outcome in terms of social variables and symptomatology.

Affective Disorders, Psychotic↗
PubMed1996

Confabulation in schizophrenia: evidence of a new form?

This study is an attempt to demonstrate confabulation in schizophrenia. Twelve patients who met DSM-III-R criteria for schizophrenia were matched for age, sex and pre-morbid IQ with 12 volunteers, 9 of whom were normal healthy subjects, with the remainder being depressed patients. To elicit confabulation, subjects were asked to recall narratives. In addition, subjects were examined on a number of neuropsychological tests. Confabulation was defined as recall of information not present in the narrative. Variable amounts of confabulation were observed in all schizophrenics, while only one control subject confabulated. The content and structure of their productions differed from previously reported forms of confabulation in that schizophrenic patients spontaneously rearranged the original narratives to produce new ideas. The amount of confabulation was found to be related to difficulties in suppressing inappropriate responses (Hayling test) and formal thought disorder, but unrelated to understanding of the gist or moral of the narratives. Tentative mechanisms for the process of confabulation are proposed, based on specific difficulties with comprehension, response monitoring and response suppression.

Adult↗
PubMed1996

Exploring 'theory of mind' in people with schizophrenia.

Mentalizing ability was studied in 46 symptomatic schizophrenic patients and 44 non-symptomatic controls. Subjects heard six stories and simultaneously were shown simple cartoon pictures depicting the action sequencing occurring in the stories. All the stories involved false belief or deception, so that it was necessary to infer the mental states of the characters in order to understand their behaviour. After each story, subjects were asked one memory/reality question (concerning an event in the story) and one question that depended on the ability to infer the mental state of one of the characters. Patients with paranoid delusions were impaired on the questions concerning mental states. Patients with behavioural signs (i.e. negative features or incoherence) were also impaired on the mental state questions, but this difficulty was associated with memory impairments. Patients with symptoms of passivity (e.g. delusions of control) and patients in remission did not differ from normal controls. These results are consistent with the hypothesis that certain of the positive symptoms of schizophrenia reflect an impairment in the ability to infer the mental states of others.

Adult↗
PubMed1996

Validation of three dimensions of schizophrenic symptoms in a large unselected sample of patients.

A principal components analysis was conducted upon current symptoms and signs rated in a sample of 329 essentially unselected patients with schizophrenia. Three dimensions emerged clearly and closely resembled those previously described in smaller, more selected samples. The clearly defined psychotic dimensions were related in turn to: (i) other mental state variables; (ii) physical treatments administered; (iii) movement disorder; (iv) demographic and historical features; and (v) cognitive function. The correlates of the three dimensions were very different. The clarity of separation achieved in this investigation provides strong support for the view that the three psychotic dimensions of 'poverty', 'hallucinations and delusions' and 'disorganization' are valid and may well have different underlying pathophysiologies.

Affect↗
PubMed1996

Facial and other non-verbal communicative behaviour in chronic schizophrenia.

Facial behaviour may be an important determinant in clinical ratings of psychopathology. A standardized objective technique was used to quantify measures of facial behaviour in 21 chronic schizophrenic subjects, in comparison with control groups of depressed, demented and Parkinsonian subjects. Facial behaviours were counted and timed from video recordings of each subjects' face during a clinical interview. Separate measurement of behaviours were obtained while subjects were speaking and silent. For most variables, the amount of facial behaviour was significantly less in schizophrenic subjects than in control groups. The groups differed significantly on a number of measures, but schizophrenics could not be reliably identified by a single facial behaviour variable. However, using a discriminant function analysis with measures for eye contact while speaking and silent, broad smiles and small smiles, discrimination between groups was good, with over 80% correctly classified as either schizophrenic, or not schizophrenic. These techniques may increase our understanding of psychopathological signs and the mechanisms that underly them.

Chronic Disease↗
PubMed1996

Is developmental dyslexia a disconnection syndrome? Evidence from PET scanning.

A rhyming and short-term memory task with visually presented letters were used to study brain activity in five compensated adult developmental dyslexics. Their only cognitive difficulty was in phonological processing, manifest in a wide range of tasks including spoonerisms, phonemic fluency and digit naming speed. PET scans showed that for the dyslexics, a subset only of the brain regions normally involved in phonological processing was activated: Broca's area during the rhyming task, temporo-parietal cortex during the short- term memory task. In contrast to normal controls these areas were not activated in concert. Furthermore the left insula was never activated. We propose that the defective phonological system of these dyslexics is due to weak connectivity between anterior and posterior language areas. This could be due to a dysfunctional left insula which may normally act as an anatomical bridge between Broca's area, superior temporal and inferior parietal cortex. The independent activation of the posterior and anterior speech areas in dyslexics supports the notion that representations of unsegmented and segmented phonology are functionally and anatomically separate.

Adult↗
PubMed1996

Functional neuroanatomy of verbal self-monitoring.

The neural correlates of verbal self-monitoring were examined by measuring the response to alterations in auditory verbal feedback while subjects read aloud. Six normal subjects were studied with PET, using H2(15)O as a tracer of regional CBF. There was no difference between the temporal cortical response to reading aloud (and hearing one's own speech) and reading silently while hearing the words spoken by someone else. Distortion of subjects' speech (by pitch elevation) while they read aloud led to a bilateral activation of lateral temporal cortex, with a greater response on the right side than the left. A similar pattern of activation was evident when subjects read aloud, but the words they heard were spoken by someone else. These data suggest that (i) self-and externally generated speech are processed in similar regions of temporal cortex, and (ii) the monitoring of self-generated speech involves the temporal cortex bilaterally, in areas associated with the processing of speech which has been generated externally.

Adult↗
PubMed1996

Brain activity during memory retrieval. The influence of imagery and semantic cueing.

The effects of imagery and semantic relatedness on cued retrieval of word pairs were examined in a functional imaging study of healthy volunteers. Subjects underwent 12 PET scans, preceded by the paced presentation of 12 paired associates. The associates were dichotomized into imageable and non-imageable groups. Within each group, the strength of semantic association between members of pairs was varied in an ordinal fashion. Subsequently, neural activity was measured while subjects were cued with the first item of each pair and required to recall the associated word. Recall of imageable words, when compared with non-imageable ones, was associated with activation of the precuneus, consistent with our hypothesis that this region is important in visual imagery at episodic retrieval. The reverse comparison, non-imageable versus imageable recall, was associated with activation of the left dorsolateral prefrontal cortex. Within both imageable and non-imageable groups, decreasing semantic association showed a corresponding increase in frontal activity bilaterally. One possible explanation is that of a practice-related effect, weaker-linked pairs having a greater number of pre-scan presentations. However, this explanation is incomplete as the most semantically distant, and most rehearsed, pairs (randomly linked) were associated with a reversal of this effect. This finding can be explained if frontal activity is associated with the difficulty of eliminating inappropriate responses at retrieval. For both randomly linked pairs and closely related pairs it is more likely that erroneous responses will be generated and, therefore, the work done to eliminate them will be greater. Our findings indicate that patterns of neural activity during cued recall depend upon the nature of the material and on the degree of association between the cue and the response.

Adult↗
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

Frontal lobe dysfunction in amyotrophic lateral sclerosis. A PET study.

PET measurements of regional cerebral blood flow (rCBF) were used to explore frontal lobe dysfunction in amyotrophic lateral sclerosis (ALS). An activation paradigm of executive frontal lobe function (verbal fluency), which contrasted rCBF during word generation and word repetition, was used. Two groups of ALS patients, defined by the presence or absence of cognitive impairment (ALSi) (impaired, n = 6: ALSu unimpaired, n = 6) were compared with healthy age-matched controls (n = 6). Patient selection was based on prior performance on a written test of verbal fluency. Additional neuropsychological assessment of the patients revealed evidence of executive and memory dysfunction in the ALSi group only, with marked deficits in tests of intrinsic generation. The ALSi patients displayed significantly (P < 0.001) impaired activation in cortical and subcortical regions including the dorsolateral prefrontal cortex (DLPFC; areas 46 and 9), lateral premotor cortex (areas 8 and 6), medial prefrontal and premotor cortices (areas 8 and 9), insular cortex bilaterally and the anterior thalamic nuclear complex. Although the three groups showed matched word generation performance on the scanning paradigm, the ALSu group displayed a relatively unimpaired pattern of activation. These results support the presence of extra-motor neuronal involvement, particularly along a thalamo-frontal association pathway, in some non-demented ALS patients. In addition, this study suggests dysfunction of DLPFC in some ALS patients with associated cognitive impairments.

Aged↗
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

The functional anatomy of memory.

A review of recent work using Positron Emission Tomography (PET) to examine brain systems involved in auditory-verbal memory is presented. Initial work delineated widespread brain regions which were, to a large extent, in agreement with existing neuropsychological literature. Expanding on this, a number of studies have examined memory encoding and retrieval separately. Additionally, experiments have been carried out to specifically address sub-components of memory such as the use of visual imagery as a mnemonic strategy, the functional anatomical evidence for the episodic/semantic memory distinction and the different brain regions involved in explicit and implicit memory tasks.

Animals↗
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↗