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C D Frith

Publications and source records attributed to C D Frith.

At least 37 records · Page 2Linked to original sources
PubMed1992

Cerebral blood flow and mental processes in schizophrenia.

The patterns of cerebral blood flow associated with three syndromes of schizophrenic symptoms are compared with the loci of cerebral activation in normal subjects during the performance of mental processes implicated in the three syndromes. The psychomotor poverty syndrome, which has been shown to involve a diminished ability to generate words, is associated with decreased perfusion of the dorsolateral prefrontal cortex at a locus which is activated in normal subjects during the internal generation of words. The disorganization syndrome, which has been shown to involve impaired suppression of inappropriate responses (eg in the Stroop test), is associated with increased perfusion of the right anterior cingulate gyrus at a location activated in normal subjects performing the Stroop test. The reality distortion syndrome, which evidence suggests arises from disordered internal monitoring of activity, is associated with increased perfusion in the medial temporal lobe at a locus activated in normal subjects during the internal monitoring of eye movements.

Adult↗
PubMed1992

Patterns of cerebral blood flow in schizophrenia.

Positron emission tomography was used to study the relationship between rCBF and symptom profiles in 30 schizophrenic patients. Factor analysis confirmed that the symptoms segregated into three syndromes--psychomotor poverty, disorganisation, and reality distortion--described previously. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in paralimbic and association cortex, and in related subcortical nuclei. The study confirmed predictions that psychomotor poverty and disorganisation are associated with altered perfusion at different loci in the pre-frontal cortex, and reality distortion with altered perfusion in the medial temporal lobe. The perfusion patterns suggest that the abnormalities of brain function underlying each of the three syndromes are not confined to single loci, but involve distributed neuronal networks.

Adult↗
PubMed1992

A test of the hypothesis that age at onset in Huntington disease is controlled by an X-linked recessive modifier.

Data from the Research Roster for Huntington Disease Patients and Families were used to assess the hypothesis that juvenile onset in Huntington disease is determined by an X-linked recessive modifying gene in the affected parent. The observed proportion of affected fathers to affected mothers who had such offspring was not compatible with this hypothesis. Furthermore, neither the excess of affected grandfathers nor the existence of juvenile-onset and adult-onset cases within a sibship would be predicted by this model. We also rejected a more general hypothesis that a major change in gene expression across generations, measured by the presence of juvenile onset and/or major anticipation, is determined by an X-linked modifier. However, the inheritance of a propensity toward juvenile onset via the affected male line could be due to an abnormal pattern of paternal genomic imprinting.

Adolescent↗
PubMed1991

Complications of pregnancy and delivery in relation to psychosis in adult life: data from the British perinatal mortality survey sample.

OBJECTIVE: To evaluate whether events occurring at or around the time of birth contribute to the onset of psychotic illness in adult life. DESIGN-Pregnancy and birth complications as possible causes of adult mental illness were studied in the population sample of the British perinatal mortality survey. Subsequent psychiatric admissions were independently identified through the Mental Health Enquiry and records of regional and special health authorities. Logistic regression was used to compare data on perinatal deaths with those on survivors to determine factors independently associated with perinatal death, and this equation was then used to calculate the risk of perinatal death for each survivor. SUBJECTS: 16,980 people born in a single week in 1958 (the British perinatal mortality survey sample), including 252 patients admitted to psychiatric care; case notes of 235 patients were supplied. MAIN OUTCOME MEASURES AND RESULTS: Patients with a schizophrenic illness (whether defined by "broad" (n = 57) or "narrow" (n = 35) diagnostic criteria) did not have a greater mean risk of perinatal death than the population in general, but there was some evidence of increased liability (relative risk 2.43; 95% confidence interval 1.17 to 5.05) for those with affective psychosis (n = 32). Specific high risk variables for affective psychosis were decreased gestation time (273.9 v 281.2 days; mean difference 7.3 days, 95% confidence interval 3.1 to 11.5; p less than 0.002) and prescription of vitamin K to the child in the first week of life (19% of patients v 5% of controls, p = 0.016). CONCLUSIONS: The findings give no support to theories that factors predicting perinatal mortality contribute significantly to causation of schizophrenic illness. Further investigation of decreased gestation length in relation to affective disorder is required.

Adult↗
PubMed1991

Willed action and the prefrontal cortex in man: a study with PET.

We used positron emission tomography to contrast changes in cerebral blood flow associated with willed and routine acts. In the six tasks used, volunteers had to make a series of responses to a sequence of stimuli. For the routine acts, each response was completely specified by the stimulus. For the willed acts, the response was open-ended and therefore volunteers had to make a deliberate choice. Willed acts in the two response modalities studied (speaking a word, or lifting a finger) were associated with increased blood flow in the dorsolateral prefrontal cortex (Brodmann area 46). Willed acts were also associated with decreases in blood flow, but the location of these decreases was modality dependent.

Acoustic Stimulation↗
PubMed1991

Investigating a network model of word generation with positron emission tomography.

By using positron emission tomography (PET) we examined the biological validity of a network model describing changes in cerebral activity associated with intrinsic and extrinsic word generation. The production of words not specified by an extrinsic stimulus constitutes willed or intrinsic generation. Perceiving a heard word is an example of extrinsic generation. The model incorporates three neuronal systems: a pool that stores word representations in a distributed fashion, an afferent system conveying sensory input to the pool and a modulating system that alters the responsivity of neurons in the pool. Simulations based on the model suggested that intrinsic generation would be associated with low activity in the pool, consequent on reduced modulation, and extrinsic generation with high activity. We measured cerebral activity with PET during intrinsic (verbal fluency) and extrinsic (responding to heard words) word generation and found this pattern of changes in the left superior temporal region. We were able to designate this region the site of the distributed word store and implicate the left dorsolateral prefrontal cortex (DLPFC) as the source of modulation. The relation between the superior temporal gyrus and DLPFC was shown by examining the correlation between the two regions in terms of cerebral activity. We conclude that the left DLPFC is responsible for modulating the responsivity of a neural system in the superior temporal gyrus and is the probable mediator of changes in attentional and intentional states that underlies the intrinsic generation of words.

Animals↗
PubMed1991

The neurotransmitter basis of cognition: psychopharmacological activation studies using positron emission tomography.

The neuromodulatory effect of manipulating monoaminergic receptor function was assessed by combining a psychological and a pharmacological activation during repeated positron emission tomographic (PET) scans. The effects of buspirone (a 5-HT1A receptor partial agonist) on changes in regional cerebral blood flow (rCBF) associated with free word recall were examined. A factorial design was used to demonstrate a significant interaction (changes in rCBF brought about by psychological activation which depend on drug administration) in the left parahippocampal region. This interaction was an attenuation of increases in local neuronal activity (rCBF) related to memory function. Buspirone-induced decreases in rCBF, independent of the memory effect, were seen in the left prefrontal and parietal cortices. We suggest that combined psychological and pharmacological activation is a way of measuring direct (main) drug effects and modulatory effects on neurotransmission associated with cognitive functions (interaction).

Adult↗
PubMed1991

A PET study of word finding.

We have used PET in conjunction with psychological activations to identify cortical areas involved in the intrinsic activation of word representations. In four normal subjects intrinsic generation of a word (verbal fluency) was associated with an increase in left dorsolateral prefrontal cortical activity (BA 46) and a bilateral decrease in activity in auditory and superior temporal cortices. Conversely, when subjects made lexical decisions about words that were heard, there was an increase in superior temporal activity with no change in area 46. We suggest that the superior temporal regions are the site of stored word representations and that inhibitory modulation of these areas by the left prefrontal cortex is the basis of intrinsic word generation.

Adult↗
PubMed1991

Can the neuropsychological case-study approach be applied to schizophrenia?

Neuropsychological studies of schizophrenia typically apply a small number of tests to a large group of patients. This approach has at least two drawbacks. First, the heterogeneity of the condition will lead to group means which may not reflect the behaviour of any individual. Secondly, it is difficult to infer the nature of the underlying cognitive impairments from a small number of tests, since good performance on a particular test depends on many different cognitive processes. In these circumstances it is more appropriate to apply the methods of cognitive neuropsychology where a large number of tests are used on a single case. This approach has proved fruitful in the study of neurological patients. We have intensively studied 5 chronic schizophrenic patients. These patients varied greatly in terms of overall ability. However, all patients, whatever their overall ability, performed badly on tests sensitive to frontal lobe lesions. This result suggests impairment of the supervisory attentional system in these patients. In addition, one patient suffered from a visual agnosia.

Adult↗
PubMed1991

Comparing functional (PET) images: the assessment of significant change.

Statistical parametric maps (SPMs) are potentially powerful ways of localizing differences in regional cerebral activity. This potential is limited by uncertainties in assessing the significance of these maps. In this report, we describe an approach that may partially resolve this issue. A distinction is made between using SPMs as images of change significance and using them to identify foci of significant change. In the first case, the SPM can be reported nonselectively as a single mathematical object with its omnibus significance. Alternatively, the SPM constitutes a large number of repeated measures over the brain. To reject the null hypothesis, that no change has occurred at a specific location, a threshold adjustment must be made that accounts for the large number of comparisons made. This adjustment is shown to depend on the SPM's smoothness. Smoothness can be determined empirically and be used to calculate a threshold required to identify significant foci. The approach models the SPM as a stationary stochastic process. The theory and applications are illustrated using uniform phantom images and data from a verbal fluency activation study of four normal subjects.

Adult↗
PubMed1991

Patterns of inheritance of the symptoms of Huntington's disease suggestive of an effect of genomic imprinting.

The interaction of symptomatology (rigidity/chorea) in Huntington's disease (HD) with age of onset (AO) was examined using data from the Research Roster for Huntington's Disease Patients and Families. It was shown that AO varies between families and between paternal and maternal transmission and that rigidity is associated specifically with very early onset, major anticipation, paternal transmission, and young parental AO. It is proposed that AO depends on the state of methylation of the HD locus, which varies as a familial trait, and as a consequence of 'genomic imprinting' determined by parental transmission. Young familial AO and paternal imprinting interact to produce, occasionally, a major change in gene expression, that is, the early onset/rigid variant.

Adolescent↗
PubMed1991

Clinical trials in Alzheimer's disease. A report from the Medical Research Council Alzheimer's Disease Clinical Trials Committee.

Recent advances in Alzheimer's disease imply a need for adequate clinical trials of new treatments which require careful design. The disorder is progressive and shows clinical heterogeneity. While large-scale trials of elderly subjects are appropriate in relation to assessment of drugs or other treatments designed to prevent progression of the disorder, the outcome measurements in such biological treatment trials require careful planning. Studies of individual patients are relevant for answering certain specific questions. Relatively short cross-over trial designs may be appropriate to some pharmacological studies. The choice of neuropsychological instruments for measuring change is critically important, particularly in excluding test/retest artefact and in avoiding floor and ceiling effects. Test scales designed for assessment of specific neuropsychological deficits, or forming part of standard IQ assessments are unlikely to prove robust. Tests can be selected and developed for individual patients, but generalisation of the results of such experiments to the disease as a whole is not inevitable. There is a need to develop psychological instruments for measuring change that are robust and relevant to the clinical problem of progressive dementia.

Aged↗
PubMed1990

Combination tricyclic antidepressant and lithium maintenance medication in unipolar and bipolar depressed patients.

In a small study of up to 3 years' duration comparison of the value of amitriptyline alone versus amitriptyline + lithium in unipolar cases (27 patients) and of that of lithium alone versus amitriptyline + lithium in bipolar cases (13 patients) showed no advantage for the combination treatments in terms of efficacy in reducing depressive relapses. There was no effect of treatment, developing depression or developing hypothyroidism upon the psychological tests which were conducted during this prolonged study. Observer and self ratings detected an increase in depression before relapse was clearly present, but of the various psychological assessments conducted only arousal showed changes in association with developing and definite relapse. The prescription of lithium but not amitriptyline + lithium or amitriptyline alone was associated with significant increases in blood pressure.

Adult↗