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C D Frith

Publications and source records attributed to C D Frith.

At least 199 records · Page 11Linked to original sources
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↗
PubMed1990

Schizophrenia and the brain: a prospective clinico-neuropathological study.

The neuropathological results from a prospective, systematically assessed, series of 56 schizophrenic patients and 56 age- and sex-matched normal controls have been presented. When compared with the normal controls, the brains of the schizophrenic subjects showed a significant reduction in brain weight and brain length with a concomitant increase in ventricular size. (All findings relate to measurements made after formalin fixation). In addition, the brains of the schizophrenic patients contained significantly more non-specific focal pathology and fibrillary gliosis than the controls. After exclusion of cases with moderate and severe Alzheimer-type change, cerebro-vascular disease and all forms of focal pathology, the structural brain changes (i.e. decrease in brain weight and brain length) continued to distinguish the schizophrenia group from the controls. Furthermore, an analysis of the clinical data showed that the structural brain changes were correlated in the schizophrenic patients with a measurement of pre-morbid function. The findings and their possible aetiological implications have been discussed.

Adult↗
PubMed1990

The relationship between global and local changes in PET scans.

In order to localize cerebral cognitive or sensorimotor function, activation paradigms are being used in conjunction with PET measures of cerebral activity (e.g., rCBF). The changes in local cerebral activity have two components: a global, region independent change and a local or regional change. As the first step in localizing the regional effects of an activation, global variance must be removed by a normalization procedure. A simple normalization procedure is division of regional values by the whole brain mean. This requires the dependence of local activity on global activity to be one of simple proportionality. This is shown not to be the case. Furthermore, a systematic deviation from a proportional relationship across brain regions is demonstrated. Consequently, any normalization must be approached on a pixel-by-pixel basis by measuring the change in local activity and change in global activity. The changes associated with an activation can be partitioned into global and local effects according to two models: one assumes that the increase in local activity depends on global values and the other assumes independence. It is shown that the increase in activity due to a cognitive activation is independent of global activity. This independence of the (activation) condition effect and the confounding linear effect of global activity on observed local activity meet the requirements for an analysis of covariance, with the "nuisance" variable as global activity and the activation condition as the categorical independent variable. These conclusions are based on analysis of data from 24 scans: six conditions over four normal subjects using a verbal fluency paradigm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Levels of consciousness in volunteers breathing sub-MAC concentrations of isoflurane.

Eight volunteers inhaled isoflurane in concentrations of 0.1, 0.2 and 0.4 MAC, and 100% oxygen as control in separate sessions more than 1 week apart. When the end-expiratory isoflurane concentration was stable, response to verbal commands was tested, and the subjects were read 30 words in two lists. Response to the commands was impaired at 0.1 MAC in three subjects and lost at 0.2 MAC in two subjects. No subject responded at 0.4 MAC. When the subjects were questioned 1 h after exposure, memory of response to commands was lost also at these concentrations. Frequently, those who responded to the command "open your eyes" failed to remember having done so; non-responders remembered nothing. At the time of that test, at 0.4 MAC, five of eight subjects had no eyelash reflex. Both recall and recognition of neutral words was lost at 0.2 MAC and greater, but the effect of attention was demonstrated by the memory of a "shock" word by four of eight subjects at 0.2 MAC.

Adult↗
PubMed1990

Further investigation of the predictors of outcome following first schizophrenic episodes.

The outcome at two years of patients who were eligible for a study of first schizophrenic episodes was assessed in terms of occupation (n = 237) and in terms of number of days spent as an in-patient from the time of first admission (n = 252), and was related to social, behavioural, mental state and neurological measures during the initial admission. Poor outcome was in general associated with more social withdrawal, inactivity and abnormal social presentation and with more 'neurological soft signs'. Good occupational outcome in patients with a relatively short pre-treatment duration of illness was associated with the prescription of placebo medication during the follow-up period.

Activities of Daily Living↗