Search PubMed⌕ Search

Biomedical subjects

C D Frith

Publications and source records attributed to C D Frith.

At least 181 records · Page 10Linked to original sources
PubMed1993

Functional mapping of brain areas implicated in auditory--verbal memory function.

Positron emission tomography measurements of regional cerebral blood flow (rCBF) were performed in normal volunteers during two auditory--verbal memory tasks: a subspan and supraspan task. The difference in rCBF between tasks was used to identify brain areas/systems involved in auditory--verbal long-term memory. Increases in rCBF were observed in the left and right prefrontal cortex, precuneus and the retrosplenial area of the cingulate gyrus. Decreases in blood flow were centred in the superior temporal gyrus bilaterally. Separate comparisons were also made between each span task and a resting state. Brain regions showing increases in rCBF in these comparisons included the thalamus, left anterior cingulate, right parahippocampal gyrus, cerebellum and the superior temporal gyrus. The brain areas identified in these comparison define a number of the neuroanatomical components of a distributed system for signal processing and storage relevant to auditory--verbal memory function.

Adult↗
PubMed1993

Dorsolateral prefrontal cortex dysfunction in the major psychoses; symptom or disease specificity?

Neurophysiological deficits in the left dorsolateral prefrontal cortex (DLPFC) have been described in positron emission tomography studies of schizophrenia and depression. In schizophrenia and depression this deficit has been associated with the syndromes of psychomotor poverty and psychomotor retardation, respectively. Such findings lead to a prediction that DLPFC dysfunction is symptom rather than disease related. This prediction was empirically tested in a retrospective study that pooled data from 40 patients meeting research diagnostic criteria for depression and 30 patients meeting DSM-III R criteria for schizophrenia. The patients were categorised into those with and without poverty of speech, a symptom that is an observable manifestation of psychomotor impairment. The profile of regional cerebral blood flow (rCBF), measured in all subjects under resting conditions, was subsequently compared in these two groups. Patients with poverty of speech had significantly lower rCBF in the left DLFPC. This reduction of rCBF was independent of diagnosis. The findings support the view that the study of symptoms, or symptom clusters, can provide information additional to that of traditional diagnostic systems in the study of the major psychoses.

Adult↗
PubMed1993

Negative features, retrieval processes and verbal fluency in schizophrenia.

Twenty chronic schizophrenic patients, ten matched normal controls and nine depressed controls performed categorical verbal fluency tasks for three minutes each on five separate occasions. On each occasion the schizophrenic patients generated significantly fewer words than the controls. Comparison of the different occasions showed that the schizophrenic patients had as many words available in their inner lexicons but were inefficient in retrieving them. The schizophrenic patients also generated fewer clusters of related words and more words outside the specified category. Reduced ability to generate words while the lexicon remained intact was more marked in patients with negative features. Patients with incoherence, in contrast, were more likely to produce inappropriate words. We propose that both poverty of speech and incoherence of speech reflect problems in the retrieval of words from the lexicon. To cope with these problems patients with poverty of speech terminate their search prematurely while the patients with incoherence commit errors in selecting words for output.

Adolescent↗
PubMed1992

Measuring the neuromodulatory effects of drugs in man with positron emission tomography.

Cognitive activation in conjunction with pharmacological challenge was used to demonstrate neuromodulation in man. Using positron emission tomography (PET), measurements of regional cerebral blood flow were made during the performance of memory tasks, before and after the administration of apomorphine (dopamine agonist), buspirone (5-HT1A partial agonist) or placebo. Drug effects on memory-induced increases in regional cerebral blood flow were assessed, on a voxel-by-voxel basis, using statistical parametric mapping. Increases of regional cerebral blood flow in response to the memory challenge were attenuated by apomorphine in the dorsolateral prefrontal cortex and augmented in the retrosplenial region of the posterior cingulate. Conversely, buspirone attenuated blood flow increases in the retrosplenial region. These interactions between drugs and a cognitive challenge can best be interpreted as neuromodulatory effects.

Adult↗
PubMed1992

Motor practice and neurophysiological adaptation in the cerebellum: a positron tomography study.

We have used positron tomography (PET) to demonstrate that some parts of the motor system exhibit physiological adaptation during the repeated performance of a simple motor task, but others do not. In contrast to the primary sensori-motor cortex, the cerebellum exhibits a decrease in physiological activation (increases in regional blood flow during performance) with practice. A new application of factorial experimental design to PET activation studies was used to make these measurements in four normal males. This design allowed adaptation to be examined by testing for an interaction between regional cerebral blood flow (rCBF) increases brought about by a motor task and the number of trials (time). These findings are interpreted as the neurophysiological correlates of synaptic changes in the cerebellum associated with motor learning in man.

Adaptation, Physiological↗
PubMed1992

Effect of the 5-HT1A partial agonist buspirone on regional cerebral blood flow in man.

Repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers before, and after, the administration of the 5-HT1A partial agonist, buspirone, or placebo. The difference in rCBF, before and after drug, (buspirone versus placebo) was used to identify brain areas affected by buspirone. Buspirone-induced changes in rCBF were studied under two behavioural conditions (5 word-list learning and 15 word-list learning). Compared to placebo, buspirone increased blood flow in the cuneus during both behavioural states. However, decreases in blood flow, centred in the left dorso-lateral prefrontal cortex and posterior cingulate cortex, were only observed under one of the two behavioural conditions. It is concluded that buspirone-induced alterations in regional cerebral blood flow are better understood, not in relation to the known distribution of monoamine neurotransmitter systems (particularly ascending 5-HT projections), but rather in relation to putative neuronal circuits possibly many synapses "downstream" of buspirone's pharmacological site of action.

Adult↗
PubMed1992

Memory for what it is and memory for what it means: a single case of Korsakoff's amnesia.

A single case of Korsakoff's syndrome, showing classic circumscribed amnesia on traditional neuropsychological tests, performed a number of learning tasks previously used in primates to demonstrate the different anatomical basis of memory systems used to learn about the properties of objects or to learn about rules of responding. The patient (CJ) performed in a manner very similar to lesioned monkeys in that he could learn evaluative tasks (e.g. a red object is nice), but not rule based tasks (e.g. a red object means go left). In consequence CJ learned an object discrimination task in a manner qualitatively different from a group of non-amnesic controls. Although he could not learn rule based tasks, CJ could perform them once he had been given the rule. Detailed analysis of learning showed that CJ could choose the object he had chosen previously, but could not say where it had been or whether he had been rewarded. Furthermore he could recognise a word as familiar, while not remembering its source. We propose that he has a specific impairment in a memory system concerned with the representation of the signification of objects in particular contexts, while representation of the properties of objects remains intact.

Alcohol Amnestic Disorder↗
PubMed1992

The Northwick Park 'Functional' Psychosis Study: diagnosis and outcome.

Three hundred and twenty-six consecutively admitted patients with functional psychotic illnesses to which no diagnostic classification had been applied were followed up after 2.5 years. They were examined in social, clinical and psychological terms and the CATEGO programme and DSM-III criteria were applied to data concerning the index episode to derive diagnostic classifications. The deterioration in occupational functioning and the hospital careers of patients with diagnostic classifications of schizophrenia were worse than those in the other groups and positive and negative features were also more severe in patients with a classification of schizophrenia. By contrast, no differences in psychological test performance were found between the groups based upon diagnostic classification. Impaired psychological test performance was found and it was strongly related to concurrent mental state abnormalities, particularly negative symptoms. It is concluded that the diagnostic classifications used were of limited value in predicting outcome in functional psychosis.

Adult↗
PubMed1992

Auditory evoked response and awareness: a study in volunteers at sub-MAC concentrations of isoflurane.

We have investigated the relationship between the auditory evoked response (AER) and simple tests of conscious awareness at four end-expiratory concentrations (0.0, 0.1, 0.2 and 0.4 MAC) of isoflurane in oxygen in each of eight anaesthetist volunteers, in random order, at least 1 week apart. The early cortical AER was recorded from electrodes at the vertex and inion. Amplitudes of the waves Pa, Nb and Pc and latencies of the waves Na, Pa, Nb, Pb and Nc were measured. All the AER variables were highly significantly related to end-expiratory anaesthetic concentration. Amplitudes decreased and latencies increased progressively with increasing anaesthetic concentration. The AER variables were also highly significantly related to the level of response. Amplitudes were greatest and the latencies shortest when there was full response to command. (Nb latency increased from 47.5 to 54.5 ms between partial and no response.) The close correlation between the effects of concentration and level of response, and between concentration and the AER implied that it was difficult to demonstrate those changes in the AER which specifically relate to changes in response. At 0.2 MAC, however, which was the concentration at which all subjects showed some deficit, the response to a shock word was distinguished clearly by Nb latency. In eight of 24 possible comparisons (eight AER variables and three types of psychological test) the AER fitted the response more closely than concentration.

Awareness↗
PubMed1992

The left medial temporal region and schizophrenia. A PET study.

Regional cerebral blood flow (rCBF) was measured in 30 schizophrenic patients with severe, persistent and stable symptoms using positron emission tomography (PET). Directed and non-directed correlational analysis of the relationship between psychopathology and rCBF was used to identify brain structures implicated in three behavioural subsyndromes of schizophrenia. Psychopathology and neurophysiology (rCBF) exhibited high correlations in the left medial temporal region, mesencephalic, thalamic and left striatal structures. The highest correlation was in the left parahippocampal region. A canonical analysis of the same data highlighted the left parahippocampal region and left striatum (globus pallidus) as sites which linked the behavioural subsyndromes in terms of shared rCBF correlates. Increasing severity of psychopathology was associated with increased rCBF in these regions. Disinhibition of left medial temporal lobe activity mediated by fronto-limbic connections is a possible explanation for these findings; however, the prefrontal component appears to be critically dependent on the behavioural subsyndrome.

Adult↗
PubMed1992

Inherited prion disease with 144 base pair gene insertion. 1. Genealogical and molecular studies.

Genealogical and molecular studies were carried out in four families in which early onset dementia is inherited as an autosomal dominant. These studies indicated that the four families derive from four siblings whose parents were born in the late 18th century in South-East England. The disease was found to be closely linked to a 144 bp insertion within the open reading frame of the prion protein (PrP) gene with a maximum LOD score of 11.02 at zero recombination. Within the general population the PrP gene is polymorphic at codon 129 (allele frequency approximately 30% valine, 70% methionine). The insertion in this family is always within a methionine-129 allele. The age at death of affected individuals whose normal allele encoded methionine at codon 129 was significantly lower than those whose normal allele encoded valine. The clinical features which were very variable and the neuropathological findings, which sometimes included spongiform encephalopathy, but which often did not, are described fully in the accompanying article (Collinge et al., 1992).

Base Sequence↗
PubMed1992

The effect of apomorphine and buspirone on regional cerebral blood flow during the performance of a cognitive task-measuring neuromodulatory effects of psychotropic drugs in man.

Psychopharmacological activation, in conjunction with positron emission tomographic measurements of regional cerebral blood flow (rCBF), was used to investigate the neurotransmitter basis of a specific cognitive function in man. Monoaminergic neurotransmission was pharmacologically manipulated during performance of auditory - verbal memory tasks. Statistical parametric mapping was used to identify the brain sites of interaction between memory-induced increases in rCBF and active drugs. Memory task-induced increases in rCBF in the left prefrontal cortex were attenuated by apomorphine, a non-selective dopamine agonist, whilst buspirone, a serotonin1A partial agonist, augmented rCBF increases in this area. In addition, apomorphine and buspirone augmented memory-induced increases in rCBF centred in the posterior cingulate cortex, whilst buspirone alone attenuated rCBF increases in the retrosplenial cortex and posterior parahippocampal gyrus. These regionally selective interactions may represent neuromodulatory effects of monoaminergic neurotransmission on a specific cognitive function in man.

Journal Article↗
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↗