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Biomedical subjects

P F Liddle

Publications and source records attributed to P F Liddle.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1994

The role of the left prefrontal cortex in verbal processing: semantic processing or willed action?

This study was designed to test the various proposed explanations (semantic processing, willed action, production of a spoken response) for the unilateral activation of the left prefrontal cortex noted in PET studies of verbal processing. Twenty subjects underwent 15O-water PET scans while undertaking a lexical task (detecting the letter 'a' in visually presented words) and a semantic task (categorizing nouns into living/non-living). The semantic task resulted in a significant unilateral left dorsolateral prefrontal activation. This finding suggests that the left inferior prefrontal cortex is the anatomical region involved in 'working with meaning', and that the activation does not reflect willed action, is not task-specific and is not attributable to the requirements of a spoken response.

Adult↗
PubMed1993

Lateral asymmetries in auditory acuity distinguish hallucinating from nonhallucinating schizophrenic patients.

Bilateral absolute auditory thresholds for frequencies ranging from 250 to 8000 Hz were examined on two occasions in schizophrenic patients and normal control subjects. Patients were classified as hallucinators and nonhallucinators on the basis of symptom ratings on both occasions. Previous evidence of better right than left ear acuity in schizophrenia was replicated but was found to characterize nonhallucinating patients only. Hallucinators showed no lateral asymmetry and inferior right ear acuity as compared with that in nonhallucinators. The results were reliable on retest. Brief Psychiatric Rating Scale scores of positive and negative symptoms in some cases differentiated hallucinators from nonhallucinators. The relationship of verbal hallucinations and right ear-left temporal lobe functions is discussed, together with complexities in cerebral laterality-syndrome relationships.

Adult↗
PubMed1993

The effect of the dopamine agonist, apomorphine, on regional cerebral blood flow in normal volunteers.

Apomorphine, a non-selective dopamine agonist, has been used as a pharmacological probe for investigating central dopaminergic neurotransmission in psychiatric illness. In this study repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers before, and after, the administration of apomorphine (5 or 10 micrograms/kg), or placebo. The difference in rCBF, before and after drug (apomorphine versus placebo), was used to identify brain areas affected by apomorphine. Compared to placebo, both doses of apomorphine increased blood flow in the anterior cingulate cortex. Apomorphine 10 micrograms/kg also increased prefrontal rCBF (right > left). No decreases in rCBF were noted following either dose of apomorphine. Apomorphine-induced increases of anterior cingulate blood flow might serve as an in vivo index of central dopamine function. Such an approach would complement established neuroendocrine challenge paradigms for investigating central dopamine neurotransmission in psychiatric illness.

Adult↗
PubMed1993

Functional connectivity: the principal-component analysis of large (PET) data sets.

The distributed brain systems associated with performance of a verbal fluency task were identified in a nondirected correlational analysis of neurophysiological data obtained with positron tomography. This analysis used a recursive principal-component analysis developed specifically for large data sets. This analysis is interpreted in terms of functional connectivity, defined as the temporal correlation of a neurophysiological index measured in different brain areas. The results suggest that the variance in neurophysiological measurements, introduced experimentally, was accounted for by two independent principal components. The first, and considerably larger, highlighted an intentional brain system seen in previous studies of verbal fluency. The second identified a distributed brain system including the anterior cingulate and Wernicke's area that reflected monotonic time effects. We propose that this system has an attentional bias.

Algorithms↗
PubMed1993

Depression and the experience of psychological deficits in schizophrenia.

A study of the relationships between depression and the subjective experience of psychological deficits was carried out in a group of 50 schizophrenic patients selected from a population of long-term mentally ill patients. Experience of psychological deficits was associated with depression, and furthermore the temporal relationships between the phenomena supported the hypothesis that experience of psychological deficits is associated with vulnerability to depression in schizophrenia. In addition, the patients' self-reporting of depressed mood and negative cognitions was congruent with an observer's assessment of depression. These findings indicate that subjective experiences of deficits characteristic of the schizophrenic illness confer vulnerability to depression, but nonetheless the patients' experience of depression resembles that typical of depressed non-schizophrenic patients.

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

The composition of the negative syndrome of chronic schizophrenia.

The clinical features of patients who satisfy a variety of criteria for the negative syndrome can be arranged in five groups of phenomena: (a) poverty of thought and speech, (b) blunted affect, (c) decreased motor activity, (d) apathy and abolition, and (e) diminished interpersonal interaction. We have shown that depressed mood and depressive cognition are not related to the negative syndrome, but there is some overlap between the specific phenomena of depressive illness and negative symptoms in schizophrenia. Items measuring cognitive impairment have a moderate correlation with the negative syndrome, but the negative syndrome accounts for less than half of the variance of cognitive performance. These items that define the negative syndrome can be as reliably measured as depressive and positive symptoms.

Activities of Daily Living↗
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↗
PubMed1993

Negative symptoms as a risk factor for tardive dyskinesia in schizophrenia.

Investigation of the relationships between negative schizophrenic symptoms, abnormal involuntary movements and age in 179 chronic schizophrenic patients confirmed that both orofacial and trunk and limb dyskinesia are associated with negative symptoms, but only orofacial dyskinesia showed a significant increase in prevalence with increasing age. Estimation of the mean age of onset of orofacial dyskinesia from the observed variation in prevalence of orofacial dyskinesia with age indicated that patients having negative symptoms tend to develop orofacial dyskinesia at an earlier age. The estimated mean age of onset was 43.6 years in patients with substantial negative symptoms, and 54.6 years in patients without substantial negative symptoms. These findings support the proposal that the pathological process underlying negative symptoms can contribute to the occurrence of both orofacial and trunk and limb dyskinesia, but, in the case of orofacial dyskinesia, there is a synergistic interaction between the pathological process underlying negative symptoms and age-related neuronal changes.

Adult↗
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

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

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↗