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Biomedical subjects

P F Liddle

Publications and source records attributed to P F Liddle.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Schizophrenic syndromes and frontal lobe performance.

A battery of neuropsychological tests sensitive to frontal lobe impairment was administered to 43 chronic schizophrenic patients to delineate the abnormality of mental processing associated with the syndromes of psychomotor poverty and disorganisation, which had been identified in a previous study of the segregation of schizophrenic symptoms. Psychomotor poverty was found to be associated with slowness of mental activity, including slowness of generating words. The disorganisation syndrome was associated with impairment in tests in which the subject is required to inhibit an established but inappropriate response.

Adult↗

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↗

The nature and prevalence of depression in chronic schizophrenic in-patients.

Out of 194 chronic schizophrenic in-patients, depressed mood (item 23 of the PSE) was present in 25 (13%). When compared with 25 matched controls, the patients with depressed mood had significantly higher scores on the MADRS and the Beck Depression Inventory. Serious suicidal ideas and auditory hallucinations were significantly more common in the depressed group. However, there were no significant differences between the matched groups in terms of negative symptoms, Parkinsonism, tardive dyskinesia, anticholinergic medication, or current dose of antipsychotic drug, which suggests that the depression identified was not related to drug treatment, nor was it a direct manifestation or misinterpretation of negative symptoms. Over three-month follow-up, the MADRS and Beck scores covaried closely with the presence or absence of depressed mood. This depressive syndrome persisted over the three months in the majority of patients originally depressed.

Aged↗

Psychiatric morbidity of a long stay hospital population with chronic schizophrenia and implications for future community care.

In the United Kingdom there are plans to close most mental hospitals over the next 10 years. There is continuing uncertainty about the effectiveness of community psychiatric services that will be expected to cope with mental hospital inpatients after discharge, most of whom have schizophrenia. A survey was conducted to assess the severity of illness among such patients and implications for their future care. All 222 patients in non-psychogeriatric long stay wards of a mental hospital who met research diagnostic criteria for schizophrenia were interviewed by two psychiatrists with the comprehensive psychopathological rating scale to establish the prevalence of psychiatric symptomatology. A complete interview was not possible for 28 patients, mainly for reasons related to their schizophrenia. Despite energetic pharmacological and social treatments almost half of the 194 patients interviewed had enduring florid psychotic symptoms that presented as one or more delusions or auditory hallucinations, or both, and a sizable proportion showed behaviour that would set them apart in a community setting. The results illustrate a problem that is still imperfectly understood by policy makers and administrators in central and local government and in health authorities who are responsible for planning and implementing services for psychiatric care in the community.

Adult↗