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Biomedical subjects

P F Liddle

Publications and source records attributed to P F Liddle.

At least 37 records · Page 2Linked to original sources
PubMed2000

A PET study of brain 5-HT2 receptors and their correlation with platelet 5-HT2 receptors in healthy humans.

RATIONALE: Platelets share many properties with brain serotonergic neurons such as active 5-hydroxytryptamine (5-HT) transport, 5-HT2 receptors, and mitochondrial monoamine oxidase. OBJECTIVES: We measured brain 5-HT2 receptors and platelet 5-HT2 receptors in healthy volunteers to determine if there was any correlation between the two measures. METHODS: Ten healthy volunteers with no lifetime history of psychiatric illness or family history in first-degree relatives were recruited. 5-HT2 receptor binding was determined for each subject with positron emission tomography and [18F]setoperone scan in the brain and with 3H-LSD binding in platelets. RESULTS: We found no significant correlation between 5-HT2 binding potential (BP) in platelets (Bmax/Kd) and a semiquantitative estimate of 5-HT2 BP in frontal, parietal, and temporal cortical regions. SPM voxel based analysis also showed no significant correlation between the 5-HT2 BP in platelets and in the brains of the study subjects. CONCLUSIONS: Brain 5-HT2 receptor binding was not significantly correlated to platelet 3H-LSD binding in healthy subjects. This raises questions about the validity of generalizing findings from platelet studies to 5-HT neurons in the brain.

Adult↗
PubMed2000

Cognitive impairment in schizophrenia: its impact on social functioning.

OBJECTIVE: To examine cognitive impairment in schizophrenia and its impact on social functioning. METHOD: Cohort studies recording cognitive and social development, studies of predictors of poor community outcome, and evidence from brain imaging studies are reviewed. RESULTS: Executive function deficits, and poor performance in verbal memory, vigilance, and working memory tests are strong predictors of poor community outcome and impairment in skills learning. PET scans of regional cerebral blood flow suggest a dynamic imbalance between different cerebral areas rather than overall loss of brain function. CONCLUSION: Chronic cognitive impairment is the strongest predictor of social disability. Results suggest that the impairment of brain function associated with executive deficits is not necessarily irreversible and may therefore be treatable with appropriate drug therapy.

Brain↗
PubMed2000

Decreased serotonin 2A receptor densities in neuroleptic-naive patients with schizophrenia: A PET study using [(18)F]setoperone.

OBJECTIVE: The authors compared serotonin receptor binding in patients with schizophrenia and healthy comparison subjects. METHOD: They used positron emission tomography with [(18)F]setoperone to examine six patients with schizophrenia who had never been given neuroleptics and seven age-matched subjects who did not have schizophrenia. RESULTS: A nondirected voxel-based analysis of the subjects' entire search volume found that serotonin 2A binding potential in the frontal cortex index was significantly smaller (by 16.3%) in patients with schizophrenia than in healthy subjects. CONCLUSIONS: The authors conclude that the decrease in serotonin receptor densities previously reported in postmortem studies of subjects with schizophrenia are present at the onset of the illness, before exposure to neuroleptics.

Adolescent↗
PubMed2000

Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk. Focal dysfunction and distributed disconnectivity reappraised.

BACKGROUND: PET studies of verbal fluency in schizophrenia report a failure of 'deactivation' of left superior temporal gyrus (STG) in the presence of activation of left dorsolateral prefrontal cortex (DLPFC), which deficit has been attributed to underlying 'functional disconnectivity'. AIM: To test whether these findings provide trait-markers for schizophrenia. METHOD: We used H2(15)O PET to examine verbal fluency in 10 obligate carriers of the predisposition to schizophrenia, 10 stable patients and 10 normal controls. RESULTS: We found no evidence of a failure of left STG deactivation in carriers or patients. Instead, patients failed to deactivate the precuneus relative to other groups. We found no differences in functional connectivity between left DLPFC and left STG but patients exhibited significant disconnectivity between left DLPFC and anterior cingulate cortex. CONCLUSIONS: Failure of left STG 'deactivation' and left fronto-temporal disconnectivity are not consistent findings in schizophrenia; neither are they trait-markers for genetic risk. Prefrontal functional disconnectivity here may characterise the schizophrenic phenotype.

Heterozygote↗
PubMed2000

Immediate effects of risperidone on cortico-striato-thalamic loops and the hippocampus.

BACKGROUND: Functional imaging studies indicate that delusions and hallucinations in schizophrenia are associated with overactivity of the left hippocampus and ventral striatum. Hippocampal neuronal firing modulates feedback to cortex via cortico-striato-thalamic loops. AIMS: To test the hypothesis that recovery from psychosis is associated with decrease in activity in cortico-striato-thalamic circuits, and, furthermore, that reduction in hippocampal activity predicts the degree of alleviation of delusions and hallucinations. METHOD: Positron emission tomography (PET) was used to measure the effects of the atypical antipsychotic, risperidone, on glucose metabolism in eight first-episode schizophrenia patients. RESULTS: A single dose of risperidone produced decreases in metabolism in ventral striatum, thalamus and frontal cortex. The magnitude of decreases in left hippocampus predicted subsequent reduction in delusions and hallucinations. After six weeks' treatment with risperidone, the decreases in frontal metabolism were more extensive. CONCLUSIONS: The mechanism of antipsychotic action of risperidone entails reduction of hippocampal activity together with reduced feedback via cortico-striato-thalamic loops.

Adult↗
PubMed2000

Error processing and the rostral anterior cingulate: an event-related fMRI study.

The anterior cingulate is believed to play a crucial role in the regulation of thought and action. Recent evidence suggests that the anterior cingulate may play a role in the detection of inappropriate responses. We used event-related functional magnetic resonance imaging techniques to examine the neural responses to appropriate (correct rejects and correct hits) and inappropriate (errors of commission) behavioral responses during a go/no-go task. Analyses of the inappropriate responses revealed extensive activation in the rostral anterior cingulate cortex and in the left lateral frontal cortex. These areas were not activated for correctly classified trials (correct rejects and correct hits). These data suggest that the rostral anterior cingulate and left lateral frontal cortex are integral components of the brain's error checking system.

Adult↗
PubMed1999

Reduced P300 responses in criminal psychopaths during a visual oddball task.

BACKGROUND: Clinicians have long recognized that psychopaths show deficits in cognitive function, but there have been few experimental studies exploring these deficits. We present here the first in a series of event-related potential (ERP) experiments designed to elucidate and characterize the neural correlates of cognitive processes of psychopaths. METHODS: We recorded ERPs from a topographic array from 11 psychopathic and 10 nonpsychopathic prison inmates, assessed with the Hare Psychopathy Checklist-Revised, during performance of a visual oddball task. ERPs to target (25% of trials) and nontarget (75% of trials) visual stimuli were analyzed. RESULTS: Consistent with previous research, there were no group differences in the latency or amplitude of the ERPs for the nontarget stimuli. For nonpsychopaths, the P300 amplitude was larger when elicited by the target stimuli than when elicited by the nontarget stimuli. In contrast, psychopaths failed to show reliable P300 amplitude differences between the target and nontarget conditions. Psychopaths had a smaller amplitude P300 to target stimuli than did nonpsychopaths. In addition, the amplitude of the P300 was less lateralized in psychopaths than in nonpsychopaths. Psychopaths also had a larger centrofrontal negative wave (N550) during the target condition than did nonpsychopaths. CONCLUSIONS: The results of this study indicate that there are substantial differences between psychopaths and others in the processing of even simple cognitive tasks and provide support for information processing models of psychopathy.

Adult↗
PubMed1999

Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment: a positron emission tomography study with fluorine-18-labeled setoperone.

BACKGROUND: The neuroreceptor changes involved in therapeutic efficacy of various antidepressants remain unclear. Preclinical studies have shown that long-term administration of various antidepressants causes down-regulation of brain serotonin 2 (5-HT2) receptors in rodents, but it is unknown if similar changes occur following antidepressant treatment in depressed patients. Our purpose, therefore, was to assess the effects of treatment with desipramine hydrochloride on brain 5-HT2 receptors in depressed patients using positron emission tomography (PET) and fluorine-18 (18F)-labeled setoperone. METHODS: Eleven patients who met DSM-IV criteria for major depression as determined by a structured clinical interview for DSM-III-R diagnosis and suitable for treatment with desipramine were recruited. Ten patients underwent a PET scan before and another after 3 to 4 weeks of treatment with desipramine. RESULTS: Eight of the 10 patients responded to desipramine treatment as indicated by more than 50% decrease in Hamilton Depression Rating Scale scores. Depressed patients showed a significant decrease in 5-HT2 receptor binding as measured by setoperone binding in frontal, temporal, parietal, and occipital cortical regions following desipramine treatment. The decrease in 5-HT2 receptor binding was observed bilaterally and was particularly prominent in frontal cortex. CONCLUSIONS: Depressed patients showed a significant reduction in available 5-HT2 receptors in the brain following desipramine treatment, but it is unknown if this change in 5-HT2 receptors is due to clinical improvement or an effect of desipramine that is unrelated to clinical status.

Antidepressive Agents, Tricyclic↗
PubMed1999

Neural pathways involved in the processing of concrete and abstract words.

The purpose of this study was to delineate the neural pathways involved in processing concrete and abstract words using functional magnetic resonance imaging (fMRI). Word and pseudoword stimuli were presented visually, one at a time, and the participant was required to make a lexical decision. Lexical decision epochs alternated with a resting baseline. In each lexical decision epoch, the stimuli were either concrete words and pseudowords, or abstract words and pseudowords. Behavioral data indicated that, as with previous research, concrete word stimuli were processed more efficiently than abstract word stimuli. Analysis of the fMRI data indicated that processing of word stimuli, compared to the baseline condition, was associated with neural activation in the bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus, and left and right inferior frontal gyrus. A direct comparison between the abstract and concrete stimuli epochs yielded a significant area of activation in the right anterior temporal cortex. The results are consistent with recent positron emission tomography work showing right hemisphere activation during processing of abstract representations of language. The results are interpreted as support for a right hemisphere neural pathway in the processing of abstract word representations.

Adult↗
PubMed1998

Neuropsychological deficits associated with schizophrenic syndromes.

A battery of computerised tests and the classical Stroop test were administered to a group of 56 patients with DSM-III-R schizophrenia and 17 controls to explore the nature of the mental processes associated with the psychomotor poverty and disorganisation syndromes. In patients with persistent illness, psychomotor poverty was associated with slower responses in a two-choice guessing task in which the appropriate response was not dictated by the circumstances. This association was not observed in patients with remitting illness, providing neuropsychological support to the distinction between 'negative' and 'deficit' symptoms in schizophrenia. Disorganisation syndrome was associated with impaired performance in the classical Stroop test, as shown in previous studies, but not with impairment in a task which required suppression of processing of irrelevant aspects of a stimulus, nor with impairment in a task which required the suppressing of a primed but irrelevant non-verbal response. This suggests that the disorganisation syndrome might be associated with a specific difficulty in suppressing irrelevant verbal responses.

Adult↗
PubMed1998

Decreased brain GABA(A)-benzodiazepine receptor binding in panic disorder: preliminary results from a quantitative PET study.

BACKGROUND: Positron emission tomography (PET) allows the measurement of benzodiazepine-gamma-aminobutyric acidA (GABA(A)) receptor kinetics. We employed flumazenil radiolabeled with carbon 11, a radioligand that labels the benzodiazepine site on the GABA(A) receptor, and fully quantitative, high-sensitivity PET to test the hypothesis that central benzodiazepine site binding is decreased in medication-free patients with panic disorder. METHODS: We compared 7 patients with panic disorder who had been off medication for at least 6 months and who had never abused alcohol with 8 healthy controls. The resulting parametric voxel-by-voxel maps were analyzed by voxel-based and region of interest-based methods using both parametric and nonparametric statistics. RESULTS: The major finding was that there is a global reduction in benzodiazepine site binding throughout the brain in patients with panic disorder compared with controls. There were sex differences in the 2 samples, but a separate analysis excluding women led to the same conclusions. In addition, the loci with the largest regional decrease in binding (right orbitofrontal cortex and right insula) were areas thought to be essential in the central mediation of anxiety. CONCLUSION: These results must be considered preliminary but are congruous with previous clinical psychopharmacologic evidence of involvement of the benzodiazepine-GABA(A) receptor and demonstrate that decreased flumazenil binding at this site may underlie panic disorder.

Adult↗
PubMed1998

Pathophysiology of 'positive' thought disorder in schizophrenia.

BACKGROUND: Formal thought disorder is a characteristic feature of psychosis, but little is known of its pathophysiology. We have investigated this in schizophrenia using positron emission tomography (PET). METHOD: Regional cerebral blood flow was measured using H2(15)O and PET while six people with schizophrenia were describing a series of 12 ambiguous pictures which elicited different degrees of thought-disordered speech. In a within-subject design, the severity of 'positive' thought disorder was correlated with cerebral blood flow across the 12 scans in each subject. RESULTS: Verbal disorganisation (positive thought disorder) was inversely correlated with activity in the inferior frontal, cingulate and left superior temporal cortex, and positively correlated with activity in the parahippocampal/anterior fusiform region bilaterally, and in the body of the right caudate (P < 0.001). The total amount of speech produced (independent of thought disorder) was positively correlated with activity in the left inferior frontal and left superior temporal cortex. CONCLUSIONS: The severity of positive thought disorder was inversely correlated with activity in areas implicated in the regulation and monitoring of speech production. Reduced activity in these regions may contribute to the articulation of the linguistic anomalies that characterise positive thought disorder. The positive correlations between positive thought disorder and parahippocampal/anterior fusiform activity may reflect this region's role in the processing of linguistic anomalies.

Adult↗
PubMed1998

Functional magnetic resonance imaging: the basics of blood-oxygen-level dependent (BOLD) imaging.

There are 2 principal techniques of functional MRI (fMRI): the blood-oxygen-level dependent (BOLD) technique, which is the favoured method because no intravenous contrast medium is required, and the dynamic or exogenous technique. The BOLD technique takes advantage of the fact that the change from diamagnetic oxyhemoglobin to paramagnetic deoxyhemoglobin that takes place with brain activation results in decreased signal intensity on MRI. Commercially available scanners can be used to conduct single-slice BOLD fMRI experiments, but echo-planar hardware is needed for multislice wholebrain experiments. Sequence choices in BOLD fMRI include spin-echo and gradient-echo sequences, to which rapid acquisition with relaxation enhancement and echoplanar techniques may be applied. Optimal imaging parameters (echo time, slice thickness, field of view and flip angle) are important in maximizing signal-to-noise ratios. Various statistical techniques and software programs have been developed to interpret the large amounts of data gathered from BOLD fMRI experiments, which presents one of the biggest challenges in performing this technique with clinical MR units. Controversy exists regarding the effects of draining veins on cortical mapping, of inflow of blood into the imaging slice or volume, and of motion artifact. BOLD fMRI has demonstrated good correlation with positron emission tomography, magneto-encephalography and electrocorticographic recordings of motor responses. It has been used to study cortical activity of visual, motor, auditory and speech tasks as well as brain centres for smell, motor imagery, complex motion and memory. As such, it holds promise for the study of brain function, but must be subjected to larger studies comparing it with the gold standard of electrocorticographic mapping.

Arousal↗
PubMed1997

A PET study of voluntary movement in schizophrenic patients experiencing passivity phenomena (delusions of alien control).

Schizophrenic patients experiencing passivity phenomena believe their thoughts and actions to be those of external, or alien, entities. We wished to test the hypothesis that voluntary motor action in such patients would be associated with aberrant patterns of activation within the cerebral motor system. We used H2(15)O PET to study patients while they performed paced joystick movements on two occasions 4-6 weeks apart. During the first scan passivity symptoms were maximal, while by the second scan these symptoms had significantly improved in five of the seven patients. Two control groups were also scanned on two occasions: deluded schizophrenic patients without passivity phenomena and normal subjects. In normal subjects, performance of freely selected joystick movements with the right hand, compared with rest, revealed relative activation of prefrontal, premotor, motor and parietal cortical regions. Schizophrenic patients with passivity showed hyperactivation of parietal and cingulate cortices. This hyperactivation remitted in those subjects in whom passivity decreased over time. This reversible hyperactivity was not a feature of schizophrenics without passivity. Given that these hyperactive cerebral regions subserve attention to internal and external bodily space, and the attribution of significance to sensory information, they provide a plausible anatomical substrate for the misattribution of internally generated acts to external entities: the cardinal feature of delusions of passivity (alien control).

Brain Mapping↗
PubMed1997

Grey matter correlates of syndromes in schizophrenia. A semi-automated analysis of structural magnetic resonance images.

BACKGROUND: Symptoms in schizophrenia cluster into syndromes, each of which may be associated with a particular pattern of cerebral blood flow. We sought to investigate whether these syndromes are also related to neuroanatomical changes. METHOD: A semi-automated method was used to examine structural magnetic resonance images in 12 patients with schizophrenia. The relationship between the relative regional grey matter volume and ratings of the syndromes of psychomotor poverty, disorganisation and reality distortion was investigated. RESULTS: There was a significant negative correlation between psychomotor poverty score and the relative volume of the left ventro-medial prefrontal grey matter, and a significant positive correlation between disorganisation and the relative volumes of the hippocampus, and the parahippocampal/fusiform gyrus bilaterally. CONCLUSION: The correlation between psychomotor poverty and left prefrontal grey matter volume resembles that previously seen with prefrontal blood flow in the same patient, suggesting that this functional abnormality is related to an underlying anatomical change.

Adult↗
PubMed1996

Functional imaging--schizophrenia.

Evidence from recent studies of brain function in schizophrenia confirms that the frontal underactivity reported in earlier studies is a feature only of cases with decreased psychomotor activity, while patients with different symptom profile have different patterns of cerebral activity. Each of the three major groups of schizophrenic symptoms reflects a specific pattern of aberrant cerebral activity in association cortex of frontal, parietal and temporal lobes, and in related subcortical nuclei. These patterns indicate imbalances between neuronal activity at diverse interconnected brain sites, rather than abnormal function at a single location. Furthermore, during the performance of executive tasks, schizophrenic subjects exhibit impaired frontal activation, while during memory tasks there a tendency towards impaired temporal lobe activation. The difficulty activating a particular region does not reflect fixed loss of function. Rather the evidence indicates that the characteristic feature of schizophrenia is disturbed connectivity between cerebral areas.

Brain↗
PubMed1995

Inner connections within domain of dementia praecox: role of supervisory mental processes in schizophrenia.

Kraepelin's conclusion that there were underlying common features justifying the amalgamation of catatonia, hebephrenia and paranoia hallucinatoria to form a single illness is confirmed by factor analytic studies delineating the various dimensions of schizophrenic psychopathology. Neuropsychological studies reveal that the three cardinal dimensions reflect disorder of the supervisory mental processes responsible for initiation, selection and monitoring of self-generated mental activity. Brain-imaging studies indicate that the underlying neuropathology entails disordered functional connectivity within the neural networks in multimodal association cortex that are the substrate of the supervisory mental processes, consistent with Kraepelin's own speculation about the essential nature of the condition.

Humans↗