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P Fletcher

Publications and source records attributed to P Fletcher.

At least 37 records · Page 2Linked to original sources
PubMed1999

Learning-related neuronal responses in prefrontal cortex studied with functional neuroimaging.

We assessed time-dependent neuronal activity accompanying learning using functional magnetic resonance imaging (fMRI). An artificial grammar learning paradigm enabled us to dissociate activations associated with individual item learning from those involved in learning the underlying grammar system. We show that a localized region of right prefrontal cortex (PFC) is preferentially sensitive to individual item learning during the early stages of the experiment, while the left PFC region is sensitive to grammar learning which occurred across the entire course of the experiment. In addition to dissociating these two types of learning, we were able to characterize the effect of rule acquisition on neuronal responses associated with explicit learning of individual items. This effect was expressed as modulation of the time-dependent right PFC activations such that the early increase in activation associated with item learning was attenuated as the experiment progressed. In a further analysis we used structural equation modelling to explore time-dependent changes in inter-regional connectivity as a function of both item and grammar rule learning. Although there were no significant effects of item learning on the measured path strengths, rule learning was associated with a decrease in right fronto-parietal connectivity and an increase in connectivity between left and right PFC. Further fronto-parietal path strengths were observed to change, with an increase in left fronto-parietal and a decrease in right fronto-parietal connectivity path strength from right PFC to left parietal cortex. We interpret our findings in terms of a left frontal system mediating the semantic analysis of study items and directly influencing a right fronto-parietal system associated with episodic memory retrieval.

Adult↗
PubMed1998

Event-related fMRI: characterizing differential responses.

We present an approach to characterizing the differences among event-related hemodynamic responses in functional magnetic resonance imaging that are evoked by different sorts of stimuli. This approach is predicated on a linear convolution model and standard inferential statistics as employed by statistical parametric mapping. In particular we model evoked responses, and their differences, in terms of basis functions of the peri-stimulus time. This facilitates a characterization of the temporal response profiles that has a high effective temporal resolution relative to the repetition time. To demonstrate the technique we examined differential responses to visually presented words that had been seen prior to scanning or that were novel. The form of these differences involved both the magnitude and the latency of the response components. In this paper we focus on bilateral ventrolateral prefrontal responses that show deactivations for previously seen words and activations for novel words.

Evoked Potentials↗
PubMed1997

The functional anatomy of verbal initiation and suppression using the Hayling Test.

This study utilised positron emission tomography (PET) to identify the cortical areas involved in verbal initiation and suppression in normal subjects whilst performing a sentence completion test (the Hayling Test). In the first condition (response initiation) subjects were required to complete a sentence from which the last word was omitted, whereas in the second condition (response suppression) subjects were asked to complete a sentence with a word which made no sense in the context of the sentence. Subjects were also required to perform a control task in which they had to read out the last word of given sentences. Compared to the control task, response initiation was associated with left-sided activation of the frontal operculum, inferior frontal gyrus, middle temporal gyrus and the right anterior cingulate gyrus, whereas response suppression was associated with left frontal operculum, inferior frontal gyrus and right anterior cingulate gyrus activation. The difference in activation between the two conditions of the Hayling Test lay in the increased activation of the left middle temporal gyrus and the left inferior frontal gyrus during response initiation.

Adult↗
PubMed1997

Transiently decreased sialylation of thyrotropin (TSH) in a patient with the euthyroid sick syndrome.

A 60-year old woman was admitted to the medical intensive care unit with respiratory distress and worsening renal function, and was found to have bilateral renal artery occlusion. Aggressive nutrition per nasogastric tube was begun on day 8 of her illness, and she eventually recovered after bilateral renal artery bypass surgery, which was performed on day 15. She developed the euthyroid sick syndrome. Levels of serum TSH, T3, and T4 fell during the first few days of her illness, then all trended to normal levels by day 28. The TSH level declined from 1.6 microU/mL on day 2 to 0.2 microU/mL on day 5, then rose to 4.5 microU/mL on day 10, and was 3.8 microU/mL on day 14. The ratios of free T4/TSH, a crude measure of the bioactivity of TSH, were 1.4, 8.0, 0.16, 0.32, and 1.14 on days 2, 5, 10, 14 and 28, respectively. TSH was immunoaffinity concentrated from serum collected on four dates. The TSH oligosaccharides were enzymatically released, treated with or without neuraminidase, labeled with a fluorescent probe, and analyzed by gel electrophoresis. The TSH oligosaccharides were found to be transiently less sialylated on day 13 as compared to days 2, 4, and 24. Three gel bands representing poorly sialylated oligosaccharides represented a mean of 20.6% of TSH oligosaccharides on days 2, 4, and 24, but represented 33.7% of TSH oligosaccharides on day 13. This is the first report of altered TSH oligosaccharide sialylation in the euthyroid sick syndrome. If confirmed by studies of additional patients, altered TSH sialylation may, in part, explain the altered TSH bioactivity that has been described in the euthyroid sick syndrome.

Chromatography, Affinity↗
PubMed1997

Verbs in the emergence of word combinations in young children with specific expressive language impairment.

Young children with specific expressive language impairment (SELI) are typically first identified by their delay in initial vocabulary learning. When their language difficulties persist they often have problems with verb constructions. The purpose of the present study was to examine the role of lexical development in children with SELI who were moving from the single-word to the multi-word stage of language production, with particular attention to verbs. The research examined the nature of the developing lexicon (lexicon size and composition) and realisation of lexical categories and their combinatorial properties transitivity of verbs) as the children began producing word combinations during a nine-week period of observation, three weeks of which involved treatment. Results indicated a moderate correlation between the developing lexicon, both in size and composition of vocabulary, and the emergence of word combinations as measured by mean length of utterance. Further, the data revealed the importance of intransitive and ditransitive verbs for children who demonstrated the greatest change in their language production. The findings are discussed in terms of their theoretical and clinical importance.

Child, Preschool↗
PubMed1996

'Theory of mind' in the brain. Evidence from a PET scan study of Asperger syndrome.

The ability to attribute mental states to others ('theory of mind') pervades normal social interaction and is impaired in autistic individuals. In a previous positron emission tomography scan study of normal volunteers, performing a 'theory of mind' task was associated with activity in left medial prefrontal cortex. We used the same paradigm in five patients with Asperger syndrome, a mild variant of autism with normal intellectual functioning. No task-related activity was found in this region, but normal activity was observed in immediately adjacent areas. This result suggests that a highly circumscribed region of left medial prefrontal cortex is a crucial component of the brain system that underlies the normal understanding of other minds.

Adult↗
PubMed1996

Omeprazole and visual disorders: seeing alternatives.

In the WHO data base, visual disorders reported spontaneously with omeprazole, ranitidine and cimetidine, are very rare in the context of the widespread use of these drugs. There is a maximum reporting rate of severe visual impairment possibly ascribed to i.v. omeprazole of 0.94 reports per million treatment days in one year and in one country, Germany. This gives the worst quantitative case scenario for omeprazole by a single route of administration, to be compared with the worldwide reporting rate of all severe visual disorders by all routes of administration--0.008 reports per million treatment days. Moreover, the reported visual abnormalities have a varied pathophysiological aetiology and their number increased in Germany after the first signal was raised in that country. Thus, apart from a direct causal relationship, solicited reporting artifact is one alternate plausible explanation for the apparent excess of cases of visual disturbance to omeprazole compared with cimetidine and ranitidine. That reporting rates of clinical events on newly marketed drugs are generally higher than with older drugs is a second factor for higher reporting rates with omeprazole. Vasculitis has been suggested as an aetiological factor, but the even lower reporting rate of this reaction makes this an unlikely hypothesis without any other supporting evidence. The authors are unaware of any drug that has caused a vasculities solely affecting the eye. Information on the prevalence of relevant visual disorders in the community would have been of considerable help in interpreting this signal, and a case control study of visual events in relationship to severe illness would be of public health interest, since no data seems to exist concerning this.

Journal Article↗
PubMed1996

The trouble with cognitive subtraction.

In this paper we present a critique of pure insertion. Pure insertion represents an implicit assumption behind many (but not all) studies that employ cognitive subtraction. The main contention is that pure insertion is not valid in relation to the neuronal instantiation of cognitive processes. Pure insertion asserts that there are no interactions among the cognitive components of a task. It is possible to evaluate and refute this assumption by testing explicitly for interactions using factorial experimental designs. It is proposed that factorial designs are more powerful than subtraction designs in characterizing cognitive neuroanatomy, precisely because they allow for interactions and eschew notions like pure insertion. In particular we suggest that the effect of a cognitive component (i.e., an effect that is independent of other components) is best captured by the main (activation) effect of that component and that the integration among components (i.e., the expression of one cognitive process in the context of another) can be assessed with the interaction terms. In this framework a complete characterization of cognitive neuroanatomy includes both regionally specific activations and regionally specific interactions. To illustrate our point we have used a factorial experimental design to show that inferotemporal activations, due to object recognition, are profoundly modulated by phonological retrieval of the object's name. This interaction implicates the inferotemporal regions in phonological retrieval, during object naming, despite the fact that phonological retrieval does not, by itself, activate this region.

Attention↗
PubMed1996

Neural activation during covert processing of positive emotional facial expressions.

Lesion studies indicate distinct neural systems for recognition of facial identity and emotion. Split-brain experiments also suggest that emotional evaluation of a stimulus can occur without conscious identification. The present study tested a hypothesis of a differential neural response, independent of explicit conscious mediation, to emotional compared to nonemotional faces. The experimental paradigm involved holding in mind an image of a face across a 45-s delay while regional cerebral blood flow was measured using positron emission tomography. Prior to the delay, a single face was presented with an explicit instruction to match it to one of two faces, photographed at different angles from the target face, presented at the end of the delay. Repeated blood flow measures were obtained while subjects held happy or neutral faces in mind or during a neutral control fixation condition without initial face presentation. The representation of emotional faces over a delay period, compared to either the nonemotional or the fixation condition, was associated with significant activation in the left ventral prefrontal cortex, the left anterior cingulate cortex, and the right fusiform gyrus. The findings support our hypothesis of a differential neural response to facial emotion, independent of conscious mediation, in regions implicated in the processing of faces and of emotions.

Adult↗
PubMed1996

Cardiovascular findings in self-reported healthy elderly. The Elite Seniors Study.

BACKGROUND: A descriptive study of self-reported healthy elderly in Newcastle was undertaken for an adequate understanding of the normal characteristics of the elderly. AIMS: We sought to determine the frequency of abnormal clinical, laboratory and echocardiographic findings in a self-reported healthy elderly population. METHODS: Volunteers aged greater than 75 years were recruited from active members of the region's bowling clubs. Forty-five subjects with no self-reported vascular or cardiac disease underwent clinical, laboratory and echocardiography assessment. RESULTS: Minor cardiovascular abnormalities were frequently detected. Echocardiography correspondingly found a high frequency of haemodynamically insignificant degenerative valvular lesions. Doppler left ventricular filling pattern of abnormal relaxation was a universal finding. CONCLUSION: There is a high prevalence of age-related echo-Doppler abnormalities in the self-reported healthy elderly with important implications for the interpretation of echo-Doppler studies.

Aged↗
PubMed1995

Dopaminergic modulation of impaired cognitive activation in the anterior cingulate cortex in schizophrenia.

Dopaminergic dysregulation remains an empirical cornerstone for theories concerning the causation of schizophrenia. Evidence for a dopamine system dysfunction in schizophrenia includes the psychosis-inducing effects of dopaminergic agonists and the antipsychotic potency of dopaminergic antagonists. Here we use positron emission tomography (PET) to examine the regulatory role of dopamine on cortical function in normal subjects and unmedicated schizophrenic patients. Using a factorial experimental design, we compared the effect of dopaminergic manipulation with apomorphine on a neural response to a cognitive task. In the schizophrenic patients, relative to controls, an impaired cognitive activation of the anterior cingulate cortex was significantly modulated by a manipulation of dopaminergic neurotransmission. Thus, after apomorphine, the schizophrenic subjects displayed a significantly enhanced cognitive activation of the anterior cingulate cortex relative to the controls. These data provide in vivo evidence that an impaired cognitive-task-induced activation of the anterior cingulate cortex in schizophrenic patients can be significantly modulated by a dopaminergic manipulation.

Adult↗
PubMed1995

Praxic and nonverbal cognitive deficits in a large family with a genetically transmitted speech and language disorder.

A pronounced speech and language disorder affecting half of the 30 members of the four-generational KE family has been attributed by some researchers to a specific defect in the generation of morphosyntactic rules. The reported selectivity of the impairment has led to the view that the affected members suffer from a grammar-specific disorder. Our investigations of the same KE family indicate that the inherited disorder has a broad phenotype which transcends impaired generation of syntactical rules and includes a striking articulatory impairment as well as defects in intellectual, linguistic, and orofacial praxic functions generally. Although the evidence from this family thus provides no support for the existence of "grammar genes," their linguistic difficulties do constitute a prominent part of their phenotype. Investigations of the neural and genetic correlates of their disorder could therefore uncover important clues to some of the bases of the primary human faculties of speech and language.

Cognition Disorders↗
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↗
PubMed1995

Benefit/risk considerations with respect to OTC-descheduling of loperamide.

The main criteria to be considered for releasing an antidiarrhoeal from a prescription to an OTC-drug are guaranteed quality control, established efficacy and safety and the evaluation of the drug experience on major markets. Besides the considerable benefits from a socio-economic point of view, the risk for potential inappropriate use of loperamide (CAS 53179-11-6) as self-medication can be minimized by its use being avoided in children of 5 years of age or less (e.g. by making available a solid formulation only), by limiting the treatment duration to 48 h, and by contraindicating the use of the drug in cases of fever (> 38 degrees C) and/or blood in the stools. On the basis of a broad review loperamide can be considered to be efficacious in acute non-specific, acute functional and traveller's diarrhoea. The agent has a good safety profile if the mentioned restrictions are born in mind. Loperamide thus satisfies the OTC criteria.

Adult↗