Biomedical subjects

P C Fletcher

Publications and source records attributed to P C Fletcher.

At least 37 records · Page 2Linked to original sources

PubMed2000

The role of the right anterior prefrontal cortex in episodic retrieval.

Regional brain activity was measured with H(2) (15)O PET while participants attempted to complete word-stem and word-fragment retrieval cues with previously studied words. The retrieval cue manipulation was employed to gain control over the monitoring operations associated with evaluating the episodic status of alternative cue completions. These operations were more constrained for fragments, which had fewer possible completions than each corresponding stem. In one condition (zero target), during the scanning interval none of the cues could be completed with studied items, whereas in another condition (high target), 80% of cues belonged to studied items. Relative to baseline tasks, right anterior prefrontal activity was greater for stems than for fragments in the zero target condition. The target density manipulation did not modulate right anterior prefrontal activity, but was associated with increased activity in right dorsolateral prefrontal cortex. These findings are consistent with the proposal that the right anterior prefrontal cortex supports monitoring operations during episodic retrieval tasks. In addition, the findings add to evidence suggesting that the dorsolateral and anterior right prefrontal cortex make functionally distinct contributions to episodic retrieval.

Adult↗

PubMed2000

"Sculpting the response space"--an account of left prefrontal activation at encoding.

Left lateral prefrontal cortex (PFC) is consistently activated in neuroimaging studies of memory encoding. Its role, however, remains unclear. We describe two functional magnetic resonance imaging (fMRI) studies addressing this question. In the first we used a blocked experimental design to explore the effect of repeated encoding of word paired associates. Initial presentation of word pairs was associated with left ventrolateral PFC activation that attenuated with subsequent presentations of the same lists. When well-learned lists were presented with word pairs rearranged, a left PFC activation, greater than that associated with the initial presentation, was observed. In a second experiment, the formation of these associative relationships was explored using an event-related design. Two types of word pairs were presented: closely related (e.g., King...Queen) and distantly related (e.g., Net...Ship). The same region of left PFC was differentially sensitive to these two event-types, showing a greater response for distantly related pairs. We suggest that left PFC activity, at memory encoding, reflects operations necessary to the formation of meaningful associations in the service of optimal learning. A crucial feature of such associative processing lies in selecting appropriate, and inhibiting inappropriate, semantic attributes of the study material.

Adult↗

PubMed2000

Reading the mind in cartoons and stories: an fMRI study of 'theory of mind' in verbal and nonverbal tasks.

Previous functional imaging studies have explored the brain regions activated by tasks requiring 'theory of mind'--the attribution of mental states. Tasks used have been primarily verbal, and it has been unclear to what extent different results have reflected different tasks, scanning techniques, or genuinely distinct regions of activation. Here we report results from a functional magnetic resonance imaging study (fMRI) involving two rather different tasks both designed to tap theory of mind. Brain activation during the theory of mind condition of a story task and a cartoon task showed considerable overlap, specifically in the medial prefrontal cortex (paracingulate cortex). These results are discussed in relation to the cognitive mechanisms underpinning our everyday ability to 'mind-read'.

Adult↗

PubMed1999

Segregating the functions of human hippocampus.

It is now accepted that hippocampal lesions impair episodic memory. However, the precise functional role of the hippocampus in episodic memory remains elusive. Recent functional imaging data implicate the hippocampus in processing novelty, a finding supported by human in vivo recordings and event-related potential studies. Here we measure hippocampal responses to novelty, using functional MRI (fMRI), during an item-learning paradigm generated from an artificial grammar system. During learning, two distinct types of novelty were periodically introduced: perceptual novelty, pertaining to the physical characteristics of stimuli (in this case visual characteristics), and exemplar novelty, reflecting semantic characteristics of stimuli (in this case grammatical status within a rule system). We demonstrate a left anterior hippocampal response to both types of novelty and adaptation of these responses with stimulus familiarity. By contrast to these novelty effects, we also show bilateral posterior hippocampal responses with increasing exemplar familiarity. These results suggest a functional dissociation within the hippocampus with respect to the relative familiarity of study items. Neural responses in anterior hippocampus index generic novelty, whereas posterior hippocampal responses index familiarity to stimuli that have behavioral relevance (i.e., only exemplar familiarity). These findings add to recent evidence for functional segregation within the human hippocampus during learning.

Adolescent↗

PubMed1999

The role of the prefrontal cortex in recognition memory and memory for source: an fMRI study.

We employed fMRI to index neural activity in prefrontal cortex during tests of recognition and source memory. At study, subjects were presented with words displayed either to the left or right of fixation, and, depending on the side, performed one of two orienting tasks. The test phase consisted of a sequence of three 10-word blocks, displayed in central vision. For one block, subjects performed recognition judgements on a mixture of two old and eight new words (low density recognition). For another block, recognition judgements were performed on a mixture of eight old and two new words (high density recognition). In the remaining block, also consisting of eight old and two new items, the requirement was to judge whether each word had been presented at study on the left or the right. Relative to the low density condition, high density recognition was associated with increased activity in right and, to a lesser extent, left, anterior prefrontal cortex (BA 10), replicating the findings of two previous PET studies. Right anterior prefrontal activity did not show any further increase during the source task. Instead, greater activity was found, relative to high density recognition, in left BA 10, left inferior frontal gyrus (BA 45/47), and bilateral opercular cortices (BA 45/47). The findings are inconsistent with the proposal that activation of right anterior prefrontal cortex during memory retrieval reflects "postretrieval" processing demands, such demands being considerably greater for judgments of source than recognition. The findings provide further evidence that the left prefrontal cortex plays a role in episodic memory retrieval when the task explicitly requires recovery of contextual as well as item information.

Adult↗

PubMed1999

Abnormal neural integration related to cognition in schizophrenia.

A striking feature of schizophrenia is the diversity of the phenomenology both within and between patients. This diversity can be contrasted with the well-circumscribed and stable deficits seen in classic neuropsychological syndromes. The argument will be advanced that the classic lesion model, based on the notion of a segregated deficit, is inappropriate in schizophrenia. Instead the idea will be developed that a more appropriate model is one derived from concepts of neural integration across large-scale brain networks. Empirical data derived from positron emission tomography (PET) within our laboratory that provide support for this suggestion will be presented. One critical observation from these data is a disruption of prefrontal-temporal interactions, under a variety of cognitive activation paradigms, in both chronic medicated and acute unmedicated schizophrenic patients. Furthermore, these data indicate that both regional and interregional neuronal function, including prefrontal-temporal interactions, can be significantly modulated by a neurochemical perturbation of ascending dopaminergic systems. The latter observations suggest that the deficit of abnormal cortico-cortical interactions are to some extent modifiable by neuromodulatory neurotransmitter systems.

Acute Disease↗

PubMed1998

Brain activations in schizophrenia during a graded memory task studied with functional neuroimaging.

BACKGROUND: Functional neuroimaging experiments have implicated prefrontal cortex (PFC) in memory processes. Several studies of schizophrenic patients have shown failure of activation in the dorsolateral region of PFC (DLPFC). We used a graded memory challenge to characterize functional neuroanatomical differences between schizophrenic and control subjects. The graded manipulation of task demands enabled us to assess group differences in the context of normal and abnormal psychological task performance. METHODS: Memory-related activity was assessed using positron emission tomography in schizophrenic patients and age-matched controls during performance of a graded memory task. Subjects underwent scanning while learning and recalling word lists of variable length. RESULTS: We used a model that assessed linear and nonlinear effects of memory load. Nonlinear group differences in DLPFC activation were observed. Controls showed a steepening slope of DLPFC increase as task demands increased. By contrast, schizophrenic subjects showed initial DLPFC increases that fell away with increasing memory load. The DLPFC response in schizophrenic subjects was closely related to measured task performance. In addition, schizophrenic subjects failed to show task-related decreases in activity in the left superior temporal and inferior parietal gyrus. CONCLUSIONS: Patients with schizophrenia showed a failure in DLPFC activation only in the face of diminished performance measures, suggesting that a full characterization of task-related changes in DLPFC activation must consider performance levels. However, striking failures of deactivation in superior temporal and inferior parietal regions were independent of task performance, possibly reflecting a core abnormality of the condition.

Adult↗

PubMed1998

Neural correlates of memory retrieval during recognition memory and cued recall.

Regional brain activity, measured by H215O PET, was investigated during recognition memory and word-stem cued recall of words in order to compare the neural correlates of two components of memory retrieval-effort and success-as a function of task. For each task there was a baseline and two retrieval conditions. In one retrieval condition (zero density), none of the test items corresponded to words encoded in a preceding study phase. Differences in activity between this condition and the baseline were employed to characterize the neural correlates of retrieval effort in each task. In the other retrieval condition (high density), 80% of the test items had been studied previously. Differences in brain activity between this condition and the zero-density condition were taken to represent the neural correlates of successful retrieval. The principal findings concern the right anterior prefrontal cortex, a region demonstrated previously to be active during episodic retrieval. Relative to baseline, this region showed no evidence of activation in the zero-density condition of the recognition task, but did show enhanced activity in the equivalent condition of the cued-recall task. In contrast, relative to the zero-density condition, the high-density condition was associated with increased right prefrontal activity during recognition, but reduced activity during cued recall. It is proposed that the right prefrontal cortex supports cognitive processes that operate on information retrieved in response to a test item and that these processes contribute to the evaluation of whether the information represents an appropriate prior episode.

Adult↗

PubMed1998

Neural correlates of depth of processing effects on recollection: evidence from brain potentials and positron emission tomography.

The probability that words would be recollected during tests of recognition memory was varied by manipulating depth of processing at study. Experiment 1 employed scalp-recorded event-related potentials (ERPs), and identified as a correlate of recollection a late (onset c. 500 ms), strongly left-lateralized positive-going modulation of the ERP waveform. The findings from experiment 2, which employed positron emission tomography (PET), indicated that recollection was associated with activation of the left hippocampal formation together with an extensive region of left temporal and frontal cortex. The findings support current ideas about the role of the hippocampal formation in episodic memory retrieval, and provide complementary information about the time course and localization of the cortical correlates of the recollection of recently experienced words.

Behavior↗

PubMed1998

The functional roles of prefrontal cortex in episodic memory. I. Encoding.

Functional neuroimaging studies of episodic memory consistently report an association between memory encoding operations and left prefrontal cortex (PFC) activation. Encoding-related activation has been described in dorsolateral, ventrolateral and anterior prefrontal regions. We tested the hypothesis that a specific component of this left PFC activation reflects organizational processes necessary for optimal memory encoding. Subjects underwent PET scans while learning auditorily presented word lists under dual task conditions. The degree to which they were required to organize word lists semantically was systematically varied across three experimental conditions. A task in which words were already organized produced the least degree of left PFC activity whereas a task requiring subjects to generate an organizational structure was associated with maximal activity in this region. This activation was localized to a region just above the inferior frontal sulcus. The functional specificity of this increased activity for organizational processes was tested using a concurrent distracting task known to disrupt these processes. Distraction resulted in a significant attenuation of this activation during the task emphasizing organizational processes but not other encoding tasks. In contrast, the distraction task resulted in reduced activity in a more ventral/anterior PFC region expressed equally for all memory tasks. The findings indicate that a key function of left dorsolateral PFC at encoding relates specifically to the use of executive processes necessary for the creation of an organizational structure. Activity in more ventral and anterior left PFC regions would appear to reflect a less specific component of episodic memory encoding.

Adult↗

PubMed1998

The functional roles of prefrontal cortex in episodic memory. II. Retrieval.

Functional neuroimaging studies of memory retrieval show consistent activation of the right prefrontal and superior parietal cortex. We examined the specific role of the prefrontal cortex during retrieval with the hypothesis that this region mediates monitoring processes necessary for optimal recall. During functional neuroimaging with PET, subjects retrieved verbal material under two conditions. In the first, an organizational structure had been provided, prior to scanning, and this formed the basis for a monitored memory search while the scan took place. A comparison condition did not require a monitored search because recall was externally cued. In both conditions, when compared with baseline tasks prefrontal cortex and medial parietal activation was observed. Within the right prefrontal cortex activation an anatomical dissociation was seen between the dorsal and ventral prefrontal cortex. The dorsal region showed greater activation when monitoring demands were emphasized, while the ventral region showed greater activation when external cueing was emphasized. An unpredicted dissociation within the superior parietal activation was also observed, a dorsal region showing activation during the monitored search task and a more ventral region showing activation under the externally cued condition. The results provide evidence for functional specialization of the right prefrontal cortex for discrete cognitive processes during episodic memory retrieval.

Adult↗

PubMed1997

Dissociating prefrontal and hippocampal function in episodic memory encoding.

Human lesion data indicate that an intact left hippocampal formation is necessary for auditory-verbal memory. By contrast, functional neuroimaging has highlighted the role of the left prefrontal cortex but has generally failed to reveal the predicted left hippocampal activation. Here we describe an experiment involving learning category-exemplar word pairs (such as 'dog...boxer') in which we manipulate the novelty of either individual elements or the entire category-exemplar pairing. We demonstrate both left medial temporal (including hippocampal) and left prefrontal activation and show that these activations are dissociable with respect to encoding demands. Left prefrontal activation is maximal with a change in category-exemplar pairings, whereas medial temporal activation is sensitive to the overall degree of novelty. Thus, left prefrontal cortex is sensitive to processes required to establish meaningful connections between a category and its exemplar, a process maximized when a previously formed connection is changed. Conversely, the left medial temporal activation reflects processes that register the overall novelty of the presented material. Our results provide striking evidence of functionally dissociable roles for the prefrontal cortex and hippocampal formation during learning of auditory-verbal material.

Association Learning↗

PubMed1997

Brain regions supporting intentional and incidental memory: a PET study.

Regional brain activity associated with intentional and incidental memory retrieval was studied with PET. Previously studied and new words were presented in either an intentional or an incidental memory task. Type of task was crossed with an encoding manipulation ('deep' vs 'shallow') which varied the probability that studied items would be remembered. In both tasks, deeply encoded items were associated with greater activation in the left hippocampus than were items that had received shallow encoding, suggesting that the involvement of the hippocampus in memory retrieval is independent of whether remembering is intentional or incidental. Right prefrontal and bilateral parietal cortex were more activated during the international task than during the incidental task, irrespective of encoding condition. Thus, these regions play a more extensive role in memory retrieval when remembering is intentional.

Brain↗

PubMed1997

The functional neuroanatomy of episodic memory.

Functional neuroimaging studies have revealed that effective encoding in episodic memory is associated with enhanced activity in left prefrontal cortex, whereas retrieval is accompanied by the enhancement of predominantly right-sided prefrontal activity. The extent of the contribution of prefrontal cortex to episodic memory, and the fact that the encoding and retrieval operations it supports are differentially lateralized, were unexpected on the basis of evidence from lesion studies. Such studies have highlighted the crucial role in episodic memory played by the hippocampus and related medial temporal lobe structures. Neuroimaging studies, however, have had only limited success in elucidating the role of the hippocampus in episodic memory. Refinements in experimental design and improved spatial resolution should promote rapid future progress with respect to this issue.

Brain↗

PubMed1996

Local and distributed effects of apomorphine on fronto-temporal function in acute unmedicated schizophrenia.

We used positron emission tomography (PET) to measure brain activity in healthy control subjects and unmedicated patients with schizophrenia. Subjects were scanned in the context of a combined psychological and pharmacological challenge, and we examined the effects of apomorphine, a drug acting on dopamine receptors, on brain systems engaged by a paced verbal fluency task. This factorial design enabled comparison of control subjects and schizophrenics in terms of the activations engendered by the cognitive task and the pharmacological challenge and the interaction of the two. We report a failure of cognitive task-related activation in anterior cingulate cortex and of task-related deactivation in the left superior temporal gyrus in the schizophrenic subjects. Compared with controls, the impaired cingulate activation was significantly reversed by apomorphine. Additionally, there was a trend for the abnormal fronto-temporal pattern of activation in schizophrenic subjects to be normalized by the drug. Overall, in schizophrenic subjects the effect of apomorphine, which we interpret in terms of a net dopaminergic antagonism, was to modify the brain activity, making the pattern more akin to that seen in control subjects. The results indicate both a regionally specific abnormality of brain function in schizophrenia and an abnormal pattern of fronto-temporal interactions.

Acute Disease↗

PubMed1996

Is multivariate analysis of PET data more revealing than the univariate approach? Evidence from a study of episodic memory retrieval.

In a functional imaging study of cued paired associate retrieval, in which the strength of association between pair members was systematically varied, we predicted increased right frontal activity as a function of weakening semantic linkage. An initial univariate analysis found the opposite effect, with greater right frontal activity during recall of strongly linked paired associates. This unexpected result led us to perform a multivariate analysis of covariance (MANCOVA), an approach which proved more informative. This analysis showed that the most significant source of task-related variance was accounted for by a nonlinear relationship not predicted by the prior hypothesis and not revealed by the standard univariate approach. This application of the MANCOVA supports the assertion that multivariate analysis can provide an important adjunct to univariate approaches like statistical parametric mapping (SPM). New perspectives engendered by the MANCOVA still allow for statistical inference but are not constrained by explicit hypotheses about specific task-dependent effects.

Adult↗

PubMed1996

Brain activity during memory retrieval. The influence of imagery and semantic cueing.

The effects of imagery and semantic relatedness on cued retrieval of word pairs were examined in a functional imaging study of healthy volunteers. Subjects underwent 12 PET scans, preceded by the paced presentation of 12 paired associates. The associates were dichotomized into imageable and non-imageable groups. Within each group, the strength of semantic association between members of pairs was varied in an ordinal fashion. Subsequently, neural activity was measured while subjects were cued with the first item of each pair and required to recall the associated word. Recall of imageable words, when compared with non-imageable ones, was associated with activation of the precuneus, consistent with our hypothesis that this region is important in visual imagery at episodic retrieval. The reverse comparison, non-imageable versus imageable recall, was associated with activation of the left dorsolateral prefrontal cortex. Within both imageable and non-imageable groups, decreasing semantic association showed a corresponding increase in frontal activity bilaterally. One possible explanation is that of a practice-related effect, weaker-linked pairs having a greater number of pre-scan presentations. However, this explanation is incomplete as the most semantically distant, and most rehearsed, pairs (randomly linked) were associated with a reversal of this effect. This finding can be explained if frontal activity is associated with the difficulty of eliminating inappropriate responses at retrieval. For both randomly linked pairs and closely related pairs it is more likely that erroneous responses will be generated and, therefore, the work done to eliminate them will be greater. Our findings indicate that patterns of neural activity during cued recall depend upon the nature of the material and on the degree of association between the cue and the response.

Adult↗

PubMed1996

Differential activation of the prefrontal cortex in successful and unsuccessful memory retrieval.

Six subjects underwent PET scans while they performed three versions of a recognition memory test for words and three versions of a control task. In each memory condition, the subjects discriminated between words presented in a prescan study list and words new to the experiment. During the 30 s scanning interval, the ratio of old and new words was 0:20, 4:16 or 16:4, depending on the experimental condition. Outside this interval, the ratio was 50:50 in all three conditions. The requirement in the control task was to discriminate between two character strings, the ratios of which were also manipulated during the 30 s scanning interval. Employing the control task as a covariate, analysis with statistical parametric mapping revealed that regional cerebral blood flow (rCBF) covaried with increasing density of old items in three regions of prefrontal cortex: right dorsolateral [Brodmann area (BA) 9/46], right medial (BA 32/8) and bilateral frontopolar cortex (BA 10). It is concluded that the prefrontal cortex, especially in the right hemisphere, is more active when a retrieval attempt succeeds than when it fails. This finding is consistent with the idea that the prefrontal cortex supports processes that operate selectively on the products of memory retrieval.

Adult↗