Biomedical subjects

P C Fletcher

Publications and source records attributed to P C Fletcher.

At least 19 recordsLinked to original sources

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↗

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↗

PubMed1995

The functional anatomy of memory.

A review of recent work using Positron Emission Tomography (PET) to examine brain systems involved in auditory-verbal memory is presented. Initial work delineated widespread brain regions which were, to a large extent, in agreement with existing neuropsychological literature. Expanding on this, a number of studies have examined memory encoding and retrieval separately. Additionally, experiments have been carried out to specifically address sub-components of memory such as the use of visual imagery as a mnemonic strategy, the functional anatomical evidence for the episodic/semantic memory distinction and the different brain regions involved in explicit and implicit memory tasks.

Animals↗

PubMed1995

The mind's eye--precuneus activation in memory-related imagery.

We examined brain activity associated with visual imagery at episodic memory retrieval using positron emission tomography (PET). Twelve measurements of regional cerebral blood flow (rCBF) were taken in six right-handed, healthy, male volunteers. During six measurements, they were engaged in the cued recall of imageable verbal paired associates. During the other six measurements, they recalled nonimageable paired associates. Memory performance was equalized across all word lists. The subjects' use of an increased degree of visual imagery during the recall of imageable paired associates was confirmed using subjective rating scales after each scan. Memory-related imagery was associated with significant activation of a medial parietal area, the precuneus. This finding confirms a previously stated hypothesis about the precuneus and provides strong evidence that it is a key part of the neural substate of visual imagery occurring in conscious memory recall.

Adult↗

PubMed1995

Other minds in the brain: a functional imaging study of "theory of mind" in story comprehension.

The ability of normal children and adults to attribute independent mental states to self and others in order to explain and predict behaviour ("theory of mind") has been a focus of much recent research. Autism is a biologically based disorder which appears to be characterised by a specific impairment in this "mentalising" process. The present paper reports a functional neuroimaging study with positron emission tomography in which we studied brain activity in normal volunteers while they performed story comprehension tasks necessitating the attribution of mental states. The resultant brain activity was compared with that measured in two control tasks: "physical" stories which did not require this mental attribution, and passages of unlinked sentences. Both story conditions, when compared to the unlinked sentences, showed significantly increased regional cerebral blood flow in the following regions: the temporal poles bilaterally, the left superior temporal gyrus and the posterior cingulate cortex. Comparison of the "theory of mind" stories with "physical" stores revealed a specific pattern of activation associated with mental state attribution: it was only this task which produced activation in the medial frontal gyrus on the left (Brodmann's area 8). This comparison also showed significant activation in the posterior cingulate cortex. These surprisingly clear-cut findings are discussed in relation to previous studies of brain activation during story comprehension. The localisation of brain regions involved in normal attribution of mental states and contextual problem solving is feasible and may have implication for the neural basis of autism.

Adolescent↗

PubMed1995

Brain systems for encoding and retrieval of auditory-verbal memory. An in vivo study in humans.

Long-term auditory-verbal memory comprises, at a neuropsychological level, a number of distinct cognitive processes. In the present study we determined the brain systems engaged during encoding (experiment 1) and retrieval (experiment 2) of episodic auditory-verbal material. In the separate experiments, PET measurements of regional cerebral blood flow (rCBF), an index of neural activity, were performed in normal volunteers during either the encoding or the retrieval of paired word associates. In experiment 1, a dual task interference paradigm was used to isolate areas involved in episodic encoding from those which would be concurrently activated by other cognitive processes associated with the presentation of paired associates, notably priming. In experiment 2, we used the cued retrieval of paired associates from episodic or from semantic memory in order to isolate the neural correlates of episodic memories. Encoding of episodic memory was associated with activation of the left prefrontal cortex and the retrosplenial area of the cingulate cortex, while retrieval from episodic memory was associated with activation of the precuneus bilaterally and of the right prefrontal cortex. These results are compatible with the patterns of activation reported in a previous PET memory experiment in which encoding and retrieval were studied concurrently. They also indicate that separate brain systems are engaged during the encoding and retrieval phases of episodic auditory-verbal memory. Retrieval from episodic memory engages a different, but overlapping, system to that engaged by retrieval from semantic memory, a finding that lends functional anatomical support to this neuropsychological distinction.

Adult↗

PubMed1994

A graded task approach to the functional mapping of brain areas implicated in auditory-verbal memory.

Positron emission tomography measurements of regional cerebral blood flow (rCBF) were performed in normal volunteers during a graded auditory-verbal memory task. Subjects were required to remember and then immediately, and freely, recall a series of auditorily presented word lists varying from two to 13 words in length. Significant regional correlations between rCBF and memory load (word list length) were identified using statistical parametric mapping. Increasing memory load correlated with increasing rCBF in the cerebellar vermis and hemispheres, thalamus bilaterally, the superior and middle frontal gyri bilaterally, anterior insular regions bilaterally, anterior cingulate, precuneus and left and right lateral premotor areas. Increasing memory load also correlated with decreasing rCBF in the left and right superior temporal/insular regions, medial frontal gyrus, Brodmann's area 37 bilaterally, cuneus, inferior parietal lobule bilaterally and the mid-portion of the cingulate cortex. The pattern of rCBF change closely resembled that identified in a previously reported study using a cognitive subtraction paradigm and provides further evidence for a widespread neural system subserving auditory-verbal memory. The patterns of rCBF response suggest that the areas identified are associated with limited capacity processes for encoding and retrieval.

Adult↗