Dissociating prefrontal contributions during a recency memory task

Neuroimaging studies of normal young adults have consistently found right prefrontal cortex (RPFC) activity during the performance of recency memory tasks. However, it is unclear whether the involvement of RPFC during these tasks reflects retrieval processes or executive processes such as: strategic ordering or monitoring. In the current study, we distinguish between those PFC regions that are more related to retrieval processes, versus strategic ordering processes. An event-related fMRI study was conducted in which eight young subjects were scanned while performing verbal episodic retrieval tasks (recognition and recency memory tasks), and verbal non-memory strategic organizing control tasks (reverse alphabetizing of words). The fMRI results show that young subjects engaged right dorsolateral PFC during recency and reverse alphabetizing control tasks. Left ventral PFC was engaged across all tasks; however, a subset of voxels within this region was more active during retrieval tasks. Left dorsolateral and right ventral PFC activity was more related to the performance of reverse alphabetizing tasks, respectively. We conclude that right dorsolateral PFC activity during recency memory reflects more general strategic organizational or monitoring processes, and is not EM-specific.     

Age-related changes in right middle frontal gyrus volume correlate with altered episodic retrieval activity

Age-related deficits in episodic retrieval have been associated with volume reductions in the middle frontal gyrus (MFG). However, it remains unclear how this age-related reduction in MFG volume correlates with neural activity during retrieval. To address this, we conducted in vivo volumetry of the frontal cortex in young and older human adults and found more volume loss on the right than on the left MFG with age. We then examined how left and right MFG volume correlated with fMRI activity during successful retrieval of item, spatial context, and temporal context information in both age groups. In young adults, larger right MFG volume was positively correlated with greater activity in a commonly found episodic retrieval network that included bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral inferior parietal cortex. Within this network, left DLPFC and right inferior parietal cortex activity predicted memory performance. In older adults, a positive structure-function association in DLPFC for either left or right MFG/DLPFC was not observed. Instead, right MFG volume was negatively correlated with activity in several regions in older adults, including the parahippocampal cortex (PHC) and anterior cingulate. Less activity in the PHC region predicted better item memory, and less activity in the anterior cingulate predicted better spatial context accuracy in older adults. We conclude that age-related change in the structure-function association in MFG/DLPFC impacts retrieval activity and performance, and those older adults with larger right MFG volume attempt to compensate for this change by modifying activity in other brain regions to help retrieval performance.     

Task-related activity in prefrontal cortex and its relation to recognition memory performance in young and old adults

Older adults often have more widespread prefrontal cortex (PFC) activation during memory retrieval tasks, compared to young adults, particularly in the left hemisphere. Recruitment of additional frontal activity in older adults has been attributed by some researchers to compensation, perhaps for reduced activity elsewhere in the brain, whereas others have described it as a non-selective response that may be due to a failure to inhibit these PFC regions. To address further the impact of PFC activity on memory in older adults, we used PET to measure brain activity during recognition memory tasks. Both young and old adults showed increased activity during recognition, compared to a control task, in bilateral PFC. Young adults showed greater activation of left hippocampus and lateral temporal cortex during recognition, whereas older adults showed greater activity in the right inferior frontal gyrus. Age differences also were seen in correlations between brain activity and memory performance. There were positive correlations between activity in the right parahippocampal gyrus and recognition performance in young adults, whereas positive correlations between activity in PFC and performance were found only in older adults. These positive correlations included the right inferior PFC region where older adults had greater activation. Activity in this right PFC region was negatively correlated with medial temporal activity in both groups. These results provide further evidence for age-specific patterns of brain activity underlying memory performance and are consistent with the idea that PFC assumes a larger role in supporting successful recognition memory with increasing age. The negative correlation between activity in PFC and medial temporal regions, as well as the age differences in how these regions were related to behavior, suggest that those older individuals who recruit PFC to a greater degree may do so as a compensatory response to reductions in medial temporal regions.     

Prefrontal contributions to domain-general executive control processes during temporal context retrieval

Neuroimaging studies have reported increased prefrontal cortex (PFC) activity during temporal context retrieval versus recognition memory. However, it remains unclear if these activations reflect PFC contributions to domain-general executive control processes or domain-specific retrieval processes. To gain a better understanding of the functional roles of these various PFC regions during temporal context retrieval we propose it is necessary to examine PFC activity across tasks from different domains, in which parallel manipulations are included targeting specific cognitive processes. In the current fMRI study, we examined domain-general and domain-specific PFC contributions to temporal context retrieval by increasing stimulus (but maintaining response number) and increasing response number (but maintaining stimulus number) across temporal context memory and ordering control tasks, for faces. The control task required subjects to order faces from youngest to oldest. Our behavioral results indicate that the combination of increased stimulus and response numbers significantly increased task difficulty for temporal context retrieval and ordering tasks. Across domains, increasing stimulus number, while maintaining response numbers, caused greater right lateral premotor cortex (BA 6/8) activity; whereas increasing response number, while maintaining stimulus number, caused greater domain-general left DLPFC (BA 9) and VLPFC (BA 44/45) activity. In addition, we found domain-specific right DLPFC (BA 9) activity only during retrieval events. These results highlight the functional heterogeneity of frontal cortex, and suggest its involvement in temporal context retrieval is related to its role in various cognitive control processes.     

Prefrontal cortex activity associated with source monitoring in a working memory task

Using functional magnetic resonance imaging (fMRI), we investigated prefrontal cortex (PFC) activity during remembering specific source information (format, location judgments) versus remembering that could be based on undifferentiated information, such as familiarity (old/new recognition [ON], recency judgments). A working memory (WM) paradigm with an immediate test yielded greater activation in the lateral PFC for format and location source memory (SM) tasks than ON recognition; this SM-related activity was left lateralized. The same regions of PFC were recruited in Experiment 2 when information was tested immediately and after a filled delay. Substituting recency for location judgments (Experiment 3) resulted in an overall shift in task context that produced greater right PFC activity associated with ON and recency tasks compared to the format task, in addition to left SM-related activity. These data extend to WM previous findings from long-term memory (LTM) indicating that the left and right PFC may be differentially involved in memory attributions depending on the specificity of information evaluated. The findings also provide evidence for the continuity of evaluative processes recruited in WM and LTM.     

Neural correlates of auditory recognition under full and divided attention in younger and older adults

We examined how aging affects the pattern of brain activity mediating retrieval under dual-task conditions. We used functional magnetic resonance imaging (fMRI) to measure brain activity in younger and older adults while they were engaged in an auditory verbal recognition test under either full or divided attention (FA or DA). During recognition under FA, older adults had more activity in bilateral dorsolateral prefrontal cortex (PFC). DA with a distracting task requiring animacy judgments to words disrupted memory more than did a task requiring odd-digit judgments to numbers. For both behavioural and brain measures we contrasted the two DA conditions to recognition under FA to identify interference with memory performance. Behaviourally, there were no age differences in the magnitude of memory interference from DA conditions, although recognition performance was poorer overall in older adults. During the DA animacy condition, younger adults showed an increase in recognition latency, and older adults an increase in distracting task costs. Younger adults in this condition showed an increase in left inferior PFC, coupled with a decrease in right hippocampal activity; these effects were diminished in older adults who instead showed an increase in bilateral middle frontal activity. During both DA conditions, older adults showed greater activity in posterior neocortex compared to the younger group. Results indicate that older adults are able to perform as well as younger adults on retrieval tasks under DA conditions due to two alterations in brain activity: a dampening of the changes characterizing younger adults during the DA animacy condition and greater recruitment of additional regions during both DA tasks.     

Lateralization of prefrontal activity during episodic memory retrieval: evidence for the production-monitoring hypothesis

We propose a new hypothesis concerning the lateralization of prefrontal cortex (PFC) activity during verbal episodic memory retrieval. The hypothesis states that the left PFC is differentially more involved in semantically guided information production than is the right PFC, and that the right PFC is differentially more involved in monitoring and verification than is the left PFC. This "production-monitoring hypothesis" differs from the existing "systematic-heuristic hypothesis," which proposes that the left PFC is primarily involved in systematic retrieval operations, and the right PFC in heuristic retrieval operations. To compare the two hypotheses, we measured PFC activity using positron emission tomography (PET) during the performance of four episodic retrieval tasks: stem cued recall, associative cued recall, context recognition (source memory), and item recognition. Recall tasks emphasized production processes, whereas recognition tasks emphasized monitoring processes. Stem cued recall and context-recognition tasks underscored systematic operations, whereas associative cued recall and item-recognition tasks underscored heuristic operations. Consistent with the production-monitoring hypothesis, the left PFC was more activated for recall than for recognition tasks and the right PFC was more activated for recognition than for recall tasks. Inconsistent with the systematic-heuristic hypothesis, the left PFC was more activated for heuristic than for systematic tasks and the right PFC showed the converse result. Additionally, the study yielded activation differences outside the PFC. In agreement with a previous recall/recognition PET study, anterior cingulate, cerebellar, and striatal regions were more activated for recall than for recognition tasks, and the converse occurred for posterior parietal regions. A right medial temporal lobe region was more activated for stem cued recall and context recognition than for associative cued recall and item recognition, possibly reflecting perceptual integration. In sum, the results provide evidence for the production-monitoring hypothesis and clarify the role of different brain regions typically activated in PET and functional magnetic resonance imaging (fMRI) studies of episodic retrieval.     

Temporal and spatial context memory in patients with focal frontal, temporal lobe, and diencephalic lesions

Patients with focal frontal, temporal lobe, or diencephalic lesions were investigated on measures of temporal (recency) and spatial (position) context memory, after manipulating exposure times to match recognition memory for targets (pictorial stimuli) as closely as possible. Patients with diencephalic lesions from an alcoholic Korsak off syndrome showed significant impairment on the temporal context (recency) task, as did patients with frontal lesions penetrating the dorsolateral frontal cortex, according to MRI (and PET) evidence. Patients with temporal lobe lesions showed only a moderate (non-significant) impairment on this task, and patients with medial frontal lesions, or large frontal lesions not penetrating the dorsolateral cortical margins, performed as well as healthy controls at this task. On the spatial context memory task, patients with lesions in the temporal lobes showed significant impairment, and patients with right temporal lesions performed significantly worse than patients with left temporal lesions. Patients with diencephalic lesions showed only a modest (non-significant) impairment on this task, and the frontal lobe group performed normally. When a group of patients with temporal lobe lesions resulting from herpes encephalitis were examined separately, an identical pattern of results was obtained, the herpes group being significantly impaired on spatial memory and showing a trend towards impairment for temporal context memory. There were strong correlations between anterograde memory quotients and context memory performance (despite the use of an exposure time titration procedure) and a weak association with one frontal/executive task (card-sorting perseverations). It is predicted that correlations between temporal context memory and frontal/executive tasks will be greater in samples of patients all of whom have frontal lesions invading the dorsolateral cortical margin.     

Group differences in anterior hippocampal volume and in the retrieval of spatial and temporal context memory in healthy young versus older adults

The ability to retrieve temporal and spatial context information from memory declines with healthy aging. The hippocampus (HC) has been shown to be associated with successful encoding and retrieval of spatio-temporal context, versus item recognition information ( [Davachi et al., 2003] , [Nadel et al., 2000] and [Ross and Slotnick, 2008] ). Aging has been linked to volume reduction in the HC ( [Bouchard et al., 2008] , [Malykhin et al., 2008] and [Raz et al., 2005] ). As such, age-associated reductions in anterior HC volume may contribute to the context memory deficits observed in older adults. In the current MRI study we investigated whether item recognition, spatial context and temporal context memory performance would be predicted by regional volumes in HC head (HH), body (HB) and tail (HT) volumes, using within group multiple regression analyses in a sample of 19 healthy young (mean age 24.3) and 20 older adults (mean age 67.7). We further examined between age-group differences in the volumes of the same HC sub-regions. Multiple regression analyses revealed that in younger adults both spatial and temporal context retrieval performance was predicted by anterior HC volume. Older age was associated with significant volume reductions in HH and HB, but not HT; and with reduced ability to retrieve spatial and temporal contextual details from episodic memory. However, HC volumes did not predict context retrieval performance in older adults. We conclude that individual differences in anterior, not posterior, HC volumes predict context memory performance in young adults. With age there may be a posterior-to-anterior shift from using HC-related processes, due to HC volume loss, to employing the prefrontal cortex to aid in the performance of cognitively demanding context memory tasks. However, due to concomitant changes in the prefrontal system with age, there are limits to compensation in the aging brain.     

Age-related differences in neural activity during item and temporal-order memory retrieval: a positron emission tomography study

Positron emission tomography (PET) was used to investigate the hypothesis that older adults' difficulties with temporal-order memory are related to deficits in frontal function. Young (mean 24.7 years) and old (mean 68.6 years) participants studied a list of words, and were then scanned while retrieving information about what words were in the list (item retrieval) or when they occurred within the list (temporal-order retrieval). There were three main results. First, whereas the younger adults engaged right prefrontal regions more during temporal-order retrieval than during item retrieval, the older adults did not. This result is consistent with the hypothesis that context memory deficits in older adults are due to frontal dysfunction. Second, ventromedial temporal activity during item memory was relatively unaffected by aging. This finding concurs with evidence that item memory is relatively preserved in old adults and with the notion that medial temporal regions are involved in automatic retrieval operations. Finally, replicating the result of a previous study (Cabeza, R., Grady, C. L., Nyberg, L., McIntosh, A. R. , Tulving, E., Kapur, S., Jennings, J. M., Houle, S., and Craik, F. I. M., 1997), the old adults showed weaker activations than the young adults in the right prefrontal cortex but stronger activations in the left prefrontal cortex. The age-related increase in left prefrontal activity may be interpreted as compensatory. Taken together, the results suggest that age-related changes in brain activity are rather process- and region-specific, and that they involve increases as well as decreases in neural activity.     

Age differences in prefontal recruitment during verbal working memory maintenance depend on memory load

Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies have revealed age-related under-activation, where older adults show less regional brain activation compared to younger adults, as well as age-related over-activation, where older adults show greater activation compared to younger adults. These differences have been found across multiple task domains, including verbal working memory (WM). Curiously, both under-activation and over-activation of dorsolateral prefrontal cortex (DLPFC) have been found for older adults in verbal WM tasks. Here, we use event-related fMRI to test the hypothesis that age-related differences in activation depend on memory load (the number of items that must be maintained). Our predictions about the recruitment of prefrontal executive processes are based on the Compensation-Related Utilization of Neural Circuits Hypothesis (CRUNCH; Reuter-Lorenz and Cappell, 2008). According to this hypothesis, more neural resources are engaged by older brains to accomplish computational goals completed with fewer resources by younger brains. Therefore, seniors are more likely than young adults to show over-activations at lower memory loads, and under-activations at higher memory loads. Consistent with these predictions, in right DLPFC, we observed age-related over-activation with lower memory loads despite equivalent performance accuracy across age groups. In contrast, with the highest memory load, older adults were significantly less accurate and showed less DLPFC activation compared to their younger counterparts. These results are considered in relation to previous reports of activation-performance relations using similar tasks, and are found to support the viability of CRUNCH as an account of age-related compensation and its potential costs.     

The effects of attention on age-related relational memory deficits: fMRI evidence from a novel attentional manipulation

Numerous studies have documented that older adults (OAs) do not perform as well as young adults (YAs) when task demands require the establishment or retrieval of a novel link between previously unrelated information (relational memory: RM). Nonetheless, the source of this age-related RM deficit remains unspecified. One of the most widely investigated factors is an age-related reduction in attentional resources. To investigate this factor, previous researchers have tested whether dividing YAs' attention during encoding equated their RM performance to that of OAs. However, results from these studies failed to replicate the age-related RM impairment observed in aging. The current study investigated whether a reduction in attentional resources for processing of relational information (i.e., relational attention) underlies age-related RM deficits. Using fMRI, we examined whether the effect of reduced attentional resources for processing of relational information is similar to that observed in aging at both behavioral and neural levels. The behavioral results showed that reduced attentional resources for relational information during encoding equated YAs RM performance to that of OAs. Furthermore, the fMRI results demonstrated that both aging, as well as reductions in relational attention in YAs, significantly reduced activity in brain areas associated with successful RM formation, namely, the ventrolateral and dorsolateral PFC, superior and inferior parietal regions, and left hippocampus. Such converging evidence from behavioral and neuroimaging studies suggests that a reduction in attentional resources for relational information is a critical factor for the RM deficit observed in aging.     

Goal-dependent modulation of declarative memory: neural correlates of temporal recency decisions and novelty detection

Declarative memory allows an organism to discriminate between previously encountered and novel items, and to place past encounters in time. Numerous imaging studies have investigated the neural processes supporting item recognition, whereas few have examined retrieval of temporal information. In the present study, functional magnetic resonance imaging (fMRI) was conducted while subjects engaged in temporal recency and item novelty decisions. Subjects encountered three-alternative forced-choice retrieval trials, each consisting of two words from a preceding study phase and one novel word, and were instructed to either identify the novel item (Novelty trials) or the more recently presented study item (Recency trials). Relative to correct Novelty decisions, correct Recency decisions elicited greater activation in a network of left-lateralized regions, including frontopolar and dorsolateral prefrontal cortex and intraparietal sulcus. A conjunction analysis revealed that these left-lateralized regions overlapped with those previously observed to be engaged during source recollection versus novelty detection, suggesting that during Recency trials subjects attempted to recollect event details. Consistent with this interpretation, correct Recency decisions activated posterior hippocampus and parahippocampal cortex, whereas incorrect Recency decisions elicited greater anterior cingulate activation. The magnitude of this latter effect positively correlated with activation in right dorsolateral prefrontal cortex. Finally, correct Novelty decisions activated the anterior medial temporal lobe to a greater extent than did correct Recency decisions, suggesting that medial temporal novelty responses are not obligatory but rather can be modulated by the goal-directed allocation of attention. Collectively, these findings advance understanding of how subjects strategically engage frontal and parietal mechanisms in the service of attempting to remember the temporal order of events, and how retrieval goals impact novelty processing within the medial temporal lobe.     

Relating medial temporal lobe volume to frontal fMRI activation for memory encoding in older adults

Neuroimaging research on the brain basis of memory decline in older adults typically has examined age-related changes either in structure or in function. Structural imaging studies have found that smaller medial temporal lobe (MTL) volumes are associated with lower memory performance. Functional imaging studies have found that older adults often exhibit bilateral frontal-lobe activation under conditions where young adults exhibit unilateral frontal activation. As yet, no one has examined whether these MTL structural and frontal-lobe functional findings are associated. In this study, we tested whether these findings were correlated in a population of healthy older adults in whom we previously demonstrated verbal memory performance was positively associated with left entorhinal cortex volume in the MTL (Rosen et al., 2003) and right frontal lobe activation during memory encoding (Rosen et al., 2002). Thirteen, non-demented, community-dwelling older adults participated both in a functional MRI (fMRI) study of verbal memory encoding and structural imaging. MRI-derived left entorhinal volume was measured on structural images and entered as a regressor against fMRI activation during verbal memory encoding. Right frontal activation (Brodmann's Area 47/insula) was positively correlated with left entorhinal cortex volume. These findings indicate a positive association between MTL volume and right frontal-lobe function that may underlie variability in memory performance among the elderly, and also suggest a two-stage model of memory decline in aging.     

Event-related fMRI of frontotemporal activity during word encoding and recognition in schizophrenia

OBJECTIVE: Neuropsychological studies have demonstrated verbal episodic memory deficits in schizophrenia during word encoding and retrieval. This study examined neural substrates of memory in an analysis that controlled for successful retrieval. METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation during word encoding and recognition in 14 patients with schizophrenia and 15 healthy comparison subjects. An unbiased multiple linear regression procedure was used to model the BOLD response, and task effects were detected by contrasting the signal before and after stimulus onset. RESULTS: Patients attended during encoding and had unimpaired reaction times and normal response biases during recognition, but they had lower recognition discriminability scores, compared with the healthy subjects. Analysis of contrasts was restricted to correct items. Previous findings of a deficit in bilateral prefrontal cortex activation during encoding in patients were reproduced, but patients showed greater parahippocampal activation rather than deficits in temporal lobe activation. During recognition, left dorsolateral prefrontal cortex activation was lower in the patients and right anterior prefrontal cortex activation was preserved, as in the authors' previous study using positron emission tomography. Successful retrieval was associated with greater right dorsolateral prefrontal cortex activation in the comparison subjects, whereas orbitofrontal, superior frontal, mesial temporal, middle temporal, and inferior parietal regions were more active in the patients during successful retrieval. CONCLUSIONS: The pattern of prefrontal cortex underactivation and parahippocampal overactivation in the patients suggests that functional connectivity of dorsolateral prefrontal and temporal-limbic structures is disrupted by schizophrenia. This disruption may be reflected in the memory strategies of patients with schizophrenia, which include reliance on rote rehearsal rather than associative semantic processing.     

fMRI differences in encoding and retrieval of pictures due to encoding strategy in the elderly

Functional MRI (fMRI) was used to examine the neural correlates of depth of processing during encoding and retrieval of photographs in older normal volunteers (n = 12). Separate scans were run during deep (natural vs. man-made decision) and shallow (color vs. black-and-white decision) encoding and during old/new recognition of pictures initially presented in one of the two encoding conditions. A baseline condition consisting of a scrambled, color photograph was used as a contrast in each scan. Recognition accuracy was greater for the pictures on which semantic decisions were made at encoding, consistent with the expected levels of processing effect. A mixed-effects model was used to compare fMRI differences between conditions (deep-baseline vs. shallow-baseline) in both encoding and retrieval. For encoding, this contrast revealed greater activation associated with deep encoding in several areas, including the left parahippocampal gyrus (PHG), left middle temporal gyrus, and left anterior thalamus. Increased left hippocampal, right dorsolateral, and inferior frontal activations were found for recognition of items that had been presented in the deep relative to the shallow encoding condition. We speculate that the modulation of activity in these regions by the depth of processing manipulation shows that these regions support effective encoding and successful retrieval. A direct comparison between encoding and retrieval revealed greater activation during retrieval in the medial temporal (right hippocampus and bilateral PHG), anterior cingulate, and bilateral prefrontal (inferior and dorsolateral). Most notably, greater right posterior PHG was found during encoding compared to recognition. Focusing on the medial temporal lobe (MTL) region, our results suggest a greater involvement of both anterior MTL and prefrontal regions in retrieval compared to encoding.     

Neural activation patterns of successful episodic encoding: Reorganization during childhood,maintenance in old age

The two-component framework of episodic memory (EM) development posits that the contributions of medial temporal lobe (MTL) and prefrontal cortex (PFC) to successful encoding differ across the lifespan. To test the framework’s hypotheses, we compared subsequent memory effects (SME) of 10–12 year-old children, younger adults, and older adults using functional magnetic resonance imaging (fMRI). Memory was probed by cued recall, and SME were defined as regional activation differences during encoding between subsequently correctly recalled versus omitted items. In MTL areas, children’s SME did not differ in magnitude from those of younger and older adults. In contrast, children’s SME in PFC were weaker than the corresponding SME in younger and older adults, in line with the hypothesis that PFC contributes less to successful encoding in childhood. Differences in SME between younger and older adults were negligible. The present results suggest that, among individuals with high memory functioning, the neural circuitry contributing to successful episodic encoding is reorganized from middle childhood to adulthood. Successful episodic encoding in later adulthood, however, is characterized by the ability to maintain the activation patterns that emerged in young adulthood.     

Age-related differences in brain activity during true and false memory retrieval

Compared to young adults, older adults show not only a reduction in true memories but also an increase in false memories. We investigated the neural bases of these age effects using functional magnetic resonance imaging and a false memory task that resembles the Deese-Roediger-McDermott (DRM) paradigm. Young and older participants were scanned during a word recognition task that included studied words and new words that were strongly associated with studied words (critical lures). During correct recognition of studied words (true memory), older adults showed weaker activity than young adults in the hippocampus but stronger activity than young adults in the retrosplenial cortex. The hippocampal reduction is consistent with age-related deficits in recollection, whereas the retrosplenial increase suggests compensatory recruitment of alternative recollection-related regions. During incorrect recognition of critical lures (false memory), older adults displayed stronger activity than young adults in the left lateral temporal cortex, a region involved in semantic processing and semantic gist. Taken together, the results suggest that older adults' deficits in true memories reflect a decline in recollection processes mediated by the hippocampus, whereas their increased tendency to have false memories reflects their reliance on semantic gist mediated by the lateral temporal cortex.     

An FMRI study of episodic encoding and recognition of words in patients with schizophrenia in remission

OBJECTIVE: Verbal memory deficits are among the most severe cognitive deficits observed in patients with schizophrenia. This study examined patterns of brain activity during episodic encoding and recognition of words in patients with schizophrenia. METHOD: Functional magnetic resonance imaging (fMRI) was used to study regional brain activation in 10 healthy male comparison subjects and 10 male outpatients with schizophrenia during performance of a modified version of the words subtest of Warrington's Recognition Memory Test. RESULTS: Despite having intact performance in word recognition, the patients with schizophrenia had less activation of the right dorsolateral and anterior prefrontal cortex, right anterior cingulate, and left lateral temporal cortex during word encoding, compared with the healthy comparison subjects. During word recognition, the patients had impairments in activation of the bilateral dorsolateral prefrontal and lateral temporal cortices. CONCLUSIONS: Schizophrenia was associated with attenuated frontotemporal activation during episodic encoding and recognition of words. These results from an fMRI study replicate earlier findings derived from a positron emission tomography study.     

Dissociating age-related changes in cognitive strategy and neural efficiency using event-related fMRI

We used event-related fMRI to measure brain activity while younger and older adults performed an item-recognition task in which the memory-set size varied between 1 and 8 letters. Each trial was composed of a 4-second encoding period in which subjects viewed random letter strings, a 12-second retention period and a 2-second retrieval period in which subjects decided whether a single probe letter was or was not part of the memory set. For both groups, reaction time increased and accuracy decreased with increasing memory set-size. There were minimal age-related differences in activation patterns with increasing memory set-size in prefrontal cortex (PFC). Regression analyses of individual subjects' performance and cortical activity indicated that speed and accuracy accounted for considerable variance in dorsal and ventral PFC activity during encoding and retrieval. These results suggest that younger and older adults utilize similar working memory (WM) strategies to accommodate increasing memory demand. They support a model of cognitive slowing in which processing rate is related to neural efficiency.