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.     

Neural correlates of memory for items and for associations: an event-related functional magnetic resonance imaging study

Although results from cognitive psychology, neuropsychology, and behavioral neuroscience clearly suggest that item and associative information in memory rely on partly different brain regions, little is known concerning the differences and similarities that exist between these two types of information as a function of memory stage (i.e., encoding and retrieval). We used event-related functional magnetic resonance imaging to assess neural correlates of item and associative encoding and retrieval of simple images in 18 healthy subjects. During encoding, subjects memorized items and pairs. During retrieval, subjects made item recognition judgments (old vs. new) and associative recognition judgments (intact vs. rearranged). Relative to baseline, item and associative trials activated bilateral medial temporal and prefrontal regions during both encoding and retrieval. Direct contrasts were then performed between item and associative trials for each memory stage. During en- coding, greater prefrontal, hippocampal, and parietal activation was observed for associations, but no significant activation was observed for items at the selected threshold. During recognition, greater activation was observed for associative trials in the left dorsolateral prefrontal cortex and superior parietal lobules bilaterally, whereas item recognition trials showed greater activation of bilateral frontal regions, bilateral anterior medial temporal areas, and the right temporo-parietal junction. Post hoc analyses suggested that the anterior medial temporal activation observed during item recognition was driven mainly by new items, confirming a role for this structure in novelty detection. These results suggest that although some structures such as the medial temporal and prefrontal cortex play a general role in memory, the pattern of activation in these regions can be modulated by the type of information (items or associations) interacting with memory stages.     

Prefrontal cortex hemispheric specialization for categorical and coordinate visual spatial memory

During visual spatial perception of multiple items, the left hemisphere has been shown to preferentially process categorical spatial relationships while the right hemisphere has been shown to preferentially process coordinate spatial relationships. We hypothesized that this hemispheric processing distinction would be reflected in the prefrontal cortex during categorical and coordinate visual spatial memory, and tested this hypothesis using functional magnetic resonance imaging (fMRI). During encoding, abstract shapes were presented in the left or right hemifield in addition to a dot at a variable distance from the shape (with some dots on the shape); participants were instructed to remember the position of each dot relative to the shape. During categorical memory retrieval, each shape was presented centrally and participants responded whether the previously corresponding dot was 'on' or 'off' of the shape. During coordinate memory retrieval, each shape was presented centrally and participants responded whether the previously corresponding dot was 'near' or 'far' from the shape (relative to a reference distance). Consistent with our hypothesis, a region in the left prefrontal cortex (BA10) was preferentially associated with categorical visual spatial memory and a region in the right prefrontal cortex (BA9/10) was preferentially associated with coordinate visual spatial memory. These results have direct implications for interpreting previous findings that the left prefrontal cortex is associated with source memory, as this cognitive process is categorical in nature, and the right prefrontal cortex is associated with item memory, as this process depends on the precise spatial relations among item features or components.     

Selective pair recognition memory impairment with no response bias in schizophrenia

Memory is one of the cognitive functions most affected in schizophrenia, but the severity of deficits varies from one task to another. In particular, greater impairments have been reported for pair recognition than item recognition. However, decision biases and how they could affect memory dysfunction in schizophrenia have received scant attention. In this study, 26 people with schizophrenia and 28 healthy controls were administrated an association item recognition task. During encoding, participants studied pairs of visual objects, and they had to memorise objects and their pairing. In a subsequent retrieval task, participants performed an item recognition test (old/new items) and a pair recognition test (intact/rearranged pairs). Results showed that both groups were better at recognizing items than pairs, with lower performance for pair recognition, but not for item recognition, in people with schizophrenia. Analyses of response biases revealed that patients had a conservative response bias for items but not for pairs. The study also provides evidence that associative impairment may not result from decisional bias but rather from impairments in mnesic processes.     

Impaired hippocampal recruitment during normal modulation of memory performance in schizophrenia.

BACKGROUND: Patients with schizophrenia demonstrate poor verbal memory, ascribed to impaired prefrontal and hippocampal function. Healthy adults can increase recall accuracy following encoding interventions, such as item repetition and the formation of semantic associations. We examined the effects of these interventions on both memory performance and retrieval-related hippocampal activity in healthy adults and patients with schizophrenia. METHODS: Twelve patients with schizophrenia and twelve healthy control subjects participated. During study, subjects counted either the number of meanings or T-junctions in words seen only once or repeated four times. At test, O15-positron emission tomography scans were acquired while subjects completed word-stems with previously studied items. RESULTS: Control subjects recalled more words overall, but both groups demonstrated similar performance benefits following deeper encoding. Both item repetition and the use of a semantic encoding task were associated with memory retrieval-related hippocampal recruitment in control but not schizophrenic participants. Patients with schizophrenia demonstrated greater activation of prefrontal cortical areas during word retrieval. CONCLUSIONS: Despite a lack of hippocampal recruitment, patients with schizophrenia showed intact modulation of memory performance following both encoding interventions. Impaired hippocampal recruitment, in concert with greater prefrontal activation, may reflect a specific deficit in conscious recollection in schizophrenia.     

Selective abnormal modulation of hippocampal activity during memory formation in first-episode psychosis

CONTEXT: Memory is one of the cognitive functions most affected in schizophrenia, with deficits observed from the first episode of psychosis (FEP). Previous studies have indicated that some memory processes may be more affected than others. OBJECTIVE: To examine the neural correlates of 3 specific memory processes in FEP by means of functional magnetic resonance imaging (fMRI). DESIGN: Case-control study. SETTING: Prevention and Early Intervention Program for Psychoses of the Douglas Hospital and Montreal Neurological Institute, McGill University. Subjects Twenty-six patients with FEP and 20 healthy controls. MAIN OUTCOME MEASURES: Behavioral performance and regional brain activity measured during memory encoding by fMRI. Our fMRI design included 3 within-subject contrasts (associative vs item-oriented encoding, encoding of arbitrary vs semantically related image pairs, and successful vs unsuccessful memory encoding) that were then used for group conjunctions and between-group analyses. RESULTS: Patients with FEP showed normal activation of several brain regions, including the prefrontal cortex, hippocampus, and parahippocampal cortex, during successful memory encoding and associative encoding. In contrast, the hippocampus and surrounding medial temporal areas showed reduced activity during the encoding of arbitrary pairs. This selective dysfunction reflected by abnormal brain activation during encoding was accompanied by a greater deficit for subsequent recognition of arbitrary pairs relative to the semantically related pairs. CONCLUSIONS: This study demonstrated that, in the same group of patients with FEP, the hippocampus could show either normal or abnormal modulation of activation depending on the specific cognitive process that was examined. The normal modulation of hippocampal activation observed during successful memory encoding in FEP argues against a general inability to recruit this region. Instead, the dysfunction was specifically linked to semantic relatedness. This selective deficit seems to affect memory performance in FEP and denotes an important representational problem that may confer greater vulnerability to psychotic disorders and would thus be interesting to examine in high-risk populations.     

Age-related differences in agenda-driven monitoring of format and task information

Age-related source memory deficits may arise, in part, from changes in the agenda-driven processes that control what features of events are relevant during remembering. Using fMRI, we compared young and older adults on tests assessing source memory for format (picture, word) or encoding task (self-, other-referential), as well as on old–new recognition. Behaviorally, relative to old–new recognition, older adults showed disproportionate and equivalent deficits on both source tests compared to young adults. At encoding, both age groups showed expected activation associated with format in posterior visual processing areas, and with task in medial prefrontal cortex. At test, the groups showed similar selective, agenda-related activity in these representational areas. There were, however, marked age differences in the activity of control regions in lateral and medial prefrontal cortex and lateral parietal cortex. Results of correlation analyses were consistent with the idea that young adults had greater trial-by-trial agenda-driven modulation of activity (i.e., greater selectivity) than did older adults in representational regions. Thus, under selective remembering conditions where older adults showed clear differential regional activity in representational areas depending on type of test, they also showed evidence of disrupted frontal and parietal function and reduced item-by-item modulation of test-appropriate features. This pattern of results is consistent with an age-related deficit in the engagement of selective reflective attention.     

Inefficient executive cognitive control in schizophrenia is preceded by altered functional activation during information encoding: an fMRI study

Working memory deficits are a core feature of schizophrenia. Previous working memory studies suggest a load dependent storage deficit. However, explicit studies of higher executive working memory processes are limited. Moreover, few studies have examined whether subcomponents of working memory such as encoding and maintenance of information are differentially affected by these deficits. Therefore, the aim of the present study was to examine the neural substrates of working memory subprocesses requiring stimulus encoding, maintenance and higher executive processing. Using functional magnetic resonance imaging a modified Sternberg working memory task involving verbal stimulus material was applied. The event-related design enabled the segregation of encoding, active maintenance and executive manipulation of information. Forty-one patients with schizophrenia and 41 healthy subjects were included. Relative to normal controls, schizophrenic patients demonstrated a significantly stronger activation pattern in a fronto-parietal network during executive information manipulation. Additionally, significant relative hypoactivity was detectable in the thalamus. Conversely, during stimulus encoding the patients demonstrated lower activation relative to controls in the prefrontal cortex and the anterior cingulate gyrus. The present findings indicate a pronounced prefrontal functional hyperactivation within the neural network subserving higher executive working memory control processes in schizophrenia. Moreover, they suggest that these altered activations during executive control are related to a preceding abnormality of information encoding. During encoding, a reduced activation in mainly dorsolateral prefrontal and anterior cingulate regions was observed. These results could be explained by increased top-down control processing from prefrontal cortex as a compensation for functional deficits occurring during encoding.     

Distinct prefrontal cortex activity associated with item memory and source memory for visual shapes

In contrast to item memory, which refers to recognition or recall of previously presented information, source memory refers to memory for the context of previously presented information. The relatively few functional MRI (fMRI) source memory studies conducted to date have provided evidence that item memory and source memory are associated with differential activity in right and left prefrontal cortex, respectively. To both confirm this distinction in prefrontal cortex and to determine whether other differences in the neural substrates associated with these cognitive functions exist, an event-related fMRI study was conducted. In this study, item memory and source memory encoding phases were identical; participants viewed a series of abstract visual shapes presented on the left or right side of the screen and were instructed to remember each shape and its spatial location. During the item memory retrieval phase, shapes from the encoding phase were intermixed with new shapes and participants made an old-new judgment. During the source memory retrieval phase, all shapes were from the encoding phase and participants made a left-right judgment. An event-related analysis of item memory and source memory revealed a right and left prefrontal cortex distinction. Moreover, only item memory was associated with activity in the medial temporal lobes. These results confirm and extend previous findings that item memory and source memory are associated with distinct neural substrates.     

Associative interference does not affect recognition memory in schizophrenia

Studies of schizophrenia suggest a specific impairment in binding different parts of a memory event into a cohesive whole, a finding that may account for the reported preferential deficits in associative recognition memory relative to item recognition. As a further test of this hypothesis and to exert greater control over task differences, we used a recognition memory interference test in which participants encoded landscape pictures that had each been divided into three segments. During encoding, subjects were presented with one segment from each of the landscapes. Then, an interference generating task followed consisting of the presentation of the second segment from half of the landscapes. Finally, a forced-choice recognition memory test consisted of the presentation of each encoding picture stimulus concurrently with the related third segment that had never been presented before. Thus, for half of the stimuli, additional related information was encoded and this is known to interfere with recognition memory. However, an impaired ability to bind this related information should reduce the interfering effect of associated stimuli. Thirty-five schizophrenia patients and 37 healthy controls were administered this memory interference task. A significant interaction between groups and recognition conditions was found with a significant interference effect observed for controls (performance dropping from 76% to 62%) but not for patients (performance remaining unchanged from 66% to 68%). These results provide further support for faulty associative memory processing in schizophrenia.     

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.     

An fMRI study on memory discriminability for complex visual scenes

The fan effect represents an increase in reaction time for the recognition of an item as a function of the amount of information associated with that item in memory. The present study used fMRI to study the neural correlates of the fan effect for complex visual scenes. We used a test in which landscape pictures were divided vertically into three equal segments. In the high discriminability condition only one segment was presented during encoding, whereas in the low discriminability condition two different segments from the same picture were presented. During a subsequent forced-choice recognition test, reaction times were significantly faster for the high discriminability condition. Increase in brain activity for the low relative to high discriminability condition was observed in the right prefrontal cortex, several regions of parietal cortex bilaterally, and several late visual processing areas, including the occipito-temporal regions, precuneus, and cuneus. These results support the hypothesis that a region of the prefrontal cortex is involved in the control of memory interference at retrieval elicited by the amount of related information in memory, and further suggests that this involvement is right-lateralized for nonverbal material. The high versus low discriminability contrast showed an increase in activity principally in the bilateral medial temporal gyrus, including the enthorinal cortex/hippocampus and in several bilateral prefrontal cortex regions mostly located in BA 10. These activations were associated with a condition, in which the stimuli were more salient in memory and thus could represent the perceptual salience of items in memory.     

Support for an auto-associative model of spoken cued recall: evidence from fMRI

Cued recall and item recognition are considered the standard episodic memory retrieval tasks. However, only the neural correlates of the latter have been studied in detail with fMRI. Using an event-related fMRI experimental design that permits spoken responses, we tested hypotheses from an auto-associative model of cued recall and item recognition [Chappell, M., & Humphreys, M. S. (1994). An auto-associative neural network for sparse representations: Analysis and application to models of recognition and cued recall. Psychological Review, 101, 103-128]. In brief, the model assumes that cues elicit a network of phonological short term memory (STM) and semantic long term memory (LTM) representations distributed throughout the neocortex as patterns of sparse activations. This information is transferred to the hippocampus which converges upon the item closest to a stored pattern and outputs a response. Word pairs were learned from a study list, with one member of the pair serving as the cue at test. Unstudied words were also intermingled at test in order to provide an analogue of yes/no recognition tasks. Compared to incorrectly rejected studied items (misses) and correctly rejected (CR) unstudied items, correctly recalled items (hits) elicited increased responses in the left hippocampus and neocortical regions including the left inferior prefrontal cortex (LIPC), left mid lateral temporal cortex and inferior parietal cortex, consistent with predictions from the model. This network was very similar to that observed in yes/no recognition studies, supporting proposals that cued recall and item recognition involve common rather than separate mechanisms.     

Anterior prefrontal cortex and the recollection of contextual information

Recollective memory can involve the retrieval of many different kinds of contextual information, including where and when an event took place, as well as our thoughts and feelings at the time. The brain regions associated with this ability were examined in an event-related fMRI experiment, where participants made decisions about words or famous faces which were presented either on the left or right of a monitor screen. Subsequently, the studied words and faces were again presented and participants underwent fMRI brain scanning while recollecting either which of the decisions they had made on each item ("task memory"), or whether it had been presented on the left or right of the screen ("position memory"). A functional dissociation was observed within anterior prefrontal cortex (principally Brodmann's area 10), with activation in lateral regions associated with remembering either type of information (relative to baseline), and a medial anterior PFC region showing significantly greater activation during the "task memory" conditions. These results suggest different roles for lateral and medial anterior prefrontal cortex in recollection.     

An fMRI study of verbal episodic memory encoding in amnestic mild cognitive impairment

Amnestic mild cognitive impairment (aMCI) is a high-risk and often prodromal state for the development of Alzheimer's disease (AD) and is characterised by isolated episodic memory impairment. Functional neuroimaging studies in healthy subjects consistently report left prefrontal cortex (PFC) activation during verbal episodic memory encoding. The PFC activation at encoding is related to semantic processing which enhances memory. The purpose of this study was to ascertain whether impaired verbal episodic memory in aMCI is related to PFC dysfunction. Using functional magnetic resonance imaging (fMRI) we compared 10 aMCI patients with 10 elderly controls during verbal encoding. The encoding task was sensitive to the effects of semantic processing. Subsequent recognition was tested to measure encoding success. Behavioural results revealed impaired recognition and a lower false recognition rate for semantically related distracters (lures) in aMCI, which suggest impaired semantic processing at encoding. Both groups activated left hemispheric PFC, insula, premotor cortex and cerebellum, but group comparisons revealed decreased activation in left ventrolateral PFC in the aMCI group. The magnitude of activation in left ventrolateral PFC during encoding was positively correlated with recognition accuracy in the control group but not in the aMCI group. We propose that verbal episodic memory impairment in aMCI is related to PFC dysfunction which affects semantic processing at encoding.     

Neural correlates of encoding within- and across-domain inter-item associations

The neural correlates of the encoding of associations between pairs of words, pairs of pictures, and word-picture pairs were compared. The aims were to determine, first, whether the neural correlates of associative encoding vary according to study material and, second, whether encoding of across- versus within-material item pairs is associated with dissociable patterns of hippocampal and perirhinal activity, as predicted by the "domain dichotomy" hypothesis of medial temporal lobe function. While undergoing fMRI scanning, subjects (n = 24) were presented with the three classes of study pairs, judging which of the denoted objects fit into the other. Outside of the scanner, subjects then undertook an associative recognition task, discriminating between intact study pairs, rearranged pairs comprising items that had been presented on different study trials, and unstudied item pairs. The neural correlates of successful associative encoding--subsequent associative memory effects--were operationalized as the difference in activity between study pairs correctly judged intact versus pairs incorrectly judged rearranged on the subsequent memory test. Pair type-independent subsequent memory effects were evident in the left inferior frontal gyrus (IFG) and the hippocampus. Picture-picture pairs elicited material-selective effects in regions of fusiform cortex that were also activated to a greater extent on picture trials than on word trials, whereas word-word pairs elicited material-selective subsequent memory effects in left lateral temporal cortex. Contrary to the domain-dichotomy hypothesis, neither hippocampal nor perirhinal subsequent memory effects differed depending on whether they were elicited by within- versus across-material study pairs. It is proposed that the left IFG plays a domain-general role in associative encoding, that associative encoding can also be facilitated by enhanced processing in material-selective cortical regions, and that the hippocampus and perirhinal cortex contribute equally to the formation of inter-item associations, regardless of whether the items belong to the same or to different processing domains.     

Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression.

BACKGROUND: A large number of studies suggest the presence of deficits in dorsolateral prefrontal cortex function during performance of working memory tasks in individuals with schizophrenia. However, working memory deficits may also present in other psychiatric disorders, such as major depression. It is not clear whether people with major depression also demonstrate impaired prefrontal activation during performance of working memory tasks. METHODS: We used functional magnetic resonance imaging to assess the patterns of cortical activation associated with the performance of a 2-back version of the N-Back task (working memory) in 38 individuals with schizophrenia and 14 with major depression. RESULTS: We found significant group differences in the activation of dorsolateral prefrontal cortex associated with working memory performance. Consistent with prior research, participants with schizophrenia failed to show activation of right dorsolateral prefrontal cortex in response to working memory tasks demands, whereas those with major depression showed clear activation of right and left dorsolateral prefrontal cortex as well as bilateral activation of inferior and superior frontal cortex. CONCLUSIONS: During performance of working memory tasks, deficits in prefrontal activation, including dorsolateral regions, are more severe in participants with schizophrenia (most of whom were recently released outpatients) than in unmedicated outpatients with acute nonpsychotic major depression.     

The influence of encoding strategy on episodic memory and cortical activity in schizophrenia.

BACKGROUND: Recent work suggests that episodic memory deficits in schizophrenia may be related to disturbances of encoding or retrieval. Schizophrenia patients appear to benefit from instruction in episodic memory strategies. We tested the hypothesis that providing effective encoding strategies to schizophrenia patients enhances encoding-related brain activity and recognition performance. METHODS: Seventeen schizophrenia patients and 26 healthy comparison subjects underwent functional magnetic resonance imaging scans while performing incidental encoding tasks of words and faces. Subjects were required to make either deep (abstract/concrete) or shallow (alphabetization) judgments for words and deep (gender) judgments for faces, followed by subsequent recognition tests. RESULTS: Schizophrenia and comparison subjects recognized significantly more words encoded deeply than shallowly, activated regions in inferior frontal cortex (Brodmann area 45/47) typically associated with deep and successful encoding of words, and showed greater left frontal activation for the processing of words compared with faces. However, during deep encoding and material-specific processing (words vs. faces), participants with schizophrenia activated regions not activated by control subjects, including several in prefrontal cortex. CONCLUSIONS: Our findings suggest that a deficit in use of effective strategies influences episodic memory performance in schizophrenia and that abnormalities in functional brain activation persist even when such strategies are applied.     

Neural correlates of retrieval processing in the prefrontal cortex during recognition and exclusion tasks

Event-related fMRI was employed to contrast the neural activity elicited in prefrontal cortex during recognition memory and exclusion tests. The study phases preceding each memory test were identical, involving the presentation of study items (visually presented words) in one of two study contexts. For the recognition test subjects were required to respond positively to all old items regardless of study context, and to respond negatively to new items. For the exclusion task, positive responses were required to old items presented in one of the study contexts only; negative responses were required both to unstudied items and studied items from the alternative context (non-targets). No prefrontal region demonstrated greater activity for new items in the exclusion task. Thus, there was no evidence that retrieval cues were processed differently according to the specificity of the sought-for information. In several regions, most notably bilateral anterior prefrontal cortex, activity was greater for old than for new items regardless of task. Activity in right dorsolateral prefrontal cortex was also greater for old than for new items; these effects however were larger in the exclusion task. The findings are consistent with previous reports that activity in anterior prefrontal cortex elicited by recognition retrieval cues is sensitive to retrieval success, and extend these findings to the exclusion task. The findings for the right dorsolateral cortex add further weight to the proposal that this region supports post-retrieval monitoring of retrieved information.     

Effects of task orientation on subsequent source memory as revealed by functional MRI

Episodic memories are composed of various interrelated elements,including those specific to items of central interest and those pertaining to related features,such as the color,shape,size,spatial location,temporal order,and media or modalities of presentation.Memory about a core item(such as a word,object,or picture)is called item memory while memory about the context or related features of a core item is defined as source memory.What determines which sources within an episode are successfully remembered is of particular interest to researchers.Behavioral evidence suggests that the orientation of a memory task influences whether the related source of the item will be remembered later.This study explored changes in the hippocampus and prefrontal cortex while participants completed two tasks:an item-oriented task and a source-oriented task.We used functional MRI to investigate the neural mechanisms by which task orientation influences source encoding.We found that subsequent source memory effects in the right prefrontal cortex and hippocampus were modulated by task orientation,whereas task orientation modulated item memory effects in the prefrontal cortex.These findings highlight the possibility that the hippocampus contributes to the intentional encoding of item-source associations,whereas the prefrontal cortex is biased toward processing information to which attention is directed.