Conscious recollection and illusory recognition: an event-related fMRI study.

In this event-related functional magnetic resonance imaging (fMRI) study we examined the neuronal correlates of the subprocesses underlying recognition memory. In an explicit memory task, participants had to discriminate studied ('old') words from semantically related and unrelated 'new' (unstudied) words. We examined whether the correct rejection of semantically related words which were similar to old words, which had elicited correct responses, was based on conscious recollection of study phase information. In this task, false-positive responses to semantically related new words can be assumed to result from the assessment of the semantic similarity between test words and studied words with minimal recollection. For correct identification of old words and correct rejection of new related words we found common activation in a variety of brain areas that have been shown to be involved in conscious recollection, among them the left middle frontal gyrus, the precuneus, the retrosplenial cortex, the left parahippocampal gyrus and the thalamus. For correct responses to old words, the frontomedian wall, the posterior cingulate cortex and the nucleus accumbens were additionally activated, suggesting an emotional contribution to these judgements. Correct rejections of related new words were associated with additional activation of the right middle frontal gyrus, suggesting higher monitoring demands for these more difficult recognition judgements. False-positive responses to semantically related new words were associated with enhanced activation in the frontomedian wall. The results point to an important role of the prefrontal cortex as well as medial temporal and medial parietal regions of the brain in successful memory retrieval and conscious recollection.     

Modulation of prefrontal cortex activation by emotional words in recognition memory

We employed event-related functional magnetic resonance imaging to examine emotional valence effects on verbal recognition memory. Using a yes/no recognition task, we focussed on prefrontal cortex responses to positive, negative and neutral words. Behavioral data confirmed enhanced processing of emotional items and functional magnetic resonance imaging revealed different subregions in the prefrontal cortex supporting retrieval of emotional words. Activations in the right mid-ventrolateral prefrontal cortex correlated with the correct retrieval conditions for negative words, whereas the right ventromedial and orbitofrontal prefrontal cortex showed enhanced responses to positive words. Additionally, differences between old and new items mainly affected bilateral orbitofrontal regions when processing positive words. The results are discussed in terms of higher monitoring demands owing to familiarity-based recognition bias for emotional words.     

Further dissociating the processes involved in recognition memory: an FMRI study

Based on an event-related potential study by Rugg et al. [Dissociation of the neural correlates of implicit and explicit memory. Nature, 392, 595-598, 1998], we attempted to isolate the hemodynamic correlates of recollection, familiarity, and implicit memory within a single verbal recognition memory task using event-related fMRI. Words were randomly cued for either deep or shallow processing, and then intermixed with new words for yes/no recognition. The number of studied words was such that, whereas most were recognized ("hits"), an appreciable number of shallow-studied words were not ("misses"). Comparison of deep hits versus shallow hits at test revealed activations in regions including the left inferior parietal gyrus. Comparison of shallow hits versus shallow misses revealed activations in regions including the bilateral intraparietal sulci, the left posterior middle frontal gyrus, and the left frontopolar cortex. Comparison of hits versus correct rejections revealed a relative deactivation in an anterior left medial-temporal region (most likely the perirhinal cortex). Comparison of shallow misses versus correct rejections did not reveal response decreases in any regions expected on the basis of previous imaging studies of priming. Given these and previous data, we associate the left inferior parietal activation with recollection, the left anterior medial-temporal deactivation with familiarity, and the intraparietal and prefrontal responses with target detection. The absence of differences between shallow misses and correct rejections means that the hemodynamic correlates of implicit memory remain unclear.     

Four types of novelty-familiarity responses in associative recognition memory of humans

Animal studies show that, like inferior temporal neurons, dorsolateral prefrontal and parietal neurons often respond more strongly to individual novel than to individual familiar stimuli. It is currently unclear whether the novelty preference of prefrontal and parietal neurons extends to associative memory. We used electromagnetic recordings (MEG/EEG) and functional magnetic resonance imaging in two groups of healthy young adults to identify neural populations outside the inferior temporal cortex that exhibit associative novelty (stronger responses for new than for old configurations of two familiar items), and to distinguish them from associative familiarity (stronger responses for old than for new configurations of two familiar items). Subjects were required to learn and were later tested for associations based on the spatial configurations of two stimuli (a face and a tool). At test, learned (old) and rearranged (new) spatial stimulus configurations had to be discriminated. This recognition memory test could only be solved through the associative relationship between individual items because all component items of the stimulus configurations were equally familiar. In both imaging modalities, right dorsolateral prefrontal cortex and right parietal cortex showed an associative novelty response, whereas the right superior temporal cortex showed an associative familiarity response. With EEG/MEG only, the right extrastriate cortex showed an early associative familiarity and a late associative novelty response, whereas the opposite pattern emerged in bilateral frontopolar cortex. Thus, through a multimodal approach, it was possible to identify four types of associative novelty/familiarity responses outside the inferior temporal cortex.     

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.     

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.     

Abnormalities in the thalamus and prefrontal cortex during episodic object recognition in schizophrenia.

BACKGROUND: Many patients with schizophrenia demonstrate memory deficits. We studied patterns of brain activity during episodic recognition of new and previously seen three-dimensional objects. METHODS: We used (15)O positron emission tomography to study regional cerebral blood flow in eight normal subjects and nine patients with schizophrenia during a visual object recognition task. RESULTS: In comparison with control subjects, patients with schizophrenia showed less regional cerebral blood flow increases in the pulvinar region of the right thalamus and the right prefrontal cortex during the recognition of new objects and significantly greater left prefrontal cortex regional cerebral blood flow increases during the recognition of previously seen objects. Patients with schizophrenia exhibited alarm rates to new objects similar to those of control subjects, but significantly lower recognition rates for previously seen objects. CONCLUSIONS: Schizophrenia is associated with attenuated right thalamic and right prefrontal activation during the recognition of novel visual stimuli and with increased left prefrontal cortical activation during impaired episodic recognition of previously seen visual stimuli. This study provides further evidence for abnormal thalamic and prefrontal cortex function in schizophrenia.     

Successful episodic memory retrieval of newly learned faces activates a left fronto-parietal network

It is easier to recognize a familiar face than a newly learned face. The neural basis of familiar face recognition has been elucidated in functional imaging and lesion studies. Behavioural and neuropsychological data indicate, however, that brain systems involved in episodic retrieval of familiar and newly learned faces are distinct. In our study, 12 subjects viewed 30 novel faces in an encoding session. In the study condition, event-related functional magnetic resonance imaging (fMRI) was used to compare brain activation during correct recognition of the recently learned faces to that observed during correct rejection of unknown control faces. Differences were present in the left inferior parietal (BA 40) and left medial frontal/anterior cingulate (BA 32/9) cortex. These two regions may be part of a pathway in the dorsal visual stream, responsible for a "feeling of familiarity" in contrast to the ventral pathway in the temporal lobes, which is mainly involved in the recognition of personal identity.     

Damage to the lateral prefrontal cortex impairs familiarity but not recollection

Frontal lobe lesions impair recognition memory but it is unclear whether the deficits arise from impaired recollection, impaired familiarity, or both. In the current study, recognition memory for verbal materials was examined in patients with damage to the left or right lateral prefrontal cortex. Words were incidentally encoded under semantic or phonological orienting conditions, and recognition memory was tested using a 6-point confidence procedure. Receiver operating characteristics (ROCs) were examined in order to measure the contributions of recollection and familiarity to recognition memory. In both encoding conditions, lateral prefrontal cortex damage led to a deficit in familiarity but not recollection. Similar deficits were observed in left and right hemisphere patients. The results indicate that the lateral prefrontal cortex plays a critical role in the monitoring or decision processes required for accurate familiarity-based recognition responses.     

Analysis of intersubject variability in activation: an application to the incidental episodic retrieval during recognition test

Since the brain may engage different neuronal systems for a single behavioral goal, activation may show intersubject variability expressed in the systematic recruitment of multiple distinct networks. We apply a principal component analysis (PCA) to activation over task conditions and subjects to reveal cortical networks that may underlie this intersubject variability. Normal subjects were presented with novel meaningless objects, which appeared in personally familiar or unfamiliar places. During a subsequent, event-related functional MRI (fMRI) experiment, each subject was presented with learned or novel objects in isolation and performed a learned/novel judgment. Recollection of places was not essential for the task, and may exhibit large intersubject variations. The right posterodorsal posterior cingulate cortex (pPCC) and left retrosplenial cortex, whose involvement in place-recognition has been previously established, were selected as regions of interest for the PCA. Neural responses to objects associated with familiar relative to unfamiliar places in pPCC, but not in the retrosplenial cortex, were negatively correlated with task-related activation (common over all objects) in the right anterolateral prefrontal cortex and the left intraparietal sulcus. The latter areas have been implicated previously in cognitive control and object recognition, respectively. These results suggest right prefrontal control over neural processes both in the left parietal cortex, related to object-recognition (enhancement), and pPCC, related to nonessential recollection of place-memory (suppression), but not in the retrosplenial cortex, related to the sense of familiarity. This analysis revealed an important aspect of functional anatomy that was not detectable using a conventional analysis of average activations.     

Recognition memory for emotional and neutral faces: an event-related potential study

This study examined emotional influences on the hypothesized event-related potential (ERP) correlates of familiarity and recollection (Experiment 1) and the states of awareness (Experiment 2) accompanying recognition memory for faces differing in facial affect. Participants made gender judgments to positive, negative, and neutral faces at study and were in the test phase instructed to discriminate between studied and nonstudied faces. Whereas old-new discrimination was unaffected by facial expression, negative faces were recollected to a greater extent than both positive and neutral faces as reflected in the parietal ERP old-new effect and in the proportion of remember judgments. Moreover, emotion-specific modulations were observed in frontally recorded ERPs elicited by correctly rejected new faces that concurred with a more liberal response criterion for emotional as compared to neutral faces. Taken together, the results are consistent with the view that processes promoting recollection are facilitated for negative events and that emotion may affect recognition performance by influencing criterion setting mediated by the prefrontal cortex.     

Event-related fMRI studies of episodic encoding and retrieval: Meta-analyses using activation likelihood estimation

The recent surge in event-related fMRI studies of episodic memory has generated a wealth of information about the neural correlates of encoding and retrieval processes. However, interpretation of individual studies is hampered by methodological differences, and by the fact that sample sizes are typically small. We submitted results from studies of episodic memory in healthy young adults, published between 1998 and 2007, to a voxel-wise quantitative meta-analysis using activation likelihood estimation [Laird, A. R., McMillan, K. M., Lancaster, J. L., Kochunov, P., Turkeltaub, P. E., & Pardo, J. V., et al. (2005). A comparison of label-based review and ALE meta-analysis in the stroop task. Human Brain Mapping, 25, 6–21]. We conducted separate meta-analyses for four contrasts of interest: episodic encoding success as measured in the subsequent-memory paradigm (subsequent Hit vs. Miss), episodic retrieval success (Hit vs. Correct Rejection), objective recollection (e.g., Source Hit vs. Item Hit), and subjective recollection (e.g., Remember vs. Know). Concordance maps revealed significant cross-study overlap for each contrast. In each case, the left hemisphere showed greater concordance than the right hemisphere. Both encoding and retrieval success were associated with activation in medial-temporal, prefrontal, and parietal regions. Left ventrolateral prefrontal cortex (PFC) and medial-temporal regions were more strongly involved in encoding, whereas left superior parietal and dorsolateral and anterior PFC regions were more strongly involved in retrieval. Objective recollection was associated with activation in multiple PFC regions, as well as multiple posterior parietal and medial-temporal areas, but not hippocampus. Subjective recollection, in contrast, showed left hippocampal involvement. In summary, these results identify broadly consistent activation patterns associated with episodic encoding and retrieval, and subjective and objective recollection, but also subtle differences among these processes.     

Functional MRI of cerebral activation during encoding and retrieval of words

The aims of the present study were to identify the cerebral structures associated with encoding and retrieval of verbal material. To circumvent the inherent disadvantages of the conventional block designs used in functional magnetic resonance imaging (MRI), an event-related design compared activation related to randomly intermixed old and new words during recognition. To support the validity of results, both nonparametric analyses in regions of interest (ROI) and statistical parametric mapping (SPM 96) were used. Twelve healthy volunteers, ages 22-35 years, performed three tasks: intentional encoding of words, recognition of old (previously learned) words, and discrimination between words and nonwords, a task to control for visual input and motor output during recognition. Echo-planar magnetic resonance imaging of blood-level, oxygen-dependent, task-related changes was used to compare cerebral activity under active and resting conditions as well as to detect event-related activity within blocks of trials. Comparable results were obtained following nonparametric statistical analysis of selected ROI and SPM. Encoding of words was associated with increased activity in the left inferior frontal gyrus, including Broca's area and in the left parietal association cortex. Event-related data analysis revealed activation of the right medial frontal gyrus, the right anterior cingulate gyrus, and parietal association cortices during recognition of previously presented words. In the lexical decision task, words in comparison with nonwords were associated with activation of the left parietal association cortex. The right medial frontal gyrus, the right anterior cingulate gyrus, and the right parietal association cortex are likely to be involved in episodic memory functions during recognition of previously presented verbal material. The comparison of event-related activation occurring within one trial block instead of among several trial blocks may significantly improve the performance of memory studies.     

Development of memory for spatial context: Hippocampal and cortical contributions

The goal of the present study was to examine age-related differences in hippocampal and cortical contribution to episodic retrieval of spatial context in 3 age groups. Children ages 8–9 and 10–11 years old, and adults ages 18–25 (N=48) encoded black and white line drawings appearing either on the right side or the left side of a screen. Functional magnetic resonance imaging (fMRI) data were acquired while participants attempted to recall where each studied drawing had originally appeared. Correct recall of spatial source indicated successful episodic retrieval of spatial context. Activity in head and body of the hippocampus was associated with episodic retrieval in adults, but not in children. In children, individual differences in hippocampal activation for recognition predicted rates of correct spatial recall. Developmental differences were also found in regions in posterior parietal cortex, anterior prefrontal cortex, and insula. Overall, these results support the view that the development of episodic memory is supported by functional changes in the hippocampus as well as cortical regions.     

The interfering effect of related events on recognition memory discriminability: a functional magnetic resonance imaging study

Retrieval of information from memory often involves the selection of an event among competing related events, a process that frequently gives rise to interference effects. The present study used a forced-choice recognition test to identify neural correlates of the interfering effect of related events on recognition memory discriminability. Participants encoded landscape pictures divided into three segments. One segment was presented during encoding, and a forced-choice recognition task contrasted a studied and a nonstudied segment for each landscape. For half of the landscapes, the third segment was presented between encoding and recognition tasks to induce associative interference by reducing recognition discriminability. A behavioral study with 40 subjects yielded a significant difference in the correct recognition rate between control and interference trials (76% and 64%, respectively, p<0.001). A subsequent event-related fMRI study with 16 subjects yielded significant activations for correct interference recognition trials relative to control trials in left superior parietal regions, which suggests that these regions play a role in the representation of stimuli and associated information. The opposite contrast yielded significant activations in inferior prefrontal regions bilaterally, right dorsolateral prefrontal cortex and right parahippocampal cortex. Since this contrast was conducted using only correctly recognized trials, these findings could reflect an index of memory discriminability or saliency which could influence conscious recollection.     

Associative memory encoding and recognition in schizophrenia: an event-related fMRI study.

BACKGROUND: We used an event-related functional Magnetic Resonance Imaging (fMRI) approach to examine the neural basis of the selective associative memory deficit in schizophrenia. METHODS: Fifteen people with schizophrenia and 18 controls were scanned during a pair and item memory encoding and recognition task. During encoding, subjects studied items and pairs of visual objects. In a subsequent retrieval task, participants performed an item recognition memory test (old/new decisions) and an associative recognition test (intact/rearranged decisions). The fMRI analysis of the recognition data was restricted to correct items only and a random effects model was used. RESULTS: At the behavioral level, both groups performed equally well on item recognition, whereas people with schizophrenia demonstrated lower performance on associative recognition relative to the control group. At the brain level, the comparison between associative and item encoding revealed greater activity in the control group in the left prefrontal cortex and cingulate gyrus relative to the schizophrenia group. During recognition, greater left dorsolateral prefrontal and right inferior prefrontal activations were observed in the control group relative to the schizophrenia group. CONCLUSION: This fMRI study implicates the prefrontal cortex among other brain regions as the basis for the selective associative memory encoding and recognition deficit seen in schizophrenia.     

Neural activity associated with episodic memory for emotional context

To address the question of which brain regions subserve retrieval of emotionally-valenced memories, we used event-related fMRI to index neural activity during the incidental retrieval of emotional and non-emotional contextual information. At study, emotionally neutral words were presented in the context of sentences that were either negatively, neutrally or positively valenced. At test, fMRI data were obtained while participants discriminated between studied and unstudied words. Recognition of words presented in emotionally negative relative to emotionally neutral contexts was associated with enhanced activity in right dorsolateral prefrontal cortex, left amygdala and hippocampus, right lingual gyrus and posterior cingulate cortex. Recognition of words from positive relative to neutral contexts was associated with increased activity in bilateral prefrontal and orbitofrontal cortices, and left anterior temporal lobe. These findings suggest that neural activity mediating episodic retrieval of contextual information and its subsequent processing is modulated by emotion in at least two ways. First, there is enhancement of activity in networks supporting episodic retrieval of neutral information. Second, regions known to be activated when emotional information is encountered in the environment are also active when emotional information is retrieved from memory.     

A role for right medial prefontal cortex in accurate feeling-of-knowing judgements: evidence from patients with lesions to frontal cortex

The hypothesis that prefrontal cortex plays a critical role in accurate predictions of episodic memory performance was tested using the feeling-of-knowing (FOK) paradigm. Fourteen patients with a broad spectrum of damage to the frontal cortex and matched controls read sentences and later were tested for recall memory, confidence judgments, and FOK accuracy using as cues the sentences with the final word missing. While frontal patients were impaired at recall and recognition memory, they were able to make accurate confidence judgments about their recall attempts. By contrast, as a group, the patients were markedly impaired in the accuracy of their prospective FOK judgments. Lesion analysis of frontal patients with clear FOK impairment revealed an overlapping region of damage in right medial prefrontal cortex. These findings provide functional and anatomical evidence for a dissociation between recall confidence and prospective memory monitoring and are discussed in terms of familiarity and access theories of FOK predictions.     

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.     

Passive tactile recognition of geometrical shape in humans: An fMRI study

Tactile shape discrimination involves frontal other than somatosensory cortex (Palva et al., 2005 [48]), but it is unclear if this frontal activity is related to exploratory concomitants. In this study, we investigated topographical details of prefrontal, premotor, and parietal areas during passive tactile recognition of 2D geometrical shapes in conditions avoiding exploratory movements. Functional magnetic resonance imaging (fMRI) was performed while the same wooden 2D geometrical shapes were blindly pressed on subjects’ passive right palm in three conditions. In the RAW condition, shapes were pressed while subjects were asked to attend to the stimuli but were not trained to recognize them. After a brief training, in the SHAPE condition subjects were asked to covertly recognize shapes. In the RECOGNITION condition, they were asked to overtly recognize shapes, using response buttons with their opposite hand. Results showed that somatosensory cortex including contralateral SII, contralateral SI, and left insula was active in all conditions, confirming its importance in processing tactile shapes. In the RAW vs. SHAPE contrast, bilateral posterior parietal, insular, premotor, prefrontal, and (left) Broca's areas were more active in the latter. In the RECOGNITION, activation of (left) Broca's area correlated with correct responses. These results suggest that, even without exploratory movements, passive recognition of tactile geometrical shapes involves prefrontal and premotor as well as somatosensory regions. In this framework, Broca's area might be involved in a successful selection and/or execution of the correct responses.