Dissociation between explicit memory and configural memory in the human medial temporal lobe

Using functional magnetic resonance imaging, the current study explored the differential mnemonic contributions of the hippocampus and surrounding medial temporal lobe (MTL) cortices to explicit recognition memory and configural learning. Using a task that required processing of repeated and novel visuospatial contexts across multiple trials, we examined MTL activation in relation to 3 forms of learning in a single paradigm: 1) context-independent procedural learning, 2) context-dependent configural learning, and 3) explicit recognition memory. Activations in hippocampus and parahippocampal cortex were associated with explicit memory, differentiating between subsequently remembered and forgotten repeated contexts, but were unrelated to context-dependent configural learning. Activations in regions of perirhinal and entorhinal cortex were associated with configural learning of repeated contexts independent from explicit memory for those contexts. Procedural learning was unrelated to activation in any MTL region. The time course of activation across learning further differed in MTL subregions with MTL cortex demonstrating repetition-related decreases and hippocampus repetition-related increases. These repetition effects were differentially sensitive to recognition with only activation in hippocampus and parahippocampal cortex tracking recognized items. These imaging findings converge with studies of amnesia and indicate dissociable roles for hippocampus in learning that supports explicit recognition and for anterior MTL cortex in configural learning.     

Postoperative reading speed does not indicate implicit memory in elderly cardiac patients after propofol and remifentanyl anaesthesia

BACKGROUND: A recent study in young patients undergoing propofol-alfentanil-nitrous oxide anaesthesia demonstrated implicit memory for stories presented during operation using a postoperative reading speed task. In this study we investigated whether patients who tolerate only small amounts of anaesthetics are prone to develop implicit and explicit memories about intraoperative events. METHODS: Thirty patients with poor physical status (ASA III-IV) undergoing cardioverter defibrillator implantation were included in the study. Patients were premedicated with intravenous midazolam and anaesthesia was maintained using propofol and remifentanil infusions. During surgery one of two audio-tapes containing two short stories was played to the patients. Reading speed for the stories played during surgery and two similar stories from the other tape was tested 4 h later. Explicit memory was tested at 4 h and 24 h after audiotape presentation using a structured interview and a forced-choice recognition test pertaining to the story content. Thirty additional awake subjects served as controls. RESULTS: Although half of the patients seemed to be awake one or more times during the operation, no explicit memories of intraoperative events were reported. The forced-choice recognition of the stories was at chance level. No effect on reading speed was found in either the patients or the control subjects. CONCLUSIONS: The possible reasons for reduced explicit and implicit memory performance in elderly patients are age and poor physical status of the patients and the modality change between study and test phases. A non-anaesthetised control group of the same age and physical status should therefore be included in all studies of implicit memory.     

Aβ Deposition in aging is associated with increases in brain activation during successful memory encoding

To investigate early effects of beta-amyloid (Aβ) on neuronal function, elderly normal controls (NCs, age range 58-97) were scanned with Pittsburgh Compound-B (PIB) positron emission tomography (a measure of Aβ) as well as functional magnetic resonance imaging (a measure of brain activation) while performing an episodic memory-encoding task of natural scenes (also performed by young NCs; age range 18-30). Relationships between Aβ and activation were assessed across task-positive (regions that activate for subsequently remembered vs. forgotten scenes) and task-negative regions (regions that deactivate for subsequently remembered vs. forgotten scenes). Significant task-related activation was present in a distributed network spanning ventrolateral prefrontal, lateral occipital, lateral parietal, posterior inferior temporal cortices, and the right parahippocampal/hippocampus, whereas deactivation was present in many default mode network regions (posteromedial, medial prefrontal, and lateral temporoparietal cortices). Task-positive activation was higher in PIB+ compared with PIB- subjects, and this activation was positively correlated with memory measures in PIB+ subjects. Although task deactivation was not impaired in PIB+ NCs, deactivation was reduced in old versus young subjects and was correlated with worse task memory performance among old subjects. Overall, these results suggest that heightened activation during episodic memory encoding is present in NC elderly subjects with high Aβ.     

On the benefits of not trying: brain activity and connectivity reflecting the interactions of explicit and implicit sequence learning

Under certain circumstances, implicit, automatic learning may be attenuated by explicit memory processes. We explored the brain basis of this phenomenon in a functional magnetic resonance imaging (fMRI) study of motor sequence learning. Using a factorial design that crossed subjective intention to learn (explicit versus implicit) with sequence difficulty (a standard versus a more complex alternating sequence), we show that explicit attempts to learn the difficult sequence produce a failure of implicit learning and, in a follow-up behavioural experiment, that this failure represents a suppression of learning itself rather than of the expression of learning. This suppression is associated with sustained right frontal activation and attenuation of learning-related changes in the medial temporal lobe and the thalamus. Furthermore, this condition is characterized by a reversal of the fronto-thalamic connectivity observed with unimpaired implicit learning. The findings demonstrate a neural basis for a well-known behavioural effect: the deleterious impact of an explicit search upon implicit learning.     

Dependence of explicit and implicit memory on hypnotic state in trauma patients

BACKGROUND: It is still unclear whether memory of intraoperative events results entirely from moments of inadequate anesthesia. The current study was designed to determine whether the probability of memory declines with increasing depth of the hypnotic state. METHOD: A list of words was played via headphones during surgery to patients who had suffered acute trauma. Several commonly used indicators of anesthetic effect, including the bispectral index, were recorded during word presentation. First, these indicators served as predictors of the memory performance in a postoperative word stem completion test. Second, general memory performance observed in the first part was separated into explicit and implicit memory using the process dissociation procedure, and then two models of memory were compared: One model assumed that the probability of explicit and implicit memory decreases with increasing depth of hypnotic state (individual differences model), whereas the other assumed equal memory performance for all patients regardless of their level of hypnotic state. RESULTS: General memory performance declined with decreasing bispectral index values. None of the other indicators of hypnotic state were related to general memory performance. Memory was still significant at bispectral index levels between 60 and 40. A comparison of the two models of memory resulted in a better fit of the individual differences model, thus providing evidence of a dependence of explicit and implicit memory on the hypnotic state. Quantification of explicit and implicit memory revealed a significant implicit but no reliable explicit memory performance. CONCLUSIONS: This study clearly indicates that memory is related to the depth of hypnosis. The observed memory performance should be interpreted in terms of implicit memory. Auditory information processing occurred at bispectral index levels between 60 and 40.     

Disturbing visual working memory: electrophysiological evidence for a role of the prefrontal cortex in recovery from interference

Single cell recordings in monkeys support the notion that the lateral prefrontal cortex (PFC) controls reactivation of visual working memory representations when rehearsal is disrupted. In contrast, recent fMRI findings yielded a double dissociation for PFC and the medial temporal lobe (MTL) in a letter working memory task. PFC was engaged in interference protection during reactivation while MTL was prominently involved in the retrieval of the letter representations. We present event-related potential data (ERP) that support PFC involvement in the top-down control of reactivation during a visual working memory task with endogenously triggered recovery after visual interference. A differentiating view is proposed for the role of PFC in working memory with respect to endogenous/exogenous control and to stimulus type. General implications for binding and retention mechanisms are discussed.     

Absence of implicit and explicit memory during propofol/remifentanil anaesthesia

BACKGROUND AND OBJECTIVE: High doses of opioid associated with low doses of hypnotic is a popular anaesthetic technique since the use of remifentanil has become widespread. This type of anaesthesia could result in a higher incidence of implicit memory. METHODS: Ten patients were anaesthetised with a target-controlled infusion of remifentanil (target concentration of 8 ng mL(-1)) combined with a target-controlled infusion of propofol with progressive stepwise increases until loss of consciousness was reached. A tape containing 20 words was then played to the patients. Bispectral index (BIS, Aspect Medical Systems, Newton, MA, USA) was continuously monitored during the whole study period. Implicit and explicit memories were tested between 2 and 4 h after recovery. RESULTS: Loss of consciousness was obtained with a mean calculated propofol plasma concentration of 1.3 +/- 0.4 microg mL(-1). At this low hypnotic concentration no implicit or explicit memory was found in the three postoperative memory tests. Median (range) BIS value during word presentation was 93 (80-98). CONCLUSIONS: In our group of young American Society of Anesthesiologists (ASA) I/II patients, no explicit or implicit memory was found when the calculated concentration of propofol combined with a high concentration of remifentanil was maintained at the level associated with loss of consciousness with high BIS values.     

Interaction of working memory and long-term memory in the medial temporal lobe

Recent findings indicate that regions in the medial temporal lobe (MTL) do not only play a crucial role in long-term memory (LTM) encoding, but contribute to working memory (WM) as well. However, very few studies investigated the interaction between these processes so far. In a new functional magnetic resonance imaging paradigm comprising both a complex WM task and an LTM recognition task, we found not only that some items were successfully processed in WM but later forgotten, but also that a significant number of items which were not successfully processed in the WM task were subsequently recognized. Activation in the parahippocampal cortex (PHC) during successful WM was predictive of subsequent LTM, but was correlated with subsequent forgetting if the WM task was not successfully solved. The contribution of the PHC to LTM encoding thus crucially depends on whether an item was successfully processed in the WM task. Functional connectivity analysis revealed that across-trial fluctuations in PHC activity were correlated with activation in extensive regions if WM and LTM tasks were correctly solved, whereas connectivity broke down during unsuccessful attempts to do the task, suggesting that activity in the PHC during WM has to be well controlled to support LTM formation.     

Learning the exception to the rule: model-based FMRI reveals specialized representations for surprising category members

Category knowledge can be explicit, yet not conform to a perfect rule. For example, a child may acquire the rule "If it has wings, then it is a bird," but then must account for exceptions to this rule, such as bats. The current study explored the neurobiological basis of rule-plus-exception learning by using quantitative predictions from a category learning model, SUSTAIN, to analyze behavioral and functional magnetic resonance imaging (fMRI) data. SUSTAIN predicts that exceptions require formation of specialized representations to distinguish exceptions from rule-following items in memory. By incorporating quantitative trial-by-trial predictions from SUSTAIN directly into fMRI analyses, we observed medial temporal lobe (MTL) activation consistent with 2 predicted psychological processes that enable exception learning: item recognition and error correction. SUSTAIN explains how these processes vary in the MTL across learning trials as category knowledge is acquired. Importantly, MTL engagement during exception learning was not captured by an alternate exemplar-based model of category learning or by standard contrasts comparing exception and rule-following items. The current findings thus provide a well-specified theory for the role of the MTL in category learning, where the MTL plays an important role in forming specialized category representations appropriate for the learning context.     

Propofol and memory: a study using a process dissociation procedure and functional magnetic resonance imaging

Thirty volunteers randomly received either mild or deep propofol sedation, to assess its effect on explicit and implicit memory. Blood oxygen level‐dependent functional magnetic resonance during sedation examined brain activation by auditory word stimulus and a process dissociation procedure was performed 4 h after scanning. Explicit memory formation did not occur in either group. Implicit memories were formed during mild but not deep sedation (p = 0.04). Mild propofol sedation inhibited superior temporal gyrus activation (Z value 4.37, voxel 167). Deep propofol sedation inhibited superior temporal gyrus (Z value 4.25, voxel 351), middle temporal gyrus (Z value 4.39, voxel 351) and inferior parietal lobule (Z value 5.06, voxel 239) activation. Propofol only abolishes implicit memory during deep sedation. The superior temporal gyrus is associated with explicit memory processing, while the formation of both implicit and explicit memories is associated with superior and middle temporal gyri and inferior parietal lobule activation.     

Comparing the effects of stimulation and propofol infusion rate on implicit and explicit memory formation

Doubt remains about the conditions under which learning persistsdespite anaesthesia. This study investigated the relative importanceof dose of anaesthetic and stimulation for learning during propofolinfusion before surgery. Thirty-six patients were randomly assignedto three groups. Group 1 received two word lists (category examplesand nonsense words) during infusion of propofol to a targetconcentration of 2 µg ml^–1. Groups 2 and3 received the word lists during infusion of propofol 5 µg ml^–1.Group 2 received nonsense words before tracheal intubation andcategory examples during intubation; Group 3 heard categoryexamples before and nonsense words during intubation. Bispectralindex was recorded as a measure of depth of sedation/anaesthesia.We assessed explicit memory on recovery using a structured interviewand a recognition test. We assessed implicit memory using acategory generation test and a preference rating task. To establishbaseline, a control group of 12 patients completed the categorygeneration test without receiving the category examples duringanaesthesia. Overall, there was no evidence for learning duringpropofol infusion, though the category generation task showeda trend towards more implicit memory for words presented duringintubation than during anaesthesia. We conclude that learningdoes not occur during anaesthesia without surgery. Br J Anaesth 2001; 86: 189–95     

Is there implicit memory after propofol sedation?

Recent evidence indicates that implicit memory may be preserved during general anaesthesia. We tested for the presence of explicit and implicit memory in patients undergoing surgical procedures with local or regional anaesthesia and sedation with propofol. Initial i.v. boluses of propofol 0.5 mg kg-1 and fentanyl 1 microgram kg-1 were administered, followed by an infusion of propofol 50 micrograms kg-1 min-1. Administration of one or more doses of propofol 30 mg i.v. during operation was controlled either by the patient or the anaesthetist. At the start of the last skin stitch, patients were presented with a list of 15 stimulus words and the most frequently associated response. The infusion was then discontinued. After 1 h in the recovery area, all patients were tested for free recall, free association, cued recall and recognition on the list presented during surgery (critical list) and a matched list not presented (neutral list). Data of all patients without free recall (explicit memory) were analysed with repeated-measures analysis of variance. Of 36 patients, five demonstrated free recall. For the remaining 31 patients, cued recall and recognition showed no evidence of explicit memory. However, the free association tests demonstrated significant priming. The mean number of critical free associations was 6.6 (SEM 0.4) compared with 5.5 (0.4) neutral free association (P < 0.05). In the absence of explicit memory, implicit memory persists after intraoperative sedation with propofol.      

Investigation of implicit memory during isoflurane anesthesia for elective surgery using the process dissociation procedure

BACKGROUND: This prospective study evaluated memory function during general anesthesia for elective surgery and its relation to depth of hypnotic state. The authors also compared memory function in anesthetized and nonanesthetized subjects. METHODS: Words were played for 70 min via headphones to 48 patients (aged 18-70 yr) after induction of general anesthesia for elective surgery. Patients were unpremedicated, and the anesthetic regimen was free. The Bispectral Index (BIS) was recorded throughout the study. Within 36 h after the word presentation, memory was assessed using an auditory word stem completion test with inclusion and exclusion instructions. Memory performance and the contribution of explicit and implicit memory were calculated using the process dissociation procedure. The authors applied the same memory task to a control group of nonanesthetized subjects. RESULTS: Forty-seven patients received isoflurane, and one patient received propofol for anesthesia. The mean (+/- SD) BIS was 49 +/- 9. There was evidence of memory for words presented during light (BIS 61-80) and adequate anesthesia (BIS 41-60) but not during deep anesthesia (BIS 21-40). The process dissociation procedure showed a significant implicit memory contribution but not reliable explicit memory contribution (mean explicit memory scores 0.05 +/- 0.14, 0.04 +/- 0.09, and 0.05 +/- 0.14; mean automatic influence scores 0.14 +/- 0.12, 0.17 +/- 0.17, and 0.18 +/- 0.21 at BIS 21-40, 41-60, and 61-80, respectively). Compared with anesthetized patients, the memory performance of nonanesthetized subjects was better, with a higher contribution by explicit memory and a comparable contribution by implicit memory. CONCLUSION: During general anesthesia for elective surgery, implicit memory persists even in adequate hypnotic states, to a comparable degree as in nonanesthetized subjects.     

Absence of explicit and implicit memory in unconscious patients using a TCI of propofol

BACKGROUND: Episodes of implicit memory have been described during propofol anaesthesia. It remains unclear whether implicit memory is caused by short periods of awareness or occurs in an unconscious subject. METHODS: Sixty patients were randomized in an experimental group (EG), a control group (CG) and a reference group (RG). Loss of consciousness (LOC) was obtained by progressive stepwise increases of propofol using a target-controlled infusion device (Diprifusor, Alaris Medical Systems, San Diego, CA). A tape containing 20 words was played to the patients in the CG before the start of anaesthesia and to the patients in the EG at a constant calculated concentration of propofol associated with LOC. The tape was not played to the patients in the RG. Three memory tests were performed postoperatively. RESULTS: Explicit and implicit memories were evidenced in the CG but not in the EG. CONCLUSION: In our group of young ASA I/II patients, in the absence of any noxious stimulus, no implicit or explicit memory was found when the calculated concentration of propofol using a Diprifusor was maintained at the level associated with LOC.     

Distinct patterns of functional and effective connectivity between perirhinal cortex and other cortical regions in recognition memory and perceptual discrimination

Traditionally, the medial temporal lobe (MTL) is thought to be dedicated to declarative memory. Recent evidence challenges this view, suggesting that perirhinal cortex (PrC), which interfaces the MTL with the ventral visual pathway, supports highly integrated object representations in recognition memory and perceptual discrimination. Even with comparable representational demands, perceptual and memory tasks differ in numerous task demands and the subjective experience they evoke. Here, we tested whether such differences are reflected in distinct patterns of connectivity between PrC and other cortical regions, including differential involvement of prefrontal control processes. We examined functional magnetic resonance imaging data for closely matched perceptual and recognition memory tasks for faces that engaged right PrC equivalently. Multivariate seed analyses revealed distinct patterns of interactions: Right ventrolateral prefrontal and posterior cingulate cortices exhibited stronger functional connectivity with PrC in recognition memory; fusiform regions were part of the pattern that displayed stronger functional connectivity with PrC in perceptual discrimination. Structural equation modeling revealed distinct patterns of effective connectivity that allowed us to constrain interpretation of these findings. Overall, they demonstrate that, even when MTL structures show similar involvement in recognition memory and perceptual discrimination, differential neural mechanisms are reflected in the interplay between the MTL and other cortical regions.     

Interactions of memory and perception in amnesia: the figure-ground perspective

The medial temporal lobes (MTLs) have been thought to function exclusively in service of declarative memory. Recent research shows that damage to the perirhinal cortex (PRC) of the MTL impairs the discrimination of objects sharing many similar parts/features, leading to the hypothesis that the PRC contributes to the perception when the feature configurations, rather than the individual features, are required to solve the task. It remains uncertain, however, whether the previous research demands a slight extension of PRC function to include working memory or a more dramatic extension to include perception. We present 2 experiments assessing the implicit effects of familiar configuration on figure assignment, an early and fundamental perceptual outcome. Unlike controls, PRC-damaged individuals failed to perceive the regions portraying familiar configurations, as figure more often, than the regions comprising the same parts rearranged into novel configurations. They were also impaired in identifying the familiar objects. In a third experiment, PRC-damaged individuals performed poorly when asked to choose a familiar object from pairs of familiar and novel objects comprising the same parts. Our results demonstrate that the PRC is involved in both implicit and explicit perceptual discriminations of novel and familiar configurations. These results reveal that complex object representations in the PRC subserve both perception and memory.     

Face repetition effects in implicit and explicit memory tests as measured by fMRI.

Recent parallels between neurophysiological and neuroimaging findings suggest that repeated stimulus processing produces decreased responses in brain regions associated with that processing--a 'repetition suppression' effect. In the present study, volunteers performed two tasks on repeated presentation of famous and unfamiliar faces during functional magnetic resonance imaging (fMRI). In the implicit task, they made fame-judgements (regardless of repetition); in the explicit task, they made episodic recognition judgements (regardless of familiarity). Only in the implicit task was repetition suppression observed: for famous faces in a right lateral fusiform region, and for both famous and unfamiliar faces in a left inferior occipital region. Repetition suppression is therefore not an automatic consequence of repeated perceptual processing of stimuli.     

Awareness, dreaming and unconscious memory formation during anaesthesia in children

Recent studies have reported an incidence of awareness in children of around 1%, while older studies reported incidences varying from 0% to 5%. Measuring awareness in children requires techniques specifically adapted to a child's cognitive development and variations in incidence may be partly explained by the measures used. The causes and consequences of awareness in children remain poorly defined, though a consistent finding is that many children do not seem distressed by their memories. There are, however, some published reports of persistent psychological symptoms after episodes of childhood awareness. Compared to explicit memory, implicit memory is more robust in young children; however there is no evidence yet for implicit memory formation during anaesthesia in children. Children less than 3 years of age do not form explicit memory, although toddlers, infants and even neonates have signs of consciousness and implicit memory formation. In these very young children the relevance of awareness remains largely unknown.     

Effect of midazolam on memory: a study of process dissociation procedure and functional magnetic resonance imaging

To assess the effects of midazolam on explicit and implicit memories, 12 volunteers were randomly divided into the two groups: one with an Observer’s Assessment of Alertness/Sedation score of 3 (mild sedation) and one with a score of 1 (deep sedation). Blood oxygen‐level‐dependent functional magnetic resonance imaging was measured before and during an auditory stimulus, then with midazolam sedation, and then during a second auditory stimulus with continuous midazolam sedation. After 4 h, explicit and implicit memories were assessed. There was no evidence of explicit memory at the two levels of midazolam sedation. Implicit memory was retained at a mild level of midazolam sedation but absent at a deep level of midazolam sedation. At a mild level of midazolam sedation, activation of all brain areas by auditory stimulus (as measured by functional magnetic resonance imaging) was uninhibited. However, a deep level of midazolam sedation depressed activation of the superior temporal gyrus by auditory stimulus. We conclude that midazolam does not abolish implicit memory at a mild sedation level, but can abolish both explicit and implicit memories at a deep sedation level. The superior temporal gyrus may be one of the target areas.     

Neural correlates of rule-based and information-integration visual category learning

An emerging theory of the neurobiology of category learning postulates that there are separate neural systems supporting the learning of categories based on verbalizeable rules (RB) or through implicit information integration (II). The medial temporal lobe (MTL) is thought to play a crucial role in successful RB categorization, whereas the posterior regions of the caudate are hypothesized to support II categorization. Functional neuroimaging was used to assess activity in these systems during category-learning tasks with category structures designed to afford either RB or II learning. Successful RB categorization was associated with relatively increased activity in the anterior MTL. Successful II categorization was associated with increased activity in the caudate body. The dissociation observed with neuroimaging is consistent with the roles of these systems in memory and dissociations reported in patient populations. Convergent evidence from these approaches consistently reinforces the idea of multiple neural systems supporting category learning.