Usefulness of language and memory testing during intracarotid amobarbital testing: observations from an fMRI study

BACKGROUND: Several procedures for testing language lateralization and memory function exist during the intracarotid amobarbital test (IAT). The use of functional magnetic resonance imaging (fMRI) gives the opportunity to assess the validity of some of these procedures, or at least to inspect the neuronal correlates. A comprehensive fMRI protocol was tested, aimed at addressing aspects of lateralization of language, as well as testing memory in relation to activation of mesiotemporal regions. Here we report observations with possible consequences for the current IAT procedures. MATERIALS AND METHODS: The protocol consisted of three language tasks (overt naming, semantic decision and silent word generation) and two memory tasks (encoding and retrieving visual scenes). The paradigms used a block-related procedure in nine right-handed normal volunteers. During the procedure dynamic weighted full brain images were acquired which are sensitive to the blood oxygenation activation effect. RESULTS : Encoding showed symmetrical bilateral activation in the mesiotemporal regions, specifically the hippocampus, parahippocampal gyrus and fusiform gyrus. With a retrieval task activation of the mesiotemporal areas was restricted to the posterior hippocampal area. Overt object naming showed results, similar to encoding tasks with bilateral activation of hippocampal areas. Silent word generation showed much stronger ability to lateralize than the other two language-related tasks and especially object naming. CONCLUSION: Activation revealed by fMRI activation shows that IAT procedures, using active semantic language processing or comprehensive procedures with multiple language tasks have the highest guarantee for individual activation lateralization. Simple object naming does not guarantee a lateralized language fMRI activation pattern. Of the different memory procedures during IAT, the procedures (Interview and the Montreal) demanding encoding processing will be related to larger areas of bilateral hippocampal activation than procedures (Seattle) exclusively requiring retrieval. Moreover, tasks using recognition of previously presented language items (naming objects) are equally effective for assessing hippocampal activation compared with presenting separate memory items.     

fMRI correlates of retrieval orientation

Processes related to the cueing of memory retrieval were investigated using fMRI during a yes/no recognition memory test. Participants studied either pictures or auditory words and were subsequently tested with visual words that either corresponded to studied items (old items) or were unstudied (new items). It was expected that neural activity would differ according to the type of information participants are trying to retrieve: a manifestation of the so-called "retrieval orientation" effect. We replicated robust old/new effects in parietal, prefrontal and anterior medial temporal lobe cortices, which did not differ according to the study material. However, we did observe differential activity to test items in temporoparietal cortex and fusiform cortex as a function of the study material. More specifically, attempts to retrieve words encoded auditorily produced greater activity in auditory cortex than attempts to retrieve words encoded as pictures, whereas the converse was found in fusiform cortex. The above pattern was found for both new and old test items. These findings implicate these regions in constraining the search for specific types of encoded information and thus are in accordance with the transfer-appropriate processing framework. Further, we propose that our results can be seen as an extension of the cortical reinstatement hypothesis, in that the same material-specific cortical regions are engaged during both encoding and retrieval, and this increases the likelihood of successful recognition, or rejection, of retrieval cues in a memory test.     

Dynamic switching between semantic and episodic memory systems

It has been suggested that episodic and semantic long-term memory systems interact during retrieval. Here we examined the flexibility of memory retrieval in an associative task taxing memories of different strength, assumed to differentially engage episodic and semantic memory. Healthy volunteers were pre-trained on a set of 36 face-name pairs over a 6-week period. Another set of 36 items was shown only once during the same time period. About 3 months after the training period all items were presented in a randomly intermixed order in an event-related fMRI study of face-name memory. Once presented items differentially activated anterior cingulate cortex and a right prefrontal region that previously have been associated with episodic retrieval mode. High-familiar items were associated with stronger activation of posterior cortices and a left frontal region. These findings fit a model of memory retrieval by which early processes determine, on a trial-by-trial basis, if the task can be solved by the default semantic system. If not, there is a dynamic shift to cognitive control processes that guide retrieval from episodic memory.     

Evidence for cortical encoding specificity in episodic memory: memory-induced re-activation of picture processing areas

Functional magnetic resonance imaging (fMRI) was used to examine whether neural pathways used to encode pictures into memory were re-activated during retrieval of those memories. At encoding, subjects semantically classified common objects presented as pictures or words. At retrieval, subjects performed yes/no recognition memory judgments on words that had been encoded as pictures or as words. The retrieval test probed memory for the encoded item, but not memory for the modality of the encoded item (picture/word). Results revealed that a subset of the brain regions involved specifically in encoding of pictures were also engaged during recognition memory for the encoded pictures. Specifically, encoding of pictures relative to words engaged bilateral extrastriate visual cortex, namely fusiform, lingual, middle occipital, and inferior temporal gyri (Broadman area (BA) 18/19/37). Recognition memory judgments about words that were encoded as pictures relative to those that were encoded as words activated fusiform and inferior temporal gyri primarily in the left hemisphere. Thus, cortical areas originally involved in perception of a visual experience become part of the long-term memory trace for that experience. These findings suggest a neural basis for encoding specificity and transfer appropriate processing in human memory.     

Implicit and Explicit Memory in Autism: Is Autism an Amnesic Disorder?

Medial temporal lobe amnesic disorder is characterized by an impairment in explicit memory (e.g., remembering a shopping list) and intact implicit memory (e.g., a woman seems familiar although you cannot remember having met her before). This study examined whether children with high-functioning autism have this same dissociation between explicit and implicit memory abilities. Children with autism and normal development participated in three memory tasks: one implicit task (perceptual identification) and two explicit tasks (recognition and recall). Children with autism showed intact implicit and explicit memory abilities. However, they did not show the typical pattern of recalling more items from both the beginning and end of a list and instead only recalled items from the end of the list. These results do not support the theory that high-functioning autism is a type of medial temporal lobe amnesia. However, these findings suggest that persons with autism use different organizational strategies during encoding or retrieval of items from memory.     

Neural correlates of working memory for sign language

Eight, early bilingual, sign language interpreters participated in a PET study, which compared working memory for Swedish Sign Language (SSL) with working memory for audiovisual Swedish speech. The interaction between language modality and memory task was manipulated in a within-subjects design. Overall, the results show a previously undocumented, language modality-specific working memory neural architecture for SSL, which relies on a network of bilateral temporal, bilateral parietal and left premotor activation. In addition, differential activation in the right cerebellum was found for the two language modalities. Similarities across language modality are found in Broca's area for all tasks and in the anterior left inferior frontal lobe for semantic retrieval. The bilateral parietal activation pattern for sign language bears similarity to neural activity during, e.g., nonverbal visuospatial tasks, and it is argued that this may reflect generation of a virtual spatial array. Aspects of the data suggesting an age of acquisition effect are also considered. Furthermore, it is discussed why the pattern of parietal activation cannot be explained by factors relating to perception, production or recoding of signs, or to task difficulty. The results are generally compatible with Wilson's [Psychon. Bull. Rev. 8 (2001) 44] account of working memory.     

When keeping in mind supports later bringing to mind: neural markers of phonological rehearsal predict subsequent remembering.

The ability to bring to mind a past experience depends on the cognitive and neural processes that are engaged during the experience and that support memory formation. A central and much debated question is whether the processes that underlie rote verbal rehearsal-that is, working memory mechanisms that keep information in mind-impact memory formation and subsequent remembering. The present study used event-related functional magnetic resonance imaging (fMRI) to explore the relation between working memory maintenance operations and long-term memory. Specifically, we investigated whether the magnitude of activation in neural regions supporting the on-line maintenance of verbal codes is predictive of subsequent memory for words that were rote-rehearsed during learning. Furthermore, during rote rehearsal, the extent of neural activation in regions associated with semantic retrieval was assessed to determine the role that incidental semantic elaboration may play in subsequent memory for rote-rehearsed items. Results revealed that (a) the magnitude of activation in neural regions previously associated with phonological rehearsal (left prefrontal, bilateral parietal, supplementary motor, and cerebellar regions) was correlated with subsequent memory, and (b) while rote rehearsal did not--on average--elicit activation in an anterior left prefrontal region associated with semantic retrieval, activation in this region was greater for trials that were subsequently better remembered. Contrary to the prevalent view that rote rehearsal does not impact learning, these data suggest that phonological maintenance mechanisms, in addition to semantic elaboration, support the encoding of an experience such that it can be later remembered.     

Dual task demands on encoding and retrieval processes: evidence from healthy adult ageing

Previous studies of dual-task performance have demonstrated that encoding and retrieval processes are differentially affected by the simultaneous performance of a secondary task. Whilst dual task demands during encoding have a detrimental effect on memory performance, dual task demands during retrieval have a detrimental effect on secondary task performance. However, dual task effects on memory during encoding appear unaffected by age, while effects at retrieval on secondary task performance are age sensitive. Most previous studies have focused on free recall or cued recall of word lists. In the current study, encoding and retrieval were examined in younger and older healthy adults performing a task typically thought to load verbal working memory, namely immediate serial ordered digit recall together with a response time (RT) task. In Experiment 1, the demands of a secondary RT task were varied as a function of response-to-stimulus interval, while in Experiment 2 the predictability of the stimulus location was manipulated. In both age groups, dual task during encoding, but not at retrieval, produced significant interference in memory performance and unlike most previous studies the impact at encoding was greater for the older group. In contrast, significantly slower RTs were demonstrated under dual task conditions during encoding and retrieval. Older adults produced significantly slower RTs than younger adults only for dual task at retrieval. Older people were more sensitive to time pressure in responding under dual task conditions, but neither group was sensitive to predictability of stimulus location. Results are consistent with the concept of a cognitive resource that supports dual task performance, and that is sensitive to the effects of age on memory encoding of items that rely heavily on the operation of verbal working memory resources. The age sensitivity to dual task only became apparent when effects at encoding and at retrieval were considered separately.     

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.     

Anterior hippocampus orchestrates successful encoding and retrieval of non-relational memory: an event-related fMRI study

Episodic memory encoding and retrieval processes have been linked to different neural networks. However, the common brain regions associated with non-relational memory processing during successful encoding (subsequent memory effect) and successful retrieval (recognition effect) have not yet been investigated. Further, the majority of functional imaging studies have been conducted in young subjects, whereas patients from lesion studies, where most neuropsychological models are still based upon, are usually older. Inferences from younger subjects cannot necessarily be applied to the elderly, an issue becoming particularly relevant with our ageing society. Using an event-related fMRI approach we studied 29 healthy elderly subjects (mean age 67.8, SD 5.4 years) with a non-associative task of intentional word list encoding and retrieval. For each subject, behavioural responses were individually classified into four event types (hits test, misses test, false alarms, correct rejections). Brain areas activated during successful memory encoding comprised the anterior left hippocampus extending into the surrounding parahippocampal gyrus. Regions associated with successful memory retrieval involved a wide-spread network of anterior left parahippocampal gyrus, bilateral temporal cortices and bilateral ventral and dorsal prefrontal areas. Regions contributing to both successful encoding and retrieval, evidenced by a conjunction analysis, revealed prominent left lateralized activations of the anterior hippocampus and the inferior parietal lobe. Our results indicate that the anterior left hippocampus plays an important role during successful memory encoding and during successful memory retrieval in a task of simple, non-associative wordlist learning in healthy elderly subjects.     

Perceptual difficulty in source memory encoding and retrieval: prefrontal versus parietal electrical brain activity

It is well established that source memory retrieval--remembering relationships between a core item and some additional attribute of an event--engages prefrontal cortex (PFC) more than simple item memory. In event-related potentials (ERPs), this is manifest in a late-onset difference over PFC between studied items which mandate retrieval of a second attribute, and unstudied items which can be immediately rejected. Although some sorts of attribute conjunctions are easier to remember than others, the role of source retrieval difficulty on prefrontal activity has received little attention. We examined memory for conjunctions of object shape and color when color was an integral part of the depicted object, and when monochrome objects were surrounded by colored frames. Source accuracy was reliably worse when shape and color were spatially separated, but prefrontal activity did not vary across the object-color and frame-color conditions. The insensitivity of prefrontal ERPs to this perceptual manipulation of difficulty stands in contrast to their sensitivity to encoding task: deliberate voluntary effort to integrate objects and colors during encoding reduced prefrontal activity during retrieval, but perceptual organization of stimuli did not. The amplitudes of ERPs over parietal cortex were larger for frame-color than object-color stimuli during both study and test phases of the memory task. Individual variability in parietal ERPs was strongly correlated with memory accuracy, which we suggest reflects a contribution of visual working memory to long-term memory. We discuss multiple bottlenecks for source memory performance.     

The effect of divided attention on encoding and retrieval in episodic memory revealed by positron emission tomography

The effects of divided attention (DA) on episodic memory encoding and retrieval were investigated in 12 normal young subjects by positron emission tomography (PET). Cerebral blood flow was measured while subjects were concurrently performing a memory task (encoding and retrieval of visually presented word pairs) and an auditory tone-discrimination task. The PET data were analyzed using multivariate Partial Least Squares (PLS), and the results revealed three sets of neural correlates related to specific task contrasts. Brain activity, relatively greater under conditions of full attention (FA) than DA, was identified in the occipital-temporal, medial, and ventral-frontal areas, whereas areas showing relatively more activity under DA than FA were found in the cerebellum, temporo-parietal, left anterior-cingulate gyrus, and bilateral dorsolateral-prefrontal areas. Regions more active during encoding than during retrieval were located in the hippocampus, temporal and the prefrontal cortex of the left hemisphere, and regions more active during retrieval than during encoding included areas in the medial and right-prefrontal cortex, basal ganglia, thalamus, and cuneus. DA at encoding was associated with specific decreases in rCBF in the left-prefrontal areas, whereas DA at retrieval was associated with decreased rCBF in a relatively small region in the right-prefrontal cortex. These different patterns of activity are related to the behavioral results, which showed a substantial decrease in memory performance when the DA task was performed at encoding, but no change in memory levels when the DA task was performed at retrieval.     

Study-test congruency affects encoding-related brain activity for some but not all stimulus materials

Memory improves when encoding and retrieval processes overlap. Here, we investigated how the neural bases of long-term memory encoding vary as a function of the degree to which functional processes engaged at study are engaged again at test. In an incidental learning paradigm, electrical brain activity was recorded from the scalps of healthy adults while they made size judgments on intermixed series of pictures and words. After a 1-hr delay, memory for the items was tested with a recognition task incorporating remember/know judgments. In different groups of participants, studied items were either probed in the same mode of presentation (word-word; picture-picture) or in the alternative mode of presentation (word-picture; picture-word). Activity over anterior scalp sites predicted later memory of words, irrespective of type of test probe. Encoding-related activity for pictures, by contrast, differed qualitatively depending on how an item was cued at test. When a picture was probed with a picture, activity over anterior scalp sites predicted encoding success. When a picture was probed with a word, encoding-related activity was instead maximal over posterior sites. Activity differed according to study-test congruency from around 100 msec after picture onset. These findings indicate that electrophysiological correlates of encoding are sensitive to the similarity between processes engaged at study and test. The time course supports a direct and not merely consequential role of encoding-retrieval overlap in encoding. However, because congruency only affected one type of stimulus material, encoding-retrieval overlap may not be a universal organizing principle of neural correlates of memory.     

fMRI evidence of word frequency and strength effects in recognition memory

We used event-related fMRI to investigate the neural correlates of encoding strength and word frequency effects in recognition memory. At test, participants made Old/New decisions to intermixed low (LF) and high frequency (HF) words that had been presented once or twice at study and to new, unstudied words. The Old/New effect for all hits vs. correctly rejected unstudied words was associated with differential activity in multiple cortical regions, including the anterior medial temporal lobe (MTL), hippocampus, left lateral parietal cortex and anterior left inferior prefrontal cortex (LIPC). Items repeated at study had superior hit rates (HR) compared to items presented once and were associated with reduced activity in the right anterior MTL. By contrast, other regions that had shown conventional Old/New effects did not demonstrate modulation according to memory strength. A mirror effect for word frequency was demonstrated, with the LF word HR advantage associated with increased activity in the left lateral temporal cortex. However, none of the regions that had demonstrated Old/New item retrieval effects showed modulation according to word frequency. These findings are interpreted as supporting single-process memory models proposing a unitary strength-like memory signal and models attributing the LF word HR advantage to the greater lexico-semantic context-noise associated with HF words due to their being experienced in many pre-experimental contexts.     

Assembling and encoding word representations: fMRI subsequent memory effects implicate a role for phonological control

Novel word learning is central to the flexibility inherent in the human language capacity. Word learning may partially depend on long-term memory formation during the assembly of phonological representations from orthographic inputs. In the present study, event-related functional magnetic resonance imaging (fMRI) examined the contributions of phonological control-a component of the verbal working memory system-to phonological assembly and word learning. Subjects were scanned while making syllable decisions about visually presented familiar (English) and novel (pseudo-English and Foreign) words, a task that required retrieval and analysis of existing phonological codes or the assembly and analysis of novel representations. Results revealed that left inferior prefrontal cortex (LIPC) and bilateral parietal cortices were differentially engaged during the processing of novel words, suggesting that this circuit is recruited during phonological assembly. A subsequent memory analysis that examined the relation between fMRI signal and the subject's ability to later remember the words (a measure of effective memory formation) revealed that the magnitude of activation in LIPC, bilateral superior parietal, and left inferior parietal cortices was positively correlated with later memory. Moreover, although the magnitude of the subsequent memory effect in parietal cortex was not significantly affected by word type, this effect was greater in posterior LIPC for novel (pseudo-English) than for familiar (English) words. In the course of subserving the assembly of novel word representations, the phonological (articulatory) control component of the phonological system appears to play a central role in the encoding of novel words into long-term memory.     

Effects of acute psychosocial stress on working memory related brain activity in men

Acute psychosocial stress in humans triggers the release of glucocorticoids (GCs) and influences performance in declarative and working memory (WM) tasks. These memory systems rely on the hippocampus and prefrontal cortex (PFC), where GC‐binding receptors are present. Previous studies revealed contradictory results regarding effects of acute stress on WM‐related brain activity. We combined functional magnetic resonance imaging with a standardized psychosocial stress protocol to investigate the effects of acute mental stress on brain activity during encoding, maintenance, and retrieval of WM. Participants (41 healthy young men) underwent either a stress or a control procedure before performing a WM task. Stress increased salivary cortisol levels and tended to increase WM accuracy. Neurally, stress‐induced increases in cortical activity were evident in PFC and posterior parietal cortex (PPC) during WM maintenance. Furthermore, hippocampal activity was modulated by stress during encoding and retrieval with increases in the right anterior hippocampus during WM encoding and decreases in the left posterior hippocampus during retrieval. Our study demonstrates that stress increases activity in PFC and PPC specifically during maintenance of items in WM, whereas effects on hippocampal activity are restricted to encoding and retrieval. The finding that psychosocial stress can increase and decrease activity in two different hippocampal areas may be relevant for understanding the often‐reported phase‐dependent opposing behavioral effects of stress on long‐term memory. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Dissecting contributions of prefrontal cortex and fusiform face area to face working memory

Interactions between prefrontal cortex (PFC) and stimulus-specific visual cortical association areas are hypothesized to mediate visual working memory in behaving monkeys. To clarify the roles for homologous regions in humans, event-related fMRI was used to assess neural activity in PFC and fusiform face area (FFA) of subjects performing a delay-recognition task for faces. In both PFC and FFA, activity increased parametrically with memory load during encoding and maintenance of face stimuli, despite quantitative differences in the magnitude of activation. Moreover, timing differences in PFC and FFA activation during memory encoding and retrieval implied a context dependence in the flow of neural information. These results support existing neurophysiological models of visual working memory developed in the nonhuman primate.     

Auditory event-related potentials during a spatial working memory task.

OBJECTIVE: Sensory cortical activity can be jointly governed by bottom-up (e.g. stimulus features) and top-down (e.g. memory, attention) factors. We tested the hypothesis that auditory sensory cortical activity is affected by encoding and retrieval of spatial information. METHODS: Auditory event-related potentials (ERPs) were recorded during working memory and passive listening conditions. Trials contained three noise bursts (two "items" at different locations, followed by a "probe"). In the working memory task subjects determined if the probe matched an item location. The influence of long-term memory was evaluated by training to one location that was always a non-match. Auditory ERPs were analyzed to items and probes (N100, P200, late positive wave-LPW). RESULTS: Reaction times varied significantly among probes (trained non-match相似文献   

Regional brain activity during shape recognition impaired by a scopolamine challenge to encoding

In the present positron emission tomography (PET) study, we examine the effect of a scopolamine-induced challenge to encoding upon the pattern of regional cerebral blood flow during recognition of a list of abstract visual shapes 3 days after encoding of these shapes. This study was conducted to test hypotheses concerning the fusiform and thalamic contributions to object recognition arising from a previous imaging study of impaired recognition. In that study, we demonstrated that activity in the fusiform cortex and the thalamus during shape recognition was modulated by memory challenges. These memory challenges included, on one hand, impaired storage as a consequence of diazepam administration during encoding, and, on the other hand, impaired retrieval caused by a perceptual challenge. Activation in the fusiform cortex decreased during impaired recognition, irrespective of the type of challenge. In contrast, thalamic activation increased only when the recognition deficit resulted from impaired memory storage. Based on these results, we hypothesized that fusiform activation during recognition reflects the matching of an incoming stimulus with a stored one, whereas thalamic activation reflects retrieval attempts. These hypotheses would receive considerable support if scopolamine, which also impairs memory storage, induced similar modulations of fusiform and thalamic activation. In the present study, we observed that a scopolamine challenge to encoding does indeed modulate the activity in the very same regions that were previously modulated by a diazepam challenge. Hence, a similar memory deficit, although primarily effected through different neurochemical pathways, was paralleled by a similar modulation of activity in the same set of nodes in the shape recognition network. In the fusiform cortex, scopolamine decreased recognition-related activity, as did the sensory challenge of retrieval. Furthermore, covariate analysis demonstrated that the level of fusiform activity linearly correlates with behavioural performance. In the thalamus, activation increased following impaired encoding. This is in accordance with the idea that enhanced thalamic activity reflects increased effort expended in retrieval. In addition, in the intraparietal sulcus, differential activation also increased following impaired memory storage, possibly reflecting enhanced visuospatial attention in an effort to compensate for impaired performance.     

Nonconscious formation and reactivation of semantic associations by way of the medial temporal lobe

A successful strategy to memorize unrelated items is to associate them semantically. This learning method is typical for declarative memory and depends on the medial temporal lobe (MTL). Yet, only a small fraction of perceived items emerge into conscious awareness and receive the status of representations in declarative memory. This functional magnetic resonance imaging (fMRI) study tackled the mnemonic fate of unrelated item pairs processed without conscious awareness. Stimuli consisted of a face and a written profession (experimental condition) or of a face (control condition) exposed very briefly between pattern masks. Although the participants were unaware of the stimuli, activity in the hippocampus and perirhinal cortex was changed in the experimental versus the control condition; perirhinal activity changes correlated with the reaction time measure of the later nonconscious retrieval. For retrieval, the previously presented faces were shown again, this time for conscious inspection. The task was to guess the professional category of each face. This task was to induce a nonconscious retrieval of previously formed face-profession associations. Remarkably, activity in the hippocampus and perirhinal cortex was enhanced when subjects were confronted with faces from the experimental versus the control condition. The degree of hippocampal and perirhinal activation changes correlated with the reaction time measure of nonconscious retrieval. Together, our findings suggest that new semantic associations can be formed and retrieved by way of the medial temporal lobe without awareness of the associations or its components at encoding or any awareness that one is remembering at retrieval.