Fragments of a larger whole: retrieval cues constrain observed neural correlates of memory encoding

Laying down a new memory involves activity in a number of brain regions. Here, it is shown that the particular regions associated with successful encoding depend on the way in which memory is probed. Event-related functional magnetic resonance imaging signals were acquired while subjects performed an incidental encoding task on a series of visually presented words denoting objects. A recognition memory test using the Remember/Know procedure to separate responses based on recollection and familiarity followed 1 day later. Critically, half of the studied objects were cued with a corresponding spoken word, and half with a corresponding picture. Regardless of cue, activity in prefrontal and hippocampal regions predicted subsequent recollection of a word. Type of retrieval cue modulated activity in prefrontal, temporal, and parietal cortices. Words subsequently recognized on the basis of a sense of familiarity were at study also associated with differential activity in a number of brain regions, some of which were probe dependent. Thus, observed neural correlates of successful encoding are constrained by type of retrieval cue, and are only fragments of all encoding-related neural activity. Regions exhibiting cue-specific effects may be sites that support memory through the degree of overlap between the processes engaged during encoding and those engaged during retrieval.     

Cognitive and neural effects of semantic encoding strategy training in older adults

Prior research suggests that older adults are less likely than young adults to use effective learning strategies during intentional encoding. This functional magnetic resonance imaging (fMRI) study investigated whether training older adults to use semantic encoding strategies can increase their self-initiated use of these strategies and improve their recognition memory. The effects of training on older adults' brain activity during intentional encoding were also examined. Training increased older adults' self-initiated semantic encoding strategy use and eliminated pretraining age differences in recognition memory following intentional encoding. Training also increased older adults' brain activity in the medial superior frontal gyrus, right precentral gyrus, and left caudate during intentional encoding. In addition, older adults' training-related changes in recognition memory were strongly correlated with training-related changes in brain activity in prefrontal and left lateral temporal regions associated with semantic processing and self-initiated verbal encoding strategy use in young adults. These neuroimaging results demonstrate that semantic encoding strategy training can alter older adults' brain activity patterns during intentional encoding and suggest that young and older adults may use the same network of brain regions to support self-initiated use of verbal encoding strategies.     

Brain activity underlying encoding and retrieval of source memory

Neural activity elicited during the encoding and retrieval of source information was investigated with event-related functional magnetic resonance imaging (efMRI). During encoding, 17 subjects performed a natural/artificial judgement on pictures of common objects which were presented randomly in one of the four quadrants of the display. At retrieval, old pictures were mixed with new ones and subjects judged whether each picture was new or old and, if old, indicated in which quadrant it was presented at encoding. During encoding, study items that were later recognized and assigned a correct source judgement elicited greater activity than recognized items given incorrect judgements in a variety of regions, including right lateral occipital and left prefrontal cortex. At retrieval, regions showing greater activity for recognized items given correct versus incorrect source judgements included the right hippocampal formation and the left prefrontal cortex. These findings indicate a role for these regions in the encoding and retrieval of episodic information beyond that required for simple item recognition.     

The relationship between study processing and the effects of cue congruency at retrieval: fMRI support for transfer appropriate processing

Using functional magnetic resonance imaging, the present study investigated whether the enhanced memory performance associated with congruent relative to incongruent retrieval cues is modulated by how items are encoded. Subjects studied a list of visually presented words and pictures and attempted to recognize these items in a later memory test. Half of the studied items were tested with a congruent cue (word-word and picture-picture), whereas the remainders were tested with an incongruent cue (word-picture and picture-word). For both words and pictures, regions where study activity was greater for congruently than incongruently cued items overlapped regions where activity differentiated the 2 classes of study material. Thus, word congruency effects overlapped regions where activity elicited by study words exceeded the activity elicited by pictures. Similarly, picture congruency effects overlapped regions demonstrating enhanced activity for pictures relative to words. In addition, several regions, including dorsolateral prefrontal cortex and intraparietal sulcus, demonstrated material-nonspecific congruency effects. The findings suggest that items benefit from a congruent retrieval cue when their study processing resembles the processing later engaged by the retrieval cue. Consistent with the principle of transfer appropriate processing, the benefit of a congruent retrieval cue derives from the interaction between study and retrieval processing.     

Spatiotemporal neural dynamics of word understanding in 12- to 18-month-old-infants

Learning words is central in human development. However, lacking clear evidence for how or where language is processed in the developing brain, it is unknown whether these processes are similar in infants and adults. Here, we use magnetoencephalography in combination with high-resolution structural magnetic resonance imaging to noninvasively estimate the spatiotemporal distribution of word-selective brain activity in 12- to 18-month-old infants. Infants watched pictures of common objects and listened to words that they understood. A subset of these infants also listened to familiar words compared with sensory control sounds. In both experiments, words evoked a characteristic event-related brain response peaking ～400 ms after word onset, which localized to left frontotemporal cortices. In adults, this activity, termed the N400m, is associated with lexico-semantic encoding. Like adults, we find that the amplitude of the infant N400m is also modulated by semantic priming, being reduced to words preceded by a semantically related picture. These findings suggest that similar left frontotemporal areas are used for encoding lexico-semantic information throughout the life span, from the earliest stages of word learning. Furthermore, this ontogenetic consistency implies that the neurophysiological processes underlying the N400m may be important both for understanding already known words and for learning new words.     

Mood states modulate activity in semantic brain areas during emotional word encoding

It is controversially discussed whether or not mood-congruent recall (i.e., superior recall for mood-congruent material) reflects memory encoding processes or reduces to processes during retrieval. We therefore investigated the neurophysiological correlates of mood-dependent memory during emotional word encoding. Event-related potentials (ERPs) were recorded while participants in good or bad mood states encoded words of positive and negative valence. Words were either complete or had to be generated from fragments. Participants had to memorize words for subsequent recall. Mood-congruent recall tended to be largest in good mood for generated words. Starting at 200 ms, mood-congruent ERP effects of word valence were obtained in good, but not in bad mood. Only for good mood, source analysis revealed valence-related activity in ventral temporal cortex and for generated words also in prefrontal cortex. These areas are known to be involved in semantic processing. Our findings are consistent with the view that mood-congruent recall depends on the activation of mood-congruent semantic knowledge during encoding. Incoming stimuli are more readily transformed according to stored knowledge structures in good mood particularly during generative encoding tasks. The present results therefore show that mood-congruent memory originates already during encoding and cannot be reduced to strategic processes during retrieval.     

The laminar pattern of connections between prefrontal and anterior temporal cortices in the Rhesus monkey is related to cortical structure and function

The laminar pattern of axonal termination from prefrontal (caudal orbitofrontal, rostral orbitofrontal and lateral areas) to anterior temporal areas (entorhinal cortex, perirhinal cortex and area TE) and from temporal to prefrontal areas was investigated with the aid of anterograde tracers. Both regions are characterized by structural heterogeneity, and include agranular, dysgranular and granular cortical types, denoting, respectively, the absence, incipience and presence of granular layer 4. In addition, both the prefrontal and anterior temporal cortices are composed of areas that have related though specialized functions. The pattern of cortical axonal termination was associated with both the structural type of the cortex of origin and the structure of the destination cortex. Thus, efferent fibers from a single origin in either prefrontal or anterior temporal cortex terminated in different patterns depending on their target area. Conversely, axons terminated in different patterns in a single target area, prefrontal or anterior temporal, depending on their area of origin. Projections from agranular or dysgranular type cortices (e.g. medial temporal areas and caudal orbitofrontal areas) terminated mostly in the upper layers of granular cortices (e.g. area TE and lateral prefrontal areas), and projections from granular cortices terminated mostly in the deep layers of agranular or dys- granular cortices. A robust projection from dysgranular orbitofrontal areas terminated in the deep layers of the agranular entorhinal cortex. Projections from prefrontal areas to area TE terminated in the upper layers, and may facilitate focused attention on behaviorally relevant stimuli processed through reciprocal pathways between prefrontal and temporal cortices.     

Relationship of prefrontal connections to inhibitory systems in superior temporal areas in the rhesus monkey

The prefrontal cortex selects relevant signals and suppresses irrelevant signals in behavior, as exemplified by its functional interaction with superior temporal cortices. We addressed the structural basis of this process by investigating quantitatively the relationship of prefrontal pathways to inhibitory interneurons in superior temporal cortices. Pathways were labeled with neural tracers, and two neurochemical classes of inhibitory interneurons were labeled with parvalbumin (PV) and calbindin (CB), which differ in mode of inhibitory control. Both markers varied significantly and systematically across superior temporal areas. Calbindin neurons were more prevalent than PV neurons, with the highest densities found in posterior high-order auditory association cortices. Axons from anterior lateral, medial prefrontal and orbitofrontal areas terminated in the anterior half of the superior temporal gyrus, targeting mostly the superficial layers (I to upper III), where CB neurons predominated. Reciprocal projection neurons were intermingled with PV neurons, and emanated mostly from the deep part of layer III and to a lesser extent from layers V-VI, in proportions matching the laminar density of inhibitory interneurons. In marked contrast, prefrontal connections in temporal polar cortex were found mostly in the deep layers, showing mismatch with the predominant upper laminar distribution of interneurons. Differences in the relationship of connections to inhibitory neurons probably affect the dynamics in distinct superior temporal cortices. These findings may help explain the reduced efficacy of inhibitory control in superior temporal areas after prefrontal cortical damage.     

Activation shift from medial to lateral temporal cortex associated with recency judgements following impoverished encoding

Recency judgements can be performed on the basis of across-event relational information that directly provides temporal order among past events. Non-relational item-based information internal to individual past events, such as information retrieved through familiarity, may also contribute to recency judgements. The present functional magnetic resonance imaging study examined neural substrates for item-based processing during recency judgements as an alternative to relational recency judgements. One half of word stimuli were encoded relationally prior to recency judgements, and the relational encoding of the other half was hampered such that the words were processed relatively in an item-based manner. Brain activity in the medial temporal lobe was observed during recency judgements for words studied with relational memory processing, whereas brain activity in the lateral temporal cortex was observed during recency judgements for words studied relatively in an item-based manner. It was revealed further that recognition of individual words per se, which can also be regarded as familiarity/recency judgements but is non-relational in nature, also activated the lateral temporal region. These results indicate multiple routes for recency judgements within the temporal lobe that are recruited depending on how past episodes are represented and retrieved for judgements of their temporal order.     

Neurodevelopmental correlates of true and false recognition

The Deese/Roediger-McDermott (DRM) false-memory effect has been extensively documented in psychological research. People falsely recognize critical lures or nonstudied items that are semantically associated with studied items. Behavioral research has provided evidence for age-related increases in the DRM false-recognition effect. The present event-related functional magnetic resonance imaging study was aimed at investigating neurodevelopmental changes in brain regions associated with true- and false-memory recognition in 8-year olds, 12-year olds, and adults. Relative to 8-year olds, adults correctly endorsed more studied items as "old" but also mistakenly endorsed more critical lures. Age-related increases in recollection were associated with changes in the medial temporal lobe (MTL) activation profile. Additionally, age-related increases in false alarms (FAs) to semantically related lures were associated with changes in the activation profile of left ventrolateral prefrontal cortex, a region associated with semantic processing. Additional regions exhibiting age-related changes include posterior parietal and anterior prefrontal cortices. In summary, concomitant changes in the MTL, prefrontal cortex, and parietal cortex underlie developmental increases in true and false recognition during childhood and adolescence.     

The relationship between aging, performance, and the neural correlates of successful memory encoding

The present functional magnetic resonance imaging (fMRI) study investigated whether age-related differences in the neural correlates of successful memory encoding are modulated by memory performance. Young (mean age 22 years; N = 16) and older (mean age 69 years; N = 32) subjects were scanned while making animacy decisions on visually presented words. Memory for the words was later assessed in a recognition test, allowing fMRI activity elicited by study words to be contrasted according to subsequent memory performance. Young and older adults exhibited equivalent subsequent memory effects (enhanced activity for later remembered items) in an extensive network that included left inferior prefrontal cortex and anterior hippocampus. In posterior cingulate cortex, reversed subsequent memory effects (greater activity for later forgotten items) were of greater magnitude in young subjects. A voxel-of-interest analysis conducted on left and right prefrontal subsequent memory effects revealed that the effects were distributed more bilaterally in older than in young subjects, replicating previous findings. This age-related difference was confined to older subjects with relatively poor recognition performance, who were also the only group to demonstrate statistically significant right prefrontal subsequent memory effects. The findings suggest that relative preservation of memory performance with increasing age does not depend upon right prefrontal "over-recruitment."     

Temporal and cerebellar brain regions that support both declarative memory formation and retrieval

Using event-related fMRI, we scanned young healthy subjects while they memorized real-world photographs and subsequently tried to recognize them within a series of new photographs. We confirmed that activity in the medial temporal lobe (MTL) and inferior prefrontal cortex correlates with declarative memory formation as defined by the subsequent memory effect, stronger responses to subsequently remembered than forgotten items. Additionally, we confirmed that activity in specific regions within the parietal lobe, anterior prefrontal cortex, anterior cingulate and cerebellum correlate with recognition memory as measured by the conventional old/new effect, stronger responses for recognized old items (hits) than correctly identified new items (correct rejections). To obtain a purer measure of recognition success, we introduced two recognition effects by comparing brain responses to hits and old items misclassified as new (misses). The positive recognition effect (hits > misses) revealed prefrontal, parietal and cerebellar contributions to recognition, and in line with electrophysiological findings, the negative recognition effect (hits < misses) revealed an anterior medial temporal contribution. Finally, by inclusive masking, we identified temporal and cerebellar brain areas that support both declarative memory formation and retrieval. For matching operations during recognition, these areas may re-use representations formed and stored locally during encoding.     

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.     

Right prefrontal activation during encoding, but not during retrieval, in a non-verbal paired-associates task

Brain imaging studies have shown that episodic encoding into long-term memory preferentially activates the left prefrontal cortex and retrieval activates the right prefrontal cortex. However, it is unclear to what degree verbal analysis contributes to the left prefrontal activation during encoding. The present study was designed to avoid verbal analysis during encoding by using abstract pictures and computer- generated sounds which were difficult to code verbally. Sounds and pictures were grouped into six stimulus-stimulus pairs. When the sound from a pair was presented, the subjects were instructed to recall and visualize the associated picture. After 2.0 s the associated picture and another picture appeared on the screen and the subjects were required to identify the associated picture. Feedback about the choice was then given. Regional cerebral blood flow (rCBF) was measured with [15O]butanol and positron emission tomography (PET) in 10 subjects during initial training on the paired-associates task (encoding scan) and after 35 min of training (retrieval scan). Performance during the encoding scan was 59% correct and during the retrieval scan 98% correct, with a mean reaction time of 709 ms during retrieval. The rCBF was also measured during a control condition without any instruction to encode or retrieve. Compared with retrieval, encoding showed significant activation of the posterior part of the right middle frontal gyrus, the right inferior parietal cortex, the cingulate cortex, the left inferior parietal cortex and the left inferior and middle temporal gyri. The rCBF increase during encoding was strongly correlated with the rate of encoding. Retrieval was compared with both encoding and control. In none of these comparisons was there any prefrontal activation. The lack of prefrontal activation during near- perfect performance of the retrieval task suggests that the prefrontal cortex is not necessarily active when retrieval is fast and accurate, or what might be called automatic. Encoding was not associated with more activation of the left than the right prefrontal cortex. This result presents a limitation to the generality of left prefrontal activation during episodic encoding, which has been found in several previous brain imaging studies. Differences between studies in the relative activation of left and right prefrontal cortex during encoding and retrieval might be due to differences in paradigms, the type of stimulus used, and the demand for working memory and verbal analysis.      

Task-dependency of the neural correlates of episodic encoding as measured by fMRI.

Using event-related functional magnetic resonance imaging (fMRI), the neural correlates of memory encoding can be studied by contrasting item-related activity elicited in a study task according to whether the items are remembered or forgotten in a subsequent memory test. Previous studies using this approach have implicated the left prefrontal cortex in the successful encoding of verbal material into episodic memory when the study task is semantic in nature. In the current study, we asked whether the neural correlates of episodic encoding differ depending on type of study task. Seventeen volunteers participated in an event-related fMRI experiment in which at study, volunteers were cued to make either animacy or syllable judgements about words. A recognition memory test followed after a delay of approximately 15 min. For the animacy task, words that were subsequently remembered showed greater activation in left and medial prefrontal regions. For the syllable task, by contrast, successful memory for words was associated with activations in bilateral intraparietal sulcus, bilateral fusiform gyrus, right prefrontal cortex and left superior occipital gyrus. These findings suggest that the brain networks supporting episodic encoding differ according to study task.     

Relationships between β-amyloid and functional connectivity in different components of the default mode network in aging

Although beta-amyloid (Aβ) deposition is a characteristic feature of Alzheimer's disease (AD), this pathology is commonly found in elderly normal controls (NC). The pattern of Aβ deposition as detected with Pittsburgh compound-B positron emission tomography (PIB-PET) imaging shows substantial spatial overlap with the default mode network (DMN), a group of brain regions that typically deactivates during externally driven cognitive tasks. In this study, we show that DMN functional connectivity (FC) during rest is altered with increasing levels of PIB uptake in NC. Specifically, FC decreases were identified in regions implicated in episodic memory (EM) processing (posteromedial cortex, ventral medial prefrontal cortex, and angular gyrus), whereas connectivity increases were detected in dorsal and anterior medial prefrontal and lateral temporal cortices. This pattern of decreases is consistent with previous studies that suggest heightened vulnerability of EM-related brain regions in AD, whereas the observed increases in FC may reflect a compensatory response.     

Convergence of neural systems processing stimulus associations and coordinating motor responses

A sensory-sensory learning paradigm was used to measure neural changes in humans during acquisition of an association between an auditory and visual stimulus. Three multivariate partial least-squares (PLS) analyses of positron emission tomography data identified distributed neural systems related to (i) processing the significance of the auditory stimulus, (ii) mediating the acquisition of the behavioral response, and (iii) the spatial overlap between these two systems. The system that processed the significance of the tone engaged primarily right hemisphere regions and included dorsolateral prefrontal cortex, putamen, and inferior parietal and temporal cortices. Activity changes in left occipital cortex were also identified, most likely reflecting the learned expectancy of the upcoming visual event. The system related to behavior was similar to that which coded the significance of the tone, including dorsal occipital cortex. The PLS analysis of the concordance between these two systems showed substantial regional overlap, and included occipital, dorsolateral prefrontal, and limbic cortices. However, activity in dorsomedial prefrontal cortex was strictly related to processing the auditory stimulus and not to behavior. Taken together, the PLS analyses identified a system that contained a sensory-motor component (comprised of occipital, temporal association and sensorimotor cortices) and a medial prefrontallimbic component, that as a group simultaneously embodied the learning-related response to the stimuli and the subsequent change in behavior.      

The effects of aging on material-independent and material-dependent neural correlates of source memory retrieval

Age-related declines in source memory have been observed for various stimuli and associated details. These impairments may be related to alterations in brain regions contributing to source memory via material-independent processes and/or regions specialized for processing specific materials. Using event-related functional magnetic resonance imaging, we investigate the effects of aging on source memory and associated neural activity for words and objects. Source accuracy was equally impaired in older adults for both materials. Imaging data revealed both groups recruited similar networks of regions to support source memory accuracy irrespective of material, including parietal and prefrontal cortices (PFC) and the hippocampus. Age-related decreases in material-independent activity linked to postretrieval monitoring were observed in right lateral PFC. Additionally, age-related increases in source accuracy effects were shown in perirhinal cortex, which were positively correlated with performance in older adults, potentially reflecting functional compensation. In addition to group differences in material-independent regions, age-related crossover interactions for material-dependent source memory effects were observed in regions selectively engaged by objects. These results suggest that older adults' source memory impairments reflect alterations in regions making material-independent contributions to source memory retrieval, primarily the lateral PFC, but may be further impacted by changes in regions sensitive to particular materials.     

A neuroanatomical construct for the amnesic effects of propofol

BACKGROUND: This study was designed to identify neuroanatomical locations of propofol's effects on episodic memory by producing minimal and maximal memory impairment during conscious sedation. Drug-related changes in regional cerebral blood flow (rCBF) were located in comparison with rCBF increases during a simple word memory task. METHODS: Regional cerebral blood flow changes were assessed in 11 healthy volunteers using H215O positron emission tomography (PET) and statistical parametric mapping (SPM99) at 600 and 1,000 ng/ml propofol target concentrations. Study groups were based on final recognition scores of auditory words memorized during PET scanning. rCBF changes during propofol administration were compared with those during the word memory task at baseline. RESULTS: Nonoverlapping memory effects were evident: low (n = 4; propofol concentration 523 +/- 138 ng/ml; 44 +/- 13% decrement from baseline memory) and high (n = 7; 829 +/- 246 ng/ml; 87 +/- 6% decrement from baseline) groups differed in rCBF reductions primarily in right-sided prefrontal and parietal regions, close to areas activated in the baseline memory task, particularly R dorsolateral prefrontal cortex (Brodmann area 46; x, y, z = 51, 38, 22). The medial temporal lobe region exhibited relative rCBF increases. CONCLUSIONS: As amnesia becomes maximal, rCBF reductions induced by propofol occur in brain regions identified with working memory processes. In contrast, medial temporal lobe structures were resistant to the global CBF decrease associated with propofol sedation. The authors postulate that the episodic memory effect of propofol is produced by interference with distributed cortical processes necessary for normal memory function rather than specific effects on medial temporal lobe structures.     

Hippocampal and neocortical gamma oscillations predict memory formation in humans

Functional magnetic resonance imaging (fMRI) of the human brain has shown that the hippocampus and the left temporal and frontal cortices play a key role in the formation of new verbal memories. We recorded electrical activity from 2349 surgically implanted intracranial electrodes in epilepsy patients while they studied and later recalled lists of common words. Using these recordings, we demonstrate that gamma oscillations (44-64 Hz) in the hippocampus and the left temporal and frontal cortices predict successful encoding of new verbal memories. This increase in gamma oscillations was not seen in other frequency bands, whose activity generally decreased during successful memory formation. These findings identify a role for gamma oscillations in verbal memory formation with the hippocampus and the left temporal and frontal cortices, the same regions implicated using noninvasive fMRI recording methods.