Fake or fantasy: rapid dissociation between strategic content monitoring and reality filtering in human memory

Memory verification is crucial for meaningful behavior. Orbitofrontal damage may impair verification and induce confabulation and inappropriate acts. The strategic retrieval account explains this state by deficient monitoring of memories' precise content, whereas the reality filter hypothesis explains it by a failure of an orbitofrontal mechanism suppressing the interference of memories that do not pertain to reality. The distinctiveness of these mechanisms has recently been questioned. Here, we juxtaposed these 2 mechanisms using high-resolution evoked potentials in healthy subjects who performed 2 runs of a continuous recognition task which contained pictures that precisely matched or only resembled previous pictures. We found behavioral and electrophysiological dissociation: Strategic content monitoring was maximally challenged by stimuli resembling previous ones, whereas reality filtering was maximally challenged by identical stimuli. Evoked potentials dissociated at 200-300 ms: Strategic monitoring induced a strong frontal negativity and a distinct cortical map configuration, which were particularly weakly expressed in reality filtering. Recognition of real repetitions was expressed at 300-400 ms, associated with ventromedial prefrontal activation. Thus, verification of a memory's concordance with the past (its content) dissociates from the verification of its concordance with the present. The role of these memory control mechanisms in the generation of confabulations and disorientation is discussed.     

The effects of age on the neural correlates of episodic encoding

Young and old adults underwent positron emission tomographic scans while encoding pictures of objects and words using three encoding strategies: deep processing (a semantic living/nonliving judgement), shallow processing (size judgement) and intentional learning. Picture memory exceeded word memory in both young and old groups, and there was an age-related decrement only in word recognition. During the encoding tasks three brain activity patterns were found that differentiated stimulus type and the different encoding strategies. The stimulus-specific pattern was characterized by greater activity in extrastriate and medial temporal cortices during picture encoding, and greater activity in left prefrontal and temporal cortices during encoding of words. The older adults showed this pattern to a significantly lesser degree. A pattern distinguishing deep processing from intentional learning of words and pictures was identified, characterized mainly by differences in prefrontal cortex, and this pattern also was of significantly lesser magnitude in the old group. A final pattern identified areas with increased activity during deep processing and intentional learning of pictures, including left prefrontal and bilateral medial temporal regions. There was no group difference in this pattern. These results indicate age-related dysfunction in several encoding networks, with sparing of one specifically involved in more elaborate encoding of pictures. These age-related changes appear to affect verbal memory more than picture memory.     

Cortical responses to auditory stimuli during isoflurane burst suppression anaesthesia

The cortical responses to auditory stimuli were studied in 12 patients during isoflurane anaesthesia producing burst suppression (ETisof (SD) 1.4 (0.2) vol.%). Earphones were used to give 3-s trains of auditory click stimuli (60 clicks, 20 clicks per second, 80 dB, 0.1 ms) at irregular intervals. In 10 patients, the electroencephalography (EEG) showed a burst suppression pattern consisting of high-amplitude activity intermingled with suppressed background activity. In eight patients with burst suppression patterns, there was a strong cortical reactivity to the termination, not to the beginning, of auditory stimuli: 80 (20)% of all stimuli presented during EEG suppression evoked high amplitude cortical response, offset-burst. The latency of these auditory offset evoked bursts was 540 (60) ms. Auditory offset evoked bursts suggest that in spite of cortical suppression during deep anaesthesia the brain retains its ability to respond to changes in the acoustic environment.     

Midazolam: Effects on Amnesia and Anxiety in Children

Background: The minimum time interval between administration of oral midazolam and separation of children from their parents that ensures good anterograde amnesia has not been previously determined. This is of particular importance in a busy operating room setting where schedule delays secondary to midazolam administration may not be tolerated.

Methods: Children (n = 113) undergoing general anesthesia and surgery completed preoperative baseline memory testing using a validated series of picture cards and were randomly assigned to one of three midazolam groups or a control group. Exactly, 5, 10, or 20 min after receiving oral midazolam (0.5 mg/kg) or 15 min after receiving placebo, children were administered a second memory test that used pictures. Anxiety of children was assessed during induction of anesthesia with use of a validated anxiety measurement tool. Postoperatively, recall and recognition for picture cards seen during baseline testing and postintervention testing were assessed.

Results: Postoperatively, recall and recognition of pictures presented to patients after drug administration (anterograde amnesia) showed significant group differences (P = 0.0001), with recall impaired in the 10- (P = 0.004) and 20-min groups (P = 0.0001). Similarly, recognition memory was impaired in the 5- (P = 0.0008), 10- (P = 0.0001) and 20-min (P = 0.0001) groups. Significant anxiolytic effects of midazolam were observed as early as 15 +/- 4 min after midazolam administration (P = 0.02).     

Midazolam: effects on amnesia and anxiety in children

BACKGROUND: The minimum time interval between administration of oral midazolam and separation of children from their parents that ensures good anterograde amnesia has not been previously determined. This is of particular importance in a busy operating room setting where schedule delays secondary to midazolam administration may not be tolerated. METHODS: Children (n = 113) undergoing general anesthesia and surgery completed preoperative baseline memory testing using a validated series of picture cards and were randomly assigned to one of three midazolam groups or a control group. Exactly, 5, 10, or 20 min after receiving oral midazolam (0.5 mg/kg) or 15 min after receiving placebo, children were administered a second memory test that used pictures. Anxiety of children was assessed during induction of anesthesia with use of a validated anxiety measurement tool. Postoperatively, recall and recognition for picture cards seen during baseline testing and postintervention testing were assessed. RESULTS: Postoperatively, recall and recognition of pictures presented to patients after drug administration (anterograde amnesia) showed significant group differences (P = 0.0001), with recall impaired in the 10- (P = 0.004) and 20-min groups (P = 0.0001). Similarly, recognition memory was impaired in the 5- (P = 0.0008), 10- (P = 0.0001) and 20-min (P = 0.0001) groups. Significant anxiolytic effects of midazolam were observed as early as 15 +/- 4 min after midazolam administration (P = 0.02). CONCLUSIONS: Midazolam administered orally produces significant anterograde amnesia when given as early as 10 min before a surgical procedure.     

Role of amygdala connectivity in the persistence of emotional memories over time: an event-related FMRI investigation

According to the consolidation hypothesis, enhanced memory for emotional information reflects the modulatory effect of the amygdala on the medial temporal lobe (MTL) memory system during consolidation. Although there is evidence that amygdala-MTL connectivity enhances memory for emotional stimuli, it remains unclear whether this enhancement increases over time, as consolidation processes unfold. To investigate this, we used functional magnetic resonance imaging to measure encoding activity predicting memory for emotionally negative and neutral pictures after short (20-min) versus long (1-week) delays. Memory measures distinguished between vivid remembering (recollection) and feelings of knowing (familiarity). Consistent with the consolidation hypothesis, the persistence of recollection over time (long divided by short) was greater for emotional than neutral pictures. Activity in the amygdala predicted subsequent memory to a greater extent for emotional than neutral pictures. Although this advantage did not vary with delay, the contribution of amygdala-MTL connectivity to subsequent memory for emotional items increased over time. Moreover, both this increase in connectivity and amygdala activity itself were correlated with individual differences in recollection persistence for emotional but not neutral pictures. These results suggest that the amygdala and its connectivity with the MTL are critical to sustaining emotional memories over time, consistent with the consolidation hypothesis.     

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.     

Oscillatory EEG correlates of episodic trace decay

Recent studies suggest that human theta oscillations appear to be functionally associated with memory processes. It is less clear, however, to what type of memory sub-processes theta is related. Using a continuous word recognition task with different repetition lags, we investigate whether theta reflects the strength of an episodic memory trace or general processing demands, such as task difficulty. The results favor the episodic trace decay hypothesis and show that during the access of an episodic trace in a time window of approximately 200-400 ms, theta power decreases with increasing lag (between the first and second presentation of an item). LORETA source localization of this early theta lag effect indicates that parietal regions are involved in episodic trace processing, whereas right frontal regions may guide the process of retrieval. We conclude that episodic encoding can be characterized by two different stages: traces are first processed at parietal sites at approximately 300 ms, then further processing takes place in regions of the medial temporal lobe at approximately 500 ms. Only the first stage is related to theta, whereas the second is reflected by a slow wave with a frequency of approximately 2.5 Hz.     

Dynamics and plasticity of stimulus-selective persistent activity in cortical network models

Persistent neuronal activity is widespread in many areas of the cerebral cortex of monkeys performing cognitive tasks with a working memory component. Modeling studies have helped understanding of the conditions under which persistent activity can be sustained in cortical circuits. Here, we first review several basic models of persistent activity, including bistable models with excitation only and multistable models for working memory of a discrete set of pictures or objects with structured excitation and global inhibition. In many experiments, persistent activity has been shown to be subject to changes due to associative learning. In cortical network models, Hebbian learning shapes the synaptic structure and, in turn, the properties of persistent activity when pictures are associated together in the course of a task. It is shown how the theoretical models can reproduce basic experimental findings of neurophysiological recordings from inferior temporal and perirhinal cortices obtained using the following experimental protocols: (i) the pair-associate task; (ii) the pair-associate task with color switch; and (iii) the delay match to sample task with a fixed sequence of samples.     

Not all false memories are created equal: the neural basis of false recognition

False recognition, a type of memory distortion where one claims to remember something that never happened, can occur in response to items that are similar but not identical to previously seen items (i.e., related false recognition) or in response to novel items (i.e., unrelated false recognition). It is unknown whether these 2 types of memory errors arise from the same or distinct neural substrates. Using functional magnetic resonance imaging, we compared the neural activity associated with true recognition, related false recognition, and unrelated false recognition for abstract shapes. True recognition and related false recognition were associated with similar patterns of neural activity, including activity in the prefrontal cortex, the parietal cortex, and the medial temporal lobe. By contrast, unrelated false recognition was associated with activity in language-processing regions. These results indicate that false recognition is not a unitary phenomenon, but rather can reflect the operation of 2 distinct cognitive and neural processes.     

Recovery of components of memory in post-traumatic amnesia

Primary objective: Post-traumatic amnesia by definition indicates significant impairment of new learning ability, however very few studies have, examined the natural history and resolution of memory and new learning during PTA. Those studies which have, tended to examine orientation separately from the memory processes required to achieve orientation. Analysis of the order of recovery of the items of the Westmead PTA scale was used to examine recovery of memory and new learning capacity.

Methods: The results of daily assessment of 34 patients with traumatic brain injury (TBI) on the Westmead PTA scale were analysed for order of recovery.

Results: The pattern of rank order of item recovery indicated that Date of Birth recovered consistently first. There was variability in the remaining items, however items reflecting long-term memory tended to recover second and items reflecting simple new learning followed. Recall of all three pictures reflecting complex new learning recovered last.

Conclusion: The pattern of recovery of memory and new learning during PTA reflects a number of complex, inter-related variables including; the familiarity with the information, amount of rehearsal both before and since the accident and the number of cues available in the environment.     

Temporary occlusion of associative motor cortical plasticity by prior dynamic motor training

A novel Hebbian stimulation paradigm was employed to examine physiological correlates of motor memory formation in humans. Repetitive pairing of median nerve stimulation with transcranial magnetic stimulation over the contralateral motor cortex (paired associative stimulation, PAS) may decrease human motor cortical excitability at interstimulus intervals of 10 ms (PAS10) or increase excitability at 25 ms (PAS25). The properties of this plasticity have previously been shown to resemble associative timing-dependent long-term depression (LTD) and long-term potentiation (LTP) as established in vitro. Immediately after training a novel dynamic motor task, the capacity of the motor cortex to undergo plasticity in response to PAS25 was abolished. PAS10-induced plasticity remained unchanged. When retested after 6 h, PAS25-induced plasticity recovered to baseline levels. After training, normal PAS25-induced plasticity was observed in the contralateral training-naive motor cortex. Motor training did not reduce the efficacy of PAS25 to enhance cortical excitability when PAS10 was interspersed between the training and application of the PAS25 protocol. This indicated that the mechanism supporting PAS25-induced plasticity had remained intact immediately after training. Behavioral evidence was obtained for continued optimization of force generation at a time when PAS25-induced plasticity was blocked in the training motor cortex. Application of the PAS protocols after motor training did not prevent the consolidation of motor skills evident as performance gains at later retesting. The results are consistent with a concept of temporary suppression of associative cortical plasticity by neuronal mechanisms involved in motor training. Although it remains an open question exactly which element of motor training was responsible for this effect, our findings may link dynamic properties of LTP formation, as established in animal experiments, with human motor memory formation and possibly dynamic motor learning.     

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.     

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.     

Parieto-frontal interactions in visual-object and visual-spatial working memory: evidence from transcranial magnetic stimulation.

This study aimed to investigate whether transcranial magnetic stimulation (TMS) can induce selective working memory (WM) deficits of visual-object versus visual-spatial information in normal humans. Thirty-five healthy subjects performed two computerized visual n-back tasks, in which they were required to memorize spatial locations or abstract patterns. In a first series of experiments, unilateral or bilateral TMS was delivered on posterior parietal and middle temporal regions of both hemispheres after various delays during the WM task. Bilateral temporal TMS increased reaction times (RTs) in the visual-object, whereas bilateral parietal TMS selectively increased RTs in the visual-spatial WM task. These effects were evident at a delay of 300 ms. Response accuracy was not affected by bilateral or unilateral TMS of either cortical region. In a second group of experiments, bilateral TMS was applied over the superior frontal gyrus (SFG) or the dorsolateral prefrontal cortex (DLPFC). TMS of the SFG selectively increased RTs in the visual-spatial WM task, whereas TMS of the DLPFC interfered with both WM tasks, in terms of both accuracy and RTs. These effects were evident when TMS was applied after a delay of 600 ms, but not one of 300 ms. These findings confirm the segregation of WM buffers for object and spatial information in the posterior cortical regions. In the frontal cortex, the DLPFC appears to be necessary for WM computations regardless of the stimulus material.     

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.      

Burst Activation of the Cerebral Cortex by Flash Stimuli during Isoflurane Anesthesia in Rats

Background: The degree of suppression of sensory functions during general anesthesia is controversial. Here, the authors investigated whether discrete flash stimuli induced cortical field potential responses at an isoflurane concentration producing burst suppression and compared the spatiotemporal properties and frequency spectra of flash-induced burst responses with those occurring spontaneously.

Methods: Rats were equipped with multiple epidural and intracortical electrodes to record cortical field potentials in the right hemisphere at several locations along the anterior-posterior axis. At isoflurane concentrations of 1.1, 1.4, and 1.8%, discrete light flashes were delivered to the left eye while cortical field potentials were continuously recorded.

Results: Isoflurane at 1.4-1.8% produced burst suppression. Each flash produced a visual evoked potential in the primary visual cortex followed by secondary bursting activity in more anterior regions. The average latency and duration of these bursts were 220 and 810 ms, respectively. The spontaneous and flash-induced bursts were similar in frequency, duration, and spatial distribution. They had maximum power in the frontal (primary motor) cortex with a dominant frequency of 10 Hz.     

Functional significance of olfactory-induced oscillations in the human amygdala

We recorded directly from the amygdalar nucleus of nine epileptic patients performing a delayed odor-matching recognition memory task. Time-frequency analysis of the responses to the odorants revealed that the stimulations elicited induced oscillatory responses, as well as already described olfactory evoked potentials. These oscillatory responses were composed of two frequency components--one in the beta band (15-25 Hz) and a faster one, in the low gamma band (25-35 Hz)--both of which lasted during the full duration of the inspiration. In pairs of identical odorants, the power of gamma oscillations was weaker for the second odorant (the target) than for the first one (the sample). We observed no such difference when the first and second odorants of a pair were different. Thus, gamma oscillations in the amygdala are weaker for repeated stimuli, a mechanism known as repetition suppression. This is consistent with an involvement of the human amygdala in the encoding and retrieval of olfactory information independently of its hedonic properties, at least in epileptic patients. Altogether, our results corroborate in humans evidence found in animals that oscillations serve as a common coding process of olfactory information.     

Separable neural bases for subprocesses of recognition in working memory

Working memory supports the recognition of objects in the environment. Memory models have postulated that recognition relies on 2 processes: assessing the degree of similarity between an external stimulus and memory representations and testing the resulting summed-similarity value against a critical level for recognition. Here, we varied the similarity between samples held in working memory and a probe to investigate these 2 processes with magnetoencephalography. Two separable components matched our expectations: First, from 280 ms after probe onset, clearly nonmatching probes differed from both similar nonmatches and matches over left frontal cortex. At 350-400 ms, these signals evolved into a pattern of gradually increasing activation as a function of sample-probe similarity, as expected for a neural representation of summed similarity. Second, a signal potentially reflecting criterion testing was observed at 600-700 ms at right frontotemporal sensors that differentiated between matches and nonmatches without further differences between similar and dissimilar probes. Thus, analysis of the time course of recognition provided strong evidence that similarity summation and criterion testing have separable neural bases. As probably both working and long-term memory recognition draw on these processes, they may be involved in many domains of behavior.     

Effects of pentobarbital and isoflurane on conditioned learning after transient global cerebral ischemia in rabbits

BACKGROUND: The acquisition of a conditioned eyeblink response has been used extensively to study the neurologic substrates of learning and memory. We examined the effects of the anesthetics isoflurane and pentobarbital, or hypothermia (30 degrees C), on the ability of rabbits to acquire an eyeblink conditioned response after 6.5 min of cerebral ischemia. METHODS: New Zealand white rabbits (n = 48) were randomly assigned to sham, normothermic, hypothermic, isoflurane, or pentobarbital groups. In the normothermic, hypothermic, isoflurane, and pentobarbital groups, 6.5 min of global cerebral ischemia was produced. In animals randomized to the isoflurane and pentobarbital groups, a pattern of burst suppression was achieved on the electroencephalogram before the start of the ischemic episode. Animals in the hypothermia group were cooled to 30 degrees C before ischemia. Seven days after ischemia, eyeblink training was started using an audible tone presented for 100 ms as the conditioned stimulus. The unconditioned stimulus was an air puff directed at the cornea. The delay between the end of conditioned stimulus and the start of the unconditioned stimulus (the trace interval) was 300 ms in duration. A conditioned response was defined as an eyeblink that was initiated during the trace interval. Eighty trials per day and 15 days of training were delivered. RESULTS: Neurologic deficits were greatest in the normothermia group, and these animals also had fewer conditioned responses than those in the sham, hypothermia, or pentobarbital groups. Animals in the isoflurane group had an intermediate number of conditioned responses that was not significantly different from the normothermia group. CONCLUSIONS: This study demonstrates that a brief episode of cerebral ischemia results in the impairment of associative learning. Hypothermia and burst-suppressive doses of pentobarbital were able to improve neurobehavioral outcome as measured by ability to acquire a trace conditioned response.