The substrate for long-lasting memory: If not protein synthesis,then what?

The prevailing textbook view that de novo protein synthesis is required for memory (e.g., [Bear, M. F., Connors, B., & Paradiso, M. 2006. Neuroscience. Lippincott, New York]) is seriously flawed and an alternative hypothesis has been proposed in which post-translational modification (PTM) of proteins already synthesized and already present within the synapse is 'the' substrate for long-lasting memory. Protein synthesis serves a replenishment role. The first part of this review discusses how long-lasting memory can be achieved with 'only' PTM of existing synaptic proteins. The second part critically reviews a recent report published in Neuron 2007 that exemplifies the current view of protein synthesis and memory while also illustrating how these results can be understood within this new PTM framework. A necessary yet unexpected conclusion to emerge from consideration of the consequences of a PTM mechanism as the necessary, sufficient and exclusive substrate for long-lasting memory, is that the central Hebbian dogma that cells that 'fire together, wire together' is an unlikely mechanism for long-lasting memory. Thus, a unique feature of the PTM model is that longevity of information storage is achieved not by stability of the synaptic mechanism, but by impermanent pseudoredundant circuits. This is so because PTM is a reversible process and thus any permanent connection, any 'lasting effect' cannot be in the form of stable synapse formation. We have therefore proposed a solution in which network level processes regulate cellular mechanisms, even as such mechanisms regulate the network. Thus, synapses are 'meta-stabilized' by regulated feedback mediated by the circuit in which the synapse is embedded. For example, spontaneous activity is proposed to be a substrate feedback mechanism we term 'cryptic rehearsal' to sustain for some period of time after learning an approximation to the state initially created by input. Additionally, because the duplication of these traces is ongoing, this provides a degenerate code for the engram. Stability is thus achieved, not by stabilizing the synapse, but by implementing a pseudo-redundant yet malleable circuitry so that memory can be protected in the face of small catastrophes in network representation.     

Switching between memory and perception: Moving attention or memory retrieval?

Weber, Burt, and Noll (1986) estimated that the time needed to switch attention between memory and perception was around 300 msec. The first two experiments in the present paper estimated switching time using a variation of their task. Subjects reported aloud lists of six items. The items were read off a computer screen (perception), recited from memory, or reported alternately from the two sources. The data show that the switching-time estimate is influenced by input/output compatibility, response-initiation times, and memory load. When these factors were controlled, estimated switching time dropped to around 100-150 msec. The data suggest, however, that the switch from perception to memory might be slower than the switch from memory to perception, which would invalidate the formula used to compute switching time. Experiment 3 tested the time for a single switch from perception to memory and a single switch from memory to perception by restricting report to one pair of items in the list. When the to-be-reported pair was precued, estimated switching time dropped to zero. When the pair was not precued, the memory-to-perception switching time remained at zero, but the perception-to-memory time was more than 400 msec. The pattern of results forced a reconceptualization of the task in terms of memory retrieval rather than attention switching. The attention-switching times appear to reflect processes required to select items from memory.     

Attention and stuttering: Do stutterers think too much about speech?

In this investigation the ability of stutterers and nonstutterers to simultaneously perform speech and nonspeech tasks was compared. Subjects were 10 stutterers and 10 nonstutterers. Two experiments were conducted. In the first, subjects performed a non-attention-demanding gross-motor task while they read aloud. In the second, subjects performed an attention-demanding task (reading comprehension) during speech. Results indicated that there was no significant change in the disfluency values of stutterers during the motor activity or as a result of the reading comprehension task. However, stutterers were found to perform significantly poorer than nonstutterers on the reading comprehension task. This finding was taken as evidence that stutterers devote more attention to speech than do nonstutterers.     

Yours or mine? Ownership and memory

An important function of the self is to identify external objects that are potentially personally relevant. We suggest that such objects may be identified through mere ownership. Extant research suggests that encoding information in a self-relevant context enhances memory (the so-called 'self-reference effect'), thus an experiment was designed to test the impact of ownership on memory performance. Participants either moved or observed the movement of picture cards into two baskets; one of which belonged to self and one which belonged to another participant. A subsequent recognition test revealed that there was a significant memory advantage for objects that were owned by self. Acting on items (i.e., moving them) had no impact on memory. Results are discussed with reference to the importance of self-object associations in cognition.     

Poor performance on cognitive tasks in depression: Doing too much or not enough?

Depressed people perform poorly on cognitive tasks. It is unclear whether these deficits are due to decreased devotion of task-related resources or to increased attention to non-task-related information. In the present study, we examined the degree to which depressed and healthy adults displayed pupillary motility that varied at the frequency of presented stimuli on a cognitive task, which we interpreted as task-related processing, and at other frequencies, which we interpreted as reflecting intrinsic processing. Depressed participants made more consecutive errors than did controls. More pupillary motility at other frequencies was associated with poorer performance, whereas more pupillary motility at the frequency of presented stimuli was associated with better performance. Depressed participants had more pupillary motility at other frequencies, which partially mediated observed deficits in cognitive performance. These findings support the hypothesis that allocating cognitive resources to intrinsic processing contributes to observed cognitive deficits in depression.     

Immediate memory for faces: Long- or short-term memory?

Immediate recognition memory span and short-term forgetting for non-verbal stimuli (“unfamiliar faces”) were investigated in normal subjects and amnesic patients. Surnames were used as a verbal control. It was found that normal subjects had a reliable immediate recognition span of one for faces and that there was no decrement in performance in the retention of three faces over a 30-s interval. Amnesic subjects were impaired on both the immediate memory span task and on the short-term forgetting task. This pattern of results contrasts with those obtained using surnames on which the results were comparable to other verbal S.T.M. tasks. It is suggested that performance on these tasks of recognition memory for faces is determined by L.T.M. processes. The implications for the interpretation of S.T.M. are discussed.     

Size overestimation among anorexics: much ado about very little?

Research on size overestimation among anorexics has failed to control for the effects of actual body size on estimated size. We obtained estimates of the size of 3 body sites from 3 groups: 13 anorexic women; 13 non-eating disordered women matched with the anorexics on actual body size; and 13 non-eating disordered women of average size. The anorexic and size-matched normal subjects did not differ in the extent to which they overestimated their body size, but both displayed significantly greater overestimation than did the subjects of average size. Both groups also estimated the actual size of their body sites to be larger than did average-size normal subjects. These findings illustrate the need for appropriate control procedures when considering body image disturbances among persons with eating disorders, and they raise questions about the psychological significance of disturbances in the perceptual component of body image.     

Semantic memory: Complexity or connectivity?

The complexity hypothesis predicts that concept-feature verification times should be directly related to the number of features associated with a concept (the fan effect). Conversely, the connectivity hypothesis predicts that for interconnected semantic relationships, this verification time should be inversely related to the number of closely associated features (the reversed fan effect). In the present experiments, although the time required for episodic recognition memory decisions tended to be directly related to the number of features associated with a concept, semantic verification times were inversely related to the complexity of the concept. In addition, the concept's complexity was at least as good a predictor of performance in semantic tasks as was the strength of association between the concept and feature. Both of these results are interpreted in terms of the connectivity hypothesis.     

Memory monitoring and memory performance: Linked closely or loosely?

Summary An experimental test of the metamemory hypothesis claiming a substantive positive relationship between memory monitoring and memory performance is provided. Forty-eight university students learned a set of abstract nouns. They were either instructed to make use of monitoring activities (experimental group), simply to learn the words (control-1) or to use non-metacognitive learning strategies (control-2). Prior to recall, the subjects had to predict the number of items they expected to remember. The experimental predictions were derived on two levels. First, prediction accuracy should be best for the experimental group. This is a necessary prerequisite for a valid test of the second prediction, namely that memory performance, too, should be best for the experimental group. Whereas the first prediction was confirmed, the second, vital for the metamemory hypothesis, was not. Thus, this hypothesis did not stand up to an experimental test, but would have been confirmed if tested by the correlation between prediction accuracy and memory performance.     

Working memory and intelligence: the same or different constructs?

Several investigators have claimed over the past decade that working memory (WM) and general intelligence (g) are identical, or nearly identical, constructs, from an individual-differences perspective. Although memory measures are commonly included in intelligence tests, and memory abilities are included in theories of intelligence, the identity between WM and intelligence has not been evaluated comprehensively. The authors conducted a meta-analysis of 86 samples that relate WM to intelligence. The average correlation between true-score estimates of WM and g is substantially less than unity (p=.479). The authors also focus on the distinction between short-term memory and WM with respect to intelligence with a supplemental meta-analysis. The authors discuss how consideration of psychometric and theoretical perspectives better informs the discussion of WM-intelligence relations.     

BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory?

It is generally believed that late-phase long-term potentiation (L-LTP) and long-term memory (LTM) require new protein synthesis. Although the full complement of proteins mediating the long-lasting changes in synaptic efficacy have yet to be identified, several lines of evidence point to a crucial role for activity-induced brain-derived neurotrophic factor (BDNF) expression in generating sustained structural and functional changes at hippocampal synapses thought to underlie some forms of LTM. In particular, BDNF is sufficient to induce the transformation of early to late-phase LTP in the presence of protein synthesis inhibitors, and inhibition of BDNF signaling impairs LTM. Despite solid evidence for a critical role of BDNF in L-LTP and LTM, many issues are not resolved. Given that BDNF needs to be processed in Golgi outposts localized at the branch point of one or few dendrites, a conceptually challenging problem is how locally synthesized BDNF in dendrites could ensure synapse-specific modulation of L-LTP. An interesting alternative is that BDNF-TrkB signaling is involved in synaptic tagging, a prominent hypothesis that explains how soma-derived protein could selectively modulate the tetanized (tagged) synapse. Finally, specific roles of BDNF in the acquisition, retention or extinction of LTM remain to be established.     

The co-witness misinformation effect: memory blends or memory compliance?

For 30 years hundreds of researchers have shown participants videos and slide-sequences of events, presented the participants with misleading information, and found that this misinformation distorted their memories. The purpose of this study was to establish whether those misled participants are reporting a memory blend of the two sources of information or whether they are simply complying with the post-event information. A total of 92 participants were shown one of two versions of six different videos, which included some subtle differences. After having watched each video individually, participants were paired with someone who had seen the other version and they discussed the clips together. They then individually answered questions about the videos, and their responses showed that some of the distorted memories were blends of the original information and the post-event information. The implications of these findings are discussed.     

Specificity and detail in autobiographical memory: Same or different constructs?

Research on autobiographical memory has focused on whether memories are coded as specific (i.e., describe a single event that happened at a particular time and place). Although some theory and research suggests that the amount of detail in autobiographical memories reflects a similar underlying construct as memory specificity, past research has not investigated whether these variables converge. Therefore, the present study compared the proportion of specific memories and the amount of detail embedded in memory responses to cue words. Results demonstrated that memory detail and proportion of specific memories were not correlated with each other and showed different patterns of association with other conceptually relevant variables. When responses to neutral cue words were examined in multiple linear and logistic regression analyses, the proportion of specific memories uniquely predicted less depressive symptoms, low emotional avoidance, lower emotion reactivity, better executive control and lower rumination, whereas the amount of memory detail uniquely predicted the presence of depression diagnosis, as well as greater depressive symptoms, subjective stress, emotion reactivity and rumination. Findings suggest that the ability to retrieve specific memories and the tendency to retrieve detailed personal memories reflect different constructs that have different implications in the development of emotional distress.     

Risk for mania and positive emotional responding: too much of a good thing?

Although positive emotion research has begun to flourish, the extremes of positive emotion remain understudied. The present research used a multimethod approach to examine positive emotional disturbance by comparing participants at high and low risk for episodes of mania, which involves elevations in positive emotionality. Ninety participants were recruited into a high or low mania risk group according to responses on the Hypomanic Personality Scale. Participants' subjective, expressive, and physiological emotional responses were gathered while they watched two positive, two negative, and one neutral film clip. Results suggested that participants at high risk for mania reported elevated positive emotion and irritability and also exhibited elevated cardiac vagal tone across positive, negative, and neutral films. Discussion focuses on the implications these findings have for the diagnosis and prevention of bipolar disorder, as well as for the general study of positive emotion.     

Age differences in implicit memory: conceptual, perceptual, or methodological?

The authors examined age differences in conceptual and perceptual implicit memory via word-fragment completion, word-stem completion, category exemplar generation, picture-fragment identification, and picture naming. Young, middle-aged, and older participants (N = 60) named pictures and words at study. Limited test exposure minimized explicit memory contamination, yielding no reliable age differences and equivalent cross-format effects. In contrast, explicit memory and neuropsychological measures produced significant age differences. In a follow-up experiment, 24 young adults were informed a priori about implicit testing. Their priming was equivalent to the main experiment, showing that test trial time restrictions limit explicit memory strategies. The authors concluded that most implicit memory processes remain stable across adulthood and suggest that explicit contamination be rigorously monitored in aging studies.     

Retrieval from memory: vulnerable or inviolable?

We show that retrieval from semantic memory is vulnerable even to the mere presence of speech. Irrelevant speech impairs semantic fluency--namely, lexical retrieval cued by a semantic category name--but only if it is meaningful (forward speech compared to reversed speech or words compared to nonwords). Moreover, speech related semantically to the retrieval category is more disruptive than unrelated speech. That phonemic fluency--in which participants are cued with the first letter of words they are to report--was not disrupted by the mere presence of meaningful speech, only by speech in a related phonemic category, suggests that distraction is not mediated by executive processing load. The pattern of sensitivity to different properties of sound as a function of the type of retrieval cue is in line with an interference-by-process approach to auditory distraction.