Memory deficits in Alzheimer's disease: the encoding hypothesis and cholinergic function

Forgetting functions generated by delayed matching-to-sample procedures allow delay-dependent effects to be distinguished from delay-independent effects on working memory. Parameters of negative exponential functions estimate initial discriminability (intercept) and rate of forgetting (slope). Forgetting functions for patients with Alzheimer's disease indicate that they differ from normal controls in terms of reduced initial discriminability—that is, in the encoding component of memory performance— but not convincingly in rate of forgetting. Reanalyses of previous studies with different species suggest that pro- and anticholinergic drugs influence initial discriminability in delayed matching-to-sample performance, but not rate of forgetting. The results of our reanalyses are consistent with the conclusion that the cholinergic system plays a role in the encoding component of working memory and that this is the main characteristic of the memory deficit shown by patients with Alzheimer's disease.     

Effects of methylphenidate on working memory in pigeons

To assess the effects of methylphenidate on working memory, pigeons were trained in a delayed matching-to-sample task. Delay interval duration (0.2, 1, 3, 6, or 12 sec) was varied within sessions in order to separate delay-dependent from delay-independent effects of the drug on performance. A reduction in the sample response requirement from five responses to one response effectively reduced attention to the stimulus and impaired overall accuracy. Methylphenidate was administered in doses of 0.0 (saline control), 0.25, 2.5, and 10 mg/kg. Relative to performance with saline, accuracy was significantly reduced with 10 mg/kg methylphenidate to the same extent in both fixed ratio (FR) 1 and FR 5 conditions. The smaller doses had no effect, and there was no evidence that accuracy improved with drug administration. Intercepts and slopes of exponential functions fitted to measures of discriminability plotted as a function of delay showed that methylphenidate affected delay-independent aspects of performance (initial discriminability), but not delay-dependent aspects (rate of forgetting).     

Marijuana effects on human forgetting functions

It has long been known that acute marijuana administration impairs working memory (e.g., the discrimination of stimuli separated by a delay). The determination of which of the individual components of memory are altered by marijuana is an unresolved problem. Previous human studies did not use test protocols that allowed for the determination of delay-independent (initial discrimination) from delay-dependent (forgetting or retrieval) components of memory. Using methods developed in the experimental analysis of behavior and signal detection theory, we tested the acute effects of smoked marijuana on forgetting functions in 5 humans. Immediately after smoking placebo, a low dose, or a high dose of marijuana (varying in delta9-THC content), subjects completed delayed match-to-sample testing that included a range of retention intervals within each test session (0.5, 4, 12, and 24 s). Performances (discriminability) at each dose were plotted as forgetting functions, as described and developed by White and colleagues (White, 1985; White & Ruske, 2002). For all 5 subjects, both delta9-THC doses impaired delay-dependent discrimination but not delay-independent discrimination. The outcome is consistent with current nonhuman studies examining the role of the cannabinoid system on delayed matching procedures, and the data help illuminate one behavioral mechanism through which marijuana alters memory performance.     

Characteristics of forgetting functions in delayed matching to sample

Performance of pigeons in delayed matching-to-sample procedures was measured in terms of an index of discriminability derived from the difference between logarithms of ratios of choice responses to comparison stimuli following the different sample stimuli. Forgetting functions that plotted discriminability as a function of delay-interval duration were well described by a simple negative exponential function with two parameters, one describing initial discriminability of sample stimuli at zero delay (log d₀) and the other describing rate of decrement in discriminability with increasing delay-interval duration (b). With the difference between wavelength values of the comparison stimuli held constant, a large difference between wavelengths of the sample stimuli resulted in a higher log d₀ value than that for a small difference between sample stimuli, without changing the rate of decrement in discriminability, b. An increase in the fixed-ratio requirement for sample-key responding produced an increase in log d₀ without affecting b, and interpolation of ambient illumination in the delay interval increased b without influencing log d₀. Both parameters changed when intertrial-interval duration was varied. The result of variation in the point of interpolation of ambient illumination in the delay interval indicated that levels of discriminability at longer delays were independent of discriminability levels at earlier delays, consistent with the properties of the exponential function. Functions relating performance to delay-interval duration were suggested to have two characteristics: discriminability of the sample stimuli in the absence of a delay between the stimuli and the behavior they occasion, and rate of attenuation in discriminability with increasing delay-interval duration.     

On the form of the forgetting function: the effects of arithmetic and logarithmic distributions of delays

Forgetting functions with 18 delay intervals were generated for delayed matching-to-sample performance in pigeons. Delay interval variation was achieved by arranging five different sets of five delays across daily sessions. In different conditions, the delays were distributed in arithmetic or logarithmic series. There was no convincing evidence for different effects on discriminability of the distributions of different delays. The mean data were better fitted by some mathematical functions than by others, but the best-fitting functions depended on the distribution of delays. In further conditions with a fixed set of five delays, discriminability was higher with a logarithmic distribution of delays than with an arithmetic distribution. This result is consistent with the treatment of the forgetting function in terms of generalization decrement.     

Writing and overwriting short-term memory

An integrative account of short-term memory is based on data from pigeons trained to report the majority color in a sequence of lights. Performance showed strong recency effects, was invariant over changes in the interstimulus interval, and improved with increases in the intertrial interval. A compound model of binomial variance around geometrically decreasing memory described the data; a logit transformation rendered it isomorphic with other memory models. The model was generalized for variance in the parameters, where it was shown that averaging exponential and power functions from individuals or items with different decay rates generates new functions that are hyperbolic in time and in log time, respectively. The compound model provides a unified treatment of both the accrual and the dissipation of memory and is consistent with data from various experiments, including thechoose-short bias in delayed recall, multielement stimuli, and Rubin and Wenzel’s (1996) meta-analyses of forgetting.     

Retrospective coding in pigeons' delayed matching-to-sample

In this study we examined how coding processes in pigeons' delayed matching-to-sample were affected by the stimuli to be remembered. In Experiment 1, two groups of pigeons initially learned 0-delay matching-to-sample with identical comparison stimuli (vertical and horizontal lines) but with different sample stimuli (red and green hues or vertical and horizontal lines). Longer delays were then introduced between sample offset and comparison onset to assess whether pigeons were prospectively coding the same events (viz., the correct line comparisons) or retrospectively coding different events (viz., their respective sample stimuli). The hue-sample group matched more accurately and showed a slower rate of forgetting than the line-sample group. In Experiment 2, pigeons were trained with either hues or lines as both sample and comparison stimuli, or with hue samples and line comparisons or vice versa. Subsequent delay tests revealed that the hue-sample groups remembered more accurately and generally showed slower rates of forgetting than the line-sample groups. Comparison dimension had little or no effect on performance. Together, these data suggest that pigeons retrospectively code the samples in delayed matching-to-sample.     

A theory of attending, remembering, and reinforcement in delayed matching to sample

A theory of attending and reinforcement in conditional discriminations is extended to working memory in delayed matching to sample by adding terms for disruption of attending during the retention interval. Like its predecessor, the theory assumes that reinforcers and disruptors affect the independent probabilities of attending to sample and comparison stimuli in the same way as the rate of overt free-operant responding as suggested by Nevin and Grace, and that attending is translated into discriminative performance by the model of Davison and Nevin. The theory accounts for the effects of sample-stimulus discriminability and retention-interval disruption on the levels and slopes of forgetting functions, and for the diverse relations between accuracy and sensitivity to reinforcement reported in the literature. It also accounts for the effects of reinforcer probability in multiple schedules on the levels and resistance to change of forgetting functions; for the effects of reinforcer probabilities signaled within delayed-matching trials; and for the effects of reinforcer delay, sample duration, and intertrial-interval duration. The model accounts for some data that have been problematic for previous theories, and makes testably different predictions of the effects of reinforcer probabilities and disruptors on forgetting functions in multiple schedules and signaled trials.     

Forgetting curves: implications for connectionist models

Forgetting in long-term memory, as measured in a recall or a recognition test, is faster for items encoded more recently than for items encoded earlier. Data on forgetting curves fit a power function well. In contrast, many connectionist models predict either exponential decay or completely flat forgetting curves. This paper suggests a connectionist model to account for power-function forgetting curves by using bounded weights and by generating the learning rates from a monotonically decreasing function. The bounded weights introduce exponential forgetting in each weight and a power-function forgetting results when weights with different learning rates are averaged. It is argued that these assumptions are biologically reasonable. Therefore power-function forgetting curves are a property that may be expected from biological networks. The model has an analytic solution, which is a good approximation of a power function displaced one lag in time. This function fits better than any of the 105 suggested two-parameter forgetting-curve functions when tested on the most precise recognition memory data set collected by. Unlike the power-function normally used, the suggested function is defined at lag zero. Several functions for generating learning rates with a finite integral yield power-function forgetting curves; however, the type of function influences the rate of forgetting. It is shown that power-function forgetting curves cannot be accounted for by variability in performance between subjects because it requires a distribution of performance that is not found in empirical data. An extension of the model accounts for intersecting forgetting curves found in massed and spaced repetitions. The model can also be extended to account for a faster forgetting rate in item recognition (IR) compared to associative recognition in short but not long retention intervals.     

An investigation of the differential-outcomes effect within sessions

The differential-outcomes effect is manifest as more accurate performance of a delayed conditional discrimination when alternative choice responses are followed by different reinforcers than when they are followed by the same reinforcer. In Experiment 1, a differential-outcomes effect was demonstrated within sessions by signaling the duration of food access for correct responses with stimuli appearing in conjunction with the sample stimuli. The delayed matching-to-sample performance of 5 pigeons was more accurate when green choice responses (matching a green sample) were followed by 3.5-s food access and red choice responses (matching a red sample) were followed by 0.5-s food access (different-outcome trials) than when the correct choice responses were both followed by 1.5-s reinforcers (same-outcome trials). In Experiment 2, the acquisition of this differential-outcomes effect was characterized by a progressive decrease in rate of forgetting on different-outcome trials and no change in rate of forgetting on same-outcome trials. In addition, accuracy at the shortest delay intervals for both different-outcome and same-outcome trials increased over acquisition, but to a greater extent for different-outcome trials. These data suggest that both memorial and attentional (time-dependent and time-independent) factors contribute to the differential-outcomes effect.     

Tactual, visual, and cross-modal transfer of texture in 5- and 8-year-old children

Children's tactual, visual, and cross-modal transfer abilities for texture were investigated in a delayed matching-to-sample paradigm. Transfer performance from vision to touch was found to increase between 5 and 8 years of age, whereas transfer performance from touch to vision did not vary with age and matched touch-to-touch performance. Asymmetrical cross-modal abilities were observed at the age of 8 years, vision-to-touch transfer performance being higher than touch-to-vision transfer performance (experiment 2). This developmental pattern could not be attributed to limitations in the tactual or visual discriminability of the textures or to differences in tactual or visual memory between the two age groups (experiment 1). It is suggested that the increase with age in vision-to-touch performance may be related to the intervention of more efficient top-down perceptual processes in the older children.     

Forgetting in retarded and nonretarded persons under conditions of minimal strategy use

Short-term memory processes of mentally retarded (mild, moderate, and severe) and nonretarded persons were compared in a delayed matching-to-sample task that minimized the use of verbal rehearsal. In addition to trials with delays up to 20 s, the inclusion of trials on which the sample and comparison stimuli occurred simultaneously made it possible to isolate memory and discriminability. Forgetting was most pronounced between the simultaneous and 0-s conditions, and nonretarded subjects forgot less than retarded subjects between these conditions. There were no group differences beyond the 0-s delay. Ease of strategy use failed to account for individual differences, and reported strategy use was not related systematically to performance. These findings are incompatible with the hypothesis that normal-retarded differences occur only on tasks involving effortful cognitive strategies. Differences between nonretarded and retarded groups in this study may be due to a failure in automatic encoding processes in retarded persons.     

Transfer of directed-forgetting cues across discrimination tasks with pigeons

Directed forgetting is shown as impaired performance on a memory test following an instruction that the presented items will not be tested. Experiments utilizing the delayed matching-to-sample (DMTS) task have demonstrated that this ability to actively control memory is present in animals; however, no study has yet confirmed that cues to forget established in one DMTS discrimination will successfully transfer to other discriminations. Lacking such evidence, it is not clear whether forgetting cues act as “higher level” task instructions or are represented more simply, perhaps as part of a sample-specific sequence of events. The present study revealed good transfer of the forget cue function in pigeons after prior training with the forget cues in a separate discrimination. This finding is discussed in relation to analogous experiments on occasion setting, in which training within more than one discriminative context has been shown to be critical to the transfer of a conditional relation.     

Reversing the course of forgetting

Forgetting functions were generated for pigeons in a delayed matching-to-sample task, in which accuracy decreased with increasing retention-interval duration. In baseline training with dark retention intervals, accuracy was high overall. Illumination of the experimental chamber by a houselight during the retention interval impaired performance accuracy by increasing the rate of forgetting. In novel conditions, the houselight was lit at the beginning of a retention interval and then turned off partway through the retention interval. Accuracy was low at the beginning of the retention interval and then increased later in the interval. Thus the course of forgetting was reversed. Such a dissociation of forgetting from the passage of time is consistent with an interference account in which attention or stimulus control switches between the remembering task and extraneous events.     

A model for stochastic drift in memory strength to account for judgments of learning

Previous research has shown that judgments of learning (JOLs) made immediately after encoding have a low correlation with actual cued-recall performance, whereas the correlation is high for delayed judgments. In this article, the authors propose a formal theory describing the stochastic drift of memory strength over the retention interval to account for the delayed-JOL effect. This is done by first decomposing the aggregated memory strength into exponential functions with slow and fast memory traces. The mean aggregated memory strength shows power-function forgetting curves. The drift of the memory strength is large for immediate JOLs (causing a low predictability) and weak for delayed JOLs (causing a high predictability). Consistent with empirical data, the model makes a novel prediction of JOL asymmetry, or that immediate weak JOLs are more predictive of future performance than are immediate strong JOLs. The JOL distributions for immediate and delayed JOLs are also accounted for.     

The response-signal method reveals age-related changes in object working memory

Sixteen healthy young adults (ages 18-32) and 16 healthy older adults (ages 67-81) completed a delayed response task in which they saw the following visual sequence: memory stimuli (2 abstract shapes; 3,000 ms), a blank delay (5,000 ms), a probe stimulus of variable duration (one abstract shape; 125, 250, 500, 1,000, or 2,000 ms), and a mask (500 ms). Subjects decided whether the probe stimulus matched either of the memory stimuli; they were instructed to respond during the mask, placing greater emphasis on speed than accuracy. The authors used D. L. Hintzman & T. Curran's (1994) 3-parameter compound bounded exponential model of speed-accuracy tradeoff to describe changes in discriminability associated with total processing time. Group-level analysis revealed a higher rate parameter and a higher asymptote parameter for the young adult group, but no difference across groups in x-intercept. Proxy measures of cognitive reserve (Y. Stern et al., 2005) predicted the rate parameter value, particularly in older adults. Results suggest that in working memory, aging impairs both the maximum capacity for discriminability and the rate of information accumulation, but not the temporal threshold for discriminability.     

Effects of acute and chronic cocaine administration on titrating-delay matching-to-sample performance

The effects of cocaine were examined under a titrating-delay matching-to-sample procedure. In this procedure, the delay between sample stimulus offset and comparison stimuli onset adjusts as a function of the subject's performance. Specifically, matches increase the delay and mismatches decrease the delay. Titrated delay values served as the primary dependent measure. After establishing stable performance in pigeons, several behaviorally-effective doses of cocaine were administered acutely. Dose-related within-session decreases in titrated delay values were observed. Following acute determinations, the dose of cocaine that produced the most rapid decline without eliminating performance was administered prior to each daily session. Chronic administration resulted in performance trending toward control levels. A redetermination of the dose-response function following chronic exposure revealed reduced potency (i.e., tolerance) under cocaine on titrated delay matching-to-sample performance. Supplemental analyses suggest that cocaine may serve as a disruptor of the stimulus conditions in which the performance was established.     

Measurement of trace strength in memory for pictures

Four experiments using a yes-no recognition task with snapshots examined (1) the effect of presenting not one but two items simultaneously, either both targets or both distractors, for a single judgment at a retention test trial; (2) the rate of forgetting; (3) the interaction between retention interval and the exposure duration at acquisition; (4) acquisition as a function of the number of times a picture was presented. In each case performance was assessed by calculating the discriminability index d'. The results supported the hypotheses that trace strength is lognormally distributed, that forgetting is exponential, and that in acquisition trace strength is a linear function of the number of presentations.