Multitrial free recall for evaluating memory.

OBJECTIVE: Much of our knowledge concerning the neural basis of human memory derives from lab-based verbal recall tasks. Outside of the lab, clinicians use validated and normed neuropsychological tests to assess patients' memory function and to evaluate clinical interventions. Here we sought to establish the clinical validity of examining memory through multitrial free recall of semantically organized and unrelated word lists. METHOD: We compare memory performance in multitrial free recall tasks with the Rey Auditory Verbal Learning Test and the California Verbal Learning Test, two common neuropsychological tests aimed at evaluating memory function in clinical settings. We compare predictive validity between the tasks by evaluating deficits in a patient sample and examining age-related declines in memory. We additionally compare test-retest reliability, establish convergent validity, and show the emergence of common recall dynamics between the tasks. RESULTS: We demonstrate that both laboratory free recall tasks have better predictive validity and test-retest reliability than the established neuropsychological tests. We further show that all tasks have good convergent validity and reveal core memory processes, including temporal and semantic organization. However, we also demonstrate the benefits of repeated trials for evaluating the dynamics of memory search and their neuropsychological sequelae. CONCLUSIONS: These results provide evidence for the clinical validity of lab-based multitrial free recall tasks and highlight their psychometric benefits over neuropsychological measures. Based on these results, we discuss the need to bridge the gap between clinical understanding of putative mechanisms underlying memory disorders and neuroscientific findings obtained using lab-based free recall tasks. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

EEG biomarkers of free recall.

Brain activity in the moments leading up to spontaneous verbal recall provide a window into the cognitive processes underlying memory retrieval. But these same recordings also subsume neural signals unrelated to mnemonic retrieval, such as response-related motor activity. Here we examined spectral EEG biomarkers of memory retrieval under an extreme manipulation of mnemonic demands: subjects either recalled items after a few seconds or after several days. This manipulation helped to isolate EEG components specifically related to long-term memory retrieval. In the moments immediately preceding recall we observed increased theta (4-8 Hz) power (+T), decreased alpha (8-20 Hz) power (-A), and increased gamma (40-128 Hz) power (+G), with this spectral pattern (+T-A + G) distinguishing the long-delay and immediate recall conditions. As subjects vocalized the same set of studied words in both conditions, we interpret the spectral +T-A + G as a biomarker of episodic memory retrieval.

Medial temporal lobe functional connectivity predicts stimulation-induced theta power.

Focal electrical stimulation of the brain incites a cascade of neural activity that propagates from the stimulated region to both nearby and remote areas, offering the potential to control the activity of brain networks. Understanding how exogenous electrical signals perturb such networks in humans is key to its clinical translation. To investigate this, we applied electrical stimulation to subregions of the medial temporal lobe in 26 neurosurgical patients fitted with indwelling electrodes. Networks of low-frequency (5-13 Hz) spectral coherence predicted stimulation-evoked increases in theta (5-8 Hz) power, particularly when stimulation was applied in or adjacent to white matter. Stimulation tended to decrease power in the high-frequency broadband (HFB; 50-200 Hz) range, and these modulations were correlated with HFB-based networks in a subset of subjects. Our results demonstrate that functional connectivity is predictive of causal changes in the brain, capturing evoked activity across brain regions and frequency bands.

Widespread theta synchrony and high-frequency desynchronization underlies enhanced cognition.

The idea that synchronous neural activity underlies cognition has driven an extensive body of research in human and animal neuroscience. Yet, insufficient data on intracranial electrical connectivity has precluded a direct test of this hypothesis in a whole-brain setting. Through the lens of memory encoding and retrieval processes, we construct whole-brain connectivity maps of fast gamma (30-100 Hz) and slow theta (3-8 Hz) spectral neural activity, based on data from 294 neurosurgical patients fitted with indwelling electrodes. Here we report that gamma networks desynchronize and theta networks synchronize during encoding and retrieval. Furthermore, for nearly all brain regions we studied, gamma power rises as that region desynchronizes with gamma activity elsewhere in the brain, establishing gamma as a largely asynchronous phenomenon. The abundant phenomenon of theta synchrony is positively correlated with a brain region's gamma power, suggesting a predominant low-frequency mechanism for inter-regional communication.

Methods for implantation of micro-wire bundles and optimization of single/multi-unit recordings from human mesial temporal lobe.

OBJECTIVE: The authors report methods developed for the implantation of micro-wire bundles into mesial temporal lobe structures and subsequent single neuron recording in epileptic patients undergoing in-patient diagnostic monitoring. This is done with the intention of lowering the perceived barriers to routine single neuron recording from deep brain structures in the clinical setting. APPROACH: Over a 15 month period, 11 patients were implanted with platinum micro-wire bundles into mesial temporal structures. Protocols were developed for (A) monitoring electrode integrity through impedance testing, (B) ensuring continuous 24-7 recording, (C) localizing micro-wire position and 'splay' pattern and (D) monitoring grounding and referencing to maintain the quality of recordings. MAIN RESULTS: Five common modes of failure were identified: (1) broken micro-wires from acute tensile force, (2) broken micro-wires from cyclic fatigue at stress points, (3) poor in vivo micro-electrode separation, (4) motion artifact and (5) deteriorating ground connection and subsequent drop in common mode noise rejection. Single neurons have been observed up to 14 days post-implantation and on 40% of micro-wires. SIGNIFICANCE: Long-term success requires detailed review of each implant by both the clinical and research teams to identify failure modes, and appropriate refinement of techniques while moving forward. This approach leads to reliable unit recordings without prolonging operative times, which will help increase the availability and clinical viability of human single neuron data.

Theta oscillations in human cortex during a working-memory task: evidence for local generators.

Cortical theta appears important in sensory processing and memory. Intracanial electrode recordings provide a high spatial resolution method for studying such oscillations during cognitive tasks. Recent work revealed sites at which oscillations in the theta range (4-12 Hz) could be gated by a working-memory task: theta power was increased at task onset and continued until task offset. Using a large data set that has now been collected (10 participants/619 recording sites), we have sufficient sampling to determine how these gated sites are distributed in the cortex and how they are synchronized. A substantial fraction of sites in occipital/parietal (45/157) and temporal (23/280) cortices were gated by the task. Surprisingly, this aspect of working-memory function was virtually absent in frontal cortex (2/182). Coherence measures were used to analyze the synchronization of oscillations. We suspected that because of their coordinate regulation by the working-memory task, gated sites would have synchronized theta oscillations. We found that, whereas nearby gated sites (<20 mm) were often but not always coherent, distant gated sites were almost never coherent. Our results imply that there are local mechanisms for the generation of cortical theta.

Reset of human neocortical oscillations during a working memory task.

Both amplitude and phase of rhythmic slow-wave electroencephalographic activity are physiological correlates of learning and memory in rodents. In humans, oscillatory amplitude has been shown to correlate with memory; however, the role of oscillatory phase in human memory is unknown. We recorded intracranial electroencephalogram from human cortical and hippocampal areas while subjects performed a short-term recognition memory task. On each trial, a series of four list items was presented followed by a memory probe. We found agreement across trials of the phase of oscillations in the 7- to 16-Hz range after randomly timed stimulus events, evidence that these events either caused a phase shift in the underlying oscillation or initiated a new oscillation. Phase locking in this frequency range was not generally associated with increased poststimulus power, suggesting that stimulus events reset the phase of ongoing oscillations. Different stimulus classes selectively modulated this phase reset effect, with topographically distinct sets of recording sites exhibiting preferential reset to either probe items or to list items. These findings implicate the reset of brain oscillations in human working memory.

Theta returns.

Recent physiological studies have implicated theta - a high-amplitude 4-8 Hz oscillation that is prominent in rat hippocampus during locomotion, orienting and other voluntary behaviors - in synaptic plasticity, information coding and the function of working memory. Intracranial recordings from human cortex have revealed evidence of high-amplitude theta oscillations throughout the brain, including the neocortex. Although its specific role is largely unknown, the observation of human theta has begun to reveal an intriguing connection between brain oscillations and cognitive processes.

An autoassociative neural network model of paired-associate learning.

Hebbian heteroassociative learning is inherently asymmetric. Storing a forward association, from item A to item B, enables recall of B (given A), but does not permit recall of A (given B). Recurrent networks can solve this problem by associating A to B and B back to A. In these recurrent networks, the forward and backward associations can be differentially weighted to account for asymmetries in recall performance. In the special case of equal strength forward and backward weights, these recurrent networks can be modeled as a single autoassociative network where A and B are two parts of a single, stored pattern. We analyze a general, recurrent neural network model of associative memory and examine its ability to fit a rich set of experimental data on human associative learning. The model fits the data significantly better when the forward and backward storage strengths are highly correlated than when they are less correlated. This network-based analysis of associative learning supports the view that associations between symbolic elements are better conceptualized as a blending of two ideas into a single unit than as separately modifiable forward and backward associations linking representations in memory.

Distinct patterns of brain oscillations underlie two basic parameters of human maze learning.

We examine how oscillations in the intracranial electroencephalogram (iEEG) relate to human maze learning. Theta- band activity (4-12 Hz in rodents; 4-8 Hz in humans) plays a significant role in memory function in rodents and in humans. Recording intracranially in humans, we have reported task-related, theta-band rhythmic activity in the raw trace during virtual maze learning and during a nonspatial working memory task. Here we analyze oscillations during virtual maze learning across a much broader range of frequencies and analyze their relationship to two task variables relevant to learning. We describe a new algorithm for detecting oscillatory episodes that takes advantage of the high signal-to-noise ratio and high temporal resolution of the iEEG. Accounting for the background power spectrum of the iEEG, the algorithm allows us to directly compare levels of oscillatory activity across frequencies within the 2- to 45-Hz band. We report that while episodes of oscillatory activity are found at various frequencies, most of the rhythmic activity during virtual maze learning occurs within the theta band. Theta oscillations are more prevalent when the task is made more difficult (manipulation of maze length). However, these oscillations do not tend to covary significantly with decision time, a good index of encoding and retrieval operations. In contrast, lower- and higher-frequency oscillations do covary with this variable. These results suggest that while human cortically recorded theta might play a role in encoding, the overall levels of theta oscillations tell us little about the immediate demands on encoding or retrieval. Finally, different patterns of oscillations may reflect distinct underlying aspects of memory function.

Gating of human theta oscillations by a working memory task.

Electrode grids on the cortical surface of epileptic patients provide a unique opportunity to observe brain activity with high temporal-spatial resolution and high signal-to-noise ratio during a cognitive task. Previous work showed that large-amplitude theta frequency oscillations occurred intermittently during a maze navigation task, but it was unclear whether theta related to the spatial or working memory components of the task. To determine whether theta occurs during a nonspatial task, we made recordings while subjects performed the Sternberg working memory task. Our results show event-related theta and reveal a new phenomenon, the cognitive "gating" of a brain oscillation: at many cortical sites, the amplitude of theta oscillations increased dramatically at the start of the trial, continued through all phases of the trial, including the delay period, and decreased sharply at the end. Gating could be seen in individual trials and varying the duration of the trial systematically varied the period of gating. These results suggest that theta oscillations could have an important role in organizing multi-item working memory.

Optic flow helps humans learn to navigate through synthetic environments.

Self-movement through an environment generates optic flow, a potential source of heading information. But it is not certain that optic flow is sufficient to support navigation, particularly navigation along complex, multi-legged paths. To address this question, we studied human participants who navigated synthetic environments with and without salient optic flow. Participants used a keyboard to control realistic simulation of self-movement through computer-rendered, synthetic environments. Because these environments comprised series of identically textured virtual corridors and intersections, participants had to build up some mental representation of the environment in order to perform. The impact of optic flow on learning was examined in two experiments. In experiment 1, participants learned to navigate multiple T-junction mazes with and without accompanying optic flow. Optic flow promoted faster learning, mainly by preventing disorientation and backtracking in the maze. In experiment 2, participants found their way around a virtual city-block environment, experiencing two different kinds of optic flow as they went. By varying the rate at which the display was updated, we created optic flow that was either fluid or choppy. Here, fluid optic flow (as compared with choppy optic flow) enabled participants to locate a remembered target position more accurately. When other cues are unavailable, optic flow can be a significant aid in wayfinding. Among other things, optic flow can facilitate path integration, which involves updating a mental representation of place by combining the trajectories of previously travelled paths [corrected].

A functional relation between learning and organization in free recall.

It is well known that multitrial free recall is accompanied by increased organization of output over learning trials, even when the order of presentation is randomized. We compared the relation between learning and organization in 30 young and 30 older adults as they learned categorized materials to a criterion of 100% recall. The importance of this age manipulation was that it allowed us to examine, using two groups that differ significantly in their learning ability, whether organization and learning follow the same function. As was expected, older adults showed less organization on any given learning trial. However, when equated for degree of learning, the older adults showed approximately the same level of organization as the young. This finding suggests that the organization-learning relation remains invariant in the face of significant differences in participants' mnemonic abilities.

Interresponse times in serial recall: effects of intraserial repetition.

The authors examined the effects of intraserial repetition on multitrial serial learning of random consonant lists, analyzing both learning rates and perfect trial interresponse times (IRTs). Lists varied along 3 dimensions: list length, presence or absence of a repeated element, and lag between repeated elements. After achieving a forward-recall criterion on a given list, participants (N = 20) attempted backward recall. At small lags, IRTs between the repeated elements were very short (compared with IRTs from identical positions in nonrepetition lists). At larger lags, the IRT to recall the second repeated item was substantially longer than in control lists. These results reveal a latency analogue of the Ranschburg pattern seen in accuracy data. A Ranschburg pattern was also found in participants' learning rates. These results both generalize the Ranschburg phenomenon and present further challenges to theories of serial order memory.

Contextual variability and serial position effects in free recall.

In immediate free recall, words recalled successively tend to come from nearby serial positions. M. J. Kahana (1996) documented this effect and showed that this tendency, which the authors refer to as the lag recency effect, is well described by a variant of the search of associative memory (SAM) model (J. G. W. Raaijmakers & R. M. Shiffrin, 1980, 1981). In 2 experiments, participants performed immediate, delayed, and continuous distractor free recall under conditions designed to minimize rehearsal. The lag recency effect, previously observed in immediate free recall, was also observed in delayed and continuous distractor free recall. Although two-store memory models, such as SAM, readily account for the end-of-list recency effect in immediate free recall, and its attenuation in delayed free recall, these models fail to account for the long-term recency effect. By means of analytic simulations, the authors show that both the end of list recency effect and the lag recency effect, across all distractor conditions, can be explained by a single-store model in which context, retrieved with each recalled item, serves as a cue for subsequent recalls.

Human theta oscillations exhibit task dependence during virtual maze navigation.

Theta oscillations (electroencephalographic activity with a frequency of 4-8 Hz) have long been implicated in spatial navigation in rodents; however, the role of theta oscillators in human spatial navigation has not been explored. Here we describe subdural recordings from epileptic patients learning to navigate computer-generated mazes. Visual inspection of the raw intracranial signal revealed striking episodes of high-amplitude slow-wave oscillations at a number of areas of the cortex, including temporal cortex. Spectral analysis showed that these oscillations were in the theta band. These episodes of theta activity, which typically last several cycles, are dependent on task characteristics. Theta oscillations occur more frequently in more complex mazes; they are also more frequent during recall trials than during learning trials.

Adult age differences in the temporal characteristics of category free recall.

Two experiments are reported that examined the temporal structure of recall for categorizable word lists by younger and older adults. All participants showed response bursting, in which recall order is clustered by semantic category, with longer interresponse times (IRTs) appearing between categories than within categories. Experiment 1 demonstrated that older adults, even when matched to younger adults in overall accuracy, differed in the rate of increase of between-category IRTs with output position, but not in within-category IRTs. Experiment 2 showed that this interaction is eliminated when the names of the response categories are provided to the participants. Results are interpreted in terms of combined effects of an age-compromised episodic memory system (between-category IRTs) accompanied by a comparatively preserved semantic system (within-category IRTs) in healthy aging.

Associative retrieval processes in free recall.

I present a new method for analyzing associative processes in free recall. While previous research has emphasized the prominence of semantic organization, the present method illustrates the importance of association by contiguity. This is done by examining conditional response probabilities in the output sequence. For a given item recalled, I examine the probability and latency that it follows an item from a nearby or distant input position. These conditional probabilities and latencies, plotted as a function of the lag between studied items, reveal several regularities about output order in free recall. First, subjects tend to recall items more often and more rapidly from adjacent input positions than from remote input positions. Second, subjects are about twice as likely to recall adjacent pairs in the forward than in the backward direction and are significantly faster in doing so. These effects are observed at all positions in the output sequence. The asymmetry effect is theoretically significant because, in cued recall, nearly symmetric retrieval is found at all serial positions (Kahana, 1995; Murdock, 1962). An attempt is made to fit the search of associative memory model (Raaijmakers & Shiffrin, 1980, 1981) with and without symmetric interitem associations to these data. Other models of free recall are also discussed.

The predictive value of discriminatory human chorionic gonadotropin levels in the diagnosis of implantation outcome in in vitro fertilization cycles.

OBJECTIVE: To determine if early serum hCG levels are predictive of implantation outcome in patients undergoing IVF-ET. DESIGN: Retrospective study of IVF cycles using receiver operator characteristic curve (ROC) analysis. SETTING: Tertiary-care, university hospital-affiliated IVF program. PATIENTS: Three hundred fifty-one conception cycles were studied. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Implantation failure, defined as chemical pregnancies, ectopic gestations, and first trimester abortions, or implantation success, defined as delivered singleton and multiple pregnancies, and second trimester abortions. RESULTS: For each post-ET day 14 to 20, mean hCG levels of the implantation success group were significantly greater than implantation failure outcomes (P < 0.0001). Using ROC curve analysis, hCG cutoff values for each post-ET day were calculated for optimal discrimination of implantation failure from implantation success cycles. A patient with an hCG measurement greater than the calculated cutoff value had a > or = 90% chance of having an implantation success after IVF-ET. CONCLUSION: Discriminatory hCG cutoff values may be useful in predicting implantation outcome in IVF-ET cycles and may guide clinicians in identifying those pregnancies at risk for adverse outcomes and instituting more intensive surveillance in this population. This information also may be useful in providing counseling to IVF patients regarding pregnancy prognosis and result in cost savings.

Classification and perceived similarity of compound gratings that differ in relative spatial phase.

Discrimination studies suggest that two, and only two, channels encode relative spatial phase shifts in compound gratings (Bennett & Banks, 1991; Field & Nachmias, 1984). The more sensitive channel consists of even-symmetric filters and responds best to cosine phase shifts (e.g., 0 degree-180 degrees); the other consists of odd-symmetric filters and responds best to sine phase shifts (e.g., 90 degrees-270 degrees). The present experiments investigated whether the two-channel model generalizes to suprathreshold perceptual tasks. Experiment 1 examined classification learning of compound gratings, consisting of a fundamental (f) and second harmonic (2f), that differed in 2f contrast and relative phase. Experiments 2 and 3 measured the perceived similarity of f + 2f gratings. The results of Experiment 1 were broadly consistent with the predictions of the two-channel model. Specifically, the classification data were best explained by assuming that classification was based on the responses of differentially sensitive even- and odd-symmetric filters. In Experiments 2 and 3, two-dimensional multidimensional scaling solutions provided a good account for the similarity judgments. In Experiment 2, Dimension 1 was strongly correlated with cosine phase, and Dimension 2 was moderately correlated with sine phase. In Experiment 3, cosine phase was again strongly related to Dimension 1, whereas the absolute value of sine phase was strongly related to Dimension 2. Overall, these results suggest that the two-channel model of phase discrimination provides a useful framework for interpreting classification and similarity judgments of compound gratings.