Baseline sensorimotor GABA levels shape neuroplastic processes induced by motor learning in older adults.

Previous research in young adults has demonstrated that both motor learning and transcranial direct current stimulation (tDCS) trigger decreases in the levels of gamma-aminobutyric acid (GABA) in the sensorimotor cortex, and these decreases are linked to greater learning. Less is known about the role of GABA in motor learning in healthy older adults, a knowledge gap that is surprising given the established aging-related reductions in sensorimotor GABA. Here, we examined the effects of motor learning and subsequent tDCS on sensorimotor GABA levels and resting-state functional connectivity in the brains of healthy older participants. Thirty-six older men and women completed a motor sequence learning task before receiving anodal or sham tDCS to the sensorimotor cortex. GABA-edited magnetic resonance spectroscopy of the sensorimotor cortex and resting-state (RS) functional magnetic resonance imaging data were acquired before and after learning/stimulation. At the group level, neither learning nor anodal tDCS significantly modulated GABA levels or RS connectivity among task-relevant regions. However, changes in GABA levels from the baseline to post-learning session were significantly related to motor learning magnitude, age, and baseline GABA. Moreover, the change in functional connectivity between task-relevant regions, including bilateral motor cortices, was correlated with baseline GABA levels. These data collectively indicate that motor learning-related decreases in sensorimotor GABA levels and increases in functional connectivity are limited to those older adults with higher baseline GABA levels and who learn the most. Post-learning tDCS exerted no influence on GABA levels, functional connectivity or the relationships among these variables in older adults.

Search asymmetry in a serial auditory task: Neural source analyses of EEG implicate attention strategies.

Here we report a detailed analysis of the fast network dynamics underlying P3a and P3b event-related potential (ERP) subcomponents generated during an unconventional serial auditory search paradigm. We dissect the electroencephalographic (EEG) data from an earlier study of ours, using a variety of advanced signal processing techniques, in order to discover how the brain is processing auditory targets differently when they possess a rare, salient, unpredictable feature not shared with distractors than when targets lack this feature but distractors have it. We find that brain regions associated with the Ventral Attention Network (VAN) are the primary neural generators of the P3a subcomponent in response to feature-present targets, whereas regions associated with the Dorsal Attention Network (DAN), as well as regions associated with detecting auditory oddball stimuli (ODD), may be the primary neural generators of the P3b, in the context of our study, and perhaps in search paradigms in general. Moreover, measurements of the time courses of oscillatory power changes and inter-regional synchronization in theta and low-gamma frequency bands were consistent with the early activation and synchronization within the VAN associated with the P3a subcomponent, and with the later activation and synchronization within the DAN and ODD networks associated with the P3b subcomponent. Implications of these finding for the mechanisms underlying search asymmetry phenomena are discussed.

Effectiveness of the method of loci is only minimally related to factors that should influence imagined navigation.

The method of loci is arguably the most famous mnemonic strategy and is highly effective for memorising lists of non-spatial information in order. As described and instructed, this strategy apparently relies on a spatial/navigational metaphor. The user imagines moving through an environment, placing (study) and reporting (recall) list items along the way. However, whether the method relies critically on this spatial/navigation metaphor is unknown. An alternative hypothesis is that the navigation component is superfluous to memory success, and the method of loci is better viewed as a special case of a larger class of imagery-based peg strategies. Training participants on three virtual environments varying in their characteristics (an apartment, an open field, and a radial-arm maze), we asked participants to use each trained environment as the basis of the method of loci to learn five 11-word lists. Performance varied significantly across environment. However, the effects were small in magnitude. Further tests suggested that navigation-relevant knowledge and ability were not major determinants of success in verbal memory, even for participants who were confirmed to have been compliant with the strategy. These findings echo neuroimaging findings that navigation-based cognition does occur during application of the method of loci, but imagined navigation is unlikely to be directly responsible for its effectiveness. Instead, the method of loci may be best viewed as a variant of peg methods.

Transient synchronization of hippocampo-striato-thalamo-cortical networks during sleep spindle oscillations induces motor memory consolidation.

Sleep benefits motor memory consolidation. This mnemonic process is thought to be mediated by thalamo-cortical spindle activity during NREM-stage2 sleep episodes as well as changes in striatal and hippocampal activity. However, direct experimental evidence supporting the contribution of such sleep-dependent physiological mechanisms to motor memory consolidation in humans is lacking. In the present study, we combined EEG and fMRI sleep recordings following practice of a motor sequence learning (MSL) task to determine whether spindle oscillations support sleep-dependent motor memory consolidation by transiently synchronizing and coordinating specialized cortical and subcortical networks. To that end, we conducted EEG source reconstruction on spindle epochs in both cortical and subcortical regions using novel deep-source localization techniques. Coherence-based metrics were adopted to estimate functional connectivity between cortical and subcortical structures over specific frequency bands. Our findings not only confirm the critical and functional role of NREM-stage2 sleep spindles in motor skill consolidation, but provide first-time evidence that spindle oscillations [11-17 Hz] may be involved in sleep-dependent motor memory consolidation by locally reactivating and functionally binding specific task-relevant cortical and subcortical regions within networks including the hippocampus, putamen, thalamus and motor-related cortical regions.

The effects of inter-trial interval on implicit learning of sequential visual isometric pinch task.

Sequential visual isometric pinch task (SVIPT) has been recently used as a visuomotor sequence task in clinical research. The influence of varying intervals between sequenced trials on the acquisition of implicit sequence learning is not yet determined for SVIPT. The aim of this study was to investigate the effects of inter-trial interval (ITI) on implicit motor sequence learning using SVIPT. A total of 32 healthy participants with mean age 31.3 ± 4.5 years participated in this study. Participants were randomly assigned to one of four ITI groups; (1, 2, 3 and 4 s). They were instructed to control their force on a force transducer to reach a number of targets which appeared on the computer screen by changing the pinch force exerted onto the transducer. In this study, outcome measures were movement time, error rate and skill, which were measured before and after training. Our results indicated that motor sequence learning similarly affected various ITIs. Indeed, all participants exhibited same improvement in implicit learning of SVIPT even though the ITIs varied from 1 to 4 s. Our findings suggest that implicit learning of SVIPT is independent of ITI within this range in healthy individuals.

The effects of ordinal load on incidental temporal learning.

How can we grasp the temporal structure of events? A few studies have indicated that representations of temporal structure are acquired when there is an intention to learn, but not when learning is incidental. Response-to-stimulus intervals, uncorrelated temporal structures, unpredictable ordinal information, and lack of metrical organization have been pointed out as key obstacles to incidental temporal learning, but the literature includes piecemeal demonstrations of learning under all these circumstances. We suggest that the unacknowledged effects of ordinal load may help reconcile these conflicting findings, ordinal load referring to the cost of identifying the sequence of events (e.g., tones, locations) where a temporal pattern is embedded. In a first experiment, we manipulated ordinal load into simple and complex levels. Participants learned ordinal-simple sequences, despite their uncorrelated temporal structure and lack of metrical organization. They did not learn ordinal-complex sequences, even though there were no response-to-stimulus intervals nor unpredictable ordinal information. In a second experiment, we probed learning of ordinal-complex sequences with strong metrical organization, and again there was no learning. We conclude that ordinal load is a key obstacle to incidental temporal learning. Further analyses showed that the effect of ordinal load is to mask the expression of temporal knowledge, rather than to prevent learning.

Disentangling beat perception from sequential learning and examining the influence of attention and musical abilities on ERP responses to rhythm.

Beat perception is the ability to perceive temporal regularity in musical rhythm. When a beat is perceived, predictions about upcoming events can be generated. These predictions can influence processing of subsequent rhythmic events. However, statistical learning of the order of sounds in a sequence can also affect processing of rhythmic events and must be differentiated from beat perception. In the current study, using EEG, we examined the effects of attention and musical abilities on beat perception. To ensure we measured beat perception and not absolute perception of temporal intervals, we used alternating loud and soft tones to create a rhythm with two hierarchical metrical levels. To control for sequential learning of the order of the different sounds, we used temporally regular (isochronous) and jittered rhythmic sequences. The order of sounds was identical in both conditions, but only the regular condition allowed for the perception of a beat. Unexpected intensity decrements were introduced on the beat and offbeat. In the regular condition, both beat perception and sequential learning were expected to enhance detection of these deviants on the beat. In the jittered condition, only sequential learning was expected to affect processing of the deviants. ERP responses to deviants were larger on the beat than offbeat in both conditions. Importantly, this difference was larger in the regular condition than in the jittered condition, suggesting that beat perception influenced responses to rhythmic events in addition to sequential learning. The influence of beat perception was present both with and without attention directed at the rhythm. Moreover, beat perception as measured with ERPs correlated with musical abilities, but only when attention was directed at the stimuli. Our study shows that beat perception is possible when attention is not directed at a rhythm. In addition, our results suggest that attention may mediate the influence of musical abilities on beat perception.

Long-term phonological knowledge supports serial ordering in working memory.

Serial ordering mechanisms have been investigated extensively in psychology and psycholinguistics. It has also been demonstrated repeatedly that long-term phonological knowledge contributes to serial ordering. However, the mechanisms that contribute to serial ordering have yet to be fully understood. To understand these mechanisms, we demonstrate 2 effects using triples of Japanese nonwords in immediate serial recall. One, a type of bielement frequency effect, is a retrograde compatibility effect. Bielement frequency effects are well-established phenomena whereby a 2-element sequence (e.g., "ka-re") that frequently appears in a language instantiates better recall of any sequence that includes this element (e.g., "ka-re-su-mo"). We demonstrate that bielement frequency affected both the first (e.g., "ka" for "ka-re"; retrograde compatibility effect) and second part of a sequence, indicating the existence of minicontext representations of 2-element sequences. The other effects are the position-element(s) frequency effects, whereby an element (e.g., the mora "ka") that more frequently appears in 1 position of a sequence (e.g., in the first mora of a word) than in other positions facilitates better recall of that element (i.e., the first mora). The effects demonstrated in this article indicate the long-term associations of position representations and elements. These effects are discussed in terms of the extensive learning hypothesis, which assumes that phonological structures are learned gradually. Implications for computational models are also discussed.

The neural basis of implicit learning of task-irrelevant Chinese tonal sequence.

The present study sought to investigate the neural basis of implicit learning of task-irrelevant perceptual sequence. A novel SRT task, the serial syllable identification task (SSI task), was used in which the participants were asked to recognize which one of two Chinese syllables was presented. The tones of the syllables were irrelevant to the task but followed an underlying structured sequence. Participants were scanned while they performed the SSI task. Results showed that, at the behavioral level, faster RTs for the sequential material indicated that task-irrelevant sequence knowledge could be learned. In the subsequent prediction test of knowledge of the tonal cues using subjective measures, we found that the knowledge was obtained unconsciously. At the neural level, the left caudate, bilateral hippocampus and bilateral superior parietal lobule were engaged during the sequence condition relative to the random condition. Further analyses revealed that greater learning-related activation (relative to random) in the right caudate nucleus, bilateral hippocampus and left superior parietal lobule were found during the second half of the training phase compared with the first half. When people reported that they were guessing, the magnitude of the right hippocampus and left superior parietal lobule activations was positively related to the accuracy of prediction test, which was significantly better than chance. Together, the present results indicated that the caudate, hippocampus and superior parietal lobule played critical roles in the implicit perceptual sequence learning even when the perceptual features were task irrelevant.

The neural correlates of speech motor sequence learning.

Speech is perhaps the most sophisticated example of a species-wide movement capability in the animal kingdom, requiring split-second sequencing of approximately 100 muscles in the respiratory, laryngeal, and oral movement systems. Despite the unique role speech plays in human interaction and the debilitating impact of its disruption, little is known about the neural mechanisms underlying speech motor learning. Here, we studied the behavioral and neural correlates of learning new speech motor sequences. Participants repeatedly produced novel, meaningless syllables comprising illegal consonant clusters (e.g., GVAZF) over 2 days of practice. Following practice, participants produced the sequences with fewer errors and shorter durations, indicative of motor learning. Using fMRI, we compared brain activity during production of the learned illegal sequences and novel illegal sequences. Greater activity was noted during production of novel sequences in brain regions linked to non-speech motor sequence learning, including the BG and pre-SMA. Activity during novel sequence production was also greater in brain regions associated with learning and maintaining speech motor programs, including lateral premotor cortex, frontal operculum, and posterior superior temporal cortex. Measures of learning success correlated positively with activity in left frontal operculum and white matter integrity under left posterior superior temporal sulcus. These findings indicate speech motor sequence learning relies not only on brain areas involved generally in motor sequencing learning but also those associated with feedback-based speech motor learning. Furthermore, learning success is modulated by the integrity of structural connectivity between these motor and sensory brain regions.

Irrelevant speech does not interfere with serial recall in early blind listeners.

Phonological working memory is known be (a) inversely related to the duration of the items to be learned (word-length effect), and (b) impaired by the presence of irrelevant speech-like sounds (irrelevant-speech effect). As it is discussed controversially whether these memory disruptions are subject to attentional control, both effects were studied in sighted participants and in a sample of early blind individuals who are expected to be superior in selectively attending to auditory stimuli. Results show that, while performance depended on word length in both groups, irrelevant speech interfered with recall only in the sighted group, but not in blind participants. This suggests that blind listeners may be able to effectively prevent irrelevant sound from being encoded in the phonological store, presumably due to superior auditory processing. The occurrence of a word-length effect, however, implies that blind and sighted listeners are utilizing the same phonological rehearsal mechanism in order to maintain information in the phonological store.

Learned together, extinguished apart: reducing fear to complex stimuli.

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window attenuates fear responding and prevents the return of fear in pure tone Pavlovian fear conditioning. Here we sought to examine whether this effect also applies to a more complex fear memory. First, we show that after fear conditioning to the simultaneous presentation of a tone and a light (T+L) coterminating with a shock, the compound memory that ensues is more resistant to fear extinction than simple tone-shock pairings. Next, we demonstrate that the compound memory can be disrupted by interrupting the reconsolidation of the two individual components using a sequential retrieval+extinction paradigm, provided the stronger compound component is retrieved first. These findings provide insight into how compound memories are encoded, and could have important implications for PTSD treatment.

Boosting human learning by hypnosis.

Human learning and memory depend on multiple cognitive systems related to dissociable brain structures. These systems interact not only in cooperative but also sometimes competitive ways in optimizing performance. Previous studies showed that manipulations reducing the engagement of frontal lobe-mediated explicit attentional processes could lead to improved performance in striatum-related procedural learning. In our study, hypnosis was used as a tool to reduce the competition between these 2 systems. We compared learning in hypnosis and in the alert state and found that hypnosis boosted striatum-dependent sequence learning. Since frontal lobe-dependent processes are primarily affected by hypnosis, this finding could be attributed to the disruption of the explicit attentional processes. Our result sheds light not only on the competitive nature of brain systems in cognitive processes but also could have important implications for training and rehabilitation programs, especially for developing new methods to improve human learning and memory performance.

Encoding location and serial order in auditory working memory: evidence for separable processes.

In this study, we investigated the interactions between temporal and spatial information in auditory working memory. In two experiments, participants were presented with sequences of sounds originating from different locations in space and were then asked to recall either their position or their serial order. In Experiment 1, attention during encoding was manipulated by contrasting 'pure' blocks (i.e., location-only or serial-order-only trials) to 'mixed' blocks (i.e., different percentages of spatial and serial-order trials). In Experiment 2, 'pure' blocks were contrasted to blocks in which spatial and serial-order trials were intermixed with a third task requiring a semantic categorization of sounds. Results from both experiments showed that, whereas serial-order recall is linearly affected by the simultaneous encoding of a concurrent feature, the recall of position is mostly unaffected by concurrent feature encoding. Contrastingly, overall performance level was lower for spatial recall than serial recall. We concluded that serial order and location of items appear to be independently encoded in auditory working memory. Serial order is easier to recall, but strongly affected by the processing of concurrent item dimensions, while item location is more difficult to recall, but relatively automatic, as shown by its strong resistance to interfering dimensions in encoding.

After-training emotional interference may modulate sequence awareness in a serial reaction time task.

The purpose of the present experiment was to investigate the effects of emotional interference on consolidation of sequential learning. In different sessions, 6 groups of subjects were initially trained on a serial reaction time task (SRTT). To modulate consolidation of the newly learned skill, subjects were exposed, after the training, to 1 of 3 (positive, negative or neutral) different classes of emotional stimuli which consisted of a set of emotional pictures combined with congruent emotional musical pieces or neutral sound. Emotional intervention for each subject group was done in 2 different time intervals (either directly after the training session or 6 h later). After a 72 h post-training interval, each group was retested on the SRTT. Re-test performance was evaluated in terms of response times and accuracy during execution of a target sequence. Emotional intervention did not influence either response times or accuracy of re-testing SRTT target task performance, both variables sensitive to implicit knowledge acquired during SRTT training. However, explicit awareness of sequence knowledge after 72 h was enhanced when negative stimuli had been applied at 0 h after training. These findings suggest that consolidation of explicit aspects of procedural learning may be more responsive toward emotional interference than implicit aspects.

Overlap of phonetic features as a determinant of the between-stream phonological similarity effect.

Serial recall from working memory is known to be impaired by the presence of irrelevant background speech, but several prior studies have concluded that the magnitude of the impairment is independent of the phonological relationship between to-be-remembered (TBR) and to-be-ignored (TBI) sources of information. In the present study, we examined the influence of between-stream phonological similarity in serial recall while attending to a heretofore uncontrolled variable, the phonetic feature. We found that TBI items sharing many phonetic features with TBR items produced significantly stronger working-memory impairments than TBI items with minimal phonetic feature overlap. In addition, participants were more likely to report remembering incorrect items that incorporated phonological characteristics of the TBI stream in the high-overlap condition. These findings provide evidence for subphonemic between-stream interactions and suggest that multiple parallel processes contribute to the irrelevant speech effect. We propose that a 2-component model, which combines the assumptions of process- and content-based accounts for the irrelevant speech effect, offers the best explanation for these findings.

Sleep-dependent consolidation of statistical learning.

The importance of sleep for memory consolidation has been firmly established over the past decade. Recent work has extended this by suggesting that sleep is also critical for the integration of disparate fragments of information into a unified schema, and for the abstraction of underlying rules. The question of which aspects of sleep play a significant role in integration and abstraction is, however, currently unresolved. Here, we examined the role of sleep in abstraction of the implicit probabilistic structure in sequential stimuli using a statistical learning paradigm, and tested for its role in such abstraction by searching for a predictive relationship between the type of sleep obtained and subsequent performance improvements using polysomnography. In our experiments, participants were exposed to a series of tones in a probabilistically determined sequential structure, and subsequently tested for recognition of novel short sequences adhering to this same statistical pattern in both immediate- and delayed-recall sessions. Participants who consolidated over a night of sleep improved significantly more than those who consolidated over an equivalent period of daytime wakefulness. Similarly, participants who consolidated across a 4-h afternoon delay containing a nap improved significantly more than those who consolidated across an equivalent period without a nap. Importantly, polysomnography revealed a significant correlation between the level of improvement and the amount of slow-wave sleep obtained. We also found evidence of a time-based consolidation process which operates alongside sleep-specific consolidation. These results demonstrate that abstraction of statistical patterns benefits from sleep, and provide the first clear support for the role of slow-wave sleep in this consolidation.

Serial conditional discrimination and temporal bisection in rats selectively lesioned in the dentate gyrus.

In positive serial conditional discrimination, animals respond during a target stimulus when it is preceded by a feature stimulus, but they do not respond when the same target stimulus is presented alone. Moreover, the feature and target stimuli are separated from each other by an empty interval. The present work aimed to investigate if two durations (4 or 16s) of the same feature stimulus (light) could modulate the operant responses of rats to different levers (A and B) during a 5-s target stimulus (tone). In the present study, lever A was associated with the 4-s light, and lever B was associated with the 16-s light. A 5-s empty interval was included between the light and the tone. In the same training procedure, the rats were also presented with the 5-s tone without the preceding light stimuli. In these trials, the responses were not reinforced. We evaluated the hippocampal involvement of these behavioral processes by selectively lesioning the dentate gyrus with colchicine. Once trained, the rats were submitted to a test using probe trials without reinforcement. They were presented with intermediate durations of the feature stimulus (light) to obtain a temporal bisection curve recorded during the exposure to the target stimuli. The rats from both groups learned to respond with high rates during tones preceded by light and with low rates during tones presented alone, which indicated acquisition of the serial conditional discrimination. The rats were able to discriminate between the 4- and 16-s lights by correctly choosing lever A or B. In the test, the temporal bisection curves from both experimental groups showed a bisection point at the arithmetic mean between 4 and 16s. Such processes were not impaired by the dentate gyrus lesion. Thus, our results showed that different durations of a feature stimulus could result in conditional properties. However, this processing did not appear to depend on the dentate gyrus alone.

Developmental gender differences in the synchronization of auditory event-related oscillations.

OBJECTIVES: The aim of the present study was to explore the neurophysiologic origins of gender differences in auditory processing mechanisms of 7-10 year-old children by means of event-related oscillations. It was tested if the developmental changes in synchronization and magnitude of oscillations in different processing conditions depended on gender. METHODS: Eighteen girls and 18 boys aged 7-10 years were pair wise matched for age and were divided into two age groups. Auditory event-related potentials (ERPs) were recorded in passive, sensorimotor and working memory conditions. Phase-locking and single-trial magnitude of ERPs were analyzed in the delta (0.5-4 Hz), theta (4-7 Hz), slow (7-10 Hz), and fast (10-14 Hz) alpha frequency bands to test the effects of gender, age, and processing condition. RESULTS: The phase-locking of auditory delta, theta, and slow alpha oscillations increased with development only in girls, independently of task processing. Only for the theta phase-locking was this effect additionally affected by the motor-related task. No changes in the magnitude of oscillations accompanied these gender differences in synchronization except for parietal delta responses that also increased with development only in girls. CONCLUSIONS: The results demonstrate that gender differences in auditory ERPs basically originate from a stronger functional synchronization of oscillatory responses generated during stimulus processing. SIGNIFICANCE: The study provides evidence that the functional maturation of oscillatory auditory networks reflected by a progressive developmental increase of synchronization, is accelerated in girls relative to boys between 7 and 10 years of age.

Evidence for model-based action planning in a sequential finger movement task.

In this article, the authors examine whether and how humans use model-free, reflexive strategies and model-based, deliberative strategies in motor sequence learning. They asked subjects to perform the grid-sailing task, which required moving a cursor to different goal positions in a 5 × 5 grid using different key-mapping (KM) rules between 3 finger keys and 3 cursor movement directions. The task was performed under 3 conditions: Condition 1, new KM; Condition 2, new goal position with learned KM; and Condition 3, learned goal position with learned KM; with or without prestart delay time. The performance improvement with prestart delay was significantly larger under Condition 2. This result provides evidence that humans implement a model-based strategy for sequential action selection and learning by using previously learned internal model of state transition by actions.