Impaired sequential and partially compensated probabilistic skill learning in Parkinson's disease

The striatal dopaminergic dysfunction in Parkinson's disease (PD) has been associated with deficits in skill learning in numerous studies, but some of the findings remain controversial. Our aim was to explore the generality of the learning deficit using two widely reported skill learning tasks in the same group of Parkinson's patients. Thirty-four patients with PD (mean age: 62.83 years, SD: 7.67) were compared to age-matched healthy adults. Two tasks were employed: the Serial Reaction Time Task (SRT), testing the learning of motor sequences, and the Weather Prediction (WP) task, testing non-sequential probabilistic category learning. On the SRT task, patients with PD showed no significant evidence for sequence learning. These results support and also extend previous findings, suggesting that motor skill learning is vulnerable in PD. On the WP task, the PD group showed the same amount of learning as controls, but they exploited qualitatively different strategies in predicting the target categories. While controls typically combined probabilities from multiple predicting cues, patients with PD instead focused on individual cues. We also found moderate to high correlations between the different measures of skill learning. These findings support our hypothesis that skill learning is generally impaired in PD, and can in some cases be compensated by relying on alternative learning strategies.     

Dorsolateral prefrontal cortex mediates working memory processes in motor skill learning

Neuroimaging studies have shown that the dorsolateral prefrontal cortex (DLPFC) is recruited during motor skill learning, which suggests the involvement of the DLPFC in working memory (WM) processes, such as selection and integration of motor representations temporarily stored in WM. However, direct evidence linking activation of the DLPFC to WM storage and manipulation during motor skill learning in real-time is rare. In this study, we conducted two experiments to investigate the causal role of DLPFC activity in WM storage and manipulation during motor skill learning under low and high WM-demand conditions. Participants received continuous theta burst stimulation (cTBS) and sham stimulation (crossover design) over the left DLPFC (experiment 1) or right DLPFC (experiment 2). Before and after stimulation, participants in both experiments performed a sequential finger-tapping (SFT) task containing repeated sequence (low-WM demand) and non-repeated sequence (high-WM demand) conditions which are used to study WM processes. The number of correct sequences (NoCS) and reproduction error rate were analyzed. Learning gains in NoCS improved significantly with the practice for both sequence types in the presence of either stimulation type. Compared to sham stimulation, cTBS over the left DLPFC resulted in significantly reduced learning gains in NoCS for non-repeated sequences. These results suggest that the left DLPFC contributes to WM manipulation during motor skill learning.     

Artificial grammar learning in Alzheimer’s disease

Patients with early Alzheimer’s disease (AD) exhibit impaired declarative memory although some forms of nondeclarative memory are intact. Performance on perceptual nondeclarative memory tasks is often preserved in AD, whereas conceptual nondeclarative memory is often impaired. A conceptual nondeclarative learning task that has been studied in amnesic patients is the artificial grammar learning (AGL) task. Healthy participants and patients with impaired declarative memory both acquire information about an underlying rule structure in this task and exhibit the ability to identify rule-conforming items, despite the subjective experience of guessing at the response. In this study, 12 patients diagnosed with early AD were tested on the AGL task and a matched recognition task. The patients were able to reliably distinguish rule-conforming items from others, indicating successful AGL. Performance of the AD patients was impaired, relative to controls, on a similar recognition task, although they were found to use information about the grammaticality of study items in an attempt to improve their recognition performance. The AD patients showed a dissociation similar to that seen in anterograde amnesia: impaired recognition memory in conjunction with successful AGL. This finding suggests that the brain areas that support AGL are not compromised early in the course of AD. In addition, the nondeclarative memory of the AD patients acquired during AGL appeared to influence their performance on a declarative memory task, suggesting an interaction between this nondeclarative memory task and declarative memory.     

左侧背外侧前额叶在程序性运动学习中的作用

程序性运动学习包括序列学习和随机学习。神经影像学研究表明背外侧前额叶皮层(DLPFC)和初级运动皮层(M1)在程序性运动学习中发挥重要作用, 但DLPFC和M1之间的联通性及其与不同程序性运动学习的关系尚不明确。本研究采用连续反应时间任务, 结合经颅磁刺激(TMS)方法, 探讨左侧DLPFC到M1的联通性在不同程序性运动学习中的差异。实验1采用两连发TMS探测DLPFC到M1的最佳投射时间点; 实验2, 被试分为2组, 分别进行序列学习和随机学习, 在学习前、后采集行为学数据, 以及M1的运动诱发电位和DLPFC-M1联通性的电生理学数据。行为学结果发现序列学习组的学习效果更佳; 电生理学结果发现, 两组被试学习前、后M1的运动诱发电位均未发生改变; 在最佳时间投射点、适当刺激强度下, 序列学习组DLPFC-M1联通性发生改变, 且与学习成绩相关, 而随机学习组没有改变。结果说明DLPFC到M1的联通性增强可能是序列学习成绩更佳的重要原因, 这一结果从电生理角度为DLPFC在运动学习中的作用提供了重要证据。     

Age effects shrink when motor learning is predominantly supported by nondeclarative, automatic memory processes: evidence from golf putting

Can motor learning be equivalent in younger and older adults? To address this question, 48 younger (M = 23.5 years) and 48 older (M = 65.0 years) participants learned to perform a golf-putting task in two different motor learning situations: one that resulted in infrequent errors or one that resulted in frequent errors. The results demonstrated that infrequent-error learning predominantly relied on nondeclarative, automatic memory processes whereas frequent-error learning predominantly relied on declarative, effortful memory processes: After learning, infrequent-error learners verbalized fewer strategies than frequent-error learners; at transfer, a concurrent, attention-demanding secondary task (tone counting) left motor performance of infrequent-error learners unaffected but impaired that of frequent-error learners. The results showed age-equivalent motor performance in infrequent-error learning but age deficits in frequent-error learning. Motor performance of frequent-error learners required more attention with age, as evidenced by an age deficit on the attention-demanding secondary task. The disappearance of age effects when nondeclarative, automatic memory processes predominated suggests that these processes are preserved with age and are available even early in motor learning.     

Age effects shrink when motor learning is predominantly supported by nondeclarative,automatic memory processes: Evidence from golf putting

Can motor learning be equivalent in younger and older adults? To address this question, 48 younger (M?=?23.5 years) and 48 older (M?=?65.0 years) participants learned to perform a golf-putting task in two different motor learning situations: one that resulted in infrequent errors or one that resulted in frequent errors. The results demonstrated that infrequent-error learning predominantly relied on nondeclarative, automatic memory processes whereas frequent-error learning predominantly relied on declarative, effortful memory processes: After learning, infrequent-error learners verbalized fewer strategies than frequent-error learners; at transfer, a concurrent, attention-demanding secondary task (tone counting) left motor performance of infrequent-error learners unaffected but impaired that of frequent-error learners. The results showed age-equivalent motor performance in infrequent-error learning but age deficits in frequent-error learning. Motor performance of frequent-error learners required more attention with age, as evidenced by an age deficit on the attention-demanding secondary task. The disappearance of age effects when nondeclarative, automatic memory processes predominated suggests that these processes are preserved with age and are available even early in motor learning.     

Learning and reminiscence in the pursuit rotor performance of normal and depressed subjects

Ten depressed in-patients were compared, after careful age- and sex-matching, with 12 normal controls on a pursuit tracking task which was performed for two 5-min periods, separated by a 10-min rest. The depressives performed significantly worse than the controls, but both groups showed within and between session improvements. This suggests that the depressive state adversely affects the performance but not the learning of a motor skill. Analysis of performance into high and low frequency components showed that the patients had specific difficulty in following high frequency target movements. This inability to follow high frequency movements was significantly correlated with tapping rate for the patient group, implying that both these measures reflect slowed motor responsivity. The result suggests that factors which interfere with the execution of a motor skill (i.e. motor retardation) do not necessarily interfere with the learning of that skill.     

Transfer of motor learning engages specific neural substrates during motor memory consolidation dependent on the practice structure

The authors investigated how brain activity during motor-memory consolidation contributes to transfer of learning to novel versions of a motor skill following distinct practice structures. They used 1 Hz repetitive Transcranial Magnetic Stimulation (rTMS) immediately after constant or variable practice of an arm movement skill to interfere with primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC). The effect of interference was assessed through skill performance on two transfer targets: one within and one outside the range of practiced movement parameters for the variable practice group. For the control (no rTMS) group, variable practice benefited delayed transfer performance more than constant practice. The rTMS effect on delayed transfer performance differed for the two transfer targets. For the within-range target, rTMS interference had no significant affect on the delayed transfer after either practice structure. However, for the outside-range target, rTMS interference to DLPFC but not M1 attenuated delayed transfer benefit following variable practice. Additionally, for the outside-range target, rTMS interference to M1 but not DLPFC attenuated delayed transfer following constant practice. This suggests that variable practice may promote reliance on DLPFC for memory consolidation associated with outside-range transfer of learning, whereas constant practice may promote reliance on M1 for consolidation and long-term transfer.     

Transfer of Motor Learning Engages Specific Neural Substrates During Motor Memory Consolidation Dependent on the Practice Structure

The authors investigated how brain activity during motor-memory consolidation contributes to transfer of learning to novel versions of a motor skill following distinct practice structures. They used 1 Hz repetitive Transcranial Magnetic Stimulation (rTMS) immediately after constant or variable practice of an arm movement skill to interfere with primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC). The effect of interference was assessed through skill performance on two transfer targets: one within and one outside the range of practiced movement parameters for the variable practice group. For the control (no rTMS) group, variable practice benefited delayed transfer performance more than constant practice. The rTMS effect on delayed transfer performance differed for the two transfer targets. For the within-range target, rTMS interference had no significant affect on the delayed transfer after either practice structure. However, for the outside-range target, rTMS interference to DLPFC but not M1 attenuated delayed transfer benefit following variable practice. Additionally, for the outside-range target, rTMS interference to M1 but not DLPFC attenuated delayed transfer following constant practice. This suggests that variable practice may promote reliance on DLPFC for memory consolidation associated with outside-range transfer of learning, whereas constant practice may promote reliance on M1 for consolidation and long-term transfer.     

Procedural learning in schizophrenia: further consideration on the deleterious effect of neuroleptics

Deficits in procedural learning remain a controversial issue in schizophrenia. This may be related to the nature of the neuroleptic treatment of schizophrenic patients as conventional neuroleptics may be more deleterious than new atypical neuroleptics. However, there is no comparative study on the effect of specific neuroleptics on procedural learning. In this study, three groups of patients treated with different neuroleptics were compared to normal controls on two procedural learning tasks. In a visuo-motor task, patients and controls showed similar learning rates, although schizophrenic patients showed generally lower performances than normal controls. However, patients treated with a conventional neuroleptic, but not those treated with the atypical neuroleptics, showed many fluctuations during the initial learning phase. In a problem-solving task, all groups were comparable in performance and learning fluctuations, but learning rates were lower in patients treated with the neuroleptic showing the higher incidence of extrapyramidal symptoms. This suggests that procedural learning abilities may be significantly affected by neuroleptics in schizophrenia, although the effect may differ between tasks and the specific neuroleptics. Fluctuations in the initial learning phase of the visuo-motor task probably results from a frontal dysfunction while reduced learning rates, such as those observed in the problem solving task, may be attributed to a striatal dysfunction. This is concordant with the differential pharmacological actions of the conventional and atypical neuroleptics in these two cerebral areas.     

Reduced susceptibility to confirmation bias in schizophrenia

Patients with schizophrenia (SZ) show cognitive impairments on a wide range of tasks, with clear deficiencies in tasks reliant on prefrontal cortex function and less consistently observed impairments in tasks recruiting the striatum. This study leverages tasks hypothesized to differentially recruit these neural structures to assess relative deficiencies of each. Forty-eight patients and 38 controls completed two reinforcement learning tasks hypothesized to interrogate prefrontal and striatal functions and their interaction. In each task, participants learned reward discriminations by trial and error and were tested on novel stimulus combinations to assess learned values. In the task putatively assessing fronto-striatal interaction, participants were (inaccurately) instructed that one of the stimuli was valuable. Consistent with prior reports and a model of confirmation bias, this manipulation resulted in overvaluation of the instructed stimulus after its true value had been experienced. Patients showed less susceptibility to this confirmation bias effect than did controls. In the choice bias task hypothesized to more purely assess striatal function, biases in endogenously and exogenously chosen actions were assessed. No group differences were observed. In the subset of participants who showed learning in both tasks, larger group differences were observed in the confirmation bias task than in the choice bias task. In the confirmation bias task, patients also showed impairment in the task conditions with no prior instruction. This deficit was most readily observed on the most deterministic discriminations. Taken together, these results suggest impairments in fronto-striatal interaction in SZ, rather than in striatal function per se.     

Event-related FMRI study of context processing in dorsolateral prefrontal cortex of patients with schizophrenia

Context processing is conceptualized as an executive function involved in voluntary, complex actions such as overcoming automatic responses. The present study tested the hypothesis that context-processing deficits in patients with schizophrenia are associated with a dysfunction of left dorsolateral prefrontal cortex (DLPFC). Using event-related functional magnetic resonance imaging (fMRI), 17 controls and 17 medicated patients performed a version of the AX task in which a learned, automatic response had to be inhibited. In controls, left DLPFC activity increased when preparing to overcome an automatic response, whereas patients with schizophrenia showed no differential activation. In controls, context processing appeared to be associated with the differential representation of cues associated with the need to provide top-down support for overcoming automatic responses. This mechanism appeared to be impaired in patients with schizophrenia.     

Neural Representations of Nondeclarative Memories

ABSTRACT— Nondeclarative learning refers to abilities characterized by a lack of awareness of what has been learned and an independence from medial temporal lobe structures that support conscious memories of facts and events. Neuroimaging approaches have been used extensively in two domains of nondeclarative learning—priming and skill learning—to investigate the neural substrates supporting performance. Recent neuroimaging studies have attempted to understand what is being learned in different tasks in order to inform psychological theories of nondeclarative memory. For example, priming may be considered a form of perceptual learning or a form of stimulus–response learning, and correlations between performance and activation patterns in different regions may suggest the nature of the brain changes that support behavior. The attainment of expertise in a skill has been characterized as greater efficiency of processing in the same neural structures that support novice performance or, alternatively, as the recruitment of additional regions. Current research suggests that, within the domains of priming and skill learning, there is much heterogeneity in the underlying brain representations and psychological theories will need to account for these variations.     

Consistency and error in motor performance

Two response measures that described the consistency and accuracy of motor performance were investigated. A pursuit tracking task was used as the vehicle whereby changes in perceptual motor performance could be monitored over several learning trials. The intra-individual variability of a subject's tracking response was compared to the root mean squared error that was accumulated during each block of trials. Whereas both response measures were sensitive to the changes in performance that occured as a result of practice, neither could be considered sufficiently informative as to be used as a sole indicator of skill acquisition. It appears that both consistency and error measures are needed to describe the subjects' performance as they acquire a perceptual motor skill.     

Consolidation of sensorimotor learning during sleep

Consolidation of nondeclarative memory is widely believed to benefit from sleep. However, evidence is mainly limited to tasks involving rote learning of the same stimulus or behavior, and recent findings have questioned the extent of sleep-dependent consolidation. We demonstrate consolidation during sleep for a multimodal sensorimotor skill that was trained and tested in different visual-spatial virtual environments. Participants performed a task requiring the production of novel motor responses in coordination with continuously changing audio-visual stimuli. Performance improved with training, decreased following waking retention, but recovered and stabilized following sleep. These results extend the domain of sleep-dependent consolidation to more complex, adaptive behaviors.     

Is implicit sequence learning impaired in schizophrenia? A meta-analysis

Cognition in schizophrenia seems to be characterized by impaired performance on most tests of explicit or declarative learning contrasting with relatively intact performance on most tests of implicit or procedural learning. At the same time there have been conflicting results for studies that have used the Serial Reaction Time (SRT) task to examine implicit learning in people with schizophrenia. In the present research, we used meta-analysis to clarify whether or not people with schizophrenia show impaired performance on the SRT task. A systematic review found nine studies published in peer review journals that had each compared the performance of a group of people with schizophrenia with healthy controls on the standard SRT task or a variant of it. The resulting meta-analysis represented the responses of 205 participants with schizophrenia and 159 healthy controls on the SRT task. The analysis found that participants with schizophrenia perform less well than controls reflected by a pooled effect size of 0.51. A secondary analysis of all nine studies found that they all reported a point estimate of the change in reaction time between sequence and random trials that was greater for the controls. We conclude that there is a moderate impairment in implicit sequence learning among people with schizophrenia and speculate on the implications of this for understanding this disorder. Suggestions for improving the methodological quality and statistical reporting of studies of this topic are made.     

Sleep-dependent consolidation of procedural motor memories in children and adults: the pre-sleep level of performance matters

In striking contrast to adults, in children sleep following training a motor task did not induce the expected (offline) gain in motor skill performance in previous studies. Children normally perform at distinctly lower levels than adults. Moreover, evidence in adults suggests that sleep dependent offline gains in skill essentially depend on the pre-sleep level of performance. Against this background, we asked whether improving children's performance on a motor sequence learning task by extended training to levels approaching those of adults would enable sleep-associated gains in motor skill in this age group also. Children (4-6 years) and adults (18-35 years) performed on the motor sequence learning task (button-box task) before and after ~2-hour retention intervals including either sleep (midday nap) or wakefulness. Whereas one group of children and adults, respectively, received the standard amount of 10 blocks of training before retention intervals of sleep or wakefulness, a further group of children received an extended training on 30 blocks (distributed across 3 days). A further group of adults received a restricted training on only two blocks before the retention intervals. Children after standard training reached lowest performance levels, whereas in adults performance after standard training was highest. Children with extended training and adults after reduced training reached intermediate performance levels. Only at these intermediate performance levels did sleep induce significant gains in motor sequence skill, whereas performance did not benefit from sleep in the low-performing children or in the high-performing adults. Spindle counts in the post-training nap were correlated with performance gains at retrieval only in the adults benefitting from sleep. We conclude that, across age groups, sleep induces the most robust gain in motor skill at an intermediate pre-sleep performance level. In low-performing children sleep-dependent improvements in skill may be revealed only after enhancing the pre-sleep performance level by extended training.     

Stimulus timing by people with Parkinson's disease

Previous literature suggests that Parkinson’s disease is marked by deficits in timed behaviour. However, the majority of studies of central timing mechanisms in patients with Parkinson’s disease have used timing tasks with a motor component. Since the motor abnormalities are a defining feature of the condition, the status of timing in Parkinson’s disease remains uncertain. Data are reported from patients with mild to moderate Parkinson’s disease (both on and off medication) and age- and IQ-matched controls on a range of stimulus timing tasks without counting. Tasks used were temporal generalization, bisection, threshold determination, verbal estimation, and a memory for duration task. Performance of patients was generally “normal” on all tasks, but significant differences from performance of controls were found on the memory for duration task. Among the “normal” effects noted were arithmetic mean bisection, asymmetric temporal generalization gradients, and subjective shortening on the memory for duration task. The results suggest (a) that some previous reports of timing “deficits” in Parkinson’s patients were possibly due to the use of tasks requiring a timed manual response and (b) small differences between patients and controls may be found on tasks where two stimuli are presented on each trial, whether patients are on medication or off it.     

Perceptual training strongly improves visual motion perception in schizophrenia

Schizophrenia patients exhibit perceptual and cognitive deficits, including in visual motion processing. Given that cognitive systems depend upon perceptual inputs, improving patients’ perceptual abilities may be an effective means of cognitive intervention. In healthy people, motion perception can be enhanced through perceptual learning, but it is unknown whether this perceptual plasticity remains in schizophrenia patients. The present study examined the degree to which patients’ performance on visual motion discrimination can be improved, using a perceptual learning procedure. While both schizophrenia patients and healthy controls showed decreased direction discrimination thresholds (improved performance) with training, the magnitude of the improvement was greater in patients (47% improvement) than in controls (21% improvement). Both groups also improved moderately but non-significantly on an untrained task—speed discrimination. The large perceptual training effect in patients on the trained task suggests that perceptual plasticity is robust in schizophrenia and can be applied to develop bottom-up behavioral interventions.     

Retroactive interference and mental practice effects on motor performance: a pilot study

This study examined the effect of similar versus dissimilar retroactive interference on the mental practice effects for performing a novel motor skill. Research has shown that mental practice of a motor task can interfere with learning and performance of the task; however, little is known about how different retroactive interference activities affect mental practice effects. 90 volunteers ages 18 to 51 years (M=26.8, SD=9.6) completed a pre-test and post-test of 10 sets of five trials of a throwing task with the non-preferred hand. In the practice phase, participants mentally practiced the throwing task and then mentally practiced a task that was similar, dissimilar, or completed an unrelated reading task. Performance for all groups improved from pre- to post-test; however, there were no differences in increases for the three groups. The findings suggest that mental practice of similar and dissimilar tasks produced no significant interference in performance.