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In the Serial Reaction Time Task, participants respond to several stimuli usually being unaware that the stimuli follow a predefined sequence while still learning the sequence. In the present study, we aimed to clearly separate explicit intentional learning from implicit incidental learning by either informing participants about all details of the sequence or not informing participants about the existence of the sequence. Further, we explored the influence of anticipatory cues during practice while anticipatory cues were either presented (extrinsically triggered anticipation) or not presented (self-reliant intrinsic anticipation). Participants were tested before and after practice in the Practice Sequence and a Control Sequence. To test automatization, tests were performed in Single-Task and Dual-Task Blocks. Results showed that after learning with explicit instructions, participants memorized the sequence more deeply and executed the sequence faster than after learning without explicit instructions. Further, by learning with anticipatory cues, participants memorized the sequence less deeply and executed the sequence slower than by learning without anticipatory cues. Unexpectedly, automatization was sequence-unspecific and independent of the practice conditions. In conclusion, detailed explicit prior information about the sequence facilitates sequence learning while anticipatory online cues during practice hamper sequence learning.

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A serial reaction time task was used to test whether the representations of a probabilistic second-order sequence structure are (i) stored in an effector-dependent, effector-independent intrinsic or effector-independent visuospatial code and (ii) are inter-manually accessible. Participants were trained either with the dominant or non-dominant hand. Tests were performed with both hands in the practice sequence, a random sequence, and a mirror sequence. Learning did not differ significantly between left and right-hand practice, suggesting symmetric intermanual transfer from the dominant to the non-dominant hand and vice versa. In the posttest, RTs were shorter for the practice sequence than for the random sequence, and longest for the mirror sequence. Participants were unable to freely generate or recognize the practice sequence, indicating implicit knowledge of the probabilistic sequence structure. Because sequence-specific learning did not differ significantly between hands, we conclude that representations of the probabilistic sequence structure are stored in an effector-independent visuospatial code.

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The cholinergic system plays a key role in motor function, but whether pharmacological modulation of cholinergic activity affects motor sequence learning is unknown. The acetylcholine receptor antagonist biperiden, an established treatment in movement disorders, reduces attentional modulation, but whether it influences motor sequence learning is not clear. Using a randomized, double-blind placebo-controlled crossover design, we tested 30 healthy young participants and showed that biperiden impairs the ability to learn sequential finger movements, accompanied by widespread oscillatory broadband power changes (4-25 Hz) in the motor sequence learning network after receiving biperiden, with greater power in the theta, alpha and beta bands over ipsilateral motor and bilateral parietal-occipital areas. The reduced early theta power during a repeated compared with random sequence, likely reflecting disengagement of top-down attention to sensory processes, was disrupted by biperiden. Alpha synchronization during repeated sequences reflects sensory gating and lower visuospatial attention requirements compared with visuomotor responses to random sequences. After biperiden, alpha synchronization was greater, potentially reflecting excessive visuospatial attention reduction, affecting visuomotor responding required to enable sequence learning. Beta oscillations facilitate sequence learning by integrating visual and somatosensory inputs, stabilizing repeated sequences and promoting prediction of the next stimulus. The beta synchronization after biperiden fits with a disruption of the selective visuospatial attention enhancement associated with initial sequence learning. These findings highlight the role of cholinergic processes in motor sequence learning.

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BACKGROUND: Digital neuropsychological tools for diagnosing neurodegenerative diseases in the older population are becoming more relevant and widely adopted because of their diagnostic capabilities. In this context, explicit memory is mainly examined. The assessment of implicit memory occurs to a lesser extent. A common measure for this assessment is the serial reaction time task (SRTT). OBJECTIVE: This study aims to develop and empirically test a digital tablet-based SRTT in older participants with cognitive impairment (CoI) and healthy control (HC) participants. On the basis of the parameters of response accuracy, reaction time, and learning curve, we measure implicit learning and compare the HC and CoI groups. METHODS: A total of 45 individuals (n=27, 60% HCs and n=18, 40% participants with CoI-diagnosed by an interdisciplinary team) completed a tablet-based SRTT. They were presented with 4 blocks of stimuli in sequence and a fifth block that consisted of stimuli appearing in random order. Statistical and machine learning modeling approaches were used to investigate how healthy individuals and individuals with CoI differed in their task performance and implicit learning. RESULTS: Linear mixed-effects models showed that individuals with CoI had significantly higher error rates (b=-3.64, SE 0.86; z=-4.25; P<.001); higher reaction times (F1,41=22.32; P<.001); and lower implicit learning, measured via the response increase between sequence blocks and the random block (ß=-0.34; SE 0.12; t=-2.81; P=.007). Furthermore, machine learning models based on these findings were able to reliably and accurately predict whether an individual was in the HC or CoI group, with an average prediction accuracy of 77.13% (95% CI 74.67%-81.33%). CONCLUSIONS: Our results showed that the HC and CoI groups differed substantially in their performance in the SRTT. This highlights the promising potential of implicit learning paradigms in the detection of CoI. The short testing paradigm based on these results is easy to use in clinical practice.

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RATIONALE: The 5-choice serial reaction time task (5-CSRTT) is commonly used to assess attention in rodents. Manipulation of this task by decreasing the light stimulus duration is often used to probe attentional capacity and causes a decrease in accuracy and an increase in omissions. However, although a decrease in response accuracy is commonly interpreted as a decrease in attention, it is more difficult to interpret an increase in omissions in terms of attentional performance. METHODS: Here we present a series of experiments in rats that seeks to investigate the origins of these key behavioral measures of attention in the 5-CSRTT. After an initial training in the 5-CSRTT, rats were tested in a variable stimulus duration procedure to increase task difficulty and probe visual attentional capacity under several specific controlled conditions. CONCLUSIONS: We found that response accuracy reflects visuospatial sustained attentional processing, as commonly interpreted, while response omission reflects rats' ignorance about the stimulus location, presumably due to failure to pay attention to the curved wall during its presentation. Moreover, when rats lack of relevant information, they choose not to respond instead of responding randomly. Finally, pretreatment with nicotine selectively decreased response omissions, without affecting response accuracy, particularly when the attentional demand was high. Overall, our results indicate that response accuracy and response omission thus correspond to two distinct attentional states.

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Administering anodal transcranial direct current stimulation (tDCS) at the primary motor cortex (M1) at various temporal loci relative to motor training is reported to affect subsequent performance gains. Stimulation administered in conjunction with motor training appears to offer the most robust benefit that emerges during offline epochs. This conclusion is made, however, based on between-experiment comparisons that involved varied methodologies. The present experiment addressed this shortcoming by administering the same 15-minute dose of anodal tDCS at M1 before, during, or after practice of a serial reaction time task (SRTT). It was anticipated that exogenous stimulation during practice with a novel SRTT would facilitate offline gains. Ninety participants were randomly assigned to one of four groups: tDCS before practice, tDCS during practice, tDCS after practice, or no tDCS. Each participant was exposed to 15 min of 2 mA of tDCS and motor training of an eight-element SRTT. The anode was placed at the right M1 with the cathode at the left M1, and the left hand was used to execute the SRTT. Test blocks were administered 1 and 24 h after practice concluded. The results revealed significant offline gain for all conditions at the 1-hour and 24-hour test blocks. Importantly, exposure to anodal tDCS at M1 at any point before, during, or after motor training failed to change the trajectory of skill development as compared to the no-stimulation control condition. These data add to the growing body of evidence questioning the efficacy of a single bout of exogenous stimulation as an adjunct to motor training for fostering skill learning.

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Implicit motor sequence learning (IMSL) is a cognitive function that is known to be associated with impaired motor function in Parkinson's disease (PD). We previously reported positive effects of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) on IMSL in 11 individuals with PD with mild cognitive impairments (MCI), with the largest effects occurring during reacquisition. In the present study, we included 35 individuals with PD, with (n = 15) and without MCI (n = 20), and 35 age- and sex-matched controls without PD, with (n = 13) and without MCI (n = 22). We used mixed-effects models to analyze anodal M1 tDCS effects on acquisition (during tDCS), short-term (five minutes post-tDCS) and long-term reacquisition (one-week post-tDCS) of general and sequence-specific learning skills, as measured by the serial reaction time task. At long-term reacquisition, anodal tDCS resulted in smaller general learning effects compared to sham, only in the PD group, p = .018, possibly due to floor effects. Anodal tDCS facilitated the acquisition of sequence-specific learning (M = 54.26 ms) compared to sham (M = 38.98 ms), p = .003, regardless of group (PD/controls). Further analyses revealed that this positive effect was the largest in the PD-MCI group (anodal: M = 69.07 ms; sham: M = 24.33 ms), p < .001. Although the observed effect did not exceed the stimulation period, this single-session tDCS study confirms the potential of tDCS to enhance IMSL, with the largest effects observed in patients with lower cognitive status. These findings add to the body of evidence that anodal tDCS can beneficially modulate the abnormal basal ganglia network activity that occurs in PD.

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Procedural memory is involved in the acquisition and control of skills and habits that underlie rule and procedural learning, including the acquisition of grammar and phonology. The serial reaction time task (SRTT), commonly used to assess procedural learning, has been shown to have poor stability (test-retest reliability). We investigated factors that may affect the stability of the SRTT in adults. Experiment 1 examined whether the similarity of sequences learned in two sessions would impact stability: test-retest correlations were low regardless of sequence similarity (r < .31). Experiment 2 added a third session to examine whether individual differences in learning would stabilise with further training. There was a small (but nonsignificant) improvement in stability for later sessions (Sessions 1 and 2: r = .42; Sessions 2 and 3: r = .60). Stability of procedural learning on the SRTT remained suboptimal in all conditions, posing a serious obstacle to the use of this task as a sensitive predictor of individual differences and ultimately theoretical advance.

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Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique which was found to have a positive modulatory effect on online sequence acquisition or offline motor consolidation, depending on the relative role of the associated brain region. Primary motor regions (M1) and dorsolateral prefrontal cortices (DLPFC) have both been related to sequential learning. However, research so far did not systematically disentangle their differential roles in online and offline learning especially in more complex sequential paradigms. In this study, the influence of anodal M1 leg area-tDCS and anodal DLPFC-tDCS applied during complex sequential learning (online and offline) was investigated using a complex whole body serial reaction time task (CWB-SRTT) in 42 healthy volunteers. TDCS groups did not differ from sham tDCS group regarding their response and reaction time (online) and also not in terms of overnight consolidation (offline). Sequence specific learning and the number of recalled items also did not differ between groups. Results may be related to unspecific parameters such as timing of the stimulation or current intensity but can also be attributed to the relative role of M1 and DLPFC during early complex learning. Taken together, the current study provides preliminary evidence that M1 leg area or DLPFC modulation by means of tDCS does not improve complex sequential skill learning. SIGNIFICANCE STATEMENT: Understanding motor learning is helpful to deepen our knowledge about the human ability to acquire new skills. Complex sequential learning tasks have only been studied, sparsely, but are particularly mimicking challenges of daily living. The present study studied early motor learning in a complex serial reaction time task while transcranial direct current stimulation (tDCS) was either applied to leg primary motor cortex or bilateral dorsolateral prefrontal cortex. TDCS did not affect sequential learning, neither directly during performance nor in terms of sequence consolidation. Results provide preliminary information that M1 or bilateral DLPFC modulation does not improve early complex motor learning.

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Excessive intake plays a significant role in the development of alcohol use disorder and impacts 15 million Americans annually, with approximately 88 000 dying from alcohol related deaths. Several facets we contribute to alcohol use disorder include impulsivity, motivation, and attention. Previous studies have used the 5-Choice Serial Reaction Time Task (5-Choice) to analyze these types of behaviors using sugar, but recently we have published using 10% alcohol as the reward. This study analyzed 48 mice that were trained to respond for alcohol in the 5-Choice. All mice distributed and analyzed first by alcohol preference and then by consumption. Here, we became interested in a new classification called "engagement". High-engaged and low-engaged mice were determined by the number of correct responses during final Late-Stage training sessions. Interestingly, during Early-Stage training, the mice began to separate themselves into two groups based on their interaction with the task. Throughout both training stages, high-engaged mice displayed a greater number of trials and correct responses, as well as a lower percentage of omissions compared to low-engaged mice. Following three weeks of intermittent access homecage drinking, low-engaged mice showed greater increase in perseverative responding relative to high-engaged. Additionally, low-engaged mice decreased their reward and correct latencies compared to high-engaged mice suggesting an increase in motivation for alcohol. Overall, engagement analysis presents two clearly different groups, with only one being motivated to work for alcohol. These two distinct phenotypes in the 5-Choice could be used to model alcohol motivated behavior, which could help us further understand alcohol use disorder.

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Despite the fact that reliability estimation is crucial for robust inference, it is underutilized in neuroscience and cognitive psychology. Appreciating reliability can help researchers increase statistical power, effect sizes, and reproducibility, decrease the impact of measurement error, and inform methodological choices. However, accurately calculating reliability for many experimental learning tasks is challenging. In this study, we highlight a number of these issues, and estimate multiple metrics of internal consistency and split-half reliability of a widely used learning task on a large sample of 180 subjects. We show how pre-processing choices, task length, and sample size can affect reliability and its estimation. Our results show that the Alternating Serial Reaction Time Task has respectable reliability, especially when learning scores are calculated based on reaction times and two-stage averaging. We also show that a task length of 25 blocks can be sufficient to meet the usual thresholds for minimally acceptable reliability. We further illustrate how relying on a single point estimate of reliability can be misleading, and the calculation of multiple metrics, along with their uncertainties, can lead to a more complete characterization of the psychometric properties of tasks.

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Uncontrollable binge drinking is becoming an increasingly prevalent issue in our society. This is a factor that plays a role in the development of alcohol use disorder (AUD). AUD impacts 15 million Americans annually, with approximately 88,000 dying from alcohol related deaths. There are several aspects of AUD that encourage a strong dependence on alcohol. Impulsivity, motivation, and attention are the primary behavioral facets we contribute to AUD. Many past studies have used the 5-Choice Serial Reaction Time Task (5-Choice) to analyze these types of behaviors using sugar as the reward. We have recently published a study where alcohol was used as a reward in the 5-Choice. 48 mice were trained to respond for alcohol in the 5-Choice, and the analyses for these animals were originally categorized by their alcohol preference and consumption. Upon looking at the data, we became more interested in a new way to classify these mice into groups. High engaged (HE) and low engaged (LE) mice were classified based on their number of correct responses in the last five late-stage sessions. During early-stage training, mice began to separate themselves into two groups based on their interaction with the task. The high-engaged (HE) mice were much more engaged with the task by having a high number of trials and correct responses, as well as a much lower percentage of omissions. The low engaged (LE) mice were not as engaged, this was apparent because of their lower number of trials and correct responses. They also had a much higher percentage of omissions in comparison to HE mice. LE mice presented no significant changes in late-stage training, while HE mice began responding and engaging more. These mice went through a period of intermittent access (IA), where they were allowed to drink alcohol in their cage for 3 weeks. After intermittent access, LE mice increased their responding which suggests an increase in motivation for alcohol as a reward. Engagement analysis presents two clearly different groups, one being motivated to work for alcohol and the other not wanting to work for this reward. These two distinct phenotypes in the 5-Choice could be used to model alcohol motivated behavior, which could help us further understand AUD.

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Action-imagery practice (AIP) is assumed to result in partly different action representations than action-execution practice (AEP). The present study investigated whether focusing on either kinesthetic or visual aspects of a task during practice amplifies or diminishes such differences between AIP and AEP. In ten sessions, four groups, using either AIP or AEP with either kinesthetic or visual focus, practiced a twelve-element sequence in a unimanual serial reaction time task. Tests involved the practice sequence, a mirror sequence, and a different sequence, each performed with the practice and transfer hand. In AIP and AEP, in both hands, reaction times (RTs) were shorter in the practice sequence than in the different sequence, indicating effector-independent visual-spatial sequence representations. Further, RTs were shorter in the practice hand than in the transfer hand in the practice sequence (but not in the different sequence), indicating effector-dependent representations in AEP and AIP. Although the representation types did not differ, learning effects were stronger in AEP than in AIP. Thus, although to a lower extent than in AEP, effector-dependent representations can be acquired using AIP. Contrary to the expectations, the focus manipulation did not have an impact on the acquired representation types. Hence, modality instructions in AIP may not have such a strong impact as commonly assumed, at least in implicit sequence learning.

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Prior research investigating whether and how multisensory information facilitates skill learning is quite mixed; whereas some research points to congruent information improving learning, other work suggests that people become reliant on the redundant information, such that its removal ultimately detracts from the ability to perform a unisensory task. We examined this question using the Serial Interception Sequence Learning (SISL) task, a visuo-motor paradigm in which participants implicitly learn a sequence embedded in noise. We investigated whether adding auditory information in different ways would enhance real time sequence learning and whether any benefits of multisensory learning would persist with visual-only testing. Auditory information was used either as feedback on the visuo-motor task (Experiments 1 and 2) or was presented synchronously with visual information during learning (Experiment 3). Robust sequence-specific performance advantages occurred across conditions and experiments; however, auditory information enhanced real-time performance only when it was synchronized with visual information. Participants were significantly more accurate, faster, and more precise with stimulus-locked auditory information during training. Notably, these benefits did not generalize to the visual-only context, suggesting that the benefits of stimulus-locked auditory information are primarily useful only when the perceptual information is present.

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In humans, it is now established that sequential regularities can be learned implicitly (i.e. without acquiring conscious knowledge) or explicitly (with acquisition of conscious knowledge). Is this dual-processing capability also the case for non-human primates? In this study, we designed a non-verbal task to probe implicit and explicit sequence learning in capuchin monkeys (Sapajus sp., n = 12), human adults (n = 12), and children from 5 to 10 years old (n = 64). After learning spatial sequences on a touchscreen, participants' conscious access to the sequences was probed with a forced choice sequence completion test. All performed above chance level in this test, without being instructed or trained to do so. However, only human adults who reported the presence of regularities performed at ceiling level. We suggest future directions that could build on our findings to disentangle implicit and explicit learning in monkeys and children.

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The Serial Reaction Time task, one of the most widely used tasks to index procedural memory, has been increasingly employed in individual differences research examining the role of procedural memory in language and other cognitive abilities. Yet, despite consistently producing robust procedural learning effects at the group level (i.e. faster responses to sequenced/probable trials versus random/improbable trials), these effects have recently been found to have poor reliability. In this meta-analysis (N = 7), comprising 719 participants (M = 20.81, s.d. = 7.13), we confirm this 'reliability paradox'. The overall retest reliability of the robust procedural learning effect elicited by the SRTT was found to be well below acceptable psychometric standards (r < 0.40). However, split-half reliability within a session is better, with an overall estimate of 0.66. There were no significant effects of sampling (participants' age), methodology (e.g. number of trials, sequence type) and analytical decisions (whether all trials were included when computing the procedural learning scores; using different indexes of procedural learning). Thus, despite producing robust effects at the group-level, until we have a better understanding of the factors that improve the reliability of this task using the SRTT for individual differences research should be done with caution.

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The serial reaction time task is a widely used task in behavioural and cognitive neuroscience to assess human and animal learning. Many publications refer to this task as a 'motor learning task', but it is also a perceptual learning task. We emphasize here that the incorrect use of the term 'motor learning' misleads researchers and medical doctors by emphasizing the motor cortex's exclusive role. It has the potential to lead to the misinterpretation of neuroscientific, neuroimaging and clinical studies. The domino effect has the potential to generate more flawed hypotheses and theories.

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Introduction: The insular cortex is involved in multiple physiological processes including working memory, pain, emotion, and interoceptive functions. Previous studies have indicated that the anterior insular cortex (aIC) also mediates interoceptive attention in humans. However, the exact cellular and physiological function of the aIC in the regulation of this process is still elusive. Methods: In this study, using the 5-choice serial reaction time task (5-CSRTT) testing paradigm, we assessed the role of the aIC in visuospatial attention and impulsiveness in mice. Results: The results showed a dramatic activation of c-Fos in the aIC CaMKIIα neurons after the 5-CSRTT procedure. In vivo fiber photometry revealed enhanced calcium signaling in aIC CaMKIIα neurons when the mice responded correctly. In addition, chemogenetic suppression of aIC CaMKIIα neurons led to increased incorrect responses within the appropriate time. Importantly, pharmacological activation of aIC CaMKIIα neurons enhanced their performance in the 5-CSRTT test. Discussion: These results provide compelling evidence that aIC CaMKIIα neurons are essential for the modulation of attentional processing in mice.

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Attention deficits are common in psychiatric and neurological disorders. The transdiagnostic nature of impaired attention suggests a common set of underlying neural circuits. Yet, there are no circuit-based treatments such as non-invasive brain stimulation currently available due to the lack of sufficiently delineated network targets. Therefore, to better treat attentional deficits, a comprehensive functional dissection of neural circuits underlying attention is imperative. This can be achieved by taking advantage of preclinical animal models and well-designed behavioral assays of attention. The resulting findings in turn can be translated to the development of novel interventions with the goal of advancing them to clinical practice. Here we show that the five-choice serial reaction time task has greatly facilitated the study of the neural circuits underlying attention in a well-controlled setting. We first introduce the task and then focus on its application in preclinical studies on sustained attention, especially in the context of state-of-the-art neuronal perturbations.

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Memory impairment in Alzheimer's disease patients is thought to be associated with the accumulation of amyloid-beta peptides and tau proteins. However, inconsistent reports of cognitive deficits in pre-clinical studies have raised questions about the link between amyloid-beta and cognitive decline. One possible explanation may be that studies reporting memory deficits often involve behavioral assessments that entail a high stress component. In contrast, in tasks without a high stress component transgenic mice do not consistently show declines in memory. The glucocorticoid cascade hypothesis of aging and the vicious cycle of stress framework suggest that stress exacerbates dementia progression by initiating a cycle of hypothalamic-pituitary-adrenal axis activation and subsequent brain deterioration. Using the APPswe/PS1dE9 mouse model of amyloidosis, we assessed whether stressor exposure prior to testing differentially impaired cognitive performance of aged male and female mice. As part of a larger study, mice performed a delayed match-to-position (DMTP) or a 3-choice serial-reaction time (3CSRT) task. Unexpectedly, these mice did not exhibit cognitive declines during aging. Therefore, at 73 and 74 weeks of age, we exposed mice to a predator odor or forced swim stressor prior to testing to determine if stress revealed cognitive deficits. We predicted stressor exposure would decrease performance accuracy more robustly in transgenic vs. non-transgenic mice. Acute stressor exposure increased accuracy in the DMTP task, but not in the 3CSRT task. Our data suggest that acute stressor exposure prior to testing does not impair cognitive performance in APPswe/PS1dE9 mice.