Atypical procedural learning in children with developmental coordination disorder: A combined behavioral and neuroimaging study.

While procedural learning (PL) has been implicated in delayed motor skill observed in developmental coordination disorder (DCD), few studies have considered the impact of co-occurring attentional problems. Furthermore, the neurostructural basis of PL in children remains unclear. We investigated PL in children with DCD while controlling for inattention symptoms, and examined the role of fronto-basal ganglia-cerebellar morphology in PL. Fifty-nine children (6-14 years; nDCD = 19, ncontrol = 40) completed the serial reaction time (SRT) task to measure PL. The Attention-Deficit Hyperactivity Disorder Rating Scale-IV was administered to measure inattention symptoms. Structural T1 images were acquired for a subset of participants (nDCD = 10, ncontrol = 28), and processed using FreeSurfer. Volume was extracted for the cerebellum, basal ganglia, and frontal regions. After controlling for inattention symptoms, the reaction time profile of controls was consistent with learning on the SRT task. This was not the case for those with DCD. SRT task performance was positively correlated with cerebellar cortical volume, and children with DCD trended towards lower cerebellar volume compared to controls. Children with DCD may not engage in PL during the SRT task in the same manner as controls, with this differential performance being associated with atypical cerebellar morphology.

Resting state electroencephalography power correlates with individual differences in implicit sequence learning.

Neuroimaging resting state paradigms have revealed synchronised oscillatory activity is present even in the absence of completing a task or mental operation. One function of this neural activity is likely to optimise the brain's sensitivity to forthcoming information that, in turn, likely promotes subsequent learning and memory outcomes. The current study investigated whether this extends to implicit forms of learning. A total of 85 healthy adults participated in the study. Resting state electroencephalography was first acquired from participants before they completed a serial reaction time task. On this task, participants implicitly learnt a visuospatial-motor sequence. Permutation testing revealed a negative correlation between implicit sequence learning and resting state power in the upper theta band (6-7 Hz). That is, lower levels of resting state power in this frequency range were associated with superior levels of implicit sequence learning. This association was observed at midline-frontal, right-frontal and left-posterior electrodes. Oscillatory activity in the upper theta band supports a range of top-down processes including attention, inhibitory control and working memory, perhaps just for visuospatial information. Our results may be indicating that disengaging theta-supported top-down attentional processes improves implicit learning of visuospatial-motor information that is embedded in sensory input. This may occur because the brain's sensitivity to this type of information is optimally achieved when learning is driven by bottom-up processes. Moreover, the results of this study further demonstrate that resting state synchronised brain activity influences subsequent learning and memory.

EEG microstates in early-to-middle childhood show associations with age, biological sex, and alpha power.

Electroencephalographic (EEG) microstates can provide a unique window into the temporal dynamics of large-scale brain networks across brief (millisecond) timescales. Here, we analysed fundamental temporal features of microstates extracted from the broadband EEG signal in a large (N = 139) cohort of children spanning early-to-middle childhood (4-12 years of age). Linear regression models were used to examine if participants' age and biological sex could predict the temporal parameters GEV, duration, coverage, and occurrence, for five microstate classes (A-E) across both eyes-closed and eyes-open resting-state recordings. We further explored associations between these microstate parameters and posterior alpha power after removal of the 1/f-like aperiodic signal. The microstates obtained from our neurodevelopmental EEG recordings broadly replicated the four canonical microstate classes (A to D) frequently reported in adults, with the addition of the more recently established microstate class E. Biological sex served as a significant predictor in the regression models for four of the five microstate classes (A, C, D, and E). In addition, duration and occurrence for microstate E were both found to be positively associated with age for the eyes-open recordings, while the temporal parameters of microstates C and E both exhibited associations with alpha band spectral power. Together, these findings highlight the influence of age and sex on large-scale functional brain networks during early-to-middle childhood, extending understanding of neural dynamics across this important period for brain development.

Implicit manual and oculomotor sequence learning in developmental language disorder.

Procedural memory functioning in developmental language disorder (DLD) has largely been investigated by examining implicit sequence learning by the manual motor system. This study examined whether poor sequence learning in DLD is present in the oculomotor domain. Twenty children with DLD and 20 age-matched typically developing (TD) children were presented with a serial reaction time (SRT) task. On the task, a visual stimulus repeatedly appears in different positions on a computer display which prompts a manual response. The children were unaware that on the first three blocks and final block of trials, the visual stimulus followed a sequence. On the fourth block, the stimulus appeared in random positions. Manual reaction times (RT) and saccadic amplitudes were recorded, which assessed sequence learning in the manual and oculomotor domains, respectively. Manual RT were sensitive to sequence learning for the TD group, but not the DLD group. For the TD group, manual RT increased when the random block was presented. This was not the case for the DLD group. In the oculomotor domain, sequence learning was present in both groups. Specifically, sequence learning was found to modulate saccadic amplitudes resulting in both DLD and TD children being able to anticipate the location of the visual stimulus. Overall, the study indicates that not all aspects of the procedural memory system are equally impaired in DLD.

Is vegetation cover in key behaviour settings important for early childhood socioemotional function? A preregistered, cross-sectional study.

The environmental influences on early childhood development are understudied. The association between vegetation cover (i.e., trees, shrubs, grassed areas) in four key behaviour settings and socioemotional functioning was investigated in 1196 young children (2-5 years). Emotional difficulties were inversely associated with vegetation cover in the home yard (OR: 0.81 [0.69-0.96]) and neighbourhood (OR: 0.79 [0.67-0.94]), but not in early childhood education and care (ECEC) centre outdoor areas or the ECEC neighbourhood. The higher odds of emotional difficulties associated with lower levels of maternal education was reduced with higher percentages of home yard vegetation cover. There was no evidence of mediation of the relationship between emotional difficulties and vegetation cover by time spent playing outside the home, day or nighttime sleep duration, or physical activity. We found no associations between vegetation cover and conduct, hyperactivity and inattention, peer difficulties, or prosocial behaviours. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=J3HeEiIjVZc.

Non-Invasive Brain Stimulation Does Not Improve Working Memory in Schizophrenia: A Meta-Analysis of Randomised Controlled Trials.

Poor working memory functioning is commonly found in schizophrenia. A number of studies have now tested whether non-invasive brain stimulation can improve this aspect of cognitive functioning. This report used meta-analysis to synthesise the results of these studies to examine whether transcranial electrical stimulation (tES) or repetitive transcranial magnetic stimulation (rTMS) can improve working memory in schizophrenia. The studies included in this meta-analysis were sham-controlled, randomised controlled trials that utilised either tES or rTMS to treat working memory problems in schizophrenia. A total of 22 studies were included in the review. Nine studies administered rTMS and 13 administered tES. Meta-analysis revealed that compared to sham/placebo stimulation, neither TMS nor tES significantly improved working memory. This was found when working memory was measured with respect to the accuracy on working memory tasks (TMS studies: Hedges' g = 0.112, CI95: -0.082, 0.305, p = .257; tES studies Hedges' g = 0.080, CI95: -0.117, 0.277, p = .427) or the speed working memory tasks were completed (rTMS studies: Hedges' g = 0.233, CI95: -0.212, 0.678, p = .305; tES studies Hedges' g = -0.016, CI95: -0.204, 0.173, p = .871). For tES studies, meta-regression analysis found that studies with a larger number of stimulation sessions were associated with larger treatment effects. This association was not found for TMS studies. At present, rTMS and tES is not associated with a reliable improvement in working memory for individuals with schizophrenia.

The mediating effect of language on the development of cognitive and affective theory of mind.

Theory of mind (ToM) development is critical to effective social functioning and appears to depend on complementary language abilities. The current study explored the mediating influence of language on the development of both cognitive and affective ToM. A total of 151 children aged 5-12 years completed ToM (cognitive and affective) and language assessments, and parents provided ratings of their children's empathic ability. Results showed that language mediated the relationship between age and both cognitive and affective ToM but not parent-reported cognitive empathy. Examination of younger and older subgroups revealed that language mediated cognitive and affective ToM differently across developmental periods. Findings highlight the dynamic role that language plays in the development of both cognitive and affective ToM throughout early and middle childhood.

Child first language and adult second language are both tied to general-purpose learning systems.

Do the mechanisms underlying language in fact serve general-purpose functions that preexist this uniquely human capacity? To address this contentious and empirically challenging issue, we systematically tested the predictions of a well-studied neurocognitive theory of language motivated by evolutionary principles. Multiple metaanalyses were performed to examine predicted links between language and two general-purpose learning systems, declarative and procedural memory. The results tied lexical abilities to learning only in declarative memory, while grammar was linked to learning in both systems in both child first language and adult second language, in specific ways. In second language learners, grammar was associated with only declarative memory at lower language experience, but with only procedural memory at higher experience. The findings yielded large effect sizes and held consistently across languages, language families, linguistic structures, and tasks, underscoring their reliability and validity. The results, which met the predicted pattern, provide comprehensive evidence that language is tied to general-purpose systems both in children acquiring their native language and adults learning an additional language. Crucially, if language learning relies on these systems, then our extensive knowledge of the systems from animal and human studies may also apply to this domain, leading to predictions that might be unwarranted in the more circumscribed study of language. Thus, by demonstrating a role for these systems in language, the findings simultaneously lay a foundation for potentially important advances in the study of this critical domain.

Sequence learning in the human brain: A functional neuroanatomical meta-analysis of serial reaction time studies.

Sequence learning underlies numerous motor, cognitive, and social skills. Previous models and empirical investigations of sequence learning in humans and non-human animals have implicated cortico-basal ganglia-cerebellar circuitry as well as other structures. To systematically examine the functional neuroanatomy of sequence learning in humans, we conducted a series of neuroanatomical meta-analyses. We focused on the serial reaction time (SRT) task. This task, which is the most widely used paradigm for probing sequence learning in humans, allows for the rigorous control of visual, motor, and other factors. Controlling for these factors (in sequence-random block contrasts), sequence learning yielded consistent activation only in the basal ganglia, across the striatum (anterior/mid caudate nucleus and putamen) and the globus pallidus. In contrast, when visual, motor, and other factors were not controlled for (in a global analysis with all sequence-baseline contrasts, not just sequence-random contrasts), premotor cortical and cerebellar activation were additionally observed. The study provides solid evidence that, at least as tested with the visuo-motor SRT task, sequence learning in humans relies on the basal ganglia, whereas cerebellar and premotor regions appear to contribute to aspects of the task not related to sequence learning itself. The findings have both basic research and translational implications.

Procedural memory in infancy: Evidence from implicit sequence learning in an eye-tracking paradigm.

Procedural memory underpins the learning of skills and habits. It is often tested in children and adults with sequence learning on the serial reaction time (SRT) task, which involves manual motor control. However, due to infants' slowly developing control of motor actions, most procedures that require motor control cannot be examined in infancy. Here, we investigated procedural memory using an SRT task adapted for infants. During the task, images appeared at one of three locations on a screen, with the location order following a five-item recurring sequence. Three blocks of recurring sequences were followed by a random-order fourth block and finally another block of recurring sequences. Eye movement data were collected for infants (n = 35) and adults (n = 31). Reaction time was indexed by calculating the saccade latencies for orienting to each image as it appeared. The entire protocol took less than 3 min. Sequence learning in the SRT task can be operationalized as an increase in latencies in the random block as compared with the preceding and following sequence blocks. This pattern was observed in both the infants and adults. This study is the first to report learning in an SRT task in infants as young as 9  months. This SRT protocol is a promising procedure for measuring procedural memory in infants.

Effects of Anodal Transcranial Direct Current Stimulation (atDCS) on Sentence Comprehension.

OBJECTIVES: This study examined the effects of anodal transcranial direct current stimulation (a-tDCS) on sentence and word comprehension in healthy adults. METHODS: Healthy adult participants, aged between 19 and 30 years, received either a-tDCS over the left inferior frontal gyrus (n=18) or sham stimulation (n=18). Participants completed sentence comprehension and word comprehension tasks before and during stimulation. Accuracy and reaction times (RTs) were recorded as participants completed both tasks. RESULTS: a-tDCS was found to significantly decrease RT on the sentence comprehension task compared to baseline. There was no change in RT following sham stimulation. a-tDCS was not found to have a significant effect on accuracy. Also, a-tDCS did not affect accuracy or RTs on the word comprehension task. CONCLUSIONS: The study provides evidence that non-invasive anodal electrical stimulation can modulate sentence comprehension in healthy adults, at least compared to their baseline performance. (JINS, 2019, 25, 331-335).

Transcranial direct current stimulation enhances retention of a second (but not first) order conditional visuo-motor sequence.

This study examined the role of the left inferior frontal gyrus in the implicit learning and retention of a 'simple' first order conditional (FOC) sequence and a relatively 'complex' second order conditional (SOC) sequence, using anodal transcranial direct current stimulation (a-tDCS). Groups of healthy adults received either a-tDCS (n = 18) over the left inferior frontal gyrus or sham/placebo (n = 18) stimulation. On separate days, participants completed a serial reaction time (SRT) task whilst receiving stimulation. On one of the days, participants were presented with a FOC sequence and in another, a SOC sequence. Both the learning and short-term retention of the sequences were measured. Results showed a-tDCS enhanced the short-term retention of the SOC sequence but not the FOC sequence. There was no effect of a-tDCS on the learning of either FOC or SOC sequences. The results provide evidence of prefrontal involvement in the retention of a motor sequence. However, its role appears to be influenced by the complexity of the sequence's structure. Additionally, the results show a-tDCS can enhance retention of an implicitly learnt motor sequence.

Primary Motor Cortex Excitability Is Modulated During the Mental Simulation of Hand Movement.

OBJECTIVES: It is unclear whether the primary motor cortex (PMC) is involved in the mental simulation of movement [i.e., motor imagery (MI)]. The present study aimed to clarify PMC involvement using a highly novel adaptation of the hand laterality task (HLT). METHODS: Participants were administered single-pulse transcranial magnetic stimulation (TMS) to the hand area of the left PMC (hPMC) at either 50 ms, 400 ms, or 650 ms post stimulus presentation. Motor-evoked potentials (MEPs) were recorded from the right first dorsal interosseous via electromyography. To avoid the confound of gross motor response, participant response (indicating left or right hand) was recorded via eye tracking. Participants were 22 healthy adults (18 to 36 years), 16 whose behavioral profile on the HLT was consistent with the use of a MI strategy (MI users). RESULTS: hPMC excitability increased significantly during HLT performance for MI users, evidenced by significantly larger right hand MEPs following single-pulse TMS 50 ms, 400 ms, and 650 ms post stimulus presentation relative to baseline. Subsequent analysis showed that hPMC excitability was greater for more complex simulated hand movements, where hand MEPs at 50 ms were larger for biomechanically awkward movements (i.e., hands requiring lateral rotation) compared to simpler movements (i.e., hands requiring medial rotation). CONCLUSIONS: These findings provide support for the modulation of PMC excitability during the HLT attributable to MI, and may indicate a role for the PMC during MI. (JINS, 2017, 23, 185-193).

Procedural learning in Parkinson's disease, specific language impairment, dyslexia, schizophrenia, developmental coordination disorder, and autism spectrum disorders: A second-order meta-analysis.

The serial reaction time task (SRTT) has been used to study procedural learning in clinical populations. In this report, second-order meta-analysis was used to investigate whether disorder type moderates performance on the SRTT. Using this approach to quantitatively summarise past research, it was tested whether autism spectrum disorder, developmental coordination disorder, dyslexia, Parkinson's disease, schizophrenia, and specific language impairment differentially affect procedural learning on the SRTT. The main analysis revealed disorder type moderated SRTT performance (p=0.010). This report demonstrates comparable levels of procedural learning impairment in developmental coordination disorder, dyslexia, Parkinson's disease, schizophrenia, and specific language impairment. However, in autism, procedural learning is spared.

Cognitive Bias Modification Training During Inpatient Alcohol Detoxification Reduces Early Relapse: A Randomized Controlled Trial.

BACKGROUND: Relapse is common in alcohol-dependent individuals and can be triggered by alcohol-related cues in the environment. It has been suggested that these individuals develop cognitive biases, in which cues automatically capture attention and elicit an approach action tendency that promotes alcohol seeking. The study aim was to examine whether cognitive bias modification (CBM) training targeting approach bias could be delivered during residential alcohol detoxification and improve treatment outcomes. METHODS: Using a 2-group parallel-block (ratio 1:1) randomized controlled trial with allocation concealed to the outcome assessor, 83 alcohol-dependent inpatients received either 4 sessions of CBM training where participants were implicitly trained to make avoidance movements in response to pictures of alcoholic beverages and approach movements in response to pictures of nonalcoholic beverages, or 4 sessions of sham training (controls) delivered over 4 consecutive days during the 7-day detoxification program. The primary outcome measure was continuous abstinence at 2 weeks postdischarge. Secondary outcomes included time to relapse, frequency and quantity of alcohol consumption, and craving. Outcomes were assessed in a telephonic follow-up interview. RESULTS: Seventy-one (85%) participants were successfully followed up, of whom 61 completed all 4 training sessions. With an intention-to-treat approach, there was a trend for higher abstinence rates in the CBM group relative to controls (69 vs. 47%, p = 0.07); however, a per-protocol analysis revealed significantly higher abstinence rates among participants completing 4 sessions of CBM relative to controls (75 vs. 45%, p = 0.02). Craving score, time to relapse, mean drinking days, and mean standard drinks per drinking day did not differ significantly between the groups. CONCLUSIONS: This is the first trial demonstrating the feasibility of CBM delivered during alcohol detoxification and supports earlier research suggesting it may be a useful, low-cost adjunctive treatment to improve treatment outcomes for alcohol-dependent patients.

Pupillometry reveals resting state alpha power correlates with individual differences in adult auditory language comprehension.

Although individual differences in adult language processing are well-documented, the neural basis of this variability remains largely unexplored. The current study addressed this gap in the literature by examining the relationship between resting state alpha activity and individual differences in auditory language comprehension. Alpha oscillations modulate cortical excitability, facilitating efficient information processing in the brain. While resting state alpha oscillations have been tied to individual differences in cognitive performance, their association with auditory language comprehension is less clear. Participants in the study were 80 healthy adults with a mean age of 25.8 years (SD = 7.2 years). Resting state alpha activity was acquired using electroencephalography while participants looked at a benign stimulus for 3 min. Participants then completed a language comprehension task that involved listening to 'syntactically simple' subject-relative clause sentences and 'syntactically complex' object-relative clause sentences. Pupillometry measured real-time processing demand changes, with larger pupil dilation indicating increased processing loads. Replicating past research, comprehending object relative clauses, compared to subject relative clauses, was associated with lower accuracy, slower reaction times, and larger pupil dilation. Resting state alpha power was found to be positively correlated with the pupillometry data. That is, participants with higher resting state alpha activity evidenced larger dilation during sentence comprehension. This effect was more pronounced for the 'complex' object sentences compared to the 'simple' subject sentences. These findings suggest the brain's capacity to generate a robust resting alpha rhythm contributes to variability in processing demands associated with auditory language comprehension, especially when faced with challenging syntactic structures. More generally, the study demonstrates that the intrinsic functional architecture of the brain likely influences individual differences in language comprehension.

Exploring aperiodic activity in first episode schizophrenia spectrum psychosis: A resting-state EEG analysis.

Abnormalities in brain oscillatory patterns have long been observed in schizophrenia and psychotic disorders more broadly. However, far less is known about aperiodic neural activity in these disorders, which has been linked to excitation/inhibition balance and neuronal population spiking within the brain. Here, we analysed resting-state electroencephalographic (EEG) recordings from 43 first episode schizophrenia spectrum psychosis (FESSP) patients and 28 healthy controls to examine whether aperiodic activity is disrupted in FESSP. We further assessed potential associations between aperiodic activity in FESSP and clinical symptom severity using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Scale for the Assessment of Positive Symptoms (SAPS). We found no significant differences in either the 1/f-like aperiodic exponent or the broadband aperiodic offset between the FESSP and healthy control groups when analysing the global neural signal averaged across all EEG electrodes. Bayesian analyses further supported these non-significant findings. However, additional non-parametric cluster-based permutation analyses did identify reduced aperiodic offset in the FESSP group, relative to controls across broad central, temporal, parietal and select frontal regions. No associations were found between either exponent or offset and clinical symptom severity when examining all FESSP participants, irrespective of antipsychotic medication status. However, offset was shown to predict BPRS and SANS scores in medication naive patients. In sum, this research presents an initial analysis of aperiodic neural activity in FESSP, offering preliminary evidence of altered aperiodic offset in this disorder. This contributes to a broader understanding of disrupted neural dynamics in early psychosis.

Neural basis of implicit motor sequence learning: Modulation of cortical power.

Implicit sequence learning describes the acquisition of serially ordered movements and sequentially structured cognitive information, that occurs without awareness. Theta, alpha and beta cortical oscillations are present during implicit motor sequence learning, but their role in this process is unclear. The current study addressed this gap in the literature. A total of 50 healthy adults aged between 19 and 37 years participated in the study. Implicit motor sequence learning was examined using the Serial Reaction Time task where participants unknowingly repeat a sequence of finger movements in response to a visual stimulus. Sequence learning was examined by comparing reaction times and oscillatory power between sequence trials and a set of control trials comprising random stimulus presentations. Electroencephalography was recorded as participants completed the task. Analyses of the behavioral data revealed participants learnt the sequence. Analyses of oscillatory activity, using permutation testing, revealed sequence learning was associated with a decrease in theta band (4-7 Hz) power recorded over frontal and central electrode sites. Sequence learning effects were not observed in the alpha (7-12 Hz) or beta bands (12-20 Hz). Even though alpha and beta power modulations have long been associated with executing a motor response, it seems theta power is a correlate of sequence learning in the manual domain. Theta power modulations on the serial reaction time task may reflect disengagement of attentional resources, either promoting or occurring as a consequence of implicit motor sequence learning.

Individual differences in procedural learning are associated with fiber specific white matter microstructure of the superior cerebellar peduncles in healthy adults.

Functional neuroimaging has consistently implicated the fronto-basal ganglia-cerebellar circuit in procedural learning-defined as the incidental acquisition of sequence information through repetition. Limited work has probed the role of white matter fiber pathways that connect the regions in this network, such as the superior cerebellar peduncles (SCP) and the striatal premotor tracts (STPMT), in explaining individual differences in procedural learning. High angular diffusion weighted imaging was acquired from 20 healthy adults aged 18-45 years. Fixel-based analysis was performed to extract specific measures of white matter microstructure (fiber density; FD) and macrostructure (fiber cross-section; FC), from the SCP and STPMT. These fixel metrics were correlated with performance on the serial reaction time (SRT) task, and sensitivity to the sequence was indexed by the difference in reaction time between the final block of sequence trials and the randomized block (namely, the 'rebound effect'). Analyses revealed a significant positive relationship between FD and the rebound effect in segments of both the left and right SCP (pFWE < .05). That is, increased FD in these tracts was associated with greater sensitivity to the sequence on the SRT task. No significant associations were detected between fixel metrics in the STPMT and the rebound effect. Our results support the likely role of white matter organization in the basal ganglia-cerebellar circuit in explaining individual differences in procedural learning.