The neuroanatomy of developmental language disorder: a systematic review and meta-analysis.

Developmental language disorder (DLD) is a common neurodevelopmental disorder with adverse impacts that continue into adulthood. However, its neural bases remain unclear. Here we address this gap by systematically identifying and quantitatively synthesizing neuroanatomical studies of DLD using co-localization likelihood estimation, a recently developed neuroanatomical meta-analytic technique. Analyses of structural brain data (22 peer-reviewed papers, 577 participants) revealed highly consistent anomalies only in the basal ganglia (100% of participant groups in which this structure was examined, weighted by group sample sizes; 99.8% permutation-based likelihood the anomaly clustering was not due to chance). These anomalies were localized specifically to the anterior neostriatum (again 100% weighted proportion and 99.8% likelihood). As expected given the task dependence of activation, functional neuroimaging data (11 peer-reviewed papers, 414 participants) yielded less consistency, though anomalies again occurred primarily in the basal ganglia (79.0% and 95.1%). Multiple sensitivity analyses indicated that the patterns were robust. The meta-analyses elucidate the neuroanatomical signature of DLD, and implicate the basal ganglia in particular. The findings support the procedural circuit deficit hypothesis of DLD, have basic research and translational implications for the disorder, and advance our understanding of the neuroanatomy of language.

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.

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.

Effects of non-invasive brain stimulation in dystonia: a systematic review and meta-analysis.

Background: Deep brain stimulation is a highly effective treatment of dystonia but is invasive and associated with risks, such as intraoperative bleeding and infections. Previous research has used non-invasive brain stimulation (NIBS) in an attempt to alleviate symptoms of dystonia. The results of these studies, however, have been variable, leaving efficacy unclear. Objectives: This study aimed to evaluate the effects of NIBS on symptoms of dystonia and determine whether methodological characteristics are associated with variability in effect size. Methods: Web of Science, Embase, and MEDLINE Complete databases were searched for articles using any type of NIBS as an intervention in dystonia patients, with changes in dystonia symptoms the primary outcome of interest. Results: Meta-analysis of 27 studies demonstrated a small effect size for NIBS in reducing symptoms of dystonia (random-effects Hedges' g = 0.21, p = .002). Differences in the type of NIBS, type of dystonia, and brain region stimulated had a significant effect on dystonia symptoms. Meta-regression revealed that 10 sessions of active stimulation and the application of concurrent motor training programs resulted in significantly larger mean effect sizes. Conclusion: NIBS has yielded small improvements to dystonic symptoms, but effect sizes depended on methodological characteristics, with more sessions of stimulation producing a larger response. Future research should further investigate the application of NIBS parallel to motor training, in addition to providing a greater quantity of sessions, to help define optimal parameters for NIBS protocols in dystonia. Registration: PROSPERO 2020, CRD42020175944.

Moral content influences facial emotion processing development during early-to-middle childhood.

Facial emotions are often processed in light of moral information, which can assist in predicting and interpreting the intentions of another. Neurophysiological measures of facial emotion processing (FEP) may be sensitive to moral content. Relatively little is known, however, about the relationship between moral content and FEP during early-to-middle childhood, and how this relationship may change across development. Eighty-four children aged 4-12 years completed a task assessing whether child faces primed within the moral harm/care domain influenced face sensitive event-related potentials (ERPs; N170 and LPP). Results demonstrated that N170 amplitude decreased with age for faces primed with positive moral content, whilst LPP amplitude decreased with age for faces primed with negative moral content. Collectively, this suggests that morally relevant content within the harm/care domain is integrated during the early stages of FEP in early-to-middle childhood. Moreover, stronger language ability was positively correlated with the LPP for fearful faces primed with negative moral content. Overall, findings provide novel evidence to suggest that FEP development may be modulated by moral content, and emotion-specific results may be influenced by language. Findings from this research highlight the complex relationship between broader social cognitive skills during child development.

Enlarged Interior Built Environment Scale Modulates High-Frequency EEG Oscillations.

There is currently no robust method to evaluate how built environment design affects our emotion. Understanding emotion is significant, as it influences cognitive processes, behavior, and wellbeing, and is linked to the functioning of physiological systems. As mental health problems are becoming more prevalent, and exposure to indoor environments is increasing, it is important we develop rigorous methods to understand whether design elements in our environment affect emotion. This study examines whether the scale of interior built environments modulate neural networks involved in emotion regulation. Using a Cave Automatic Virtual Environment (CAVE) and controlling for indoor environmental quality (IEQ), 66 adults (31 female, aged 18-55) were exposed to context-neutral enclosed indoor room scenes to understand whether built environment scale affected self-report, autonomic nervous system, and central nervous system correlates of emotion. Our results revealed enlarged scale increased electroencephalography (EEG) power in the ß bandwidth. Frontal midline low-γ and high-γ power were also found to increase with enlarged scale, but contrary to our hypothesis, scale did not modulate frontal midline power or lateralization in the θ or α bandwidths. We did not detect an effect of scale on autonomic indicators or self-reported emotion. However, we did find increased range in skin conductance response (SCR) and heart rate variability (HRV) to the built environment conditions. This study provides a rigorous empirical framework for assessing the environmental impact of a design characteristic on human emotion and suggests that measures of high-frequency oscillations may provide a useful marker of the response to built environment.

Built environment color modulates autonomic and EEG indices of emotional response.

Understanding built environment exposure as a component of environmental enrichment has significant implications for mental health, but little is known about the effects design characteristics have on our emotions and associated neurophysiology. Using a Cave Automatic Virtual Environment while monitoring indoor environmental quality (IEQ), 18 participants were exposed to a resting state (black), and two room scenes, control (white) and condition (blue), to understand if the color of the virtual walls affected self-report, autonomic nervous system, and central nervous system correlates of emotion. Our findings showed that exposure to the chromatic color condition (blue) compared to the achromatic control (white) and resting-state (black, no built environment) significantly increased the range in respiration and skin conductance response. We also detected a significant increase in alpha frontal midline power and frontal hemispheric lateralization relative to blue condition, and increased power spectral density across all electrodes in the blue condition for theta, alpha, and beta bandwidths. The ability for built environment design to modulate emotional response has the potential to deliver significant public health, economic, and social benefits to the entire community. The findings show that blue coloring of the built environment increases autonomic range and is associated with modulations of brain activity linked to emotional processing.

Resting state electroencephalography (EEG) correlates with children's language skills: Evidence from sentence repetition.

Spontaneous neural oscillatory activity reflects the brain's functional architecture and has previously been shown to correlate with perceptual, motor and executive skills. The current study used resting state electroencephalography to examine the relationship between spontaneous neural oscillatory activity and children's language skills. Participants in the study were 52 English-speaking children aged around 10-years. Language was assessed using a sentence repetition task. The main analysis revealed resting state theta power negatively correlated with this task. No significant correlations were found in the other studied frequency bands (delta, alpha, beta, gamma). As part of typical brain development, spontaneous theta power declines across childhood and adolescence. The negative correlation observed in this study may therefore be indicating children's language skills are related to the maturation of theta oscillations. More generally, the study provides further evidence that oscillatory activity in the developing brain, even at rest, is reliably associated with children's language skills.

Periodic and aperiodic neural activity displays age-dependent changes across early-to-middle childhood.

The neurodevelopmental period spanning early-to-middle childhood represents a time of significant growth and reorganisation throughout the cortex. Such changes are critical for the emergence and maturation of a range of social and cognitive processes. Here, we utilised both eyes open and eyes closed resting-state electroencephalography (EEG) to examine maturational changes in both oscillatory (i.e., periodic) and non-oscillatory (aperiodic, '1/f-like') activity in a large cohort of participants ranging from 4-to-12 years of age (N = 139, average age=9.41 years, SD=1.95). The EEG signal was parameterised into aperiodic and periodic components, and linear regression models were used to evaluate if chronological age could predict aperiodic exponent and offset, as well as well as peak frequency and power within the alpha and beta ranges. Exponent and offset were found to both decrease with age, while aperiodic-adjusted alpha peak frequency increased with age; however, there was no association between age and peak frequency for the beta band. Age was also unrelated to aperiodic-adjusted spectral power within either the alpha or beta bands, despite both frequency ranges being correlated with the aperiodic signal. Overall, these results highlight the capacity for both periodic and aperiodic features of the EEG to elucidate age-related functional changes within the developing brain.

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.

Facial emotion processing and language during early-to-middle childhood development: An event related potential study.

Facial emotion processing (FEP) is critical to social cognitive ability. Developmentally, FEP rapidly improves in early childhood and continues to be fine-tuned throughout middle childhood and into adolescence. Previous research has suggested that language plays a role in the development of social cognitive skills, including non-verbal emotion recognition tasks. Here we investigated whether language is associated with specific neurophysiological indicators of FEP. One hundred and fourteen children (4-12 years) completed a language assessment and a FEP task including stimuli depicting anger, happiness, fear, and neutrality. EEG was used to record key event related potentials (ERPs; P100, N170, LPP at occipital and parietal sites separately) previously shown to be sensitive to faces and facial emotion. While there were no main effects of language, the P100 latency to negative expressions appeared to increase with language, while LPP amplitude increased with language for negative and neutral expressions. These findings suggest that language is linked to some early physiological indicators of FEP, but this is dependent on the facial expression. Future studies should explore the role of language in later stages of neural processing, with a focus on processes localised to ventromedial prefrontal regions.

Large-scale analysis of interindividual variability in single and paired-pulse TMS data.

OBJECTIVE: This study brought together over 60 transcranial magnetic stimulation (TMS) researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of factors driving response variability. METHODS: Authors of previously published studies were contacted and asked to share deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to variability in response to single and paired-pulse TMS data. RESULTS: 687 healthy participant's data were pooled across 35 studies. Target muscle, pulse waveform, neuronavigation use, and TMS machine significantly predicted an individual's single-pulse TMS amplitude. Baseline motor evoked potential amplitude, motor cortex hemisphere, and motor threshold (MT) significantly predicted short-interval intracortical inhibition response. Baseline motor evoked potential amplitude, test stimulus intensity, interstimulus interval, and MT significantly predicted intracortical facilitation response. Age, hemisphere, and TMS machine significantly predicted MT. CONCLUSIONS: This large-scale analysis has identified a number of factors influencing participants' responses to single and paired-pulse TMS. We provide specific recommendations to minimise interindividual variability in single and paired-pulse TMS data. SIGNIFICANCE: This study has used large-scale analyses to give clarity to factors driving variance in TMS data. We hope that this ongoing collaborative approach will increase standardisation of methods and thus the utility of single and paired-pulse TMS.

A Daytime Nap Does Not Enhance the Retention of a First-Order or Second-Order Motor Sequence.

This study examined the effects of a daytime nap on the retention of implicitly learnt "first-order conditional" (FOC) and "second-order conditional" (SOC) motor sequences. The implicit learning and retention of a motor sequence has been linked to the neural processes undertaken by the basal ganglia and primary motor cortex (i.e., procedural memory system). There is evidence, however, suggesting that SOC learning may further rely on the hippocampus-supported declarative memory system. Sleep appears to benefit the retention of information processed by the declarative memory system, but not the procedural memory system. Thus, it was hypothesized that sleep would benefit the retention of a SOC motor sequence but not a FOC sequence. The implicit learning and retention of these sequences was examined using the Serial Reaction Time Task. In this study, healthy adults implicitly learnt either a FOC (n = 20) or a SOC sequence (n = 20). Retention of both sequences was assessed following a daytime nap and period of wakefulness. Sleep was not found to improve the retention of the SOC sequence. There were no significant differences in the retention of a FOC or a SOC sequence following a nap or period of wakefulness. The study questions whether the declarative memory system is involved in the retention of implicitly learnt SOC sequences.

The development of neural responses to emotional faces: A review of evidence from event-related potentials during early and middle childhood.

Facial emotion processing (FEP) develops throughout childhood and provides crucial social information necessary for the interpretation and prediction of others' behaviour. This systematic review, which includes a meta-regression component, sought to explore the development of FEP event-related potentials (P100, N170, and late positive potential [LPP]) in children aged three to twelve years. Thirty-four studies, representing data from 1511 children, were included in the review. The combination of meta-regression and systematic review suggest that P100 amplitude decreases with increasing age in response to emotional facial stimuli. P100 latency may show a gradual decrease around the age of ten. In terms of the N170, it is suggested that amplitude follows a non-linear trend with age, and latency may decrease in early childhood before plateauing during middle childhood. Of note, review of the literature indicates that substantial methodological differences and high levels of heterogeneity exist. We suggest future research considers these results within the context of emotion-specific development, whilst also acknowledging how this may relate to individual social functioning skills across early-to-middle childhood.

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.

The effect of empathy and context on face-processing ERPs.

The investigation of emotional face processing has largely used faces devoid of context, and does not account for within-perceiver differences in empathy. The importance of context in face perception has become apparent in recent years. This study examined the interaction of the contextual factors of facial expression, knowledge of a person's character, and within-perceiver empathy levels on face processing event-related potentials (ERPs). Forty-two adult participants learned background information about six individuals' character. Three types of character were described, in which the character was depicted as deliberately causing harm to others, accidently causing harm to others, or undertaking neutral actions. Subsequently, EEG was recorded while participants viewed the characters' faces displaying neutral or emotional expressions. Participants' empathy was assessed using the Empathy Quotient survey. Results showed a significant interaction of character type and empathy on the early posterior negativity (EPN) ERP component. These results suggested that for those with either low or high empathy, more attention was paid to the face stimuli, with more distinction between the different characters. In contrast, those in the middle range of empathy tended to produce smaller EPN with less distinction between character types. Findings highlight the importance of trait empathy in accounting for how faces in context are perceived.

Large-scale analysis of interindividual variability in theta-burst stimulation data: Results from the 'Big TMS Data Collaboration'.

BACKGROUND: Many studies have attempted to identify the sources of interindividual variability in response to theta-burst stimulation (TBS). However, these studies have been limited by small sample sizes, leading to conflicting results. OBJECTIVE/HYPOTHESIS: This study brought together over 60 TMS researchers to form the 'Big TMS Data Collaboration', and create the largest known sample of individual participant TBS data to date. The goal was to enable a more comprehensive evaluation of factors driving TBS response variability. METHODS: 118 corresponding authors of TMS studies were emailed and asked to provide deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to iTBS and cTBS response variability. RESULTS: 430 healthy participants' TBS data was pooled across 22 studies (mean age = 41.9; range = 17-82; females = 217). Baseline MEP amplitude, age, target muscle, and time of day significantly predicted iTBS-induced plasticity. Baseline MEP amplitude and timepoint after TBS significantly predicted cTBS-induced plasticity. CONCLUSIONS: This is the largest known study of interindividual variability in TBS. Our findings indicate that a significant portion of variability can be attributed to the methods used to measure the modulatory effects of TBS. We provide specific methodological recommendations in order to control and mitigate these sources of variability.

The Effect of Visual Articulatory Information on the Neural Correlates of Non-native Speech Sound Discrimination.

Behavioral studies have shown that the ability to discriminate between non-native speech sounds improves after seeing how the sounds are articulated. This study examined the influence of visual articulatory information on the neural correlates of non-native speech sound discrimination. English speakers' discrimination of the Hindi dental and retroflex sounds was measured using the mismatch negativity (MMN) event-related potential, before and after they completed one of three 8-min training conditions. In an audio-visual speech training condition (n = 14), each sound was presented with its corresponding visual articulation. In one control condition (n = 14), both sounds were presented with the same visual articulation, resulting in one congruent and one incongruent audio-visual pairing. In another control condition (n = 14), both sounds were presented with the same image of a still face. The control conditions aimed to rule out the possibility that the MMN is influenced by non-specific audio-visual pairings, or by general exposure to the dental and retroflex sounds over the course of the study. The results showed that audio-visual speech training reduced the latency of the MMN but did not affect MMN amplitude. No change in MMN amplitude or latency was observed for the two control conditions. The pattern of results suggests that a relatively short audio-visual speech training session (i.e., 8 min) may increase the speed with which the brain processes non-native speech sound contrasts. The absence of a training effect on MMN amplitude suggests a single session of audio-visual speech training does not lead to the formation of more discrete memory traces for non-native speech sounds. Longer and/or multiple sessions might be needed to influence the MMN amplitude.

Cerebral Cortical Activity Following Non-invasive Cerebellar Stimulation-a Systematic Review of Combined TMS and EEG Studies.

The cerebellum sends dense projections to both motor and non-motor regions of the cerebral cortex via the cerebellarthalamocortical tract. The integrity of this tract is crucial for healthy motor and cognitive function. This systematic review examines research using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) to the cerebellum with combined cortical electroencephalography (EEG) to explore the temporal features of cerebellar-cortical connectivity. A detailed discussion of the outcomes and limitations of the studies meeting review criteria is presented. Databases were searched between 1 December 2017 and 6 December 2017, with Scopus alerts current as of 23 July 2019. Of the 407 studies initially identified, 10 met review criteria. Findings suggested that cerebellar-cortical assessment is suited to combined TMS and EEG, although work is required to ensure experimental procedures are optimal for eliciting a reliable cerebellar response from stimulation. A distinct variation in methodologies and outcome measures employed across studies, and small sample sizes limited the conclusions that could be drawn regarding the electrophysiological signatures of cerebellar-cortical communication. This review highlights the need for stringent protocols and methodologies for cerebellar-cortical assessments via combined TMS and EEG. With these in place, combined TMS and EEG will provide a valuable means for exploring cerebellar connectivity with a wide range of cortical sites. Assessments have the potential to aid in the understanding of motor and cognitive function in both healthy and clinical groups, and provide insights into long-range neural communication generally.