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.

Procedural learning is associated with microstructure of basal ganglia-cerebellar circuitry in children.

In adults, individual differences in procedural learning (PL) are associated with white matter organization within the basal ganglia-cerebellar circuit. However, no research has examined whether this circuitry is related to individual differences in PL during childhood. Here, 28 children (Mage = 10.00 ± 2.31, 10 female) completed the serial reaction time (SRT) task to measure PL, and underwent structural magnetic resonance imaging (MRI). Fixel-Based Analysis was performed to extract specific measures of white matter fiber density (FD) and fiber cross-section (FC) from the superior cerebellar peduncles (SCP) and the striatal premotor tracts (STPMT), which underlie the fronto-basal ganglia-cerebellar system. These fixel metrics were correlated with the 'rebound effect' from the SRT task - a measure of PL proficiency which compares reaction times associated with generating a sequence, to random trials. While no significant associations were observed at the fixel level, a significant positive association was observed between average FD in the right SCP and the rebound effect, with a similar trend observed in the left SCP. No significant effects were detected in the STPMT. Our results indicate that, like in adults, microstructure of the basal ganglia-cerebellar circuit may explain individual differences in childhood PL.

Adolescents with ADHD and co-occurring motor difficulties show a distinct pattern of maturation within the corticospinal tract from those without: A longitudinal fixel-based study.

It is well documented that attention-deficit hyperactivity disorder (ADHD) often presents with co-occurring motor difficulties. However, little is known about the biological mechanisms that explain compromised motor skills in approximately half of those with ADHD. To provide insight into the neurobiological basis of poor motor outcomes in ADHD, this study profiled the development of white matter organization within the cortico-spinal tract (CST) in adolescents with ADHD with and without co-occurring motor problems, as well as non-ADHD control children with and without motor problems. Participants were 60 children aged 9-14 years, 27 with a history of ADHD and 33 controls. All underwent high-angular resolution diffusion MRI data at up to three time points (115 in scans total). We screened for motor impairment in all participants at the third time point (≈14 years) using the Developmental Coordination Disorder Questionnaire (DCD-Q). Following pre-processing of diffusion MRI scans, fixel-based analysis was performed, and the bilateral CST was delineated using TractSeg. Mean fiber density (FD) and fiber cross-section (FC) were extracted for each tract at each time-point. To investigate longitudinal trajectories of fiber development, linear mixed models were performed separately for the left and right CST, controlling for nuisance variables. To examine possible variations in fiber development between groups, we tested whether the inclusion of group and the interaction between age and group improved model fit. At ≈10 years, those with ADHD presented with lower FD within the bilateral CST relative to controls, irrespective of their prospective motor status. While these microstructural abnormalities persisted into adolescence for individuals with ADHD and co-occurring motor problems, they resolved for those with ADHD alone. Divergent maturational pathways of motor networks (i.e., the CST) may, at least partly, explain motor problems individuals with ADHD.

The feasibility and acceptability of a classroom-based physical activity program for children attending specialist schools: a mixed-methods pilot study.

BACKGROUND: Children with disabilities often engage in less than the recommended amount of daily physical activity (PA). Classroom-based PA breaks are a favourable method of promoting PA for children. However, evaluations of these programs in specialist schools are scarce, with even less research into their feasibility and acceptability. This may hinder effective implementation and program scalability. This pilot study investigated the feasibility and acceptability of implementing a classroom-based PA break program in Australian specialist school classrooms, using the Australian Joy of Moving (AJoM) program. METHODS: Forty primary/junior classes and their teachers across five specialist schools implemented the AJoM program for eight weeks as the intervention group within a pilot cluster randomised controlled trial. A mixed-methods design investigated classroom teachers' (N = 22; 6 males, 16 females) perspectives of the feasibility and acceptability of the program after implementation through semi-structured telephone interviews (n = 7 teachers), qualitative survey responses (n = 18 teachers) and quantitative survey items (n = 19 teachers). Qualitative data were analysed using predominantly deductive thematic analysis. Quantitative data were analysed using descriptive statistics. RESULTS: Classroom-based PA breaks may be feasible for getting children with disabilities more active at school. However, considerable variation exists in teachers' perception of the AJoM experience. While several teachers indicate that the program content could be pertinent for their class, common divergences in perceptions of feasibility and acceptability appear to relate to the age and developmental level or needs of the students in the class. CONCLUSIONS: This study provides preliminary evidence for the feasibility and acceptability of implementing classroom-based PA breaks in specialist schools. However, results demonstrate the importance of (1) allowing a high level of flexibility in the design and implementation of programs to meet the varying needs of class groups and (2) providing a large variety of resources to cater to the heterogeneity of the children. TRIAL REGISTRATION: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12619000193178 ) on 11 February 2019.

Manual dexterity in late childhood is associated with maturation of the corticospinal tract.

PURPOSE: Despite the important role of manual dexterity in child development, the neurobiological mechanisms associated with manual dexterity in childhood remain unclear. We leveraged fixel-based analysis (FBA) to examine the longitudinal association between manual dexterity and the development of white matter structural properties in the corticospinal tract (CST). METHODS: High angular diffusion weighted imaging (HARDI) data were acquired for 44 right-handed typically developing children (22 female) aged 9-13 across two timepoints (timepoint 1: mean age 10.5 years ± 0.5 years, timepoint 2: 11.8 ± 0.5 years). Manual dexterity was assessed using the Grooved Pegboard Test, a widely used measure of manual dexterity. FBA-derived measures of fiber density and morphology were generated for the CST at each timepoint. Connectivity-based fixel enhancement and mixed linear modelling were used to examine the longitudinal association between manual dexterity and white matter structural properties of the CST. RESULTS: Longitudinal mixed effects models showed that greater manual dexterity of the dominant hand was associated with increased fiber cross-section in the contralateral CST. Analyses further demonstrated that the rate of improvement in manual dexterity was associated with the rate of increase in fiber cross-section in the contralateral CST between the two timepoints. CONCLUSION: Our longitudinal data suggest that the development of manual dexterity in late childhood is associated with maturation of the CST. These findings significantly enhance our understanding of the neurobiological systems that subserve fine motor development and provide an important step toward mapping normative trajectories of fine motor function against microstructural and morphological development in childhood.

Fixel-based Analysis of Diffusion MRI: Methods, Applications, Challenges and Opportunities.

Diffusion MRI has provided the neuroimaging community with a powerful tool to acquire in-vivo data sensitive to microstructural features of white matter, up to 3 orders of magnitude smaller than typical voxel sizes. The key to extracting such valuable information lies in complex modelling techniques, which form the link between the rich diffusion MRI data and various metrics related to the microstructural organization. Over time, increasingly advanced techniques have been developed, up to the point where some diffusion MRI models can now provide access to properties specific to individual fibre populations in each voxel in the presence of multiple "crossing" fibre pathways. While highly valuable, such fibre-specific information poses unique challenges for typical image processing pipelines and statistical analysis. In this work, we review the "Fixel-Based Analysis" (FBA) framework, which implements bespoke solutions to this end. It has recently seen a stark increase in adoption for studies of both typical (healthy) populations as well as a wide range of clinical populations. We describe the main concepts related to Fixel-Based Analyses, as well as the methods and specific steps involved in a state-of-the-art FBA pipeline, with a focus on providing researchers with practical advice on how to interpret results. We also include an overview of the scope of all current FBA studies, categorized across a broad range of neuro-scientific domains, listing key design choices and summarizing their main results and conclusions. Finally, we critically discuss several aspects and challenges involved with the FBA framework, and outline some directions and future opportunities.

Does fMRI repetition suppression reveal mirror neuron activity in the human brain? Insights from univariate and multivariate analysis.

Mirror neurons (MN) have been proposed as the neural substrate for a wide range of clinical, social and cognitive phenomena. Over the last decade, a commonly used tool for investigating MN activity in the human brain has been functional magnetic resonance (fMRI) repetition suppression (RS) paradigms. However, the available evidence is mixed, largely owing to inconsistent application of the methodological criteria necessary to infer MN properties. This raises concerns about the degree to which one can infer the presence (or absence) of MN activity from earlier accounts that adopted RS paradigms. We aimed to clarify this issue using a well-validated fMRI RS paradigm and tested for mirror properties by rigorously applying the widely accepted criteria necessary to demonstrate MN activity using traditional univariate techniques and Multivariate Pattern Analysis (MVPA). While univariate whole brain analysis in healthy adults showed uni-modal RS effects within the supplementary motor area, no evidence for cross-modal RS effects consistent with mirror neuron activity was found. MVPA on the other hand revealed a region along the anterior intraparietal sulcus that met the criteria for MN activity. Taken together, these results clarify disparate evidence from earlier RS studies, highlighting that traditional univariate analysis of RS data may not be sensitive for detecting MN activity when rigorously applying the requisite criteria. In light of these findings, we recommend that short of increasing sample sizes substantially, future studies using RS paradigms to investigate MNs across the human brain consider the use of MVPA.

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).

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).

Developmental improvements in reaching correction efficiency are associated with an increased ability to represent action mentally.

We investigated the purported association between developmental changes in the efficiency of online reaching corrections and improved action representation. Younger children (6-7 years), older children (8-12 years), adolescents (13-17 years), and young adults (18-24 years) completed a double-step reaching paradigm and a motor imagery task. Results showed similar nonlinear performance improvements across both tasks, typified by substantial changes in efficiency after 6 or 7 years followed by incremental improvements. Regression showed that imagery ability significantly predicted reaching efficiency and that this association stayed constant across age. Findings provide the first empirical evidence that more efficient online control through development is predicted, partly, by improved action representation.

Childhood development of brain white matter myelin: a longitudinal T1w/T2w-ratio study.

Myelination of human brain white matter (WM) continues into adulthood following birth, facilitating connection within and between brain networks. In vivo MRI studies using diffusion weighted imaging (DWI) suggest microstructural properties of brain WM increase over childhood and adolescence. Although DWI metrics, such as fractional anisotropy (FA), could reflect axonal myelination, they are not specific to myelin and could also represent other elements of WM microstructure, for example, fibre architecture, axon diameter and cell swelling. Little work exists specifically examining myelin development. The T1w/T2w ratio approach offers an alternative non-invasive method of estimating brain myelin. The approach uses MRI scans that are routinely part of clinical imaging and only require short acquisition times. Using T1w/T2w ratio maps from three waves of the Neuroimaging of the Children's Attention Project (NICAP) [N = 95 (208 scans); 44% female; ages 9.5-14.20 years] we aimed to investigate the developmental trajectories of brain white matter myelin in children as they enter adolescence. We also aimed to investigate whether longitudinal changes in myelination of brain WM differs between biological sex. Longitudinal regression modelling suggested non-linear increases in WM myelin brain wide. A positive parabolic, or U-shaped developmental trajectory was seen across 69 of 71 WM tracts modelled. At a corrected level, no significant effect for sex was found. These findings build on previous brain development research by suggesting that increases in brain WM microstructure from childhood to adolescence could be attributed to increases in myelin.

White matter organisation of sensorimotor tracts is associated with motor imagery in childhood.

Despite the important role of motor imagery (MI) in motor development, our understanding of the contribution of white matter fibre properties to MI performance in childhood remains limited. To provide novel insight into the white matter correlates of MI performance, this study examined the association between white matter fibre properties and motor imagery performance in a sample of typically developing children. High angular diffusion weighted imaging data were collected from 22 typically developing children aged 6-14 years (12 female, MAge= 10.56). Implicit motor imagery performance was assessed using a mental hand rotation paradigm. The cerebellar peduncles and the superior longitudinal fasciculus were reconstructed using TractSeg, a semi-automated method. For each tract, white matter microstructure (fibre density, FD) and morphology (fibre bundle cross-section, FC) were estimated using Fixel-Based Analysis. Permutation-based inference testing and partial correlation analyses demonstrated that higher FC in the middle cerebellar peduncles was associated with better MI performance. Tract-based region of interest analyses showed that higher FC in the middle and superior cerebellar peduncles were associated with better MI performance. Results suggest that white matter connectivity along the cerebellar peduncles may facilitate MI performance in childhood. These findings advance our understanding of the neurobiological systems that underlie MI performance in childhood and provide early evidence for the relevance of white matter sensorimotor pathways to internal action representations.

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.

Longitudinal Trajectories of White Matter Development in Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Few longitudinal studies have investigated whether white matter development reflects differential outcomes for children with and without attention-deficit/hyperactivity disorder (ADHD). To examine whether deviations from typical trajectories of white matter development were associated with the persistence or remission of ADHD symptoms, this study examined microstructural and morphological properties of 71 white matter tracts from 390 high angular diffusion scans acquired prospectively for 62 children with persistent ADHD, 37 children remitted from ADHD, and 85 children without ADHD. METHODS: Participants (mean age at wave 1 = 10.39 years, scan interval = 18 months) underwent up to 3 magnetic resonance imaging assessments. White matter tracts were reconstructed using TractSeg, a semiautomated method. For each tract, we derived measures of fiber density (microstructure) and fiber bundle cross-section (morphology) using fixel-based analysis. Linear mixed models were used to compare trajectories of fiber development between the persistent ADHD, remitted ADHD, and non-ADHD groups. RESULTS: Compared with the non-ADHD group, the remitted and persistent ADHD groups showed accelerated fiber development in thalamic pathways, striatal pathways, and the superior longitudinal fasciculus. In the remitted ADHD group, accelerated fiber development in corticospinal, frontopontine, striatal-premotor, and thalamo-premotor pathways was associated with greater reductions in ADHD symptom severity. The persistent ADHD group showed ongoing white matter alterations along sensorimotor pathways. CONCLUSIONS: These results suggest that variations in white matter development are associated with different clinical trajectories in ADHD. The findings advance our understanding of the neurobiological mechanisms underpinning ADHD symptom progression and provide novel evidence in support of developmental models of ADHD.

An Investigation of Age-related Neuropathophysiology in Autism Spectrum Disorder Using Fixel-based Analysis of Corpus Callosum White Matter Micro- and Macrostructure.

Fixel-based analysis was used to probe age-related changes in white matter micro- and macrostructure of the corpus callosum between participants with (N = 54) and without (N = 50) autism spectrum disorder (ASD). Data were obtained from the Autism Brain Imaging Data Exchange-II (ABIDE-II). Compared to age-matched controls, young adolescents with ASD (11.19 ± 7.54 years) showed reduced macroscopic fiber cross-section (logFC) and combined fiber-density and cross-section (FDC). Reduced fiber-density (FD) and FDC was noted in a marginally older (13.87 ± 3.15 years) ASD cohort. Among the oldest ASD cohort (17.07 ± 3.56 years), a non-significant trend indicative of reduced FD was noted. White matter aberration appears greatest and most widespread among younger ASD cohorts. This supports the suggestion that some early neuropathophysiological indicators in ASD may dissipate with age.

Sex- and age-related differences in autistic behaviours in children with neurofibromatosis type 1.

This study investigated sex and age differences in autistic behaviours in children with neurofibromatosis type 1 (NF1) who scored within the clinical range on the Social Responsiveness Scale - Second Edition (T score ≥ 60). Thirty-four males and 28 females (3-16 years) were assessed with the Autism Diagnostic Observation Schedule - Second Edition and Autism Diagnostic Interview - Revised. Across both measures, males exhibited greater social communication deficits relative to females. Age-related abatement of social communication difficulties was observed for males but not females. Conversely, no sex differences were found for restricted/repetitive behaviours, which were stable over time for both males and females. The findings are discussed within the context of broader neurodevelopmental considerations that are common in NF1.

White matter and sustained attention in children with attention/deficit-hyperactivity disorder: A longitudinal fixel-based analysis.

Sustained attention is a cognitive function with known links to academic success and mental health disorders such as attention/deficit-hyperactivity disorder (ADHD). Several functional networks are critical to sustained attention, however the association between white matter maturation in tracts linking functional nodes and sustained attention in typical and atypical development is unknown. 309 diffusion-weighted imaging scans were acquired from 161 children and adolescents (80 ADHD, 81 control) at up to three timepoints over ages 9-14. A fixel-based analysis approach was used to calculate mean fiber density and fiber-bundle cross section in tracts of interest. Sustained attention was measured using omission errors and response time variability on the out-of-scanner sustained attention to response task. Linear mixed effects models examined associations of age, group and white matter metrics with sustained attention. Greater fiber density in the bilateral superior longitudinal fasciculus (SLF) I and right SLF II was associated with fewer attention errors in the control group only. In ADHD and control groups, greater fiber density in the left ILF and right thalamo-premotor pathway, as well as greater fiber cross-section in the left SLF I and II and right SLF III, was associated with better sustained attention. Relationships were consistent across the age span. Results suggest that greater axon diameter or number in the dorsal and middle SLF may facilitate sustained attention in neurotypical children but does not assist those with ADHD potentially due to disorder-related alterations in this region. Greater capacity for information transfer across the SLF was associated with attention maintenance in 9-14-year-olds regardless of diagnostic status, suggesting white matter macrostructure may also be important for attention maintenance. White matter and sustained attention associations were consistent across the longitudinal study, according with the stability of structural organization over this time. Future studies can investigate modifiability of white matter properties through ADHD medications.

Longitudinal developmental trajectories of inhibition and white-matter maturation of the fronto-basal-ganglia circuits.

Response inhibition refers to the cancelling of planned (or restraining of ongoing) actions and is required in much of our everyday life. Response inhibition appears to improve dramatically in early development and plateau in adolescence. The fronto-basal-ganglia network has long been shown to predict individual differences in the ability to enact response inhibition. In the current study, we examined whether developmental trajectories of fiber-specific white matter properties of the fronto-basal-ganglia network was predictive of parallel developmental trajectories of response inhibition. 138 children aged 9-14 completed the stop-signal task (SST). A subsample of 73 children underwent high-angular resolution diffusion MRI data for up to three time points. Performance on the SST was assessed using a parametric race modelling approach. White matter organization of the fronto-basal-ganglia circuit was estimated using fixel-based analysis. Contrary to predictions, we did not find any significant associations between maturational trajectories of fronto-basal-ganglia white matter and developmental improvements in SST performance. Findings suggest that the development of white matter organization of the fronto-basal-ganglia and development of stopping performance follow distinct maturational trajectories.

Assessment of cortical inhibition depends on inter individual differences in the excitatory neural populations activated by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is used to probe inhibitory intracortical neurotransmission and has been used to infer the neurobiological dysfunction that may underly several neurological disorders. One technique, short-interval intracortical inhibition (SICI), indexes gamma-aminobutyric acid (GABA) mediated inhibitory activity and is a promising biomarker. However emerging evidence suggests SICI does not exclusively represent GABAergic activity because it may be influenced by inter-individual differences in the specific excitatory neural populations activated by TMS. Here we used the latency of TMS motor evoked potentials (MEPs) to index these inter-individual differences, and found that a significant proportion of the observed variability in SICI magnitude was accounted for by MEP latency, r = - 0.57, r2 = 0.33, p = .014. We conclude that SICI is influenced by inter-individual differences in the excitatory neural populations activated by TMS, reducing the precision of this GABAergic probe. Interpreting SICI measures in the context of MEP latency may facilitate a more precise assessment of GABAergic intracortical inhibition. The reduced cortical inhibition observed in some neuropathologies could be influenced by reduced activity in specific excitatory neural populations. Including MEP latency assessment in research investigating SICI in clinical groups could assist in differentiating the cortical circuits impacted by neurological disorders.

The role of the primary motor cortex in motor imagery: A theta burst stimulation study.

While mentally simulated actions activate similar neural structures to overt movement, the role of the primary motor cortex (PMC) in motor imagery remains disputed. The aim of the study was to use continuous theta burst stimulation (cTBS) to modulate corticospinal activity to investigate the putative role of the PMC in implicit motor imagery in young adults with typical and atypical motor ability. A randomized, double blind, sham-controlled, crossover, offline cTBS protocol was applied to 35 young adults. During three separate sessions, adults with typical and low motor ability (developmental coordination disorder [DCD]), received active cTBS to the PMC and supplementary motor area (SMA), and sham stimulation to either the PMC or SMA. Following stimulation, participants completed measures of motor imagery (i.e., hand rotation task) and visual imagery (i.e., letter number rotation task). Although active cTBS significantly reduced corticospinal excitability in adults with typical motor ability, neither task performance was altered following active cTBS to the PMC or SMA, compared to performance after sham cTBS. These results did not differ across motor status (i.e., typical motor ability and DCD). These findings are not consistent with our hypothesis that the PMC (and SMA) is directly involved in motor imagery. Instead, previous motor cortical activation observed during motor imagery may be an epiphenomenon of other neurophysiological processes and/or activity within brain regions involved in motor imagery. This study highlights the need to consider multi-session theta burst stimulation application and its neural effects when probing the putative role of motor cortices in motor imagery.