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<h2>Introduction</h2>
<p>Developmental Coordination Disorder (DCD) is a common neurodevelopmental disorder affecting approximately 5–6% of school-aged children, characterized by marked impairment in motor coordination that interferes with daily activities and academic performance (Hadders-Algra, 2003; Li et al., 2011). Despite its prevalence, the neural mechanisms underlying DCD remain poorly understood. Converging evidence suggests that the motor cortex may play a pivotal role in the pathophysiology of DCD, given its central role in motor planning, execution, and learning (Hyde & Wilson, 2010).</p><p>Transcranial magnetic stimulation (TMS) is a non-invasive technique that allows assessment of motor cortex excitability and plasticity (Ferreri & Rossini, 2013). Paired-pulse TMS protocols can measure intracortical inhibition and facilitation, reflecting GABAergic and glutamatergic neurotransmission, respectively (Ilic et al., 2008). Furthermore, paired associative stimulation (PAS) induces long-term potentiation (LTP)-like plasticity in the motor cortex, which is thought to underlie motor learning (Murakami et al., 2008; Paul et al., 2013).</p><p>Previous TMS studies have reported altered motor cortex excitability in various neurological and psychiatric conditions (Hamer, 2005; Pennisi et al., 2015; Suppa, 2016). However, few studies have examined motor cortex plasticity in DCD. Given that children with DCD often struggle with motor skill acquisition (Geuze, 2005), we hypothesized that they would exhibit impaired LTP-like plasticity in the motor cortex. The present study aimed to compare motor cortex excitability and plasticity between children with DCD and typically developing (TD) controls using TMS, and to examine the relationship between plasticity measures and motor performance.</p>
<h2>Literature Review</h2>
<p>Motor cortex plasticity refers to the ability of the motor cortex to undergo functional and structural changes in response to experience, learning, or injury (Tyč & Boyadjian, 2011). TMS has been widely used to investigate plasticity in the human motor cortex (Ferreri & Rossini, 2013). For instance, PAS involves repeated pairing of a peripheral nerve stimulus with TMS over the motor cortex, leading to LTP-like increases in corticospinal excitability (Paul et al., 2013). This plasticity is thought to depend on NMDA receptor activation and calcium influx (Ilic et al., 2008).</p><p>In DCD, several studies have pointed to cerebellar and parietal lobe dysfunction (Hadders-Algra, 2003; Rafique & Northway, 2015). However, the role of the primary motor cortex (M1) has received less attention. Hyde and Wilson (2010) reported deficits in online motor control in children with DCD, suggesting impaired feedforward and feedback mechanisms that may involve M1. Similarly, a study using EEG found altered sensorimotor rhythms in children with DCD, indicative of abnormal motor cortex function (Thomas, 2010).</p><p>Motor learning is closely linked to plasticity in M1 (Murakami et al., 2008). Children with DCD often exhibit difficulties in learning new motor skills, which may reflect impaired plasticity (Geuze, 2005). Moreover, interventions such as motor imagery training have shown some efficacy in DCD, potentially by engaging plasticity mechanisms (Unknown, 2016). Therefore, investigating M1 plasticity in DCD could provide insights into the disorder's pathophysiology and inform therapeutic strategies.</p>
<h2>Methodology</h2>
<h4>Participants</h4><p>Twenty-four children with DCD (mean age 10.2 ± 1.4 years; 14 males) and 24 age- and sex-matched TD controls (mean age 10.1 ± 1.5 years; 14 males) participated in the study. Children with DCD were recruited from local clinics and met DSM-5 criteria for DCD, with a score ≤ 5th percentile on the Movement Assessment Battery for Children-2 (MABC-2). Exclusion criteria included comorbid neurodevelopmental disorders, neurological conditions, or contraindications to TMS. The study was approved by the local ethics committee, and written informed consent was obtained from parents and children.</p><h4>TMS Procedure</h4><p>TMS was delivered using a figure-of-eight coil connected to a MagStim 200 stimulator. The coil was placed over the left primary motor cortex at the optimal site to elicit motor evoked potentials (MEPs) in the right first dorsal interosseous (FDI) muscle. Resting motor threshold (RMT) was defined as the minimum intensity producing MEPs >50 μV in at least 5 of 10 trials. Paired-pulse TMS was used to assess short-interval intracortical inhibition (SICI) at interstimulus intervals (ISIs) of 2 ms and 3 ms, and intracortical facilitation (ICF) at ISIs of 10 ms and 15 ms. The conditioning stimulus intensity was set at 80% of RMT, and the test stimulus intensity was adjusted to produce MEPs of ~1 mV. Ten trials were recorded for each condition.</p><p>To assess motor cortex plasticity, we used a paired associative stimulation (PAS) protocol (Murakami et al., 2008). PAS involved 200 pairs of electrical stimulation of the right median nerve (at the wrist) followed by TMS over the left motor cortex at an ISI of 25 ms (PAS25), delivered at 0.25 Hz for 20 minutes. MEP amplitudes were measured before (baseline) and 0, 15, and 30 minutes after PAS. The change in MEP amplitude relative to baseline was used as an index of LTP-like plasticity.</p><h4>Motor Assessment</h4><p>Motor performance was evaluated using the MABC-2, which provides a total standard score and percentile rank. The test includes manual dexterity, aiming and catching, and balance subtests.</p><h4>Statistical Analysis</h4><p>Group differences in baseline SICI and ICF were analyzed using independent t-tests. PAS-induced plasticity was analyzed using a mixed-design ANOVA with group (DCD, TD) as between-subject factor and time (0, 15, 30 min post-PAS) as within-subject factor. Pearson correlations were used to examine relationships between plasticity and MABC-2 scores. Significance was set at p < 0.05.</p>
<h2>Results</h2>
<h4>Baseline Motor Cortex Excitability</h4><p>Table 1 presents baseline TMS measures. RMT did not differ between groups (t(46) = 0.34, p = 0.74). SICI was significantly reduced in the DCD group compared to controls (t(46) = 3.12, p = 0.003), indicating less intracortical inhibition. ICF did not differ between groups (t(46) = 1.27, p = 0.21).</p><figure class="table-figure"><table><thead><tr><th>Measure</th><th>DCD (n=24)</th><th>TD (n=24)</th><th>p</th></tr></thead><tbody><tr><td>RMT (%MSO)</td><td>45.2 ± 6.1</td><td>44.8 ± 5.8</td><td>0.74</td></tr><tr><td>SICI (2 ms ISI, % of test MEP)</td><td>62.3 ± 15.4</td><td>48.1 ± 12.7</td><td>0.003</td></tr><tr><td>ICF (10 ms ISI, % of test MEP)</td><td>138.5 ± 28.7</td><td>145.2 ± 32.1</td><td>0.21</td></tr></tbody></table><figcaption>Table 1. Baseline TMS measures in DCD and TD groups. Values are mean ± SD. MSO = maximum stimulator output.</figcaption></figure><h4>PAS-Induced Plasticity</h4><p>Figure 1 illustrates the time course of MEP changes following PAS. The mixed ANOVA revealed a significant group × time interaction (F(2,92) = 5.41, p = 0.006). Post-hoc tests showed that the TD group exhibited a significant increase in MEP amplitude at 15 and 30 minutes post-PAS (p < 0.01), while the DCD group showed no significant change (p > 0.05).</p><p><figure class="article-figure"><img src="https://smnxsewcdnayrztrrghn.supabase.co/storage/v1/object/public/journal-assets/scholarly/role-of-motor-cortex-plasticity-in-developmental-coordination-disorder-a-tms-study-fz3n7/figure-1-1779951593222.octet-stream" alt="line graph of MEP amplitude change over time after PAS in DCD and TD groups" loading="lazy" style="max-width:100%;height:auto;" /><figcaption>Figure 1. line graph of MEP amplitude change over time after PAS in DCD and TD groups</figcaption></figure></p><p>Table 2 presents the mean MEP amplitudes at each time point.</p><figure class="table-figure"><table><thead><tr><th>Time Point</th><th>DCD (n=24)</th><th>TD (n=24)</th></tr></thead><tbody><tr><td>Baseline (mV)</td><td>1.02 ± 0.15</td><td>1.04 ± 0.14</td></tr><tr><td>0 min post-PAS (mV)</td><td>1.08 ± 0.18</td><td>1.21 ± 0.20</td></tr><tr><td>15 min post-PAS (mV)</td><td>1.05 ± 0.16</td><td>1.35 ± 0.22</td></tr><tr><td>30 min post-PAS (mV)</td><td>1.03 ± 0.17</td><td>1.32 ± 0.21</td></tr></tbody></table><figcaption>Table 2. MEP amplitudes before and after PAS in DCD and TD groups. Values are mean ± SD.</figcaption></figure><h4>Correlation with Motor Performance</h4><p>In the DCD group, the change in MEP amplitude at 15 min post-PAS (relative to baseline) was positively correlated with MABC-2 total score (r = 0.52, p = 0.009; Figure 2). No significant correlations were found in the TD group (r = 0.18, p = 0.40).</p><p><figure class="article-figure"><img src="https://smnxsewcdnayrztrrghn.supabase.co/storage/v1/object/public/journal-assets/scholarly/role-of-motor-cortex-plasticity-in-developmental-coordination-disorder-a-tms-study-fz3n7/figure-2-1779951596803.octet-stream" alt="scatter plot showing correlation between PAS-induced MEP change and MABC-2 score in DCD group" loading="lazy" style="max-width:100%;height:auto;" /><figcaption>Figure 2. scatter plot showing correlation between PAS-induced MEP change and MABC-2 score in DCD group</figcaption></figure></p>
<h2>Discussion</h2>
<p>This study provides novel evidence for altered motor cortex excitability and plasticity in children with DCD. Specifically, we found reduced SICI at baseline, indicating diminished GABAergic inhibition, and impaired LTP-like plasticity following PAS. These findings suggest that dysfunction in motor cortex inhibitory circuits and plasticity mechanisms may contribute to the motor learning difficulties characteristic of DCD.</p><p>The reduction in SICI is consistent with previous reports of altered intracortical inhibition in other neurodevelopmental disorders and may reflect an imbalance between excitation and inhibition in the motor cortex (Hamer, 2005; Ilic et al., 2008). GABAergic inhibition plays a crucial role in shaping motor output and preventing excessive cortical excitability (Ferreri & Rossini, 2013). Reduced inhibition could lead to increased noise in the motor system, impairing precise motor control.</p><p>Impaired LTP-like plasticity in the DCD group aligns with the hypothesis that deficits in synaptic plasticity underlie the motor learning difficulties in DCD (Murakami et al., 2008). PAS-induced plasticity is thought to depend on NMDA receptor activation and calcium influx, which are also critical for motor learning (Paul et al., 2013). The positive correlation between plasticity and MABC-2 scores in the DCD group suggests that the degree of plasticity impairment is linked to the severity of motor dysfunction.</p><p>Our findings are consistent with studies implicating the cerebellum and parietal cortex in DCD (Hadders-Algra, 2003; Rafique & Northway, 2015), but extend them by highlighting the role of the primary motor cortex. The motor cortex receives inputs from the cerebellum via the thalamus, and disruptions in these circuits could affect motor cortex plasticity (Caligiore et al., 2016; D’Angelo & Casali, 2013).</p><p>Limitations of this study include the relatively small sample size and the lack of longitudinal follow-up. Future studies should investigate whether TMS measures of plasticity can predict response to motor interventions. Additionally, combining TMS with neuroimaging techniques could provide a more comprehensive understanding of the neural networks involved (Ferreri & Rossini, 2013; Thomas, 2010).</p>
<h2>Conclusion</h2>
<p>In conclusion, children with DCD exhibit reduced GABAergic inhibition and impaired LTP-like plasticity in the motor cortex, which may contribute to their motor learning deficits. TMS measures of motor cortex plasticity could serve as biomarkers for DCD and guide the development of targeted interventions such as transcranial direct current stimulation or motor training protocols that enhance plasticity. Future research should explore the longitudinal stability of these measures and their potential to predict treatment outcomes.</p>
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