Cortical Contributions to Motor Sequence Learning: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cortical Contributions to Motor Sequence Learning (NCT04138953), a randomized na study. The primary outcome is Serial Reaction Time Task (SRTT) Performance.

2. Clinical Question

The study's rationale is to use temporary disruption during practice to investigate whether activity in particular cortical regions contributes to learning. The primary outcome is a measure of sequenced skill derived from response times on the Serial Reaction Time Task (SRTT). In the registry description, a higher sequenced-skill value indicates greater skill. The planned observation points are baseline before training, after training, and a retention test. The record describes training as usually lasting for 3 hours and places the retention test 30 mins following training.

This question is about a difference in learning-related task performance across randomized stimulation groups, not simply about whether participants can perform the task. It also involves distinguishing performance after training from performance retained at a later test. The registry record does not provide the group-level endpoint values, estimated contrasts, uncertainty intervals, or inferential results needed to assess those comparisons.

3. Trial Design

The study, titled “Cortical Contributions to Motor Sequence Learning,” is a randomized, parallel-group trial sponsored by Emory University. The registry lists its phase as NA, its masking as none, and its status as completed. Enrollment is 64. The recorded start date is 2019-12-05, and the primary completion date is 2023-08-04. These registration details describe the trial structure, not the size or precision of any treatment effect.

Three groups are described: TMS over the premotor cortex (PMC), TMS over the primary motor cortex (M1), and sham TMS. The study summary describes stimulation during motor-skill training as a way to create a transient “virtual lesion.” It states that MRI may be used to acquire a structural brain image to target noninvasive stimulation. The record does not report further operational details about stimulation delivery or training procedures beyond the descriptions of the arms and outcome timeframe.

Random allocation can help make groups comparable at the start of a study, while a parallel design means participants are assigned to one group rather than crossing through all groups. The record lists no masking, so it does not describe the study as blinded. It does not report the allocation sequence method, concealment procedures, or whether outcome assessors were masked. The number assigned to each arm is not reported in the registry record in the design information; adverse-event risk counts are reported separately and should not be treated as randomized arm sizes or primary-outcome analysis counts.

The listed intervention types are TMS and Sham TMS. A secondary outcome is cortical excitability measured by motor evoked potentials (MEPs). The record lists 2 outcome measures and 0 analyses. It therefore gives the trial's broad design and intended measurement schedule, but does not give an analyzed comparison of SRTT performance or MEPs. A detailed protocol, prespecified statistical analysis plan, and sample-size justification are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The population in this analysis includes participants who completed the indicated study visit and had usable data. Five participants in the PMC group are not included due to technical issues; for 2 participants the stimulation target could not be confirmed during data analysis and 3 participants had different timing values than other members of their cohort. Of participants with usable pre- and post- test data, 11 from the M1 group and 12 from the PMC group completed the retention test.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Serial Reaction Time Task (SRTT) Performance, measured over Pre-test (baseline), Post-test (training usually lasts for 3 hours), Retention Test (30 mins following training).

The primary endpoint is Serial Reaction Time Task (SRTT) Performance, measured in milliseconds (ms). Participants press a key corresponding to a target square displayed on a monitor. The endpoint description defines sequenced skill (SS) by subtracting response time for sequenced key presses from response time for random key presses within and across a test block. An increase in SS indicates an increase in sequenced skill and is described as preferable in the registry.

The measure is intended to capture performance associated with responding to a learned sequence, rather than response time alone. Comparing sequenced and random responses helps express the sequence-related component of task performance using the task's own response-time measures. The registry lists the outcome parameter as a mean and the dispersion measure as a standard deviation. These summaries would describe the average endpoint value and variability among participants at a given visit; they do not, by themselves, quantify a between-group treatment effect.

Measurements are specified at pre-test (baseline), post-test (training usually lasts for 3 hours), and a retention test (30 mins following training). The repeated time points matter because immediate post-training performance and later retention address different aspects of task performance. However, the registry record does not report the endpoint means or standard deviations for any group or visit, nor a prespecified primary contrast among visits or groups. It also does not report a numerical effect estimate or confidence interval. The intended measurement is clear, but the posted record does not supply results with which to judge the magnitude or precision of group differences.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpreting this study requires separating its design, its endpoint definition, and its analysis results. The registry identifies a randomized parallel-group design and three groups, but gives no primary-outcome analysis. The endpoint is continuous: sequenced skill is calculated from response times, and the record identifies a mean and standard deviation as the summary measures. Continuous outcomes are commonly described by a mean to indicate the central level and a standard deviation to describe variability around that mean. Those statistics become informative for a group comparison only when the values, comparison, and analysis population are available.

What does randomization contribute?

General statistical explanation: randomization assigns participants to groups by chance, which can reduce systematic differences between groups at the outset. It does not guarantee that all participant characteristics will be identical, particularly in a study with limited enrollment. Analysis should respect the randomized comparison and explain how participants with missing or unusable outcome data are handled. The registry record says the trial was randomized, but does not report the sequence-generation or allocation-concealment methods. It also does not provide a primary-outcome analysis population by randomized group.

How should the repeated measurements be understood?

The SRTT is specified at baseline, post-test, and retention. A change from baseline describes within-participant change over time, while a comparison between groups addresses whether change differs across stimulation conditions. These are different quantities. An analysis might compare values at a follow-up visit while adjusting for baseline, compare changes from baseline, or model all visits together; these approaches answer related but not identical questions and rely on different modeling choices. The registry record does not report which approach was used, or identify a single primary comparison across the time points.

General statistical explanation: repeated measurements from the same participant are correlated, so they should not ordinarily be treated as if each measurement came from a different person. A suitable repeated-measures analysis accounts for that within-person dependence. The registry record does not report a model, covariance structure, or other details that would establish how such dependence was handled. It also does not report whether the primary analysis used all recorded visits or a subset.

Why are effect estimates and uncertainty important?

A group mean alone describes a group at a visit; it does not show the difference between groups. A contrast estimates the difference relevant to the research question, such as the difference in sequenced-skill change between a stimulation group and sham. A confidence interval communicates uncertainty around that estimated contrast. General statistical explanation: uncertainty depends on factors including the amount of outcome variability and the number of participants with usable data. The enrollment figure is not a substitute for the analysis sample size, because the registry record identifies a subset with usable data for the stated analysis population and notes technical exclusions in the PMC group.

No such means, contrasts, or confidence intervals for the primary endpoint are reported in the registry record. Consequently, there is no effect estimate to interpret, and no recalculation from posted summary statistics can be made. The sponsor's own analysis takes precedence when a discrepancy with a recalculation exists, but a sponsor analysis is not listed in this record.

What does the planning illustration represent?

General statistical explanation: a sample-size calculation asks how many participants may be needed under chosen assumptions about the effect to detect, variability, allocation, significance level, and desired power. The registry's stated illustration uses an observed effect as its basis, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It is described as planning rather than as the trial's own design calculation. Any resulting sample sizes are planning illustrations, not observed power and not a retrospective statement about the chance that this completed study detected an effect. The record does not report a protocol-based sample-size justification. The observed effect and numeric planning outputs are not reported in the registry record in the information available for this analysis.

General statistical explanation: over-dispersion means that observed variability is greater than a model assumes. If that occurs, standard errors based on the lower assumed variability can be too small, making estimates appear more precise than warranted. This is a general issue in statistical modeling; the registry record does not report evidence of over-dispersion or a model for which it could be assessed. No claim about it can therefore be made for this trial.

How should the event counts be distinguished from outcome analysis?

Adverse-event counts are descriptive safety summaries, while SRTT results are continuous performance outcomes. A count of participants with events is not an analysis of motor learning, and a count of participants at risk is not a primary-outcome denominator. The record gives safety risk counts by group but does not report primary-outcome denominators or group-specific performance summaries. The two types of information answer different questions and should not be interchanged.

Finally, the registry lists 0 analyses. No inferential method, adjustment set, model specification, missing-data procedure, or multiplicity strategy for the primary endpoint is reported in the registry record. Statistical details beyond the stated design and endpoint should therefore be treated as unknown rather than inferred from common practice.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint has several categories or time points and is not reduced in the registry record to one comparison. Baseline, post-test, and retention measurements can support multiple possible comparisons, and the study has three groups. Testing several group contrasts or time-point contrasts raises a multiplicity question: if many hypotheses are tested, the chance of at least one apparently unusual result can increase. General statistical explanation: analysis plans often define a primary contrast in advance or use an adjustment strategy to address multiple testing. The registry record does not report a primary contrast, hierarchy of comparisons, or multiplicity adjustment.

Missing-data handling is also not reported in the registry record. The stated analysis population includes participants who completed the indicated study visit and had usable data. Five participants in the PMC group are excluded because of technical issues. The record explains that the stimulation target could not be confirmed for 2 participants, then gives an incomplete explanation for the remaining 3 participants. It does not report how many participants had usable data in each arm at each visit, whether other data were missing, or whether any imputation or sensitivity analysis was used.

The information does not establish whether the primary analysis followed an intention-to-treat principle, included only participants with observed outcomes, or used another population definition. The analysis population is therefore not fully characterized in the registry record. Since 0 analyses are listed, it is also not possible to determine whether any missingness assumptions were examined or whether conclusions were robust to alternative handling. These unknowns limit interpretation of precision and comparability, even apart from the absence of reported endpoint estimates.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The adverse-event record reports 0 serious adverse events, 0 other adverse events, and 0 deaths in each of the three groups. The reported participants at risk are 20 for Sham TMS, 20 for TMS Over Primary Motor Cortex (M1), and 24 for TMS Over Premotor Cortex (PMC), for both serious and other adverse events. These are the registry's safety counts and do not establish the number included in the primary-outcome analysis.

General statistical explanation: observing no events in a study does not establish that an event is impossible. Event counts are most informative when read with their observation periods, event definitions, and methods of collection. Those details are not reported in the registry record in the information available for this analysis. The record also lists no top serious adverse-event terms.

These safety summaries are descriptive, not evidence of comparative safety from a reported statistical analysis. The registry record does not provide risk estimates, uncertainty intervals, or tests comparing groups. The zero counts should therefore be read exactly as posted: no events were recorded in the listed categories for the participants at risk, without extending that observation to other settings or populations.

12. What the Result Does, and Does Not, Mean

This trial addresses a causal research question: whether disrupting activity in premotor cortex or primary motor cortex during motor-skill training is associated with a different pattern of learning than sham stimulation. The design is relevant to that question because participants were randomized to parallel groups and the study summary describes stimulation during training. The primary outcome is a task-based measure of sequenced skill at baseline, after training, and at retention.

The registry record does not report the primary-outcome analysis. It therefore does not establish whether sequenced skill increased or decreased in any group, whether the groups differed, or how precisely a difference was estimated. It also does not establish that the groups were equivalent. A missing analysis result cannot be interpreted as a null finding.

The study summary states a hypothesis that PMC is necessary to learn a new motor skill. A trial can investigate a hypothesis without the registry record containing enough results to answer it. For conclusions about that hypothesis, the outcome values, analysis definition, between-group estimates, and uncertainty would be needed. The record lists a secondary cortical-excitability measure based on MEPs but does not report its analysis either.

The safety record reports zero serious adverse events, other adverse events, and deaths in the listed groups. That information describes recorded events among the participants at risk; it does not prove that risks are absent or quantify comparative safety. The study's enrollment and completion status likewise describe the record and do not establish statistical precision or efficacy.

General statistical explanation: statistical evidence and scientific interpretation depend on both the estimated effect and its uncertainty, alongside the design and quality of measurement. A task outcome can serve as a research measure without directly answering broader questions beyond the measured task and study conditions. Since the registry record supplies no analyzed endpoint results, interpretation should remain at the level of study rationale, design, and posted safety counts rather than claims about the direction or size of a learning effect.

13. Why This Trial Matters Statistically

The statistical interest of this study lies in its effort to connect a behavioral learning measure with targeted disruption of distinct cortical regions. The three-group design distinguishes stimulation over PMC, stimulation over M1, and sham stimulation. The primary endpoint is also measured at multiple stages: baseline, after training, and retention. Together, these features make the intended comparison more informative than a single post-training score, but they also make clear definitions of the primary contrast and analysis population important.

Several statistical questions follow from that design. A comparison may concern post-training performance, change from baseline, retention, or differences in change across groups. These are not interchangeable estimands. Multiple groups and time points also make prespecification and multiplicity handling relevant. The registry record does not report how those choices were made, and it lists 0 analyses.

The analysis population deserves attention because the registry describes usable visit data and identifies technical exclusions in the PMC group. Group-specific outcome availability can affect both precision and the interpretation of randomized comparisons. The record does not report complete visit-level analysis counts or the methods used to address missing data.

Finally, the record illustrates why trial status and enrollment should not be confused with reported evidence. The study is marked completed and enrollment is 64, yet no primary-outcome estimates or inferential results are listed. The study question and design remain clear, but the registry record does not permit an assessment of effect magnitude, uncertainty, or the stated hypothesis. Statistically, that distinction between a completed design and reported analysis is central to responsible interpretation.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation for statistical interpretation is that the registry record lists 0 analyses and does not report numerical primary-outcome results. There are no group means or standard deviations for the SRTT endpoint, no contrasts across groups or time points, and no confidence intervals or p-values. The direction and precision of any outcome differences therefore cannot be assessed.

The endpoint is specified across baseline, post-test, and retention, but a single primary comparison is not identified in the registry record. The record does not describe a statistical model or a multiplicity strategy. It also does not report the analysis sample size at each visit, the treatment of missing observations, or a complete analysis-population definition. Five participants in the PMC group are excluded for technical issues; the explanation for 3 of those exclusions is incomplete in the record.

Other design details relevant to interpretation are not reported in the registry record, including allocation-sequence generation, concealment, assessor masking, and detailed procedures for stimulation and outcome collection. The record lists no masking. It is not possible to infer which, if any, additional safeguards were used.

Although a sample-size illustration is described as being based on an observed effect, the registry record does not report a protocol-based sample-size justification or the endpoint estimates needed to assess precision. The illustration should not be read as observed power. Safety counts are also limited to the recorded event categories and participants at risk; event-collection details and comparative safety analyses are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cortical Contributions to Motor Sequence Learning — NCT04138953.
• Registry record last updated 2024-08-28; status last verified 2024-08.
• Results first posted 2024-08-28.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT04138953, “Cortical Contributions to Motor Sequence Learning,” is a completed randomized parallel-group study sponsored by Emory University. The registry lists enrollment of 64, no masking, and phase NA. Its groups received TMS over PMC, TMS over M1, or sham TMS. The stated aim is to investigate cortical contributions to motor-skill learning using stimulation during training.

The primary outcome is SRTT performance, expressed as sequenced skill derived from response times and specified at baseline, post-test, and retention. MEPs are listed as a secondary outcome. The record reports 0 analyses and does not report analyzed primary-outcome results, effect estimates, or uncertainty intervals. It also does not report the analysis plan, missing-data methods, or multiplicity approach.

The adverse-event record lists zero serious adverse events, other adverse events, and deaths in each group. Those counts are descriptive and do not substitute for the missing performance analyses.