This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders (NCT03398070), a registered phase not stated study. The primary outcome is Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03398070 |
| Phase | Phase not stated |
| Condition | Conversion Disorder |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Patients with clinically established motor functional neurological disorder (FND), also called conversion disorder. The cohort description includes functional movement disorders, psychogenic nonepileptic seizures and functional limb weakness. The record says 30 participants were initially enrolled and 22 provided follow-up data.
Intervention
Participants received standard of care. This is not presented as an assigned experimental treatment. The project’s broader aim was to examine whether structural and functional MRI measures could serve as biomarkers related to prognosis.
Comparator
No separate comparator group is described. The study is not a randomized comparison, and allocation is not stated. The primary question concerns associations within the motor FND cohort rather than a contrast between treatments or between randomized arms.
Primary question
Do baseline gray matter volumes, particularly in limbic and paralimbic regions affiliated with the salience network, relate to mental or physical health outcomes at six months among people receiving standard of care? The registry describes the outcome as a peak voxel z-score from voxel-based morphometry. It does not report the z-score values or the corresponding outcome estimates, so the direction and magnitude of any specific association cannot be assessed from the registry record.
3. Trial Design
This completed study is titled “Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders” and is sponsored by Massachusetts General Hospital. The registry lists a start date of 2017-09-01 and a primary completion date of 2023-01-20. The listed enrollment is 30, and the study condition is conversion disorder.
The cohort description concerns patients with clinically established motor FND, including functional movement disorders, psychogenic nonepileptic seizures and functional limb weakness. Participants received standard of care. The intervention entry is “Standard of Care,” classified as “OTHER.” No separate control arm is described, and the study is not a randomized comparison; allocation is not stated. Accordingly, the primary question is about the relation between baseline neuroimaging and later clinical outcomes within the cohort, not the comparative effect of an assigned treatment.
The primary outcome description focuses on gray matter volume measured with voxel-based morphometry and clinical outcomes at baseline and six months. It describes associations between baseline gray matter volume and change in mental or physical health scores. The project’s broader stated goal also encompasses structural and functional MRI measures, including cortical thickness, resting-state functional connectivity and diffusion tensor imaging tractography.
The record lists three outcome measures and zero analyses. It reports that 22 participants provided follow-up data, but does not explain the analysis population for each outcome or how participants without follow-up were handled. The exact statistical plan, outcome instruments, and details of how standard of care was delivered are not reported in the registry record. The available registry information therefore supports a description of the study question and cohort, but not a full reconstruction of the study’s analytical conduct.
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
| Stage | Motor Functional Neurological Disorder. |
|---|---|
| STARTED | 30 |
| COMPLETED | 22 |
| NOT COMPLETED | 8 |
Analysis population for the primary outcome, as defined in the registry: For this study, of an initially enrolled 30 participants, 22 provided followup data.
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.
| Characteristic | Unit | Motor Functional Neurological Disorder. |
|---|---|---|
| Participants analysed | 22 | |
| Age, Continuous | years | 41.7 (SD 11.0) |
| Sex: Female, Male: Female | Participants | 19 |
| Sex: Female, Male: Male | Participants | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 22 |
| Region of Enrollment: United States | Participants | 22 |
6. Primary Endpoint
The registry lists the primary outcome as Gray Matter Volume Biomarkers of 6 Month Prognosis as Measured by Voxel Based Morphometry - Within Group Comparison, measured over baseline and 6 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | peak voxel z-score |
| Endpoint classification | not reduced to a single comparison |
The primary measure is described as the peak voxel z-score from voxel-based morphometry, used to express the strength of the association between baseline gray matter volume and a clinical outcome at six months. The outcomes of interest are changes in mental health or physical health scores among participants receiving standard of care. The description particularly identifies limbic and paralimbic regions associated with the salience network as regions of interest, while framing the analysis as a structural brain–prognosis investigation.
In general, voxel-based morphometry is an approach for examining regional differences in brain tissue volume across an image. A peak voxel is the location within an analyzed region or image where the reported statistic reaches its maximum. A z-score expresses a standardized statistical quantity; in this record, the endpoint description says that absolute values are reported, that the lowest value is 0, and that a higher value represents a stronger correlation at the peak voxel. The row title is described as indicating whether the association is positive or negative.
The endpoint is relevant to the stated prognostic question because it links a baseline imaging feature with a later clinical outcome. It is not itself a measure of treatment benefit, and an association does not establish that the brain measure causes the outcome. No peak voxel values, corresponding directions, or clinical outcome estimates are reported in the registry record, so the observed association cannot be quantified from this entry.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a neuroimaging prognosis study in a cohort receiving standard of care, with baseline gray matter volume related to clinical outcomes assessed at six months. Its primary endpoint is a peak voxel z-score, where the record says a higher absolute z-score indicates a stronger correlation at that location. The direction of an association is meant to be identified separately in the row title. These details define how the intended statistic should be read, but they do not supply the actual peak values or the estimated clinical relationships.
As a result, the registry record does not establish whether any of the proposed associations were positive or negative, how large they were, how uncertain they were, or whether they met a prespecified statistical criterion. It also does not report confidence intervals or p-values for the primary outcome. A z-score without the associated outcome estimates and uncertainty information is not enough to judge the precision or clinical relevance of a prognostic relationship. In particular, the description of a stronger correlation at a peak voxel should not be read as evidence that the imaging measure predicts outcomes accurately for individual patients.
The record’s population information says that 30 participants were initially enrolled and 22 provided follow-up data. This indicates that the follow-up information available in the registry description is not complete for everyone initially enrolled. The reasons for missing follow-up, the handling of missing observations, and the number included in each primary analysis are not reported in the registry record. Those omissions matter because incomplete follow-up can affect which participants contribute to an association estimate and how representative that estimate is of the enrolled cohort.
The project addresses a prognostic biomarker question, not a randomized treatment comparison. The presence of standard of care does not make the study an evaluation of the effect of a particular care strategy. Without a comparator group or a randomized allocation, any association between baseline MRI and later health scores would be observational. Such an association could be useful for developing hypotheses about prognosis, but it would not by itself show that changing gray matter volume changes clinical outcomes.
The registry lists three outcome measures but zero analyses, and provides no numerical primary result. Thus the posted registry information permits interpretation of the intended endpoint and study question, but not of an observed effect. The proper conclusion is limited: the registry records a planned or described analysis of baseline structural MRI in relation to six-month clinical outcomes, while numerical evidence needed to characterize the findings is not reported in the registry record.
9. Statistical Methods Explained
The primary endpoint uses voxel-based morphometry (VBM) to relate baseline gray matter volume to a clinical outcome assessed at six months. VBM is a structural MRI analysis approach that compares or models the amount of gray matter at locations across the brain after image processing. General explanation: the method converts a complex image into spatially indexed measurements, making it possible to examine whether local tissue measures vary with a clinical score. The registry identifies the peak voxel z-score as the reported statistic, but it does not give the underlying images, processing choices, model specification, or actual z-score values.
What does a peak voxel z-score convey?
As a general statistical concept, a z-score expresses a statistic on a standardized scale relative to a reference distribution under a statistical model. The registry’s endpoint description gives a specific reading rule: z-scores are shown as absolute values, the lowest value is 0, and higher values represent stronger correlations between gray matter volume at the peak voxel and the mental or physical health measure. Because the absolute value does not itself preserve the sign, the record says that the row title identifies a positive or negative association. No peak values or row-specific directions are present in the registry record, so the stated convention cannot be used to recover any actual result.
A peak statistic also needs context. A high value at one location does not alone indicate how precisely the association is estimated, whether it persists across neighboring locations, or whether it is clinically useful. General explanation: a confidence interval describes the range of estimates compatible with the data and the statistical model at a stated confidence level. The registry record does not provide confidence intervals, p-values, or clinical effect estimates for the primary outcome. Nor does it describe validation of a prediction rule or its performance for individual participants.
Why is multiplicity relevant to voxel-based analyses?
The primary description says that structural analyses correct for multiple comparisons. In general, an image-based analysis can involve evaluating many locations, so the chance of finding an apparently strong result by chance can increase if the multiplicity of tests is not addressed. A correction procedure aims to account for that multiplicity when assessing evidence. The registry does not report which correction method was used, what threshold was applied, or how the set of tests was defined. Consequently, the general purpose of correction can be explained, but the exact inferential standard used for this study cannot be reconstructed from the record.
How should the broader MRI methods be understood?
The project description names voxel-based morphometry, cortical thickness, resting-state functional connectivity and diffusion tensor imaging tractography as components of its multimodal MRI approach. In general, these approaches capture different aspects of brain structure or function: VBM assesses regional gray matter volume; cortical thickness estimates the thickness of the cerebral cortex; resting-state connectivity evaluates coordinated activity patterns when a participant is not performing a specified task; and diffusion tractography uses diffusion imaging to characterize pathways in white matter. These broad descriptions do not establish which methods generated reported findings or how each was modeled. The registry’s primary outcome specifically concerns gray matter volume measured by VBM, and it does not provide numerical results for that measure.
The clinical outcome is described as a change in either mental health or physical health scores. The names of the instruments, scoring rules, and clinical meaning of score changes are not reported in the registry record. General explanation: relating a baseline marker to a later outcome is a prognostic analysis. It differs from a treatment-effect analysis, which compares outcomes under alternative assigned interventions. Here, the record describes participants receiving standard of care and does not describe a randomized treatment contrast.
What do the planning illustrations mean?
The sample-size planning illustrations are described as calculations based on an observed effect, not as the study’s original design. Their assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target effect stated as a fraction of the observed effect. For time-to-event illustrations, the total number of events is used; for other illustrations, the quantity is participants per arm. These assumptions describe hypothetical planning exercises. They do not show that this cohort had two randomized arms, establish the study’s enrollment rationale, or represent observed power. The registry record does not report the study’s sample-size justification or the numerical planning results.
Overall, the methods description defines the intended biomarker relationship and several general analytical ideas, but leaves important implementation details unresolved. The model covariates, handling of repeated or changing clinical scores, missing-data methods, exact multiplicity correction and uncertainty estimates are not reported in the registry record. Without the numerical analysis results and these details, the endpoint can be interpreted conceptually but not independently evaluated in full.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome description states that structural analyses corrected for multiple comparisons. That is important for a voxel-based analysis, where many locations may be evaluated and uncorrected testing can overstate evidence. The registry does not specify the correction procedure, the threshold for declaring a result noteworthy, the number or scope of tests included, or whether the same approach applied across all outcomes. The record lists three outcome measures and zero analyses, but does not provide a multiplicity plan or a set of numerical results. It is therefore not possible to determine from the registry entry how the stated correction affected any particular finding.
For missing data, the record reports that 30 participants were initially enrolled and 22 provided follow-up data. It does not report why the remaining participants lacked follow-up, whether their missingness was related to health status or imaging measures, or whether any sensitivity analysis assessed the impact of missing observations. General explanation: results based only on participants with observed follow-up can be biased if those participants differ systematically from those without follow-up. That possibility cannot be assessed from the registry information alone.
The analysis population is also unclear. The record does not state how many participants contributed baseline MRI data, how many contributed each six-month clinical outcome, or whether the analyzed population differed across measures. No imputation or other missing-data procedure is described. The numerical results needed to understand the effect of these choices are not reported in the registry record. These gaps limit assessment of both the robustness of the primary analysis and the extent to which it represents the initially enrolled cohort.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Motor Functional Neurological Disorder. | 0 | 22 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Motor Functional Neurological Disorder. | 0 of 22 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Motor Functional Neurological Disorder. | 0 of 22 |
The registry lists one group, Motor Functional Neurological Disorder., with 22 participants at risk for serious adverse events and 0 affected. It also lists 22 at risk for other adverse events and 0 affected, with 0 deaths. These are event counts as recorded for the cohort; they are not a comparison between randomized treatment groups.
Zero reported events means that the registry lists no events in those categories for the participants counted as at risk. It does not establish that no adverse events occurred outside the recorded categories, that every event was captured, or that standard of care caused or prevented any event. The record does not give a detailed adverse-event collection period, event definitions, monitoring procedures, or information about exposure time. It also does not describe a comparator group that could support a comparative safety estimate.
These figures should therefore be read as a limited registry summary of reported event counts, not as evidence that the care context is risk-free. The safety information does not quantify event rates, and no rate should be inferred from these counts. The registry record does not report additional serious adverse event terms.
12. What the Result Does, and Does Not, Mean
This study addresses an important scientific question: whether structural or functional brain measures are associated with prognosis in motor FND. Its primary outcome description focuses on baseline gray matter volume and mental or physical health outcomes at six months. The registry also identifies a broader multimodal MRI goal, including structural and functional measures. That focus provides a rationale for examining brain–outcome relationships in a clinically diverse cohort.
What the posted registry information does not provide is the numerical primary result. Although it defines the peak voxel z-score and says how its absolute value and association direction should be interpreted, no actual z-score, clinical outcome estimate, confidence interval or p-value is reported. Therefore, the magnitude, direction and precision of the proposed association cannot be described from this record. The registry lists three outcome measures and zero analyses, which further means that no analysis estimates are available in the entry to assess.
Even if an association were reported, its interpretation would remain prognostic and observational. A baseline MRI feature associated with later health scores would not establish that the feature causes the outcome, nor that modifying it would alter the outcome. The study is not a randomized comparison, and no separate comparator group is described. It therefore does not test whether one treatment is better than another, nor does the record establish an effect of a specific treatment.
The reported follow-up information is also incomplete relative to enrollment: 30 participants were initially enrolled and 22 provided follow-up data. The registry does not explain the missing follow-up or how it was handled. This limits the ability to judge selection effects and the scope of any result. The appropriate reading is that the study was designed to investigate neuroimaging biomarkers of prognosis, while the registry record does not contain enough numerical results or analysis details to determine whether a particular biomarker was associated with outcome or how reliably it might predict outcome for individuals.
13. Why This Trial Matters Statistically
Statistically, this study illustrates the difference between a biomarker hypothesis and a demonstrated prognostic tool. A baseline imaging measure may be associated with a later clinical score, but a useful predictor requires more than a test statistic at a peak voxel. General evaluation typically considers the estimated association, its uncertainty, the stability of the finding, and whether it predicts outcomes in people beyond those used to develop the model. The registry record does not report the numerical estimates or prediction performance needed for those assessments.
The study also highlights the challenge of multiplicity in neuroimaging. Analyses may examine many locations and more than one kind of MRI measure or clinical outcome. The endpoint description acknowledges correction for multiple comparisons in structural analyses, but the correction method and its implementation are not reported. Without those details, readers cannot evaluate how the analysis distinguished a strong localized association from chance findings across a broad set of tests.
Follow-up completeness is another statistical concern. The record says that 22 of the initially enrolled 30 participants provided follow-up data, but does not describe why follow-up was unavailable for others or whether missingness was addressed. Such information matters because the participants with observed outcomes may not fully represent the cohort at enrollment.
Finally, the planning illustrations should be distinguished from the study design and from observed power. Their stated assumptions describe hypothetical planning calculations, including equal allocation between two arms, whereas the registry does not describe a randomized comparison. Statistical planning scenarios cannot substitute for a reported analysis, and they do not show that the study had a particular probability of detecting its results. These distinctions help keep the biomarker question, the actual cohort structure and the available evidence separate.
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 registry record leaves several trial-specific limitations that constrain interpretation. The cohort is described as including multiple motor FND presentations: functional movement disorders, psychogenic nonepileptic seizures and functional limb weakness. The record does not report whether results were estimated separately by presentation or how clinical heterogeneity was handled. It is therefore not possible to tell whether a pooled association, if one had been reported, would apply similarly across the included presentations.
The primary question relates baseline gray matter volume to six-month mental or physical health score changes, but the outcome instruments and scoring details are not reported in the registry record. The exact MRI acquisition and processing procedures, model covariates, and approach to repeated clinical measurements are also not described. These details can affect the interpretation and reproducibility of imaging associations.
Follow-up was available for 22 participants from an initially enrolled 30. Reasons for missing follow-up, participant characteristics among those with and without follow-up, and the missing-data strategy are not reported. The record also does not state the exact number contributing to each outcome analysis. No numerical primary results, confidence intervals, p-values, or analysis estimates are listed; the registry reports zero analyses. Consequently, the magnitude, direction, precision and robustness of any finding cannot be assessed from this entry.
The study is not a randomized comparison, allocation is not stated, and no separate control group is described. Associations in this cohort cannot isolate a causal effect of care or establish that an imaging feature causes subsequent health outcomes. The multiplicity correction is mentioned for structural analyses, but the procedure and threshold are not reported. Together, these omissions limit replication, assessment of bias, and judgments about how broadly any potential biomarker relationship could be generalized.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders — NCT03398070.
- Registry record last updated 2023-08-29; status last verified 2023-08.
- Results first posted 2023-08-29.
- 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.
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18. Record Summary
NCT03398070 is a completed study titled “Neuroimaging Biomarkers of Prognosis in Motor Functional Neurological Disorders,” sponsored by Massachusetts General Hospital. The registry lists enrollment of 30, a start date of 2017-09-01 and a primary completion date of 2023-01-20. The cohort received standard of care and included patients with motor FND presentations.
The primary outcome concerns the peak voxel z-score from voxel-based morphometry, relating baseline gray matter volume to mental or physical health outcomes at six months. The record says absolute z-scores indicate association strength and that the row title indicates direction. It also states that structural analyses corrected for multiple comparisons. The registry reports that 22 participants provided follow-up data, lists three outcome measures and lists zero analyses.
No numerical primary result, confidence interval or p-value is reported in the registry record. The design is not a randomized comparison, and allocation is not stated. The available entry describes the study question and endpoint but does not establish the direction, magnitude or precision of a biomarker association.