Transcranial Focused Ultrasound (tFUS) Modulation of Reward Network: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Transcranial Focused Ultrasound (tFUS) Modulation of Reward Network (NCT05986019), a randomized na study. The primary outcome is Resting State Functional Connectivity.

2. Clinical Question

3. Trial Design

This is a randomized, parallel-arm device study listed as phase NA. The registry record reports a completed study with an enrollment of 10 and two groups: Active tFUS and Sham tFUS. Each group has five participants in the posted outcome data. The intervention is transcranial focused ultrasound, administered in an MRI scanner and directed to the nucleus accumbens.

The active arm description specifies two 10-min stimulation sessions, separated by 10 min. The sham description says ultrasound is not delivered and participants will not know or be told whether they are receiving active or sham stimulation. The registry classifies masking as single. Its brief summary also calls the study a single-visit, open-label pilot. The record does not explain how those descriptions relate to each other, who is masked, or which study personnel know the assignment.

The record lists a start date of 2023-07-25 and a primary completion date of 2023-10-06. The summary describes resting-state imaging before and after stimulation. The primary outcome timeframe is 24 minutes. More detail about the visit schedule or the timing of image acquisition is not reported in the registry record.

Random assignment and a parallel-arm structure define how the groups are organized, but the record does not report the sequence-generation method, concealment procedures, or other operational details. The posted outcome includes group means and standard errors. A comparative analysis is not posted, so the randomized design alone does not establish the size or precision of an effect in these data.

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

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 Resting State Functional Connectivity, measured over 24 minutes.

The primary endpoint is titled Resting State Functional Connectivity and is reported in z value units. The registry description defines resting state functional connectivity as a statistical dependence between time series related to electrophysiological activity and blood oxygenation in distinct brain regions. The study’s stated interest is connectivity between the nucleus accumbens and connected regions, especially the prefrontal cortex and anterior cingulate cortex.

The registry summary frames the primary hypothesis around whether tFUS reduces PFC–NAc connectivity. Resting-state imaging is used to characterize relationships in brain activity when participants are not performing a specified task, which fits the study’s stated interest in connectivity rather than task performance. The brief summary says measurements are taken before and after stimulation, while the posted primary outcome has a timeframe of 24 minutes.

The outcome description also discusses modularity, a measure on a −1 to 1 scale, and explains that higher modularity represents stronger separation into interconnected networks. However, it does not clarify how modularity relates to the reported connectivity endpoint or identify the specific brain regions and processing steps used to generate each participant’s outcome value. The outcome is summarized as a mean with standard error. The registry record does not report a more detailed endpoint computation or a participant-level analysis method.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous and is summarized with a mean and standard error. A mean describes the central value of a set of measurements. The standard error describes the precision of an estimated mean: in general, a smaller standard error indicates a more precise estimate, while a larger standard error indicates greater uncertainty. It is not the same as the standard deviation, which describes variation among individual measurements.

A trial comparison generally focuses on a contrast between groups, rather than on whether each group’s mean is separately distinguishable from a particular reference value. For this study, the relevant contrast would compare the outcome under active tFUS with the outcome under sham tFUS, using a clearly specified analysis. The registry record does not post such a contrast. It identifies values missing or not estimable for a two-arm comparison of the continuous endpoint, and it lists no analyses. The arm means and standard errors should not be treated as a substitute for that missing comparison.

A confidence interval is a range of values compatible with the data and the assumptions of a statistical method. It communicates the uncertainty around an estimate, such as a treatment contrast. General interpretation depends on the interval’s width and the clinical or scientific context; an interval is not a guarantee that the true value lies within it. No confidence interval for the active-versus-sham contrast is reported in the registry record. The record also gives no interval limits for the individual arm summaries.

A p-value, when reported, measures how compatible the observed data are with a specified null hypothesis under a particular model. It does not measure the probability that the null hypothesis is true, and it does not describe the size or practical importance of an effect. No p-value or inferential test for the primary comparison is posted. It would be inappropriate to infer one from the arm summaries without the underlying data and a specified method.

Randomization is intended to make treatment assignment independent of participant characteristics, on average over repeated assignments. In a small trial, chance imbalances can still occur, and estimates can remain uncertain. Randomization does not itself guarantee that the observed groups are alike in every respect, nor does it compensate for missing outcome information or an unreported analysis. The record identifies a randomized parallel design but does not describe the randomization procedure or any adjustment strategy.

The registry record also contains a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, a normal approximation, and the target effect expressed as a stated fraction of the observed effect. Such calculations are hypothetical planning exercises, not outcomes observed in the trial and not evidence that a study had a particular probability of detecting an effect. The registry record does not report the study’s own sample-size justification. Any planning illustration should be distinguished from the trial’s enrollment and from an observed treatment effect.

Over-dispersion is a general concern when a model assumes less variability than the data actually contain. If present, it can make standard errors too small and statistical evidence appear more precise than warranted. The record does not report a model for the endpoint, a dispersion assessment, or a variance adjustment, so no claim about over-dispersion in this study can be made. More broadly, the posted summary does not identify the test, model, covariates, or handling of repeated measurements that would be used to estimate the treatment contrast.

Finally, the outcome description refers to both functional connectivity and modularity. A reproducible analysis would need to specify how the imaging signal becomes the reported z value, which regions are included, and whether the primary quantity is connectivity, modularity, or another summary. Those methodological details are not reported in the registry record. Without the comparative estimate and a sufficiently described analysis, the posted arm summaries support a limited descriptive reading rather than a full evaluation of the study hypothesis.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Active tFUS", "Sham tFUS")
n   <- c(5, 5)
m   <- c(0.069, 0.16)
sp  <- c(0.088, 0.094)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Active tFUS  5  0.069  0.197  -0.175  0.313
CARM  Sham tFUS  5  0.160  0.210  -0.101  0.421

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and zero posted secondary outcomes. It lists zero analyses. No inferential result for the primary comparison, or for any secondary endpoint, is posted. The record does not report a multiplicity plan, such as how multiple outcomes, time points, or imaging regions would be handled if more than one were analyzed. The number of reported outcomes alone does not establish what analyses were planned.

The brief summary describes resting-state measurements before and after stimulation and mentions the nucleus accumbens, prefrontal cortex, and anterior cingulate cortex. The registry does not specify whether these represent separate planned tests, how they would be combined, or whether any multiplicity adjustment was intended. Those details are not reported in the registry record, so the extent of any multiplicity issue cannot be determined from the posted information.

Missing-data procedures and the analysis population are also not reported in the registry record. The record does not state how many randomized participants completed imaging, whether all enrolled participants were included in the posted means, or how unusable or absent measurements were handled. The listed arm counts total the reported group sizes for the outcome, but they do not by themselves describe a prespecified analysis population or confirm that no data were missing.

The registry marks a two-arm comparison for the continuous endpoint as not estimable. This is a limit of the posted comparative result, not a stated explanation of why data or an estimate are unavailable. The record does not say whether the obstacle was missing observations, analysis choices, or another issue. Without that explanation, the comparative result cannot be reconstructed or interpreted as a null finding.

12. 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 registry reports serious adverse event figures separately for Active tFUS and Sham tFUS. In each group, five participants are listed at risk for serious adverse events, and zero are listed as affected. The recorded number of deaths is zero in each group. No serious adverse event terms are listed.

These counts are descriptive safety information for the participants represented in the registry record. They do not establish that no adverse events of any kind occurred: the record separately tracks serious events and other adverse events, and it lists zero affected participants in both categories for each group. The figures also do not provide a comparative statistical analysis or an estimate of risk difference.

With five participants per arm in the safety record, the counts are limited observations from a small study. Zero recorded events should not be interpreted as proof that an event cannot occur or that the interventions have been established as safe. The registry record does not provide further detail about event definitions, surveillance procedures, duration of follow-up, or how adverse events were collected. The figures should therefore be read as the reported event counts, not as a comprehensive safety conclusion.

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

This completed pilot trial addresses a focused neuroimaging question: whether active tFUS directed to the nucleus accumbens changes resting state functional connectivity, particularly between the nucleus accumbens and prefrontal cortex, compared with sham. The posted primary endpoint is summarized with an arm-specific mean and standard error. Those summaries are useful for describing the recorded outcome but do not answer the between-group question on their own.

The main limit is that the registry record does not report an estimable two-arm comparison or any analyses. It therefore does not provide a quantified treatment contrast, confidence interval, or inferential result. The active-arm mean of 0.069 and the sham-arm mean of 0.16 should not be converted into a new effect estimate or treated as proof of a difference. Nor does the lack of a posted comparison mean that the groups were shown to be equivalent.

The record’s stated hypothesis is directional: tFUS is expected to reduce PFC–NAc connectivity. The available summaries do not report pre-stimulation and post-stimulation outcomes separately or a comparative analysis of change. As a result, they do not establish whether the hypothesized change occurred. The endpoint description’s reference to modularity also leaves uncertainty about the exact imaging quantity represented by the posted outcome.

The record describes a randomized pilot study with five participants in each arm and reports zero serious adverse events, zero other adverse events, and zero deaths in both groups. These counts are observations in a small sample, not definitive evidence about uncommon harms. The study’s status is completed, but completion does not imply that a full inferential result has been posted.

Overall, the record offers a description of the study design and two arm-level outcome summaries, while leaving the central comparative statistical question unresolved. It does not support a conclusion that active tFUS increases, decreases, or leaves connectivity unchanged relative to sham.

14. Why This Trial Matters Statistically

This study is statistically interesting because it links a randomized device intervention to a brain-imaging endpoint rather than to a conventional clinical event. The stated question concerns functional connectivity between the nucleus accumbens and connected regions, especially the prefrontal cortex. That makes clear endpoint definition and transparent analysis particularly important: readers need to know exactly which signal is summarized and how the treatment contrast is estimated.

The record gives an opportunity to distinguish descriptive summaries from comparative inference. An arm mean describes the outcome in that group; a standard error describes uncertainty in that group mean. Neither alone answers whether outcomes differ between randomized groups. The registry’s explicit note that a two-arm comparison is not estimable highlights this distinction. Reporting the comparative estimate and its uncertainty would be central to evaluating the stated hypothesis.

The pilot scale also matters for interpretation. With five participants per arm, estimates are likely to be sensitive to individual observations, and uncertainty must be considered alongside the point summaries. The record’s planning illustration is not the same as observed evidence and does not establish the trial’s original design rationale. Keeping planning calculations separate from results helps prevent a hypothetical detectable effect from being mistaken for a finding.

Finally, the description combines functional connectivity with a discussion of modularity, and describes both before-and-after imaging and a 24-minute outcome timeframe. Clarifying the endpoint’s operational definition, timing, and analysis would make the findings easier to reproduce and compare. These are general lessons for imaging studies: an interpretable statistical result depends on a well-defined outcome and a reported contrast, not only on group-level summaries.

15. 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 posted result is limited by the absence of an estimable active-versus-sham comparison. The registry record provides the two arm means and standard errors but no comparative estimate, confidence interval, p-value, or analysis method. Consequently, the size and precision of the treatment contrast cannot be evaluated from the posted results.

The enrollment is 10, with five participants in each reported arm. This is a small pilot sample, and the record does not report a sample-size justification for the trial. The planning illustration described in the record is based on the observed effect and stated assumptions; it should not be read as the trial’s original design rationale or as observed power.

The endpoint description leaves methodological ambiguity. It defines resting state functional connectivity but also discusses modularity and its interpretation. It does not make clear whether modularity is the reported primary quantity, how the z value is calculated, which region pairs form the endpoint, or what image-processing steps are used. The record also does not provide the before-and-after values described in the study summary.

Other trial details are not reported in the registry record, including the randomization procedure, masking roles, missing-data handling, analysis population, and method for comparing groups. The brief summary describes the study as open-label, while the record lists single masking and says participants will not know whether they receive active or sham stimulation; the relationship among these descriptions is not explained.

Finally, the safety counts are limited to the recorded events and small groups. Follow-up duration and event-collection procedures are not reported in the registry record. These limitations restrict what can be concluded about both the primary imaging question and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Transcranial Focused Ultrasound (tFUS) Modulation of Reward Network — NCT05986019.
• Registry record last updated 2025-04-06; status last verified 2025-04.
• Results first posted 2025-04-06.
• 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.

19. Record Summary

NCT05986019 is a completed randomized, parallel-arm pilot study of transcranial focused ultrasound in healthy individuals. The record lists an enrollment of 10, with five participants in the Active tFUS group and five in the Sham tFUS group. Active stimulation targeted the nucleus accumbens inside an MRI scanner; the sham group received no ultrasound.

The primary outcome is Resting State Functional Connectivity, reported as a mean with standard error in z value units at a timeframe of 24 minutes. The active-arm mean is 0.069 with standard error 0.088; the sham-arm mean is 0.16 with standard error 0.094. A two-arm comparison is not estimable in the registry record, and no analyses are posted.

The registry reports zero serious adverse events, zero other adverse events, and zero deaths in each group. The record does not report a detailed analysis plan, missing-data method, or sample-size justification.