Source 1review2025MED
Toolkit/transcranial pulse stimulation
transcranial pulse stimulation
Also known as: TPS
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Non-invasive brain stimulations (NIBS), such as transcranial magnetic stimulation, transcranial direct current stimulation, transcranial alternating current stimulation, transcranial focused ultrasound, and transcranial pulse stimulation (TPS), employ electric currents or acoustic waves to induce and modulate neuroplasticity in humans.
Usefulness & Problems
No literature-backed usefulness or problem-fit explainer has been materialized for this record yet.
Published Workflows
Objective: Re-analyze sham-controlled clinical trial fMRI and cognitive data to test whether long-term effects of transcranial pulse stimulation in Alzheimer's disease could be explained by persistent auditory confounds.
Why it works: The workflow isolates possible auditory contributions by testing multiple contrast conditions and examining both task-evoked and resting-state auditory-network measures together with cognitive correlations.
persistent auditory network activation as a possible confoundair-conducted sound effectscombined air- and possibly bone-conducted sound effectsbone-conduction-specific effectstask-based fMRI re-analysisresting-state fMRI re-analysiscontrast-based frameworkcorrelation with neuropsychological test battery scores
Stages
- 1.Task-based auditory cortex co-activation analysis(functional_characterization)
This stage tests whether task-evoked auditory cortical activity persists long after TPS and could explain reported therapeutic effects.
Selection: Assess whether long-term task-based fMRI shows auditory cortex activation consistent with persistent auditory confounds.
- 2.Resting-state auditory and dorsal attention network connectivity analysis(secondary_characterization)
This stage examines whether the network modulated in the original study could instead reflect persistent auditory-network interaction.
Selection: Test whether resting-state functional connectivity between auditory and dorsal attention networks is altered.
- 3.Auditory network global efficiency analysis(secondary_characterization)
This stage broadens the confound test from focal activation and pairwise connectivity to network-level auditory organization.
Selection: Measure whether global efficiency within the auditory network changes after TPS.
- 4.Correlation of auditory metrics with neuropsychological scores(confirmatory_validation)
This stage checks whether any auditory-network measure tracks neuropsychological outcomes, which would strengthen a confound explanation if present.
Selection: Test whether auditory metrics are associated with cognitive performance.
Steps
- 1.Re-analyze task-based and resting-state fMRI data from the sham-controlled TPS clinical studyintervention under analysis
Use existing clinical trial imaging data to test long-term auditory confound hypotheses.
The study begins from the available largest sham-controlled dataset because the confound question concerns interpretation of previously reported long-term TPS effects.
- 2.Apply contrast-based framework for air-conducted, combined air/bone-conducted, and bone-conduction-specific effects
Isolate possible auditory contributions under multiple confound models.
The contrast framework is applied before interpreting imaging outcomes so that different possible auditory pathways can be separated analytically.
- 3.Assess task-based auditory cortex co-activation
Determine whether long-term auditory cortical activation is present.
This provides a direct test of persistent auditory activation before moving to broader network and behavioral association analyses.
- 4.Measure resting-state connectivity between auditory and dorsal attention networks
Test whether the network modulated in the original study shows persistent coupling to auditory networks.
After checking focal auditory activation, the analysis examines whether longer-range network interactions could still support an auditory confound explanation.
- 5.Quantify global efficiency within the auditory network
Evaluate whether distributed auditory network organization is altered long-term.
This follows pairwise connectivity analysis to test a broader network-level signature of persistent auditory effects.
- 6.Correlate auditory metrics with neuropsychological test battery scores
Determine whether any auditory-network measure relates to cognitive performance.
Behavioral correlation is used as a final interpretive check after imaging metrics are computed, because a confound explanation for therapeutic outcomes would require relevance to cognition.
Objective: Systematically synthesize clinical evidence on TPS effects on cognition, motor function, mental health, and safety across neurological and psychiatric disorders.
Why it works: The review first identifies relevant studies across multiple databases, then applies independent study selection and data extraction before formal quality assessment, allowing outcome synthesis to be interpreted in light of study quality and bias.
literature searchstudy selectiondata extractionquality assessmentrisk-of-bias assessmentmeta-analysis
Stages
- 1.Literature search(in_silico_filter)
To identify the available TPS literature across databases before screening and synthesis.
Selection: Searches were conducted in MEDLINE, PsycINFO & PsycArticles, CENTRAL, Web of Science, and Google Scholar for the period January 2013 to December 2024.
- 2.Study selection(decision_gate)
To narrow the search results to studies eligible for inclusion in the review.
Selection: Two independent reviewers conducted the study selection.
- 3.Data extraction and quality assessment(functional_characterization)
To collect outcome and safety data in a structured way and assess study quality before interpretation.
Selection: Two independent reviewers conducted the data extraction and quality assessment.
- 4.Risk-of-bias assessment by study design(counter_screen)
To evaluate internal validity using tools matched to study design before drawing conclusions about TPS effects.
Selection: RoB2 was used for randomized studies and ROBINS-I for non-randomized studies.
- 5.Outcome synthesis and interpretation(confirmatory_validation)
To summarize whether TPS appears promising while explicitly accounting for study limitations.
Selection: Included studies were synthesized for cognitive, motor, mental health, and safety outcomes.
Steps
- 1.Search multiple literature databases over a defined date range
Capture the available TPS evidence base across relevant bibliographic sources.
Broad retrieval must occur before any study selection, extraction, or quality assessment can be performed.
- 2.Use two independent reviewers for study selection
Determine which retrieved studies are eligible for inclusion.
Selection follows retrieval so that only eligible studies move into extraction and synthesis.
- 3.Use two independent reviewers for data extraction and quality assessment
Collect study outcomes and assess study quality in a structured manner.
Extraction and quality assessment require a finalized included-study set from the prior selection step.
- 4.Apply RoB 2 to randomized studies and ROBINS-I to non-randomized studiesrisk-of-bias assessment tools
Assess bias using a tool matched to study design.
Design-specific bias assessment is performed after studies are identified and extracted so that interpretation can be conditioned on study quality.
- 5.Synthesize efficacy and safety outcomes while accounting for study limitations
Generate a review-level conclusion about TPS effects and safety.
Synthesis comes after extraction and bias assessment so conclusions can be interpreted in the context of evidence quality.
Objective: Systematically identify randomized sham-controlled trials of low-intensity ultrasound neuromodulation for major depressive disorder and synthesize efficacy and safety evidence.
Why it works: The review first narrows evidence to randomized sham-controlled trials, then pools depressive symptom change quantitatively while summarizing adverse events narratively. This ordering supports a focused efficacy estimate while retaining safety information even when event reporting may be too sparse or heterogeneous for pooling.
database searchingindependent study screeningdata extractionrandom-effects meta-analysisheterogeneity quantificationnarrative adverse-event synthesis
Stages
- 1.Literature search for eligible randomized sham-controlled LIUN trials(in_silico_filter)
This stage identifies the candidate evidence base before manual screening and synthesis.
Selection: Search multiple bibliographic and trial-registry sources for randomized controlled trials comparing active LIUN versus sham in adults with MDD.
- 2.Independent screening and data extraction(hit_picking)
Independent screening narrows the search results to included studies and prepares structured data for synthesis.
Selection: Two reviewers independently screened studies and extracted data.
- 3.Quantitative efficacy synthesis(functional_characterization)
This stage estimates overall efficacy across included RCTs while accounting for between-study variation.
Selection: Pool depressive symptom change using a random-effects model and quantify heterogeneity with I².
- 4.Narrative safety synthesis(secondary_characterization)
Safety is assessed alongside efficacy because a clinically useful neuromodulation intervention must also be tolerable.
Selection: Summarize adverse events narratively across included trials.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A delivery strategy grouped with the mechanism branch because it determines how a system is instantiated and deployed in context.
Techniques
No technique tags yet.
Target processes
No target processes tagged yet.
Input: Chemical
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Observations
successHuman Clinicaltherapeutic usehuman
task-based fMRI
Inferred from claim c2 during normalization. No significant long-term activation of auditory cortices was observed in task-based fMRI following transcranial pulse stimulation. Derived from claim c2.
Source:
Supporting Sources
Source 2review2025PPR
Source 3review2025MED
Source 4primary paper2026MED
Ranked Claims
Persistent auditory confounds are unlikely to be a key factor underlying the long-term cognitive network effects observed with transcranial pulse stimulation in typical verum-sham settings.
No significant long-term activation of auditory cortices was observed in task-based fMRI following transcranial pulse stimulation.
Resting-state analyses showed no altered connectivity between auditory and dorsal attention networks, no changes in auditory network global efficiency, and no associations between auditory metrics and cognitive performance following transcranial pulse stimulation.
TPS shows promising evidence for symptom modulation in clinical populations spanning neurocognitive disorders, common mental disorders, and neurodevelopmental disorders.
The emerging NIBS treatment modality TPS demonstrates promising evidence in modulating symptoms in clinical population of neurocognitive disorders, common mental disorders, and neurodevelopmental disorders.
Interpretation of TPS efficacy is limited by small sample sizes, lack of control groups, retrospective analyses, and heterogeneity of study protocols and measurements.
The current randomized evidence base for low-intensity ultrasound neuromodulation in major depressive disorder is preliminary and insufficiently standardized, requiring larger parameter-standardized trials and long-term safety assessment.
However, the small number of heterogeneous trials underscores the need for larger, parameter-standardized RCTs to confirm efficacy, optimize sonication protocols, and establish long-term safety.
Standardized protocol procedures and larger sham-controlled trials are needed to better assess the potential of TPS.
Non-invasive brain stimulation modalities including TPS use electric currents or acoustic waves to induce and modulate neuroplasticity in humans.
Non-invasive brain stimulations (NIBS), such as transcranial magnetic stimulation, transcranial direct current stimulation, transcranial alternating current stimulation, transcranial focused ultrasound, and transcranial pulse stimulation (TPS), employ electric currents or acoustic waves to induce and modulate neuroplasticity in humans.
Across three randomized sham-controlled trials in adults with major depressive disorder, low-intensity ultrasound neuromodulation produced a small-to-moderate reduction in depressive symptoms versus sham.
LIUN yielded a small-to-moderate reduction in depressive symptoms compared to sham (SMD = –0.55; 95 % CI: − 1.07 to − 0.02; p = 0.04). Between-stud heterogeneity was low (I² = 23 %).
95% confidence interval lower bound -1.0795% confidence interval upper bound -0.02completers 68I squared 23 %p value 0.04randomized participants 78standardized mean difference -0.55
The review used RoB 2 for randomized studies and ROBINS-I for non-randomized studies to assess risk of bias.
Future TPS research should investigate underlying neurophysiological and biochemical effects, sustainability, and use higher-quality randomized controlled trials with larger sample sizes.
Thus, it is essential to encourage future research to investigate the underlying neurophysiological and biochemical effects of TPS, as well as its sustainability, by incorporating high-quality randomized controlled trials with larger sample sizes to strengthen the validation of its effects.
Across fifteen included studies, TPS showed positive effects on cognitive, motor, and mental health outcomes in a majority of studies and outcome parameters.
Adverse events reported for low-intensity ultrasound neuromodulation in the included MDD trials were generally mild and self-limiting.
Adverse events—transient headache, scalp ingling, and skin redness—were generally mild and self-limiting.
The review reports a high safety profile for TPS across the included neurological and psychiatric disorder studies.
The efficacy of TPS in treating neuropsychiatric disorders remains unknown according to the review.
The efficacy of TPS in treating neuropsychiatric disorders is still unknown; hence, this article reviews the currently available clinical studies on the therapeutic effectiveness of TPS on symptom reduction in the clinical population to inform future neuropsychiatric treatments and research directions.
TPS has been well tolerated across age groups from adolescents to older adults.
It has been well tolerated across age groups, from adolescents to older adults.
Approval Evidence
5 sources12 linked approval claimsfirst-pass slug transcranial-pulse-stimulation
This exploratory study is the first to examine whether long-term cognitive and neural effects of transcranial pulse stimulation (TPS) in AD are linked to persistent auditory network activation.
Source:
Non-invasive brain stimulations (NIBS), such as transcranial magnetic stimulation, transcranial direct current stimulation, transcranial alternating current stimulation, transcranial focused ultrasound, and transcranial pulse stimulation (TPS), employ electric currents or acoustic waves to induce and modulate neuroplasticity in humans.
Source:
Low-intensity ultrasound neuromodulation (LIUN), which includes low-intensity focused ultrasound (LIFU) and transcranial pulse stimulation (TPS)... Three RCTs ... met inclusion criteria ... and two TPS trials (Cheung et al., 2022; QIN, 2025).
Source:
Transcranial pulse stimulation (TPS) is an innovative non-invasive brain stimulation technique using ultrasonic waves.
Source:
The supplied web research summary states that explicit related modality/component names include transcranial pulse stimulation (TPS).
Source:
mechanistic interpretationsupports
Persistent auditory confounds are unlikely to be a key factor underlying the long-term cognitive network effects observed with transcranial pulse stimulation in typical verum-sham settings.
Source:
negative resultsupports
No significant long-term activation of auditory cortices was observed in task-based fMRI following transcranial pulse stimulation.
Source:
negative resultsupports
Resting-state analyses showed no altered connectivity between auditory and dorsal attention networks, no changes in auditory network global efficiency, and no associations between auditory metrics and cognitive performance following transcranial pulse stimulation.
Source:
clinical signal summarysupports
TPS shows promising evidence for symptom modulation in clinical populations spanning neurocognitive disorders, common mental disorders, and neurodevelopmental disorders.
The emerging NIBS treatment modality TPS demonstrates promising evidence in modulating symptoms in clinical population of neurocognitive disorders, common mental disorders, and neurodevelopmental disorders.
Source:
evidence limitationmixed
Interpretation of TPS efficacy is limited by small sample sizes, lack of control groups, retrospective analyses, and heterogeneity of study protocols and measurements.
Source:
future directionsupports
Standardized protocol procedures and larger sham-controlled trials are needed to better assess the potential of TPS.
Source:
mechanism scopesupports
Non-invasive brain stimulation modalities including TPS use electric currents or acoustic waves to induce and modulate neuroplasticity in humans.
Non-invasive brain stimulations (NIBS), such as transcranial magnetic stimulation, transcranial direct current stimulation, transcranial alternating current stimulation, transcranial focused ultrasound, and transcranial pulse stimulation (TPS), employ electric currents or acoustic waves to induce and modulate neuroplasticity in humans.
Source:
research gapsupports
Future TPS research should investigate underlying neurophysiological and biochemical effects, sustainability, and use higher-quality randomized controlled trials with larger sample sizes.
Thus, it is essential to encourage future research to investigate the underlying neurophysiological and biochemical effects of TPS, as well as its sustainability, by incorporating high-quality randomized controlled trials with larger sample sizes to strengthen the validation of its effects.
Source:
review summarysupports
Across fifteen included studies, TPS showed positive effects on cognitive, motor, and mental health outcomes in a majority of studies and outcome parameters.
Source:
safety summarysupports
The review reports a high safety profile for TPS across the included neurological and psychiatric disorder studies.
Source:
therapeutic evidence summarymixed
The efficacy of TPS in treating neuropsychiatric disorders remains unknown according to the review.
The efficacy of TPS in treating neuropsychiatric disorders is still unknown; hence, this article reviews the currently available clinical studies on the therapeutic effectiveness of TPS on symptom reduction in the clinical population to inform future neuropsychiatric treatments and research directions.
Source:
tolerability summarysupports
TPS has been well tolerated across age groups from adolescents to older adults.
It has been well tolerated across age groups, from adolescents to older adults.
Source:
Comparisons
No literature-backed comparison notes have been materialized for this record yet.
Ranked Citations
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