Effects of Cerebellar Stimulation on Brain ActivationNCT06108336
Cerebellar Involvement in Cognitive Sequencing
A study testing TMS during sequence-demanding task, No TMS during sequence-demanding task and TMS during non-sequence-demanding task in people with Effects of Cerebellar Stimulation on Brain Activation, run by Johns Hopkins University at 1 site in United States.
Trial summary
Although there is increasing recognition that the cerebellum is involved in cognition as well as motor function, the manner in which the cerebellum contributes to cognition is uncertain. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Effects of Cerebellar Stimulation on Brain Activation
- What is being tested?
- TMS during sequence-demanding task, No TMS during sequence-demanding task and TMS during non-sequence-demanding task
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2024to 31 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 1) Age 18-50;
- 2) educational attainment of at least 8 years;
- 3) capable of giving informed consent;
- 4) fluent speaker of English by self-report;
- 5) right handed.
Who cannot join
- 1) illicit drug use within 30 days of MRI scanning;
- 2) neurological or systemic disorder which can cause dementia or cognitive dysfunction;
- 3) history of an Axis I psychiatric disorder including substance use disorder;
- 4) history of definite stroke;
- 5) focal lesion on MRI exam;
- 6) uncorrected visual deficits by self-report
Show all 9Show fewer
- 7) contraindications for MRI scanning
- 8) use of anxiolytic, antidepressant, neuroleptic, or sedative medication
- 9) Additional exclusion criteria recommended by Wassermann for TMS neuromodulation, including: History of seizure or a family history of epilepsy, heart disease, intracardiac lines, increased intracranial pressure, history of head trauma, and history of respiratory disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21205
John E. Desmond, Ph.D.
About this study
Official title: Investigation of Cerebellar Involvement in Cognitive Sequencing
Although there is increasing recognition that the cerebellum is involved in cognition as well as motor function, the manner in which the cerebellum contributes to cognition is uncertain. One theory that might account for both motor and cognitive contributions of the cerebellum is that the cerebellum is involved in sequencing of relevant events or stimuli. Previous experiments have suggested that disruption of the cerebellum impairs the prediction of the next event in a sequence. The present experiment will examine the impact of cerebellar stimulation on brain activation during the performance of both sequence-demanding and non-sequence-demanding tasks.
Read the detailed description
Although there is increasing recognition that the cerebellum, which contains half of the brain's neurons, is involved in cognition as well as motor function, the manner in which the cerebellum contributes to cognition is uncertain. The uniform circuitry of the cerebellum and the extensive connectivity of the cerebellum with numerous neocortical regions has suggested to some researchers that there is a common computation that the cerebellum performs for both motor and cognitive functions. The cerebellar sequencing hypothesis posits that the cerebellum acquires sequence information, makes sequence predictions, and detects sequence violations. These functions, executed via a forward model, could underlie cerebellar involvement in both motor and cognitive behavior. In motor control, such predictions can be used to guide limb trajectory without reliance on movement-generated sensory feedback. In cognition, sequencing requirements are prominent in both verbal working memory (VWM) and language acquisition; eg, in VWM, keeping a phone number in mind requires encoding and rehearsing a sequence of digits. In language, words consist of sequences of syllables, and the learning of syllable transition probabilities is an important component of recognizing legal words in a language. Importantly, prominent cerebellar activation has been observed in many functional MRI (fMRI) VWM and language studies. However, the brainstem/cerebellar neural correlates of sequencing in cognition, and the influence of cerebellar sequence predictions on neocortical targets, are poorly understood. In this experiment, studying healthy individuals the investigators will Investigate the cerebellum as a source of sequence prediction and its influence on forebrain areas. The cerebellum is hypothesized to provide its forward model sequence prediction to forebrain targets, but to date no study has attempted to visualize with concurrent TMS/fMRI the consequences of disrupting this cerebellar input on forebrain activation. In the investigators previous work, the investigators show that transcranial magnetic stimulation (TMS) during the rehearsal of a sequence of letters results in errors in determining if a probe letter matches the next letter in the sequence, suggesting that TMS disrupted this predictive input. In accordance with this finding, the investigators hypothesize that, using concurrent TMS/fMRI, TMS disruption during a sequencing task will produce greater changes in neocortical activation relative to an analogous control task that does not have the predictive component brought out by sequencing demands. The investigators further hypothesize that different patterns of neocortical activations in response to cerebellar TMS will be observed depending on whether a probe letter matches the expected next letter in a sequence.
- Being tested
- TMS during sequence-demanding task, No TMS during sequence-demanding task, TMS during non-sequence-demanding task, No TMS during non-sequence-demanding task
- Keywords
- sequencing, cerebellum, transcranial magnetic stimulation, TMS, functional MRI, fMRI, verbal working memory
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMS during sequence-demanding taskProcedure or surgery
Also called Transcranial magnetic stimulation
TMS is administered during the execution of sequence-demanding task. Transcranial magnetic stimulation (TMS) is a safe and non-invasive technique for transiently modulating brain activity
No TMS during sequence-demanding taskProcedure or surgery
TMS is not administered during the execution of sequence-demanding task.
TMS during non-sequence-demanding taskProcedure or surgery
TMS is administered during the execution of non-sequence-demanding task. Transcranial magnetic stimulation (TMS) is a safe and non-invasive technique for transiently modulating brain activity
No TMS during non-sequence-demanding taskProcedure or surgery
TMS is not administered during the execution of non-sequence-demanding task
| Study group | Role | What they receive |
|---|---|---|
| Cerebellar Stimulation | Experimental | TMS will be administered to the cerebellum on half the trials of a sequence-demanding task, and on half the trials of a non-sequence-demanding task. Task order will be counterbalanced. Receives: Procedure: TMS during sequence-demanding task; Procedure: No TMS during sequence-demanding task; Procedure: TMS during non-sequence-demanding task; Procedure: No TMS during non-sequence-demanding task |
| Occipital Stimulation | Active comparator | TMS will be administered to an occipital control region on half the trials of a sequence-demanding task, and on half the trials of a non-sequence-demanding task. Task order will be counterbalanced. Receives: Procedure: TMS during sequence-demanding task; Procedure: No TMS during sequence-demanding task; Procedure: TMS during non-sequence-demanding task; Procedure: No TMS during non-sequence-demanding task |
What is being measured
The primary outcome is the main question the study is designed to answer.
functional magnetic resonance imaging brain activation
functional magnetic resonance imaging brain activation. For the sequential task, a sequence of letters is presented and the subject is presented with number signs, one at a time, to guide rehearsal of the sequence. At some point a probe letter is presented and the subject indicates by button press if the probe is the next letter in the sequence. For the non-sequential task, subjects do not have a guided rehearsal, and the response to the probe indicates if the probe was one of the letters originally presented. Brain activation in response to the probe will be measured with brain stimulation vs no brain stimulation for each task
Measured: during scan up to 1 hour
Secondary outcomes (2)
percent correct of behavioral responses
percent correct of behavioral responses. For the sequential task, a sequence of letters is presented and the subject is presented with # signs, one at a time, to guide rehearsal of the sequence. At some point a probe letter is presented and the subject indicates by button press if the probe is the next letter in the sequence. For the non-sequential task, subjects do not have a guided rehearsal, and the response to the probe indicates if the probe was one of the letters originally presented. Behavioral accuracy consists of the percent of correct responses to the probe, with higher numbers indicating better performance
Measured: during scan up to 1 hour
behavioral reaction time (milliseconds)
behavioral reaction time to respond to the probe. Increases in reaction time indicate greater difficulty for the subject to respond
Measured: during scan up to 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2023
- Study start1 Mar 2024
- Primary completion30 Nov 2026 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Effects of Cerebellar Stimulation on Brain ActivationStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Cerebellar and Occipital stimulation groups will be tested under sequence-demanding and non-sequence demanding tasks (in counterbalanced order)
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- John E Desmond, Ph.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06108336
- Sponsor's protocol ID
- IRB00328214
- Other IDs
- R01MH128278
- Status last verified
- Sep 2026
- First submitted
- 25 Oct 2023
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Cerebellar Involvement in Cognitive Sequencing
- ClinicalTrials.gov ID
- NCT06108336
- Acronym / sponsor ID
- IRB00328214
- Keywords
- sequencing, cerebellum, transcranial magnetic stimulation, TMS, functional MRI, fMRI, verbal working memory
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Mar 2024 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 31 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Although there is increasing recognition that the cerebellum is involved in cognition as well as motor function, the manner in which the cerebellum contributes to cognition is uncertain. One theory that might account for both motor and cognitive contributions of the cerebellum is that the cerebellum is involved in sequencing of relevant events or stimuli. Previous experiments have suggested that disruption of the cerebellum impairs the prediction of the next event in a sequence. The present experiment will examine the impact of cerebellar stimulation on brain activation during the performance of both sequence-demanding and non-sequence-demanding tasks.
Detailed description
Although there is increasing recognition that the cerebellum, which contains half of the brain's neurons, is involved in cognition as well as motor function, the manner in which the cerebellum contributes to cognition is uncertain. The uniform circuitry of the cerebellum and the extensive connectivity of the cerebellum with numerous neocortical regions has suggested to some researchers that there is a common computation that the cerebellum performs for both motor and cognitive functions. The cerebellar sequencing hypothesis posits that the cerebellum acquires sequence information, makes sequence predictions, and detects sequence violations. These functions, executed via a forward model, could underlie cerebellar involvement in both motor and cognitive behavior. In motor control, such predictions can be used to guide limb trajectory without reliance on movement-generated sensory feedback. In cognition, sequencing requirements are prominent in both verbal working memory (VWM) and language acquisition; eg, in VWM, keeping a phone number in mind requires encoding and rehearsing a sequence of digits. In language, words consist of sequences of syllables, and the learning of syllable transition probabilities is an important component of recognizing legal words in a language. Importantly, prominent cerebellar activation has been observed in many functional MRI (fMRI) VWM and language studies. However, the brainstem/cerebellar neural correlates of sequencing in cognition, and the influence of cerebellar sequence predictions on neocortical targets, are poorly understood. In this experiment, studying healthy individuals the investigators will Investigate the cerebellum as a source of sequence prediction and its influence on forebrain areas. The cerebellum is hypothesized to provide its forward model sequence prediction to forebrain targets, but to date no study has attempted to visualize with concurrent TMS/fMRI the consequences of disrupting this cerebellar input on forebrain activation. In the investigators previous work, the investigators show that transcranial magnetic stimulation (TMS) during the rehearsal of a sequence of letters results in errors in determining if a probe letter matches the next letter in the sequence, suggesting that TMS disrupted this predictive input. In accordance with this finding, the investigators hypothesize that, using concurrent TMS/fMRI, TMS disruption during a sequencing task will produce greater changes in neocortical activation relative to an analogous control task that does not have the predictive component brought out by sequencing demands. The investigators further hypothesize that different patterns of neocortical activations in response to cerebellar TMS will be observed depending on whether a probe letter matches the expected next letter in a sequence.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Cerebellar and Occipital stimulation groups will be tested under sequence-demanding and non-sequence demanding tasks (in counterbalanced order)
| Arm | Type | Receives |
|---|---|---|
| Cerebellar Stimulation | Experimental | Procedure: TMS during sequence-demanding task, Procedure: No TMS during sequence-demanding task, Procedure: TMS during non-sequence-demanding task, Procedure: No TMS during non-sequence-demanding taskTMS will be administered to the cerebellum on half the trials of a sequence-demanding task, and on half the trials of a non-sequence-demanding task. Task order will be counterbalanced. |
| Occipital Stimulation | Active comparator | Procedure: TMS during sequence-demanding task, Procedure: No TMS during sequence-demanding task, Procedure: TMS during non-sequence-demanding task, Procedure: No TMS during non-sequence-demanding taskTMS will be administered to an occipital control region on half the trials of a sequence-demanding task, and on half the trials of a non-sequence-demanding task. Task order will be counterbalanced. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 1) Age 18-50;
- 2) educational attainment of at least 8 years;
- 3) capable of giving informed consent;
- 4) fluent speaker of English by self-report;
- 5) right handed.
Key exclusion criteria (9 listed)
- 1) illicit drug use within 30 days of MRI scanning;
- 2) neurological or systemic disorder which can cause dementia or cognitive dysfunction;
- 3) history of an Axis I psychiatric disorder including substance use disorder;
- 4) history of definite stroke;
- 5) focal lesion on MRI exam;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TMS during sequence-demanding taskAlso: Transcranial magnetic stimulationTMS is administered during the execution of sequence-demanding task. Transcranial magnetic stimulation (TMS) is a safe and non-invasive technique for transiently modulating brain activity | Procedure or surgery | Cerebellar Stimulation, Occipital Stimulation |
| No TMS during sequence-demanding taskTMS is not administered during the execution of sequence-demanding task. | Procedure or surgery | Cerebellar Stimulation, Occipital Stimulation |
| TMS during non-sequence-demanding taskTMS is administered during the execution of non-sequence-demanding task. Transcranial magnetic stimulation (TMS) is a safe and non-invasive technique for transiently modulating brain activity | Procedure or surgery | Cerebellar Stimulation, Occipital Stimulation |
| No TMS during non-sequence-demanding taskTMS is not administered during the execution of non-sequence-demanding task | Procedure or surgery | Cerebellar Stimulation, Occipital Stimulation |
Primary outcome
functional magnetic resonance imaging brain activation
Time frame: during scan up to 1 hour
functional magnetic resonance imaging brain activation. For the sequential task, a sequence of letters is presented and the subject is presented with number signs, one at a time, to guide rehearsal of the sequence. At some point a probe letter is presented and the subject indicates by button press if the probe is the next letter in the sequence. For the non-sequential task, subjects do not have a guided rehearsal, and the response to the probe indicates if the probe was one of the letters originally presented. Brain activation in response to the probe will be measured with brain stimulation vs no brain stimulation for each task
2 secondary outcomes
percent correct of behavioral responses
Time frame: during scan up to 1 hour
behavioral reaction time (milliseconds)
Time frame: during scan up to 1 hour
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
John E Desmond, Ph.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TMS during sequence-demanding task, No TMS during sequence-demanding task and TMS during non-sequence-demanding task in people with Effects of Cerebellar Stimulation on Brain Activation, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact John E Desmond, Ph.D. (410-502-3583, jdesmon2@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
functional magnetic resonance imaging brain activation (time frame: during scan up to 1 hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026; AzTrials last refreshed its copy on 1 Nov 2026.