HealthyNCT05797636
Criticality, Working Memory, and Effort
A study testing transcranial magnetic stimulation in people with Healthy, run by Brown University at 1 site in United States.
Trial summary
The project examines electroencephalography, MRI, and behavioral measures indexing flexibility (critical state dynamics) in the brain when healthy young adults do demanding cognitive tasks, and in response to transcranial magnetic stimulation. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- transcranial magnetic stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Mar 2023to 30 Jun 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study and availability for the duration of the study
- Males and females; Ages 18-45
- Healthy, neurologically normal with no diagnosed mental or physical illness
- Willingness to adhere to the MRI and two session stimulation protocol
- Fluent in English
Show all 9Show fewer
- Normal or corrected to normal vision
- At least twelve years of education (high school equivalent)
- Right-handed
Who cannot join
- Ongoing drug or alcohol abuse
- Diagnosed psychiatric or mental illness
- Currently taking psychoactive medication
- Prior brain injury
- Metal in body
- History of seizures or diagnosis of epilepsy
Show all 10Show fewer
- Claustrophobia
- Pregnant or possibly pregnant
- Younger than 18 or older than 45
- Use of medications which potentially lower the usage threshold
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Theta-burst Stimulation Modulates Criticality, Working Memory and Subjective Effort
The project examines electroencephalography, MRI, and behavioral measures indexing flexibility (critical state dynamics) in the brain when healthy young adults do demanding cognitive tasks, and in response to transcranial magnetic stimulation.
Read the detailed description
The healthy human brain is a complex, dynamical system which is hypothesized to lie near a phase transition at rest - at the boundary between order and chaos. Proximity to this critical point is functionally adaptive as it affords maximal flexibility, dynamic range, and information handling capacity, with implications for working memory function. Divergence from this critical point has become correlated with diverse forms of psychopathology and neuropathy suggesting that distance from a critical point is both a potential biomarker of disorder and also a target for intervention in disordered brains. The Investigators have further hypothesized that subjective cognitive effort is a reflection of sub-criticality induced by engagement with demanding tasks.
A key control parameter determining distance from criticality in a resting brain is hypothesized to be the balance of cortical excitation to inhibition (the "E/I balance"). Transcranial magnetic stimulation is a widely used experimental and clinical tool for neuromodulation and theta-burst stimulation (TBS) protocols are thought to modulate the E/I balance. Here the Investigators test whether cortical dynamics can be systematically modulated away from the critical point with continuous theta-burst stimulation (cTBS), which is thought to decrease the E/I balance, and thereby impact on working memory function and subjective cognitive effort during performance of the working memory tasks.
- Conditions
- Healthy
- Being tested
- transcranial magnetic stimulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transcranial magnetic stimulationDevice
The study intervention is modulation of cortical excitation to inhibition (E/I) balance in the dorsolateral prefrontal cortex (dlPFC) by means of 2 trains of spaced continuous theta burst stimulation (cTBS) using a transcranial magnetic stimulation device. As prior work (Huang et al 2005; Chung et al. 2018) has shown that cTBS reliably decreases the cortical E/I ratio with diverse cortical targets, the Investigators expect to replicate a reduction in E/I balance when applied. The mechanism of action is thought to be an increase in inhibitory neurotransmission across diverse timescales. The endpoint of this stimulation will be a decrease in the local E/I ratio that should last at least 60 minutes post-stimulation (Chung et al., 2018).
In separate sessions, all participants will receive stimulation to either the dorsolateral prefrontal cortex (dlPFC) or to the angular gyrus (AG). The Investigators will contrast the effects of dlPFC cTBS with control cTBS to the AG.
| Study group | Role | What they receive |
|---|---|---|
| Transcranial magnetic stimulation participants | Experimental | All participants will be recruited into a single arm where, across two sessions they will receive transcranial magnetic stimulation in separate session to either the dorsolateral prefrontal cortex or the angular gyrus. Session order will be counter-balanced across participants, and stimulation target will be blinded to the participants until after their participation is complete. Receives: Device: transcranial magnetic stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drive to exert cognitive effort
Likert ratings of subjective effort dimensions (the Need for Cognition Scale) with scores ranging from 1 to 21 with higher scores indicating a greater propensity to engage with cognitively demanding activities
Measured: This baseline measurement will be made once, 20 minutes before stimulation, during each participant's first transcranial magnetic stimulation session.
Critical dynamics - immediate effects of target stimulation
Long-range temporal correlations quantified by the scaling exponent, which is derived from EEG data, via detrended fluctuation analysis. Scores range from 0.5 (uncorrelated time series) to 1.0 (correlated time series). Higher scores, indicating stronger correlations, are expected before versus immediately after transcranial magnetic stimulation. So, the change score should be negative, indicating a reduction in long-range temporal correlations as a result of transcranial magnetic stimulation, immediately after stimulation.
Measured: Change in long-range temporal correlations measured immediately after, versus immediately before target transcranial magnetic stimulation.
Critical dynamics - immediate effects of sham stimulation
Long-range temporal correlations quantified by the scaling exponent, which is derived from EEG data, via detrended fluctuation analysis. Scores range from 0.5 (uncorrelated time series) to 1.0 (correlated time series). Higher scores, indicating stronger correlations, are expected before versus immediately after transcranial magnetic stimulation. So, the change score should be negative, indicating a reduction in long-range temporal correlations as a result of transcranial magnetic stimulation, immediately after stimulation.
Measured: Change in long-range temporal correlations measured immediately after, versus immediately before sham transcranial magnetic stimulation.
Critical dynamics - prolonged effects of target stimulation
Long-range temporal correlations quantified by the scaling exponent, which is derived from EEG data, via detrended fluctuation analysis. Exponents range from 0.5 (uncorrelated time series) to 1.0 (correlated time series). Higher exponents, indicating stronger correlations, are expected before versus after transcranial magnetic stimulation, but are expected to recover slowly to pre-stimulation strength over the 1 hour duration of the session, following stimulation. So, the change score should show partially recovered correlations by the 40 minute post-stimulation mark.
Measured: Change in long-range temporal correlations measured 40 minutes after, versus immediately before target transcranial magnetic stimulation.
Critical dynamics - prolonged effects of sham stimulation
Long-range temporal correlations quantified by the scaling exponent, which is derived from EEG data, via detrended fluctuation analysis. Exponents range from 0.5 (uncorrelated time series) to 1.0 (correlated time series). Higher exponents, indicating stronger correlations, are expected before versus after transcranial magnetic stimulation, but are expected to recover slowly to pre-stimulation strength over the 1 hour duration of the session, following stimulation. So, the change score should show partially recovered correlations by the 40 minute post-stimulation mark.
Measured: Change in long-range temporal correlations measured 40 minutes after, versus immediately before sham transcranial magnetic stimulation.
Critical dynamics - dissipated effects of target stimulation
Long-range temporal correlations quantified by the scaling exponent, which is derived from EEG data, via detrended fluctuation analysis. Exponents range from 0.5 (uncorrelated time series) to 1.0 (correlated time series). Higher exponents, indicating stronger correlations, are expected before versus after transcranial magnetic stimulation, but are expected to recover fully to pre-stimulation strength by the end of the 1 hour duration of the session, following stimulation. So, the change score should show minimal difference between pre-stimulation and the 1 hour post-stimulation time point.
Measured: Change in long-range temporal correlations measured 1 hour after, versus immediately before target transcranial magnetic stimulation.
Critical dynamics - dissipated effects of sham stimulation
Long-range temporal correlations quantified by the scaling exponent, which is derived from EEG data, via detrended fluctuation analysis. Exponents range from 0.5 (uncorrelated time series) to 1.0 (correlated time series). Higher exponents, indicating stronger correlations, are expected before versus after transcranial magnetic stimulation, but are expected to recover fully to pre-stimulation strength by the end of the 1 hour duration of the session, following stimulation. So, the change score should show minimal difference between pre-stimulation and the 1 hour post-stimulation time point.
Measured: Change in long-range temporal correlations measured 1 hour after, versus immediately before sham transcranial magnetic stimulation.
Working memory performance - target versus sham stimulation
Accuracy on the N-back working memory task, as quantified by the average discrimination index d-prime across load levels. Typical average d-prime scores of accurate discrimination range from 2.5 to 0.75, with higher scores indicating a higher rate of hits and fewer false alarms. Transcranial magnetic stimulation to the target site (dorsolateral prefrontal cortex) is predicted to undermine working memory performance to a greater extent than the sham stimulation site (angular gyrus). Thus, the average discrimination index scores should be lower following target versus sham stimulation.
Measured: Change in accuracy for the task performed immediately after stimulation, for target versus sham stimulation.
Subjective effort discounting - target versus sham stimulation
Subjective values as estimated from an effort discounting procedure as an area under the discounting curve measure ranging from 0.0 to 1.0. Lower values indicate that people find subjective effort of the working memory tasks to be more costly. Transcranial magnetic stimulation to the target site (dorsolateral prefrontal cortex) is predicted to amplify subjective effort to a greater extent than the sham stimulation site (angular gyrus). Thus, the area under the discounting curve should be smaller following target versus sham stimulation.
Measured: Change in area under the discounting curve estimated 45 minutes after stimulation, for target versus sham stimulation.
Avalanche size statistics - immediate effects of target stimulation
Avalanche size statistics described as the power-law exponent estimated from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards smaller avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. So, the change score should be negative, indicating a reduction in the typical avalanche size, following transcranial magnetic stimulation
Measured: Change in the exponent estimated from EEG data immediately before versus immediately after target transcranial magnetic stimulation.
Avalanche size statistics - immediate effects of sham stimulation
Avalanche size statistics described as the power-law exponent estimated from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards smaller avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. So, the change score should be negative, indicating a reduction in the typical avalanche size, following transcranial magnetic stimulation
Measured: Change in the exponent estimated from EEG data immediately before versus immediately after sham transcranial magnetic stimulation.
Avalanche size statistics - prolonged effects of target stimulation
Avalanche size statistics described as the power-law exponent estimated from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards smaller avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation, but should slowly recover to baseline statistics over the 1 hour following stimulation. So, the change score should reflect a partial recovery to baseline statistics by the 40 minute mark, post-stimulation.
Measured: Change in the exponent estimated from EEG data immediately before versus 40 minutes after target transcranial magnetic stimulation.
Avalanche size statistics - prolonged effects of sham stimulation
Avalanche size statistics described as the power-law exponent estimated from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards smaller avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation, but should slowly recover to baseline statistics over the 1 hour following stimulation. So, the change score should reflect a partial recovery to baseline statistics by the 40 minute mark, post-stimulation.
Measured: Change in the exponent estimated from EEG data immediately before versus 40 minutes after sham transcranial magnetic stimulation.
Avalanche size statistics - dissipated effects of target stimulation
Avalanche size statistics described as the power-law exponent estimated from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards smaller avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation, but should fully recover to baseline statistics 1 hour following stimulation. So, the change score should reflect minimal change with respect to baseline.
Measured: Change in the exponent estimated from EEG data immediately before versus 1 hour after target transcranial magnetic stimulation.
Avalanche size statistics - dissipated effects of sham stimulation
Avalanche size statistics described as the power-law exponent estimated from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards smaller avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation, but should fully recover to baseline statistics 1 hour following stimulation. So, the change score should reflect minimal change with respect to baseline.
Measured: Change in the exponent estimated from EEG data immediately before versus 1 hour after sham transcranial magnetic stimulation.
Avalanche duration statistics - immediate effects of target stimulation
Avalanche duration statistics described as the power-law exponent estimate from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards shorter avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. So, the change score should be negative, indicating a reduction in the typical avalanche duration, following transcranial magnetic stimulation
Measured: Change in the exponent estimated from EEG data immediately before versus immediately after target transcranial magnetic stimulation.
Avalanche duration statistics - immediate effects of sham stimulation
Avalanche duration statistics described as the power-law exponent estimate from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards shorter avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. So, the change score should be negative, indicating a reduction in the typical avalanche duration, following transcranial magnetic stimulation
Measured: Change in the exponent estimated from EEG data immediately before versus immediately after sham transcranial magnetic stimulation.
Avalanche duration statistics - prolonged effects of target stimulation
Avalanche duration statistics described as the power-law exponent estimate from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards shorter avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. Slopes should slowly recover during the 1-hour session following stimulation. So, the change score should reflect partial recovery of avalanche duration statistics 40 minutes following transcranial magnetic stimulation
Measured: Change in the exponent estimated from EEG data immediately before versus 40 minutes after target transcranial magnetic stimulation.
Avalanche duration statistics - prolonged effects of sham stimulation
Avalanche duration statistics described as the power-law exponent estimate from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards shorter avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. Slopes should slowly recover during the 1-hour session following stimulation. So, the change score should reflect partial recovery of avalanche duration statistics 40 minutes following transcranial magnetic stimulation
Measured: Change in the exponent estimated from EEG data immediately before versus 40 minutes after sham transcranial magnetic stimulation.
Avalanche duration statistics - dissipated effects of target stimulation
Avalanche duration statistics described as the power-law exponent estimate from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards shorter avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. Slopes should slowly recover during the 1-hour session following stimulation. So, the change score should reflect full recovery of avalanche duration statistics 1 hour following transcranial magnetic stimulation
Measured: Change in the exponent estimated from EEG data immediately before versus 1 hour after target transcranial magnetic stimulation.
Avalanche duration statistics - dissipated effects of sham stimulation
Avalanche duration statistics described as the power-law exponent estimate from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards shorter avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. Slopes should slowly recover during the 1-hour session following stimulation. So, the change score should reflect full recovery of avalanche duration statistics 1 hour following transcranial magnetic stimulation
Measured: Change in the exponent estimated from EEG data immediately before versus 1 hour after sham transcranial magnetic stimulation.
Secondary outcomes (6)
E/I balance - immediate target stimulation effects
Functional excitation-inhibition balance estimated from an EEG-derived measure relating the amplitude of the signal to its fluctuation function. A functional excitation-inhibition ratio of 1.0 implies that excitation and inhibition are balanced. Transcranial magnetic stimulation should promote inhibition, thus lowering the functional excitation-inhibition ratio immediately after stimulation.
Measured: Change in the functional E/I balance immediately after versus immediately before target transcranial magnetic stimulation.
E/I balance - immediate sham stimulation effects
Functional excitation-inhibition balance estimated from an EEG-derived measure relating the amplitude of the signal to its fluctuation function. A functional excitation-inhibition ratio of 1.0 implies that excitation and inhibition are balanced. Transcranial magnetic stimulation should promote inhibition, thus lowering the functional excitation-inhibition ratio immediately after stimulation.
Measured: Change in the functional E/I balance immediately after versus immediately before sham transcranial magnetic stimulation.
E/I balance - prolonged target stimulation effects
Functional excitation-inhibition balance estimated from an EEG-derived measure relating the amplitude of the signal to its fluctuation function. A functional excitation-inhibition ratio of 1.0 implies that excitation and inhibition are balanced. Transcranial magnetic stimulation should promote inhibition, thus lowering the functional excitation-inhibition ratio immediately after stimulation. A protracted recovery of excitation-inhibition balance in the hour after stimulation is expected.
Measured: Change in the functional E/I balance 40 minutes after versus immediately before target transcranial magnetic stimulation.
E/I balance - prolonged sham stimulation effects
Functional excitation-inhibition balance estimated from an EEG-derived measure relating the amplitude of the signal to its fluctuation function. A functional excitation-inhibition ratio of 1.0 implies that excitation and inhibition are balanced. Transcranial magnetic stimulation should promote inhibition, thus lowering the functional excitation-inhibition ratio immediately after stimulation. A protracted recovery of excitation-inhibition balance in the hour after stimulation is expected.
Measured: Change in the functional E/I balance 40 minutes after versus immediately before sham transcranial magnetic stimulation.
E/I balance - dissipated effects of target stimulation
Functional excitation-inhibition balance estimated from an EEG-derived measure relating the amplitude of the signal to its fluctuation function. A functional excitation-inhibition ratio of 1.0 implies that excitation and inhibition are balanced. Transcranial magnetic stimulation should promote inhibition, thus lowering the functional excitation-inhibition ratio immediately after stimulation. A protracted recovery of excitation-inhibition balance in the hour after stimulation is expected.
Measured: Change in the functional E/I balance 1 hour after after versus immediately before target transcranial magnetic stimulation.
E/I balance - dissipated effects of sham stimulation
Functional excitation-inhibition balance estimated from an EEG-derived measure relating the amplitude of the signal to its fluctuation function. A functional excitation-inhibition ratio of 1.0 implies that excitation and inhibition are balanced. Transcranial magnetic stimulation should promote inhibition, thus lowering the functional excitation-inhibition ratio immediately after stimulation. A protracted recovery of excitation-inhibition balance in the hour after stimulation is expected.
Measured: Change in the functional E/I balance 1 hour after after versus immediately before sham transcranial magnetic stimulation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2023
- Study start15 Mar 2023
- Primary completion30 Jun 2023
- Study completion30 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- The study will involve two sessions of within-subject, sham-controlled continuous theta burst stimulation delivered either at the left dorsolateral prefrontal cortex or angular gyrus.
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- John A Westbrook, PhD, Principal investigator, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05797636
- Sponsor's protocol ID
- 2106003016
- Other IDs
- K99MH125021
- Status last verified
- Jul 2023
- First submitted
- 17 Feb 2023
- Last updated
- 2 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: All anonymized data will be made publicly available at the conclusion of the trial at Rutgers University's (RUresearch) Data Portal.
Publications
Chung SW, Rogasch NC, Hoy KE, Fitzgerald PB. The effect of single and repeated prefrontal intermittent theta burst stimulation on cortical reactivity and working memory. Brain Stimul. 2018 May-Jun;11(3):566-574. doi: 10.1016/j.brs.2018.01.002. Epub 2018 Jan 8.
PubMed 29352668Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.
PubMed 15664172
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Theta-burst Stimulation Modulates Criticality, Working Memory and Subjective Effort
- ClinicalTrials.gov ID
- NCT05797636
- Acronym / sponsor ID
- 2106003016
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 15 Mar 2023 (actual)
- Primary completion
- 30 Jun 2023 (actual)
- Study completion
- 30 Jun 2023 (actual)
- First posted
- 4 Apr 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.
The project examines electroencephalography, MRI, and behavioral measures indexing flexibility (critical state dynamics) in the brain when healthy young adults do demanding cognitive tasks, and in response to transcranial magnetic stimulation.
Detailed description
The healthy human brain is a complex, dynamical system which is hypothesized to lie near a phase transition at rest - at the boundary between order and chaos. Proximity to this critical point is functionally adaptive as it affords maximal flexibility, dynamic range, and information handling capacity, with implications for working memory function. Divergence from this critical point has become correlated with diverse forms of psychopathology and neuropathy suggesting that distance from a critical point is both a potential biomarker of disorder and also a target for intervention in disordered brains. The Investigators have further hypothesized that subjective cognitive effort is a reflection of sub-criticality induced by engagement with demanding tasks.
A key control parameter determining distance from criticality in a resting brain is hypothesized to be the balance of cortical excitation to inhibition (the "E/I balance"). Transcranial magnetic stimulation is a widely used experimental and clinical tool for neuromodulation and theta-burst stimulation (TBS) protocols are thought to modulate the E/I balance. Here the Investigators test whether cortical dynamics can be systematically modulated away from the critical point with continuous theta-burst stimulation (cTBS), which is thought to decrease the E/I balance, and thereby impact on working memory function and subjective cognitive effort during performance of the working memory tasks.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study will involve two sessions of within-subject, sham-controlled continuous theta burst stimulation delivered either at the left dorsolateral prefrontal cortex or angular gyrus.
| Arm | Type | Receives |
|---|---|---|
| Transcranial magnetic stimulation participants | Experimental | Device: transcranial magnetic stimulationAll participants will be recruited into a single arm where, across two sessions they will receive transcranial magnetic stimulation in separate session to either the dorsolateral prefrontal cortex or the angular gyrus. Session order will be counter-balanced across participants, and stimulation target will be blinded to the participants until after their participation is complete. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study and availability for the duration of the study
- Males and females; Ages 18-45
- Healthy, neurologically normal with no diagnosed mental or physical illness
- Willingness to adhere to the MRI and two session stimulation protocol
Key exclusion criteria (10 listed)
- Ongoing drug or alcohol abuse
- Diagnosed psychiatric or mental illness
- Currently taking psychoactive medication
- Prior brain injury
- Metal in body
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 |
|---|---|---|
| transcranial magnetic stimulationThe study intervention is modulation of cortical excitation to inhibition (E/I) balance in the dorsolateral prefrontal cortex (dlPFC) by means of 2 trains of spaced continuous theta burst stimulation (cTBS) using a transcranial magnetic stimulation device. As prior work (Huang et al 2005; Chung et al. 2018) has shown that cTBS reliably decreases the cortical E/I ratio with diverse cortical targets, the Investigators expect to replicate a reduction in E/I balance when applied. The mechanism of action is thought to be an increase in inhibitory neurotransmission across diverse timescales. The endpoint of this stimulation will be a decrease in the local E/I ratio that should last at least 60 minutes post-stimulation (Chung et al., 2018). In separate sessions, all participants will receive stimulation to either the dorsolateral prefrontal cortex (dlPFC) or to the angular gyrus (AG). The Investigators will contrast the effects of dlPFC cTBS with control cTBS to the AG. | Device | Transcranial magnetic stimulation participants |
Primary outcome
Drive to exert cognitive effort
Time frame: This baseline measurement will be made once, 20 minutes before stimulation, during each participant's first transcranial magnetic stimulation session.
Likert ratings of subjective effort dimensions (the Need for Cognition Scale) with scores ranging from 1 to 21 with higher scores indicating a greater propensity to engage with cognitively demanding activities
Critical dynamics - immediate effects of target stimulation
Time frame: Change in long-range temporal correlations measured immediately after, versus immediately before target transcranial magnetic stimulation.
Long-range temporal correlations quantified by the scaling exponent, which is derived from EEG data, via detrended fluctuation analysis. Scores range from 0.5 (uncorrelated time series) to 1.0 (correlated time series). Higher scores, indicating stronger correlations, are expected before versus immediately after transcranial magnetic stimulation. So, the change score should be negative, indicating a reduction in long-range temporal correlations as a result of transcranial magnetic stimulation, immediately after stimulation.
Critical dynamics - immediate effects of sham stimulation
Time frame: Change in long-range temporal correlations measured immediately after, versus immediately before sham transcranial magnetic stimulation.
Long-range temporal correlations quantified by the scaling exponent, which is derived from EEG data, via detrended fluctuation analysis. Scores range from 0.5 (uncorrelated time series) to 1.0 (correlated time series). Higher scores, indicating stronger correlations, are expected before versus immediately after transcranial magnetic stimulation. So, the change score should be negative, indicating a reduction in long-range temporal correlations as a result of transcranial magnetic stimulation, immediately after stimulation.
Critical dynamics - prolonged effects of target stimulation
Time frame: Change in long-range temporal correlations measured 40 minutes after, versus immediately before target transcranial magnetic stimulation.
Long-range temporal correlations quantified by the scaling exponent, which is derived from EEG data, via detrended fluctuation analysis. Exponents range from 0.5 (uncorrelated time series) to 1.0 (correlated time series). Higher exponents, indicating stronger correlations, are expected before versus after transcranial magnetic stimulation, but are expected to recover slowly to pre-stimulation strength over the 1 hour duration of the session, following stimulation. So, the change score should show partially recovered correlations by the 40 minute post-stimulation mark.
Critical dynamics - prolonged effects of sham stimulation
Time frame: Change in long-range temporal correlations measured 40 minutes after, versus immediately before sham transcranial magnetic stimulation.
Long-range temporal correlations quantified by the scaling exponent, which is derived from EEG data, via detrended fluctuation analysis. Exponents range from 0.5 (uncorrelated time series) to 1.0 (correlated time series). Higher exponents, indicating stronger correlations, are expected before versus after transcranial magnetic stimulation, but are expected to recover slowly to pre-stimulation strength over the 1 hour duration of the session, following stimulation. So, the change score should show partially recovered correlations by the 40 minute post-stimulation mark.
Critical dynamics - dissipated effects of target stimulation
Time frame: Change in long-range temporal correlations measured 1 hour after, versus immediately before target transcranial magnetic stimulation.
Long-range temporal correlations quantified by the scaling exponent, which is derived from EEG data, via detrended fluctuation analysis. Exponents range from 0.5 (uncorrelated time series) to 1.0 (correlated time series). Higher exponents, indicating stronger correlations, are expected before versus after transcranial magnetic stimulation, but are expected to recover fully to pre-stimulation strength by the end of the 1 hour duration of the session, following stimulation. So, the change score should show minimal difference between pre-stimulation and the 1 hour post-stimulation time point.
Critical dynamics - dissipated effects of sham stimulation
Time frame: Change in long-range temporal correlations measured 1 hour after, versus immediately before sham transcranial magnetic stimulation.
Long-range temporal correlations quantified by the scaling exponent, which is derived from EEG data, via detrended fluctuation analysis. Exponents range from 0.5 (uncorrelated time series) to 1.0 (correlated time series). Higher exponents, indicating stronger correlations, are expected before versus after transcranial magnetic stimulation, but are expected to recover fully to pre-stimulation strength by the end of the 1 hour duration of the session, following stimulation. So, the change score should show minimal difference between pre-stimulation and the 1 hour post-stimulation time point.
Working memory performance - target versus sham stimulation
Time frame: Change in accuracy for the task performed immediately after stimulation, for target versus sham stimulation.
Accuracy on the N-back working memory task, as quantified by the average discrimination index d-prime across load levels. Typical average d-prime scores of accurate discrimination range from 2.5 to 0.75, with higher scores indicating a higher rate of hits and fewer false alarms. Transcranial magnetic stimulation to the target site (dorsolateral prefrontal cortex) is predicted to undermine working memory performance to a greater extent than the sham stimulation site (angular gyrus). Thus, the average discrimination index scores should be lower following target versus sham stimulation.
Subjective effort discounting - target versus sham stimulation
Time frame: Change in area under the discounting curve estimated 45 minutes after stimulation, for target versus sham stimulation.
Subjective values as estimated from an effort discounting procedure as an area under the discounting curve measure ranging from 0.0 to 1.0. Lower values indicate that people find subjective effort of the working memory tasks to be more costly. Transcranial magnetic stimulation to the target site (dorsolateral prefrontal cortex) is predicted to amplify subjective effort to a greater extent than the sham stimulation site (angular gyrus). Thus, the area under the discounting curve should be smaller following target versus sham stimulation.
Avalanche size statistics - immediate effects of target stimulation
Time frame: Change in the exponent estimated from EEG data immediately before versus immediately after target transcranial magnetic stimulation.
Avalanche size statistics described as the power-law exponent estimated from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards smaller avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. So, the change score should be negative, indicating a reduction in the typical avalanche size, following transcranial magnetic stimulation
Avalanche size statistics - immediate effects of sham stimulation
Time frame: Change in the exponent estimated from EEG data immediately before versus immediately after sham transcranial magnetic stimulation.
Avalanche size statistics described as the power-law exponent estimated from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards smaller avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. So, the change score should be negative, indicating a reduction in the typical avalanche size, following transcranial magnetic stimulation
Avalanche size statistics - prolonged effects of target stimulation
Time frame: Change in the exponent estimated from EEG data immediately before versus 40 minutes after target transcranial magnetic stimulation.
Avalanche size statistics described as the power-law exponent estimated from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards smaller avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation, but should slowly recover to baseline statistics over the 1 hour following stimulation. So, the change score should reflect a partial recovery to baseline statistics by the 40 minute mark, post-stimulation.
Avalanche size statistics - prolonged effects of sham stimulation
Time frame: Change in the exponent estimated from EEG data immediately before versus 40 minutes after sham transcranial magnetic stimulation.
Avalanche size statistics described as the power-law exponent estimated from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards smaller avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation, but should slowly recover to baseline statistics over the 1 hour following stimulation. So, the change score should reflect a partial recovery to baseline statistics by the 40 minute mark, post-stimulation.
Avalanche size statistics - dissipated effects of target stimulation
Time frame: Change in the exponent estimated from EEG data immediately before versus 1 hour after target transcranial magnetic stimulation.
Avalanche size statistics described as the power-law exponent estimated from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards smaller avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation, but should fully recover to baseline statistics 1 hour following stimulation. So, the change score should reflect minimal change with respect to baseline.
Avalanche size statistics - dissipated effects of sham stimulation
Time frame: Change in the exponent estimated from EEG data immediately before versus 1 hour after sham transcranial magnetic stimulation.
Avalanche size statistics described as the power-law exponent estimated from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards smaller avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation, but should fully recover to baseline statistics 1 hour following stimulation. So, the change score should reflect minimal change with respect to baseline.
Avalanche duration statistics - immediate effects of target stimulation
Time frame: Change in the exponent estimated from EEG data immediately before versus immediately after target transcranial magnetic stimulation.
Avalanche duration statistics described as the power-law exponent estimate from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards shorter avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. So, the change score should be negative, indicating a reduction in the typical avalanche duration, following transcranial magnetic stimulation
Avalanche duration statistics - immediate effects of sham stimulation
Time frame: Change in the exponent estimated from EEG data immediately before versus immediately after sham transcranial magnetic stimulation.
Avalanche duration statistics described as the power-law exponent estimate from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards shorter avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. So, the change score should be negative, indicating a reduction in the typical avalanche duration, following transcranial magnetic stimulation
Avalanche duration statistics - prolonged effects of target stimulation
Time frame: Change in the exponent estimated from EEG data immediately before versus 40 minutes after target transcranial magnetic stimulation.
Avalanche duration statistics described as the power-law exponent estimate from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards shorter avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. Slopes should slowly recover during the 1-hour session following stimulation. So, the change score should reflect partial recovery of avalanche duration statistics 40 minutes following transcranial magnetic stimulation
Avalanche duration statistics - prolonged effects of sham stimulation
Time frame: Change in the exponent estimated from EEG data immediately before versus 40 minutes after sham transcranial magnetic stimulation.
Avalanche duration statistics described as the power-law exponent estimate from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards shorter avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. Slopes should slowly recover during the 1-hour session following stimulation. So, the change score should reflect partial recovery of avalanche duration statistics 40 minutes following transcranial magnetic stimulation
Avalanche duration statistics - dissipated effects of target stimulation
Time frame: Change in the exponent estimated from EEG data immediately before versus 1 hour after target transcranial magnetic stimulation.
Avalanche duration statistics described as the power-law exponent estimate from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards shorter avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. Slopes should slowly recover during the 1-hour session following stimulation. So, the change score should reflect full recovery of avalanche duration statistics 1 hour following transcranial magnetic stimulation
Avalanche duration statistics - dissipated effects of sham stimulation
Time frame: Change in the exponent estimated from EEG data immediately before versus 1 hour after sham transcranial magnetic stimulation.
Avalanche duration statistics described as the power-law exponent estimate from the slope of a fit to a log-log plot of avalanche size distributions estimated from EEG data. Steeper slopes, indicating a shift towards shorter avalanches, are expected immediately after versus immediately before transcranial magnetic stimulation. Slopes should slowly recover during the 1-hour session following stimulation. So, the change score should reflect full recovery of avalanche duration statistics 1 hour following transcranial magnetic stimulation
6 secondary outcomes
E/I balance - immediate target stimulation effects
Time frame: Change in the functional E/I balance immediately after versus immediately before target transcranial magnetic stimulation.
E/I balance - immediate sham stimulation effects
Time frame: Change in the functional E/I balance immediately after versus immediately before sham transcranial magnetic stimulation.
E/I balance - prolonged target stimulation effects
Time frame: Change in the functional E/I balance 40 minutes after versus immediately before target transcranial magnetic stimulation.
E/I balance - prolonged sham stimulation effects
Time frame: Change in the functional E/I balance 40 minutes after versus immediately before sham transcranial magnetic stimulation.
E/I balance - dissipated effects of target stimulation
Time frame: Change in the functional E/I balance 1 hour after after versus immediately before target transcranial magnetic stimulation.
E/I balance - dissipated effects of sham stimulation
Time frame: Change in the functional E/I balance 1 hour after after versus immediately before sham transcranial magnetic stimulation.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2023.
- Background: PubMed 29352668Chung SW, Rogasch NC, Hoy KE, Fitzgerald PB. The effect of single and repeated prefrontal intermittent theta burst stimulation on cortical reactivity and working memory. Brain Stimul. 2018 May-Jun;11(3):566-574. doi: 10.1016/j.brs.2018.01.002. Epub 2018 Jan 8.
- Background: PubMed 15664172Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.
- Individual participant dataSharing planned: No. All anonymized data will be made publicly available at the conclusion of the trial at Rutgers University's (RUresearch) Data Portal.
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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. This study is not recruiting at the moment.
John A Westbrook, PhD principal investigator
Brown 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 transcranial magnetic stimulation in people with Healthy, run by Brown 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 9 inclusion and 10 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: finished, as of the sponsor's last update on 2 Aug 2023. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Drive to exert cognitive effort (time frame: This baseline measurement will be made once, 20 minutes before stimulation, during each participant's first transcranial magnetic stimulation session.). The study lists 21 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05797636, which also lists 2 linked publications.
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 2 Aug 2023.