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Completed

NCT Number: NCT05797636

Criticality, Working Memory, and 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.

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Key information

Conditions

Healthy

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Brown University

Providence, Rhode Island, 02912, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • Normal or corrected to normal vision
  • At least twelve years of education (high school equivalent)
  • Right-handed

Exclusion criteria

  • 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
  • Claustrophobia
  • Pregnant or possibly pregnant
  • Younger than 18 or older than 45
  • Use of medications which potentially lower the usage threshold

Treatment and study plan

Transcranial Magnetic Stimulation

Device

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.

Primary outcomes

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

Secondary outcomes

  1. 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.

    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.

  2. 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.

    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.

  3. 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.

    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.

  4. 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.

    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.

  5. 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.

    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.

  6. 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.

    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.

Sponsors and collaborators

Lead sponsor

Brown University

Other

Collaborators

  • National Institute of Mental Health (NIMH)

Registry information

Official study title

Theta-burst Stimulation Modulates Criticality, Working Memory and Subjective Effort

Important dates

Study start
2023
Primary completion
2023
Study completion
2023
First posted
Apr 4, 2023
Registry last updated
Aug 2, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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