Clinical trial NCT05797636: Criticality, Working Memory, and Effort
Official title: Theta-burst Stimulation Modulates Criticality, Working Memory and Subjective Effort
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Lead sponsor: Brown University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2023-04-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study and availability for the duration of the study
3. Males and females; Ages 18-45
4. Healthy, neurologically normal with no diagnosed mental or physical illness
5. Willingness to adhere to the MRI and two session stimulation protocol
6. Fluent in English
7. Normal or corrected to normal vision
8. At least twelve years of education (high school equivalent)
9. Right-handed

Exclusion Criteria:

1. Ongoing drug or alcohol abuse
2. Diagnosed psychiatric or mental illness
3. Currently taking psychoactive medication
4. Prior brain injury
5. Metal in body
6. History of seizures or diagnosis of epilepsy
7. Claustrophobia
8. Pregnant or possibly pregnant
9. Younger than 18 or older than 45
10. Use of medications which potentially lower the usage threshold

Primary outcomes:
measure: Drive to exert cognitive effort
timeFrame: This baseline measurement will be made once, 20 minutes before stimulation, during each participant's first transcranial magnetic stimulation session.
measure: Critical dynamics - immediate effects of target stimulation
timeFrame: Change in long-range temporal correlations measured immediately after, versus immediately before target transcranial magnetic stimulation.
measure: Critical dynamics - immediate effects of sham stimulation
timeFrame: Change in long-range temporal correlations measured immediately after, versus immediately before sham transcranial magnetic stimulation.
measure: Critical dynamics - prolonged effects of target stimulation
timeFrame: Change in long-range temporal correlations measured 40 minutes after, versus immediately before target transcranial magnetic stimulation.
measure: Critical dynamics - prolonged effects of sham stimulation
timeFrame: Change in long-range temporal correlations measured 40 minutes after, versus immediately before sham transcranial magnetic stimulation.
measure: Critical dynamics - dissipated effects of target stimulation
timeFrame: Change in long-range temporal correlations measured 1 hour after, versus immediately before target transcranial magnetic stimulation.
measure: Critical dynamics - dissipated effects of sham stimulation
timeFrame: Change in long-range temporal correlations measured 1 hour after, versus immediately before sham transcranial magnetic stimulation.
measure: Working memory performance - target versus sham stimulation
timeFrame: Change in accuracy for the task performed immediately after stimulation, for target versus sham stimulation.
measure: Subjective effort discounting - target versus sham stimulation
timeFrame: Change in area under the discounting curve estimated 45 minutes after stimulation, for target versus sham stimulation.
measure: Avalanche size statistics - immediate effects of target stimulation
timeFrame: Change in the exponent estimated from EEG data immediately before versus immediately after target transcranial magnetic stimulation.
measure: Avalanche size statistics - immediate effects of sham stimulation
timeFrame: Change in the exponent estimated from EEG data immediately before versus immediately after sham transcranial magnetic stimulation.
measure: Avalanche size statistics - prolonged effects of target stimulation
timeFrame: Change in the exponent estimated from EEG data immediately before versus 40 minutes after target transcranial magnetic stimulation.
measure: Avalanche size statistics - prolonged effects of sham stimulation
timeFrame: Change in the exponent estimated from EEG data immediately before versus 40 minutes after sham transcranial magnetic stimulation.
measure: Avalanche size statistics - dissipated effects of target stimulation
timeFrame: Change in the exponent estimated from EEG data immediately before versus 1 hour after target transcranial magnetic stimulation.
measure: Avalanche size statistics - dissipated effects of sham stimulation
timeFrame: Change in the exponent estimated from EEG data immediately before versus 1 hour after sham transcranial magnetic stimulation.
measure: Avalanche duration statistics - immediate effects of target stimulation
timeFrame: Change in the exponent estimated from EEG data immediately before versus immediately after target transcranial magnetic stimulation.
measure: Avalanche duration statistics - immediate effects of sham stimulation
timeFrame: Change in the exponent estimated from EEG data immediately before versus immediately after sham transcranial magnetic stimulation.
measure: Avalanche duration statistics - prolonged effects of target stimulation
timeFrame: Change in the exponent estimated from EEG data immediately before versus 40 minutes after target transcranial magnetic stimulation.
measure: Avalanche duration statistics - prolonged effects of sham stimulation
timeFrame: Change in the exponent estimated from EEG data immediately before versus 40 minutes after sham transcranial magnetic stimulation.
measure: Avalanche duration statistics - dissipated effects of target stimulation
timeFrame: Change in the exponent estimated from EEG data immediately before versus 1 hour after target transcranial magnetic stimulation.
measure: Avalanche duration statistics - dissipated effects of sham stimulation
timeFrame: Change in the exponent estimated from EEG data immediately before versus 1 hour after sham transcranial magnetic stimulation.
Secondary outcomes:
measure: E/I balance - immediate target stimulation effects
timeFrame: Change in the functional E/I balance immediately after versus immediately before target transcranial magnetic stimulation.
measure: E/I balance - immediate sham stimulation effects
timeFrame: Change in the functional E/I balance immediately after versus immediately before sham transcranial magnetic stimulation.
measure: E/I balance - prolonged target stimulation effects
timeFrame: Change in the functional E/I balance 40 minutes after versus immediately before target transcranial magnetic stimulation.
measure: E/I balance - prolonged sham stimulation effects
timeFrame: Change in the functional E/I balance 40 minutes after versus immediately before sham transcranial magnetic stimulation.
measure: E/I balance - dissipated effects of target stimulation
timeFrame: Change in the functional E/I balance 1 hour after after versus immediately before target transcranial magnetic stimulation.
measure: E/I balance - dissipated effects of sham stimulation
timeFrame: Change in the functional E/I balance 1 hour after after versus immediately before sham transcranial magnetic stimulation.
Other outcomes:
Locations:
city: Providence
country: United States
facility: Brown University
state: Rhode Island
Study officials:
affiliation: Brown University
name: John A Westbrook, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Huang 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.