Clinical trial NCT06344559: Brain Criticality, Oculomotor Control, and Cognitive Effort
Official title: Theta-burst Stimulation Modulates Criticality and Cognitive Control
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Healthy
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
First posted: 2024-04-03
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study will involve three sessions of within-subject, crossover, double-blind transcranial magnetic stimulation with either 1) active intermittent theta burst stimulation, 2) active continuous theta burst stimulation or 3) sham intermittent or continuous theta burst stimulation.
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 operate, at rest, near a phase transition - at the boundary between order and chaos. Proximity to this critical point is functionally adaptive as it affords maximal flexibility, dynamic range, and information transmission capacity, with implications for short term memory and cognitive control. 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 task performance depends on how closely brains operate to criticality during task performance and also that subjective cognitive effort is a reflection of divergence from 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) and intermittent theta-burst stimulation (iTBS), which is thought to decrease and increase E/I balance, respectively. Depending on baseline E/I balance prior to stimulation, this will make people's brains either operate closer to, or farther away from critiality and thereby impact on cognitive control and subjective cognitive effort during performance of control-demanding 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)

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: Critical dynamics - immediate effects of cTBS versus sham stimulation
timeFrame: Change in correlations recorded during rest, immediately after stimulation, for active versus sham stimulation.
measure: Functional E/I balance - immediate effects of cTBS versus sham stimulation
timeFrame: Change in the functional E/I balance recorded during rest, immediately after stimulation, for active versus sham stimulation.
measure: Avalanche branching ratio - immediate effects of cTBS versus sham stimulation
timeFrame: Change in the avalanche branching ratio recorded during rest, immediately after stimulation, for active versus sham stimulation.
measure: Critical dynamics - immediate effects of iTBS versus sham stimulation
timeFrame: Change in correlations recorded during rest, immediately after stimulation, for active versus sham stimulation.
measure: Functional E/I balance - immediate effects of iTBS versus sham stimulation
timeFrame: Change in the functional E/I balance recorded during rest, immediately after stimulation, for active versus sham stimulation.
measure: Avalanche branching ratio - immediate effects of iTBS versus sham stimulation
timeFrame: Change in the avalanche branching ratio recorded during rest, immediately after stimulation, for active versus sham stimulation.
measure: Memory-guided saccade accuracy - effects of cTBS versus sham stimulation
timeFrame: Change in degrees of visual angle error estimated 44 minutes after stimulation, for cTBS versus sham stimulation.
measure: Memory-guided saccade accuracy - effects of iTBS versus sham stimulation
timeFrame: Change in degrees of visual angle error estimated 44 minutes after stimulation, for iTBS versus sham stimulation.
measure: Anti-saccade accuracy - effects of cTBS versus sham stimulation
timeFrame: Change in percent accuracy estimated 12 minutes after stimulation, for cTBS versus sham stimulation.
measure: Anti-saccade accuracy - effects of iTBS versus sham stimulation
timeFrame: Change in percent accuracy estimated 12 minutes after stimulation, for iTBS versus sham stimulation.
measure: Subjective effort discounting - cTBS versus sham stimulation
timeFrame: Change in subjective value estimated 72 minutes after stimulation, for cTBS versus sham stimulation.
measure: Subjective effort discounting - iTBS versus sham stimulation
timeFrame: Change in subjective value estimated 72 minutes after stimulation, for iTBS versus sham stimulation.
measure: Subjective effort rating - cTBS versus sham stimulation
timeFrame: Change in subjective value estimated 70 minutes after stimulation, for cTBS versus sham stimulation.
measure: Subjective effort rating - iTBS versus sham stimulation
timeFrame: Change in subjective value estimated 70 minutes after stimulation, for iTBS versus sham stimulation.
Secondary outcomes:
Other outcomes:
Locations:
city: Piscataway
country: United States
facility: Center for Advanced Human Brain Imaging Research
state: New Jersey
Study officials:
affiliation: Rutgers University
name: John A Westbrook, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3.