Evaluating the Neurocomputational Mechanisms of Explore-Exploit Decision Making in Older Adults

NCT05178381 | Completed DMC FDA Device

• 1 other identifier: R01AG061888
• Study Type: interventional
• Target: 248
• Locations: 1 country
• Sites: 1

Brief Summary

The full experiment involves participants coming into the lab on five separate occasions for neuropsychological testing, a decision making battery, functional and structural MRI, and two TMS sessions for stimulation of the target or control stimulation site. The clinical trial component concerns only the last two sessions where subjects will be randomly assigned to different groups to receive different TMS interventions. In particular, the TMS experiments will ask two main questions:

1. 1.What is the causal role of frontal pole in explore-exploit behavior in younger and older adults?
2. 2.What is the causal role of IFG in explore-exploit behavior in younger and older adults?
3. 3.cTBS applied to frontal pole inhibits directed exploration within the younger and older groups
4. 4.cTBS applied to IFG promotes both directed and random exploration within the younger and older groups

Conditions

Healthy Aging

Keywords

decision making; exploration; reinforcement learning; function magnetic resonance imaging; transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (2)

• Directed exploration

  Change in directed exploration as a result of stimulation to target vs control site. Directed exploration will be measured using the Horizon Task (Wilson et al. 2014) in which directed exploration is defined as the change in p(high info) between horizon 1 and horizon 6.

  Between TMS session 1 and TMS session 2 (1-2 weeks)

• Random exploration

  Change in random exploration as a result of stimulation to target vs control site. Random exploration will be measured using the Horizon Task (Wilson et al. 2014) in which random exploration is defined as the change in p(low mean) between horizon 1 and horizon 6.

  Between TMS session 1 and TMS session 2 (1-2 weeks)

Study Arms (4)

Target: frontal pole; Order: frontal pole first

EXPERIMENTAL

In this arm the target stimulation site is the frontal pole, the control stimulation site is the vertex. Participants will receive the frontal pole stimulation in the first TMS session and vertex stimulation in the second TMS session.

Device: Continuous theta burst transcranial magnetic stimulation

Target: frontal pole; Order: vertex first

EXPERIMENTAL

In this arm the target stimulation site is the frontal pole, the control stimulation site is the vertex. Participants will receive the vertex stimulation in the first TMS session and frontal pole stimulation in the second TMS session.

Device: Continuous theta burst transcranial magnetic stimulation

Target: IFG; Order: IFG first

EXPERIMENTAL

In this arm the target stimulation site is the IFG, the control stimulation site is the vertex. Participants will receive IFG stimulation in the first TMS session and vertex stimulation in the second TMS session.

Device: Continuous theta burst transcranial magnetic stimulation

Target: IFG; Order: vertex first

EXPERIMENTAL

In this arm the target stimulation site is the IFG, the control stimulation site is the vertex. Participants will receive vertex stimulation in the first TMS session and IFG stimulation in the second TMS session.

Device: Continuous theta burst transcranial magnetic stimulation

Interventions

Continuous theta burst transcranial magnetic stimulation DEVICE

Participants will receive cTBS (50Hz stimulation at 80% AMT for 40 seconds). Stimulation will be applied to either the target area (frontal pole or IFG) or control area (vertex). Targeting of each region will be achieved using a frameless neuronavigation system with a Polaris Spectra infrared camera that enables stimulation to be centered on specific coordinates in Montreal Neurological Institute space. We will use coordinates \[x,y,z\] = \[35,50,15\] for frontal pole and \[x,y,z\] = \[56,16,22\] for right IFG based on the location of our activations in the young pilot group (Figure 4). The vertex control site is defined as the Cz position of a 10-20 EEG system. After receiving TMS, participants will stare at a white wall for 1 minute before performing the Horizon Task for 45 minutes.

Also known as: cTBS

Target: IFG; Order: IFG first; Target: IFG; Order: vertex first; Target: frontal pole; Order: frontal pole first; Target: frontal pole; Order: vertex first

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18-30 (younger adults) or 65-74 (older adults)
• No subjective memory complaints
• Fluent in English or formal education in English starting from at least the age of 5
• Telephone Interview for Cognitive Status (TICS) score \> 31
• Montreal Cognitive Assessment (MoCA) \> 25
• Score ≤ 10 on the Hamilton Depression Rating Scale (Hamilton, 1960)
• No significant neurological, psychiatric, medical illness or injury that would affect cognitive function
• No history of concussion with greater than 5 minutes of loss of consciousness
• No history of a psychoactive substance use disorder
• Able and willing to provide informed consent

You may not qualify if:

• Subjective memory complaints
• Telephone Interview for Cognitive Status (TICS) score less than or equal to 31
• Montreal Cognitive Assessment (MoCA) less than or equal to 25
• Score less than one standard deviation below the age, education, and sex adjusted mean from the NACC UDS version 3 normative cohort (Albert et al. 2011; McKhann et al., 2011
• Criteria for DSM-5 diagnosis or history of serious psychiatric disease or diagnosed learning disabilities
• Any other neurological, psychiatric, or medical illness or injury expected to interfere with cognitive function or memory including but not limited to stroke (diagnosed with evidence of stroke), head injury, epilepsy, Parkinson's, brain cancer, depression. Migraines OK. May have TIAs with no sign of impairment and no sequelae following the event
• Active substance abuse disorder i.e. alcohol, nicotine. Previous substance abuse of cocaine, Ecstasy, LSD, IV drugs
• History of seizure disorder as child or currently experiencing or on medications for seizures. Exception is febrile seizures as a child.
• Currently taking the following medications, which are contraindications for TMS: tricyclic antidepressants (Amitriptyline, Clomipramine, Doxepine, Imapramine, Maprotiline, Nortriptyline), anti-psychotic medication (Clozapine), Anti-virals (Foscarnet, Ganciclovir, Ritonavir), Bronchodilator (Theophylline), Amphetamines, gamma-Hydroxybutyrate, Ketamine
• Have recently stopped taking the following medications, which are contraindications for TMS: Alcohol, Benzodiazepines, Barbiturates, Chloral Hydrate, Meprobamate
• Any condition which may prevent the subject from adhering to the study protocol, as determined by the PI, i.e. reported learning disability, cataracts impairing vision, colorblindness.
• The presence of any metallic implant or foreign body, including dental bridges excludes participants from MRI. Removable body piercings/implants okay. Movement disorders that prevent the subject from being still for the MRI. Other contraindications to MRI including being a professional metal worker or welder, having recurring panic attacks or being claustrophobic, being pregnant, or an abnormally high weight or height to fit in scanner. Patients with these MRI contraindications will not be enrolled.

Sponsors & Collaborators

• University of Arizona: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Arizona

Tucson, Arizona, 85721, United States

Location

Related Publications (6)

• Wilson RC, Geana A, White JM, Ludvig EA, Cohen JD. Humans use directed and random exploration to solve the explore-exploit dilemma. J Exp Psychol Gen. 2014 Dec;143(6):2074-81. doi: 10.1037/a0038199. Epub 2014 Oct 27.

  PMID: 25347535 BACKGROUND

• Daw ND, O'Doherty JP, Dayan P, Seymour B, Dolan RJ. Cortical substrates for exploratory decisions in humans. Nature. 2006 Jun 15;441(7095):876-9. doi: 10.1038/nature04766.

  PMID: 16778890 BACKGROUND

• Zajkowski WK, Kossut M, Wilson RC. A causal role for right frontopolar cortex in directed, but not random, exploration. Elife. 2017 Sep 15;6:e27430. doi: 10.7554/eLife.27430.

  PMID: 28914605 BACKGROUND

• Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.

  PMID: 19833552 BACKGROUND

• 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.

  PMID: 15664172 BACKGROUND

• Wischnewski M, Schutter DJ. Efficacy and Time Course of Theta Burst Stimulation in Healthy Humans. Brain Stimul. 2015 Jul-Aug;8(4):685-92. doi: 10.1016/j.brs.2015.03.004. Epub 2015 Mar 26.

  PMID: 26014214 BACKGROUND

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Because stimulation occurs at different locations on the scalp participants will be able to distinguish between the two conditions. However, because they will be unaware of our hypothesis, they will not know which condition is the control condition and which is the target condition.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: The main analyses in this study will ask whether cTBS applied to frontal pole and IFG changes explore-exploit behavior relative to the control condition where cTBS is applied to vertex within age group. Our main predictions are: (1) frontal pole will reduce directed exploration in both age groups, and (2) IFG stimulation will increase both directed and random exploration in both age groups. To test these hypotheses we will perform separate repeated-measures ANOVAs for the different age groups (younger and older adults), for different types of exploration (directed vs random), and for the different target stimulation sites (frontal pole vs IFG), yielding 8 different analyses. Each ANOVA will include TMS condition (vertex vs target) as a within subject factor and order (vertex first vs target first) as a between-subjects factor. The key question is whether there is a main effect of TMS condition on our measures of directed and random exploration.

Study Record Dates

• First Submitted: May 18, 2021
• First Posted: January 5, 2022
• Study Start: October 1, 2022
• Primary Completion: July 31, 2024
• Study Completion: August 1, 2024
• Last Updated: May 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Data will be deposited into the repositories as soon as possible but no later than within one year of the completion of the funded project period for the parent award or upon acceptance of the data for publication, or public disclosure of a submitted patent application, whichever is earlier.
• Access Criteria: Any user with an account at dataverse.org, openneuro.org or GitHub will be able to access data and/or code.

Locations

US (1)