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

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. What is the causal role of frontal pole in explore-exploit behavior in younger and older adults?
2. What is the causal role of IFG in explore-exploit behavior in younger and older adults?

The investigators will use continuous theta-burst transcranial magnetic stimulation (cTBS, Huang et al. 2005) to inhibit neural activity in each region for approximately 50 minutes (Wischnewski \& Schutter, 2015) and measure the downstream effects on behavior in younger and older adults. Consistent with their respective roles in the explore-exploit circuit (Figure 5 in Research Strategy), the investigators predict that inhibition of frontal pole will lead to a selective reduction in directed, but not random, exploration, while inhibition of IFG will decrease exploitation and lead to increases in both types of exploration.

Participants in each age group will be pseudo-randomly assigned to either the frontal pole group or IFG group such that the study will have 42 participants (21 males, 21 females) in each group. Thus there will be four distinct groups of subjects older frontal pole, younger frontal pole, older IFG, younger IFG. Each participant will take part in two TMS sessions, one target and one control session. The order of sessions will be counterbalanced across subjects.

The primary endpoints of the study are to determine whether:

1. cTBS applied to frontal pole inhibits directed exploration within the younger and older groups
2. cTBS applied to IFG promotes both directed and random exploration within the younger and older groups

The study is powered to answer these questions with 80% power at a threshold of p \< 0.05.

Conditions

• Healthy Aging

Interventions

DEVICE

Continuous theta burst transcranial magnetic stimulation

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.

Sponsors & Collaborators

• National Institute on Aging (NIA)

  collaborator NIH

• University of Arizona

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-10-01

Primary Completion

2024-07-31

Completion

2024-08-01

FDA Device

Yes

Countries

• United States

Study Locations