Investigating Cognitive Flexibility Training

NCT07556250 | Not Yet Recruiting

• 1 other identifier: IRB-2025-1325
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators' previous research identified two distinct subtypes of Cognitive Flexibility (CF), termed CF1 (shifting flexibility) and CF2 (strategy flexibility). The present study aims to determine whether these forms of CF can be trained, how they differ, and the extent to which improvements transfer to broader learning and cognitive skills. In addition, social functioning outcomes and the extent to which social factors moderate the effects of cognitive flexibility training are assessed. The investigators will employ a multi-modal approach combining cognitive-behavioural and neuroimaging methods to examine how brain mechanisms and cognitive performance change following CF-targeted training intervention (Structure learning) compared with active control and a no-training paradigm (passive control).

Conditions

Healthy

Keywords

Structure Learning; Cognitive Flexibility; Neural Activation; Intervention; Predictive statistics

Outcome Measures

Primary Outcomes (35)

• Structure Learning Outcome 1 - Performance Index (PI) Relative

  Performance index (PI) is the minimum overlap between the distribution of participant responses and the distribution of presented targets per context. The overall PI is then the average of the performance indices across contexts. The PI relative is a normalised PI measure that quantifies participant's performance relative to random guessing.

  Through training completion (adaptive, up to 12 days)

• Structure Learning Outcome 2 - Strategy choice

  Strategy choice is the difference between the Kullback-Leibler (KL) divergence from model matching to the response-based model and the KL divergence from model maximization to the response-based model. Positive strategy choice values indicate a strategy closer to matching, whereas negative values indicate a strategy closer to maximization.

  Through training completion (adaptive, up to 12 days)

• Structure Learning Outcome 3 - Strategy ICD index (measured by the integral curve difference)

  Derived by calculating the integral of each participant's strategy curve and subtracting it from the integral of the exact matching curve, as defined by model matching across training.

  Through training completion (adaptive, up to 12 days)

• Structure Learning Outcome 4 - Learning rate

  Rate of learning across the training sessions or days.

  Through training completion (adaptive, up to 12 days)

• Structure Learning Outcome 5 - Strategy shifting rate

  Rate of strategy change across the training sessions or days.

  Through training completion (adaptive, up to 12 days)

• 'All You Can E.T.' (AYCET) Outcome 1 - Accuracy

  Accuracy is defined as the proportion of correct responses across trials, based on whether the participant selects the correct food or drink item for each alien according to the currently active rule set (e.g., colour, shape, or appearance rules). Accuracy may be computed overall and across levels of rule complexity.

  Through training completion (adaptive, up to 12 days)

• 'All You Can E.T.' (AYCET) Outcome 2 - Response Time (RT)

  Response Time (RT) is defined as the latency between stimulus presentation and participant response on each trial. Mean or median RT will be computed across correct trials to index processing speed under changing rule demands. RT may also be summarized across levels of rule complexity.

  Through training completion (adaptive, up to 12 days)

• Cognitive Flexibility (Strategy) Outcome 1 - Wisconsin Card Sorting Test (WCST): Proportion of perseverative errors

  Proportion of error trials where participants incorrectly choose a deck based on the rule from the previous set.

  Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Strategy) Outcome 2 - Wisconsin Card Sorting Test (WCST): Learning rate

  This is a parameter extracted from a sequential learning model fitted to WCST data and represents how quickly participants updated their beliefs about the values associated with choices following respective negative and positive feedback.

  Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Strategy) Outcome 3 - Wisconsin Card Sorting Test (WCST): Decision consistency

  This is a parameter extracted from a sequential learning model fitted to WCST data and influenced the estimated probability of choosing a specific stimulus per trial. Larger values indicated increased exploitation whereas lower values indicated increased exploration.

  Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Strategy) Outcome 4 - Intra/Extra-Dimensional Set Shifting (IED): Extra-dimensional set errors

  The number of times that the subject failed to select the stimulus compatible with the current rule on the stage where the extra-dimensional shift occurs.

  Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Strategy) Outcome 5 - Intra/Extra-Dimensional Set Shifting (IED): Extra-dimensional reversal errors

  This is the total number of errors made in Stage 9. Lower errors mean better performance.

  Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Strategy) Outcome 6 - Intra/Extra-Dimensional Set Shifting (IED): Learning rate

  Parameter extracted from Feature Reinforcement Model.

  Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Strategy) Outcome 7 - Intra/Extra-Dimensional Set Shifting (IED): Choice determinism

  Parameter extracted from Feature Reinforcement Model.

  Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Strategy) Outcome 8 - Intra/Extra-Dimensional Set Shifting (IED): Dimension primacy

  Parameter extracted from Feature Reinforcement Model.

  Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Strategy) Outcome 9 - Probabilistic Reversal Learning (PRL): Perseveration

  Number of trials until the participant updates their response after the rule reversal.

  Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Strategy) Outcome 10 - Probabilistic Reversal Learning (PRL): Switch probability

  Number of switches in the participant responses following negative feedback (i.e. trap trials: when the less likely object is correct).

  Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Strategy) Outcome 11 - Probabilistic Reversal Learning (PRL): Trials to criterion in block 2 (Reversal)

  Number of trials before participant reach defined learning criterion during the Reversal phase.

  Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Strategy) Outcome 12 - Probabilistic Reversal Learning (PRL): Learning rates

  Parameter extracted from the Reinforcement Learning Model based on the Rescorla-Wagner rule. Two learning rates i.e., one for positive error/reward and one for negative error/punishment can be extracted from the model.

  Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Strategy) Outcome 13 - Probabilistic Reversal Learning (PRL): Reinforcement sensitivity

  Parameter extracted from the Reinforcement Learning Model based on the Rescorla-Wagner rule.

  Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Strategy) Outcome 14 - Probabilistic Reversal Learning (PRL): Stickiness

  Parameter extracted from the Reinforcement Learning Model based on the Rescorla-Wagner rule.

  Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Shifting) Outcome 1 - Task Set Switching - Where (TSS-Where): Task switch cost in RT

  Switch cost in terms of reaction time (ms) is defined as the difference between the mean reaction time across switch trials with that of repeat trials.

  Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Shifting) Outcome 2 - Task Set Switching - Where (TSS-Where): Task switch cost in Accuracy

  Switch cost in terms of accuracy is defined as the difference between the accuracy in switch trials with that of repeat trials.

  Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Shifting) Outcome 3 - Task Set Switching - What (TSS-What): Task switch cost in RT

  Switch cost in terms of reaction time (ms) is defined as the difference between the mean reaction time across switch trials with that of repeat trials.

  Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Shifting) Outcome 4 - Task Set Switching - What (TSS-What): Task switch cost in Accuracy

  Switch cost in terms of accuracy is defined as the difference between the accuracy in switch trials with that of repeat trials.

  Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Shifting) Outcome 5 - Colour Shape Task (CST): Task switch cost in RT

  Switch cost in terms of reaction time (ms) is defined as the difference between the mean reaction time across switch trials with that of repeat trials. Also used for matching between Control and Training groups.

  Baseline (pre-intervention and within two weeks prior to pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Shifting) Outcome 6 - Colour Shape Task (CST): Task switch cost in Accuracy

  Switch cost in terms of accuracy is defined as the difference between the accuracy in switch trials with that of repeat trials. Also used for matching between Control and Training groups.

  Baseline (pre-intervention and within two weeks prior to pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Shifting) Outcome 7 - Colour Shape Task (CST): Change in task switch cost in RT

  Change in switch cost as indexed by reaction time between pre and post intervention.

  Baseline (pre-intervention and within two weeks prior to pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Shifting) Outcome 8 - Colour Shape Task (CST): Change in task switch cost in accuracy

  Change in switch cost as indexed by accuracy between pre and post intervention.

  Baseline (pre-intervention and within two weeks prior to pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Cognitive Flexibility (Shifting) Outcome 9 - Trail Making Test (TMT): Ratio between time to complete Trail B to Trail A

  Participants are asked to complete Trail A (draw lines to connect numbered items in sequence) and subsequently Trail B (draw lines to connect a set of items alternating between letters and numbers) as quickly and as accurately as possible. The ratio of the completion time of Trail B to Trail A is used to examine completion time of Trail B relative to Trail A.

  Post-intervention (within one week after post-MRI scan)

• Working Memory Outcome 1 - Backwards Digit Span (BDS): Total items correct

  Number of digit sequences that participant successfully recalled in the reverse order.

  Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)

• Working Memory Outcome 2 - Spatial Working Memory (SWM): Between search errors

  The number of times the subject incorrectly revisits a box in which a token has previously been found. Calculated across all assessed four, six and eight token trials.

  Post-intervention (within one week after post-MRI scan)

• Working Memory Outcome 3 - Spatial Working Memory (SWM): Strategy score

  The number of times a subject begins a new search pattern from the same box they started with previously. If search is always begun from the same starting point, it is inferred that the subject is employing a planned strategy for finding the tokens. Therefore, a low score indicates high strategy use (1 = always begin the search from the same box), a high score indicates that they are beginning their searches from many different boxes. Calculated across assessed trials with 6 tokens or more.

  Post-intervention (within one week after post-MRI scan)

• Inhibition Outcome 1 - Stroop Task: Interference measure for RT

  Difference between response latency of all correct congruent trials and response latency of all correct incongruent trials.

  Baseline (pre-intervention and within two weeks prior to pre-MRI scan)

• Inhibition Outcome 2 - Stroop Task: Interference measure for accuracy

  Difference between proportion correct of all congruent trials and proportion correct of all incongruent trials.

  Baseline (pre-intervention and within two weeks prior to pre-MRI scan)

Secondary Outcomes (82)

• Stress Outcome 1 - Perceived Stress Scale (PSS): Perceived Stress Scale Score

  Baseline (pre-intervention and within two weeks prior to pre-MRI scan) and Post-intervention (within two weeks after post-MRI scan)

• Sleep Quality Outcome 1 - Pittsburgh Sleep Quality Index (PSQI): Global PSQI Score

  Post-intervention (within two weeks after post-MRI scan)

• Literacy and Numeracy Outcome 1 - Wide Range Achievement Test-5

  Pre-intervention (within one week before pre-MRI) and Post-intervention (within one week after post-MRI scan)

• Decision Making Outcome 1 - Social Value Orientation: Social Preference Score

  Baseline (pre-intervention and within two weeks prior to pre-MRI scan) and Post-intervention (within two weeks after post-MRI scan)

• Decision Making Outcome 2 - Prisoner's Dilemma: Proportion of cooperative choices

  Baseline (pre-intervention and within two weeks prior to pre-MRI scan) and Post-intervention (within two weeks after post-MRI scan)

Other Outcomes (6)

• Mood and State Outcome 1 - Self-Assessment Manikin (SAM)

  Through training completion (adaptive, up to 12 days)

• Mood and State Outcome 2 - Self-Assessment Manikin (SAM)

  Pre-intervention (at pre-MRI scan) and Post-intervention (at post-MRI scan) with maximum 6-12 days scan interval

• Mood and State Outcome 3 - Training Feedback: Task enjoyment level

  Through training completion (adaptive, up to 12 days)

Study Arms (3)

Implicit Training: Structure Learning Training

EXPERIMENTAL

Structure learning training taps on participant's ability to extract patterns from prior stimuli presentations to make predictions. Participants will view different visual stimuli, such as varying alien symbols on the screen. These are presented in sequence that are determined first by frequency statistics (the probability of a given stimulus occurring). Upon mastery, these are followed by more complex context-based statistics (the probability of a given stimulus occurring, depending on the preceding stimuli). Participants will be asked to make responses to indicate the visual stimulus they predict will appear, given variable length sequences. Participants will perform the task in the absence of explicit feedback; instead, they will be required to implicitly learn the task under uncertain conditions, such as changing frequency statistics. In such contexts, individuals must actively generate, update, or discard internal rules in response to changing patterns.

Behavioral: Experimental (Implicit Training): Structure Learning Training

Active Control (Explicit Training): 'All You Can E.T.'

ACTIVE COMPARATOR

The active control group will use the "All You Can E.T." (AYCET) set- shifting task developed by Prof Jan Plass (NYU-CREATE Lab), which has been shown to produce near-transfer effects on cognitive flexibility. Players must apply frequently shifting rule sets to provide differently coloured and shaped aliens with the correct food or drink that they need to survive. As the game progresses, the levels increase in rule complexity (such as the alien's food choice, their colour or appearance), number of aliens and speed of response. These changing factors require participants to continually update, switch, and inhibit their current response set. Immediate feedback is embedded into AYCET to support learning. Aliens' response accordingly to receiving the correct or incorrect item, enabling players to detect discrepancies in their current response rules.

Behavioral: Active Control (Explicit Training): 'All You Can E.T.'

Passive Control

NO INTERVENTION

The passive control group will not receive any intervention but will receive the same pre-post cognitive-behavioural and neuroimaging intervention assessments. A message containing a brain fact will be sent to participants every day to keep them engaged (to have similar daily contact with the research team).

Interventions

Experimental (Implicit Training): Structure Learning Training BEHAVIORAL

Participants will undergo 6-12 sessions of Structure Learning or set-shifting training in the active control training group lasting up to 30 minutes each. Each session will be conducted in a remote-guided manner with an approximate 1-day gap in between sessions. The entire training will span a maximum of 12 days. Across the task, difficulty will progressively increase through changes in probabilistic contingencies. For example, following each symbol, one subsequent symbol may occur with 75% probability and an alternative symbol with 25% probability. Participants will first learn symbol-based contingencies (e.g., 75/25), followed by contingency reversals (25/75) requiring updating of learned associations. An additional stimulus dimension (frames surrounding symbols) will then be introduced with similar probabilistic contingencies and subsequent reversals, requiring flexible adaptation to shifting rules.

Implicit Training: Structure Learning Training

Active Control (Explicit Training): 'All You Can E.T.' BEHAVIORAL

The protocol for the active control condition will mirror that of the experimental arm. Participants will complete an equivalent number of training sessions, and total task time will be matched between the experimental and control groups.

Active Control (Explicit Training): 'All You Can E.T.'

Eligibility Criteria

• Age: 18 Years - 29 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteer (male of female) between 18 and 29 years who gave written informed consent to participate

You may not qualify if:

• Current and/or prior history of learning disabilities
• Current and/or prior history of neurological disorder
• Current and/or prior history of psychiatric disorder
• Current and/or prior history of cardiovascular disorder
• Predominantly left-handed
• Contraindications for MRI (e.g., pacemakers, implanted pumps, metal objects in the body)
• Claustrophobic
• Pregnancy (females)
• Lactation (females)
• Pronounced visual or auditory impairments

Sponsors & Collaborators

• Nanyang Technological University: lead
• University of Cambridge: collaborator

Study Sites (1)

Centre for Lifelong Learning and Individualised Cognition (CLIC), Nanyang Technological University

Singapore, 637335, Singapore

Location

Related Publications (13)

• Parong, J., Wells, A., & Mayer, R. E. (2020). Replicated evidence towards a cognitive theory of game-based training. Journal of Educational Psychology, 112(5), 922-937.

  BACKGROUND

• Tong, K., Uchiyama, R., Fischer, N. L., Langley, C., Cheng, X., Kalaivanan, K., Melia, N., Feng, S., Fu, X., Marzuki, A. A., Talwar, A., Chan, Y. N., Fauziana, R., Hoo, N., Lee, K. M., Lee, L. L., Lee, T., Melani, I., Pei, J. Y., ... Leong, V. Cognitive flexibility: Separate shifting and strategy factors [Manuscript under review]

  BACKGROUND

• Tong, K., Uchiyama, R., Feng, S., Cheng, X., Kalaivanan, K. D., Leong, V., … Robbins, T. W. (2021, December 22). Assessing cognitive flexibility, other executive functions, and learning in healthy young adults [Preregistration]. OSF.

  BACKGROUND

• Tong K, Chan YN, Cheng X, Cheon B, Ellefson M, Fauziana R, Feng S, Fischer N, Gulyas B, Hoo N, Hung D, Kalaivanan K, Langley C, Lee KM, Lee LL, Lee T, Melani I, Melia N, Pei JY, Raghani L, Sam YL, Seow P, Suckling J, Tan YF, Teo CL, Uchiyama R, Yap HS, Christopoulos G, Hendriks H, Chen A, Robbins T, Sahakian B, Kourtzi Z, Leong V; CLIC Phase 1 Consortium. Study protocol: How does cognitive flexibility relate to other executive functions and learning in healthy young adults? PLoS One. 2023 Jul 20;18(7):e0286208. doi: 10.1371/journal.pone.0286208. eCollection 2023.

  PMID: 37471399 BACKGROUND

• Parong, J., Mayer, R. E., Fiorella, L., MacNamara, A., Homer, B. D., & Plass, J. L. (2017). Learning executive function skills by playing focused video games. Contemporary Educational Psychology, 51, 141-151.

  BACKGROUND

• Mayer, R. E., Parong, J., & Bainbridge, K. (2019). Young adults learning executive function skills by playing focused video games. Cognitive Development, 49, 43-50.

  BACKGROUND

• Lee, L. Y., Healy, M. P., Fischer, N. L., Tong, K., Chen, A. S. H., Sahakian, B. J., & Kourtzi, Z. (2024). Cognitive flexibility training for impact in real-world settings. Current Opinion in Behavioural Sciences, 59(101413), 101413.

  BACKGROUND

• Holland, J.L., Daiger, D.C., & Power, P.G. (1980). My Vocational Situation. Palo Alto, CA: Consulting Psychologists Press.

  BACKGROUND

• Gupta, A., Chong, S., & Leong, F. T. L. (2015). Development and validation of the Vocational Identity Measure. Journal of Career Assessment, 23(1), 79-90.

  BACKGROUND

• Wang R, Shen Y, Tino P, Welchman AE, Kourtzi Z. Learning Predictive Statistics: Strategies and Brain Mechanisms. J Neurosci. 2017 Aug 30;37(35):8412-8427. doi: 10.1523/JNEUROSCI.0144-17.2017. Epub 2017 Jul 31.

  PMID: 28760866 BACKGROUND

• Wang R, Shen Y, Tino P, Welchman AE, Kourtzi Z. Learning predictive statistics from temporal sequences: Dynamics and strategies. J Vis. 2017 Oct 1;17(12):1. doi: 10.1167/17.12.1.

  PMID: 28973111 BACKGROUND

• Uddin LQ. Cognitive and behavioural flexibility: neural mechanisms and clinical considerations. Nat Rev Neurosci. 2021 Mar;22(3):167-179. doi: 10.1038/s41583-021-00428-w. Epub 2021 Feb 3.

  PMID: 33536614 BACKGROUND

• Hart Y, Mayo AE, Mayo R, Rozenkrantz L, Tendler A, Alon U, Noy L. Creative foraging: An experimental paradigm for studying exploration and discovery. PLoS One. 2017 Aug 2;12(8):e0182133. doi: 10.1371/journal.pone.0182133. eCollection 2017.

  PMID: 28767668 BACKGROUND

Study Officials

• Annabel SH Chen, PhD

  Nanyang Technological University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kastoori Kalaivanan, PhD

CONTACT

+6569081458; kastoori.k@ntu.edu.sg

Laura R Edmondson Chua, PhD

CONTACT

+6569081458; Laura.chua@ntu.edu.sg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are pseudo-randomly assigned to one of three intervention groups, matched on age, sex, general cognitive abilities and baseline set-shifting ability. These groups target each of the following: (1) Experimental group training strategy flexibility (2) Active Control focusing on shifting flexibility and (3) Passive Control with no training. The two subtypes of cognitive flexibility will be operationalised using distinct training paradigms. Experimental group one will train on strategy flexibility using Structure Learning. Active control targeting shifting flexibility will use explicit set-shifting training 'All You Can E.T.'.

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 29, 2026
• Study Start: April 23, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: As soon as data collection commenced.
• Access Criteria: Researchers may apply for access to data.

Locations

SG (1)