Investigating Cognitive Flexibility Training

Condition(s) studied

Investigational drug(s) / intervention(s)

Experimental (Implicit Training): Structure Learning Training: 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.

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

Study 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).

Eligibility

Primary outcome measure(s)

• Structure Learning Outcome 1 - Performance Index (PI) Relative — Through training completion (adaptive, up to 12 days)
  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.
• Structure Learning Outcome 2 - Strategy choice — Through training completion (adaptive, up to 12 days)
  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.
• Structure Learning Outcome 3 - Strategy ICD index (measured by the integral curve difference) — Through training completion (adaptive, up to 12 days)
  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.
• Structure Learning Outcome 4 - Learning rate — Through training completion (adaptive, up to 12 days)
  Rate of learning across the training sessions or days.
• Structure Learning Outcome 5 - Strategy shifting rate — Through training completion (adaptive, up to 12 days)
  Rate of strategy change across the training sessions or days.
• 'All You Can E.T.' (AYCET) Outcome 1 - Accuracy — Through training completion (adaptive, up to 12 days)
  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.
• 'All You Can E.T.' (AYCET) Outcome 2 - Response Time (RT) — Through training completion (adaptive, up to 12 days)
  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.
• Cognitive Flexibility (Strategy) Outcome 1 - Wisconsin Card Sorting Test (WCST): Proportion of perseverative errors — Post-intervention (within one week after post-MRI scan)
  Proportion of error trials where participants incorrectly choose a deck based on the rule from the previous set.
• Cognitive Flexibility (Strategy) Outcome 2 - Wisconsin Card Sorting Test (WCST): Learning rate — Post-intervention (within one week after post-MRI scan)
  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.
• Cognitive Flexibility (Strategy) Outcome 3 - Wisconsin Card Sorting Test (WCST): Decision consistency — Post-intervention (within one week after post-MRI scan)
  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.
• Cognitive Flexibility (Strategy) Outcome 4 - Intra/Extra-Dimensional Set Shifting (IED): Extra-dimensional set errors — Post-intervention (within one week after post-MRI scan)
  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.
• Cognitive Flexibility (Strategy) Outcome 5 - Intra/Extra-Dimensional Set Shifting (IED): Extra-dimensional reversal errors — Post-intervention (within one week after post-MRI scan)
  This is the total number of errors made in Stage 9. Lower errors mean better performance.
• Cognitive Flexibility (Strategy) Outcome 6 - Intra/Extra-Dimensional Set Shifting (IED): Learning rate — Post-intervention (within one week after post-MRI scan)
  Parameter extracted from Feature Reinforcement Model.
• Cognitive Flexibility (Strategy) Outcome 7 - Intra/Extra-Dimensional Set Shifting (IED): Choice determinism — Post-intervention (within one week after post-MRI scan)
  Parameter extracted from Feature Reinforcement Model.
• Cognitive Flexibility (Strategy) Outcome 8 - Intra/Extra-Dimensional Set Shifting (IED): Dimension primacy — Post-intervention (within one week after post-MRI scan)
  Parameter extracted from Feature Reinforcement Model.
• Cognitive Flexibility (Strategy) Outcome 9 - Probabilistic Reversal Learning (PRL): Perseveration — Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  Number of trials until the participant updates their response after the rule reversal.
• Cognitive Flexibility (Strategy) Outcome 10 - Probabilistic Reversal Learning (PRL): Switch probability — Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  Number of switches in the participant responses following negative feedback (i.e. trap trials: when the less likely object is correct).
• Cognitive Flexibility (Strategy) Outcome 11 - Probabilistic Reversal Learning (PRL): Trials to criterion in block 2 (Reversal) — Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  Number of trials before participant reach defined learning criterion during the Reversal phase.
• Cognitive Flexibility (Strategy) Outcome 12 - Probabilistic Reversal Learning (PRL): Learning rates — Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  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.
• Cognitive Flexibility (Strategy) Outcome 13 - Probabilistic Reversal Learning (PRL): Reinforcement sensitivity — Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  Parameter extracted from the Reinforcement Learning Model based on the Rescorla-Wagner rule.
• Cognitive Flexibility (Strategy) Outcome 14 - Probabilistic Reversal Learning (PRL): Stickiness — Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  Parameter extracted from the Reinforcement Learning Model based on the Rescorla-Wagner rule.
• Cognitive Flexibility (Shifting) Outcome 1 - Task Set Switching - Where (TSS-Where): Task switch cost in RT — Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  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.
• Cognitive Flexibility (Shifting) Outcome 2 - Task Set Switching - Where (TSS-Where): Task switch cost in Accuracy — Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  Switch cost in terms of accuracy is defined as the difference between the accuracy in switch trials with that of repeat trials.
• Cognitive Flexibility (Shifting) Outcome 3 - Task Set Switching - What (TSS-What): Task switch cost in RT — Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  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.
• Cognitive Flexibility (Shifting) Outcome 4 - Task Set Switching - What (TSS-What): Task switch cost in Accuracy — Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  Switch cost in terms of accuracy is defined as the difference between the accuracy in switch trials with that of repeat trials.
• Cognitive Flexibility (Shifting) Outcome 5 - Colour Shape Task (CST): Task switch cost in RT — Baseline (pre-intervention and within two weeks prior to pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  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.
• Cognitive Flexibility (Shifting) Outcome 6 - Colour Shape Task (CST): Task switch cost in Accuracy — Baseline (pre-intervention and within two weeks prior to pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  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.
• Cognitive Flexibility (Shifting) Outcome 7 - Colour Shape Task (CST): Change in task switch cost in RT — Baseline (pre-intervention and within two weeks prior to pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  Change in switch cost as indexed by reaction time between pre and post intervention.
• Cognitive Flexibility (Shifting) Outcome 8 - Colour Shape Task (CST): Change in task switch cost in accuracy — Baseline (pre-intervention and within two weeks prior to pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  Change in switch cost as indexed by accuracy between pre and post intervention.
• Cognitive Flexibility (Shifting) Outcome 9 - Trail Making Test (TMT): Ratio between time to complete Trail B to Trail A — Post-intervention (within one week after post-MRI scan)
  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.
• Working Memory Outcome 1 - Backwards Digit Span (BDS): Total items correct — Pre-intervention (within one week before pre-MRI scan) and Post-intervention (within one week after post-MRI scan)
  Number of digit sequences that participant successfully recalled in the reverse order.
• Working Memory Outcome 2 - Spatial Working Memory (SWM): Between search errors — Post-intervention (within one week after post-MRI scan)
  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.
• Working Memory Outcome 3 - Spatial Working Memory (SWM): Strategy score — Post-intervention (within one week after post-MRI scan)
  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.
• Inhibition Outcome 1 - Stroop Task: Interference measure for RT — Baseline (pre-intervention and within two weeks prior to pre-MRI scan)
  Difference between response latency of all correct congruent trials and response latency of all correct incongruent trials.
• Inhibition Outcome 2 - Stroop Task: Interference measure for accuracy — Baseline (pre-intervention and within two weeks prior to pre-MRI scan)
  Difference between proportion correct of all congruent trials and proportion correct of all incongruent trials.

Trial sites (1)

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