Weight Loss After Obesity Disrupts Cognitive Flexibility Through Reinforcement Learning Strategies

Area of Science:

• Neuroscience
• Behavioral Science
• Metabolic Research

Background:

• Weight regain is common after obesity treatment, but cognitive factors are poorly understood.
• Cognitive flexibility, crucial for adaptive behavior, may be affected by obesity and subsequent weight loss.

Purpose of the Study:

• To investigate if obesity induces cognitive flexibility deficits in the weight loss state.
• To examine sex-specific effects on cognitive flexibility and motivation after weight normalization.

Main Methods:

• Mice models of diet-induced obesity were used, followed by a weight loss period.
• Cognitive flexibility was assessed using a probabilistic reversal learning (PRL) task.
• Motivation was evaluated with a progressive-ratio (PR) task, and reinforcement learning (RL) modeling was applied.

Main Results:

• Mice post-weight loss showed persistent impairments in PRL efficiency.
• Sex-specific deficits were observed: males had reduced late-phase reversal efficiency, while females showed early inefficiency with later recovery.
• RL modeling indicated reduced learning rates, signifying impaired value updating, despite normal motivation levels.

Conclusions:

• Weight loss following obesity resulted in sex-specific reinforcement learning (RL) deficits.
• These findings distinguish motivational drive from cognitive flexibility, identifying maladaptive decision-making as a post-weight loss characteristic.
• Targeted interventions are needed to address cognitive barriers that may impede sustained weight management.