Pharmacological stress impairs working memory performance and attenuates dorsolateral prefrontal cortex glutamate...

Area of Science:

• Neuroscience
• Cognitive Psychology
• Psychiatry

Background:

• Working memory is crucial for cognitive function and is associated with the dorsolateral prefrontal cortex (dlPFC).
• Previous studies using proton functional magnetic resonance spectroscopy (¹H fMRS) show dlPFC glutamate increases during working memory tasks, indicating heightened excitatory neural activity.
• Acute stress is known to negatively impact working memory performance.

Purpose of the Study:

• To investigate the effect of acute stress on dlPFC glutamate modulation during working memory.
• To compare working memory performance and dlPFC glutamate changes under placebo versus acute stress conditions.

Main Methods:

• A double-blind, randomized crossover study involving 19 participants.
• Participants completed a letter 2-back task (working memory) while undergoing left dlPFC ¹H fMRS under placebo (lactose) and acute stress (yohimbine + hydrocortisone) conditions.
• Glutamate levels were quantified using LCModel, and modulation was calculated as the percentage change from rest to task.

Main Results:

• Acute stress significantly attenuated working memory-induced dlPFC glutamate modulation compared to placebo.
• Participants exhibited impaired 2-back task accuracy under acute stress.
• Physiological stress markers confirmed the effectiveness of the stress-inducing agent.

Conclusions:

• Acute stress impairs dlPFC function, specifically reducing excitatory neural activity during working memory tasks.
• This provides a neurobiological basis for how stress can disrupt cognitive processes and potentially exacerbate psychiatric conditions.
• Further research is needed to differentiate the roles of noradrenaline and cortisol and to explore interventions.