State-dependent dual-site prefrontal TMS bidirectionally modulates working-memory accuracy

Area of Science:

• Neuroscience
• Cognitive Science
• Neuromodulation

Background:

• Working memory (WM) is crucial for cognition and a target for neuromodulation.
• Transcranial magnetic stimulation (TMS) studies on dorsolateral prefrontal cortex (DLPFC) show variable WM outcomes.
• Current methods may not engage distributed brain networks or account for brain states.

Purpose of the Study:

• To investigate if dual-site sequential TMS modulates WM performance differently than single-site TMS.
• To determine if this modulation is state-dependent, considering factors like fatigue.
• To compare excitatory intermittent theta-burst stimulation (iTBS) over left DLPFC with inhibitory continuous theta-burst stimulation (cTBS) over medial prefrontal cortex (mPFC).

Main Methods:

• Thirty-seven healthy adults participated in a within-subjects design.
• Participants completed 0-back and 2-back WM tasks.
• Dual-site (left DLPFC + mPFC) and single-site (DLPFC) TMS protocols were applied.
• Self-reported fatigue indicated cognitive state.

Main Results:

• Dual-site TMS improved 2-back WM accuracy in low-fatigue states.
• Dual-site TMS impaired 2-back WM accuracy in high-fatigue states.
• No significant effects were observed for the 0-back task or reaction time.

Conclusions:

• Dual-site prefrontal TMS can bidirectionally modulate WM accuracy based on cognitive state.
• Stimulation effects are state-dependent, emphasizing the need for personalized approaches.
• Network-sensitive and state-aware neuromodulation is key for cognitive enhancement.