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Causal Evidence for Prefrontal-Motor Coupling in Reward-Responsive Goal-Directed Behavior.

Justin Riddle1,2,3,4, Lewis P Edwards3,4, Moria Smoski5

  • 1Department of Psychology, Florida State University, Tallahassee, Florida 32304 justin.riddle@fsu.edu Flavio_frohlich@med.unc.edu.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|January 29, 2026
PubMed
Summary
This summary is machine-generated.

Major depressive disorder (MDD) anhedonia is linked to impaired reward-responsive goal-directed behavior. Targeting left prefrontal cortex delta-beta coupling with non-invasive brain stimulation causally improved this behavior in MDD patients.

Keywords:
anhedoniacross-frequency couplingdecision-makingelectroencephalographymajor depressive disordertranscranial alternating current stimulation

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Computational Neuroscience

Background:

  • Anhedonia, a core symptom of major depressive disorder (MDD), is associated with blunted reward processing.
  • The precise electrophysiological mechanisms linking prefrontal cortex dysfunction to anhedonia remain poorly understood.
  • Non-invasive brain stimulation often targets the left lateral prefrontal cortex for anhedonia, but optimal targets require mechanistic insight.

Purpose of the Study:

  • To investigate the neural mechanisms underlying reward processing deficits in MDD, specifically focusing on anhedonia.
  • To identify specific components of reward processing (effort motivation, reward valuation, goal-directed behavior) related to anhedonia severity.
  • To determine if modulating prefrontal-motor neural coupling can causally improve reward-responsive goal-directed behavior in MDD.

Main Methods:

  • Participants with MDD completed an adaptive expenditure of effort for reward task (Adaptive-EEfRT) while electroencephalography (EEG) was recorded.
  • Spectral and cross-frequency coupling analyses were used to examine prefrontal and motor cortex activity during reward processing.
  • Cross-frequency transcranial alternating current stimulation (tACS) was applied to modulate prefrontal-motor delta-beta coupling, with behavioral outcomes compared to placebo and active controls.

Main Results:

  • Anhedonia severity in MDD was most strongly correlated with blunted reward-responsive goal-directed behavior.
  • EEG revealed increased left prefrontal delta and decreased motor cortex beta oscillations, with significant delta-beta phase-amplitude coupling across these regions during reward tasks.
  • tACS targeting prefrontal-motor delta-beta coupling significantly improved reward-responsive goal-directed behavior compared to sham and active-control stimulation.

Conclusions:

  • Deficits in reward-responsive goal-directed behavior are a key neural correlate of anhedonia in MDD.
  • Left prefrontal cortex and motor cortex delta-beta cross-frequency coupling is a critical mechanism for translating goals into action.
  • Targeting this specific prefrontal-motor coupling with non-invasive brain stimulation offers a promising avenue for novel MDD interventions for anhedonia.