Theta-frequency subthalamic stimulation enhances conflict resolution in Parkinson’s disease patients with freezing of gait through frontal cortex modulation

Abstract

Freezing of gait (FOG) in Parkinson’s disease (PD) is a debilitating motor symptom linked to executive dysfunction, particularly impaired conflict resolution. However, the underlying neural mechanisms and optimal treatment remain unclear. We assessed conflict resolution using a modified Flanker task in 90 PD patients (52 with FOG) and 37 healthy controls. PD-FOG patients exhibited significantly greater conflict costs than patients without FOG and healthy controls. Task-based fMRI revealed enhanced frontal cortical activation associated with conflict processing deficits in PD-FOG, positively correlating with FOG severity. In a subgroup of 18 PD-FOG patients undergoing fMRI during subthalamic nucleus deep brain stimulation (STN-DBS), theta-frequency (5 Hz) stimulation improved conflict resolution and increased frontal activation, whereas high-frequency (130 Hz) stimulation primarily activated motor regions without cognitive benefit. These findings indicate that frontal dysfunction contributed to the conflict resolution deficits in PD-FOG and support theta-frequency STN-DBS as a promising therapeutic approach for enhancing cognitive function.