Cortical electrical stimulation applied twice weekly for 12 weeks preserved nigrostriatal dopaminergic neurons and improved motor function in MitoPark transgenic mice, a well-established Parkinson's disease model. The intervention began at 8 weeks of age, before significant neurodegeneration occurs, and enhanced tyrosine hydroxylase-positive neuron survival while maintaining striatal fiber density compared to controls. This neuroprotective approach represents a significant departure from current Parkinson's treatments, which primarily manage symptoms rather than slow disease progression. The timing proves crucial—early intervention during the presymptomatic phase appears key to maximizing benefits. While deep brain stimulation has shown clinical success for advanced Parkinson's, this non-invasive cortical approach could potentially be applied much earlier in disease progression, when more neurons remain viable for protection. The MitoPark model's mitochondrial dysfunction closely mirrors human Parkinson's pathophysiology, lending credibility to these findings. However, translating twice-weekly electrical stimulation protocols to humans will require careful optimization of parameters and delivery methods. This represents confirmatory evidence that neuromodulation can influence disease trajectory, not just symptoms.