Medial parietal alpha-frequency transcranial alternating current stimulation for chronic insomnia: A randomized sham-controlled trial

Background Patients with chronic insomnia are characterized by alterations in default mode network and alpha oscillations, for which the medial parietal cortex (MPC) is a key node and thus a potential target for interventions. Methods Fifty-six adults with chronic insomnia were randomly assigned to 2 mA, alpha-frequency (10 Hz), 30 min active or sham transcranial alternating current stimulation (tACS) applied over the MPC for 10 sessions completed within two weeks, followed by 4- and 6-week visits. The connectivity of the dorsal and ventral posterior cingulate cortex (vPCC) was calculated based on resting functional MRI. Results For the primary outcome, the active group showed a higher response rate (≥ 50% reduction in Pittsburgh Sleep Quality Index (PSQI)) at week 6 than that of the sham group (71.4% versus 3.6%) (risk ratio 20.0, 95% confidence interval 2.9 to 139.0, p = 0.0025). For the secondary outcomes, the active therapy induced greater and sustained improvements (versus sham) in the PSQI, depression (17-item Hamilton Depression Rating Scale), anxiety (Hamilton Anxiety Rating Scale), and cognitive deficits (Perceived Deficits Questionnaire-Depression) scores. The response rates in the active group decreased at weeks 8-14 (42.9%-57.1%). Improvement in sleep was associated with connectivity between the vPCC and the superior frontal gyrus and the inferior parietal lobe, whereas vPCC-to-middle frontal gyrus connectivity was associated with cognitive benefits and vPCC-to-ventromedial prefrontal cortex connectivity was associated with alleviation in rumination. Conclusions Targeting the MPC with alpha-tACS appears to be an effective treatment for chronic insomnia, and vPCC connectivity represents a prognostic marker of treatment outcome.