Sleep, circadian rhythms and deep brain stimulation: clinical importance and progress towards a next-generation ‘chronotherapy’ platform
Year: 2025
Type: article
Abstract: Subdural cortical stimulation for treatment-resistant depression (TRD) has been underexplored due to challenges in precisely targeting networks within individuals, due in part to the substantial variability in cortical network topography across individuals.Various neurophysiological models have been proposed to explain the complex symptomatology of depression, implicating networks such as the Default Mode Network (DMN), Fronto-Parietal Networks (FPN), and the Salience Network (SN).Precision functional mapping (PFM) using resting state fMRI data, can yield personalized network organization maps of the brain, allowing for specific stimulation targeting multiple dysfunctional networks.Using 50 minutes of low motion resting-state functional connectivity, PFM was conducted with both a supervised or unsupervised approach network mapping algorithm.These maps revealed aberrant regions within the SN (enlarged relative to controls, t¼-2.93 p<0.01), and DMN (smaller relative to controls, t¼2.39 p<0.01).Utilizing a 3D model of the brain and a 3D model of four multicontact electrodes (Abbott Laboratories, FDA approved for spinal stimulation), placements targeting SN, DMN, and FP network motifs were planned.A volumetric image with the desired placements was then used for stereotactic neuronavigation and implantation.With Bayesian optimization of stimulation settings over time, we demonstrate that personally targeted bilateral subdural prefrontal cortical stimulation (PCS) of emotion regulation and attention allocation networks decreased depressive symptoms over time (full resolution of symptoms on HRSD after 6 month follow-up).A postsurgical CT scan confirmed accurate placement with pre-surgical targets.DWI-based tractography further revealed distinct stimulation of white matter tracts within the left and right superior longitudinal fasciculus, left and right anterior corticostriatal tract, frontoocciptal fasciculus, anterior insular tracts and forceps minor tract.Together, we demonstrate that PCS has the potential to become an effective antidepressant treatment option for severe and chronic depression.
Source: Brain stimulation
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,430
OpenAlex ID: W4407935021