Time-frequency signatures evoked by single-pulse deep brain stimulation to the subcallosal cingulate

Area of Science:

• Neuroscience
• Neuromodulation
• Biomedical Engineering

Background:

• Precision targeting of the subcallosal cingulate (SCC) is crucial for effective deep brain stimulation (DBS) in treatment-resistant depression (TRD).
• Objective methods to confirm optimal target engagement within the heterogeneous SCC region are needed for standardized treatment protocols.
• The time-frequency characteristics of SCC-evoked potentials (SCC-EPs), such as spectral power and phase clustering, remain unexamined.

Purpose of the Study:

• To investigate the time-frequency features of SCC-EPs, specifically evoked power and phase clustering, in TRD patients undergoing SCC DBS.
• To determine if these spectral features can serve as objective markers for precise stimulation targeting within the SCC.
• To explore the relationship between SCC-EP spectral features and stimulation location, white matter density, and potential shared generative mechanisms with other evoked potentials.

Main Methods:

• EEG was recorded from 8 TRD patients with implanted SCC stimulators during wakeful rest.
• Electrical stimulation location within the SCC was experimentally manipulated.
• EEG data were analyzed using Morlet wavelets for evoked power and inter-trial phase clustering in a 50-150 ms time window at frontal sensors with an average reference.

Main Results:

• Enhanced theta-frequency (4-7 Hz) phase clustering was consistently observed across all subjects during left SCC stimulation and correlated with SCC-EP magnitude.
• Dorsal SCC stimulation resulted in stronger phase clustering compared to ventral SCC stimulation.
• An increase in evoked delta power (2-4 Hz) was coincident with SCC-EP but less consistent; a weak correlation was found between phase clustering and white matter density.

Conclusions:

• DBS-evoked time-frequency features, particularly theta-phase clustering, can accurately reflect mm-scale stimulation location changes within the SCC.
• These findings suggest that phase clustering may indicate shared neural mechanisms across different types of evoked potentials.
• Understanding how electrical stimulation impacts cortical activity is vital for developing adaptive DBS technologies tailored to individual neurophysiology for TRD treatment.