Decoding depression during subcallosal cingulate deep brain stimulation

Abstract

Deep brain stimulation of subcallosal cingulate white matter (SCCwm-DBS) alleviates symptoms of treatment resistant depression (TRD) over months of therapy. Readouts of depression symptom severity derived from neural recordings are needed for more systematic study and improvement of the therapy. In this study, we measured local field potentials (LFP) multiple times a day alongside seven months of therapy using the Activa PC+S™ in six patients treated with SCCwm-DBS. We found significant changes in oscillatory power between early and late therapy after accounting for stimulation-related distortions, particularly within the β band. We then used a decoder strategy to identify oscillatory activity that tracked with depression measurements over seven months, with asymmetric δ and β oscillations contributing to a statistically significant prediction of 10% of the measured depression signal. Simulating its use in clinical decision-making, we demonstrated that the DR-SCC yield clinically meaningful information that can augment other measures of depression state. Ultimately, this DR-SCC provides a data-driven first-step towards objectively tracking chronic recovery after antidepressant DBS implantation and developing adaptive DBS strategies in the presence of active stimulation.

Network Action of Subcallosal Cingulate White Matter Deep Brain Stimulation

“…The symmetry of this second mode suggests a more balanced, secondary response not mediated by the engaged white matter that demonstrates significant asymmetry (Figure 5d). Notably, the oscillatory correlations in this second mode are aligned with a chronic depression readout identified in the SCC [45]. This mode’s positive coefficients in channels at the middle of the midline are consistent with the spatial extent of bilateral SCC, though it more direct links between short- and long-term activity using EEG is needed to interpret more completely.…”

“…This remote action is predominantly in the right hemisphere during bilateral stimulation, and is specific to precise SCCwm-DBS. The action consistent of two major spatio-oscillatory modes: a primary broad low-frequency correlation, and a secondary δ + β anticorrelated with θ + α , consistent with chronic SCC activity that reflects recovery from depression [45]. Further work is needed to verify this network action in larger cohorts with consistent neural recordings, but this preliminary characterization clarifies the immediate actions of antidepressant DBS targeted at the SCC, with implications for future clinical trials and therapeutic optimization.…”

“…Here, we clarify the network-level mechanism and find evidence supportive of blockade of signaling along right cingulum bundle over the initial treatment initiation. More effort is needed to understand the dynamics that SCCwm-DBS evokes across scalp measurements [14] and the link to long-term δ − β changes that track with depression symptom recovery [45]. The support model approach taken here can be extended with neural mass models to more directly link tractography, dynamic responses, and candidate DBS mechanisms for likelihood-based inference of long-term therapeutic mechanism.…”

Mitigating Mismatch Compression in Differential Local Field Potentials

“…Even with hardware improvements, analytical mitigation strategies may enable low-cost bdDBS devices that can achieve similar readout utility. Ultimately, this work enables more reliable oscillatory analyses using ∂LFP devices, including first-generation Active PC+S ™ , particularly using supervised machine learning that leverages behavioral signals to isolate neural readouts [ 49 ].…”