Cingulate dynamics track depression recovery with deep brain stimulation.

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD)1. However, achieving stable recovery is unpredictable2, typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting3. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient's current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment.

Learning Internal Representations of 3D Transformations From 2D Projected Inputs.

We describe a computational model for inferring 3D structure from the motion of projected 2D points in an image, with the aim of understanding how biological vision systems learn and internally represent 3D transformations from the statistics of their input. The model uses manifold transport operators to describe the action of 3D points in a scene as they undergo transformation. We show that the model can learn the generator of the Lie group for these transformations from purely 2D input, providing a proof-of-concept demonstration for how biological systems could adapt their internal representations based on sensory input. Focusing on a rotational model, we evaluate the ability of the model to infer depth from moving 2D projected points and to learn rotational transformations from 2D training stimuli. Finally, we compare the model performance to psychophysical performance on structure-from-motion tasks.