Figure 4.

Schematic illustration of connectomic lesioning. (A) Current clinical lesions (blue sphere) may intersect white matter connections associated with clinical benefit (red fibres) but also detrimental connections associated with less benefit or side effects (blue fibres). In the future, optimized lesions (green sphere) can be guided by connectivity to intersect only beneficial tracts while avoiding the detrimental ones. Red and blue fibre tracts are taken from a recent study of beneficial and detrimental connections for improving obsessive-compulsive disorder (OCD) following deep brain stimulation (DBS) to the anterior limb of the internal capsule.⁹⁴ (B) Schematic illustrating how the clinical value of lesions versus DBS could change as the precision of our therapeutic target increases. When the therapeutic target is unclear, DBS has a major advantage over lesions due to reversibility and tunability. As the target and lesioning technique become more precise, this advantage is diminished, and we may reach an inflection point where lesions become preferable over DBS (due to lower infection risk and higher convenience). It should be noted that this schematic does not account for other possible future developments, such as closed-loop DBS, which could increase the benefit of DBS. MRgFUS = magnetic resonance-guided focused ultrasound.