Table 2.
Comparative summary of closed-loop biomarkers, control strategies, and evidence levels across major clinical applications.
| Indication | Sensed Signal | Biomarker | Stimulation Target | Stimulation Modality | Controller Type | Loop Latency | Developmental Stage | Principal Outcome | Evidence Level | Clinical Maturity |
|---|---|---|---|---|---|---|---|---|---|---|
| Focal epilepsy | ECoG | Ictal/pre-ictal pattern | Seizure focus/thalamus | RNS (electrical) | Threshold-triggered | ~100–500 ms | FDA-approved (RNS System) | 82% median seizure reduction at 3 years (n = 324); 41% with ≥90% reduction (Eliashiv et al., 2026) | I (RCT + real-world) | Established |
| Parkinson’s disease | LFP (STN) | Beta-band (13–30 Hz) power | STN | aDBS (electrical) | Dual-threshold adaptive | ~100–300 ms | CE-marked; FDA investigational | 35% greater motor improvement (MDS-UPDRS III) vs. cDBS (n = 5) (Cernera et al., 2025); comparable motor control with reduced side effects (n = 62) (Li et al., 2025) | II (multiple cohort) | Emerging |
| Treatment-resistant depression | Intracranial LFP | Amygdala gamma activity | VC/VS | DBS (electrical) | Personalized threshold | ~200–500 ms | n-of-1/early pilot | Rapid and sustained remission in single patient (Scangos et al., 2021) | IV (n-of-1) | Exploratory |
| Chronic pain | ECAP | Spinal cord neural response amplitude | Dorsal column | SCS (electrical) | PID/closed-loop amplitude | ~50–100 ms | FDA-approved; CE-marked | 79% patients with ≥50% pain reduction at 12 months; 48% with ≥80% relief (Shariati et al., 2025) | I (RCT) | Established |
| Stroke rehabilitation | EEG/ECoG | Motor intent (mu/beta desync) | Cortex or peripheral nerves | BCI-triggered FES/exoskeleton | ML classifier | ~200–600 ms | Research/pilot RCTs | FMA-UE improvement: mean difference of 3.26 points (95% CI: 2.73–3.78) favoring BCI (Siapas & Wilson, 1998) | II (RCT) | Emerging |
| Spinal cord injury | ECoG/cortical spikes | Decoded motor trajectory | Spinal cord (epidural) | Brain-spine interface (electrical) | Decoder + pattern generator | ~300–500 ms | First-in-human (n = 1) | Standing and walking with assistance in chronic tetraplegia (Clark et al., 2024) | IV (single case) | Exploratory |
Evidence level: I, meta-analysis/randomized controlled trial; II, controlled trial without randomization; III, observational study; IV, case series/n-of-1. Clinical maturity: Established, routine clinical use; Emerging, multiple ongoing trials; Exploratory, early-phase or proof-of-concept.