A 3.3 x 3.2mm(2) SoC in 0.35 mu m 2P/4M CMOS combines neurochemical sensing, on-the-fly chemometrics, and feedback-controlled stimulation to realize a "neurochemical thermostat" by differentiating electrically evoked brain dopamine levels from interferents in complex signals recorded in vivo and maintaining the levels between two user-set thresholds via closed-loop neuromodulation. The SoC features duty cycling in intermittent neurochemical sensing and digital signal processing to dissipate 127.5 mu W at 2.5V.