A 64-channel 0.13- $\mu \text{m}$ CMOS system on a chip (SoC) for neuroelectrical monitoring and responsive neurostimulation is presented. The $\Delta \Sigma $ -based neural channel records signals with rail-to-rail dc offset at the input without any area-intensive dc-removing passive components, which leads to a compact 0.013-mm2 integration area of recording and stimulation circuits. The channel consumes 630 nW, yields a signal to noise and distortion ratio of 72.2 dB, a 1.13- $\mu $ Vrms integrated input-referred noise over 0.1–500 Hz frequency range, and a noise efficiency factor of 2.86. Analog multipliers are implemented in each channel with minimum additional area cost by reusing the multi-bit current-digital to analog converter that is originally placed for current-mode stimulation. The multipliers are used for compact implementation of bandpass finite impulse response filters, as well as voltage gain scaling. A tri-core low-power DSP conducts phase-synchrony-based neurophysiological event detection and triggers a subset of 64 programmable arbitrary-waveform current-mode stimulators for subsequent neuromodulation. Two ultra-wideband (UWB) wireless transmitters communicate to receivers located at 10 cm to 2 m distance from the implanted SoC with data rates of 10–46 Mb/s, respectively. An inductive link that operates at 1.5 MHz provides power to the SoC and is also used to communicate commands to an on-chip ASK receiver. The chip occupies 6 mm2 while consuming 1.07 and 5.44 mW with delay-based and voltage controlled oscillator-based UWB transmitters, respectively. The SoC is validated in vivo using epilepsy monitoring (seizure detection) and treatment (seizure suppression) experiments.