OBJECTIVE: The purpose of this paper is to demonstrate how the integration of the multi-channel measurement capabilities of near-infrared spectroscopy (NIRS), electrocorticography (ECoG), and negative temperature coefficient thermistor sensors into a single device compact enough for subdural implantation can provide beneficial information on various aspects of brain cortical activity and prove a powerful medical modality for pre-, intra-, and post-operative diagnoses in neurosurgery. METHODS: The development of a flexible multi-modal multi-channel probe for the simultaneous measurement of the NIRS, ECoG, and surficial temperature obtained from the cerebral cortex was carried out. Photoelectric bare chips for NIRS channels, miniature temperature-coefficient thermistors for measuring localized temperature variation, and 3-mm-diameter platinum plates for ECoG recording were assembled on a polyimide-based flexible printed circuit to create six channels for each modality. A conformal coating of Parylene-C was applied on all the channels except the ECoG to make the probe surface biocompatible. RESULTS: As a first-in-human study, the simultaneous measurement capability of the multi-modality probe, with sufficient signal-to-noise ratio and accuracy, to observe pathological neural activities in subjects during surgery and post-operative monitoring, with no complications two weeks since the implantation, was confirmed. CONCLUSION: The feasibility of using a single device to assess the dynamic pathological activity from three different aspects was determined for human patients. SIGNIFICANCE: The simultaneous and accurate multi-channel recording of electrical, hemodynamic, and thermographic cortical activities in a single device small enough for subdural implantation is likely to have major implications in neurosurgery and neuroscience.