Why not record from every electrode with a CMOS scanning probe?
Authors: Dimitriadis George , Neto Joana P. , Aarts Arno , Alexandru Andrei , Ballini Marco , Battaglia Francesco , Calcaterra Lorenza , Chen Susu , David Francois , Fiáth Richárd , Frazão João , Geerts Jesse P , Gentet Luc J. , Van Helleputte Nick , Holzhammer Tobias , van Hoof Chris , Horváth Domonkos , Lopes Gonçalo , Lopez Carolina M. , Maris Eric , Marques-Smith Andre , Márton Gergely , McNaughton Bruce L. , Meszéna Domokos , Mitra Srinjoy , Musa Silke , Neves Hercules , Nogueira Joana , Orban Guy A. , Pothof Frederick , Putzeys Jan , Raducanu Bogdan C. , Ruther Patrick , Schroeder Tim , Singer Wolf , Steinmetz Nicholas A. , Tiesinga Paul , Ulbert Istvan , Wang Shiwei , Welkenhuysen Marleen , Kampff Adam R. 
Published: March 2018

It is an uninformative truism to state that the brain operates at multiple spatial and temporal scales, each with each own set of emergent phenomena. More worthy of attention is the point that our current understanding of it cannot clearly indicate which of these phenomenological scales are the significant contributors to the brain’s function and primary output (i.e. behaviour). Apart from the sheer complexity of the problem, a major contributing factor to this state of affairs is the lack of instrumentation that can simultaneously address these multiple scales without causing function altering damages to the underlying tissue. One important facet of this problem is that standard neural recording devices normally require one output connection per electrode. This limits the number of electrodes that can fit along the thin shafts of implantable probes generating a limiting balance between density and spread. Sharing a single output connection between multiple electrodes relaxes this constraint and permits designs of ultra-high density probes.

Here we report the design and in-vivo validation of such a device, a complementary metal-oxide-semiconductor (CMOS) scanning probe with 1344 electrodes; the outcome of the European research project NeuroSeeker. We show that this design targets both local and global spatial scales by allowing the simultaneous recording of more than 1000 neurons spanning 7 functional regions with a single shaft. The neurons show similar recording longevity and signal to noise ratio to passive probes of comparable size and no adverse effects in awake or anesthetized animals. Addressing the data management of this device we also present novel visualization and monitoring methods. Using the probe with freely moving animals we show how accessing a number of cortical and subcortical brain regions offers a novel perspective on how the brain operates around salient behavioural events. Finally, we compare this probe with lower density, non CMOS designs (which have to adhere to the one electrode per output line rule). We show that an increase in density results in capturing neural firing patterns, undetectable by lower density devices, which correlate to self-similar structures inherent in complex naturalistic behaviour.

To help design electrode configurations for future, even higher density, CMOS probes, recordings from many different brain regions were obtained with an ultra-dense passive probe.