Sensing local field potentials with a directional and scalable depth electrode array.

Objective. A variety of electrophysiology tools are available to the neurosurgeon for diagnosis, functional therapy, and neural prosthetics. However, no tool can currently address these three critical needs: (a) access to all cortical regions in a minimally invasive manner; (b) recordings with microscale, mesoscale, and macroscale resolutions simultaneously; and (c) access to spatially distant multiple brain regions that constitute distributed cognitive networks.Approach.We modeled, designed, and demonstrated a novel device for recording local field potentials (LFPs) with the form factor of a stereo-electroencephalographic electrode and combined with radially distributed microelectrodes.Main results. Electro-quasistatic models demonstrate that the lead body amplifies and shields LFP sources based on direction, enablingdirectional sensitivity andscalability, referred to as thedirectional andscalable (DISC) array.In vivo,DISC demonstrated significantly improved signal-to-noise ratio, directional sensitivity, and decoding accuracy from rat barrel cortex recordings during whisker stimulation. Critical for future translation, DISC demonstrated a higher signal to noise ratio (SNR) than virtual ring electrodes and a noise floor approaching that of large ring electrodes in an unshielded environment after common average referencing. DISC also revealed independent, stereoscopic current source density measures whose direction was verified after histology.Significance. Directional sensitivity of LFPs may significantly improve brain-computer interfaces and many diagnostic procedures, including epilepsy foci detection and deep brain targeting.

A gravity-based three-dimensional compass in the mouse brain.

Gravity sensing provides a robust verticality signal for three-dimensional navigation. Head direction cells in the mammalian limbic system implement an allocentric neuronal compass. Here we show that head-direction cells in the rodent thalamus, retrosplenial cortex and cingulum fiber bundle are tuned to conjunctive combinations of azimuth and tilt, i.e. pitch or roll. Pitch and roll orientation tuning is anchored to gravity and independent of visual landmarks. When the head tilts, azimuth tuning is affixed to the head-horizontal plane, but also uses gravity to remain anchored to the allocentric bearings in the earth-horizontal plane. Collectively, these results demonstrate that a three-dimensional, gravity-based, neural compass is likely a ubiquitous property of mammalian species, including ground-dwelling animals.

Response to "Fallacies of Mice Experiments".

In a recent Editorial, De Schutter commented on our recent study on the roles of a cortico-cerebellar loop in motor planning in mice (De Schutter 2019, Neuroinformatics, 17, 181-183, Gao et al. 2018, Nature, 563, 113-116). Two issues were raised. First, De Schutter questions the involvement of the fastigial nucleus in motor planning, rather than the dentate nucleus, given previous anatomical studies in non-human primates. Second, De Schutter suggests that our study design did not delineate different components of the behavior and the fastigial nucleus might play roles in sensory discrimination rather than motor planning. These comments are based on anatomical studies in other species and homology-based arguments and ignore key anatomical data and neurophysiological experiments from our study. Here we outline our interpretation of existing data and point out gaps in knowledge where future studies are needed.

A cortico-cerebellar loop for motor planning.

Persistent and ramping neural activity in the frontal cortex anticipates specific movements1-6. Preparatory activity is distributed across several brain regions7,8, but it is unclear which brain areas are involved and how this activity is mediated by multi-regional interactions. The cerebellum is thought to be primarily involved in the short-timescale control of movement9-12; however, roles for this structure in cognitive processes have also been proposed13-16. In humans, cerebellar damage can cause defects in planning and working memory13. Here we show that persistent representation of information in the frontal cortex during motor planning is dependent on the cerebellum. Mice performed a sensory discrimination task in which they used short-term memory to plan a future directional movement. A transient perturbation in the medial deep cerebellar nucleus (fastigial nucleus) disrupted subsequent correct responses without hampering movement execution. Preparatory activity was observed in both the frontal cortex and the cerebellar nuclei, seconds before the onset of movement. The silencing of frontal cortex activity abolished preparatory activity in the cerebellar nuclei, and fastigial activity was necessary to maintain cortical preparatory activity. Fastigial output selectively targeted the behaviourally relevant part of the frontal cortex through the thalamus, thus closing a cortico-cerebellar loop. Our results support the view that persistent neural dynamics during motor planning is maintained by neural circuits that span multiple brain regions17, and that cerebellar computations extend beyond online motor control13-15,18.