A future for neuronal oscillation research

Abstract

Neuronal oscillations represent the most obvious feature of electrical activity in the brain. They are linked in general with global brain state (awake, asleep, etc.) and specifically with organisation of neuronal outputs during sensory perception and cognitive processing. Oscillations can be generated by individual neurons on the basis of interaction between inputs and intrinsic conductances but are far more commonly seen at the local network level in populations of interconnected neurons with diverse arrays of functional properties. It is at this level that the brain's rich and diverse library of oscillatory time constants serve to temporally organise large-scale neural activity patterns. The discipline is relatively mature at the microscopic (cell, local network) level - although novel discoveries are still commonplace - but requires a far greater understanding of mesoscopic and macroscopic brain dynamics than we currently hold. Without this, extrapolation from the temporal properties of neurons and their communication strategies up to whole brain function will remain largely theoretical. However, recent advances in large-scale neuronal population recordings and more direct, higher fidelity, non-invasive measurement of whole brain function suggest much progress is just around the corner.

Keywords: Alpha; beta; cognition; coherence; cross-frequency coupling; delta; electroencephalogram; filtering; neuron; population; resonance; synapse; theta.

Figure 1.

Recording methods used to understand neuronal oscillation mechanism and function. (a) Past – EEG dominated the early history of oscillation research. Top panel reproduces part of one of Hans Berger’s original report figures. Middle panel shows the first demonstration of a link between the output of neurons, controlled by oscillations, and sensory input as recorded in vivo from hippocampus of behaving rats (O’Keefe and Dostrovsky, 1971). Bottom panel illustrates intracellular recordings from rat hippocampal neurons during an experimental model of gamma rhythms (authors’ own data from 1998). (b) Present – Upper panel: EEG technology is very much still in use but for research purposes has been surpassed by MEG combined with beamforming routines to construct many multiples of concurrent recording sites non-invasively in human brain. Panel shows authors’ own data illustrating the causal influence of thalamus on neocortical delta rhythms during sleep. Middle panel shows data illustrating the rich diversity of neuronal outputs in vivo in populations stimulated optogenetically (Okun et al., 2015). Bottom panel shows data from the current state of the art multi-patch technology allowing concurrent recordings from up to eight identified neurons used to quantify both multiple neuronal outputs and, more importantly, the network origins of synaptic inputs that cause them (Böhm et al., 2015). (c) Future – the largest technical problem facing oscillation research is the inability to record from many multiple neurons concurrently and non-invasively in humans. While individual regions can be functionally identified with ease (top panel), we still cannot interrogate the local networks, and their global interactions in this manner. In experimental preparations, optical recording shows the best promise so far. However, they require direct optical access to the cortex and genetic manipulation of neurons to allow a readout of changes in intracellular calcium levels (GCaMP6 as illustrated in the middle panel (Chen et al., 2013)). What is required is a near-real time, massively parallel, direct measure of neuronal inputs and outputs in humans. Where the technology to do this will come from is unknown, but there are a number of promising avenues (see text).