Volitional control of individual neurons in the human brain.

Brain-machine interfaces allow neuroscientists to causally link specific neural activity patterns to a particular behaviour. Thus, in addition to their current clinical applications, brain-machine interfaces can also be used as a tool to investigate neural mechanisms of learning and plasticity in the brain. Decades of research using such brain-machine interfaces have shown that animals (non-human primates and rodents) can be operantly conditioned to self-regulate neural activity in various motor-related structures of the brain. Here, we ask whether the human brain, a complex interconnected structure of over 80 billion neurons, can learn to control itself at the most elemental scale-a single neuron. We used the unique opportunity to record single units in 11 individuals with epilepsy to explore whether the firing rate of a single (direct) neuron in limbic and other memory-related brain structures can be brought under volitional control. To do this, we developed a visual neurofeedback task in which participants were trained to move a block on a screen by modulating the activity of an arbitrarily selected neuron from their brain. Remarkably, participants were able to volitionally modulate the firing rate of the direct neuron in these previously uninvestigated structures. We found that a subset of participants (learners), were able to improve their performance within a single training session. Successful learning was characterized by (i) highly specific modulation of the direct neuron (demonstrated by significantly increased firing rates and burst frequency); (ii) a simultaneous decorrelation of the activity of the direct neuron from the neighbouring neurons; and (iii) robust phase-locking of the direct neuron to local alpha/beta-frequency oscillations, which may provide some insights in to the potential neural mechanisms that facilitate this type of learning. Volitional control of neuronal activity in mnemonic structures may provide new ways of probing the function and plasticity of human memory without exogenous stimulation. Furthermore, self-regulation of neural activity in these brain regions may provide an avenue for the development of novel neuroprosthetics for the treatment of neurological conditions that are commonly associated with pathological activity in these brain structures, such as medically refractory epilepsy.

Music in epilepsy: Predicting the effects of the unpredictable.

Epilepsy is the most common serious neurological disorder in the world. Despite medical and surgical treatment, many individuals continue to have seizures, suggesting adjunctive management strategies are required. Promising effects of daily listening to Mozart K.448 on reducing seizure frequency in individuals with epilepsy have been demonstrated. In our recent randomized control study, we reported the positive effect of daily listening to Mozart K.448 on reducing seizures compared to daily listening to a control piece with an identical power spectrum to the Mozart piece yet devoid of rhythmic structure. Despite the promising effect of listening to Mozart K.448 on reducing seizure in individuals with epilepsy, the mechanism(s) underlying such an effect is largely unknown. In this paper, we specifically review how auditory stimulation alters brain dynamics, in addition to computational approaches to define the structural features of classical music, to then propose a plausible mechanism for the underlying anti-convulsant effects of listening to Mozart K.448. We review the evidence demonstrating that some Mozart pieces in addition to compositions from other composers such as Joplin contain less predictable rhythmic structure in comparison with other composers such as Beethoven. We propose through both entrainment and 1/f resonance mechanisms that listening to musical pieces containing the least predictable rhythmic structure, might reduce the self similarity of brain activity which in turn modulates low frequency power, situating the brain in a more "noise like" state and away from brain dynamics that can lead to seizures.

Neurostimulation stabilizes spiking neural networks by disrupting seizure-like oscillatory transitions.

An improved understanding of the mechanisms underlying neuromodulatory approaches to mitigate seizure onset is needed to identify clinical targets for the treatment of epilepsy. Using a Wilson-Cowan-motivated network of inhibitory and excitatory populations, we examined the role played by intrinsic and extrinsic stimuli on the network's predisposition to sudden transitions into oscillatory dynamics, similar to the transition to the seizure state. Our joint computational and mathematical analyses revealed that such stimuli, be they noisy or periodic in nature, exert a stabilizing influence on network responses, disrupting the development of such oscillations. Based on a combination of numerical simulations and mean-field analyses, our results suggest that high variance and/or high frequency stimulation waveforms can prevent multi-stability, a mathematical harbinger of sudden changes in network dynamics. By tuning the neurons' responses to input, stimuli stabilize network dynamics away from these transitions. Furthermore, our research shows that such stabilization of neural activity occurs through a selective recruitment of inhibitory cells, providing a theoretical undergird for the known key role these cells play in both the healthy and diseased brain. Taken together, these findings provide new vistas on neuromodulatory approaches to stabilize neural microcircuit activity.

Arbitrary-Waveform Electro-Optical Intracranial Neurostimulator With Load-Adaptive High-Voltage Compliance.

A hybrid 16-channel current-mode and the 8-channel optical implantable neurostimulating system is presented. The system generates arbitrary-waveform charge-balanced current-mode electrical pulses with an amplitude ranging from 50 [Formula: see text] to 10 mA. An impedance monitoring feedback loop is employed to automatically adjust the supply voltage, yielding a load-optimized power dissipation. The 8-channel optical stimulator drives an array of LEDs, each with a maximum of 25 mA current amplitude, and reuses the arbitrary-waveform generation function of the electrical stimulator. The LEDs are assembled within a custom-made 4×4 ECoG grid electrode array, enabling precise optical stimulation of neurons with a 300 [Formula: see text] pitch between the LEDs and simultaneous monitoring of the neural response by the ECoG electrode, at different distances of the stimulation site. The hybrid stimulation system is implemented on a mini-PCB, and receives power and stimulation commands inductively through a second board and a coil stacked on top of it. The entire system is sized at 3×2 . 5×1 cm3 and weighs 7 grams. The system efficacy for electrical and optical stimulation is validated in-vivo using separate chronic and acute experiments.