Phase-Specific Microstimulation Differentially Modulates Beta Oscillations and Affects Behavior

Abstract

It is widely accepted that Beta-band oscillations play a role in sensorimotor behavior. To further explore this role, we developed a hybrid platform to combine neural operant conditioning and phase-specific intracortical microstimulation (ICMS). We trained monkeys, implanted with 96 electrode arrays in the motor cortex, to volitionally enhance local field potential (LFP) Beta-band (20-30 Hz) activity at selected sites using a brain-machine interface. We find that Beta oscillations of LFP and single-unit spiking activity increase dramatically with brain-machine interface training and that pre-movement Beta power is anti-correlated with task performance. We also find that phase-specific ICMS modulates the power and phase of oscillations, shifting local networks between oscillatory and non-oscillatory states. Furthermore, ICMS induces phase-dependent effects in animal reaction times and success rates. These findings contribute to unraveling the functional role of cortical oscillations and to the future development of clinical tools for ameliorating abnormal neuronal activities in brain disease.

Real-time suppression and amplification of frequency-specific neural activity using stimulation evoked oscillations

“…While we deliver stimulation based on the phase of neural oscillations, it should be noted that the rationale behind using phase feedback is different to that of methods that are intended to induce phase desynchronization across interconnected neurons [11,12], alter short-term plasticity [13], or modulate the balance between depolarization and hyperpolarization of neurons in the proximity of the stimulating electrodes [15]. The approach presented here differs in that it continuously overwrites the inputs of targeted neuronal populations to amplify or suppress oscillations via interference created with "new" oscillations evoked by electrical pulses.…”

“…A study with PD patients undergoing DBS implantation surgery suggested that open-loop, isochronal, low-frequency stimulation delivered dorsal to the subthalamic nucleus (STN) could alter the amplitude of low-frequency oscillations recorded in the STN, whenever consecutive stimulation pulses landed at specific phase angles of these oscillations [14]. A recent study with nonhuman primates has also shown that brief stimulation bursts of intra-cortical microstimulation aligned with the peaks or troughs of neural oscillations in the motor cortex can result in changes in the amplitude of LFP oscillations near the stimulating electrodes, neuronal firing, and motor performance when delivered during a neuro-feedback task [15]. While phase-locked stimulation holds promise for modulating oscillatory activity within a neuronal ensemble, an approach to actively and predictably suppress or amplify neural oscillations in the circuitlevel by using implantable electrodes remains to be developed.…”

Phase-dependent closed-loop modulation of neural oscillations in vivo

“…Thus, between this study and that of Sanabria and colleagues there is evidence that phase dependent stimulation can effectively modulate beta oscillations across a wide range of spatial, spectral and temporal parameters that encompass those described in patients. Notably, two separate studies using healthy primates have also demonstrated that phase-dependent stimulation of cortical beta oscillations can modulate plasticity (Zanos et al, 2018) and behavioural performance (Peles et al, 2020), demonstrating the utility of such neuromodulation.…”

“…While implementation of phase-loop stimulation has clear translational utility, there are even wider implications and applications of this approach for fundamental science (Siegle and Wilson, 2014, Nicholson et al, 2018, Zanos et al, 2018, Kanta et al, 2019, Peles et al, 2020. The long running debate as to how or whether neuronal oscillations contribute to computation has been hampered by the lack of tools to target oscillatory processes over other parameters of neural activity.…”

“…Maximising the effects of such phase-dependent stimulation necessitates highly accurate closed-loop stimulation, whereby the instantaneous phase of the target oscillation is tracked online and used to drive the stimulus train. Several studies have provided proof-of-principle evidence that such an approach can be used to modulate the amplitude of ongoing neuronal oscillations (Nicholson et al, 2018, Kanta et al, 2019, Peles et al, 2020.…”