Electrical Stimulation publications

Facial paralysis can be a devastating condition, causing disfiguring facial droop, slurred speech, eye dryness, scarring and blindness. This study investigated the utility of closed-loop functional electric stimulation (FES) for reanimating paralyzed facial muscles in a quantitative rodent model. The right buccal and marginal mandibular branches of the rat facial nerve were transected for selective, unilateral paralysis of whisker muscles. Microwire electrodes were implanted bilaterally into the facial musculature for FES and electromyographic (EMG) recording. With the rats awake and head-fixed, whisker trajectories were tracked bilaterally with optical micrometers. First, the relationship between EMG and volitional whisker movement was quantified on the intact side of the face. Second, the effect of FES on whisker trajectories was quantified on the paralyzed side. Third, closed-loop experiments were performed in which the EMG signal on the intact side triggered FES on the paralyzed side to restore symmetric whisking. The results demonstrate a novel in vivo platform for developing control strategies for neuromuscular facial prostheses.

The pulvinar complex is interconnected extensively with brain regions involved in spatial processing and eye movement control. Recent inactivation studies have shown that the dorsal pulvinar (dPul) plays a role in saccade target selection; however, it remains unknown whether it exerts effects on visual processing or at planning/execution stages. We used electrical microstimulation of the dPul while monkeys performed saccade tasks toward instructed and freely chosen targets. Timing of stimulation was varied, starting before, at, or after onset of target(s). Stimulation affected saccade properties and target selection in a time-dependent manner. Stimulation starting before but overlapping with target onset shortened saccadic reaction times (RTs) for ipsiversive (to the stimulation site) target locations, whereas stimulation starting at and after target onset caused systematic delays for both ipsiversive and contraversive locations. Similarly, stimulation starting before the onset of bilateral targets increased ipsiversive target choices, whereas stimulation after target onset increased contraversive choices. Properties of dPul neurons and stimulation effects were consistent with an overall contraversive drive, with varying outcomes contingent upon behavioral demands. RT and choice effects were largely congruent in the visually-guided task, but stimulation during memory-guided saccades, while influencing RTs and errors, did not affect choice behavior. Together, these results show that the dPul plays a primary role in action planning as opposed to visual processing, that it exerts its strongest influence on spatial choices when decision and action are temporally close, and that this choice effect can be dissociated from motor effects on saccade initiation and execution. SIGNIFICANCE STATEMENT Despite a recent surge of interest, the core function of the pulvinar, the largest thalamic complex in primates, remains elusive. This understanding is crucial given the central role of the pulvinar in current theories of integrative brain functions supporting cognition and goal-directed behaviors, but electrophysiological and causal interference studies of dorsal pulvinar (dPul) are rare. Building on our previous studies that pharmacologically suppressed dPul activity for several hours, here we used transient electrical microstimulation at different periods while monkeys performed instructed and choice eye movement tasks, to determine time-specific contributions of pulvinar to saccade generation and decision making. We show that stimulation effects depend on timing and behavioral state and that effects on choices can be dissociated from motor effects.

We report on the superior electrochemical properties, in-vivo performance and long term stability under electrical stimulation of a new electrode material fabricated from lithographically patterned glassy carbon. For a direct comparison with conventional metal electrodes, similar ultra-flexible, micro-electrocorticography (μ-ECoG) arrays with platinum (Pt) or glassy carbon (GC) electrodes were manufactured. The GC microelectrodes have more than 70% wider electrochemical window and 70% higher CTC (charge transfer capacity) than Pt microelectrodes of similar geometry. Moreover, we demonstrate that the GC microelectrodes can withstand at least 5 million pulses at 0.45 mC/cm 2 charge density with less than 7.5% impedance change, while the Pt microelectrodes delaminated after 1 million pulses. Additionally, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) was selectively electrodeposited on both sets of devices to specifically reduce their impedances for smaller diameters (<60 μm). We observed that PEDOT-PSS adhered significantly better to GC than Pt, and allowed drastic reduction of electrode size while maintaining same amount of delivered current. The electrode arrays biocompatibility was demonstrated through in-vitro cell viability experiments, while acute in vivo characterization was performed in rats and showed that GC microelectrode arrays recorded somatosensory evoked potentials (SEP) with an almost twice SNR (signal-to-noise ratio) when compared to the Pt ones.

Neural sensing and stimulation have been the backbone of neuroscience research, brain-machine interfaces and clinical neuromodulation therapies for decades. To-date, most of the neural stimulation systems have relied on sharp metal microelectrodes with poor electrochemical properties that induce extensive damage to the tissue and significantly degrade the long-term stability of implantable systems. Here, we demonstrate a flexible cortical microelectrode array based on porous graphene, which is capable of efficient electrophysiological sensing and stimulation from the brain surface, without penetrating into the tissue. Porous graphene electrodes show superior impedance and charge injection characteristics making them ideal for high efficiency cortical sensing and stimulation. They exhibit no physical delamination or degradation even after 1 million biphasic stimulation cycles, confirming high endurance. In in vivo experiments with rodents, same array is used to sense brain activity patterns with high spatio-temporal resolution and to control leg muscles with high-precision electrical stimulation from the cortical surface. Flexible porous graphene array offers a minimally invasive but high efficiency neuromodulation scheme with potential applications in cortical mapping, brain-computer interfaces, treatment of neurological disorders, where high resolution and simultaneous recording and stimulation of neural activity are crucial.

Auditory information relayed by auditory nerve fibers and somatosensory information relayed by granule cell parallel fibers converge on the fusiform cells (FCs) of the dorsal cochlear nucleus, the first brain station of the auditory pathway. In vitro, parallel fiber synapses on FCs exhibit spike-timing-dependent plasticity with Hebbian learning rules, partially mediated by the NMDA receptor (NMDAr). Well-timed bimodal auditory-somatosensory stimulation, in vivo equivalent of spike-timing-dependent plasticity, can induce stimulus-timing-dependent plasticity (StTDP) of the FCs spontaneous and tone-evoked firing rates. In healthy guinea pigs, the resulting distribution of StTDP learning rules across a FC neural population is dominated by a Hebbian profile while anti-Hebbian, suppressive and enhancing LRs are less frequent. In this study, we investigate in vivo, the NMDAr contribution to FC baseline activity and long term plasticity. We find that blocking the NMDAr decreases the synchronization of FC- spontaneous activity and mediates differential modulation of FC rate-level functions such that low, and high threshold units are more likely to increase, and decrease, respectively, their maximum amplitudes. Three significant alterations in mean learning-rule profiles were identified: transitions from an initial Hebbian profile towards (1) an anti-Hebbian; (2) a suppressive profile; and (3) transitions from an anti-Hebbian to a Hebbian profile. FC units preserving their learning rules showed instead, NMDAr-dependent plasticity to unimodal acoustic stimulation, with persistent depression of tone-evoked responses changing to persistent enhancement following the NMDAr antagonist. These results reveal a crucial role of the NMDAr in mediating FC baseline activity and long-term plasticity which have important implications for signal processing and auditory pathologies related to maladaptive plasticity of dorsal cochlear nucleus circuitry.

The cochlear nucleus (CN) is the first site of multisensory integration in the ascending auditory pathway. The principal output neurons of the dorsal cochlear nucleus (DCN), fusiform cells, receive somatosensory information relayed by the CN granule cells from the trigeminal and dorsal column pathways. Integration of somatosensory and auditory inputs results in long-term enhancement or suppression in a stimulus-timing-dependent manner. Here, we demonstrate that stimulus-timing-dependent plasticity (STDP) can be induced in DCN fusiform cells using paired auditory and transcutaneous electrical stimulation of the face and neck to activate trigeminal and dorsal column pathways to the CN, respectively. Long-lasting changes in fusiform cell firing rates persisted for up to 2 h after this bimodal stimulation, and followed Hebbian or anti-Hebbian rules, depending on tone duration, but not somatosensory stimulation location: 50 ms paired tones evoked predominantly Hebbian, while 10 ms paired tones evoked predominantly anti-Hebbian plasticity. The tone-duration-dependent STDP was strongly correlated with first inter-spike intervals, implicating intrinsic cellular properties as determinants of STDP. This study demonstrates that transcutaneous stimulation with precise auditory-somatosensory timing parameters can non-invasively induce fusiform cell long-term modulation, which could be harnessed in the future to moderate tinnitus-related hyperactivity in DCN.

The efficacy of spinal cord stimulators is dependent on the ability of the device to functionally activate targeted structures within the spinal cord, while avoiding activation of near-by non-targeted structures. In theory, these objectives can best be achieved by delivering electrical stimuli directly to the surface of the spinal cord. The current experiments were performed to study the influence of different stimulating electrode positions on patterns of spinal cord electrophysiological activation. A custom-designed spinal cord neurostimulator was used to investigate the effects of lead position and stimulus amplitude on cortical electrophysiological responses to spinal cord stimulation. Brain recordings were obtained from subdural grids placed in four adult sheep. We systematically varied the position of the stimulating lead relative to the spinal cord and the voltage delivered by the device at each position, and then examined how these variables influenced cortical responses. A clear relationship was observed between voltage and electrode position, and the magnitude of high gamma-band oscillations. Direct stimulation of the dorsal column contralateral to the grid required the lowest voltage to evoke brain responses to spinal cord stimulation. Given the lower voltage thresholds associated with direct stimulation of the dorsal column, and its possible impact on the therapeutic window, this intradural modality may have particular clinical advantages over standard epidural techniques now in routine use.