Visuotactile synchrony of stimulation-induced sensation and natural somatosensation.

OBJECTIVE: Previous studies suggest that somatosensory feedback has the potential to improve the functional performance of prostheses, reduce phantom pain, and enhance embodiment of sensory-enabled prosthetic devices. To maximize such benefits for amputees, the temporal properties of the sensory feedback must resemble those of natural somatosensation in an intact limb. APPROACH: To better understand temporal perception of artificial sensation, we characterized the perception of visuotactile synchrony for tactile perception restored via peripheral nerve stimulation. We electrically activated nerves in the residual limbs of two trans-tibial amputees and two trans-radial amputees via non-penetrating nerve cuff electrodes, which elicited sensations referred to the missing limbs. MAIN RESULTS: Our findings suggest that with respect to vision, stimulation-induced sensation has a point of subjective simultaneity (PSS; processing time) and just noticeable difference (JND; temporal sensitivity) that are similar to natural touch. The JND was not significantly different between the participants with upper- and lower-limb amputations. However, the PSS indicated that sensations evoked in the missing leg must occur significantly earlier than those in the hand to be perceived as maximally synchronous with vision. Furthermore, we examined visuotactile synchrony in the context of a functional task during which stimulation was triggered by pressure applied to the prosthesis. Stimulation-induced sensation could be delayed up to 111 ± 62 ms without the delay being reliably detected. SIGNIFICANCE: The quantitative temporal properties of stimulation-induced perception were previously unknown and will contribute to design specifications for future sensory neuroprostheses.

Amyloid beta modulation of neuronal network activity in vitro.

In vitro assays offer a means of screening potential therapeutics and accelerating the drug development process. Here, we utilized neuronal cultures on planar microelectrode arrays (MEA) as a functional assay to assess the neurotoxicity of amyloid-ß 1-42 (Aß42), a biomolecule implicated in the Alzheimer׳s disease (AD). In this approach, neurons harvested from embryonic mice were seeded on the substrate-integrated microelectrode arrays. The cultured neurons form a spontaneously active network, and the spiking activity as a functional endpoint could be detected via the MEA. Aß42 oligomer, but not monomer, significantly reduced network spike rate. In addition, we demonstrated that the ionotropic glutamate receptors, NMDA and AMPA/kainate, play a role in the effects of Aß42 on neuronal activity in vitro. To examine the utility of the MEA-based assay for AD drug discovery, we tested two model therapeutics for AD, methylene blue (MB) and memantine. Our results show an almost full recovery in the activity within 24h after administration of Aß42 in the cultures pre-treated with either MB or memantine. Our findings suggest that cultured neuronal networks may be a useful platform in screening potential therapeutics for Aß induced changes in neurological function.

Differential responses to ω-agatoxin IVA in murine frontal cortex and spinal cord derived neuronal networks.

ω-Agatoxin-IVA is a well known P/Q-type Ca(2+) channel blocker and has been shown to affect presynaptic Ca(2+) currents as well postsynaptic potentials. P/Q-type voltage gated Ca(2+) channels play a vital role in presynaptic neurotransmitter release and thus play a role in action potential generation. Monitoring spontaneous activity of neuronal networks on microelectrode arrays (MEAs) provides an important tool for examining this neurotoxin. Changes in extracellular action potentials are readily observed and are dependent on synaptic function. Given the efficacy of murine frontal cortex and spinal cord networks to detect neuroactive substances, we investigated the effects of ω-agatoxin on spontaneous action potential firing within these networks. We found that networks derived from spinal cord are more sensitive to the toxin than those from frontal cortex; a concentration of only 10nM produced statistically significant effects on activity from spinal cord networks whereas 50 nM was required to alter activity in frontal cortex networks. Furthermore, the effects of the toxin on frontal cortex are more complex as unit specific responses were observed. These manifested as either a decrease or increase in action potential firing rate which could be statistically separated as unique clusters. Administration of bicuculline, a GABAA inhibitor, isolated a single response to ω-agatoxin, which was characterized by a reduction in network activity. These data support the notion that the two clusters detected with ω-agatoxin exposure represent differential responses from excitatory and inhibitory neuronal populations.