Inducing Neural Plasticity and Modulation Using Multisensory Stimulation: Techniques for Sensory Disorder Treatment

Abstract

In this dissertation, we characterized the modulatory and plasticity effects of paired multisensory stimulation on neural firing in sensory systems across the brain. In the auditory system, we discovered that electrical somatosensory stimulation can either suppress or facilitate neural firing in the inferior colliculus (IC) and primary auditory cortex (A1) depending stimulation location. We also tested plasticity effects in A1 in response to paired somatosensory and acoustic stimulation with different inter-stimulus delays in anesthetized guinea pigs, and found that plasticity induced by paired acoustic and right mastoid stimulation was consistently suppressive regardless of delay, but paired acoustic and pinna stimulation was timing-dependent, where one inter-stimulus delay was consistently suppressive while other delays induced random changes. These experiments were repeated in awake animals with paired acoustic and pinna stimulation, and two animal groups of different stress levels were used to assess stress effects on plasticity. We found that in low-stress animals, the same inter-stimulus delay was consistently suppressive and a neighboring delay was consistently facilitative across all animals, which matches previous invasive spike-timing dependent plasticity studies (anesthesia may have affected these trends). Meanwhile, high-stress animal results were not consistent with expected time dependence and exhibited no trends across inter-stimulus delays, indicating that stress can have adverse effects on neuromodulation plasticity outcomes. In all other primary sensory cortices, we found that differential effects can be induced with paired sensory stimulation such that the location, amount, type, and timing of plasticity can be controlled by strategically choosing sensory stimulation parameters for modulation of each sensory cortex. We also investigated the ability to target subpopulations of neurons within a brain region and found that by stimulating at levels near activation thresholds, specific subpopulations of IC neurons can be targeted by varying somatosensory stimulation location. Furthermore, acoustic stimulation can excite or modulate specific areas of somatosensory cortex, and we mapped the guinea pig homunculus to characterize this. Overall, these findings illustrate the immense interconnectivity between sensory systems, and multisensory stimulation may provide a noninvasive neuromodulation approach for inducing controlled plasticity to disrupt pathogenic neural activity in neural sensory disorders, such as tinnitus and pain.