Descending projections from the cortex to subcortical structures are critical for auditory plasticity, including the ability for central neurons to adjust their frequency tuning to relevant and meaningful stimuli. We show that focal electrical stimulation of primary auditory cortex in guinea pigs produces excitatory responses in the central nucleus of the inferior colliculus (CNIC) with two tonotopic patterns: a narrow tuned pattern that is consistent with previous findings showing direct frequency-aligned projections; and a broad tuned pattern in which the auditory cortex can influence multiple frequency regions. Moreover, excitatory responses could be elicited in the caudomedial portion along the isofrequency laminae of the CNIC but not in the rostrolateral portion. This descending organization may underlie or contribute to the ability of the auditory cortex to induce changes in frequency tuning of subcortical neurons as shown extensively in previous studies.

Neuromodulation is an increasingly accepted treatment for neurological and psychiatric disorders but is limited by its invasiveness or its inability to target deep brain structures using noninvasive techniques. We propose a new concept called Multimodal Synchronization Therapy (mSync) for achieving targeted activation of the brain via noninvasive and precisely timed activation of auditory, visual, somatosensory, motor, cognitive, and limbic pathways. In this initial study in guinea pigs, we investigated mSync using combined activation of just the auditory and somatosensory pathways, which induced differential and timing dependent plasticity in neural firing within deep brain and cortical regions of the auditory system. Furthermore, by varying the location of somatosensory stimulation across the body, we increased or decreased spiking activity across different neurons. These encouraging results demonstrate the feasibility of systematically modulating the brain using mSync. Considering that hearing disorders such as tinnitus and hyperacusis have been linked to abnormal and hyperactive firing patterns within the auditory system, these results open up the possibility for using mSync to decrease this pathological activity by varying stimulation parameters. Incorporating multiple types of pathways beyond just auditory and somatosensory inputs and using other activation patterns may enable treatment of various brain disorders.

The brain is a densely interconnected network that relies on populations of neurons within and across multiple nuclei to code for features leading to perception and action. However, the neurophysiology field is still dominated by the characterization of individual neurons, rather than simultaneous recordings across multiple regions, without consistent spatial reconstruction of their locations for comparisons across studies. There are sophisticated histological and imaging techniques for performing brain reconstructions. However, what is needed is a method that is relatively easy and inexpensive to implement in a typical neurophysiology lab and provides consistent identification of electrode locations to make it widely used for pooling data across studies and research groups. This paper presents our initial development of such an approach for reconstructing electrode tracks and site locations within the guinea pig inferior colliculus (IC) to identify its functional organization for frequency coding relevant for a new auditory midbrain implant (AMI). Encouragingly, the spatial error associated with different individuals reconstructing electrode tracks for the same midbrain was less than 65 μm, corresponding to an error of ~1.5% relative to the entire IC structure (~4–5 mm diameter sphere). Furthermore, the reconstructed frequency laminae of the IC were consistently aligned across three sampled midbrains, demonstrating the ability to use our method to combine location data across animals. Hopefully, through further improvements in our reconstruction method, it can be used as a standard protocol across neurophysiology labs to characterize neural data not only within the IC but also within other brain regions to help bridge the gap between cellular activity and network function. Clinically, correlating function with location within and across multiple brain regions can guide optimal placement of electrodes for the growing field of neural prosthetics.

Objective The corticofugal system can alter coding along the ascending sensory pathway. Within the auditory system, electrical stimulation of the auditory cortex (AC) paired with a pure tone can cause egocentric shifts in the tuning of auditory neurons, making them more sensitive to the pure tone frequency. Since tinnitus has been linked with hyperactivity across auditory neurons, we sought to develop a new neuromodulation approach that could suppress a wide range of neurons rather than enhance specific frequency-tuned neurons. Approach We performed experiments in the guinea pig to assess the effects of cortical stimulation paired with broadband noise (PN-Stim) on ascending auditory activity within the central nucleus of the inferior colliculus (CNIC), a widely studied region for AC stimulation paradigms. Main results All eight stimulated AC regions induced extensive suppression of activity across the CNIC that was not possible with noise stimulation alone. This suppression built up over time and remained after the PN-Stim paradigm. Significance We propose that the corticofugal system is designed to decrease the brain’s input gain to irrelevant stimuli and PN-Stim is able to artificially amplify this effect to suppress neural firing across the auditory system. The PN-Stim concept may have potential for treating tinnitus and other neurological disorders.

-Current noninvasive treatments for tinnitus have shown mixed results. There have been encouraging developments in using invasive brain or vagal nerve stimulation to modulate neural populations driving the tinnitus percept. However, these invasive treatments can only be used in a small patient population with severe conditions. In this preliminary study, we present a new treatment option we call Multimodal Synchronization Therapy (MST), which attempts to achieve synchronized and localized brain activation without invasive neural stimulation. MST combines multiple sensory, motor, limbic, and cognitive inputs to elicit activation of multimodal neurons to potentially modulate specific neurons driving the tinnitus percept. We present preliminary data in a guinea pig model showing activation of somatosensory and auditory pathways to alter neural activity within the inferior colliculus, a multimodal integration region that has shown pathological changes in animals and patients with tinnitus. Electrical stimulation of different body locations induced excitatory responses in the inferior colliculus, eliciting responses in up to 41% of all recording sites for a given somatic site. Paired somatic and acoustic stimulation resulted in enhanced or suppressed acoustic-driven neural activity in the inferior colliculus that varied depending on stimulation and recording location. Similar modulation effects were observed in the auditory cortex, which may relate to changes in auditory perception. Further studies need to incorporate multiple multimodal pathways and must also confirm that MST can suppress the abnormal neural patterns that directly drive the tinnitus percept.

The topographic organization identified by this study provides further evidence for the presence of functional zones across an ICC lamina with locations consistent with those identified by previous studies. Clinically, these results suggest that co-activating different neural populations in the rostral-lateral ICC rather than the caudal-medial ICC using the AMI may improve or elicit different types of hearing capabilities.

http://www.clinicaltrials.gov; Unique identifier: CT01629160.

URL: http://www.clinicaltrials.gov . Unique identifier: NCT01629160.