Investigating a new neuromodulation treatment for brain disorders using synchronized activation of multimodal pathways

Abstract

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.

Ultrasound Produces Extensive Brain Activation via a Cochlear Pathway

“…However, DBS and other invasive approaches have risks associated with surgery and involve high costs. TMS, tDCS, and other noninvasive approaches do not require surgery, but they often do not sufficiently achieve targeted activation (Brunoni et al, 2011;Deng et al, 2013;Markovitz et al, 2015a). More recently, ultrasound (US) stimulation has emerged as a potential approach that can address the trade-offs faced by modern neuromodulation technologies in that it can be applied noninvasively with the ability to activate or modulate targeted brain regions.…”

Ultrasound Produces Extensive Brain Activation via a Cochlear Pathway

“…For A1 activation, the US transducer was placed over A1 and coupled directly to the brain via agarose gel. The A1 probe was placed such that electrical stimulation resulted in ICC activation, based on previous studies (Markovitz et al, 2015a). US paradigms (single pulse or 10 Hz-1.5 kHz PRF, 0.1-10 msec PD, 25 kPa-2 MPa pressure, 500 msec PD; Table S1) were tested in A1.…”

“…However, DBS and other invasive 5 approaches have risks associated with surgery and involve high costs. TMS, tDCS and other noninvasive 6 approaches do not require surgery, but they do not sufficiently achieve targeted activation (Brunoni et al, 7 2011;Deng et al, 2013;Markovitz et al, 2015a). More recently, ultrasound (US) stimulation has emerged 8 as a potential approach that can address the trade-offs faced by modern neuromodulation technologies, in 9 that it can be applied noninvasively but with the ability to activate or modulate targeted brain regions.…”

High-Resolution Transcranial Electrical Simulation for Living Mice Based on Magneto-Acoustic Effect

“…However, given that electromagnetic fields obey Laplace's equation, it is impossible to create local maxima in the field intensity, no matter what the configuration of the source coils (Norton, 2003). TMS often does not achieve adequate spatial resolution on the millimeter scale, and it is helpless for specific activation of neuronal cells in a region less than 5 mm (Deng et al, 2013;Markovitz et al, 2015;Guo et al, 2018). In addition, because its magnetic focusing becomes poorer as the penetration depth increases, TMS is not suitable for the stimulation of deep brain tissues.…”