Translingual Neurostimulation (TLNS): A Novel Approach to Neurorehabilitation

Research Article

Phys Med Rehabil Int. 2017; 4(2): 1117.

Translingual Neurostimulation (TLNS): A Novel Approach to Neurorehabilitation

Danilov Y* and Paltin D

Department of Kinesiology, University of Wisconsin, USA

*Corresponding author: Yuri Danilov, Department of Kinesiology, University of Wisconsin, USA

Received: May 23, 2017; Accepted: June 27, 2017; Published: July 04, 2017

Abstract

CN-NINM technology represents a synthesis of a new non-invasive brain stimulation technique with applications in physical medicine, cognitive, and affective neurosciences. Our new stimulation method appears promising for the treatment of a full spectrum of movement disorders, and for both attention and memory dysfunction associated with traumatic brain injury. The integrated CN-NINM therapy proposed here aims to restore function beyond traditionally expected limits by employing both newly developed therapeutic mechanisms for progressive physical and cognitive training - while simultaneously applying brain stimulation through a portable neurostimulation device PoNS™. Based on our previous research and recent pilot data, we believe a rigorous in-clinic CN-NINM training program, followed by regular at-home exercises that will also be performed with CN-NINM, will simultaneously enhance, accelerate, and extend recovery from multiple impairments (e.g. movement, vision, speech, memory, attention, and mood), based on divergent, but deeply interconnected neurophysiological mechanisms of neuroplasticity.

Keywords: Neurorehabilitation; Neuromodulation; Translingual Neurostimulation; PoNS Device; Targeted Therapy; Cranial nerve; Neuroplasticity

Abbreviations

TLNS: Translingual Neurostimulation; CN-NINM: Cranial- Nerve Non-Invasive Neurostimulation; TNS: Trigeminal Nerve Stimulation; VNS: Vagal Nerve Stimulation

Introduction

The goal of the current paper is to introduce our approach to neurorehabilitation called Cranial Nerve Non-Invasive Neuromodulation (CN-NINM) technology. CN-NINM is a method of intervention that combines Translingual Neurostimulation (TLNS), the Portable neurostimulation Stimulator (PoNS™) device, and targeted training designed for movement control rehabilitation.

The basic principles of CN-NINM technology, as a platform technology, build foundation for the development of future directions of neurorehabilitation such as a headache, tinnitus, sleep, depression, etc., using neurostimulation to access brain networks through the cranial nerves, such as those found in the tongue. It is noteworthy, that the principles and corresponding treatment regimens, based on CN-NINM technology, were already successfully implemented for neurorehabilitation of other neurological conditions such as balance, gait, eye movement control, speech and cognitive functions [1,2]. Therefore, CN-NINM technology should be considered as a practical realization of several theoretical concepts, based on recent scientific discoveries in the field of neuroscience.

First, we would like to consider abnormal neurological conditions, in the view of modern network science, that result from disruption in similar brain networks. The current understanding of neural-network organization can describe the variety of structural and functional network changes in many neurological and psychiatric diseases, especially in dementia, epilepsy and schizophrenia, but also in traumatic brain injury (TBI), Parkinson’s disease, multiple sclerosis (MS), cerebrovascular disease, coma and many other conditions categorized as neuronal network disorders [3-5].

The complexly distributed neuronal network, with multiple cortical and subcortical components, is the physical substrate for any sensory, motor and sensory-motor integrative system, providing, in turn, normal physiological or behavioural function – vision, hearing, postural and eye movement control and multiple others. Damage to or malfunction of any part of said functional network leads to dysfunction of the whole sensory-motor system (spatial and/or temporal abnormalities) that frequently manifests as clinical symptoms.

Second, the situation with the rehabilitation of many neurological symptoms is very similar. Neurological disorders, like TBI, stroke, neurodegenerative disorders or drug overdose (chemical trauma), can affect many distributed networks on many different levels in many different locations. So far, it is almost impossible to identify the exact place and extent of such damages or the extent of malfunctioning tissues, as a result of abnormal connectivity with damaged areas. The abnormalities in the functional relationship between areas and structures, and the abnormalities in the spatio-temporal organization of separate neurons and clusters of neurons are still beyond our reach for assessment and evaluation. As a result of such uncertainty, the therapeutic and rehabilitation resources are significantly limited. For example, there are no effective rehabilitation programs for chronic stage patients after stroke and TBI; the majority of MS symptoms are considered non-recoverable; and there is no effective treatment for tinnitus. Physical therapy can help these conditions to some extent, but not dramatically.

TLNS technology was originally designed to modulate complex networks for the purpose of neurorehabilitation. We started from the balance sensory-motor integration network, specifically from postural control rehabilitation after peripheral vestibular damages [6- 8]. Later we extended our approach to the proprioceptive component of balance (multiple sclerosis, amputee), to gate control rehabilitation (Parkinson’s disease, MS, TBI, stroke, cerebral palsy), and eye movement control. The combination of neurostimulation (using the PoNSTM device) and targeted therapy (a set of challenging exercises, explicitly targeting the affected network) became the mainframe of TLNS therapy that is applicable to rehabilitation of many neurological disorders, so far mainly considered untreatable [1,2,9].

Neurostimulation

Although brain stimulation is well known since ancient Greek and Roman times, from Galen and Scribonius Largus, who used electric eels to treat headaches and various other disorders, the current “explosion” of new neurostimulation methods, devices, and applications are hard to even count. Currently, more than a dozen forms of brain stimulation are undergoing development and evaluation as interventions for neurological and psychiatric disorders [10].

Neurostimulation and neuromodulation techniques are unique forms of treatment distinctly different from pharmacology, psychotherapy, or physical therapy. While these terms are often used interchangeably, for the purpose of this essay and the benefit of this ever-expanding and dynamic field, we propose an important differentiation: Neurostimulation refers to the physical action of stimulating the nervous system, whereas Neuromodulation is the product or result of said stimulation.

Types of neurostimulation

Specificity and applicability of different neurostimulation methods depend on several key factors: the anatomical location of the stimulation target, physical properties, and the spatio-temporal parameters of stimulation.

The human nervous system is a complex set of interrelated and interacting sub-systems with hierarchical modularity. The modules correspond to major functional systems, such as motor, sensory and association networks. The sub-systems are characterized and called both by their anatomic positions and by their functional specificity.

At the highest level, the nervous system is divided into central and peripheral nervous systems. The central nervous system (CNS) is comprised of the brain and spinal cord and the peripheral nervous system (PNS) incorporates all the remaining neural structures found outside the CNS. The PNS is further divided functionally into the somatic (voluntary) and autonomic (involuntary) nervous systems. The PNS can also be described structurally as being comprised of afferent (sensory) nerves, which carry information toward the CNS, and efferent (motor) nerves, which carry commands away from the CNS [11].

The PNS also consist of spinal nerves and cranial nerves. Although twelve pairs of cranial nerves emerge directly from the brain (anatomically they are part of CNS), and ten pairs of them arise from the brainstem, they are formally considered as a part of PNS.

Correspondingly, all neurostimulation systems can be distinct at the site of application: cranial, spinal cord, spinal ganglion or sciatic nerve neurostimulation systems. It is vital to note that the stimulation of specific brain regions produces equally specific rehabilitation functions

Neurostimulation systems can either be invasive or not invasive. According to the National Institute of Health, non-invasive devices can be defined as those that do not require surgery and do not penetrate the brain parenchyma. Furthermore, the devices for cranial stimulation can be segregated by type of energy source and include, but are not limited to, those used for focused ultrasound stimulation, magnetic seizure therapy, electroconvulsive therapy, static magnets, transcranial alternating current stimulation, transcranial direct current stimulation, transcranial magnetic stimulation, electromagnetic stimulation in radio frequency range, in addition several new systems coming based on optical stimulation of the brain tissue, including infra-red light [1,12,13].

It is important to note that neurostimulation can be external, exogenous, or generated outside of the neural system (transcranial magnetic stimulation, TMS and transcranial direct current stimulation, tDCS) and still attempt to affect excitable neuronal membranes directly by inducing or suppressing neural activity in the brain network [1]. This kind of stimulation is artificial (rather than natural) activation of brain structures by electrical or magnetic fields, or electrical current, or light, or ultrasound (usually applied from outside the body or skull) and is fundamentally different from natural (internal, indigenous) activation.

The natural source of brain activation is neural impulses or spikes that are generated by billions of specialized natural receptors located in depth of skin or internal body tissues. That is internal stimulation from impulses streaming to the spinal cord and brain via nerves and distributed across multiple brain structures [1]. Engagement with natural pathways results in the activation of complex neuronal networks using naturally designed spatial and temporal patterns, unique for different brain structures and based on anatomical and physiological type of neurons, and patterns of interneuron connections. Similar to these processes, are neurostimulation systems that activate the specific receptors, free nerve endings or nerve trunks creating the spike flow. In which case the primary stimulation on the periphery of the neural system is also artificial, but the real factor affecting the CNS is the flow of natural spikes, generated and distributed internally.

Cranial Nerve Stimulation and Neurorehabilitation

One of the major problems of neurorehabilitation is complexity and diversity of the brain’s damage. Acquired brain injury (ABI) and neurodegenerative disorders create multiple sites of malfunctioning or physically damaged neural tissue. As a result, various functional systems become inefficient or desynchronized; multiple symptoms developed almost simultaneously. Diversified nature of neural network malfunctions and luck of the methods for localization of such damages become an overwhelming complication for efficient neurorehabilitation, making full spectrum symptoms and disorders “untreatable.”

The majority of existing methods of neurostimulation are limited in several ways. The functional specificity of stimulation creates an extended family of systems for management of selected body parts (bladder) or muscular groups (foot drop). The anatomical specificity and localization of electrodes also restrains efficiency of neurostimulation for functional recovery. The surgical precision of DBS stimulation and the small volume of affected tissue (several cubic millimetres) allow changing activity only in the single node of widely distributed functional network.

The amount of brain tissue affected by TMS, in opposite, might be extended to dozens of cubic centimetres, but activated in an unnatural manner and without functional specificity.

Cranial nerve stimulation might help to solve some these problems. Cranial nerves are the most powerful nerves directly connected to the brain and spinal cord [1]. It is vital to note that all primary sensory systems are streaming information into the CNS. Vision and hearing, smell and taste, vestibular signal and proprioception of the face and tongue continuously directly or indirectly activate the whole brain by cranial nerves.

If we assume, that “multidimensional” damage needs “multidimensional” rehabilitation, then cranial nerve stimulation might be the solution.

TLNS is a unique way to directly and simultaneously activate multiple brain networks by natural spike flow generated on the periphery. The non-invasive and safe “injection” of natural neural activity into damaged neural network initiates the recovery process, based on mechanisms of activity-dependent plasticity.

Existing methods

The family of cranial nerve stimulation systems is small in comparison with the variety of other neurostimulation systems, and relatively young. The first US FDA approval for vagal nerve stimulation (VNS, Cyberonics, Inc.) was received in 1997. It is a small wonder that the reception of all new methods of neurostimulation, in general, remains controversial and not widely accepted. Many cranial nerve neurostimulation systems are currently under development. The olfactory nerve was not used for neurostimulation purpose yet. The optic and auditory nerves are mainly under development of various sensory prosthetic devices, for example, artificial retinas and cochlear implants.

However, one system for retina and optic nerve stimulation should be mentioned here: trans-corneal electrical stimulation (TcES) that involves the use of a low-intensity electrical current in the treatment of ophthalmic diseases, including injuries of optic nerve, light-induced photoreceptor degeneration, ocular ischemia, macular dystrophy and retinitis pigmentosa.

Among the others, three pairs of cranial nerves are intensively under investigation for neurorehabilitation purposes: vagal nerve and trigeminal nerve. Both are large, mixed (sensory and motor) cranial nerves.

Vagal Nerve Stimulation (VNS)

Primary applications for VNS are epilepsy, depression, anxiety, obesity. The target of vagal nerve stimulation (VNS) is the tenth cranial nerve that emerges from the brain at the medulla (brainstem) [13]. It is the longest cranial nerve, extending into the chest and abdominal cavity. Typically, a battery-operated generator is implanted subcutaneously in the left chest wall. An attached electrode is then tunnelled under the skin and wrapped around the left vagal nerve in the neck.

Adverse effects of VNS can be separated into those associated with the complications of the surgery and those resulting from the side effects of stimulation. While risks associated with surgery are minimal, they remain important considerations for both clinicians and patients [13].

There is one non-invasive method, which transcutaneously stimulates the auricular branch of the vagal nerve. It was developed for the treatment of a chronic migraine (NEMOS®, Cerbomed, Erlangen, Germany). A recent study provides evidence that stimulation using NEMOS at 1Hz for four hours daily is effective for chronic migraine prevention over three months [14,15].

Trigeminal Nerve Stimulation (TNS)

TNS targets the upper, ophthalmic branches of the trigeminal nerve. There are two devices, NeuroSigma and Cephaly, which were originally developed to treat drug resistant epilepsy and sleep disorder, respectively. Side effects of NeuroSigma were mild and included skin irritation, tingling, forehead pressure, and headache [16]. Miller et al. [17] found no side or adverse effects from using Cephaly, which is consistent with our experience using the PoNSTM device.

PoNS™ Device

The PoNS™ device, both versions 2 and 4 (Figure 1 & 2 respectively), achieves localized electrical stimulation of afferent nerve fibres on the dorsal surface of the tongue via small surface electrodes. Because of the resulting tactile sensation, which, depending on stimulation waveform typically feels like vibration, mild tingling, or pressure; it is certain that tactile nerve fibres are activated. Taste sensations are infrequently reported, although it is not known whether gustatory afferents are in fact stimulated, given the non-physiological patterns of activation likely to result from PoNS-induced stimulation of these fibres [1].

Citation: Danilov Y and Paltin D. Translingual Neurostimulation (TLNS): A Novel Approach to Neurorehabilitation. Phys Med Rehabil Int. 2017; 4(2): 1117. ISSN:2471-0377