Introduction to The NeuromodTM-Select Research Device

A Personalized Neuroelectronic Treatment Approach using the NeuromodTM-Select device

NM medical devices have advanced to a level where it is now possible to modulate targeted structures within a specific cortical network including some subcortical structures. This is possible through the combination of techniques and procedures including individualized target optimization (iTO) and the use of high-definition electrodes and montages. iTO uses a patient’s MRI or age-specific template if the patient does not have MRI images available.

Waveforms and Neuroanatomical Targets

The NeuromodTM-Select is able to produce multiple waveforms: tDCS, tACS, tRNS, ms-tDCS, so-tDCS, IF-tACS, tAVSN/pAVSN, tCVNS, and tTNS and can operate in Sham mode double-blind controlled experiments for all waveforms.

Transcranial direct current stimulation (tDCS) 

A non-invasive neuromodulation technique inducing prolonged brain excitability changes and promoting cerebral plasticity is a promising option for neurorehabilitation. tDCS modulates spontaneous neuronal activity through a weak direct current delivered on the scalp inducing prolonged functional after-effects in the brain. The current is transmitted into the brain (anodal stimulation) over a cortical region leading to excitatory effects and collected from the brain (cathodal stimulation) leading to inhibitory effects. tDCS produces short term effects on neuronal excitability, and longer lasting effects thought to be related to long-term modulation effects via synaptic modification when used repetitively. The stimulating electrode is placed over the target area and the reference electrode can be placed on the scalp (‘bicephalic or bipolar tDCS’) or on a different body part, usually the right shoulder (‘monocephalic or monopolar tDCS’) (Nitsche MA, et al., 2003; Poreisz C, et al.,2007).

Transcranial alternating-current stimulation (tACS)

Transcranial alternating current stimulation (tACS) is the external application of oscillating electrical currents which is able to influence cortical excitability and activity (Antal et al., 2008; Chaiebet al., 2011; Moliadze et al., 2012; Wach et al., 2013).  Its simple form uses sinusoidal stimulation; however, any other waveform appears possible, such as rectangular current shapes.  Amplitude, frequency, and phase across stimulation electrodes can be defined.  tACS allows for coupling with specified  oscillatory frequencies.

Transcranial random noise stimulation (tRNS)

Transcranial random noise stimulation (tRNS) is a non-invasive electrical stimulation of the brain whereby a weak alternating current oscillating at random frequencies is delivered through the scalp using a pair of electrodes. In this approach alternating current is applied to the scalp with a constantly changing frequency ranging from 0.1 to 640 Hz, the highest physiologically measured human electric brain oscillation in somatosensory-evoked potentials.The neuromodulatory effects of tRNS are said to facilitate or inhibit neuronal activity by syncronising or desyncronising it (Grenier, Timofeev, & Steriade, 2001; Moss, Ward, & Sannita, 2004; Ponomarenko, Li, Korotkova, Huston, & Haas, 2008).   

Monophasic Sinusoidal Direct Current Stimulation (ms-tDCS)

A modified version of tACS is transcranial monophasic sinusoidal direct current stimulation (ms-tDCS) (Antal et. al., 2008) where the stimulation is monophasic due to a DC bias added to the sinusoid.  This technique allows the NeuromodTM-Select to modulate a neuroanatomic target at a specified frequency.

Slow-oscillatory Direct Current Stimulation (so-tDCS)

The NeuromodTM-Select is capable of enhancing slow-oscillatory (so) amplitude/power and the duration of slow-wave sleep via so-transcranial direct current stimulation (so-tDCS).  A specific bilateral frontocentral montage is used applying slow range oscillating currents (<1 hz) during sleep (see Marshall et al. for a detailed description of procedures). so-tDCS stimulation begins 4 minutes after the first onset of stable NREM stage two sleep with a 10 second ramp up phase and continues for five minutes.  Each 5- minute block is separated by 1-minute stimulation-free rest intervals. To further enhance the duration of slow-wave sleep and the amplitude of slow wave oscillations, the NeuromodTM-Select pairs so-tDCS as described above with auditory stimulation using pink noise in 50 msec burts.  

Interferential transcranial Alternating Current Stimulation (IF-tACS)

In 1965, Interferential Stimulation was proposed by a Russian scientist (Brown, 1975). Interferential or sometimes referred to as Temporal Interference Stimulation consisted of having two pairs of electrodes energized with sine waves of slightly shifted frequencies. The intention of this approach was that through pulsation the higher frequencies would create a lower frequency, where the two frequencies intersect.  Using the TO software built into the NEP, the NeuromodTM-Select IF-tACS can modulate deep cortical and subcortical structures without adversely affecting the outer cortex.  

Transcutaneous and Percutaneous Auricular branch of the Vagus Nerve Stimulation (tAVNS/ptAVNS)

The vagus nerve (VN) plays a crucial role in sensing and regulating bodily states while forming brain-body connections.  Most VN fibers (about 80%) are afferent sensory fibers carrying somatic and visceral information to the brainstem and thus providing a unique entrance to the brain (Berthoud and Neuhuber, 2001; Groves and Brown, 2005). Most afferent fibers of VN end in the nucleus of the solitary tract (NTS) in the brain stem where connection from this and other nuclei project to the hypothalamus and to various cortical regions. The rest of VN fibers (about 20%) are efferent visceromotor fibers governing neurogenic, myogenic, and endocrine actions within projected organs.  A major function of the VN is to mediate the parasympathetic branch of the Autonomic Nervous System (ANS). Increasing the vagal tone of this nerve activates the parasympathetic nervous system (Olshansky et al., 2008; Barella et al., 2014).  The antagonistic action of the activated parasympathetic system over the sympathetic is one of the expected therapeutic mechanisms of aVNS.  The external ear is the only place on the body where VN sends its only peripheral branch.  Within the ear, the middle region of the pinna, the central concha, is mostly innervated by the auricular branch of the vagus nerve (aVN).  Using a transilluminator, the aVN was found in 100% of cases in the cymba concha (Peuker and Filler, 2002).

The NeuromodTM-Select uses open-loop and closed-loop algorithmic-driven activation/adjustment of aVNS based on individual physiological biofeedback provided back to the stimulator allowing for optimization and personalization of aVNS therapy. The particular choice of physiological signals employed as biofeedback depends on the therapeutic/target.  

Transcutaneous Cervical Branch of the Vagus Nerve Stimulation (tCVNS)

The afferent branches of the cervical VN can also be noninvasively stimulated via surface skin electrodes using the NeuromodTM-Select device applied at the neck.  The transcutaneous stimulation uses two surface electrodes and is intermittently activated.  In order to stimulate VN relatively deep under the neck surface, the stimulation is performed using bipolar bursts of a relatively high frequency (e.g., 5 kHz) for the burst duration of 1 ms, with a periodic bursting at lower frequencies (e.g. 25 Hz). 

Transcutaneous Trigeminal Nerve Stimulation (tTNS) 

The NeuromodTM-Select also can administer transcutaneous stimulation to the trigeminal nerve (tTNS) at the supraorbital V1 branch of the TN using gel based electrodes.  For tTNS, the NeuromodTM-Select can be programmed to generate 1-200 Hz biphasic pulsed wave with a 50-250 s pulse width with a range of intensities.

Sham Stimulation Application 

A treatment or procedure that is performed as a control and that is similar to, but omits a key therapeutic element of the treatment or procedure under investigation. This is a useful tool when conducting single or double blind randomized control studies.