Neuromodulation
The North American Neuromodulation Society (NANS), founded in 1994, roughly defines neuromodulation as encompassing a number of treatment modalities that exert their effect on the nervous system, typically using implantable techniques and including the stimulation of nerves in the central, peripheral or autonomic nervous systems or through the use of implanted drug delivery systems. The International Modulation Society (INS), founded in 1989, defines neuromodulation as the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body. These definitions, conspicuous in their ambiguity, are a reflection of an emerging and rapidly evolving field with an ever-expanding list of treatments and indications.
Techniques involving implanted devices
Deep brain stimulation
Deep brain stimulation (DBS) is used for the treatment of movement disorders and is the most invasive neuromodulation strategy (see Chapter 29 ).
- •
1997: DBS granted US Food and Drug Administration (FDA) approval for essential tremor.
- •
2002: DBS granted FDA approval for Parkinson’s disease (PD) and is quickly adopted as a popular and effective treatment for PD and essential tremor.
- •
2003: FDA provided humanitarian device exemption for DBS treatment of dystonia.
- •
2009: FDA provided humanitarian device exemption for DBS treatment of obsessive-compulsive disorder.
- •
In the subsequent decade, investigational and off-label uses of DBS were reported in the treatment of various conditions, including pain, major depression, Tourette syndrome and other tic disorders and dyskinesias, obesity, anorexia, addiction, pathological aggression, dementia, and epilepsy
- •
2016: A systematic review examined 78 individual cases in 19 articles discussing the use of DBS for treatment of disorders of consciousness (DoCs) and concluded that no clear evidence exists to support DBS for restoration of consciousness in DoC patients and that in cases where benefit was reported, spontaneous recovery was too confounding
- •
2018: DBS granted FDA approval for treatment resistant epilepsy after the Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE) trial and other trials demonstrated sustained efficacy and safety in a treatment-resistant population
Motor cortex stimulation
Motor cortex stimulation (MCS) is a neuromodulation technique that is one degree less invasive than DBS and uses implanted cortical electrodes.
- •
Used for various neuropathic pain syndromes
- •
Greatest efficacy observed in the treatment of deafferentation pain caused by either peripheral (trigeminal nerve injury, phantom limb) or central (post stroke) lesions
- •
An emerging technique in MCS patient selection has been the use of repetitive transcranial magnetic stimulation (rTMS), which is noninvasive, to predict a positive response to MCS.
Noninvasive techniques
Developments in noninvasive brain stimulation are rapid as increases in both the technology and the understanding of the brain continue.
Transcranial electrical stimulation
Transcranial electrical stimulation (TES) involves stimulation through the use of scalp electrodes.
- •
1980: Merton and Morton first published on this technique.
- •
High-voltage TES stimulates the cortex underlying the anode, activating corticospinal tract neurons and generating a motor evoked potential (MEP).
- •
TES is credited as the first technique to allow for the noninvasive study of excitability and propagation along CNS fibers in living, cooperative human beings.
- •
TES is uncomfortable.
Transcranial magnetic stimulation
Transcranial magnetic stimulation (TMS) uses electromagnetic induction as a painless way to induce a current in the brain.
- •
1985: TMS is developed, and because it is painless, it becomes preferred over TES. ,
- •
TMS of the motor cortex can be used to provide information regarding disease-related changes of corticospinal output in conditions such as multiple sclerosis, stroke, cervical myelopathy, and amyotrophic lateral sclerosis through analysis of MEPs.
- •
TMS has been used to map brain function; initially it was used to map the motor homunculus through use of the MEP, a convenient output measure.
- •
The combination of TMS and EEG creates vast possibilities; TMS-evoked cortical activity can be measured and used to study cortical excitability, connectivity, and plasticity.
- •
These developments have been part of the neuroscience revolution that has shaped the neurorehabilitation approach to incorporate principles of neuroplasticity and motor learning.
- •
Many therapeutic applications of TMS have surfaced:
- •
TMS is approved by the FDA as a preoperative navigational tool.
- •
Several TMS devices have now been FDA approved for treating depression.
- •
2014 European expert panel published evidence-based guidelines for therapeutic use of, TMS and ascribed:
- 1.
Level A evidence (definite efficacy) to the antidepressant effect of high-frequency repetitive TMS (HFrTMS) on the left dorsolateral prefrontal cortex (DLPFC)
- 2.
Level A evidence for the analgesic efficacy of HFrTMS on the primary motor cortex (M1) of the contralateral hemisphere
- 3.
Level B evidence (probable efficacy) for low-frequency rTMS (LFrTMS) for depression, HFrTMS on the left DLPFC for the negative symptoms of schizophrenia, and LFrTMS of the contralesional M1 for motor recovery in chronic motor stroke
- 4.
Several indications reached possible efficacy (Level C) including tinnitus and auditory hallucinations
- 1.
- •
Peripheral nerve stimulation techniques
Peripheral nerve stimulation techniques are numerous and varied. Some applications of interest to the brain injury specialist include treatments for neurogenic bowel, neurogenic bladder, and chronic pain.
Various neuromodulation strategies exist for treatment of migraine. These include noninvasive vagus nerve stimulation (nVNS), external trigeminal nerve stimulation, occipital and supraorbital transcutaneous nerve stimulation, transcranial direct current stimulation, and alternating current stimulation in addition to TMS. The nVNS device is the only device that is FDA approved for acute and preventive use in cluster headache and that has strong evidence to suggest efficacy in acute and preventive treatment of migraine. Left cervical vagus nerve stimulation is an approved therapy for epilepsy and treatment-resistant depression, but its treatment efficacy for depression has been called into question .
In terms of neuromodulation strategies that use drug delivery systems, most brain injury medicine specialists are familiar with intrathecal pumps. Agents approved by the FDA for intrathecal therapy include morphine and ziconotide for pain and baclofen for spasticity, although several other agents are used off label for the treatment of pain. Intrathecal baclofen (ITB) has also been suggested to be of benefit in patients with paroxysmal sympathetic hyperactivity (PSH) caused by severe TBI.
Neuroprosthetics and brain computer interface
In parallel to the field of neuromodulation, neuroprosthetics is a domain that also involves devices that interface with the nervous system to restore function—the most successful and well known being the cochlear implant. At the heart of neuroprosthetics is the brain computer interface (BCI), which is defined as “a system that measures central nervous system activity and converts it into artificial output that replaces, restores, enhances, supplements or improves natural CNS output and thereby changes the ongoing interactions between the CNS and its external or internal environment.”
There are five stages making up a typical BCI :
- 1.
Brain signal acquisition
- 2.
Preprocessing
- 3.
Feature extraction/selection
- 4.
Classification
- 5.
Application interface
To put it another way: Brain signals are recorded, processed by a translational algorithm, and then routed to drive a chosen application. One way to categorize BCIs is in terms of invasiveness of signal recording. As a rule, the more invasive the system, the higher/better the signal resolution.
The most common recording methods in the CNS are:
- •
Scalp EEG
- •
Electrocorticography (ECoG) that records from the cortical surface of the brain via an implanted electrode array
- •
Intracortical and depth electrodes, the most invasive technique
- •
Other modalities for brain signal acquisition include magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI), and functional near infrared spectroscopy (fNIRS)
- •
Bidirectional systems, capable of electrical stimulation and recording, are also being explored
- •
Initially, BCI systems were used to allow the user to control output for environmental control or communication.
- •
This has been explored for augmentative and alternative communication for patients who have severely limited ability to control a communication device such as in amyotrophic lateral sclerosis or locked-in syndrome.
- •
In 2015, Coyle et al. reported four patients in a minimally conscious state who demonstrated consistent and appropriate brain activation on EEG through visual and auditory feedback, suggesting that patients in MCS may be able to operate a BCI-based communication system.
- •
A newly emerging application of BCI and a new frontier in neurorehabilitation is the use of BCI to enhance of motor learning. As an example, a 2018 study demonstrated that BCI coupled to functional electrical stimulation (FES) elicited a clinically relevant and lasting motor recovery in chronic stroke survivors compared with sham FES. In addition, these authors were also able to demonstrate through EEG mapping increased functional connectivity between motor areas of the affected hemisphere in the treatment group, suggesting that BCI–FES therapy can drive functional recovery through “purposeful plasticity.”
Review questions
- 1.
Which of these statements regarding deep brain stimulation (DBS) are true?
- a.
The US Food and Drug Administration (FDA) has approved DBS as treatment for dystonia and other movement disorders.
- b.
The Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE) trial demonstrated that DBS was safe and effective treatment for treatment-resistant epilepsy, leading to the FDA approval for this indication in 2018.
- c.
DBS has been shown to improve communication in patients with disorders of consciousness (DoC), but it has not been adopted as a popular treatment because decreased access to treatment.
- d.
All of the above
- e.
None of the above
- a.
- 2.
Which of these treatments are FDA approved for the treatment of depression?
- a.
Transcranial magnetic stimulation (TMS)
- b.
Left cervical vagus stimulation
- c.
Noninvasive vagus nerve stimulation (nVNS)
- d.
A and B
- e.
A and C
- a.
- 3.
Which of these treatments are incorrectly paired with the approved indication?
- a.
DBS/Parkinson’s tremor, essential tremor, epilepsy
- b.
TMS/preoperative navigation, depression
- c.
Intrathecal baclofen (ITB)/paroxysmal sympathetic hyperactivity (PSH)
- d.
Noninvasive vagus nerve stimulation (nVNS)/cluster headache
- e.
Left cervical vagus nerve stimulation/epilepsy, depression
- a.
Answers on page 403.
Access the full list of questions and answers online.
Available on ExpertConsult.com
- 4.
Choose the correct statement.
- a.
High-frequency, repetitive TMS (HFrTMS) on the left dorsolateral prefrontal cortex (DLPFC) has strong efficacy in depression.
- b.
Low-frequency, repetitive TMS (LFrTMS) on the primary motor cortex (M1) has strong efficacy in depression.
- c.
Low-frequency, repetitive TMS (LFrTMS) on the left dorsolateral prefrontal cortex (DLPFC) has poor efficacy in depression.
- d.
High-frequency, repetitive TMS (HFrTMS) on the primary motor cortex (M1) of the ipsilateral hemisphere has strong efficacy for chronic pain.
- e.
None of the above
- a.
- 5.
What are the stages of brain computer interface (BCI)?
- a.
Brain signal acquisition → preprocessing → feature extraction/selection → classification → application interface
- b.
Brain signal acquisition → neuroprosthetic interface
- c.
Electroencephalogram (EEG) recording → translational algorithm → control of output device
- d.
Motor imagery → EEG recording → translational algorithm → control of neuroprosthetic
- e.
Brain signal acquisition → coupling with functional electrical stimulation → purposeful plasticity
- a.
References
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
