Targeted Neuroplasticity Training: An Operational Neuroethical Risk Assessment,

Mitigation Paradigm, and Further Speculation

Aneesh Rahangdale

Dr. James Giordano

Abstract:

The program Targeted Neuroplasticity Training, TNT, is part of the BRAIN

Initiative, a White House program started in 2013 to bring advances in neuroscience and

technology. Development for TNT started in the Fall of 2016 under the BRAIN Initiative.

TNT augments cognitive function past the boundaries of current known limits to man. As

such, this Operational Neuroethical Risk Assessment and Mitigation Protocol

(ONRAMP) aims to determine what TNT should and should not be used for, what TNT

could be used/misused for, what could come about from TNT, and what should be done

to mitigate potential problems and concerns resulting from TNT. This assessment deals

with neuroethico-legal and social issues arising from TNT and suggests strategies for

dealing with the issues, ranging from continuity of clinical care to establishing programs

allowing for expanded access to the technology.

________________________________________________________________________

With neuroscience and technology progressing to an intellectual frontier, a

thorough examination of ethics must accompany the human race as we move into

uncharted territory. This comes in the form of optimizing various processes that involve

modifying humans. To detail modifications made to humans, one may differentiate

between types of enhancements which advance capabilities beyond normal levels. While

an enablement adjusts changeable physiology within the given situation of socially

common and constant activities, an augmentation aims to create a special and/or unique

modification (Shook & Giordano). To elucidate, an enablement hopes to bring about

inclusion and fully integrate individuals into society, while an augmentation allows for

specialized performance and can affect self, self-worth, and self-identity of persons,

requiring heightened ethical scrutiny. Pushing the envelope of the limits to mankind,

neuroscience and technology can alter neural functions to optimize aspects of cognitive

and behavioral performance.

Recent developments in neuroscience and technology recover memory, restore

cognitive function, and allow for improved prosthetics, and alleviate mental illnesses

such as schizophrenia and depression (National Research Council (US) Committee on

Military and Intelligence Methodology for Emergent Neurophysiological and

Cognitive/Neural Research in the Next Two Decades; Morrison). Additionally, the White

House commenced the BRAIN Initiative (Brain Research through Advancing Innovative

Neurotechnologies) in 2013 in order to further our understanding of the brain and

advance developments in neuroscience and technology (National Institutes of Health). By

researching how the brain functions, operates, and learns, the BRAIN Initiative hopes to

not only enable individuals to bring various skills up to par in their respective

communities but also augment individuals to perform at a previously unreached higher

level.

The Defense Advanced Research Projects Agency, DARPA, has a number of

programs under the BRAIN Initiative. For example, the Electrical Prescriptions (ElectRx)

program aims to help the human body heal itself “through neuromodulation of organ

functions using ultraminiaturized devices, approximately the size of individual nerve

fibers, which could be delivered through minimally invasive injection” (Defense

Advanced Research Projects Agency). In addition to this, DARPA is also developing the

Hand Proprioception and Touch Interfaces (HAPTIX) program, which seeks to create

neural-interface microsystems in order to allow amputees to feel naturalistic sensations

(Defense Advanced Research Projects Agency). Another project, the Neural Engineering

System Design (NESD) program, hopes to provide “unprecedented signal resolution and

data-transfer bandwidth between the brain and digital world” (Defense Advanced

Research Projects Agency). In conjunction with this, the Neuro Function, Activity,

Structure, and Technology (Neuro-FAST) program, seeks to learn more about how the

brain operates by visualizing and decoding brain activity in order to assess and address

threats to the human brain (Defense Advanced Research Projects Agency). Further,

DARPA hopes to create a wireless, implantable device that will recover and recall

memories and learned skills through the Restoring Active Memory (RAM) Replay

program (Defense Advanced Research Projects Agency). Additionally, the

Revolutionizing Prosthetics program seeks to improve functionality of upper limb

prosthetics (Defense Advanced Research Projects Agency). Moreover, the Systems-

Based Neurotechnology for Emerging Therapies (SUBNETS) program aims to treat

neuropsychological illnesses (Defense Advanced Research Projects Agency). While all of

these programs will likely work in conjunction with one another in order to effectively

and successively accomplish their goals, one program under the BRAIN Initiative in

particular stretches the bounds of the mind.

In the fall of 2016, DARPA began developing the Targeted Neuroplasticity Training

(TNT) program, with the aims of combining conventional training practices with

peripheral nerve stimulation in order to “boost the release of brain chemicals, such as

acetylcholine, dopamine, serotonin, and norepinephrine, which play a role in regulating

synaptic plasticity, the process by which connections between neurons change to improve

brain function during learning, in order to speed up the learning processes in the brain”

(Weber). TNT hopes to address the current problem of expensive and time-consuming

training of individuals in the Defense Department, especially because individuals must

learn a lot of information for the sake of the specific missions. Presently, those in the

Defense Department often take months at a time to learn new skills and information, such

as languages, foreign cultures, and symbols. With this new approach, Targeted

Neuroplasticity Training intends to speed up the learning process of cognitive activities

with the precise activation of peripheral nerves that can in turn promote and strengthen

neuronal connections in the brain. If successful, the immediate impact would be to

significantly save time and money in education and training of operatives by reducing the

amount of time and resources needed for the training of military personnel. The speed at

which individuals can learn and the retention of learned information will measure the

success of the TNT program. As of now, the organization of TNT includes 8 research

programs at 7 universities across the United States, which can be seen below in Table 1

(DARPA Public Affairs).

Table 1. Eight research programs at seven different universities across the United

States are investigating the capacities and capabilities of Targeted Neuroplasticity

Training (TNT). This research aims to optimize application of the TNT program with

respect to nerve stimulation, plasticity, invasiveness, and types of cognitive skills

affected.

Location of Research Goal of Research

Arizona State University Targeting stimulation of the trigeminal

nerve to promote synaptic plasticity in the

sensorimotor and visual systems of the

brain -- one group studying intelligence,

surveillance, reconnaissance, and another

group practicing marksmanship and

decision-making

Johns Hopkins University Focusing on regions of the brain involved

in speech and hearing to understand the

effects of plasticity on language learning

University of Florida (2) Identifying which neural pathways in the

brain Vagal Nerve Stimulation, VNS,

activates and the impact of VNS on

perception, executive function, decision-

making, and spatial navigation &

Optimizing VNS parameters around this

circuitry to accelerate learning

University of Maryland Studying the impact of VNS on foreign

language learning, particularly looking at

electroencephalography (EEG) to examine

the effects of VNS on neural function

during speech perception, vocabulary, and

grammar training

University of Texas at Dallas Identifying optimal stimulation parameters

to maximize plasticity, comparing the

effects of invasive versus non-invasive

stimulation, and investigating the longevity

of stimulation effects to determine if

follow-up training is needed for long-term

retention of learned skills

University of Wisconsin Measuring the influence of vagal and

trigeminal nerve stimulation on boosting

activity of neuromodulatory neurons in the

brain

Wright State University Identifying epigenetic markers of

neuroplasticity and indicators of an

individual’s response to VNS

As a program, DARPA is developing Targeted Neuroplasticity Training for

government officials and operatives of the US Defense Department, but this does not

limit the potential for this program to be mimicked or expanded for commercial use or

foreign military use. TNT presents a case of reverse dual use, which is when a program

initially developed for military purposes becomes corporatized for civilian use. As the

idea of TNT is rather attractive because of its potential to increase human productivity

and functioning, the chance of reverse dual use is rather high.

When developing any new neuroscience and technology, there are a number of

neuroethico-legal and social issues (NELSI) created by “imperatives for innovation,

novelty of approaches, limitations of knowledge, and resultant uncertainties of benefits,

burdens, and harms” (Giordano). By developing how and why Targeted Neuroplasticity

Training gives rise to such concerns, a preparatory paradigm for assessing, addressing,

and mitigating resulting NELSI can be developed. These issues can be a result of the

nature of TNT itself or a result of the use, misuse, or distribution of TNT in a social

context. In reality, these issues all are “interactive and reciprocal in effect,” thereby

requiring a multilateral, intersectional assessment (Giordano).

Issues from the inherent nature of TNT are the uncertainties in the effectiveness

of TNT, the safety of TNT, and how TNT will push the frontier of developments.

Additionally, these uncertainties are difficult to resolve until after TNT has been tested,

but this puts constraints upon informed consent, as nobody can study long-term

consequences of TNT until someone tries TNT. The extent to which TNT will improve

cognitive function is unknown at the time, and whether TNT will cause an unexpected

health risk – either in the short term or long term – is impossible to know without first

testing the program. Furthermore, derivative social issues highlight changing norms,

altered autonomy, personality, and/or sense of self, distributive justice, and legal

concerns. For example, varying psychological effects may be common amongst all

participants or dependent upon the particular individual treated, so determining whether

TNT affects autonomy may be trickier than assessing the first batch of treated

individuals. Additionally, establishing a way of making TNT accessible for many people

– as the product will probably be of high demand and thus elicit reverse dual use – will be

an important issue to tackle (Marchant and Gulley). Also, the concerns arising from the

nature of TNT can overlap with social issues; e.g. constraints upon informed consent can

present legal concerns. Nonetheless, by not only carefully monitoring development of the

program and actively informing participants in the Targeted Neuroplasticity Training

program of the capacities, consequences, character, and contexts of the research but also

continuously providing clinical care and developing cutting-edge research, we can

attempt to mitigate these NELSI.

Some technical and practical considerations, constraints, and concerns with the

program are more easily addressable than others. Easily addressable concerns include

whether there are enough trials and participants consenting to participate in the research

and how the program will identify an improvement in cognition due solely to the TNT

device (i.e. how confounding will be avoided in research trials). By performing double-

blind experiments with a sufficient number of trials, these concerns can be made moot.

However, the potential for TNT to improve in the future presents an issue for the

individuals who do not receive the newest edition of the Targeted Neuroplasticity

Training. Further, the prospect of unforeseen, long-term medical consequences because

of the treatment is a tricky concern, as these consequences are difficult to determine

without first performing the treatment on individuals. At this time, the best way to

address this issue is to support both the provision of TNT as well as the continuity of

research and care necessary for sound translation of the treatment.

In performing an Operational Neuroethical Risk Assessment and creating a

Mitigation Paradigm (ONRAMP) for the Targeted Neuroplasticity Training program, all

research and advances pertaining to TNT ought to abide by the ethical principles of self-

creativity (“the right of persons to recreate themselves to enrich their lives”),

nonobsolescence (“the duty to avoid the creation of obsolete people”), empowerment (the

duty to increase the capabilities of people to live autonomous and fulfilling lives”), and

citizenship (“the duty to promote free, equal, law-abiding, and participatory citizenship”)

(Giordano; Shook and Giordano). By respecting these principles, we may respect the

body, the self, and the person of the treated participants and ensure that the program

progresses in an ethically sound fashion by committing to preserving beneficence,

nonmaleficence, justice, and autonomy.

When considering neuroethico-legal and social issues, questions, and concerns,

the most useful protocol is in developing a dialectic approach. As TNT may affect the

self, self-worth, self-identity of persons, consciousness, agency, and the affected

individuals’ personality, the program will require heightened ethical scrutiny, as this

would stem from the very nature of the TNT program. Whether TNT would create a new

identity for those participating is a matter that is highly subjective to the particular

individual. Increased cognitive function and the ability to learn faster may create a more

enlightened and thereby entirely different individual if the program can augment certain

personality traits in addition to cognitive functions. To argue for TNT, if the treatment

can augment beneficial personality traits, people with the treatment may feel more

confident in themselves and more capable and non-obsolete. While people’s personalities

may change, the change may be positive, such as being more confident, understanding, or

resourceful. On the other hand, the argument against TNT can highlight that people with

the treatment may feel their self-worth attached and dependent upon the TNT program.

As a result, TNT would also be negatively affecting individuals’ sense of agency by

disempowering them affecting their sense of self-creativity. Also, there is the potential of

people’s personalities becoming different in a negative way with increased cognitive

function; an increased since of nonobsolescence and agency with the program could lead

treated individuals to become arrogant, dismissive, vindictive, or manipulative.

Determining the effects of TNT on personality a priori is difficult to do before treatment,

as there may not be a significant effect on an individual’s personality and how the

treatment affects certain people may likely be on a case-by-case basis.

While TNT can affect many aspects of the self and potentially expand the

possibilities of the human brain past known bounds, there inevitably will be limits of

TNT’s effects. As TNT will increase cognitive function with electrical stimulation to the

peripheral nervous system, whether the effects will continue or fade away after

implementation is to be determined. If the effects fade, this program could lead to

individuals feeling the need to have the device to learn anything else after using the

device. Further, there most likely will be a point at which TNT will not be able to boost

cognitive function any further without new research and development. These issues

describe post-enablement syndrome, which is when affected individuals will feel disabled

without TNT or discouraged when a peak where performance cannot get any better is

reached (Shook and Giordano). At this point, treated individuals will need to be

accommodated or included back into regular society, which may yield a series of various

effects.

One potential solution is reversibility in contexts of discontinuation of effect for

cause, as to allow treated individuals to assimilate back into society without any potential

judgment from being cognitively advanced. Nonetheless, this solution may be more

problematic, as affected individuals may feel disabled without TNT, leading to various

aspects of post-enablement syndrome. In addition to this, affected individuals may have

trouble assimilating back into society after being treated with TNT, or worse, treated

individuals may refuse to go back to not having augmented abilities. If this becomes the

case, the presence of a few augmented individuals could cause a domino effect of people

clamoring for TNT and/or an elite military-industrial class of geniuses, unless this

program is corporatized and brought to the market. Furthermore, treated individuals who

have an older version of the treatment may not feel accommodated or included with

individuals who have a newer version of TNT. Additionally, TNT-affected individuals

may be unable to cooperate or function on a normal, person-to-person basis with other

people who were not treated with TNT. At the highest level, even a widespread use of

TNT can lead to an eventual normalization of TNT that would negate the comparative

advantages of its application in the first place. While this would increase the baseline of

cognitive function, the norms and expectations of productivity also would increase.

While much speculation can and should be done for the potential consequences of

the research and its translation with regards to reverse dual-use, the direct consequences

resulting from the military application of Targeted Neuroplasticity Training should first

be considered. There will be a reduced timeframe for acquiring necessary skills for

operatives in the US Defense Department, which may translate to decreased costs. As

such, the direct argument for TNT is that the program is economically and strategically

advantageous to the United States. On the other hand, when speculating consequences of

TNT further down the line, many of the above concerns become apparent. The argument

against TNT, even in just considering the consequences of the military employing the

technology, can highlight its potential short-term risk in leading to overspecialized

operatives and exploitation of employees by the state department and its potential long-

term risk in changing many aspects of civil-military relations.

By framing the conditions and goals under which the TNT program ought to

function, an Operational Risk Assessment and Mitigation Paradigm can be prescribed in

order to address, assess, and mitigate technically and socially derived ethico-legal issues

with regards to relative benefits, burdens, risks, and harms. As TNT can improve the

process and speed at which individuals learn various cognitive functions, the premise for

the technology is established. However, the capacities of TNT and the extent to which

this program can improve cognitive learning is not yet known and is currently being

assessed in research trials (Pellerin). When considering the neuroethical argument for

TNT, this void of knowledge is fascinating as much of the capacities and capabilities for

TNT and its application are yet to be explored. Nevertheless, the argument against TNT

could frame this lack of knowledge as problematic and dangerous in that we do not know

the extent to which the treatment will increase cognitive abilities and affect treated

individuals. Yet, the project is much like a catch-22 because we cannot know the full

capacities and constraints of TNT before pursuing the program, but as a result, we cannot

fully inform those participating in the research of the full extent and capacities of TNT.

As such, considering the character of the research and how its products may affect

individuals and communities is extremely relevant.

At the moment, Targeted Neuroplasticity Training is being developed exclusively

for military personnel through the Defense Advanced Research Projects Agency to

optimize functional goals. One may argue that augmentation of beneficence that may

result from TNT augmenting good morals in individuals and allowing individuals to have

more freedom in choosing what actions to take may yield empowerment, as the program

allows operatives to have more time available to accomplish more good things with their

time. Further, this can allow treated individuals to feel more nonobsolescent and creative

because of these augmented skills and morals. Another may argue that TNT could create

an elite military class of geniuses that may threaten the regular citizenry of our country

and even democracy. To mitigate this concern, the Department of Defense can restrict

access to TNT and establish strict legal parameters and limitations for the use of TNT

devices. Establishing context in which Targeted Neuroplasticity Training may be used

within various situations, institutions, and socio-cultural contingencies can mitigate many

of the ethical conundrums.

While this research is initially being developed exclusively for certain operatives,

there is the potential of the commercialization of this technology. In fact, the likelihood

of commercialization of this technology is very high, considering the appeal of

potentially becoming smarter, more productive, and better as a human. Looking at the

past, in the military/medical silos there is considerable non-intentional permeability and

directly intentional permeability that enables “leakage” into other domains of possible

public use, such as with Cooperative Research and Development Agreements (CRADAs)

in which colleagues from government, business, and academia join together to pursue

common research and/or to develop and leverage research and development efforts, and

with the internet (Office of Technology Transfer, Office of Intramural Research, National

Institutes of Health; Leiner, Cerf, and Clark). With regards to TNT, this history suggests

that commercialization is ever more likely to occur. While keeping TNT extremely

restricted to the military is the easiest solution to deal with the slew of resulting

neuroethico-social and legal issues, addressing how to deal with the commercialization of

TNT is prudent, as this is highly probable.

This expansion and dispersal of TNT may further improve the condition of our

human race. Augmentation of cognitive abilities can augment autonomy,

nonobsolescence, self-creativity, and empowerment, as increased knowledge as a result

of this program can allow persons to recreate themselves in never-before-realized ways to

enrich their lives. On the other hand, commercialization as a means of distribution of

TNT could widen the socioeconomic divide between classes in the United States, and, at

a larger scale, between developed and developing countries, as the rich and privileged

would have easy access to the technology while others may not have that same access to

TNT. In addition to this, there are many types of potential public health scenarios

requiring attention with the application of TNT. With TNT, the capabilities of humans

will expand past once thought boundaries, but there may be unforeseen medical

consequences down the road from using TNT – perhaps epileptic seizures, as repeated

electrical stimulation of neurons in an unnatural way may wear on the internal intricacies

and homeostasis of the brain. Another plausible situation is for a lack of TNT treatment

to cause depression, as individuals may perceive themselves as inadequate and feel

obsolete. In the socioeconomic sector, TNT may worsen already wide income gaps (Cobb

and Stevens). Within a developed country like the United States of America, the

socioeconomic divide can deepen between the rich, who can afford this treatment and

thus accomplish things unimaginable to those without the treatment, and everyone else

who does not have access to the treatment.

One way to mitigate these potential issues that is not restricting access to TNT

and banning its commercialization is to establish strict legal parameters and limitations

for the use of TNT devices. Perhaps, the commercialized version can be a limited version

of the full-fledged technology in the military. Further, the US could establish government

welfare programs for distribution of TNT devices to underprivileged communities by

surveying socioeconomic status domestically and distributing TNT through health

insurance, welfare, or other public facilities, and this may even provide more jobs.

Nonetheless, orchestrating such a massive government program will require a political

and bureaucratic reorganization of available government assets and funds.

Internationally, the US can assist other countries in developing their own forms of TNT

to allow wider reaching access by sharing the infrastructure for the technology with those

other countries. Ultimately, making TNT more accessible can address the potential of

gigantic divides.

Continuity of clinical care and research to address and manage effects of TNT

will be paramount. If arguing for TNT, this expansion and continuous improving of TNT

is necessary to further improve the condition of our human race by becoming more

intelligent and efficient. Additionally, augmentation of cognitive abilities can augment

autonomy in individuals by allowing them more freedom in choosing what actions to take

and empower treated individuals, allowing participants to feel more nonobsolescent and

creative because of these augmented skills and morals. To avoid making others obsolete,

those employing TNT should strive for as much distribution of access as possible to

allow for justice. If arguing against TNT, one may highlight the large monetary costs of a

continual revamping of the program. TNT can render both non-participants and initial

participants in the program obsolete, as the initial participants could become obsolete if

not cared for and treated with upgrades given to later participants and non-participants

could become obsolete for not partaking in the program and thereby not becoming as

useful or efficient. In the same vein of thought, if this costly continual treatment of those

affected is necessary and the number of people treated with TNT increases, the cost will

continually increase, as well. Whether the benefits of the program, such as increases in

productivity and decreases in the time to learn information and skills, would outweigh the

costs of the program is difficult to determine a priori. Establishing strict legal parameters,

limitations for the use of TNT devices, and government welfare programs can allow for a

marketization of TNT. Further, assisting other countries in developing their own forms of

TNT and including consistent checkups to assure continuity of clinical care will be key in

the implementation of the program. Nonetheless, the most important aspect of the

application of TNT, whether the program is strictly limited or expanded, will be consent.

Consent will be paramount in integrating TNT in both clinical trials and military

personnel application. By ensuring continuity of clinical care and access throughout the

entire TNT program and allowing participants to opt out at any time upon receiving

updates and upgrades, the Targeted Neuroplasticity Training program can ensure proper

and legitimate consent.

As much is still unknown about the capacities and constraints of TNT, at this

time, the best way to promise fully informed consent would be to restrict access to TNT

to specified individuals with military clearance. As the program develops and more

information about the technology is elucidated, establishing legal parameters and

limitations for the use of TNT devices can protect treated individuals. As such, extant

ethical principles might not completely capture the specificity and diversity of aspects

necessary to guide use-in-practice, particularly when considering both community and

more cosmopolitan applications.

TNT has the potential to change the way the world functions in scientific

research, military application, and corporate efficiency. Still, caution and strict limitations

ought to be enforced if TNT is commercialized. Furthermore, constant therapy and

continuous medical evaluations should be conducted on test participants to ensure no

major negative changes are happening to the core parts of the human, e.g. personality,

consciousness, agency, and self-worth. While an effort to make TNT accessible should be

made if TNT is expanded, distributing TNT domestically will require large bureaucratic

changes to government programs, and establishing TNT internationally will be even more

strenuous, particularly with the divide between developing and developed countries.

Above all, continuity of clinical research and care for affected individuals will be of the

utmost importance. As technology improves and expands, the use of Targeted

Neuroplasticity Training and other biotechnological programs seems inevitable, but

employment of such programs must be sufficiently careful and cautious.

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