Frédéric Gilbert

Novel predictive and advisory brain implants have been tested with significant success for the first time in a human clinical trial. These implantable brain devices are programmed to predict brain activity patterns before specific outcomes occur and provide information to help patients to respond to the upcoming neuronal events that are forecast. Being guided by predictive and advisory information provided through an invasive brain technology offers enormous potential to benefit individuals by increasing control on upcoming symptoms, enhancing decision-making and quality of life. However, these potential benefits do not come free of ethical concerns. What role, if any, do predictive and advisory functionalities play in either impairing or reinstating a patient’s capacity to exercise her/his autonomy? There currently is a gap in our knowledge concerning the consequences of these functionalities on patients’ postoperative life, in particular how it might impact patients’ decision-making as free and autonomous agent. This paper addresses this gap by exploring whether predictive and advisory brain implants are an indispensable feature of autonomy. In order to address this gap in knowledge, the first part of this manuscript explores ethical concerns regarding who is “in control” when patients are experiencing postoperative feelings of “loss of control”. Section two examines what could be morally wrong with having predictive and advisory brain system “in control”. The third section reports findings resulting from a study we conducted with patients implanted with these novel brain devices. Our conclusion discusses how these findings are evidence that, rather than being a threat, predictive and advisory brain devices are an indispensable feature of autonomy.

The world's first-inhuman clinical trial using invasive intelligent brain devices—devices that predict specific neuronal events directly to the implanted person—has been completed with significant success. Predicting brain activity before specific outcomes occur brings a raft of unprecedented applications, especially when implants offer advice on how to respond to the neuronal events forecasted. Although these novel predictive and advisory implantable devices offer great potential to positively affect patients following surgery by enhancing quality of life (e.g., provide control over symptoms), substantial ethical concerns remain. The invasive nature of these novel devices is not unique; however, the inclusion of predictive and advisory functionalities within the implants, involving permanent monitoring of brain activity in real time, raises new ethical issues to explore, especially in relation to concerns for patient autonomy. What might be the effects of ongoing monitoring of predictive and advisory brain technologies on a patient's postoperative sense of autonomy? The role played by predictive and advisory implantable brain devices on patient's feelings of autonomy following surgery is completely unknown. The first section of this article addresses this shortcoming by reporting on a pilot study that we conducted with one of the patients implanted with one of these novel brain devices. The second section examines how overreliance on predictive and advisory brain technologies may threaten patients' autonomy. The third section looks into ethical problems concerning how devices delivering automated therapeutic responses might, hypothetically speaking, be used to monitor and control individual's autonomy through inhibition of undesirable behaviors.

A possible relationship between brain tumours and ac- quired behavioural changes, including criminal conduct, has been and is still the focus of a multidisciplinary debate (Gilbert and Focquaert 2015). A significant num- ber of clinical cases demonstrating behavioural changes and cognitive impairment due to brain lesions have been reported in the medical literature for many decades (Vidor 1951; Lishman 1968). A previous study we conducted on eighty-six patients suffering from brain lesions, revealing that 38 per cent developed disruptive personality and behavioural changes (including hyper- sexuality and aggressiveness), aligns with these clinical reports (Vranič and Gilbert 2014). However, even if a correlation between acquired behavioural changes and brain tumours seems to be a plausible medical hypoth- esis, its exact legal and ethical interpretation is not. (First para).

Some argue neuroethicists have an obligation to prepare for and anticipate the future of invasive brain devices. No- body can deny that upcoming technologies will develop fu- ture generations of implantable brain devices and, as such, these novel developments deserve our careful ethical atten- tion. However, while thinking too far ahead raises the risk of articulating ethical prophecies, it also neglects current and urgent ethical issues. Consequently, in both scenarios, thinking ahead “too much” may force us to buy into specu- lative ethics. The danger of speculative ethics is not only that it fails to capture any practical issues, but also that it wastes our ethical resources. In the long term, we believe speculative ethics may negatively affect the authority of neuroethics as a credible narrative within the scientific literature. (First para).

Applied ethics issue: Since most neuroscientists support neurobiological determinism, does it entail the end of free will or even criminal responsibility?

Methods: We explore whether the notion of neurobiological determinism is compatible with the concept of criminal responsibility. Based on this exploration, we analyse the notions of free will, determinism and responsibility. Our central goal is to confront common philosophical arguments about free will with neurobiological evidence. We try to find whether responsibility is necessarily linked to free will, and if not, we examine whether this should imply the end of responsibility.

Results: We propose to liberate ethical debate from a traditional libertarian conception of free will, according to which a person could have decided to act differently given the same initial conditions. Our purpose is to argue that, although criminals are somehow determined by known or unknown neurobiological causes, administering the appropriate treatment to them based on their choices and decisions is still justified on consequentialist grounds.

This article reviews the current neurobiological literature on the aetiology of developmental and acquired paedophilia and examines what the consequences could be in terms of responsibility and treatment for the latter. Addressing the question of responsibility and punishment of offenders with acquired paedophilia from a neurobiological perspective is controversial. Consequently it is essential to avoid hasty conclusions based strictly on neurobiological abnormality justifications. This study establishes a distinction between developmental and acquired paedophilia. The article investigates whether offenders who fulfil the diagnosis of acquired paedophilia should be held fully responsible, particularly in cases where the offender's conduct appears to result from volitionally controlled behaviour that is seemingly incompatible with a neurological cause. Moreover, the article explores how responsibility can be compromised when offenders with acquired paedophilia have (partially) pr...

Although it is necessary to avoid hasty conclusions based strictly on biological explanations, what are the consequences for criminal justice if the origin of paedophilic crimes is the result of biological propensities? In order to protect society in the long term, the purpose of this paper is to examine whether the applicability of an exclusive retributive justice is appropriate to tackle paedophilic crime.

The goal of this article is to shed light on Deep Brain Stimulation (DBS) postoperative suicidality risk factors within Treatment Resistant Depression (TRD) patients, in particular by focusing on the ethical concern of enrolling patient with history of self-estrangement, suicide attempts and impulsive–aggressive inclinations. In order to illustrate these ethical issues we report and review a clinical case associated with postoperative feel- ings of self-estrangement, self-harm behaviours and sui- cide attempt leading to the removal of DBS devices. Could prospectively identifying and excluding patients with suicidality risk factors from DBS experimental tri- als—such as history of self-estrangement, suicide attempts and impulsive–aggressive inclinations—lead to minimizing the risk of suicidality harm?

Degeneration, disease, cancer and trauma are the conditions that determine not only human longevity but also function. What gives life its fulfillment is the ability for each person to express himself or herself not only emotionally and spiritually but also physically. Independence and freedom to move are highly dependent on normally functioning systems. (First para).

Concussion and Mild Traumatic Brain Injury (mTBI) affect millions of people worldwide. mTBI has been called the Bsignature injury^ of the recent conflicts in Iraq and Afghanistan, affecting thousands of active duty service men and women, and veterans. Sport- related concussion represents a significant public health problem, with elite and professional athletes, and mil- lions of youth and amateur athletes worldwide suffering concussions annually. These brain injuries have re- ceived scant attention from neuroethicists, and the focus of this special issue is on defining the ethical consider- ations and developing and elucidating the neuroethical contributions to the discussion about concussion and mTBI.

Current discussions about concussion in sport are based on a crucial epistemological question: whether or not we should believe that repetitive mild Traumatic Brain Injury (mTBI) causes Chronic Traumatic Enceph- alopathy (CTE). This epistemological question is essen- tial to understanding the ethics at stake in treating these cases: indeed, certain moral obligations turn on whether or not we believe that mTBI causes CTE. After discussing the main schools of thought, namely the CTE-sceptic position (which does not admit a causal relation between mTBI and CTE) and the CTE- orthodox position (as defended by those who see a causal association between mTBI and CTE), this article examines the concussion debate in sport and asks if its current articulation helps to answer whether or not we should call for responsive, ethical action(s).

Although being generally safe, the use of Deep Brain Stimulation (DBS) has been associated with a significant number of patients experiencing postoperative psychological and neurological harm within experimental trials (i.e. self-estrangement, hypersexuality, hypomania, suicidality, impulse control disorders, etc.). A proportion of these post- operative severe adverse effects have lead to the decision to medically prescribe device deactivation or removal. However, there is little debate in the literature as to what is in the patient’s best interest when device removal has been prescribed; in par- ticular, what should be the conceptual approach to ethically guide the decision to remove or maintain implants. The purpose of this article is to examine the ethical issues raised when patients refuse brain device explantation despite medical prescription. In order to illustrate these issues, we report and dis- cuss a clinical case involving a patient suffering from treatment resistant depression who experi- enced forms of postoperative self-estrangement, as well as suicidal attempts, but who resists giving consent to device explantation.

High-grade meningiomas are rare extra-axial tumors, frequently causing brain invasion and prominent brain edema. Patients harboring high-grade meningiomas occasionally present with behavior changes. Data about frequency and prognostic importance of preoperative behavior changes in patients with high-grade meningiomas is missing. 86 patients with primary high-grade meningiomas were analyzed. Statistical analysis was performed to determine correlation of preoperative behavior changes with tumor location, preoperative brain edema, tumor cleavability, tumor grade, Ki67 proliferation index, and microscopic brain invasion. Survival analysis was performed. 30 (34.9%) patients presented with preoperative behavior changes. These changes were more frequent with male patients (𝑃 = 0.066) and patients older than 55 years (𝑃 = 0.018). They correlated with frontal location (𝑃 = 0.013), tumor size (𝑃 = 0.023), microscopic brain invasion (𝑃 = 0.015), and brain edema (𝑃 = 0.006). Preoperative behavior changes did not correlate with duration of symptoms, tumor cleavability, tumor malignancy grade, and Ki67 proliferation index. They were not significantly related to overall survival or recurrence-free survival of patients with primary high-grade meningiomas. Preoperative behavior changes are frequent in patients harboring primary high-grade meningiomas. They correlate with tumor size, microscopic brain invasion, and brain edema. Preoperative behavior changes do not predict prognosis in patients with primary high-grade meningiomas.

Christen and colleagues’ (2014) article offers key insights on today’s international use of deep brain stimulation (DBS). In particular, they report international evidence of significant variation between targeted neuronal sites for treatment of the same neurodegenerative disease, namely Parkinson’s. According to their study, “European PD patients are more likely to be stimulated in the STN than were U.S. patients” (72). Christen and colleagues’ findings are important to help us understand that these variations between targeted areas for treating the same pathology illustrate a lack of consistency and uniformity in today international DBS practices. I think this deficit of unifor- mity within DBS practices may fail to protect patients dur- ing experimental trials, especially psychiatric patients. I use treatment-resistant depression (TRD) to discuss these ethical issues. (First para).

In his paper “Diminishing and Enhancing Free Will,” Walter
Glannon (2011) uses the example of a surgeonwho takes
drugs to enhance her or his capacities. He concludes that
“the surgeon would be responsible for performing more surgeries, but not more responsible for performing them,”
and argues that an increase in the content of responsibility
does not entail an increase in the degree of responsibility
(15). The question of whether the degree of responsibility can be affected by the use of performance-enhancing substancesis fundamental in ethics and law because it impactsdirectly on the normative practices and legal consequences associated with enhancement (Downie et al. in press). (First para).

This chapter examines the emerging ethical challenges raised by implementation of nanotechnology in brain devices for enhancement purposes in subjects with healthy brains. This chapter will proceed in
five steps. The first section introduces brain implants and discusses how their status may be changed by nanotechnologies for enhancement purposes. The second section explores whether the ethics of nano- bionic devices for cognitive enhancement purposes in healthy, informed subjects might be helped by referring to the treatment-enhancement distinction. Such a distinction could serve to illuminate guidelines and policies. The third section examines whether the designs for nano-bionic devices for cognitive enhancement raise a number of intrinsically new ethical problems if applied to healthy subjects. The fourth section looks at whether nano-bionic devices used for the purpose of enhancement introduce novel ethical difficulties to the informed consent of healthy and free subjects. The fifth section sketches the preliminary ethics that have to be established before a healthy individual could undergo an informed consent process for invasive nano-bionics brain intervention.

Although an invasive medical intervention, Deep Brain
Stimulation (DBS) has been regarded as an efficient and
safe treatment of Parkinson’s disease for the last
20 years. In terms of clinical ethics, it is worth asking
whether the use of DBS may have unanticipated
negative effects similar to those associated with other
types of psychosurgery. Clinical studies of epileptic
patients who have undergone an anterior temporal
lobectomy have identified a range of side effects and
complications in a number of domains: psychological,
behavioural, affective and social. In many cases, patients
express difficulty adjusting from being chronically ill to
their new status as ‘treated’ or ‘seizure free’. This
postoperative response adjustment has been described
in the literature on epilepsy as the ‘Burden of Normality’
(BoN) syndrome. Most of the discussion about DBS
postoperative changes to self is focused on abnormal
side effects caused by the intervention (ie,
hypersexuality, hypomania, etc). By contrast, relatively
little attention is paid to the idea that successfully
‘treated’ individuals might experience difficulties in
adjusting to becoming ‘normal’. The purpose of this
paper is (1) to articulate the postoperative DBS
psychosocial adjustment process in terms of the BoN
syndrome, (2) to address whether the BoN syndrome
illustrates that DBS treatment poses a threat to the
patient’s identity, and (3) to examine whether the
current framework for rehabilitation after DBS
procedures should be updated and take into account the
BoN syndrome as a postoperative self-change response.

From graphic brain tumors to micro-neurological lesions, the increasing sophistication of
neuroimaging technologies has greatly contributed to the accuracy of neuronal diagnostics.
Concurrent with the development of these technologies, metaphors associated with the readability of
the brain have evolved within the scientific literature. A cursory glance at recently published articles
from Nature Journals reveals many references to the brain readability metaphor, from “developments in neuroimaging…including the reading of brain states”1 to “neurotechnologies such as brain reading.”2 (First paragraph).

In early 2009, President Obama overturned the ban on federal funding for research involving the derivation of human embryonic stem cells (hESC). The Food and Drug Administration (FDA) also approved Geron’s first-in-human hESC trial for spinal cord injury (SCI) patients. We anticipate an increase in both research in the United States to derive hESC and applications to the FDA for approval of clinical trials involving transplantation of hESCs. An increase of such clinical trials will require a concomitant increase in the number of preceding preclinical assays. We examine important issues concerning the use of animals in SCI stem cell research that require a reevaluation of the moral permissibility of studies such as Geron’s.

Postmortem evidence of chronic traumatic
encephalopathy (CTE) in the brains of American
National Football League players who suffered
concussions while playing have intensified concerns
about the risks of concussion in sport.1 Concussions are
frequently sustained by amateur and professional players
of Australia’s three most popular football codes (Australian
football, rugby league, and rugby union) and, to a lesser
extent, other contact sports such as soccer. This raises
major concerns about possible long-term neurological
damage,2-4 cognitive impairment and mental health
problems5 in players of these sports. (First para).

Geron recently announced that it had begun enrolling patients in the world's first-in-human clinical trial involving cells derived from human embryonic stem cells (hESCs). This trial raises important questions regarding the future of hESC-based therapies, especially in spinal cord injury (SCI) patients. We address some safety and efficacy concerns with this research, as well as the ethics of fair subject selection. We consider other populations that might be better for this research: chronic complete SCI patients for a safety trial, subacute incomplete SCI patients for an efficacy trial, and perhaps primary progressive multiple sclerosis (MS) patients for a combined safety and efficacy trial.

In the section “How New is Neuroenhancement?” Lucke
and colleagues (2011) demonstrate that the debate concerning
enhancing human cognitive capacity through research
with psychoactive stimulants drugs was common in the
19th and 20th centuries. However, neuroenhancement in
particular, and enhancement in general, is a recasting of an
even older debate that can be traced from the 16th to the
18th centuries. (First para).