IN 1961, Wilder Penfield, the great Canadian neurosurgeon, was invited to speak at a neuroscience conference at the University of California (Penfield 1963). At that point, his reputation as a clinician, surgeon, and scientist had been firmly established, and he had long achieved pioneer status in the field of surgical epilepsy, as well as medical education. His talk, which he titled “The physiological basis of the mind,” wasn’t his first or last foray into the mind–body debate. Indeed, he would author a book, and several chapters on the topic, and was already an invited speaker and honorary member of the American Philosophical Society (Penfield 1977). Having synthesized his years of operations on awake epileptic patients, for whom he had resected epileptogenic cortex after meticulous cortical stimulation and mapping, he found himself in the ideal position to comment on the makeup of the mind, and hypothesize about its organic origins. His talk surprised many by describing a separate mind that was beyond the brain’s physical mechanisms, but more importantly for Penfield, the talk did not in the least represent a digression from his neurosurgical practice. His philosophy was a direct extension of his clinical practice and was informed by concrete physical findings from his operating room, effectively his laboratory. Penfield provided his listeners with first-hand accounts of mind exploration occurring in real time, in real life, and which contextualized his hypotheses and ideas. Not only was this not unusual for him, it was perfectly natural. The recipient of a classical, and enviable, neurosurgical training under the likes of Charles Sherrington and Ramón y Cajal, Penfield learned early on the value of translational research, as well as the importance of a healthy respect and love for the humanities, philosophy, in his case (Penfield 1977). For Penfield it required no leap of reason or imagination, for a neurosurgeon to be invited to a neuroscience conference and speak about an age-old philosophical argument. Philosophers, for the aging neurosurgeon, held no monopoly on the mind.
When thinking about the role of neurosurgery in neuroethics, one needs to first reflect, briefly, on the development of the specialty and its origins. Penfield’s career, and that of his contemporaries was largely possible because of a substantial shift in the 1920s and 30s that saw the role of the neurosurgeon change from one of passive receiver of instruction and executor of risky and complex interventions to that of active prescriber and clinician (Bliss 2007). With the development of ventriculography, rudimentary radiography, and eventually angiography, neurosurgeons freed themselves from their reliance on neurologists for their localizations, and proceeded to independently diagnose, localize, and treat nervous system pathology. Neurosurgery, born a hybrid of general surgery, pathology, and neurology, matured and grew into its own, respectable profession, as clinicians also began to realize the power of their field to explore the myriad functions of the human brain. Further advances in the mid-20th century and onward, including those in anesthesia, critical and ventilatory care, and specific to neurosurgery, the development of stereotaxy, and microsurgery, solidified the neurosurgeon’s role as chief navigator through the sea of complex and challenging central nervous system pathology. As with other surgical specialties, the establishment of structured academic residency programs in neurosurgery coupled to a spirit of innovation and inquiry led to a flurry of development. The difference, however, was that neurosurgeons dealt with scenarios unique to the nervous system, and found themselves then, as now, confronted with ethical dilemmas on a routine basis in their clinical practices. Issues such as brain death, withdrawal of care, autonomy of brain-damaged patients, informed consent, and the application of new and novel technology, were issues that although were not monopolized by neurosurgery, certainly acquired a new dimension for those practitioners dealing with the organ responsible for their patients personality, memory and higher human faculties.
We can think of ethical questions in neurosurgery as falling into two categories, namely those surrounding what neurosurgeons are currently doing, i.e. their current practices, and those surrounding what neurosurgeons will, theoretically, be capable of doing in the future, i.e. their future practices. Further categorizations can be made according to whether ethical questions are related to a given technology or innovation (e.g. its use, safety and efficacy) those surrounding the disease or pathology (e.g. its classification and definition), and those surrounding the patient (e.g. including their understanding of informed consent etc.; see Table 24.1. for examples).
Neurosurgery, as mentioned, does not lack ethical challenges. Patients who are moribund, comatose, terminally ill, traumatized, or at the very least neurologically unstable make up a large portion of the clinician’s challenges (Diringer et al. 2001). These patients, and their associated management challenges, are beyond the scope of this chapter, and therefore will not be addressed in great detail. Instead, we will focus on the growth of functional neurosurgery as a discipline and scientific field, which contains not only a dramatically different patient population but an entirely new set of ethical challenges and questions. For the first time, neurosurgeons have the option to electively intervene in diseases of brain function, in morphologically normal brains, with an array of novel technologies. When they should intervene, with what kind of technology, for which conditions and in which patients, are questions that are now under intense scrutiny.
Table 24.1 Classifying ethical challenges in functional neurosurgery, with examples
Functional neurosurgery is a subspecialty of neurosurgery that deals with restoration of function through stereotactic means. According to the World Society of Stereotactic and Functional Neurosurgery (WSSFN), the most appropriate definition for the field is:
…a branch of neurosurgery that utilizes dedicated structural and functional neuroimaging to identify and target discrete areas of the brain and to perform specific interventions (for example ablation, neurostimulation, neuromodulation, neurotransplantation, and others) using dedicated instruments and machinery in order to relieve a variety of symptoms of neurological and other disorders and to improve function of both the structurally normal and abnormal nervous system. (WSSFN 2009)
Although many areas within neurosurgery are fraught with ethical challenges, functional neurosurgery offers practitioners a unique set of those challenges, and will continue to do so in the years to come. This is for several reasons. It is often the case that the pathology being addressed through functional means is not visible on conventional diagnostic imaging, such as computed tomography or magnetic resonance imaging scanning. For example, movement disorders, pain syndromes, and epilepsy, with some notable exceptions, frequently have no findings on neuroimaging and diagnoses are made based on the clinical picture. Surgeons are thus effectively operating on “normal” brains, and dealing macroscopically with a process most likely taking place on a microscopic, cellular level. Furthermore, functional neurosurgery makes its primary objective to alter brain function. Nervous system pathology, such as brain tumors, aneurysms, and congenital malformations, are all associated with changes in brain function, which of course can also be a consequence of their treatment. Changes in memory and personality, for example, can accompany an indolent frontal lobe tumor, but so can prolonged retraction on the frontal lobes during the clipping of an aneurysm. In both cases, brain function is altered, in the former as a direct consequence of the disease, and in the latter as an indirect, incidental consequence of treatment. With functional neurosurgery, the primary objective is a change in brain function, be it the perception of pain, the reduction of a tremor, or the improvement of mood.
Here we will divide our discussion into the current and emerging applications of functional neurosurgery as well as the future controversies that will stem from them. Our discussion will be limited to psychosurgery, enhancement (cognitive and physical) and brain–machine interface (BMI), in order to illustrate the pertinent ethical challenges and the role of the neurosurgeon in helping to address them. Of note, psychosurgery represents less than 10% of the current functional surgeons’ clinical practice, with enhancement and brain machine interface currently under investigation only. These three applications represent natural extensions of each other, as exploration of the underlying mechanisms of psychopathology will ultimately provide insight into normal brain function. The neurosurgeon, and the neuroethicist, will by necessity need to be involved at every stage.
In 1997 the Food and Drug Administration in the United States approved the use of deep brain stimulation (DBS) for the treatment of medically refractory essential tremor (Yu and Neimat 2008). This was followed several years later by similar approval for the treatment of Parkinson’s disease and then dystonia. Its success in neurodegenerative disease and movement disorders in general, underscored the increasing utility of stimulation technology. Neuromodulation, up until then had largely been restricted to ablative procedures, which although very effective were irreversible, allowing practitioners essentially one chance to identify the correct deep brain target. DBS was not only reversible, i.e. the internalized leads can be removed or the current turned off, it allowed titration of effect, monitoring of side-effects, and facilitated double-blind, controlled trials effectively proving the utility of the technology. A detailed discussion of the proposed mechanisms of DBS is outside the scope of this chapter, but several hypotheses do exist (for review, see Dostrovsky and Lozano 2002; McIntyre et al. 2004; Montgomery and Gale 2008). Most theories center on the influence of chronic high-frequency stimulation on either inhibitory or excitatory neuronal pathways, mediated by the neurotransmitters GABA and glutamate, respectively. Whether stimulation involves a “jamming” of circuits or the promotion of specific neuronal firing rates, which facilitate physiologic functioning, is unknown. What has been recognized, however, is that stimulation in one part of the brain, for example, the globus pallidus internus, can influence the physiologic milieu in a more remote brain region, such as supplementary motor cortex (Davis et al. 1997). This suggests that various neuroanatomic regions can be influenced as distinct “nodes” along a physiologic circuit, and in this way potentially modulate activity along that circuit. The implications for disorders of not only movement, but of cognition and mood, are thus broad and far-reaching, and raise important questions about the possibility of modulating both normal and pathological behavior.
It has been known for nearly 70 years that different circuits mediate different brain functions from voluntary movement to affect (Kopell et al. 2004; Fins et al. 2006; Wind and Anderson 2008). Mayberg and colleagues hypothesized that since it is known that the cingulate cortex is involved in a specific cortico-striato-thalamo-cortical circuit mediating the brain functions believed dysfunctional in depression, then modulation of the cingulate with stimulation should attenuate those maladaptive behaviors (Mayberg et al. 2005). Done together with a team of neurosurgeons, the first study examining DBS for depression, showed that four of six study patients achieved “…sustained clinical response or remission at the end of six months” (Mayberg et al. 2005). The age of modern neurosurgery for psychiatric indications had effectively been reborn, now with a stimulation twist.
The study was picked up and reported widely in the popular press. Newspapers, magazines and television news reported the successful treatment of refractory depression with brain surgery and touted its potential and promise (Canada.com 2009; Globe and Mail.com 2009). Similar attention had greeted the results of other studies with DBS in the movement disorder literature, reflecting a trend of increasing media attention to the neurosciences and to neuromodulation in particular (Racine et al. 2007). Clearly, the idea of “brain implants” affecting human mood and behavior, tapped into a collective public interest in the brain and its inherent mysteries; the presence of mind control, brain chips, androids, and telekinesis in the science fiction and general literature speaks to that interest as well.
The principal investigators of the Depression study, wary of the tarnished past of “psychosurgery” had selected patients carefully, with independent review by psychiatrists and involvement of family members at all stages of the study. Ethical issues and their consideration permeated the study, and were given as much attention as other methodological details in the final manuscript. Indeed, attention to the acquisition of informed consent, independent review and patient selection, as well as proper post-procedural follow-up have become staples of any manuscript attempting to present clinical evidence of stimulation effectiveness for any psychiatric indication. The tentative, early success in depression spurred researchers to explore DBS for other psychiatric indications. Although reports of DBS for refractory obsessive–compulsive disorder (OCD) had been known for at least 2 years prior to the DBS and depression study, research and trial development accelerated after 2005. Several high quality trials, including at least one randomized double blind study (Mallet et al. 2008), have been done and are in progress evaluating DBS for depression, OCD, Tourette’s syndrome and alcoholism (Kuhn et al. 2007; Zabek et al. 2008; Mink 2009). In parallel with the seemingly exponential growth, and interest, in surgical psychiatry, the bioethics literature has grown correspondingly, and neuroethics emerged as a result of the growing advances in the neuromodulation field (Glannon 2006).
Despite the early successes, it appears that the specter of surgery for psychiatric indications is still unnerving to some in the healthcare community, as well as in the media and general public. Most likely, this is due to a perceptual error, that generates a natural resistance to and fear of an external agent, be it another individual, a chip or an implanted electrode, taking ownership over one’s own mind. The thought of an external force applied to change one’s thoughts and behaviors, in general, is unappealing, and has been the source of many a Hollywood horror film. Whether it is a positive change, defined as a change resulting in some alternate action not in keeping with the individuals’ interests (e.g. aliens or government agents controlling the mind and body) or a negative change, defined as a change resulting in the individual being stripped of their ability to act (e.g. zombies) people find the idea of mind-tampering disturbing. Precisely why this is disturbing is unclear, but most likely has something to do with the inability to conceive of oneself as being disconnected from one’s own sense of self. Feelings such as deja vu, depersonalization, and even migrainous or pre-ictal auras, are all associated with similar “strangeness” and discomfort that one cannot describe but can instantly recognize. Is this the cause of the general fascination, and possible trepidation, surrounding the idea of neuromodulation?
We conducted a qualitative interview based study asking patients undergoing neurosurgery for brain tumors, who are presumably well versed in the risks of surgery, about their attitudes towards surgery for psychiatry, identity change and neuro-enhancement (Lipsman et al. 2009). Patients were, perhaps surprisingly, overwhelmingly in favor of surgery for psychiatric disease citing the prerequisite importance of informed consent and the proven safety and efficacy of a given intervention. Also surprising was that patients viewed the hypothetical enhancement of a negative trait, for example greed or short-temperedness, as less ethically troublesome than the enhancement of an ostensibly normal trait, such as improving one’s mood from average to above average. Not only did patients not universally dismiss neuromodulation for pathological states they expressed some approval for modifying non-pathological traits as well. Could it be that societal and cultural conditions are changing, and that neuromodulation, for pathologic indications or not, is not as unpalatable as it once was?
Definitions of enhancement have been difficult to formulate and are perhaps made more difficult in the context of functional neurosurgery. Does improving the mood of a depressed patient count as enhancement? Does one need to exclude the presence of pathology and focus only on the improvement from a seemingly “normal” state? Most modern definitions focus on the latter, with enhancement being generally defined and understood as an “improvement in the absence of medical need” (DeGrazia 2005). According to this definition, neurosurgeons have yet to be involved in the application of true enhancement technology. However, any member of a functional neurosurgical team who has seen the results of surgery for psychiatry, pain, movement disorders, or epilepsy, knows that this is not the case. We propose that definitions of enhancement include any improvement in functional status, cognitive or physical, as measured by objective, standardized measures, that allow the subject to engage in or perform activities otherwise not possible as a direct consequence of their pre-enhancement state. With this definition, a depressed patient that resumes their occupation following DBS would have been enhanced, as would a hearing impaired child who has received a cochlear implant, and a hypothetical patient of the future who receives memory enhancement technology to achieve a better SAT score. More than simply an “improvement,” enhancement needs to demonstrate objective evidence that there has been a change, beyond that possible without the aid of technology. Distinguishing medical or therapeutic enhancement, from elective or “non-medical” enhancement, implies an endorsement of one, the former, and a rejection of the other, the latter. By removing health and pathology from the definition, we are including both possibilities.
As with all medical applications, improving the lives of the healthy must not come at the expense, be it financial or otherwise, of improving the health of the ill and disabled. The role of BMI, DBS, motor cortex stimulation and gamma-knife radiosurgery as they all relate to pathology must be well enough established prior to exploring their use in healthy populations. That ethical imperative must remain unwavering, and accordingly, the involvement of neurosurgeons in enhancement technology should be focused largely on how that improvement in health will come about. However, two points need to be mentioned, both related to the enhancement definition posed above. First, as cultural definitions of disease evolve and change, the notion of patient health will change accordingly. As diagnostic criteria contract and expand with increasing knowledge and research, as well as the changing proclivities of the societies that prescribe them, one generations ill and disabled may be another generations normal variant, and vice versa. As several authors have argued, to base a definition of enhancement on what is “normal” or “healthy” will in due course prove to be inadequate (Hansson 2005). Second, although neurosurgery’s involvement in enhancement and its expanding role in psychiatry is still in its infancy, neurosurgeons must be engaged now, prior to developing trials and engaging in clinical research, to ensure their research is ethically oriented. This will be of particular importance when researchers begin to tackle some of functional neurosurgery’s most fascinating, and controversial, applications.
The application of DBS and other implantable technology to patients in a minimally conscious state (MCS) (Schiff et al. 2007; Schiff 2009) as well as those who have suffered the devastating effects of motor-neuron disease or strokes (Birbaumer et al. 2009) has shown some promise. In the former, DBS allowed a patient in a MCS to obtain statistically significant “functional improvement” (Schiff et al. 2007). With such studies, motor volition and consciousness itself are the respective substrates, but the theoretically possible substrates are limited only by the myriad functions of the human brain. As in plastic surgery, where technology and innovation first meant to treat pathology and disfigurement was ultimately used for elective, aesthetic procedures, we have previously used the term cosmetic neurosurgery to prophesy a similar direction in functional neurosurgery (Lipsman et al. 2009). Clearly, however, important differences exist between cosmetic plastic surgery and neurosurgery for cognitive or physical enhancement. The brain is the seat of memory, affect, and personal identity, all of which can potentially be altered with neurosurgical operations. Further, as a science we are very far from understanding the anatomy, let alone the physiology and circuitry of many of the traits and conditions that some have hypothesized will be the targets of enhancement, or modification, such as memory or creativity. Also, issues such as fair and equal access to enhancement technology are much more salient and carry much broader societal and cultural implications when discussing memory enhancement, for example, versus breast augmentation. Despite these differences, however, similarities do exist, but need to be compared on an equal footing: if the science is far enough along, and strict federal regulations are put in place, one can easily argue that a personality “defect” such as predilection to addiction, or even greed and pessimism, are more “harmful” or disruptive to one’s life than a smaller than average bust size. Is enhancement with a safe and effective technology not permissible then? We are currently conducting several qualitative studies gauging the attitudes of neurosurgery patients, and neurosurgeons towards these and similar questions. Preliminary results look promising, and suggest that, as with our previous results, individuals find the correction of a negative personality trait ethically permissible, and the improvement of a “normal” trait or the use of neuromodulation in a coercive setting (e.g. with prisoners) as ethically ambiguous at best, and generally inappropriate.
Neurosurgeons, and their collaborators, will need to consider these questions soon. With regards to psychosurgery, as functional imaging, tractography, tracer studies and animal models evolve and improve, questions will shift from what drives a certain behavior to how can the behavior be prevented or modified. Several centers have already reported results on DBS for alcoholism (Kuhn et al. 2007), obesity (Halpern et al. 2008), and hypothesized targets for schizophrenia (Mikell et al. 2009), just as some critics argue that the biology of these diseases and others for whom DBS has been considered are not close to being understood. Until then, they argue, surgical treatment should not be performed. This is only partially true. Most centers have used DBS as a last resort, and moreover as a research tool to learn more about the diseases in question. Few, if any, centers are suggesting that DBS or any neuromodulation procedure will cure psychiatric disease, but all centers judiciously report their results in an effort to identify important targets, eliminate dangerous or ineffective ones and further our knowledge about the underlying circuitry of these conditions. Importantly, as the conditions that become candidates for surgical treatment change, ethical issues, such as adequate informed consent and respect for patient autonomy, remain unchanged and indeed acquire an additional complexity. The adequacy of proxy consent, the impossibility of foretelling all known risks and the questionable voluntariness of sometimes desperate and often unstable patients, remain unaddressed and will be sources of future investigation.
The future of enhancement in a neurosurgical context will likely involve a significant overlap with BMI. Some authors have already hypothesized about the potential uses of implantable technology and how these will change the face of society and what it ultimately means to be human: “Brain-machine interfaces will put new forms of stress on privacy, autonomy, and justice, and more importantly, on what it means to be human” (McGee and Maguire 2007). Although some of their predictions sound like science fiction to us, they are right that the time to establish regulations is now. Certainly, as technology is made available that will provide paralyzed patients with greater independence and strength; similar technology will gradually begin to be adapted to less severe pathology and eventually to healthy individuals. One can easily envision a DBS device or subdural recordings that guide the thought evoked movements of a quadriplegic patient, being applied to a hemiplegic patient, and then to a victim of stroke with a mild deficit, and ultimately, to a healthy fighter pilot acquiring targets with his mind. Each step is in turn accompanied by further debate, and a shift in cultural values and definitions of “impairment.”
Concerns about the future of implantable technology, and the neurosurgeon’s role in installing them, need to be addressed. The issues of privacy of thoughts and actions, and even the loss of human nature and the changing dynamic between society and the individual, are not minor and reflect a general fear that enhancement and/or implantable technology will either: (1) be usurped for less than noble means; (2) represent a shift towards a paternalistic, big-brother society; or (3) either create chasms of inequality between the enhanced or unenhanced, or homogenize society so that aptitude, cognitive or physical, will be commonplace and effectively mundane. All are valid concerns, but not insurmountable, given adequate preparation and transparent discussion. The future practice of the functional neurosurgeon will involve several points of contact with a multidisciplinary team that will, by necessity, include non-medical members. Between development and implementation, the surgeon’s role will be to synthesize the legal, ethical, and moral dimensions of a proposed intervention as he or she will ultimately be responsible for the pre- and postoperative care of these patients. This can start now, with clinical trials that recognize the value of oversight, supervision and transparency, as well as the active involvement of neurosurgeons in ethical debates surrounding implantable and enhancement technology.
In July of 2009, the Journal of Neurosurgery, the flagship publication of the American Association of Neurological Surgeons published a special issue on the development and promise BMIs. Among articles exploring the science and clinical perspectives of the technology, an official statement from the National Institute of Neurological Disorders and Stroke outlined their fervent support for BMI in improving the lives of stroke patients and those stricken by neurodegenerative disease. “[BMI] offers the promise of restoring communication, enabling control of assistive devices, and allowing volitional control of extremities in paralyzed individuals” (Pancrazio 2009). Although both the National Institute of Health and NINDS have a long history of funding research into BMI, most notably leading to cochlear implant technology, their statement in a neurosurgical journal is significant. It recognizes that neurosurgeons will be involved in many of the developmental steps in BMI, from conceptualization to implementation and that engaging them early is vital to progress in the field.
The future applications of functional neurosurgery, including psychiatry, enhancement and BMIs, are certainly exciting and hold much promise. Within the cast of characters, the neurosurgeon will play a prominent role, not only in research and implementation but also hopefully in allaying the fears that the technology may foster. One important step is recognizing that we cannot use the highly hypothetical, often fanciful scenarios quoted in the implant literature, which strike equal parts fear and excitement in the reader, to establish current regulatory guidelines. We are indeed very far off from our brains melding into machines and from being able to download our brains onto microchips. Instead, those interested in the development of the field need to work together to identify the weaknesses of current research, and to immunize protocols and designs at an early stage from the detractors who will question their merits and value (Fins et al. 2006; Kimmelman et al. 2009). Bioethicists interested in neuromodulation have all ready begun this important work, and are identifying vulnerabilities in functional research that may hamper further progress (Bell et al. 2009; Ford 2009).
Wilder Penfield’s participation in the mind–body debate was both prescient and ahead of its time. Surely he would have been fascinated with the latest developments in the search for the cortical representation of self and consciousness that is now an intense area of investigation (David et al. 2008; Schwartz and Schwartz 2008; Immordino-Yang et al. 2009). Although his legacy in epilepsy surgery and brain mapping will continue to live on, he was also the first neurosurgeon to engage the non-surgical world in a conversation about the mind, philosophy, and ethics, and grounded his opinions in clinical research. He saw beyond the brain, and explored the mind, and recognized the chance that neurosurgeons have on a daily basis to explore the most human of human qualities: our selves. The future of functional neurosurgery will involve building on that legacy and exploring corners of the mind previously out of reach to clinicians and philosophers alike.
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