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Deep brain stimulation (DBS) is a powerful clinical tool that has provided remarkable therapeutic benefits for otherwise treatment-resistant movement and affective disorders. The precise mechanisms of action for DBS remain uncertain but are likely to result through causal manipulation of both local and distributed brain networks. Recently, non-invasive neuroimaging methods such as magnetoencephalography have started to be used in conjunction with DBS in order to map the fundamental mechanisms of normal and abnormal oscillatory synchronization underlying human brain function. This chapter begins with an introductory overview of the current state-of-art of DBS and the previous use of neuroimaging techniques with DBS. It then describes the methods and results of using MEG to measure both low and high frequency stimulation. It discusses the importance of the findings, as well as potential confounds and future possibilities of combining MEG and DBS.

This chapter describes the effects of deep brain stimulation on speech in Parkinson's disease (PD). The process involves the implantation of two electrodes either in the ventro-intermediate nucleus (Vim) of the thalamus, or the globus pallidus internum (Gpi) or the subthalamic nucleus (STN), depending on the symptomatology. Speech outcome is variable following DBS in the STN with improvement noted in some acoustic measures and oro-motor non-speech tasks, but deterioration of speech intelligibility in the majority of patients. Factors affecting speech response following STN-DBS are partly surgical, i.e., current spread and contact location. There is the need for further research into ways speech is affected by deep brain stimulation in order to maximize the benefits of the treatment.

Besides pain, Parkinson's disease represents an excellent model to study the neurobiological mechanisms of the placebo effect. The placebo effect in Parkinson's disease is mediated by dopamine release in the striatum and is associated to changes in activity of neurons in the subthalamic nucleus. The therapeutic effects of deep brain stimulation are powerfully modulated by placebos as well. As to migraine, although migraine clinical trials show very high rates of improvement in those patients who received placebo, the underlying mechanisms are not known. Many other neurological diseases, like epilepsy, show improvements in placebo groups, but the mechanisms are completely unknown.

This chapter considers the use of deep-brain stimulation as a treatment for neurological and psychiatric disorders. It addresses the question of whether a person with a disease of the mind can consent to stimulation of the brain, and how patients and medical teams weigh the potential benefits and risks of the treatment. It also describes some of the trade-offs between physical and psychological effects of stimulation. The medical and moral justification of this technique depends not only on whether it corrects brain dysfunction but also on how it affects all the psychological properties of the person.

Over the past several decades, models of basal ganglia function that describe the pathophysiology of Parkinson disease (PD) have emerged from studies in both nonhuman primates and rodents. One influential experimental paradigm has relied upon infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a piperidine derivative, to acutely induce irreversible symptoms of Parkinsonism, including bradykinesia and rigidity, in animals. Investigators then use electrophysiological recordings in specific basal ganglia nuclei and cortical areas to relate behavioral deficits with electrophysiological recordings. Based on this experimental paradigm, clinically relevant models of basal ganglia and cortical function have been developed, and these models have led to new therapeutic interventions in humans with PD, such as deep brain stimulation. However, since the MPTP model causes a rapid degeneration of most of the cells in the substantia nigra, its significance for early-stage PD is less clear, because the development of PD symptoms in humans occurs more gradually. In addition, these models typically characterize the motor deficits of PD, with less focus on the nonmotor deficits of PD. In humans, most behavioral and brain imaging studies in PD have focused on patients with the disease who are more advanced in their symptomology, and who have already received symptomatic treatment. This can make it difficult to isolate the effects of the disease itself from the effects of the treatment on brain activation and behavior. As such, this chapter focuses on what is currently known regarding the motor and nonmotor features of patients with early-stage PD who have not yet started any symptomatic treatment (i.e., de novo PD). A substantial part of the chapter examines brain imaging studies of de novo PD.

This chapter summarizes the contribution of imaging to the current understanding of the mechanisms underlying surgical interventions for PD. Structural imaging studies using MRI techniques have served to improve the accuracy of stereotaxic targeting. That said, functional imaging with positron emission tomography (PET), single photon emission tomography (SPECT), and fMRI have provided an in vivo method to assess changes in brain function in the vicinity of the surgical target and in remote, interconnected brain regions within a spatially distributed neural network. This chapter provides an overview of functional/anatomical models of basal ganglia circuitry, followed by a discussion of the changes mediated by surgery at both the regional and network levels. Specific attention is dedicated to the effects of deep brain stimulation (DBS) on network organization and on disease progression.

Parkinson’s disease (PD) tremor has been found to be a variable clinical feature of the disease both across patients and within individual patients over the disease course. Clinical ratings of tremor severity have been found to have limited utility as objective measures of this poorly understood disease manifestation. Recent advances in functional neuroimaging methods have, however, provided new insights into the pathophysiology of PD tremor. This chapter reviews concepts of tremor pathogenesis in PD in light of recent imaging studies and discuss the use of imaging methods to differentiate tremor due to PD from essential tremor (ET). The chapter also provides an in depth discussion of the potential utility of image-based tremor biomarkers in delineating the natural history of PD tremor and in the objective assessment of its response to specific therapeutic interventions such as deep brain stimulation (DBS).

This chapter summarizes techniques used for the placement of deep brain stimulation (DBS) electrodes. These procedures are performed primarily for the treatment of movement disorders such as Parkinson's disease, essential tremor, and dystonia. We describe radiologic atlas-based targeting using computed tomography and magnetic resonance imaging, physiological localization using microelectrode recordings, and macrostimulation techniques. We summarize the standard intraoperative surgical and mapping procedures used to localize the ventral intermediate nucleus of the thalamus (Vim), sub thalamic nucleus (STN), and globus pallidus pars interna (GPi).

Psychiatric neurosurgery is defined as neurosurgery for treating psychiatric disorders that do not have identified structural brain anomalies. Early psychiatric neurosurgery procedures such as lobotomy became discredited in the 1970s because of severe complications. After a nearly 30-year hiatus until the late 1990s, psychiatric neurosurgery experienced a revival. Today, modern psychiatric neurosurgery is more precise and safer than its historical predecessors. Deep brain stimulation has become an established treatment for treatment-refractory Parkinson’s disease, and has been tested in several hundreds of patients with different psychiatric disorders. Reports about its successful application have also stimulated the development and application of ablative psychiatric neurosurgery such as thermal or radiofrequency ablation, as well as Gamma Knife^® radiosurgery and magnetic resonance-guided focused ultrasound. This chapter analyzes the pros and cons of a range of different existing and emerging psychiatric neurosurgical procedures and evaluates them ethically.

It is clear that management of tinnitus requires alterations of neural activity in the CNS. The neural substrates of tinnitus suggest various approaches to modify neural processing and change the properties of tinnitus and so obtain some alleviation of it. The interventions for tinnitus include compensation of missing activity in the output of the cochlea via specially tailored acoustic environments, and via amplification of environmental sounds in the hearing frequency range, i.e., by hearing aids. In deaf persons the missing sounds can be applied by a cochlear implant. A non-invasive method that may be useful to suppress tinnitus is based on trans cranial magnetic stimulation. Tinnitus Retraining Therapy and cognitive behavioral therapy are effective in reducing the annoyance and impact of tinnitus. Pharmacological approaches have so far produced disappointing results in humans and the somewhat more promising findings in animals.

The phrase “brain stimulation” conjures a vast range of emotions from different segments of society, with fear or apprehension being a common and understandable reaction. The brain reigns as the control center for breathing, eating, and moving, to relating, feeling, and understanding. Changing these functions with electricity or magnetism can fundamentally change how we interact with our environment and one another. Even if this change is beneficial, there can still be a cause for concern. Brain stimulation technologies are currently used for several therapeutic purposes, but they also have the potential for enhancing those without an illness. Enjoying the advantages that enhancement might bring could be intoxicating, as can be the case with having great wealth, prestige, beauty, or athletic ability. This chapter explores the implications of such possible enhancement uses, as well as the notion that it could create a dependence on the stimulation akin to an addiction.

Besides pain, Parkinson’s disease represents an excellent model to study the neurobiological mechanisms of the placebo effect. The placebo effect in Parkinson’s disease is mediated by dopamine release in the striatum and is associated with changes in activity of neurons in the subthalamic nucleus. The therapeutic effects of deep-brain stimulation are powerfully modulated by placebos as well. As to migraine, although migraine clinical trials show very high rates of improvement in those patients who received placebo, the underlying mechanisms are not known. Recent research suggests that the cyclooxygenase–prostaglandins pathway could be involved. Many other neurological diseases, like epilepsy, show improvements in placebo groups, but the mechanisms are completely unknown.

Neuroethics traditionally pays little attention to neural degeneration and regeneration, areas central to much of current neuroscience. Underlying these interests is the ongoing plasticity of the mature brain, and the ability of stem cells to produce new neurons in adult life. Against this background there have been many attempts to tackle the motor deficits of Parkinson’s disease using neural grafts. The succession of clinical trials since the late 1980s is traced to assess the extent to which symptoms are alleviated by implanting fetal midbrain grafts. The results are ambivalent with some limited improvements in some patients. The part played by a paradigm of optimism is highlighted, while ongoing problems revolve around clinical equipoise, and the place of controls. Deep brain stimulation raises questions of authenticity and alienation. Both approaches to treatment point to the importance for ethics of an appreciation of fundamental understanding of brain connectivity, complexity, and ongoing neurogenesis.

This chapter summarizes the primary-process (“core”) positive emotions that are the birthrights of mammals and the foundations of the human mind, and which are next to impossible to understand through human research alone. However, the use of affective neuroscience strategies in animal emotion research provides novel paths toward a better understanding of primal human emotions and how they can move in and out of balance. The goal of this chapter is to 1) provide historical background into the study of human and animal emotions, 2) summarize cross-species work on positive core-affects through current animal research, 3) describe the subcortical emotion circuits that promote positive affects, and 4) discuss how affective neuroscience strategies can be used to facilitate development of positive affect enhancing psychotherapies. Acceptance of a cross-species strategy to such issues, long resistant to scientific analysis, promotes research efforts that can lead to a deep neuroscientific understanding of positive affects and their beneficial effects on human thriving and resilience.

Deep brain stimulation (DBS) for psychiatric illness raises challenges for informed consent. Some of these are well recognized, such as vulnerability and unrealistic expectations, problems with capacity to consent, and scientific and safety uncertainties in implantable device research. The next generation of DBS for treatment of psychiatric illnesses may be closed-loop (or brain–computer interface-modulated) or volitionally controlled. That is, the activity of deep brain stimulating electrodes will be modulated with feedback from additional cortical or deep brain implanted recording electrodes. Six challenges for informed consent in next-generation psychiatric DBS are reviewed. These challenges are illustrated by expanding on results of a recently published qualitative study of individuals in research trials of DBS for depression and obsessive–compulsive disorder. An argument is offered that engaging with end users and potential end users of neural devices about ethical concerns is an important step in improving informed consent practices related to emerging neurotechnologies.

The chapter first describes the policy options that are available to policy makers to regulate research, marketing, and individual use of cognitive enhancement technologies. It then examines the current legal landscape regarding these technologies and the range of policy issues they raise. In order to illuminate the difficulties and subtleties facing policy makers, the chapter then analyzes the policy options pertinent to a range of drugs, devices, and procedures used for enhancement Although all potential enhancement techniques elicit similar broad policy concerns, they differ widely in efficacy, potential usage, and risk. The chapter also discusses competing ethical frameworks that might guide public policy on cognitive enhancement drugs or devices and examines what, if any, boundaries of social justification there are for mandatory use, regulations, economic incentives and disincentives, or prohibition of cognitive enhancement technologies.

As investigators look to “next-generation” deep brain stimulation (DBS) approaches, renewed enthusiasm is emerging for DBS for psychiatric disorders. This commentary on Chapter 13 (“Informed Consent for Next-Generation Deep Brain Stimulation Psychiatric Research: Engaging End Users to Understand Risks and Improve Practice”) provides additional insight into the challenges related to informed consent described by Klein. We argue that the sorts of vulnerability described by Klein warrant further attention, in particular, to help address the question of whether patients with psychiatric disorders are uniquely vulnerable, in ways that patients with other illnesses are not. Ethics research, such as that conducted by Klein, in which end users of brain-based devices are interviewed, is critical. It will also be important to compare brain-based intervention research with other forms of research; we do not want to end up engaging in ethics “exceptionalism” as a result of failure to conduct rigorous studies on ethics-related questions.

Deep brain stimulation and wireless deep brain stimulation have the potential to reduce or control violent dispositions. This raises the question of whether enhancing the morality of those who are likely to harm others is ethically acceptable. The implications of controlling harmful dispositions for free will is a feature of the enhancement debate, and it was a feature of worries about other techniques earlier in the twentieth century. In A Clockwork Orange, Burgess expresses the concern that a new technique that controls the violent dispositions of the central character in the book and film, Alex, violates him as a person. This chapter distinguishes a number of worries about the treatment given to Alex, and argues that we should not be concerned that altering dispositions in this way removes free will, if the conditions described in the chapter are met. Neurointerventions to control desires can be ethical when they are consistent with a person’s second-order volitions about the kinds of desires they wish to act upon. So long as a person can genuinely fit new dispositions within a stable self-conception, these new dispositions seem to enable rather than violate their free will.

As its name implies, the main characteristics of obsessive-compulsive disorder (OCD) are obsessions and/or compulsions. Different types of obsessions and compulsions make OCD a heterogeneous condition. Also, OCD exists on a continuum from mild cases to those with extremely severe and incapacitating manifestations generally not seen in other anxiety disorders. Clinical manifestations of OCD are striking and leave few people who observe them unimpressed. This is arguably due to the seriousness with which persons with OCD take their own obsessions and compulsions along with concurrent realization that these same obsessions and compulsions are senseless and should be gotten rid of. Indeed, there are few other examples in psychopathology where insight and deficiency of insight stand together, and where espousing and fighting the absurd are so intertwined. For all these reasons, OCD is often portrayed as a puzzling or intriguing disorder; in addition, it often represents a treatment challenge. Obsessive-compulsive disorder is probably the least controversial condition within the anxiety disorders because its clinical features are well described and relatively easily recognized and because hardly anyone doubts its existence as a psychopathological entity. What is controversial about OCD, however, is where it belongs and how it should be classified. This is a consequence of a number of features of OCD that make it look different from other anxiety disorders and of the close relationship that OCD has with some conditions outside of the realm of anxiety disorders. Listed below are a number of key questions about OCD…. 1. In view of its different clinical features and the vastly different severity of these features, should OCD be considered a unitary condition or divided into subtypes? 2. If OCD is to be divided into subtypes, on the basis of what criteria should it be done? Types of obsessions and compulsions, reasons for performing compulsions, severity of illness, degree of insight, age of onset, or something else? 3. Should neutralizing responses other than compulsions be given a more prominent role in the description and conceptualization of OCD? 4. How does insight contribute to the conceptualization of OCD? 5. What are the core features of OCD? Is OCD primarily an affective disorder, is it characterized by a primary disturbance in thinking, or is it essentially a disorder of repetitive behaviors?