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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.

Transcranial magnetic stimulation (TMS) is a neuroscientific technique that induces an electric current in the brain via application of a localized magnetic field pulse. The pulse penetrates the scalp and skull non-invasively and, depending on the parameters of stimulation, facilitates or depresses the local neuronal response with effects that can be transient or long lasting. While the mechanisms by which TMS acts remain largely unknown, the behavioral effects of the stimulation are reproducible and, in some cases, are highly beneficial. This chapter reviews the technique in detail and discusses safety as the paramount ethics issue for TMS. It further examines the ethical arguments for and against neuroenhancement with TMS and how the framework for acceptable practice must differ for patient and non-patient populations.

This chapter considers possible defenses of the claim that the conscious aspects of experience supervene on the experiencing subject's brain. Considerations discussed include the very occurrence of hallucinations, thought experiments, brain stimulation experiments, and facts about the way the brain processes visual information. It is then shown how the theory of hallucination presented in Chapter 4 can explain conditions such as akinetopsia and achromatopsia and how the ‘binding problem’ can be solved. The chapter concludes with an explanation of how this theory can accommodate the intuition that a subject whose brain was artificially stimulated in exactly the same way as it would have been stimulated in a veridical case would have an utterly convincing hallucination.

This chapter examines the ethical issues raised by new technologies that allow investigators to monitor and control the brain, and how they are distinctive from those raised by other medical technologies, such as genetic testing. It begins with a brief review of some new technologies that have emerged from neuroscience. These devices are intended to stimulate selected regions of the brain or peripheral nervous system for therapeutic purposes, or, more recently, as brain-computer interfaces to allow the brain to exchange information with the outsideworld through direct recording of potentials measured by means of electrodes implanted in the motor cortex, or placed on the surface of the head.

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 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.

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 examines the neural bases of aggression and describes how they affect human functioning. It describes the results of lower animal research on the effects of brain stimulation and lesioning. It identifies the brain stem and the limbic system as important neural influences on aggression. The findings of stimulation studies indicate that aggressive behaviours can be produced in several species and the primary areas concerned are the hypothalamus, amygdala, and the central gray of the midbrain.

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.

Transcranial Magnetic Stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique increasingly utilized in clinics and research laboratories around the world. Exploiting the properties of electromagnetic induction, TMS can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized, time-varying magnetic field pulses. Until recently, the ethical considerations guiding the practice and application of TMS were largely concerned with aspects of subject safety and patient population in controlled clinical trials or experimental protocols. While safety remains of paramount importance, the recent approval by the Food and Drug Administration (FDA) in the United States of the Neuronetics NeuroStar. TMS device for the treatment of certain patients with medication-resistant depression has engendered a surfeit of unexamined ethical concerns. Some of these are nuanced elaborations of previously-addressed issues, but others-such as matters of training and certification, marketing, and possible off-label use-represent recent and complex concerns. These issues are likely to be relevant to a rapidly-growing number of patients, as the possible uses for TMS and other developing forms of brain stimulation (both invasive and non-invasive) expand to include the treatment of a wide range of neuropsychiatric conditions. This chapter provides an overview of these emerging issues and discusses ways in which some of them might best be addressed.

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 discusses the history of the so-called anhedonia hypothesis. The term anhedonia was first used in 1978 in connection with the assertion that pimozide blocks the reward quality of food. The anhedonia hypothesis was based largely on studies of psychomotor stimulant, brain stimulation, and food and water reinforcement. It also discusses brain stimulation reward, opiate reinforcement, and several other drugs of abuse that activate the dopamine system.

Therapies treat diseases, while enhancement improves normal abilities. We have referred to this notion of inorganically boosting the neural functions of healthy individuals as “cosmetic neurology.” In the past decade, noninvasive brain stimulation techniques, especially transcranial direct current stimulation (tDCS), has been used increasingly in experimental settings to transiently enhance performance in otherwise healthy individuals. In this chapter, we will survey recent cognitive neuroscience studies in which tDCS has been used to manipulate and enhance cognition in a variety of cognitive domains including executive functions, language, learning and memory, and visuospatial abilities. We will also review a few illustrative areas in which recent studies seem to support the use of tDCS for potential real-world applications. Based on the assembled evidence presented in this chapter, we conclude that there is still much to be investigated about the specific tDCS parameters before its widespread applications in cognitive enhancement.

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 aim of this chapter is to contribute to the discussion of the cognitive neuroscience of brain stimulation. In doing so, the authors emphasize work from their own laboratory that focuses both on working memory training and transcranial direct current stimulation. Transcranial direct current stimulation is one of the most commonly used and extensively researched methods of transcranial electrical stimulation. The chapter focuses on implementation of transcranial direct current stimulation to enhance and inform research on working memory training, and not on the underlying mechanisms of transcranial direct current stimulation. Thus, while respecting the intricacies and unknowns of the inner workings of electrical stimulation on the brain, the chapter relies on the premise that transcranial direct current stimulation is able to directly affect the electrophysiological profile of the brain and provides evidence that this in turn can influence behavior given the right parameters.

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).

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.

This chapter explores the anatomical and temporal origins of the experience of will. It examines issues of where the will arises by considering first the anatomy of voluntary action—how it differs from involuntary action and where in the body it appears to arise. The chapter then moves on to the sensation of effort in the muscles and mind during action to learn how the perception of the body influences the experience of will, and then looks directly at the brain sources of voluntary action through studies of brain stimulation. These anatomical travels are supplemented by a temporal itinerary, an examination of the time course of events in mind and body as voluntary actions are produced.