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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).

This chapter examines neuromodulation for some neurological and psychiatric disorders. Deep brain stimulation (DBS) has been used experimentally in attempts to increase the levels of awareness and other cognitive and motor functions in patients with prolonged disorders of consciousness. Studies showing limited functional recovery after use of this technique raise questions about whether or to what extent these patients can benefit from it. DBS and responsive neurostimulation (RNS) may prevent or reduce the incidence of epileptic seizures by modulating electrical activity in the cortex. Although activation of electrodes modulates the electrical activity in their brains, people with these implants can turn them on and off and regulate the frequency and duration of the stimulation. There is both unconscious control by the implant and conscious control by the person with the implant. This conscious control can make persons responsible for how they use the devices and the consequences of this use. DBS can also enable people with addiction and aggressivity to inhibit hyperactivity in brain regions associated with these disorders and regain control of their behaviour. This includes not only physical actions but also the cognitive ability to foresee the probable consequences of activating and deactivating the device. The chapter also examines questions about fairness in access to neurostimulation devices in studies and clinical trials.

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 is dedicated to motor disorders, first and foremost Parkinson’s disease, the area together with pain where most of the knowledge about the mechanisms of the placebo effect comes from. 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, substantia nigra pars reticulata, and motor thalamus. Deceptive verbal instructions about changes in drug dosage can affect the pharmacological effect of levodopa in the treatment of Parkinson’s disease. The therapeutic effects of deep brain stimulation are powerfully modulated by placebos. Migraine is another disease of the nervous system that shows very high rates of improvement in patients who received placebo, although the mechanisms are little understood. Other neurological diseases, like epilepsy, show improvements in placebo groups, but the mechanisms are not known.

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.

This chapter discusses different techniques to treat pathologies of forgetting and remembering. Deep brain stimulation can modulate hypoactive engram cells and synaptic connections in the hippocampal–entorhinal circuit or other cortical regions to improve memory encoding and retrieval. This same technique can modulate hyperactivity in the hippocampal–amygdala circuit to weaken or suppress emotionally charged memories. It can also erase memories by inducing electrophysiological silence in neurons associated with the memory trace. The chapter also explains the design and mechanism of a hippocampal prosthetic to restore encoding and retrieval in people with damaged hippocampi resulting in spatial, working, semantic, and episodic memory impairment. By regulating neural firing patterns necessary to form and access memories, this prosthetic could ameliorate anterograde and retrograde amnesia. Like other neural prosthetics, this would depend on how well the hippocampal prosthetic integrated into the brain and interacted with multiple cell fields in the declarative memory network. Although this prosthetic would not select some memories as being more meaningful than others in forming a personal narrative, its ability to restore encoding and retrieval functions would be necessary for this constructive process.

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.

This chapter provides an introduction to Parkinson’s disease (PD) for the nonmedical specialist reader. It covers the history and prevalence of PD, the disease process and its symptoms (motor and non-motor), disease diagnosis, the stages of Parkinson’s, rates of progression, and treatment approaches. Although no form of treatment stops the disease process, there are treatments that can ease its symptoms. These approaches include pharmacological options, such as carbidopa/levodopa; technological devices, surgical interventions, such as deep brain stimulation; and lifestyle practices, such as regular vigorous exercise. The latter has also been shown to slow disease progression. The chapter concludes with a description of current and future research into treating and possibly stopping the progression of Parkinson’s disease.