Brief history of electrical cortical stimulation: A journey in time from Volta to Penfield.

OBJECTIVE: To recount the evolution of Electrical Cortical Stimulation (ECS) in localizing brain functions with an emphasis on epilepsy, and a discussion of related instruments and personnel. DESIGN/METHODS: Literature review through historical archives implementing chain-referral sampling. RESULTS: There were important milestones leading to the incorporation of ECS into practice: 1. Aldini's (1802) first known stimulation of exposed brain to defend Galvani's views on excitability in the frog-leg experiment against Volta's, ironically by employing the Voltaic pile. 2. Animal experiments in the 19th-century to study the brain and to optimize the procedure: Rolando (1809) reported on motor induction, Fritsch and Hitzig (ca. 1870) introduced the concepts of bipolar and threshold stimulation, and Ferrier (1873) generated reproducible homunculi in animals. 3. Parallel to 2, advances were made based on clinical observations by Bravais, Todd, Jackson, and Broca among others. 4. First known stimulation in conscious humans by Bartholow (1874) led to catastrophic outcomes. Horsley (1886) performed first intraoperative stimulation on Jackson's epileptic patient. 5. Advances accelerated in the first-half of the 20th century with Cushing (1909) performing first awake-craniotomy eliciting sensory responses to Penfield's work culminating in standardization of clinical use and generation of detailed maps including the famous sensory-motor homunculi. Parallel advances in instrumentation were made from the Leyden jar (1745) to present customizable current-controlled stimulators. CONCLUSIONS: ECS is commonly used in neurosurgery for localization of brain functions and is the benchmark for research studies. Significant leaps have been made since ECS first used in the 19th century. It evolved to remain the gold standard for localization of human brain functions in the 21st century.

Deep Brain Stimulation in Movement Disorders: From Experimental Surgery to Evidence-Based Therapy.

Deep brain stimulation (DBS) of 3 different targets is the most important therapeutic innovation of the past 30 years for patients with fluctuating Parkinson's disease (PD), disabling dystonia, tremors, and refractory Gilles de la Tourette syndrome. When compared with medical treatment alone, controlled studies have shown better motor, nonmotor, and particularly quality-of-life outcomes with large effect sizes for advanced complicated PD that cannot be improved with medication, and also for PD patients with only early fluctuations. Class 1 studies have also shown superiority over medical treatment for generalized, segmental, and botulinum-toxin refractory focal cervical dystonia. Long-term efficacy is established for all indications with open studies. For tremors, open studies have shown that DBS is remarkably effective on PD and essential tremor, but efficacy on severe essential tremor and cerebellar tremors is limited by a tendency for tolerance/habituation, including concerns about long-term efficacy. Open studies of disabling Gilles de la Tourette syndrome show an improvement in tics. New developments hold a promise for further improvement. New hardware with directional stimulation and new stimulation paradigms are further areas of research. The targets of DBS are refined with new imaging processing that will help to diversify the surgical targets. New indications are being explored. Closed-loop DBS using brain or peripheral sensor signals have shown favorable clinical short-term results. Long-term data are lacking, and it is hoped that similar approaches for other movement or behavioral disorders may be developed. Exciting new developments carry the hope for a more pathophysiology-based approach for DBS for various brain circuit disorders. © 2019 International Parkinson and Movement Disorder Society.

Deep Brain Stimulation for the Treatment of Resistant Depression: Systematic Review of the Literature

Depression is the leading cause of disability worldwide, and it is related to high suicide rates. Furthermore, a great number of patients do not respond to any of the available treatments. Deep brain stimulation (DBS), a versatile technology with expanding indications, is considered a potential treatment for resistant depression. However, in over 10 years of clinical research, its efficacy has not been completely proven. Although new trials using DBS for treatment-resistant depression keep emerging, two of the three Level I evidence-based studies recently conducted have not provided conclusive data. Methodological limitations andmajor biases have compromised the obtention of clearer results. In this systematic review of the literature, we intend to critically assess the clinical trials performed in this field.

The Nucleus Basalis of Meynert and Its Role in Deep Brain Stimulation for Cognitive Disorders: A Historical Perspective.

The nucleus basalis of Meynert (nbM) was first described at the end of the 19th century and named after its discoverer, Theodor Meynert. The nbM contains a large population of cholinergic neurons that project their axons to the entire cortical mantle, the olfactory tubercle, and the amygdala. It has been functionally associated with the control of attention and maintenance of arousal, both key functions for appropriate learning and memory formation. This structure is well-conserved across vertebrates, although its degree of organization varies between species. Since early in the investigation of its functional and pathological significance, its degeneration has been linked to various major neuropsychiatric disorders. For instance, Lewy bodies, a hallmark in the diagnosis of Parkinson's disease, were originally described in the nbM. Since then, its involvement in other Lewy body and dementia-related disorders has been recognized. In the context of recent positive outcomes following nbM deep brain stimulation in subjects with dementia-associated disorders, we review the literature from an historical perspective focusing on how the nbM came into focus as a promising therapeutic option for patients with Alzheimer's disease. Moreover, we will discuss what is needed to further develop and widely implement this approach as well as examine novel medical indications for which nbM deep brain stimulation may prove beneficial.

The Montreal procedure: The legacy of the great Wilder Penfield.

Wilder Penfield pioneered the early practice of brain surgery. In binding together the disciplines of neurosurgery, neurology, neuropathology, psychology, and related basic sciences, Penfield transformed our understanding of the field of neuroscience. He brought to the operating room the meticulous techniques of Sherrington, combined with methods of stimulation described by Foerster, which he complemented with expert knowledge of the neurocytology of nervous tissue. While developing surgical treatments for epilepsy, Penfield began to map the brain. He established the "Montreal procedure" for the surgical treatment of epilepsy. His scientific contributions on neurostimulation were transformative in their time and continue to resonate today. This article reviews the life of Wilder Penfield and summarizes key scientific contributions. Specifically, we detail the Montreal procedure. We additionally present a painting by Canadian artist Iris Hauser, which purports to display the hidden treasures of the human mind.

Cushing, Penfield, and cortical stimulation.

Harvey Cushing and Wilder Penfield enjoyed a unique professional and personal relationship. Shortly before his retirement from Harvard University in 1933, Cushing sent Penfield 8 sketches that he drew in 1902 and 1903 while he was at Johns Hopkins Hospital. The first series of 3 sketches illustrate the relationship between a cortical hemorrhagic lesion and the motor strip in a patient with focal motor seizures. The second series also comprises 3 sketches. These depict the operative findings in a patient in whom Cushing had electrically stimulated the precentral gyrus, before resecting the cortex subserving motility of the upper extremity to control painful dyskinetic movements. The third series consists of 2 sketches that illustrate the results of stimulation of the motor strip as an aid in the safe resection of an epileptogenic focus in a patient with Jacksonian seizures. These sketches are the subjects of this paper. They add to the relatively sparse record of Cushing's activities in cortical stimulation and in the treatment of functional disorders.

Dr. Robert G. Heath: a controversial figure in the history of deep brain stimulation.

The history of psychosurgery is filled with tales of researchers pushing the boundaries of science and ethics. These stories often create a dark historical framework for some of the most important medical and surgical advancements. Dr. Robert G. Heath, a board-certified neurologist, psychiatrist, and psychoanalyst, holds a debated position within this framework and is most notably remembered for his research on schizophrenia. Dr. Heath was one of the first physicians to implant electrodes in deep cortical structures as a psychosurgical intervention. He used electrical stimulation in an attempt to cure patients with schizophrenia and as a method of conversion therapy in a homosexual man. This research was highly controversial, even prior to the implementation of current ethics standards for clinical research and often goes unmentioned within the historical narrative of deep brain stimulation (DBS). While distinction between the modern practice of DBS and its controversial origins is necessary, it is important to examine Dr. Heath's work as it allows for reflection on current neurosurgical practices and questioning the ethical implication of these advancements.

Exploring the brain through posterior hypothalamus surgery for aggressive behavior.

Neurological surgery offers an opportunity to study brain functions, through either resection or implanted neuromodulation devices. Pathological aggressive behavior in patients with intellectual disability is a frequent condition that is difficult to treat using either supportive care or pharmacological therapy. The bulk of the laboratory studies performed throughout the 19th century enabled the formulation of hypotheses on brain circuits involved in the generation of emotions. Aggressive behavior was also studied extensively. Lesional radiofrequency surgery of the posterior hypothalamus, which peaked in the 1970s, was shown to be an effective therapy in many reported series. As with other surgical procedures for the treatment of psychiatric disorders, however, this therapy was abandoned for many reasons, including the risk of its misuse. Deep brain stimulation (DBS) offers the possibility of treating neurological and psychoaffective disorders through relatively reversible and adaptable therapy. Deep brain stimulation of the posterior hypothalamus was proposed and performed successfully in 2005 as a treatment for aggressive behavior. Other groups reported positive outcomes using target and parameter settings similar to those of the original study. Both the lesional and DBS approaches enabled researchers to explore the role of the posterior hypothalamus (or posterior hypothalamic area) in the autonomic and emotional systems.

My 25 Stimulating Years with DBS in Parkinson's Disease.

The year 2017 marks the 30th anniversary of the birth of modern deep brain stimulation (DBS), which was introduced by Benabid, Pollak et al. in 1987, initially targeting the motor thalamus to treat tremor, and subsequently targeting the subthalamic nucleus (STN) for treatment of symptoms of advanced Parkinson's disease (PD). STN DBS is undoubtedly "the most important discovery since levodopa", as stated by David Marsden in 1994. In 2014, The Lasker- DeBakey Clinical Medical Research Award to "honor two scientists who developed deep brain stimulation of the subthalamic nucleus", was bestowed upon Benabid and DeLong. STN DBS remains today the main surgical procedure for PD, due to its effectiveness in ameliorating PD symptoms and because it is the only surgical procedure for PD that allows a radical decrease in medication. Future improvements of DBS include the possibility to deliver a "closed-loop", "on demand" stimulation, as highly preliminary studies suggest that it may improve both axial and appendicular symptoms and reduce side effects such as dysarthria. Even though DBS of the subthalamic nucleus is the main surgical procedure used today for patients with PD, all patients are not suitable for STN DBS; as a functional neurosurgeon performing since more than 25 years various surgical procedures the aim of which is not to save life but to improve the patient's quality of life, I consider that the surgery should be tailored to the patient's individual symptoms and needs, and that its safety is paramount.

Our first decade of experience in deep brain stimulation of the brainstem: elucidating the mechanism of action of stimulation of the ventrolateral pontine tegmentum.

The region of the pedunculopontine tegmental nucleus (PPTg) has been proposed as a novel target for deep brain stimulation (DBS) to treat levodopa resistant symptoms in motor disorders. Recently, the anatomical organization of the brainstem has been revised and four new distinct structures have been represented in the ventrolateral pontine tegmentum area in which the PPTg was previously identified. Given this anatomical reassessment, and considering the increasing of our experience, in this paper we revisit the value of DBS applied to that area. The reappraisal of clinical outcomes in the light of this revisitation may also help to understand the consequences of DBS applied to structures located in the ventrolateral pontine tegmentum, apart from the PPTg. The implantation of 39 leads in 32 patients suffering from Parkinson's disease (PD, 27 patients) and progressive supranuclear palsy (PSP, four patients) allowed us to reach two major conclusions. The first is that the results of the advancement of our technique in brainstem DBS matches the revision of brainstem anatomy. The second is that anatomical and functional aspects of our findings may help to explain how DBS acts when applied in the brainstem and to identify the differences when it is applied either in the brainstem or in the subthalamic nucleus. Finally, in this paper we discuss how the loss of neurons in brainstem nuclei occurring in both PD and PSP, the results of intraoperative recording of somatosensory evoked potentials, and the improvement of postural control during DBS point toward the potential role of ascending sensory pathways and/or other structures in mediating the effects of DBS applied in the ventrolateral pontine tegmentum region.

Deep brain stimulation for obesity: past, present, and future targets.

The authors review the history of deep brain stimulation (DBS) in patients for treating obesity, describe current DBS targets in the brain, and discuss potential DBS targets and nontraditional stimulation parameters that may improve the effectiveness of DBS for ameliorating obesity. Deep brain stimulation for treating obesity has been performed both in animals and in humans with intriguing preliminary results. The brain is an attractive target for addressing obesity because modulating brain activity may permit influencing both sides of the energy equation--caloric intake and energy expenditure.

Unlocking pain: deep brain stimulation might be the key to easing depression and chronic pain.

Depression and chronic pain know no geographical boundaries. About 350 million people around the world experience long-lasting sadness and an unshakeable sense of hopelessness, and one person out of ten tries to live each day to its fullest despite continuous physical pain. These two difficult conditions frequently coexist, becoming more common with age. Looking ahead, we can expect the incidence of depression and chronic illness to grow, since more people over age 65 will populate the world by 2020 than children younger than five.

Inside tract: can deep brain stimulation survive its reputation for success?

When she was 37, Clare developed a tremor down her left side. At 39, she was diagnosed with Parkinson's disease and put on a series of medications. These helped for a time, but the effect didn't last. Within a few years, her tremors had grown so severe that Clare was dropping food at her waitressing job. She couldn't seat guests, and she burned herself when she tried to help out in the kitchen. Increasingly unable to support herself and at a loss for other options, Clare began to look into something called deep brain stimulation (DBS).