History of Brain Stimulation
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Brain stimulation refers to neurosurgical or non-invasive techniques that apply electrical or magnetic currents to modulate neural activity. These techniques have been developed and used to treat various neurological and psychiatric disorders. The field has evolved significantly over the past century, transitioning from crude electrical methods to precise, targeted interventions.
Early Origins and Electroconvulsive Therapy
- Early attempts to treat mental disorders by inducing seizures date back to the 16th century with the use of substances like camphor.
- In 1938, Italian scientists Ugo Cerletti and Luigi Bini first applied electrical current to the scalp of human patients to induce a generalized epileptic seizure, developing Electroconvulsive Therapy (ECT).
- Initially, ECT was used for schizophrenia, based on observations by Meduna, but its use and effectiveness were established for depression by 19418.
- ECT rapidly spread, notably introduced in the US around 1940.
- By the 1950s, the methodology improved with the introduction of anesthesia and muscle relaxants (modified ECT) to reduce side effects like bone fractures.
- Despite past socio-political and cultural concerns about brain damage, anatomical brain imaging and post-mortem studies after successful ECT courses have partly refuted this notion.
- ECT remains a widely administered treatment, although utilization rates and practices vary globally. It is a largely considered treatment for severe and drug-resistant major depressive disorders in Western countries, while in some Eastern countries, it is mainly applied as a first-line treatment for schizophrenia.
- Brief-pulse wave ECT is recommended as the standard treatment today, preferred over longer pulse-width stimulation due to reduced cognitive side effects9…. Bilateral electrode placement is commonly preferred, though unilateral is also used.
The Advent of Stereotaxy and Intracranial Stimulation
- The ability to accurately localize intracranial structures was crucial for the development of targeted therapies.
- The stereotactic apparatus was pioneered by Horsley and Clarke in 1908, followed by Spiegel and Wycis who developed the first human stereotactic apparatus in 1947.
- This led to a wealth of publications on focused stereotactic lesioning for various disorders, including the first successful electro-coagulation for pain by Talairach in 1948 and pallidotomy for Parkinson’s disease by Narabayashi in 1953.
- Intracranial stimulation developed alongside stereotaxy, initially used by neurosurgeons to aid localization and explore effects before lesioning.
- As early as the 1950s, researchers noted that while low-frequency stimulation might worsen tremor, high-frequency stimulation could effectively abolish it.
- Neurophysiologist Sem-Jacobsen used stimulation and recording through implanted electrodes in patients for several weeks to improve surgical lesion accuracy in the late 1950s and early 1960s.
- In the early 1970s, the Russian neurophysiologist Bechtereva first proposed chronic therapeutic neurostimulation as an alternative to destructive ablation, coining the term ‘therapeutic electrical stimulation. She demonstrated the safety and efficacy of chronic deep brain stimulation (DBS), implanting electrodes for up to 1.5 years.
- Also in the early 1970s, the neurophysiologist Albe-Fessard in Paris pioneered the technique of intracranial microrecordings to delineate deep grey nuclei before lesioning.
The Beginnings of Modern Deep Brain Stimulation (DBS)
- The clinical use of cardiac pacemakers in 1958 paved the way for similar battery technologies to be used for neurostimulation.
- In the early 1970s, two different groups first employed neurostimulation for chronic pain management: Mazars and colleagues in France and Hosobuchi and colleagues in California.
- A major breakthrough occurred in the late 1980s and early 1990s with the work of the Grenoble team, led by Benabid and Pollak. Building on previous experience, DBS first proved efficacy for tremor in the late 1980s. The publication of the first cases of subthalamic nucleus (STN) DBS for advanced Parkinson’s disease in the early 1990s showed remarkable clinical benefit. David Marsden notably called STN DBS “the most important discovery since levodopa”.
- DBS has since expanded to manage other movement disorders like dystonia and Tourette’s syndrome, as well as epilepsy, headache, and certain psychiatric disorders.
- To date, approximately 200,000 patients worldwide have received DBS for movement disorders.
- DBS is currently approved for movement disorders (PD, essential tremor, dystonia) and focal-onset epilepsy, and under humanitarian grounds for obsessive-compulsive disorder. Emerging indications are still under study.
Development of Non-Invasive Brain Stimulation (NIBS)
- A new era opened in 1985 with the introduction of Transcranial Magnetic Stimulation (TMS) by Antony Barker. TMS is well-tolerated and generally safe.
- Repetitive Transcranial Magnetic Stimulation (rTMS), which delivers recurring pulses, became popular as a potential antidepressant treatment after studies in 1994 demonstrated long-lasting excitability changes.
- rTMS targets the dorsolateral prefrontal cortex (DLPFC) based on neuroimaging findings in depression, which revealed functional abnormalities and interhemispheric asymmetry. Therapeutic strategies involve inhibitory low-frequency rTMS on the right DLPFC or excitatory high-frequency rTMS on the left DLPFC.
- Transcranial Direct Current Stimulation (tDCS) is another NIBS technique using low-amplitude electrical current delivered via scalp electrodes to modulate neural activity. Anodal tDCS generally increases cortical excitability, while cathodal tDCS reduces it. Recent advancements include the development of home-based tDCS.
- Magnetic Seizure Therapy (MST) is a variant related to ECT but uses magnetic pulses to induce seizures, explored as an alternative for depression.
- Transcranial Ultrasound Stimulation (TUS) is an innovative, relatively recent NIBS technique that uses low-intensity ultrasonic waves to target brain regions with millimeter resolution, including deep structures. It is considered clinically safe with mostly mild and transient side effects. TUS is being tested for various conditions, including Alzheimer’s disease, Parkinson’s disease, epilepsy, major depressive disorder, chronic pain, disorders of consciousness, and schizophrenia.
Technological and Procedural Advancements
- Targeting methods in DBS evolved from ‘indirect targeting’ using anatomical coordinates based on atlases (initially defined by ventriculography) to ‘direct targeting’ based on patient-specific imaging (CT and MRI), which became the norm. Neuroimaging advances have also allowed for better visualization of targets using dedicated sequences.
- Microelectrode recordings (MER) have been used intraoperatively to refine target localization.
- Developments in implantable pulse generators, including longer battery life and rechargeable options, have improved the practicality of DBS.
- Advanced programming techniques and targeting strategies are being explored, including ‘sweet spot’ mapping and ‘connectomic’ approaches which aim to target syndrome- or symptom-specific fibre tracts based on brain connectivity data.
- Adaptive or closed-loop stimulation systems are also being developed.
- Surgical approaches have been refined, including techniques for reducing hemorrhagic complications and the consideration of awake versus asleep procedures for DBS implantation.
Evolving Clinical Landscape and Future Directions
- The clinical application of brain stimulation is constantly evolving, with ongoing research into its mechanisms and new applications.
- Neurostimulation methods are seen as promising therapeutic options for mood disorders, complementing existing pharmacological and psychological treatments. Recent research focuses on enhancing efficacy and safety, reducing treatment duration and relapse, and understanding the underlying neural mechanisms.
- Future studies are needed to fully understand the neurobiology of brain stimulation and explore new physical modalities and protocols, particularly for specific patient populations and comorbid conditions.
- The development of personalized approaches is a goal for the future of brain stimulation therapies.
- Currently, clinicians must make pragmatic decisions regarding which neuromodulation technique to use, understanding the evidence, advantages, and disadvantages of each, as comparative trials are often lacking.