Deep Brain Stimulation
Deep Brain Stimulation (DBS) is a technique used by functional neurosurgeons whereby electrodes are implanted into a target brain structure for the continuous administration of electrical stimulation. Electrodes are typically connected to an internal neurostimulator implanted under the skin, which can be tuned to an optimally therapeutic pulse width, frequency, and amplitude. A frequency of 30-60 Hertz is typically considered excitatory and can be used for electrical excitation of target structures. On the other hand, high frequency stimulation (HFS) using a frequency of greater than or equal to 100 Hertz is considered inhibitory and can take the place of more permanent techniques of structure ablation. Electrodes are typically inserted while the patient is awake and under local anesthesia using stereotaxic techniques. The brain target is localized using Magnetic resonance imaging (MRI), Ventriculography, Microrecording (MER), Microstimulation, and Macrostimulation and the electrode is implanted via the least disruptive path through less central brain structures. Most complications are mild and reversible. Psychophysiological side effects vary with site of implantation and surgical complications include skin infection, intracranial infection, and hemorrhage. [1]
History
Electrical stimulation of the brain first gained popularity with Wilder Penfield’s brain maps in the 1950s. Penfield was a neurosurgeon who treated epilepsy via surgical ablation of epileptic foci in the brain. Surgery involved the stimulation of proposed epileptic foci, opening the door for Penfield to create a detailed functional mapping of brain structures from the microstimulation data. [2] [13]
James Olds performed one of the first experiments about the functional effects of brain stimulation in 1958. Olds studied self-stimulation of reward pathways in rats, discovering that rats showed continual self-stimulation when electrodes were implanted in the rhinencephalon, hypothalamus, and related structures. Conversely, rats showed avoidance when stimulated in small areas of the midbrain and in certain adjacent parts of the thalamus and hypothalamus. [12]
Robert G. Heath conducted some of the first experiments of brain stimulation in humans in 1963. Heath tested whether deep brain stimulation of the septal region in humans would produce the pleasure-response in humans. Indeed, Heath found that subjects would self-administer stimulation into the septal regions with high frequency, subjectively reporting pleasure. [4]
It is commonly stated that the roots of modern day deep brain stimulation started with Benabid, Pollack and coworker’s publication of “Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease” in 1987. In this publication, the authors developed the modern-day deep brain stimulator in conjunction with Medtronic©. [5] In a subsequent publication, Benabid and Pollack introduced DBS in the subthalamic nucleus as treatment for tremors in Parkinson’s disease in 1993. [2] The first DBS therapy was approved in Canada, Europe, and Australia for Essential Tremor in 1993 and in the US in 2002 for Parkinson’s disease. [5] As of 2008, over 40,000 Parkinson’s patients have been implanted with deep brain stimulators. [6]
Clinical Uses
Parkinson’s Disease
Long term, high frequency stimulation using DBS has been used for the treatment of the tremor associated with Parkinson’s disease since 1997. The optimal candidates for DBS are idiopathic Parkinson’s patients with motor fluctuations and levodopa induced dyskinesias. Bilateral stimulation of the subthalamic nucleus (STN) has been shown to be the most successful target in addressing akinesia, rigidity, and dyskinesias in Parkinson’s patients, although stimulation in the Ventrointermediate Nucleus (VIM) reduces tremor, stimulation in the centrum medianum-parafascicularis complex (CM-Pf) reduces tremor and dyskinesias, and stimulation of globulus pallidus (GPi) significantly reduces dyskinesias and moderately reduces akinesia, and rigidity. [1]
After surgery, the neurologic team must find an optimal combination of drug dosage and stimulation frequency in order to produce optimal results with minimal side effects. Although subthalamic nucleus DBS has been shown to significantly decrease motor and speech symptoms of Parkinson’s disease, DBS has not been shown to be neuroprotective in slowing the progression of the disease . [1] DBS treatment mechanism for Parkinson’s may involve disruption of abnormal neural signals from the basal ganglia (BG) via inhibitory action. [1]
Obsessive-Compulsive Disorder
Deep brain stimulation was fist described for the treatment of very severe treatment-resistant OCD in 2008 by Greenberg et al. For best results, electrodes are typically implanted at the junction of the anterior capsule, anterior commissure, and posterior ventral striatum. Overall, roughly two thirds of severe OCD patients treated with DBS observe a significant reduction in symptoms and significant functional improvement. [3] In 2009, the US Food and Drug Administration approved DBS for use in refractory OCD under a humanitarian device exemption so as to allow for development of treatment for the rare form of severe treatment-resistant OCD. [11] In addition to reducing symptoms of OCD, many patients were shown by Greenberg et al (2008) to have an increase in mood from the DBS surgery. This serendipitous finding has lead to the research of DBS in treatment-resistant major depressive disorder. [11]
Major Depressive Disorder
Major depressive disorder is a highly prevalent disorder worldwide, but at least 30% of patients show no improvement using typical pharmacological antidepressants [8] and 20% show no response to either antidepressant medications or psychotherapy. [11] Although the optimal neuroanatomical target is not known, some of the common target structures include the anterior limb of the internal capsule, the ventral internal capsule/ventral striatum, the nucleus accumbens, and the subthalamic nucleus. [1] [11] The ventral striatum (VS) is a promising neural target for DBS because depressed patients show a significantly lower VS response to positive stimuli than controls. Additionally, the subgenual cingulated region has been shown to be more metabolically active in patients with major depressive disorder. [11] One study of the long-term treatment outcome of DBS in the subcallosal cingulate gyrus showed that over 50% of patients had positive outcomes such as return to employment, fewer medications, and a higher quality of life. [8]
Alzheimer’s Disease
Deep brain stimulation for the improvement of memory was first found to be effective during an experimental brain surgery aimed to reduce appetite in a severely obese 50-year-old man. Electrodes were implanted into his hypothalamus in an attempt to curb his apatite, but instead the man reported experiencing memories during hypothalamic stimulation. In addition, after continuous hypothalamic stimulation for three weeks, the man performed better on learning tasks. As a result of this unforeseen finding, researchers conducted a Phase I clinical trial for memory improvement in Alzheimer’s patients using DBS in the hypothalamus and fornix. [6] The study of 6 patients with Alzheimer’s disease found that not only was it safe to use DBS in the hypothalamus and fornix, but it may possibly slow the rate of cognitive decline associated with the disease. Also, less severely effected individuals showed more benefit. More research about the possible therapeutic benefit of DBS for memory enhancement needs to be done before the clinical use of DBS in Alzheimer’s patients. [9]
Epilepsy
Cooper et al was the first to attempt to treat epilepsy via brain stimulation in 1970. [10] Since then, it has been illuminated that electrical stimulation of subcortical structures can modulate and interrupt epileptic seizures. Although the mechanism behind this effect is not completely known, many hypothesize that some subcortical structures modulate seizure generators throughout the brain. Optimal region for DBS stimulation may depend on the type of epilepsy involved, but regions of interest include the cerebellum, caudate nucleus, anterior and centromedian nucleus of the thalamus, subthalamic nucleus, and substantia nigra. [7]
Ethics
Since deep brain stimulation is an inherently invasive procedure capable of causing major changes in brain activation, it is necessary to be cautious when prescribing DBS for the treatment of diseases and disorders. In order to ensure maximal efficacy in the use of DBS, it should be ensured that all patients have received an accurate diagnosis, have the ability to provide informed consent, have a severe form of the illness, and have not responded to less invasive treatment options. As a result, DBS should be used solely for clinical use and not personal augmentation. It is also important that DBS only be prescribed and administered by expert neurosurgeons and psychiatrists in keeping with regulations from an institutional review board and FDA policy. Finally, in order to monitor the efficacy of long-term use of DBS, it is also necessary for longitudinal studies to monitor the progress of DBS patients. [11]
Thanks for Reading!
And finally, this is what happens when you research DBS for too long:
References
- Benabid AL. Deep Brain stimulation for Parkinson’s Disease. Curr Opin Neurol. 2003;13: 969-706.
- Blomstedt P & Hariz MI. Deep brain stimulation for movement disorders before DBS for movement disorders. Parkinsonism. Relat. Disord. 2010;16: 429-433.
- Greenberg BD, Gabriels LA, Malone DA Jr, et al.. Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Mol Psychiatry 2010;15:64-79.
- Heath RG. Electrical self-stimulation of the brain in man. Am J Psychiatry, 1963; 120: 571-577.
- History of medtronic dbs therapy. (n.d.). Retrieved from http://www.epda.eu.com/en/parkinsons/in-depth/surgery/deep-brain-stimulation/history/
- Jeremy, L. (2008, January 30). Scientists discover way to reverse loss of memory. Independent.co.uk, Retrieved from http://www.independent.co.uk/news/science/scientists-discover-way-to-reverse-loss-of-memory-775586.html?service=Print
- Kahane P, Depaulis A. Deep brain stimulation in epilepsy: what is next? Curr Opin Neurol. 2010; 23: 177-82.
- Kennedy SH, Giacobbe P, Rizvi SJ. et al. Deep brain stimulation for treatment-resistant depression: follow-up after 3 to 6 years. Am J Psychiatry, 2011; 168:502-510.
- Laxton AW, Tang-Wai DF, McAndrews MP, et al.. A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease. Ann Neurol 2010;68:521-34.
- Loddenkemper T, Pan A, Neme S, Baker KB, Rezai AR, Dinner DS, Montgomery EB, Luders HO. Deep brain stimulation in epilepsy. J. Clin. Neurophysiol. 2001;18: 514-532.
- Malone D. Use of deep brain stimulation in treatment-resistant depression. Cleveland Clin. J. Medicine. 2010;77:S77-80.
- Olds J. Self-Stimulation in the Brain. Science. 1958; 127:315-324.
- Penfield, W. (1958). The excitable cortex in conscious man. (pp. 5-42). Montreal: Liverpool University Press.
Click picture links for picture references