Deep Brain Stimulation – A New Frontier in Psychiatry

By Shaheen E Lakhan, MS, MEd, PhD, MD | 7 Comments |

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For as long as the brain has been seen as the site of mental activity, it has followed that altering brain function should be implemented to treat mental illness. Second generation antidepressants and psychotherapy are currently the least invasive ways of affecting brain function but they leave too many patients only partially improved, and have proved completely ineffective for some. Estimates of treatment unresponsiveness are unreliable, but 30% to 40% patients with depression and obsessive compulsive disorder (OCD) probably become treatment failures. For these patients, techniques like deep brain stimulation (DBS) provide a promising treatment alternative.

In the middle of the twentieth century, the lesioning of areas of the brain was discovered to be an effective treatment for certain movement disorders. Unfortunately, there were damaging side effects as a result of these lesions. In the 1980s, it was determined that the same effects could be accomplished by stimulating the tissue with electricity. DBS was approved by the FDA as a treatment for movement disorders in 2002. Although still in the research stage, DBS appears to also be a major advance in the treatment of OCD and treatment resistant depression (TRD).

Electrophysiology and modern imaging allow the very precise placement of electrodes. Response can be optimized by changing location and adjusting stimulus site parameters. Since the patient cannot detect the simulation, periods of active stimulation and sham (zero voltage) can be alternated to provide single or double-blind controls. After the sites and parameters for DBS are selected, the stimulator is placed under the skin, usually below the clavicle (collar bone), and connecting wires are run under the skin to the stimulating electrodes in the brain. Although the sites for stimulation vary, they basically fall into two groups: a basal ganglia group and a cingulate gyrus group.

Callaway and I systematically reviewed the literature on DBS for TRD and OCD. Our research findings were recently published in BMC Research Notes. While the number of cases was small — nine for OCD, seven for TRD, and one for both — these were extremely treatment-resistant patients. While not everyone responded, about half the patients did show dramatic improvement. Associated adverse events were generally trivial in younger psychiatric patients but often severe in older movement disorder patients.

While still in the research stage, DBS promises to be a major advance. Modern imaging methods allows precise placement of electrodes. Electrophysiological micro-recordings from implanted electrodes before and during stimulation aid in defining the electrode locations. Measurement of cerebral blood flow (CBF) before and after stimulation provides additional accuracy. Location and parameters of the stimulation can be changed to individualize and optimize treatment. Since the patient usually cannot detect whether stimulation is on or off, artificial stimulation can easily be used to deceive participants and provide a control condition. This ability to use patients as their own controls is a powerful tool for reducing placebo effects.

There are also ethical considerations of DBS that need to be carefully considered. Would all people have equal access to treatment? If not, who would determine when a depression is severe or unresponsive enough for DBS? If it proves effective, should we allow DBS to be used for neural enhancement and pleasure?

DBS is a very promising new development for the treatment of severe treatment-resistant depression and obsessive-compulsive disorder. So far the clinical samples are small, and some of the theoretical rationales are less than clear. Nonetheless, the results so far are very impressive, and it is certain that present shortcomings will be addressed in the near future.

Reference

Lakhan, S., & Callaway, E. (2010). Deep brain stimulation for obsessive-compulsive disorder and treatment-resistant depression: systematic review BMC Research Notes, 3 (60) DOI: 10.1186/1756-0500-3-60

Shaheen E Lakhan, MS, MEd, PhD, MD

Dr. Lakhan is executive director of the Global Neuroscience Initiative Foundation (GNIF). He is a published scholar in several fields including medicine, proteomic biomarkers, bioethics, biotechnology, education technology, and intellectual property. He serves on the editorial board of several scholarly publications and has been honored by the U.S. President and Congress.

7 Responses

Dan says:
March 12, 2010 at 10:34 am
I recently commented on a sciencedaily.com article reporting success with TRD and deep brain stimulation. You touch on many issues, not the least important being access. If these procedures prove to be effective, then who decides who get’s them? I know in the states, without the single payer option, insurance companies regulate which procedures are covered and I’m not sure what they allow regarding DBS. In other countries, who decides? None the less, the work looks interesting and promising.
Is there the chance that there will be wider trials for TRD and DBS?
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Shaheen E Lakhan, MS, MEd, PhD, MD says:
March 12, 2010 at 12:19 pm
Dear Dan,
There is certainly much clinical interest in this field. ClinicalTrials.gov reports at least 20 studies on DBS for depression. However, many are primarily for movement disorders with additional investigation into concomitant mood/cognitive disorders, some are not recruiting/inactive, others are complete and the results have been included in my article, and most of the remaining trials are recruiting by invitation only. The key is now identifying the optimal areas for stimulation with more pilot studies and then pursuing larger clinical trials. Thank you.
Sincerely,
Shaheen
Reply
Dirk Hanson says:
March 25, 2010 at 1:13 pm
Specifically, do we know why electrical stimulation of these two brain areas produces an effect on depression for some people? What is your theory on why this works? How do these findings connect with serotonin/dopamine models of depressive illness?
Reply
Shaheen E Lakhan, MS, MEd, PhD, MD says:
March 25, 2010 at 1:35 pm
Dear Dirk,
Those are excellent questions; the first two are actually somewhat addressed in our article:
Knowledge of specific pathways involved in OCD and TRD is obviously critical to further advances in the uses of DBS for psychiatric disorders. Tractography, also known as diffusion tensor imaging, is a relatively new procedure for determining functional connections between brain locations in living humans. Although the mathematics involved is complex, the MRI is simply used to measure the movement of oxygen along pathways from a “seed” voxel to areas that receive signals from the seed. A good discussion on it has been made by Taylor [43].
More germane to the DBS discussion, Gutman [3] has used tractographic analysis to examine the connections from seeds in the cingulate gyrus (CG) to the AL/IC. These are the two areas for DBS that are featured prominently in Table 1. They found that CG connected to the medial frontal cortex, anterior and posterior cingulate, medial temporal lobe, medial thalamus, hypothalamus, nucleus accumbens and dorsal brain stem. AL/IC projected to frontal pole, median temporal lobe, cerebellum, nucleus accumbens, thalamus, hypothalamus, and brainstem. While the two seeds were connected to some common areas, those connections seemed to be via different white matter bundles. Gutman suggested the two locations exist within separate neural networks that include common nodes. Larger studies, including both control subjects and patients, are needed for further clarification but until in vivo tract tracing in human is possible, results cannot be fully verified.
On the latter question on trying to find correlations with serotonin/dopamine (or any of the neurotransmitter) models, in my opinion, it would be very premature to link the effects of DBS for depression with a molecular model . Therefore, I would rather defer my answer on this issue until some other key studies are published. Stay tuned…
Thank you.
Sincerely,
Shaheen
Reply
Tools For Healing says:
March 31, 2010 at 12:16 am
DBS may be useful however is it accessible to the general public when they most need it? If not then it certainly has its limitations. Another form of effective brain stimulation is adio visual stimulation AVS which is a type of brainwave entrainment (see link) – you can have sound with the option of light. This is an effective method of stimulating the brain and can help whoever uses it to enter into different states of consciousness. I know for example that people who have depression and ADD may have difficulty producing beta waves which are associated with alertness – there brains tend to be more in the theta alpha range with minimal beta. Therefore their inability to remain focused and their brains possibly chemical imbalance leading to the depression. Entrainment soundtrackes are easy to use and accessible to all. All you have to do is listen once or twice a day and you will begin to see results fast.
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Antonio J R M says:
June 10, 2010 at 3:54 am
We believe it is a delicate practiced. Even little is known the ranks of mV, nanoamper and Hz of neurons and synapses for network efficient or there is a patron investigated in human living and healthy.
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