It is being studied as a treatment of last resort for disorders such as depression, Tourette’s syndrome, obesity, anorexia, stroke recovery, traumatic brain injury, epilepsy, cluster headaches, chronic pain and addiction.
Nice insight into the history of this new treatment.
The U.S. Food and Drug Administration in 1997 approved deep brain stimulation for treatment of Parkinson’s and essential tremor, a much more common disorder that causes trembling. It now also is approved to treat dystonia, a rare movement disorder that involves disabling muscle spasms
One of the fear’s is that tinkering with emotional centers of the brain may alter a person’s personality.
“I think I’ve become less concerned because what I’ve seen is these people returning to how they felt before depression. In other words, we don’t seem to be turning on some kind of happy circuit that overrides their depression,” said Dr. Donald Malone, the psychiatrist who cares for all the patients in the Clinic’s trials.
St. Jude Medical Inc. (STJ) has garnered Food and Drug Administration approval to launch a trial the company plans to use to pursue U.S. approval for a pacemaker-like device that uses electricity to treat severe depression.
St. Jude Medical, Inc. Investor Relations Angela Craig, 651-481-7789 or Media Relations Kathleen Janasz, 651-415-7042 or St. Jude Medical, ANS Division Media Relations Denise Landry, 972-309-8085 St. Jude Medical, Inc. (NYSE:STJ) today announced it has received an Investigational Device Exemption (IDE) from the U.S. Food and Drug Administration (FDA) to begin enrollment in a controlled, multi-site, blinded, clinical study
Can someone explain to me why money is involved so explicitly?
Electrical stimulation of areas deep within the brain could improve memory, early research suggests. A team of doctors in Canada were attempting to treat a morbidly obese man through deep brain stimulation (DBS) for his obesitas. Their long-standing interest in functional neurosurgery and DBS made them consider the possibility of a neurosurgical treatment. They wanted to stimulate the hypothalamus for appetite control. Hypothalamic lesion surgery had been used previously to treat obesity. Hypothalamic stimulation was proposed based on experimental studies of appetite control in rodents, dogs, and nonhuman primates.
DBS electrodes were implanted bilaterally in the ventral hypothalamus with the patient receiving local anesthesia without sedation. During stimulation the patient vividly remembered a situation from the past:
being in a park with friends, a familiar scene to him. He felt he was younger, around 20 years old. He recognized his epoch-appropriate girlfriend among the people. He did not see himself in the scene, but instead was an observer. The scene was in color; people were wearing identifiable clothes and were talking, but he could not decipher what they were saying. As the stimulation intensity was increased from 3.0 to 5.0 volts, he reported that the details in the scene became more vivid.
These recollections were tested under double blind conditions.
The effects of stimulation on memory were further characterized using recognition tasks with high sensitivity and specificity for hippocampus-dependent retrieval processes. Each task was performed twice, with the stimulator on or off in a double-blinded fashion.
Shortly after recovery of the operation as well as after a year the patient performed better in memory tests than he had previously done.
The patient performed well in memory tests when the electrodes were stimulated, but less well when they were switched off.
The results suggest it might be possible to use deep brain stimulation directly to boost memory.
Maybe a new treatment for Alzheimer? Sounds to good to be true. I remember ECT and Morbus Parkinson. ECT can help but as the disease progresses the results diminishes.
The conclusion of the authors:
Electrical stimulation in this high-density area could be affecting a number of neural elements. We cannot be sure how much of the effect is related to stimulation of nuclei versus axons coursing in the hypothalamus. At this time, we believe that the results are consistent with driving the activity of the hippocampal memory circuit through stimulation of the fornix. The effects of hypothalamic stimulation on memory shown here represent an unanticipated collateral effect in the context of a putative treatment for morbid obesity.
The strongest evidence exists for Broadman Area 25 as target for deep brain stimulation in treatment resistant depression. This area in the brain is depicted in te figure above and is from the most important publication about DBS and depression in Neuron march 2005 by Helen Mayberg. Functional neuroimaging as well as antidepressant treatment effects suggest that this area plays an important role in modulating negative mood states. A decrease in activity is reported with clinical response to antidepressants and electroconvulsive therapy (ECT).
But depression is not a disease of a single brain region nor neurotransmitter system. It is now generally viewed as a systems-level disorder affecting integrated pathways linking select cortical, subcortical, and limbic brain regions with their related neurotransmitter systems.
Suggestions of other brain localizations for treatment with DBS for depression comes from case reports with DBS for other indications than depression. In a case report of a 56 year old patient with obsessive compulsive disorder and major depression suggests that deep brain stimulation of the ventral caudate nucleus could be a promising strategy for treatment of refractory cases of both OCD and major depression. The caudate nucleus is depicted in the figure below.
In another case report DBS was used to treat severe tardive dyskinesia in a patient suffering from major depression. DBS was performed bilaterally in the globus pallidus. The dyskinesia as well as the depression improved substantially.
In another case report deep brain stimulation was used for treatment resistant depression in a patient with borderline personality disorder and bulimia. Stimulation was targeted bilateral with eight-contact electrodes of areas at and around the inferior thalamic peduncle. The inferior thalamic peduncle is depicted in the figure below with a light blue circle. There was a good effect on depression. Depression improved progressively over a period of eight months to normal level. On an Off period of stimulation the depression took a fluctuating course. Therefore the authors were not able to prove that the electrical current induced the beneficial effects. Complete return of depression in an Off period would have. Bulimia did not subside with DBS.
Since these are case reports possible influences by placebo effect or other explanations for success can not be ruled out and these results should be interpreted with caution. Nevertheless since the authors usually select the targets based on hypothesis of function and relationships with depression further research on these techniques should be used in an extended study with treatment resistant depression.
Two other area’s are suggested in two publications in Medical Hypotheses in 2006 and 2007. Broadman area 24a and the lateral habenula are suggested in these articles as targets for deep brain stimulation for treatment refractory depression. The habenula is depicted with number 5 in the figure below. Both hypotheses are based on findings of clinical imaging studies, animal models, SPECT and PET scans.
Articles Discussed: Sartorius A, Henn FA. 1 Deep brain stimulation of the lateral habenula in treatment resistant major depression. Med Hypotheses. 2007;69(6):1305-8. Epub 2007 May 10. PMID: 17498883 [PubMed – indexed for MEDLINE]
2: Kosel M, Sturm V, Frick C, Lenartz D, Zeidler G, Brodesser D, Schlaepfer TE. Mood improvement after deep brain stimulation of the internal globus pallidus for tardive dyskinesia in a patient suffering from major depression. J Psychiatr Res. 2007 Nov;41(9):801-3. Epub 2006 Sep 8. PMID: 16962613 [PubMed – indexed for MEDLINE]
3: Aouizerate B, Martin-Guehl C, Cuny E, Guehl D, Amieva H, Benazzouz A, Fabrigoule C, Bioulac B, Tignol J, Burbaud P. Deep brain stimulation for OCD and major depression. Am J Psychiatry. 2005 Nov;162(11):2192. No abstract available. PMID: 16263870 [PubMed – indexed for MEDLINE]
4: Schlaepfer TE, Lieb K. Deep brain stimulation for treatment of refractory depression. Lancet. 2005 Oct 22-28;366(9495):1420-2. No abstract available. PMID: 16243078 [PubMed – indexed for MEDLINE]
5: Jiménez F, Velasco F, Salin-Pascual R, Hernández JA, Velasco M, Criales JL, Nicolini H. A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle. Neurosurgery. 2005 Sep;57(3):585-93; discussion 585-93. PMID: 16145540 [PubMed – indexed for MEDLINE]
6: Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH. Deep brain stimulation for treatment-resistant depression. Neuron. 2005 Mar 3;45(5):651-60. PMID: 15748841 [PubMed – indexed for MEDLINE]
What sets the latest trial apart is that it’s “the first and only study that’s executed as a prospective, randomized, double-blind trial,” for Tourette’s patients, lead author, Robert Maciunas, a neurosurgeon at Case Western Reserve University School of Medicine tells the Health Blog. “We found dramatic, life-changing results.” The results appear in this month’s issue of the Journal of Neurosurgery. The study was done by University Hospitals Case Medical Center.
Patients may be appropriate candidates for investigational studies into deep brain stimulation for depression if they meet the following criteria. (They should know that the procedure is invasive and only experimental at this point.)
1) have a diagnosis of major depression (bipolar patients are not currently being enrolled) 2) have had the illness for at least five years and are significantly disabled by it 3) current episode of depression has lasted for at least two years 4) has failed at least four trials of antidepressants (at least two different classes) as well as augmentation with at least two agents known to be effective in this group (lithium, thyroid, antipsychotics, stimulants) 5) no psychotic symptoms outside of an episode of depression (patient cannot currently be psychotic) 6) no severe personality disorder present which would interfere with safety or compliance 7) past treatment with ECT to which the patient has either been refractory or intolerant 8) ability to comply with study demands (monthly visits, prolonged testing visits, etc.)
This article on Popsci.com is a compelling story of a depressed patients treated with deep brain stimulation after failing several antidepressants and electroconvulsive therapy.
Besides the story of the patients this article covers a lot of information about DBS and the ongoing trials testing this treatment.
A 38 year old man in Minimal Conscious State (MCS) for 6 years after closed head injury after an assault was implanted bilateral Deep Brain Stimulation electrodes in his head with the tips in the central thalamus. The electrodes were turned off and on at random during different periods of 30 days. The patient was assessed by a neuro-rehabilitation team ignorant of the stimulation schedule. The patient was more alert during the DBS-on periods, he could use his limbs after instruction, and he could chew and swallow food when it was placed on his tongue. The observed improvements in arousal, motor control and behavioural persistence were due to the DBS. It seems there is another indication for DBS coming: chronic Minimal Conscious State with widely preserved brain structure and clear evidence of interactive behaviour (command following, verbalisation and inconsistent communication). Progression and long term outcome has to be assessed after this promising result. DBS is already used for Parkinson’s disease when all other options failed and sporadically for depression, again when all other options have failed. From: Nature 448, 600-603 (2 August 2007) | doi:10.1038/nature06041; Received 13 April 2007; Accepted 22 June 2007
Behavioural improvements with thalamic stimulation after severe traumatic brain injury
N. D. Schiff, J. T. Giacino, K. Kalmar, J. D. Victor, K. Baker, M. Gerber, B. Fritz, B. Eisenberg, J. O’Connor, E. J. Kobylarz, S. Farris, A. Machado, C. McCagg, F. Plum, J. J. Fins & A. R. Rezai
This is an excellent cartoon film showing the procedure of implanting deep brain stimulation for Parkinson’s disease. It teached me a lot about the operation. It’s an interactive application made by the Ohio State University. It’s amazing, want to be a neurosurgeon now.
A new neurosurgical procedure may prove helpful for patients with treatment-resistant depression. Bilateral epidural prefrontal cortical stimulation (EpCS) was found generally safe and provided significant improvement of depressive symptoms in a small group of patients
The location for Brain Stimulation in EpCS targets electrical stimulation to the anterior frontal poles and the lateral prefrontal cortex. Two different places on both hemispheres, resulting in four separate paddle leads which are connected to two small generators surgically implanted in the upper chest area of the patient. The leads are placed through a burr hole in the skull but above the dura mater and thus remain separated from the underlying cortical region by the arachnoid space. ECS is more direct than transcranial magnetic stimulation (TMS) and or vagus nerve stimulation (VNS) and potentially safer than deep brain stimulation (DBS), which involves passing the electrodes through brain tissue.
Of five patients three reached remission. Overall after seven months, the average improvement was 54.9 percent based on the Hamilton Rating Scare for Depression.
Advantages according to the team:
“Cortical stimulation has several advantages provided that it shows efficacy in treating depression. It is reversible, non-destructive and potentially safer than other forms of invasive brain stimulation since the stimulating paddles don’t come in direct contact with the brain.”
Deep Brain Stimulation (DBS) is mostly used for Parkinson’s Disease. DBS for Obsessive Compulsive Disorder and Depression is just starting to be used. It is unclear how DBS works for Parkinson’s Disease.