Deep Brain Stimulation: Rekindling a Neurosurgical Approach to Psychiatry

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Over the years, advancements in the understanding of psychopathology involved (literally) probing into the human brain through psychosurgery. Through various forms of lobotomy and brain stimulation, mankind was able to further explore the connection between the brain and behavior.

However, psychosurgery has been as equally hazardous and controversial as it has been insightful and revolutionary. Psychiatric disorders have been tackled using a combination of psychotherapy and psychotropic medications. However, even today, victims of psychiatric conditions continue to be marred by poor prognoses, high relapse rates, and ineffective alleviation of symptomatology.

Recently, there has been a revival of a neurosurgical approach to psychiatry, not through ablative measures, but through focal neurostimulation, particularly, deep brain stimulation (DBS).

DBS as a Proven Therapeutic Procedure- for Parkinson’s Disease

DBS is an invasive stereotactic procedure that involves implanting electrodes to send electrical impulses to stimulate various regions of the brain. Through stimulation of subcortical regions within the brain such as the subthalamic nucleus (STN) and the Globus pallidus (GPi), DBS has garnered growing interest as a psychiatric procedure, particularly because of its proven therapeutic effectiveness for medication-refractory tremors, akinesias, and dystonias associated with Parkinson’s Disease (PD) (Johnson et al., 2008).

The mechanisms underlying DBS’ therapeutic activity are complex, but DBS appears to improve PD motor symptoms, in large part, through acting like a ‘reversible lesion.’ It reversibly inhibits the aberrant firing of neurons within the STN and GPi which are in proximity to implanted electrodes (Herrington, Cheng, & Eskandar, 2016).

While it does not cure PD entirely, through alleviating Parkinsonian motor symptoms, DBS has been effective in improving the quality of life for PD patients.

DBS and Depression

Given the debilitating nature of major depressive disorder (MDD), coupled with a high incidence of treatment-resistant depression (TRD), DBS could potentially benefit a large demographic of patients struggling with clinical depression.

Recent clinical research findings suggest that the stimulation of the medial forebrain bundle (MFB) has a high level of antidepressant efficacy. This stems from the well-established notion that the mesolimbic “reward” pathway, involving the neurotransmitter dopamine, exists within the MFB, and using DBS to stimulate a ‘feel good’ pathway could ameliorate depression (Delaloye & Holtzheimer, 2014).

Other findings suggest that stimulating another structure within the dopaminergic pathway, the Nucleus Accumbens (NAcc), could also potentially treat depression. DBS of the NAcc has been found to sustain antidepressant effects for up to four years in patients with TRD (Bewernick et al., 2012).

While more research is needed to substantiate DBS as a therapeutic for depression, such findings augur well for this procedure in the future.

DBS and Obsessive-Compulsive Disorder (OCD)

Recent findings suggest that using DBS to stimulate the subthalamic nucleus (STN), the nucleus accumbens, and striatal regions of the brain can improve the symptomatology of OCD by at least 50%. This has reflected through lower scores over time on the Yale–Brown Obsessive Compulsive Scale (YBOCS), the gold standard assessment of OCD severity.

Patients have reported improvements in global functioning and marked reductions in compulsive behavior (Naesström, Blomstedt, & Bodlund, 2016). Given that up to 60% of OCD cases do not respond to conventional treatments, DBS could provide an invaluable dimension of treatment for the disorder.

Within the last decade, the FDA has approved DBS as a treatment for OCD (FDA, 2009). In fact, in Spring 2015, Sara and Amanda Eldritch, twin sisters from Colorado suffering from severe OCD since puberty, were the first patients in their state to undergo DBS for their condition.

Their case received widespread media attention, including on the television talk show, The Doctors. They cited the surgery as a “godsend,” with a significant decrease in their compulsive showering, and were able to get “a little bit of control back” after being “hijacked for 30 years.”

Unfortunately, given that the two also suffered from previous depression, the two eventually succumbed to suicide this year (Washington Post, 2018). However, this outcome appears to be a case of a long-term escalation of their OCD, comorbidity with other mental health issues, and a case of DBS being ‘too little too late’ for these twins.

Regardless, the improvements in OCD symptoms in these twins prior to their suicide still highlight the benefits that DBS can elicit in those with OCD, especially sufferers of severe OCD.

Expanding Into Other Avenues of Psychiatry

DBS is now being investigated as a potential treatment for symptoms underlying a much wider array of psychiatric conditions, such as epilepsy, Alzheimer’s Disease (AD), and even anorexia nervosa (AN).

For epilepsy, associated with seizures because of the excessive firing of neurons, DBS is believed to inhibit the propagation of these abnormal impulses through creating a ‘pseudo-lesion’ within regions of the thalamus. Thalamic stimulation using DBS has been found to reduce seizure frequency by as much as 69%. Moreover, DBS has also been associated with improvements in mood and cognition in epileptic patients (Chan et al., 2018).

As for Alzheimer’s Disease, DBS of the fornix, a nerve fiber bundle within the brain, has been shown to stimulate activity of the hippocampus, manifesting in improved memory performances in maze tasks in animal models (Hescham et al., 2016; Stypulkowski, Stanslaski, & Giftakis, 2017). In humans, there has been some therapeutic effect in patients over 65, such as slower cognitive decline and an increase in cerebral glucose metabolism, indicating greater brain activity (Lozano et al., 2016).

With respect to anorexia nervosa (AN), within the last two years, neurosurgeons at the Hospital del Mar in Barcelona have been attempting DBS on four AN patients, through stimulating brain regions controlling mood and the mesolimbic pathway.

So far, early results show three of the four patients having gained weight, with one patient, who has suffered from AN for 27 years, eating seafood for the first time. Given that this psychiatric condition has the highest mortality rate, and a high rate of relapse, this (option) could be a revolutionary finding in the quest to improve the prognosis of such a dangerous eating disorder (Bertran & Prieto, 2018). 

Risks and Complications of DBS

As with many invasive and surgical procedures, DBS also comes with its fair share of complications. For instance, DBS, because of  its inherent stimulation of brain regions, carries a risk of eliciting other movement disorders, such as dyskinesias, as well as reduced coordination and disturbances to speech and gait. However, given that DBS is reversible, these side effects are not permanent.

Other extremely rare, but potential complications include issues with surgical error such as misplaced devices, or in particularly rare cases, bleeding and brain hemorrhages (Davies, 2018). However, these are risks associated with any major neurosurgical procedure.

What the Future Holds for DBS in Psychiatry

As promising as the above findings are, the psychiatric application of DBS is still in its infancy. Much more research is needed to substantiate its effectiveness in the future. However, early clinical findings suggest a potentially groundbreaking role for DBS in psychiatry.

Moreover, given the comorbidity of a number of mental illnesses, DBS could also be effective in treating multiple psychiatric conditions at once. There is ever-growing room to expand the clinical applications of DBS, which will lead to much greater overlap between neurosurgery and psychiatry. In the end, this overlap could save and improve the lives of millions of psychiatric patients now and in the future.

References

Bertran, M., & Prieto, G. (2018, July 12). Tractament pioner contra l’anorèxia crònica amb la implantació d’elèctrodes al cervell. Corporació Catalana De Mitjans Audiovisuals. Retrieved July 14, 2018, from http://www.ccma.cat/324/tractament-pioner-contra-l-anorexia-cronica-amb-la-implantacio-d-electrodes-al-cervell/noticia/2866214/

Bewernick, B. H., Kayser, S., Sturm, V., & Schlaepfer, T. E. (2012). Long-Term Effects of Nucleus Accumbens Deep Brain Stimulation in Treatment-Resistant Depression: Evidence for Sustained Efficacy. Neuropsychopharmacology37(9), 1975–1985. http://doi.org/10.1038/npp.2012.44

Chan, A. Y., Rolston, J. D., Rao, V. R., & Chang, E. F. (2018). Effect of neurostimulation on cognition and mood in refractory epilepsy. Epilepsia Open3(1), 18–29. http://doi.org/10.1002/epi4.12100

Davies, N. (2018, July 10). Weighing the Risks of Deep Brain Stimulation. Retrieved July 14, 2018, from https://www.neurologyadvisor.com/movement-disorders-advisor/deep-brain-stimulation-movement-disorders-risk/article/779159/?check=true

Delaloye, S., & Holtzheimer, P. E. (2014). Deep brain stimulation in the treatment of depression. Dialogues in Clinical Neuroscience16(1), 83–91.

Herrington, T. M., Cheng, J. J., & Eskandar, E. N. (2016). Mechanisms of deep brain stimulation. Journal of Neurophysiology115(1), 19–38. http://doi.org/10.1152/jn.00281.2015

Hescham, S., Temel, Y., Schipper, S., Lagiere, M., Schönfeld, L., Blokland, A., & Jahanshahi, A. (2016). Fornix deep brain stimulation induced long-term spatial memory independent of hippocampal neurogenesis. Brain Structure and Function, 222(2), 1069-1075. doi:10.1007/s00429-016-1188-y

Johnson, M. D., Miocinovic, S., McIntyre, C. C., & Vitek, J. L. (2008). Mechanisms and targets of deep brain stimulation in movement disorders. Neurotherapeutics5(2), 294–308. http://doi.org/10.1016/j.nurt.2008.01.010

 Lozano, A. M., Fosdick, L., Chakravarty, M. M., Leoutsakos, J.-M., Munro, C., Oh, E., … Smith, G. S. (2016). A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer’s Disease. Journal of Alzheimer’s Disease54(2), 777–787. http://doi.org/10.3233/JAD-160017

Naesström, M., Blomstedt, P., & Bodlund, O. (2016). A systematic review of psychiatric indications for deep brain stimulation, with focus on major depressive and obsessive-compulsive disorder. Nordic Journal of Psychiatry, 70(7), 483-491. doi:10.3109/08039488.2016.1162846

Stypulkowski, P. H., Stanslaski, S. R., & Giftakis, J. E. (2017). Modulation of hippocampal activity with fornix Deep Brain Stimulation. Brain Stimulation, 10(6), 1125-1132. doi:10.1016/j.brs.2017.09.002

US Food and Drug Administration (FDA). FDA News Release: FDA Approves Humanitarian Device Exemption for Deep Brain Stimulator for Severe Obsessive-Compulsive Disorder. February 19, 2009. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2009/ucm149529.htm. Accessed July 14, 2018.

Washington Post. (2018, April 4). Twin sisters known for battle with debilitating OCD die in possible ‘suicide pact’. The Washington Post. Retrieved July 14, 2018, from https://www.washingtonpost.com/news/morning-mix/wp/2018/04/04/

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