Deep brain stimulation (DBS) at the interface of neurology and psychiatry

The Journal of clinical investigation (Impact Factor: 13.22). 11/2013; 123(11):4546-56. DOI: 10.1172/JCI68341
Source: PubMed


Deep brain stimulation (DBS) is an emerging interventional therapy for well-screened patients with specific treatment-resistant neuropsychiatric diseases. Some neuropsychiatric conditions, such as Parkinson disease, have available and reasonable guideline and efficacy data, while other conditions, such as major depressive disorder and Tourette syndrome, have more limited, but promising results. This review summarizes both the efficacy and the neuroanatomical targets for DBS in four common neuropsychiatric conditions: Parkinson disease, Tourette syndrome, major depressive disorder, and obsessive-compulsive disorder. Based on emerging new research, we summarize novel approaches to optimization of stimulation for each neuropsychiatric disease and we review the potential positive and negative effects that may be observed following DBS. Finally, we summarize the likely future innovations in the field of electrical neural-network modulation.

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    • "While DBS is currently FDA-approved for the treatment of obsessive–compulsive disorder (OCD), limited but promising results have been reported in regard to mood and cognitive disorders (Ashkan et al., 2013; Tye et al., 2009; Williams and Okun, 2013). Therefore, DBS is currently being tested for the treatment of patients who are non-responsive to all evidence-based therapies for TRD (Williams and Okun, 2013). Despite an incomplete understanding of the mechanisms involved in the therapeutic response, DBS seems to produce a significant reduction in symptoms and high rates of remission in TRD (Anderson et al., 2012). "
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    ABSTRACT: Despite a wide variety of therapeutic interventions for major depressive disorder (MDD), treatment resistant depression (TRD) remains to be prevalent and troublesome in clinical practice. In recent years, deep brain stimulation (DBS) has emerged as an alternative for individuals suffering from TRD not responding to combining antidepressants, multiple adjunctive strategies and electroconvulsive therapy (ECT). Although the best site for TRD-DBS is still unclear, pilot data suggests that the medial forebrain bundle (MFB) might be a key target to accomplish therapeutic efficacy in TRD patients. To explore the anatomic, electrophysiologic, neurocognitive and treatment data supporting the MFB as a target for TRD-DBS. The MFB connects multiple targets involved in motivated behavior, mood regulation and antidepressant response. Specific phenomenology associated with TRD can be linked specifically to the superolateral branch (sl) of the MFB (slMFB). TRD patients who received DBS-slMFB reported high response/remission rates with an improvement in functioning and no significant adverse outcomes in their physical health or neurocognitive performance. Discussion The slMFB is an essential component of a network of structural and functional pathways connecting different areas possibly involved in the pathogenesis of mood disorders. Therefore, the slMFB should be considered as an exciting therapeutic target for DBS therapy to achieve a sustained relief in TRD patients. There is an urgent need for clinical trials exploring DBS-slMFB in TRD. Further efforts should pursue measuring baseline pro-inflammatory cytokines, oxidative stress, and cognition as possible biomarkers of DBS-slMFB response in order to aid clinicians in better patient selection. Copyright © 2014 Elsevier Inc. All rights reserved.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 12/2014; 58. DOI:10.1016/j.pnpbp.2014.12.003 · 3.69 Impact Factor
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    • "mechanosensation), which has already been demonstrated in macaques via microstimulation of somatosensory cortex (Berg et al., 2013; O'Doherty et al., 2011; Tabot et al., 2013). Beyond the experimental domain, electrical stimulation of the brain, spinal cord and peripheral nerves via implanted electrodes is in use clinically for the treatment of movement disorders (Williams and Okun, 2013), psychiatric disorders (Williams and Okun, 2013), chronic pain (Plow et al., 2012), epilepsy (Bergey, 2013), neurogenic bladder (Lay and Das, 2012) and for the restoration of lost sensory functions such as hearing (Carlson et al., 2012; Shepherd et al., 2013). Currently, the most commercially successful sensory prosthesis is the cochlear implant for treatment of neural deafness, of which the US National Institutes of Health reports there were 324,200 recipients worldwide in "
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    ABSTRACT: The field of neurobionics offers hope to patients with sensory and motor impairment. Blindness is a common cause of major sensory loss, with an estimated 39 million people worldwide suffering from total blindness in 2010. Potential treatment options include bionic devices employing electrical stimulation of the visual pathways. Retinal stimulation can restore limited visual perception to patients with retinitis pigmentosa, however loss of retinal ganglion cells precludes this approach. The optic nerve, lateral geniculate nucleus and visual cortex provide alternative stimulation targets, with several research groups actively pursuing a cortically-based device capable of driving several hundred stimulating electrodes. While great progress has been made since the earliest works of Brindley and Dobelle in the 1960s and 70s, significant clinical, surgical, psychophysical, neurophysiological, and engineering challenges remain to be overcome before a commercially-available cortical implant will be realized. Selection of candidate implant recipients will require assessment of their general, psychological and mental health, and likely responses to visual cortex stimulation. Implant functionality, longevity and safety may be enhanced by careful electrode insertion, optimization of electrical stimulation parameters and modification of immune responses to minimize or prevent the host response to the implanted electrodes. Psychophysical assessment will include mapping the positions of potentially several hundred phosphenes, which may require repetition if electrode performance deteriorates over time. Therefore, techniques for rapid psychophysical assessment are required, as are methods for objectively assessing the quality of life improvements obtained from the implant. These measures must take into account individual differences in image processing, phosphene distribution and rehabilitation programs that may be required to optimize implant functionality. In this review, we detail these and other challenges facing developers of cortical visual prostheses in addition to briefly outlining the epidemiology of blindness, and the history of cortical electrical stimulation in the context of visual prosthetics.
    Brain Research 11/2014; DOI:10.1016/j.brainres.2014.11.020 · 2.84 Impact Factor
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    • "For these treatment - resistant patients , high - frequency electrical stimulation of sub - cortical brain structures , known as deep brain stimulation ( DBS ) , presents a highly successful therapeutic alternative ( Benabid et al . , 2005 ; Williams and Okun , 2013 ) . DBS is FDA - approved for the treatment of Parkinson ' s disease ( PD ) and essential tremor ( ET ) ( Benabid et al . "
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    ABSTRACT: Current strategies for optimizing deep brain stimulation (DBS) therapy involve multiple postoperative visits. During each visit, stimulation parameters are adjusted until desired therapeutic effects are achieved and adverse effects are minimized. However, the efficacy of these therapeutic parameters may decline with time due at least in part to disease progression, interactions between the host environment and the electrode, and lead migration. As such, development of closed-loop control systems that can respond to changing neurochemical environments, tailoring DBS therapy to individual patients, is paramount for improving the therapeutic efficacy of DBS. Evidence obtained using electrophysiology and imaging techniques in both animals and humans suggests that DBS works by modulating neural network activity. Recently, animal studies have shown that stimulation-evoked changes in neurotransmitter release that mirror normal physiology are associated with the therapeutic benefits of DBS. Therefore, to fully understand the neurophysiology of DBS and optimize its efficacy, it may be necessary to look beyond conventional electrophysiological analyses and characterize the neurochemical effects of therapeutic and non-therapeutic stimulation. By combining electrochemical monitoring and mathematical modeling techniques, we can potentially replace the trial-and-error process used in clinical programming with deterministic approaches that help attain optimal and stable neurochemical profiles. In this manuscript, we summarize the current understanding of electrophysiological and electrochemical processing for control of neuromodulation therapies. Additionally, we describe a proof-of-principle closed-loop controller that characterizes DBS-evoked dopamine changes to adjust stimulation parameters in a rodent model of DBS. The work described herein represents the initial steps toward achieving a "smart" neuroprosthetic system for treatment of neurologic and psychiatric disorders.
    Frontiers in Neuroscience 06/2014; 8(8):169. DOI:10.3389/fnins.2014.00169 · 3.66 Impact Factor
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