Deep Brain Stimulation of the Human Reward System for Major Depression—Rationale, Outcomes and Outlook

Abstract

Deep brain stimulation (DBS) as a putative approach for treatment-resistant depression (TRD) has now been researched for about a decade. Several uncontrolled studies--all in relatively small patient populations and different target regions-have shown clinically relevant antidepressant effects in about half of the patients and very recently, DBS to a key structure of the reward system, the medial forebrain bundle, has yielded promising results within few days of stimulation and at much lower stimulation intensities. On the downside, DBS procedures in regions are associated with surgical risks (eg, hemorrhage) and psychiatric complications (suicidal attenuation, hypomania) as well as high costs. This overview summarizes research on the mechanisms of brain networks with respect to psychiatric diseases and--as a novelty--extrapolates to the role of the reward system in DBS for patients with treatment-resistant depression. It further evaluates relevant methodological aspects of today's research in DBS for TRD. On the scientific side, the reward system has an important yet clearly under-recognized role in both neurobiology and treatment of depression. On the methodological side of DBS research in TRD, better animal models are clearly needed to explain clinical effects of DBS in TRD. Larger sample sizes, long-term follow-up and designs including blinded sham control are required to draw final conclusions on efficacy and side effects. Practical research issues cover study design, patient tracking, and the discussion of meaningful secondary outcome measures.

Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases

“…First, the patient populations treated with invasive or noninvasive brain stimulation are starting to converge. For example, the primary indication for TMS is depression, and the primary indication for DBS is Parkinson's disease, but DBS is being investigated as a treatment for depression, and TMS is being investigated as a treatment for Parkinson's disease (4,(20)(21)(22)(23)(24)(25). Second, although therapeutic mechanisms remain unknown, invasive and noninvasive brain stimulation share important properties.…”

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

“…By contrast, stimulation of the hippocampal electrode was reported as only mildly pleasurable, and stimulation of the tegmental electrode led the patient to complain of extreme discomfort, and he devised a method to block the button so it could not be pushed. These early studies inspired by the discovery of ICSS in rats contributed to technologies and research themes that persist today under the rubric of "deep brain stimulation" (Hariz et al, 2010;Schlaepfer et al, 2014).…”

Exploratory meta-analysis on deep brain stimulation in treatment-resistant depression

“…Be that as it may, at least 10 additional clinical trials on deep brain stimulation in depressed subjects are currently underway, according to records available at clinicaltrials.gov. Perhaps the outcome of those studies, once published, can provide further insight concerning the ultimate value of sham The information in the first three columns is summarised from a very recent review (2). The estimates of sham response were obtained by expert opinion plus random number software (http://www.random.org/integers/) (see 'Materials and methods' section).…”

“…Direct electrical stimulation in the brain continues to attract much attention for relief of treatment-resistant depression (1,2). There is, however, still great uncertainty concerning efficacy, due in part to lack of information on sham responding to the intensive selection and surgical procedures (3).…”