Elsevier

World Neurosurgery

Volume 111, March 2018, Pages e471-e477
World Neurosurgery

Original Article
Acute Effects of Electrical Stimulation of the Bed Nucleus of the Stria Terminalis/Internal Capsule in Obsessive-Compulsive Disorder

https://doi.org/10.1016/j.wneu.2017.12.084Get rights and content

Background

Deep brain stimulation (DBS) has been introduced as a treatment option for treatment-resistant obsessive-compulsive disorder (OCD). However, the optimal stimulation target and the corresponding stimulation settings remain unclear. Furthermore, there is limited knowledge about the acute effects of DBS.

Methods

In 3 patients with treatment-resistant OCD, DBS electrodes were implanted in the bed nucleus of the stria terminalis (BNST)/internal capsule (IC). On the next day, different electrode pairs (BNST only, IC only, and BNST/IC) were stimulated at different voltages (1, 2, and 3.5 V) for 5 minutes each. Afterwards, patients rated their perceived OCD symptoms and various emotional states on corresponding visual analog scales.

Results

Across locations, low voltage stimulation (1 and 2 V) was associated with reduction of OCD symptoms (i.e., anxiety and tension), in particular when the IC was stimulated. High voltage stimulation (3.5 V), in particular when BNST was involved, led to less reduction of OCD symptoms. Moreover, 3.5-V stimulation of the BNST (BNST only and BNST/IC) induced higher levels of anxiety, tension, and discomfort. Subjects also reported an increase in vegetative sensations.

Conclusions

In summary, we demonstrate that both stimulation site and voltage settings show sweet spots (2 V at IC or BNST/IC) at which OCD symptom severity decreased while negative effects were minimal. Stimulation of IC fibers might be relevant both for acute and chronic effects. Whether acute effects are useful for outcome prediction remains to be shown in future studies.

Introduction

Deep brain stimulation (DBS) is a well-established treatment of movement disorders such as Parkinson disease, tremor, and dystonia.1 A growing amount of evidence has proven its therapeutic benefit also in treatment-resistant neuropsychiatric disorders such as Tourette syndrome, major depressive disorder, and treatment-resistant obsessive-compulsive disorder (trOCD).2, 3, 4, 5 To date, >110 patients suffering from trOCD have received DBS.6, 7, 8, 9, 10 However, the optimal target for stimulation is still a matter of debate.11, 12 As of yet, up to 5 different brain regions have been investigated to treat the suspected underlying disturbances in the frontal, orbital, and cortico-striatal-thalamo-cortical circuitries responsible for the development of obsessive-compulsive disorder (OCD).8, 9 Although the nucleus accumbens has been favored as a site for DBS by several groups, more recently the bed nucleus of the stria terminalis (BNST) has been introduced as another target within the cortico-striato-thalamo-cortical neuroanatomic network thought to be involved in the pathophysiology underlying OCD.4 The BNST is considered part of the extended amygdala, and there is evidence both from clinical observations13, 14 and animal studies15 to support its involvement in OCD. Thus far, however, there is no evidence to support the superiority of one target over the other.5 Different responses to acute stimulation have been reported, such as smiling, euphoria and laughter,16, 17 panic,18 and aggression.19 Furthermore, changes in mood, anxiety, spontaneity, verbal fluency, and facial expressiveness with chronic DBS of the ventral striatum have been reported.20, 21 Interestingly, intense laughter has been suggested as a possible predictor of outcome in OCD patients.22, 23

Here, we report on 3 patients with trOCD and describe the acute effects of electrical stimulation of different stimulation settings on OCD symptoms and mood state after implantation of DBS electrodes in the BNST/internal capsule (IC).24, 25 To our knowledge, acute effects after DBS in this particular area have not been described before, in particular in response to different stimulation settings.26

Section snippets

Participants

This study received approval by the local ethics committee, and all participants gave informed written consent before entering the study. Inclusion criteria were 1) diagnosis of trOCD for a minimum duration of 10 years; 2) a score ≥25 on the Yale-Brown Obsessive Compulsive Scale; 3) the presence of therapy-refractory symptoms after 3 treatment attempts with selective serotonin-reuptake inhibitors, of which one had to be clomipramine; 4) additive therapy with an (atypical) neuroleptic; and 5)

Effect of Different Stimulation Conditions on OCD Symptoms

Across electrode locations, stimulation at 1 and 2 V was associated with lower self-reported OCD symptoms compared with baseline. In contrast, the reduction in OCD symptoms compared with no stimulation was much smaller at 3.5-V stimulation for BNST, however not for BNST/IC (Figure 2).

Effect of Different Stimulation Conditions on Positive and Negative Emotions

At low voltages (1 and 2 V), patients reported less anxiety and tension across all electrode locations (Figure 3). Furthermore, all patients started smiling at these voltages. Comfort, discomfort, and joy were not

Discussion

Thus far, the optimal site for chronic DBS in trOCD remains unclear.1, 7 Notably, stimulation of both BNST and the nucleus accumbens also involves stimulation of fiber tracts in the IC.4, 13, 30 It also appears that there is no uniform pattern of stimulation of lower contacts (located in the nucleus accumbens or in BNST) versus upper contacts (located in IC) in published studies. With that regard, it is likely that stimulation of both nuclei and fiber tracts exerts differential effects that not

Conclusions

Taken together, we describe acute effects of electrical stimulation at different sites (BNST only, IC only, and BNST/IC) with different voltages (1, 2, and 3.5 V). Limitations of our study are the number of patients included and the inherent reliance on subjective perceptions in patients with neuropsychiatric disorders such as OCD. Further, the effects of acute stimulation may not be compared with those of chronic stimulation where often higher voltages are needed both regarding thresholds for

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      Recently, the BNST has emerged as a therapeutic target against mood disorders. Long-term deep brain stimulation in the BNST improves severe obsessive–compulsive disorder symptoms (Winter et al., 2018), treatment resistant anorexia nervosa, and major depressive disorder (Blomstedt et al., 2017). Circuitry between the BNST and reward and mood-related areas contribute to drug-associated behaviors, including drug-seeking and the affective symptoms of withdrawal and intoxication (Vranjkovic et al., 2017).

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    Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

    Lotta Winter and Ivo Heitland are co–first authors.

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