Original ArticleAcute Effects of Electrical Stimulation of the Bed Nucleus of the Stria Terminalis/Internal Capsule in Obsessive-Compulsive Disorder
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
References (32)
- et al.
Stereotactic treatment of Gilles de la Tourette syndrome by high frequency stimulation of thalamus
Lancet
(1999) - et al.
Deep brain stimulation for treatment-resistant depression
Neuron
(2005) - et al.
Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder
Lancet
(1999) - et al.
Surgical approaches in psychiatry: a survey of the world literature on psychosurgery
World Neurosurg
(2017) - et al.
Deep brain stimulation in the treatment of obsessive-compulsive disorder
World Neurosurg
(2013) - et al.
Neuromodulation in obsessive-compulsive disorder
Psychiatr Clin North Am
(2014) - et al.
Smile and laughter induction and intraoperative predictors of response to deep brain stimulation for obsessive-compulsive disorder
Neuroimage
(2011) - et al.
A meta-analysis of functional neuroimaging in obsessive-compulsive disorder
Psychiatry Res
(2004) - et al.
Network perspectives on the mechanisms of deep brain stimulation
Neurobiol Dis
(2010) - et al.
Deep brain stimulation of the nucleus accumbens and bed nucleus of stria terminalis for obsessive-compulsive disorder: a case series
World Neurosurg
(2015)
The application of deep brain stimulation in the treatment of psychiatric disorders
Int Rev Psychiatry
Current status of deep brain stimulation for obsessive-compulsive disorder: a clinical review of different targets
Curr Psychiatry Rep
A systematic review of psychiatric indications for deep brain stimulation, with focus on major depressive and obsessive-compulsive disorder
Nord J Psychiatry
Role of the dorsal anterior cingulate cortex in obsessive-compulsive disorder: converging evidence from cognitive neuroscience and psychiatric neurosurgery
J Neurosurg
Deep brain stimulation for obsessive-compulsive disorder: a systematic review and meta-analysis
Psychol Med
Deep brain stimulation for obsessive-compulsive disorder: systematic review and evidence-based guideline sponsored by the American Society for Stereotactic and Functional Neurosurgery and the Congress of Neurological Surgeons (CNS) and endorsed by the CNS and American Association of Neurological Surgeons
Neurosurgery
Cited by (20)
Deep brain stimulation in the bed nucleus of the stria terminalis: A symptom provocation study in patients with obsessive-compulsive disorder
2022, Journal of Psychiatric ResearchCitation Excerpt :Informal (non-standardized) symptom provocation has typically been part of the post-operative parameter selection procedure at our center. Furthermore, as mentioned above, acute ‘improvement’ with DBS has been described repeatedly (e.g., reduction of anxiety and tension, smiling, lightened mood), although it is important to note that comprehensive symptom relief often takes much more time to develop (Denys et al., 2010; Luyten et al., 2016; Okun et al., 2007; Provenza et al., 2021; Tsai et al., 2014; Winter et al., 2018). Apart from providing fundamental insights in the effects of unilateral versus bilateral BST stimulation for the first time, this study is thus also a first endeavor to select stimulation contacts purely guided by their anatomical position and a brief, standardized symptom provocation task.
Deep Brain Stimulation in the Bed Nucleus of Stria Terminalis in Obsessive-Compulsive Disorder—1-Year Follow-up
2021, World NeurosurgeryCitation Excerpt :The same group has also demonstrated that the symptom reduction was stable over time.36 Acute positive effects on obsessions have also been reported with BNST stimulation in a study of 3 patients who were stimulated with low-voltage stimulation the day after surgery.37 When discussing the results of BNST DBS, it is important to keep in mind that the effect is not necessarily achieved from stimulating the nucleus itself.
Long-Term Deep Brain Stimulation in Treatment-Resistant Obsessive-Compulsive Disorder: Outcome and Quality of Life at Four to Eight Years Follow-Up
2021, NeuromodulationCitation Excerpt :Adjustment of stimulation settings was continuously performed by a neurosurgeon who had greater than ten years experience with programming of DBS devices during outpatient visits. Determination of optimal stimulation settings in each patient was based on clinical effects starting directly after postoperative test stimulation (21). Descriptive data on the variables of interest are given throughout the results.
Functional anatomy of the bed nucleus of the stria terminalis–hypothalamus neural circuitry: Implications for valence surveillance, addiction, feeding, and social behaviors
2021, Handbook of Clinical NeurologyCitation Excerpt :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).
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.