Judy Luigjes

Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder

Little is known about the underlying neural mechanism of deep brain stimulation (DBS). We found that DBS targeted at the nucleus accumbens (NAc) normalized NAc activity, reduced excessive connectivity between the NAc and prefrontal cortex, and decreased frontal low-frequency oscillations during symptom provocation in patients with obsessive-compulsive disorder. Our findings suggest that DBS is able to reduce maladaptive activity and connectivity of the stimulated region.

Deep brain stimulation in addiction: a review of potential brain targets

Deep brain stimulation (DBS) is an adjustable, reversible, non-destructive neurosurgical intervention using implanted electrodes to deliver electrical pulses to areas in the brain. DBS is currently investigated in psychiatry for the treatment of refractory obsessive–compulsive disorder, Tourette syndrome and depressive disorder. Although recent research in both animals and humans has indicated that DBS may be an effective intervention for patients with treatment-refractory addiction, it is not yet entirely clear which brain areas should be targeted. The objective of this review is to provide a systematic overview of the published literature on DBS and addiction and outline the most promising target areas using efficacy and adverse event data from both preclinical and clinical studies. We found 7 animal studies targeting six different brain areas: nucleus accumbens (NAc), subthalamic nucleus (STN), dorsal striatum, lateral habenula, medial prefrontal cortex (mPFC) and hypothalamus, and 11 human studies targeting two different target areas: NAc and STN. Our analysis of the literature suggests that the NAc is currently the most promising DBS target area for patients with treatment-refractory addiction. The mPFC is another promising target, but needs further exploration to establish its suitability for clinical purposes. We conclude the review with a discussion on translational issues in DBS research, medical ethical considerations and recommendations for clinical trials with DBS in patients with addiction.

Deep brain stimulation for treatment-refractory obsessive compulsive disorder: a systematic review.

BackgroundObsessive-compulsive disorder is one of the most disabling of all psychiatric illnesses. Despite available pharmacological and psychotherapeutic treatments about 10% of patients remain severely affected and are considered treatment-refractory. For some of these patients deep brain stimulation offers an appropriate treatment method. The scope of this article is to review the published data and to compare different target structures and their effectiveness.MethodsPubMed search, last update June 2013, was conducted using the terms “deep brain stimulation” and “obsessive compulsive disorder”.ResultsIn total 25 studies were found that reported five deep brain stimulation target structures to treat obsessive-compulsive disorder: the anterior limb of the internal capsule (five studies including 14 patients), nucleus accumbens (eight studies including 37 patients), ventral capsule/ventral striatum (four studies including 29 patients), subthalamic nucleus (five studies including 23 patients) and inferior thalamic peduncle (two studies including 6 patients). Despite the anatomical diversity, deep brain stimulation treatment results in similar response rates for the first four target structures. Inferior thalamic peduncle deep brain stimulation results in higher response rates but these results have to be interpreted with caution due to a very small number of cases. Procedure and device related adverse events are relatively low, as well as stimulation or therapy related side effects. Most stimulation related side effects are transient and decline after stimulation parameters have been changed.ConclusionDeep brain stimulation in treatment-refractory obsessive-compulsive disorder seems to be a relatively safe and promising treatment option. However, based on these studies no superior target structure could be identified. More research is needed to better understand mechanisms of action and response predictors that may help to develop a more personalized approach for these severely affected obsessive compulsive patients.

Surgery for psychiatric disorders.

Surgery in psychiatric disorders has a long history and has regained momentum in the past few decades with deep brain stimulation (DBS). DBS is an adjustable and reversible neurosurgical intervention using implanted electrodes to deliver controlled electrical pulses to targeted areas of the brain. It holds great promise for therapy-refractory obsessive-compulsive disorder. Several double-blind controlled and open trials have been conducted and the response rate is estimated around 54%. Open trials have shown encouraging results with DBS for therapy-refractory depression and case reports have shown potential effects of DBS on addiction. Another promising indication is Tourette syndrome, where potential efficacy of DBS is shown by several case series and a few controlled trials. Further research should focus on optimizing DBS with respect to target location and increasing the number of controlled double-blinded trials. In addition, new indications for DBS and new target options should be explored in preclinical research.

Deep brain stimulation increases impulsivity in two patients with obsessive-compulsive disorder.

Deep brain stimulation (DBS) is an adjustable, reversible, nondestructive neurosurgical intervention using implanted electrodes to deliver electrical pulses to areas in the brain. DBS has recently shown promising results as an experimental treatment of refractory obsessive–compulsive disorder (OCD). The novelty of the treatment requires careful observation of symptoms and possible side effects in patients. This case report describes two patients with treatment-refractory OCD in whom increased voltage of deep brain stimulation targeted at the nucleus accumbens increased impulsivity. Voltage increase of stimulation resulted in an immediate inflation of self-confidence, irritability and impulsive behaviour and was reversed only after lowering the voltage. The mechanisms behind DBS are not yet fully understood. Possibly, stimulation in the area of the nucleus accumbens affects the corticostriatal circuitry, which plays an important role in impulsivity. Location and amplitude of stimulation might be critical in inducing these behaviours. These two cases underline the importance of a careful clinical assessment of impulsive behaviours during DBS for OCD.

Compulsivity in obsessive-compulsive disorder and addictions

Compulsive behaviors are driven by repetitive urges and typically involve the experience of limited voluntary control over these urges, a diminished ability to delay or inhibit these behaviors, and a tendency to perform repetitive acts in a habitual or stereotyped manner. Compulsivity is not only a central characteristic of obsessive-compulsive disorder (OCD) but is also crucial to addiction. Based on this analogy, OCD has been proposed to be part of the concept of behavioral addiction along with other non-drug-related disorders that share compulsivity, such as pathological gambling, skin-picking, trichotillomania and compulsive eating. In this review, we investigate the neurobiological overlap between compulsivity in substance-use disorders, OCD and behavioral addictions as a validation for the construct of compulsivity that could be adopted in the Research Domain Criteria (RDoC). The reviewed data suggest that compulsivity in OCD and addictions is related to impaired reward and punishment processing with attenuated dopamine release in the ventral striatum, negative reinforcement in limbic systems, cognitive and behavioral inflexibility with diminished serotonergic prefrontal control, and habitual responding with imbalances between ventral and dorsal frontostriatal recruitment. Frontostriatal abnormalities of compulsivity are promising targets for neuromodulation and other interventions for OCD and addictions. We conclude that compulsivity encompasses many of the RDoC constructs in a trans-diagnostic fashion with a common brain circuit dysfunction that can help identifying appropriate prevention and treatment targets.

The role of habits and motivation in human drug addiction: a reflection.

This Research Topic in Addictive Disorders and Behavioral Dyscontrol, a section of the journal Frontiers in Psychiatry, focuses on motivational mechanisms underlying substance use, abuse, and dependence. This is an important topic in addiction research, since most psychobiological models of drug addiction consider the motivational or reinforcing aspects of drugs to be the central drive for drug use [for an extensive overview of craving and motivation-based addiction models, see a review by Skinner and Aubin (1)]. However, motivational models alone do not seem to fully cover the complexity of addictive behaviors observed in humans, especially in relation to the more chronic, highly relapsing patterns of addiction. In recent years, habit formation theory has become more prominent for explaining the persistent pattern of addiction despite decreasing reinforcing properties of the drug and increasing negative consequences of continued drug use. According to this model, there is a shift from motivated goal-directed behavior toward more automatic and habitual behavior over the course of long-term drug abuse, which is extensively described by Everitt and Robbins (2–4). Within this framework, which is derived primarily from animal studies, habits and goal-directed behaviors (the latter being behavior motivated by the desirability of the goal) are opposing ends of the spectrum. However, human behavior is more complex than observed in laboratory animal settings, as is confirmed by clinical observations, and translation from animal to human behavior remains a challenge. Moreover, motivations and habits could be more intertwined than previously assumed. Therefore, some questions rise considering the construct of habits: is habitual behavior completely devoid of motivational underpinnings (i.e., goal-directedness) or is it possible that motivation still plays a role in habitual behavior? Moreover, is habit a unitary construct or are there different types of habituation? In this article, we present considerations in the context of human addiction and motivation in order to open the discussion toward a more careful consideration of the concept of habit and its role in drug addiction.

Is deep brain stimulation a treatment option for addiction

Keywords: Addiction; deep brain stimulation; feasibility; neuromodulation; recruitment; substance dependence

The Desire for Amputation or Paralyzation: Evidence for Structural Brain Anomalies in Body Integrity Identity Disorder (BIID).

Background Body Integrity Identity Disorder (BIID) is a condition in which individuals perceive a mismatch between their internal body scheme and physical body shape, resulting in an absolute desire to be either amputated or paralyzed. The condition is hypothesized to be of congenital nature, but evidence for a neuro-anatomical basis is sparse. Methods We collected T1-weighted structural magnetic resonance imaging scans on a 3T scanner in eight individuals with BIID and 24 matched healthy controls, and analyzed the data using voxel-based morphometry. Results The results showed reduced grey matter volume in the left dorsal and ventral premotor cortices and larger grey matter volume in the cerebellum (lobule VIIa) in individuals with BIID compared to controls. Conclusion The premotor cortex and cerebellum are thought to be crucial for the experience of body-ownership and the integration of multisensory information. Our results suggest that BIID is associated with structural brain anomalies and might result from a dysfunction in the integration of multisensory information, leading to the feeling of disunity between the mental and physical body shape.

Doubt in the Insula: Risk Processing in Obsessive-Compulsive Disorder

Extensive cleaning or checking of patients with obsessive-compulsive disorder (OCD) are often interpreted as strategies to avoid harm and as an expression of the widespread belief that OCD patients are more risk-averse. However, despite its clinical significance, the neural basis of risk attitude in OCD is unknown. Here, we investigated neural activity during risk processing using functional magnetic resonance imaging and simultaneously assessed risk attitude using a separate behavioral paradigm in OCD patients with different symptoms versus healthy controls (HCs). We found opposite insula responses to high versus low risk in OCD patients compared to HCs: a positive correlation between insula activity and risk-aversion in patients versus a negative correlation in controls. Although OCD patients overall were not more risk-averse than controls, there were differences between subgroups of OCD patients: patients with doubt/checking symptoms were more risk-averse than other patients. Taken together, OCD patients show a reversed pattern of risk processing by the insula compared to HCs. Moreover, the data suggest that increased activation of the insula signals an abnormal urge to avoid risks in the subpopulation of OCD patients with doubt and checking symptoms. These results indicate a role for the insula in excessive risk-avoidance relevant to OCD.