Current Status of Deep Brain Stimulation for Obsessive-Compulsive Disorder: A Clinical Review of Different Targets

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder that affects 2% of the general population. Despite optimal cognitive-behavioral and pharmacologic therapy, approximately 10% of patients remain treatment resistant. Currently, deep brain stimulation (DBS) is being investigated as an experimental therapy for treatment-refractory OCD. This review focuses on the efficacy and adverse events of all published DBS targets for OCD: anterior limb of the internal capsule, ventral striatum/ventral capsule, nucleus accumbens, nucleus subthalamicus, and inferior thalamic peduncle. Small studies with various designs indicate an overall average Yale-Brown Obsessive Compulsive Scale score decrease ranging from 6.8 to 31 points. The average overall responder rate is ±50%. The frequency of adverse events seems to be limited. Larger prospective studies including neuroimaging are needed to estimate adequately the true potential of DBS in treatment of OCD and to elucidate its underlying mechanism of action and optimal brain target. We conclude that DBS may be a promising and safe therapy for treatment-resistant OCD.     

Deep brain stimulation of the anterior limb of the internal capsule for treatment of therapy-refractory obsessive compulsive disorder (OCD): a case study highlighting neurocognitive and psychiatric changes

Obsessive compulsive disorder (OCD) is an anxiety disorder characterized by repeated, unwanted thoughts and behaviors. Individuals with this condition often experience significant emotional distress secondary to their symptoms. Additionally, impairments in attention/concentration, processing speed, and executive functions are typically observed. The exact pathology of OCD remains unknown; consequently, it can be difficult to treat patients with severe symptomatology. Deep brain stimulation (DBS) may be a viable treatment option for individuals who do not respond to medication and/or cognitive behavioral therapy. The following case discusses DBS of the anterior limb of the internal capsule for a patient with severe, therapy-refractory OCD, including pre- to postoperative neurocognitive and psychiatric changes.     

Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience

Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a 'learning curve' both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior-posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.     

Deep Brain Stimulation for Treatment-resistant Depression: Systematic Review of Clinical Outcomes

Major depressive disorder (MDD) is a widespread, severe, debilitating disorder that markedly diminishes quality of life. Medication is commonly effective, but 20–30 % of patients are refractory to medical therapy. The surgical treatment of psychiatric disorders has a negative stigma associated with it owing to historical abuses. Various ablative surgeries for MDD have been attempted with marginal success, but these studies lacked standardized outcome measures. The recent development of neuromodulation therapy, especially deep brain stimulation (DBS), has enabled controlled studies with sham stimulation and presents a potential therapeutic option that is both reversible and adjustable. We performed a systematic review of the literature pertaining to DBS for treatment-resistant depression to evaluate the safety and efficacy of this procedure. We included only studies using validated outcome measures. Our review identified 22 clinical research papers with 5 unique DBS approaches using different targets, including nucleus accumbens, ventral striatum/ventral capsule, subgenual cingulate cortex, lateral habenula, inferior thalamic nucleus, and medial forebrain bundle. Among the 22 published studies, only 3 were controlled trials, and 2, as yet unpublished, multicenter, randomized, controlled trials evaluating the efficacy of subgenual cingulate cortex and ventral striatum/ventral capsule DBS were recently discontinued owing to inefficacy based on futility analyses. Overall, the published response rate to DBS therapy, defined as the percentage of patients with?>?50 % improvement on the Hamilton Depression Rating Scale, is reported to be 40–70 %, and outcomes were comparable across studies. We conclude that DBS for MDD shows promise, but remains experimental and further accumulation of data is warranted.     

Animal-Assisted Intervention for Autism Spectrum Disorder: A Systematic Literature Review

The inclusion of animals in therapeutic activities, known as animal-assisted intervention (AAI), has been suggested as a treatment practice for autism spectrum disorder (ASD). This paper presents a systematic review of the empirical research on AAI for ASD. Fourteen studies published in peer-reviewed journals qualified for inclusion. The presentation of AAI was highly variable across the studies. Reported outcomes included improvements for multiple areas of functioning known to be impaired in ASD, namely increased social interaction and communication as well as decreased problem behaviors, autistic severity, and stress. Yet despite unanimously positive outcomes, most studies were limited by many methodological weaknesses. This review demonstrates that there is preliminary “proof of concept” of AAI for ASD and highlights the need for further, more rigorous research.     

Risk Factors Associated with Self-Injurious Behaviors in Children and Adolescents with Autism Spectrum Disorders

While self-injurious behaviors (SIB) can cause significant morbidity for children with autism spectrum disorders (ASD), little is known about its associated risk factors. We assessed 7 factors that may influence self-injury in a large cohort of children with ASD: (a) atypical sensory processing; (b) impaired cognitive ability; (c) abnormal functional communication; (d) abnormal social functioning; (e) age; (f) the need for sameness; (g) rituals and compulsions. Half (52.3%, n?=?126) of the children (n?=?241, aged 2–19?years) demonstrated SIB. Abnormal sensory processing was the strongest single predictor of self-injury followed by sameness, impaired cognitive ability and social functioning. Since atypical sensory processing and sameness have a greater relative impact on SIB, treatment approaches that focus on these factors may be beneficial in reducing self-harm in children with ASD.     

Restricted and repetitive behaviors and psychiatric symptoms in youth with autism spectrum disorders

Children with autism spectrum disorders (ASD) are at high risk for co-occurring psychiatric disorders. Previous research has suggested that restricted and repetitive behaviors (RRB) are associated with symptoms of co-occurring psychiatric disorders in individuals with ASD, but this relationship is not well understood. The current study investigated the relationship between RRB and co-occurring psychiatric symptoms, including depressive, anxiety, attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms, while considering the role of level of functioning. Participants were 72 parents of youth diagnosed with an ASD (ages 5–17). They completed the Social Communication Questionnaire (SCQ), the Repetitive Behavior Scale-Revised (RBS-R), an abridged version of the Child Symptom Inventory-4 (CSI-4) and the Conceptual domain of the Adaptive Behavior Assessment System, 2nd Edition (ABAS-II). Results indicated that RRB do predict psychopathology. Ritualistic and sameness behavior is predictive of anxiety, depression and ODD while stereotypy is predictive of ADHD. Restricted interests were a negative predictor of depression. Level of functioning moderated the relationship between self-injurious behavior (SIB) and both anxiety and depressive symptoms as well as the relationship between ritualistic and sameness behavior and depressive symptoms. Understanding the relationship between RRB and psychiatric symptoms could help clarify the presentation of ASD phenotypes as well as etiological variables.     

Self-injurious behavior and tuberous sclerosis complex: frequency and possible associations in a population of 257 patients

Self-injurious behavior (SIB) has been observed in people with tuberous sclerosis complex (TSC), although the frequency of SIB in TSC is largely unknown. SIB is associated with intellectual and developmental disabilities, but there is no single cause of SIB. We retrospectively examined the frequency of SIB in a population of 257 patients with TSC and determined possible associations with SIB. We found a 10% frequency of SIB in our TSC population. When compared with patients without psychiatric symptoms, we identified a significantly higher rate of electroencephalographic interictal spikes in the left frontal lobe and a significantly lower number of tubers in the left occipital, parietal, and posterior temporal lobes. We also found that frequency of TSC2 mutation, history of infantile spasms, history of seizures, mental retardation, and autism are significantly associated with SIB.     

Behavioral assessment and treatment of self-injurious behavior in autism

Self-injurious behaviors (SIB) are common in individuals who have autism and related developmental disabilities. When an individual engages in SIB, these behaviors frequently become the primary treatment target because of the potential for injury. A thorough behavioral assessment aimed at determining the function of the behaviors is the first step to developing a treatment plan. This article presents a brief background of SIB and a discussion of the behavioral assessment and treatment of these behaviors to familiarize readers with the behavioral perspective on SIB in individuals who have autism and other developmental disabilities.     

Self-injurious behavior and tuberous sclerosis complex: Frequency and possible associations in a population of 257 patients

Self-injurious behavior (SIB) has been observed in people with tuberous sclerosis complex (TSC), although the frequency of SIB in TSC is largely unknown. SIB is associated with intellectual and developmental disabilities, but there is no single cause of SIB. We retrospectively examined the frequency of SIB in a population of 257 patients with TSC and determined possible associations with SIB. We found a 10% frequency of SIB in our TSC population. When compared with patients without psychiatric symptoms, we identified a significantly higher rate of electroencephalographic interictal spikes in the left frontal lobe and a significantly lower number of tubers in the left occipital, parietal, and posterior temporal lobes. We also found that frequency of TSC2 mutation, history of infantile spasms, history of seizures, mental retardation, and autism are significantly associated with SIB.     

Axonal pathways linked to therapeutic and nontherapeutic outcomes during psychiatric deep brain stimulation

Objective:

The underlying hypothesis of our work is that specific clinical neuropsychiatric benefits can be achieved by selective activation of specific axonal pathways during deep brain stimulation (DBS). As such, the goal of this study was to develop a method for identifying axonal pathways whose activation is most likely necessary for achieving therapeutic benefits during DBS.

Experimental design:

Our approach combined clinical data, diffusion tensor tractography, and computer models of patient‐specific neurostimulation to identify particular axonal pathways activated by DBS and determine their correlations with individual clinical outcome measures. We used this method to evaluate a cohort of seven treatment‐resistant depression patients treated with DBS of the ventral anterior internal capsule and ventral striatum (VC/VS).

Principal observations:

Clinical responders exhibited five axonal pathways that were consistently activated by DBS. All five pathways coursed lateral and medial to the VS or dorsal and lateral to the nucleus accumbens; however, details of their specific trajectories differed. Similarly, one common pathway was identified across nonresponders.

Conclusions:

Our method and preliminary results provide important background for studies aiming to expand scientific characterization of neural circuitry associated with specific psychiatric outcomes from DBS. Furthermore, identification of pathways linked to therapeutic benefit provides opportunities to improve clinical selection of surgical targets and stimulation settings for DBS devices. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

     

Using Functional Communication Training to Reduce Self-Injurious Behavior for Individuals with Autism Spectrum Disorder

Journal of Autism and Developmental Disorders - Children with autism spectrum disorders (ASD) have a high risk of developing self-injurious behavior (SIB), which is often a result of deficits in...     

Panic and fear induced by deep brain stimulation

BACKGROUND: Mood, cognitive, and behavioural changes have been reported with deep brain stimulation (DBS) in the thalamus, globus pallidus interna, and anterior limb of the internal capsule/nucleus accumbens region. OBJECTIVE: To investigate panic and fear resulting from DBS. METHODS: Intraoperative DBS in the region of the right and then left anterior limb of the internal capsule and nucleus accumbens region was undertaken to treat a 52 year old man with treatment refractory obsessive-compulsive disorder (OCD). Mood, anxiety, OCD, alertness, heart rate, and subjective feelings were recorded during intraoperative test stimulation and at follow up programming sessions. RESULTS: DBS at the distal (0) contact (cathode 0-, anode 2+, pulse width 210 ms, rate 135 Hz, at 6 volts) elicited a panic attack (only seen at the (0) contact). The patient felt flushed, hot, fearful, and described himself as having a "panic attack." His heart rate increased from 53 to 111. The effect (present with either device) was witnessed immediately after turning the device on, and abruptly ceased in the off condition CONCLUSIONS: DBS of the anterior limb of the internal capsule and nucleus accumbens region caused severe "panic." This response may result from activation of limbic and autonomic networks.     

Symptom severity and challenging behavior in children with ASD

The prevalence of challenging behaviors in the autism spectrum disorders (ASD) population is often assumed to be high but relatively little research has actually been published on it. Furthermore, challenging behaviors are likely to impede progress in evidence-based treatment programs, such as early intensive behavioral intervention (EIBI). Little or no previous research has evaluated the prevalence of various topographies of challenging behavior in a population of children with ASD receiving EIBI services, nor evaluated the relationship between such behaviors and the severity of ASD symptoms. Using data from the ASD–DC and the ASD–BPC in 84 children with autism receiving EIBI services, the current study conducted a regression analysis of relations between endorsement of challenging behaviors and ASD symptom severity. Results indicated that 94% of the sample reported the presence of challenging behavior, stereotypical behaviors were the most commonly reported, and that the presence of challenging behavior was predicted by ASD severity.     

Self-injurious behavior in frontotemporal dementia

Abstract

Frontotemporal dementia (FTD) may be one of the most common neurodegenerative dementias with onset before age 65. Investigators have only recently characterized FTD, which encompasses Pick's disease as well as non-specific degeneration of the frontal lobes. Neuropsychiatric symptoms are the main features of FTD and include disinhibition, apathy, obsessive-compulsive behavior, and the Kluver-Bucy syndrome. We report a patient with FTD who developed prominent self-injurious behavior (SIB) consisting of persistent self-biting and hair-pulling. Stereotypical, repetitive SIB usually occurs in patients with autism or mental retardation; SIB is rarely discussed in patients with dementia. This report extends the neuropsychiatric spectrum of FTD to encompass SIB and discusses the potential mechanisms for SIB in these patients. The most likely contributing source for their self-injury is the development of obsessive-compulsive behaviors in the presence of coincident self-directed behaviors. Hyperorality from anterior temporal Involvement and the release of primitive grooming behavior from frontal degeneration are self-directed behaviors that contribute to the specific manifestations of SIB among FTD patients. The pharmacological management of SIB emphasizes drugs that work through opioid, serotonergic, or dopaminergic systems.     

Pilot study of deep brain stimulation in refractory obsessive-compulsive disorder ethnic Chinese patients

Aims: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is a promising alternative to ablative surgery in treatment of refractory obsessive–compulsive disorder (OCD). A pilot study was conducted to assess 15‐month outcomes of DBS in patients with refractory OCD in Taiwan. Methods: Four adult patients with a 3‐year or more history of refractory OCD (Yale–Brown Obsessive–Compulsive Scale [Y‐BOCS] score of at least 28) met the criteria for DBS surgery. DBS electrodes were implanted bilaterally in the VC/VS. Stimulation was adjusted for therapeutic benefit and absence of adverse effects. Psychiatric evaluation was conducted preoperatively, postoperatively, and at follow up at every 3 months for 15 months. Primary outcome measure was Y‐BOCS. Secondary outcomes included the Hamilton Depression Rating Scale (HAM‐D), and the Global Assessment of Function Scale. Results: Mean severity of OCD was a Y‐BOCS score of 36.3 ± 2.1. At the end of 15 months' follow up, there was a 33.06% decrease in OCD severity (P = 0.001). Similar findings were seen for HAM‐D (32.51% reduction, P = 0.005), and Global Assessment of Function Scale (31.03% increase, P = 0.026). In terms of adverse effects, two patients suffered from hypomania episodes after several weeks of DBS stimulation, and one had transient hypomania‐like syndrome during DBS initial programming. One patient (Case 1) had an allergic reaction to implantation of the pulse generator in the chest, and another patient (Case 3) exhibited vertigo. Conclusions: We confirm that DBS of the VC/VS appears to be beneficial for improvements in function and mood among patients with treatment‐resistant OCD. Compared to previous studies examining the therapeutic effects of DBS, no serious adverse effects were observed.     

Psychiatric problems of Chinese college students with high autism traits

Recent research has documented increased psychiatric problems in individuals who report elevated traits of autism spectrum disorder (ASD). However, most of the studies are conducted in Western countries, and suicidal behaviors in particular are scarcely examined in this population. The objective of the current study was to examine the prevalence of Chinese college students who surpassed a clinical cutoff for ASD, the correlations between ASD traits and psychiatric problems (i.e., depression, anxiety, obsessive-compulsive disorder [OCD], suicidal behaviors), and factors that possibly mediated the relations between ASD traits and suicidal behaviors. Results indicated that 1.50% of individuals in the sample surpassed the clinical cutoff score for ASD. Among this group who surpassed the clinical cutoff for ASD, severity of OCD symptoms was the highest among the measured psychiatric problems. ASD traits were significantly positively correlated with depression, anxiety, suicide ideation and plans, as well as OCD and its six dimensions (i.e., ordering, washing, hoarding, checking, obsession, and neutralizing). After controlling other psychiatric indicators, however, partial correlation analysis indicated that associations between ASD traits and suicide behaviors were no longer significant. Though, depression symptoms were found to mediate the link between the ASD traits and suicide ideation (for females and males) and suicide plans (for males only). Overall, these results provide a deeper insight into the characteristics of ASD traits, as well as the relationship between ASD traits and co-occurring psychiatric symptoms in a non-Western sample of Chinese college students.     

Psychosocial and behavioural factors associated with self injurious behaviour (SIB) in individuals with autism spectrum disorders (ASD)

BackgroundSelf-injurious behaviour (SIB) is a persistent and distressing difficulty which may be more prevalent and enduring for individuals with an Autism Spectrum Disorder (ASD). SIB has been largely conceptualised in research as a challenging behaviour or a repetitive and restricted behaviour, rather than a unique construct to research. As its own construct, the aetiology of SIB has been conceptualised from a neurobiological perspective, however there remains a need to explore psychosocial and behavioural factors associated with SIB and ASD. A review was conducted to compile evidence and establish current understanding of this behaviour.Method6 databases were systematically searched for research exploring factors relating specifically to SIB limited to ASD populations. Studies were critically appraised using a tool developed for the purpose of this review, adapted from the CASP, AXIS and STROBE quality appraisal tools.Results15 studies met the eligibility criteria. SIB was found to be associated with impairments in adaptive ability, communicative ability, IQ, sleep, atypical sensory processing, and impulsivity/over-activity. There were mixed findings supporting an association between autism severity and self-injury.ConclusionsThe development of SIB in ASD populations is complex. The range of factors associated with SIB and ASD imply a clinical need for a robust assessment and a multi-disciplinary approach to intervention. Theoretical perspectives regarding the role of impaired behavioural inhibition, communication, and sensory processing difficulties are considered. Limitations and future research are discussed.     

Potential Risk Factors for the Development of Self-Injurious Behavior among Infants at Risk for Autism Spectrum Disorder

Prevalence of self-injurious behavior (SIB) is as high as 50% among children with autism spectrum disorder (ASD). Identification of risk factors for the development of SIB is critical to early intervention and prevention. However, there is little empirical research utilizing a prospective design to identify early risk factors for SIB. The purpose of this study was to evaluate behavioral characteristics predicting SIB at age 2 years among 235 infants at high familial risk for ASD. Logistic regression results indicated that presence of SIB or proto-SIB and lower developmental functioning at age 12 months significantly predicted SIB at 24 months. A pattern of persistent SIB over this period was associated with a diagnosis of autism and poorer cognitive and adaptive outcomes.