Anterior Limb Of The Internal Capsule Research Articles

Cognitive behavioral therapy in patients with deep brain stimulation for obsessive-compulsive disorder: a matched controlled study.

Deep brain stimulation (DBS) is effective for refractory obsessive-compulsive disorder (OCD). Post-operative cognitive behavioral therapy (CBT) may augment the effects of DBS, but previous results are conflicting. Here, we investigated whether CBT augments the effect of DBS for OCD. Patients with and without CBT following DBS of the ventral anterior limb of the internal capsule were included. First, we analyzed Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Hamilton Depression Rating Scale (HAM-D) scores before, during and after CBT in all patients with CBT. Second, we matched patients with and without CBT based on clinical baseline variables and initial response to DBS and compared the course of Y-BOCS and HAM-D scores over the same timeframe. In total, 36 patients with and 16 patients without CBT were included. Average duration of CBT was 10.4 months (s.d. 6.4). In the 36 patients with CBT, Y-BOCS scores decreased on average by 3.8 points (14.8%) from start until end of CBT (p = 0.043). HAM-D scores did not decrease following CBT. Second, 10 patients with CBT were matched to 10 patients without CBT. In both groups, Y-BOCS scores decreased equally from start until end of CBT or over a similar timeframe (10% in CBT group v. 13.1% in no-CBT group, p = 0.741). Obsessive-compulsive symptoms decreased over time in patients with and without post-operative CBT. Therefore, further improvement may be attributed to late effects of DBS itself. The present study emphasizes the need for prospective randomized controlled studies, examining the effects of CBT.

A population-normalized tractographic fiber atlas of the anterior limb of the internal capsule: relevance to surgical neuromodulation.

The anterior limb of the internal capsule (ALIC) is a white matter highway that connects several subcortical structures to the prefrontal cortex. Although surgical interventions in the ALIC have been used to treat a number of psychiatric illnesses, there is significant debate regarding what fibers are targeted for intervention. This debate is partially due to an incomplete understanding of connectivity in the region. To better understand this complex structure, the authors employed a novel tractography-based approach to examine how fibers from the thalamus and subthalamic nucleus (STN) traverse the ALIC. Furthermore, the authors analyzed connections from the medial dorsal nucleus, anterior nucleus, and ventral anterior nucleus of the thalamus. The results showed that there is an organizational gradient of thalamic fibers medially and STN fibers laterally in the ALIC that fades more anteriorly. These findings, in combination with the known corticotopic organization described by previous studies, allow for a more thorough understanding of the organization of the white matter fibers in the ALIC. These results are important for understanding and targeting of neuromodulatory therapies in the ALIC and may help explain why differences in therapeutic effect are observed for different areas of the ALIC.

Internal Capsule/Nucleus Accumbens Deep Brain Stimulation Increases Impulsive Decision Making in Obsessive-Compulsive Disorder

BackgroundDeep brain stimulation of the anterior limb of the internal capsule (ALIC)/nucleus accumbens is an effective treatment in patients with obsessive-compulsive disorder but may increase impulsive behavior. We aimed to investigate how active stimulation alters subdomains of impulsive decision making and whether respective effects depend on the location of stimulation sites. MethodsWe assessed 15 participants with obsessive-compulsive disorder performing the Cambridge Gambling Task during active and inactive ALIC/nucleus accumbens deep brain stimulation. Specifically, we determined stimulation-induced changes in risk adjustment and delay aversion. To characterize underlying neural pathways, we computed probabilistic stimulation maps and applied fiber filtering based on normative structural connectivity data to identify “hot” and “cold” spots/fibers related to changes in impulsive decision making. ResultsActive stimulation significantly reduced risk adjustment while increasing delay aversion, both implying increased impulsive decision making. Changes in risk adjustment were robustly associated with stimulation sites located in the central ALIC and fibers connecting the thalamus and subthalamic nucleus with the medial and lateral prefrontal cortex. Both hot spots and fibers for changes in risk adjustment were robust to leave-one-out cross-validation. Changes in delay aversion were similarly associated with central ALIC stimulation, but validation hereof was nonsignificant. ConclusionsOur findings provide experimental evidence that ALIC/nucleus accumbens stimulation increases impulsive decision making in obsessive-compulsive disorder. We show that changes in risk adjustment depend on the location of stimulation volumes and affected fiber bundles. The relationship between impulsive decision making and long-term clinical outcomes requires further investigation.

White matter abnormalities and multivariate pattern analysis in anti-NMDA receptor encephalitis.

ObjectiveThis study aimed to investigate white matter (WM) microstructural alterations and their relationship correlation with disease severity in anti-NMDA receptor (NMDAR) encephalitis. Multivariate pattern analysis (MVPA) was applied to discriminate between patients and healthy controls and explore potential imaging biomarkers.MethodsThirty-two patients with anti-NMDAR encephalitis and 26 matched healthy controls underwent diffusion tensor imaging. Tract-based spatial statistics and atlas-based analysis were used to determine WM microstructural alterations between the two groups. MVPA, based on a machine-learning algorithm, was applied to classify patients and healthy controls.ResultsPatients exhibited significantly reduced fractional anisotropy in the corpus callosum, fornix, cingulum, anterior limb of the internal capsule, and corona radiata. Moreover, mean diffusivity was increased in the anterior corona radiata and body of the corpus callosum. On the other hand, radial diffusivity was increased in the anterior limb of the internal capsule, cingulum, corpus callosum, corona radiata, and fornix. WM changes in the cingulum, fornix, and retrolenticular part of the internal capsule were correlated with disease severity. The accuracy, sensitivity, and specificity of fractional anisotropy-based classification were each 78.33%, while they were 67.71, 65.83, and 70% for radial diffusivity.ConclusionWidespread WM lesions were detected in anti-NMDAR encephalitis. The correlation between WM abnormalities and disease severity suggests that these alterations may serve a key role in the pathophysiological mechanisms of anti-NMDAR encephalitis. The combination of tract-based spatial statistics and MVPA may provide more specific and complementary information at the group and individual levels.

Tractography-based versus anatomical landmark-based targeting in vALIC deep brain stimulation for refractory obsessive-compulsive disorder.

Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is effective for refractory obsessive-compulsive disorder (OCD). Retrospective evaluation showed that stimulation closer to the supero-lateral branch of the medial forebrain bundle (slMFB), within the vALIC, was associated with better response to DBS. The present study is the first to compare outcomes of DBS targeted at the vALIC using anatomical landmarks and DBS with connectomic tractography-based targeting of the slMFB. We included 20 OCD-patients with anatomical landmark-based DBS of the vALIC that were propensity score matched to 20 patients with tractography-based targeting of electrodes in the slMFB. After one year, we compared severity of OCD, anxiety and depression symptoms, response rates, time to response, number of parameter adjustments, average current, medication usage and stimulation-related adverse effects. There was no difference in Y-BOCS decrease between patients with anatomical landmark-based and tractography-based DBS. Nine (45%) patients with anatomical landmark-based DBS and 13 (65%) patients with tractography-based DBS were responders (BF10 = 1.24). The course of depression and anxiety symptoms, time to response, number of stimulation adjustments or medication usage did not differ between groups. Patients with tractography-based DBS experienced fewer stimulation-related adverse effects than patients with anatomical landmark-based DBS (38 vs 58 transient and 1 vs. 17 lasting adverse effects; BF10 = 14.968). OCD symptoms in patients with anatomical landmark-based DBS of the vALIC and tractography-based DBS of the slMFB decrease equally, but patients with tractography-based DBS experience less adverse effects.

Deep brain stimulation for extreme behaviors associated with autism spectrum disorder converges on a common pathway: a systematic review and connectomic analysis.

Individuals with autism spectrum disorder (ASD) may display extreme behaviors such as self-injury or aggression that often become refractory to psychopharmacology or behavioral intervention. Deep brain stimulation (DBS) is a surgical alternative that modulates brain circuits that have yet to be clearly elucidated. In the current study the authors performed a connectomic analysis to identify brain circuitry engaged by DBS for extreme behaviors associated with ASD. A systematic review was performed to identify prior reports of DBS as a treatment for extreme behaviors in patients with ASD. Individual patients' perioperative imaging was collected from corresponding authors. DBS electrode localization and volume of tissue activated modeling were performed. Volumes of tissue activated were used as seed points in high-resolution normative functional and structural imaging templates. The resulting individual functional and structural connectivity maps were pooled to identify networks and pathways that are commonly engaged by all targets. Nine patients with ASD who were receiving DBS for symptoms of aggression or self-injurious behavior were identified. All patients had some clinical improvement with DBS. Connectomic analysis of 8 patients (from the systematic review and unpublished clinical data) demonstrated a common anatomical area of shared circuitry within the anterior limb of the internal capsule. Functional analysis of 4 patients identified a common network of distant brain areas including the amygdala, insula, and anterior cingulate engaged by DBS. This study presents a comprehensive synopsis of the evidence for DBS in the treatment of extreme behaviors associated with ASD. Using network mapping, the authors identified key circuitry common to DBS targets.

Ablation Surgeries for Treatment-Resistant Depression: A Meta-Analysis and Systematic Review of Reported Case Series

Background and Objectives: Ablative lesion procedures remain as the last option in treatment of refractory depression. Contemporary ablative psychosurgeries involve producing lesions in the anterior limb of the internal capsule (bilateral anterior capsulotomy – BAC), the supragenual anterior cingulate gyrus and cingulum (bilateral anterior cingulotomy – BACING), and subgenual anterior cingulate gyrus and subcortical orbitofrontal white matter (bilateral subcaudate tractotomy – BST). A combination of BACING and BST is known as limbic leukotomy (bilateral limbic leukotomy – BLL). All procedures claim some success, but cohorts are small, depression assessment instruments differ, and inclusion and outcome criteria and follow-up duration vary. In some cohorts, more than one type of surgery was performed in several patients, further confounding interpreting the available data. Current evidence is equivocal on which surgical target works best. Method and Aim: This systematic review and meta-analysis using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standard on published cohorts was conducted to review and identify which is the best standalone ablative procedure for treatment-resistant depression (TRD) based on response rate (event rate) and adverse-effect profile using the Comprehensive Meta-Analysis software. Results and Conclusion: As a standalone neurosurgical procedure, we found that BAC appears to be the most effective and safest of all the ablative targets for TRD. A major limitation of this conclusion is the paucity of published case series where sample sizes are small and all are open label.

Long-term comparative effectiveness of deep brain stimulation in severe obsessive-compulsive disorder

BackgroundTwenty years after the first use of Deep Brain Stimulation (DBS) in obsessive-compulsive disorder (OCD), our knowledge of the long-term effects of this therapeutic option remains very limited. ObjectiveOur study aims to assess the long-term effectiveness and tolerability of DBS in OCD patients and to look for possible predictors of long-term response to this treatment. MethodsWe studied the course of 25 patients with severe refractory OCD treated with DBS over an average follow-up period of 6.4 years (±3.2) and compared them with a control group of 25 patients with severe OCD who refused DBS and maintained their usual treatment. DBS was implanted at the ventral anterior limb of the internal capsule and nucleus accumbens (vALIC-Nacc) in the first six patients and later at the bed nucleus of stria terminalis (BNST) in the rest of patients. Main outcome was change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score between the two groups assessed using mixed models. Secondary effectiveness outcomes included Hamilton Depression Rating Scale (HDRS) and Global Assessment of Functioning (GAF) scores. ResultsObsessive symptoms fell by 42.5% (Y-BOCS score) in patients treated with DBS and by 4.8% in the control group. Fifty-six per cent of DBS-treated patients could be considered responders at the end of follow-up and 28% partial responders. Two patients among those who rejected DBS were partial responders (8%), but none of the non-DBS group achieved criteria for complete response. HDRS and GAF scores improved significantly in 39.2% and 43.6% among DBS-treated patients, while did not significantly change in those who rejected DBS (improvement limited to 6.2% in HDRS and 4.2% in GAF scores). No statistically significant predictors of response were found. Mixed models presented very large comparative effect sizes for DBS (4.29 for Y-BOCS, 1.15 for HDRS and 2.54 for GAF). Few patients experienced adverse effects and most of these effects were mild and transitory. ConclusionsThe long-term comparative effectiveness and safety of DBS confirm it as a valid option for the treatment of severe refractory OCD.

Efficacy and quality of life after 6–9 years of deep brain stimulation for depression

BackgroundGiven the invasiveness of deep brain stimulation (DBS), the effect should prove to be stable over the long-term and translate into an improvement of quality of life (QOL). ObjectiveTo study the effectiveness and QOL up to nine years after the DBS surgery. MethodsWe treated 25 adult patients with major depression with DBS of the ventral anterior limb of the internal capsule (vALIC). We followed them up naturalistically for 6–9 years after surgery (mean: 7.7 [SD:1.5] years), including a randomized crossover phase after the first year comparing sham with active DBS. Symptom severity was quantified using the Hamilton Depression Scale with response defined as a ≥50% decrease of the score compared to baseline. Quality of life was measured using the WHOQOL-BREF, assessing 5 domains (general, physical, psychological, social, environmental). ResultsIntention-to-treat response rates remained mostly stable from Year 3 to last follow-up (Year 3, 5 and 6: 40%; Year 4: 36%; Last observation: 44%). General, physical, psychological (all P < 0.001) and the environmental (P = 0.02) domain scores increased during DBS optimization and remained stable over the long term. No statistically significant changes were detected on the social domain. Patients scored significantly higher during active than sham DBS on the psychological, social and environmental domains, and trended towards a higher score on the general and physical domains. ConclusionThis study shows continued efficacy of vALIC DBS in depression, which translates into an improvement of QOL providing further support for DBS as a durable treatment for TRD.

White Matter Diffusion Properties in Chronic Temporomandibular Disorders: An Exploratory Analysis.

ObjectiveTo determine differences in diffusion metrics in key white matter (WM) tracts between women with chronic temporomandibular disorders (TMDs) and age- and sex-matched healthy controls.DesignCross sectional study compared diffusion metrics between groups and explored their associations with clinical variables in subjects with TMDs.MethodsIn a total of 33 subjects with TMDs and 33 healthy controls, we performed tractography to obtain diffusion metrics (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) from the cingulum near the cingulate gyrus (CGC), the cingulum near the hippocampus (CGH), the fornix, the anterior limb of the internal capsule (ALIC), the posterior limb of the internal capsule (PLIC), and the uncinate fasciculus (UF). We compared diffusion metrics across groups and explored the relationships between diffusion metrics and clinical measures (pain chronicity and intensity, central sensitization, somatization, depression, orofacial behavior severity, jaw function limitations, disability, and interference due to pain) in subjects with TMDs.ResultsWe observed differences in diffusion metrics between groups, primarily in the right side of the brain, with the right CGC having lower FA and the right UF having lower FA and higher MD and RD in subjects with TMDs compared to healthy controls. No clinical measures were consistently associated with diffusion metrics in subjects with TMDs.ConclusionThe UF showed potential microstructural damage in subjects with TMDs, but further studies are needed to confirm any associations between diffusion changes and clinical measures.

Tract-Based Spatial Statistics Analysis of Diffusion Tensor Imaging in Older Adults After the PICMOR Intervention Program: A Pilot Study.

Diffusion tensor imaging (DTI) enables the investigation of white matter properties in vivo by applying a tensor model to the diffusion of water molecules in the brain. Using DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), an attempt has been made to detect age-related alterations in the white matter microstructure in aging research. However, the use of comprehensive DTI measures to examine the effects of cognitive intervention/training on white matter fiber health in older adults remains limited. Recently, we developed a cognitive intervention program called Photo-Integrated Conversation Moderated by Robots (PICMOR), which utilizes one of the most intellectual activities of daily life, conversations. To examine the effects of PICMOR on cognitive function in older adults, we conducted a randomized controlled trial and found that verbal fluency task scores were improved by this intervention. Based on these behavioral findings, we collected in this pilot study diffusion-weighted images from the participants to identify candidate structures for white matter microstructural changes induced by this intervention. The results from tract-based spatial statistics analyses showed that the intervention group, who participated in PICMOR-based conversations, had significantly higher FA values or lower MD, AD, or RD values across various fiber tracts, including the left anterior corona radiata, external capsule, and anterior limb of the internal capsule, compared to the control group, who participated in unstructured free conversations. Furthermore, a larger improvement in verbal fluency task scores throughout the intervention was associated with smaller AD values in clusters, including the left side of these frontal regions. The present findings suggest that left frontal white matter structures are candidates for the neural underpinnings responsible for the enhancement of verbal fluency. Although our findings are limited by the lack of comparable data at baseline, we successfully confirmed the hypothesized pattern of group differences in DTI indices after the intervention, which fits well with the results of other cognitive intervention studies. To confirm whether this pattern reflects intervention-induced white matter alterations, longitudinal data acquisition is needed in future research.

A narrative review on invasive brain stimulation for treatment-resistant depression.

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Paradoxical Neuroethical Crisis of Agency and Identity in an Obsessive-Compulsive Disorder Deep Brain Stimulation Patient

IntroductionDeep Brain Stimulation is an increasingly viable, well-established treatment for medication refractory obsessive-compulsive disorder. Yet, its neuromodulatory effects on the brain have led to varying and opposing neuroethical debates about its potential influence on a range of phenomena such as human agency, sense of nonauthenticity and identity.ObjectivesEstablish the importance of maintaining the psychotherapeutic alliance in a long-term DBS patient who reported minimal device side effect and no brain-technology interface interpersonal issues; yet struggled with a paradoxical phenomenon of psychic distress surrounding issues of agency and identity, not through device implantation, but through morphology of cognitions from negativistic interpersonal dynamics and spousal victim-blaming due to the necessity for such a device.MethodsCase-report of a 60+-year-old gentleman with a history of childhood-onset, treatment refractory OCD with a 15-year history of bilateral DBS lead placed via a ventral caudate/ ventral striatum trajectory through the anterior limb of the internal capsule to the nucleus accumbens.ResultsYears later he was only minimally improved above baseline; yet now with a few-years increasing degree of distress over a perceived atrophy of his capabilities that he felt was validated through what he described as his failure of artificial bionics. Extensive device setting re-optimization did not improve efficacy and with supportive therapy, the DBS device was weaned, and turned off.ConclusionsThe following year the therapeutic foci were on interpersonal identity, existential acceptance of breakthrough symptoms, and engagement of spouse into marital counseling leading to subsequent resolution of distress with improved quality of life.DisclosureNo significant relationships.

A Longitudinal Magnetoencephalographic Study of the Effects of Deep Brain Stimulation on Neuronal Dynamics in Severe Anorexia Nervosa.

Anorexia Nervosa (AN) is a debilitating psychiatric disorder characterized by the relentless pursuit of thinness, leading to severe emaciation. Magnetoencephalography (MEG)was used to record the neuronal response in seven patients with treatment-resistant AN while completing a disorder-relevant food wanting task. The patients underwent a 15-month protocol, where MEG scans were conducted pre-operatively, post-operatively prior to deep brain stimulation (DBS) switch on, twice during a blind on/off month and at protocol end. Electrodes were implanted bilaterally into the nucleus accumbens with stimulation at the anterior limb of the internal capsule using rechargeable implantable pulse generators. Three patients met criteria as responders at 12 months of stimulation, showing reductions of eating disorder psychopathology of over 35%. An increase in alpha power, as well as evoked power at latencies typically associated with visual processing, working memory, and contextual integration was observed in ON compared to OFF sessions across all seven patients. Moreover, an increase in evoked power at P600-like latencies as well as an increase in γ-band phase-locking over anterior-to-posterior regions were observed for high- compared to low-calorie food image only in ON sessions. These findings indicate that DBS modulates neuronal process in regions far outside the stimulation target site and at latencies possibly reflecting task specific processing, thereby providing further evidence that deep brain stimulation can play a role in the treatment of otherwise intractable psychiatric disorders.

Noninvasive Capsulotomy for Refractory Depression by Frameless Stereotactic Radiosurgery

Effective treatment options for refractory depression are needed. Recent advancements permit both precise ablative radiation and functional neurologic connectome analysis using standard magnetic resonance imaging. We combined these innovations to perform stereotactic radiosurgical capsulotomy for the treatment of medically refractory major depressive disorder and study connectome response using a novel tractography-based approach. Patients with medically refractory depression were enrolled on a prospective pilot single-arm observational trial from 2020 to 2021 at a single academic tertiary referral center. Bilateral ablation of the anterior limb of the internal capsule was accomplished by mask-based linear accelerator stereotactic radiosurgery. Beck's Depression Inventory measured efficacy. Montreal Cognitive Assessment evaluated cognition. Three patients were enrolled. Depression burden was improved by 88% at 12-month follow-up and by 55% at 18-month follow-up for patient 1 and 2, respectively. Patient 1 discontinued ketamine therapy, and patient 2 discontinued electroconvulsive therapy. Patient 3 reported global improvement in symptoms and function at 3 months. All 3 patients had reduction or resolution of suicidal ideation. No patient experienced cognitive decline or neurologic toxicity, and Montreal Cognitive Assessment score, as well as subjective patient-reported evaluations of concentration and attention, were superior after treatment. Tractography confirmed intended disruption of the cortico-striatal-thalamo-cortical loop with structural reorganization in the connectome. Connectome change was consistent between patients. Observed increases in caudate and putamen connectivity and decreases in thalamic connectivity may explain improved concentration, attention, and depression. The diversity and magnitude of connectome change may correlate with degree of clinical response. In 3 patients with refractory depression, radiosurgical capsulotomy significantly reduced the burden of depression. Functional connectome reorganization offers neurobiological evidence to support further investigations of the role of radiosurgery in depression.

Axial Diffusivity of the Left Anterior Limb of the Internal Capsule Associated with Slow Wave Sleep in Warfighters with Traumatic Brain Injury (P16-6.003)

Axial Diffusivity of the Left Anterior Limb of the Internal Capsule Associated with Slow Wave Sleep in Warfighters with Traumatic Brain Injury (P16-6.003)

P343. Deep Brain Stimulation Normalizes Amygdala Responsivity in Major Depressive Disorder

Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is a promising intervention for treatment-resistant major depressive disorder (MDD). Depression has been associated with aberrant amygdala responsivity to emotional stimuli. We therefore tested whether vALIC DBS could normalize amygdala responsivity to emotional faces.

Deep Brain Stimulation of the Nucleus Accumbens in Severe Enduring Anorexia Nervosa: A Pilot Study.

IntroductionAnorexia nervosa (AN) is one of the most debilitating psychiatric disorders, becoming severe and enduring in a third of cases; with few effective treatments. Deep brain stimulation is a reversible, adjustable neurosurgical procedure that has been gaining ground in psychiatry as a treatment for depression and obsessive–compulsive disorder, yet few studies have investigated AN. Abnormal eating behavior and the compulsive pursuit of thinness in AN is, in part, a consequence of dysfunction in reward circuitry and the nucleus accumbens (NAcc) is central to reward processing.MethodsPhase 1 prospective open-label pilot study of seven individuals with severe enduring AN. Electrodes were implanted bilaterally into the NAcc with stimulation at the anterior limb of the internal capsule using rechargeable implantable pulse generators. The protocol of 15 months included 12 months of deep brain stimulation incorporating two consecutive, randomized blind on-off fortnights 9 months after stimulation onset. The primary objectives were to investigate safety and feasibility, together with changes in eating disorder psychopathology.ResultsFeasibility and safety was demonstrated with no serious adverse events due to deep brain stimulation. Three patients responded to treatment [defined as > 35% reduction in Eating Disorders Examination (EDE) score at 12 months] and four patients were non-responders. Responders had a statistically significant mean reduction in EDE scores (50.3% reduction; 95% CI 2.6–98.2%), Clinical Impairment Assessment (45.6% reduction; 95% CI 7.4–83.7%). Responders also had a statistically significant mean reduction in Hamilton Depression Scale, Hamilton Anxiety Scale and Snaith-Hamilton pleasure scale. There were no statistically significant changes in Body Mass Index, Yale-Brown-Cornell Eating Disorder Scale, Yale-Brown Obsessive–Compulsive Scale and World Health Organization Quality of Life Psychological subscale.ConclusionThis study provides some preliminary indication that deep brain stimulation to the NAcc. Might potentially improve some key features of enduring AN. In this small study, the three responders had comorbid obsessive-compulsive disorder which predated AN diagnosis. Future studies should aim to further elucidate predictors of outcome.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [Project ID 128658].

Abnormal White Matter Microstructure in the Limbic System Is Associated With Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders.

ObjectiveTuberous sclerosis complex (TSC) is a genetic disease that arises from TSC1 or TSC2 abnormalities and induces the overactivation of the mammalian/mechanistic target of rapamycin pathways. The neurological symptoms of TSC include epilepsy and tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). Although TAND affects TSC patients' quality of life, the specific region in the brain associated with TAND remains unknown. We examined the association between white matter microstructural abnormalities and TAND, using diffusion tensor imaging (DTI).MethodsA total of 19 subjects with TSC and 24 age-matched control subjects were enrolled. Tract-based spatial statistics (TBSS) were performed to assess group differences in fractional anisotropy (FA) between the TSC and control groups. Atlas-based association analysis was performed to reveal TAND-related white matter in subjects with TSC. Multiple linear regression was performed to evaluate the association between TAND and the DTI parameters; FA and mean diffusivity in seven target regions and projection fibers.ResultsThe TBSS showed significantly reduced FA in the right hemisphere and particularly in the inferior frontal occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), and genu of corpus callosum (CC) in the TSC group relative to the control group. In the association analysis, intellectual disability was widely associated with all target regions. In contrast, behavioral problems and autistic features were associated with the limbic system white matter and anterior limb of the internal capsule (ALIC) and CC.ConclusionThe disruption of white matter integrity may induce underconnectivity between cortical and subcortical regions. These findings suggest that TANDs are not the result of an abnormality in a specific brain region, but rather caused by connectivity dysfunction as a network disorder. This study indicates that abnormal white matter connectivity including the limbic system is relevant to TAND. The analysis of brain and behavior relationship is a feasible approach to reveal TAND related white matter and neural networks. TAND should be carefully assessed and treated at an early stage.

144 Interstitial Laser Anterior Capsulotomy for Obsessive-compulsive Disorder: Lesion Size and Tractography Correlate with Outcome

INTRODUCTION: Anterior capsulotomy is a well-established treatment for refractory obsessive-compulsive disorder (OCD) and has been performed with radiofrequency ablation, stereotactic radiosurgery, and focused ultrasound. MRI-guided laser interstitial thermal therapy (LITT) allows creation of larger, more demarcated lesions with the safety conferred by real-time imaging of the ablation volume. METHODS: Patients with severe OCD refractory to pharmacotherapy and cognitive-behavioral therapy underwent bilateral anterior capsulotomy via LITT. The primary outcome was percent reduction in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score over time. Lesion size was measured on post-ablation MRI. Disconnection of the anterior limb of the internal capsule (ALIC) was assessed via individual and normative tractography. RESULTS: Eighteen patients underwent laser anterior capsulotomy. Median follow-up was 6 months (range 3-51 months). Time occupied by obsessions improved immediately (median Y-BOCS item 1 score 4 to 1, P = 0.0002). Mean (± standard deviation) decrease in Y-BOCS score at last follow-up was 46 ± 32% (16 ± 11 points; P = 0.0002). Sixty-one percent of patients were responders. One patient had an asymptomatic intracerebral hemorrhage. Reduction in Y-BOCS score was positively associated with ablation volume (P = 0.006). Individual tractography demonstrated durable ALIC disconnection. Normative tractography revealed a dorsal-ventral gradient, with disconnection of orbitofrontal streamlines most strongly associated with a positive response to surgery (P &lt; 0.0001). CONCLUSION: Laser anterior capsulotomy resulted in immediate, marked improvement in OCD symptom severity. Larger lesions can be created safely and permit greater disconnection of the prefrontal-subcortical pathways involved in OCD. The importance of greater disconnection is presumably related to variation in ALIC structure and the complex role of the PFC in OCD.