Microelectrode recording characterization of the nucleus accumbens and the anterior limb of internal capsule in patients with addiction.

The nucleus accumbens (NAc) and the anterior limb of internal capsule (ALIC) are effective targets for treating addiction using deep brain stimulation (DBS). However, there have been no reports on the electrophysiological characteristics of addiction nuclei at the single-cell level in humans. This study aimed to investigate the electrical activity characteristics of neurons in the NAc and ALIC using microelectrode recording (MER) during DBS surgery in patients with addiction, and six patients with addiction were included (five with heroin addiction and one with alcohol addiction). The microelectrode recording trajectories were reconstructed and recording sites at different depths were determined by merging the pre- and post-operative images in the FrameLink system. The results showed that among the 256 neurons, 204 (80 %) were burst neurons. NAc neurons accounted for the majority (57 %), and the mean firing rate (MFR) was the highest (1.94 Hz). ALIC neurons accounted for the least (14 %), and MFR was the lowest (0.44 Hz). MFR increased after entering the NAc and decreased after entering the ALIC. In the patients with addiction treated using DBS, the single-cell level electrophysiological characteristics of the different nuclei were found to be distinct along the surgical trajectory.

Acute motor deficit and subsequent remyelination-associated recovery following internal capsule demyelination in mice.

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by accumulated motor disability. However, whether remyelination promotes motor recovery following demyelinating injury remains unclear. Damage to the internal capsule (IC) is known to result in motor impairment in multiple sclerosis and stroke. Here, we induced focal IC demyelination in mice by lysophosphatidylcholine (LPC) injection, and examined its effect on motor behavior. We also compared the effect of LPC-induced IC damage to that produced by endothelin-1 (ET1), a potent vasoconstrictor used in experimental stroke lesions. We found that LPC or ET1 injections induced asymmetric motor deficit at 7 days post-lesion (dpl), and that both lesion types displayed increased microglia/macrophage density, myelin loss, and axonal dystrophy. The motor deficit and lesion pathology remained in ET1-injected mice at 28 dpl. In contrast, LPC-injected mice regained motor function by 28 dpl, with corresponding reduction in activated microglia/macrophage density, and recovery of myelin staining and axonal integrity in lesions. These results suggest that LPC-induced IC demyelination results in acute motor deficit and subsequent recovery through remyelination, and may be used to complement future drug screens to identify drugs for promoting remyelination.

Stereotactic radiofrequency thermocoagulation application in the anterior limbs of patients' internal capsules in treating intractable tic disorders.

Purpose: To investigate the effect of applying stereotactic radiofrequency thermocoagulation in the anterior limbs of patients' internal capsules in treating intractable tic disorders.Materials and methods: Patients diagnosed with intractable tic disorders were prospectively enrolled and treated using stereotactic radiofrequency thermocoagulation in the anterior limbs of the internal capsules. Periprocedural complications, effects, and follow-up outcomes were then analyzed.Results: Fifty patients were enrolled, including 38 with Tourette syndrome and 12 with persistent refractory vocal or motor tic disorders. The radiofrequency thermocoagulation procedure was performed successfully in all patients. Five participants (10%) experienced periprocedural complications, including one having a slight hemiplegia, two developing fevers (4%), and two developing urination disorders (4%). The participants underwent a follow-up for 12 months, with excellent effects being achieved in 23 patients (46%), prominent results in 13 (26%), good results in 10 (20%), and invalid results in 4 (8%), reaching an efficacy rate of 92% (46/50). Thirty-six patients experienced excellent and prominent effects, with no additional management after the radiofrequency ablation being needed, achieving a success rate of 72%. After radiofrequency thermocoagulation, the Yale Global Tic Severity Scale (YGTSS) scores were significantly reduced (p < .01) when compared with those before the procedure. Following this procedure, participants' serum dopamine levels (SDA) significantly decreased (p < .05), while their serotonin levels were significantly elevated (p < .05) when compared to the measurements taken before the procedure.Conclusion: Stereotactic radiofrequency thermocoagulation applied to the anterior limbs of patients' internal capsules may be effective for treating intractable tic disorders, without risk of serious complications.

The anterior limb of the internal capsule: Anatomy, function, and dysfunction.

The last two decades have seen a re-emergence of neurosurgery for severe, refractory psychiatric diseases, largely due to the advent of more precise and safe operative techniques. Nevertheless, the optimal targets for these surgeries remain a matter of debate, and are often grandfathered from experiences in the late 20th century. To better explore the rationale for one target in particular - the anterior limb of the internal capsule (ALIC) - we comprehensively reviewed all available literature on its role in the pathophysiology and treatment of mental illness. We first provide an overview of its functional anatomy, followed by a discussion on its role in several prevalent psychiatric diseases. Given its structural integration into the limbic system and involvement in a number of cognitive and emotional processes, the ALIC is a robust target for surgical treatment of refractory psychiatric diseases. The advent of novel neuroimaging techniques, coupled with image-guided therapeutics and neuromodulatory treatments, will continue to enable study on the ALIC in mental illness.

The dynamics of revascularization after white matter infarction monitored in Flt1-tdsRed and Flk1-GFP mice.

Subcortical white matter infarction causes ischemic demyelination and loss of brain functions, as the result of disturbances of the blood flow. Although angiogenesis is one of the recovery processes after cerebral infarction, the dynamics of revascularization after white matter infarction still remains unclear. We induced white matter infarction in the internal capsule of Flk1-GFP::Flt1-tdsRed double transgenic mice by injection of endothelin-1 (ET-1), a vasoconstrictor peptide, together with N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and followed the changes in Flk1 and Flt1 expression in the vascular system in the infarct area. Reduction of Flt1-tdsRed-positive blood vessels 1 day after the injection and increase of Flk1-GFP-strongly-positive blood vessels 3 days after the injection were apparent. PDGFRß-strongly-positive (PDGFRß+) cells appeared in the infarct area 3 days after the injection and increased their number thereafter. Three days after the injection, most of these cells were in close contact with Flk1-GFP-positive endothelial cells, indicating these cells are bona fide pericytes. Seven days after the injection, the number of PDGFRß+ cells increased dramatically, and the vast majority of these cells were not in close contact with Flk1-GFP-positive endothelial cells. Taken together, our results suggest revascularization begins early after the ischemic insult, and the emerging pericytes first ensheath blood vessels and then produce fibroblast-like cells not directly associated with blood vessels.

Comparison of probabilistic tractography and tract-based spatial statistics for assessing optic radiation damage in patients with autoimmune inflammatory disorders of the central nervous system.

Background: Diffusion Tensor Imaging (DTI) can evaluate microstructural tissue damage in the optic radiation (OR) of patients with clinically isolated syndrome (CIS), early relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorders (NMOSD). Different post-processing techniques, e.g. tract-based spatial statistics (TBSS) and probabilistic tractography, exist to quantify this damage. Objective: To evaluate the capacity of TBSS-based atlas region-of-interest (ROI) combination with 1) posterior thalamic radiation ROIs from the Johns Hopkins University atlas (JHU-TBSS), 2) Juelich Probabilistic ROIs (JUEL-TBSS) and tractography methods using 3) ConTrack (CON-PROB) and 4) constrained spherical deconvolution tractography (CSD-PROB) to detect OR damage in patients with a) NMOSD with prior ON (NMOSD-ON), b) CIS and early RRMS patients with ON (CIS/RRMS-ON) and c) CIS and early RRMS patients without prior ON (CIS/RRMS-NON) against healthy controls (HCs). Methods: Twenty-three NMOSD-ON, 18 CIS/RRMS-ON, 21 CIS/RRMS-NON, and 26 HCs underwent 3 T MRI. DTI data analysis was carried out using JUEL-TBSS, JHU-TBSS, CON-PROB and CSD-PROB. Optical coherence tomography (OCT) and visual acuity testing was performed in the majority of patients and HCs. Results: Absolute OR fractional anisotropy (FA) values differed between all methods but showed good correlation and agreement in Bland-Altman analysis. OR FA values between NMOSD and HC differed throughout the methodologies (p-values ranging from p < 0.0001 to 0.0043). ROC-analysis and effect size estimation revealed higher AUCs and R2 for CSD-PROB (AUC = 0.812; R2 = 0.282) and JHU-TBSS (AUC = 0.756; R2 = 0.262), compared to CON-PROB (AUC = 0.742; R2 = 0.179) and JUEL-TBSS (AUC = 0.719; R2 = 0.161). Differences between CIS/RRMS-NON and HC were only observable in CSD-PROB (AUC = 0.796; R2 = 0.094). No significant differences between CIS/RRMS-ON and HC were detected by any of the methods. Conclusions: All DTI post-processing techniques facilitated the detection of OR damage in patient groups with severe microstructural OR degradation. The comparison of distinct disease groups by use of different methods may lead to different - either false-positive or false-negative - results. Since different DTI post-processing approaches seem to provide complementary information on OR damage, application of distinct methods may depend on the relevant research question.

Oscillatory local field potentials of the nucleus accumbens and the anterior limb of the internal capsule in heroin addicts.

OBJECTIVES: The nucleus accumbens (NAc) is known to regulate the motivation and underlie addictive behaviors, and the anterior limb of the internal capsule (ALIC) is involved in several psychiatric disorders. Our study aimed to explore the functions of NAc and ALIC electrophysiologically. METHODS: The local field potentials (LFPs) of the NAc and ALIC were recorded from 7 heroin addicts treated with deep brain stimulation. Correlation analysis was made between LFP powers in various frequency bands and the subjects' neuropsychological test scores; coherence was calculated for the LFPs in NAc and ALIC. RESULTS: Both the NAc and ALIC exhibited prominent theta and alpha frequency band activity in the LFP power spectra. Additionally, a distinct beta band peak was detected in the power spectra of ALIC LFPs, which may represent the activity of striatal bridge cells. There was a significant negative correlation between the power of the theta frequency band of ALIC LFPs and visual analogue scale (VAS) scores indicative of cravings (Spearman's ρ = -0.758, P = 0.002), and a significant positive correlation was found between the power of the alpha frequency band of NAc LFPs and subjects' scores on the Hamilton depression inventory (ρ = 0.727, P = 0.005). LFPs of the NAc and ALIC exhibited higher coherence values in the theta and alpha frequency bands. CONCLUSIONS: The results suggest that theta power in the ALIC/dorsal striatum and alpha power in the NAc may be associated with drug cravings and depressive symptoms, respectively, in heroin addicts. For these subjects, the neural activities in the dorsal and ventral striatum were mainly coordinated within the low-frequency band. SIGNIFICANCE: The study illustrates the neurophysiologic characteristics of heroin addiction and its comorbidities, providing a potential theoretical basis for optimizing deep brain stimulation (DBS) therapy.

Impact of deep brain stimulation of the ventral anterior limb of the internal capsule on cognition in depression.

BACKGROUND: Preliminary studies report no negative and a possible positive impact of deep brain stimulation (DBS) on cognition of patients with treatment-resistant depression (TRD). However, these studies neither controlled for practice effects nor compared active with sham stimulation. METHOD: To address these limitations, we compared 25 TRD patients, who underwent DBS of the ventral anterior limb of the internal capsule (vALIC), with 21 healthy controls (HCs) matched on gender, age and education level. Both groups did subtests of the Cambridge Neuropsychological Test Automated Battery assessing verbal and visuospatial memory, attention, cognitive flexibility, psychomotor functioning, planning and object naming. TRD patients were tested 3 weeks prior to DBS surgery (baseline), 3 weeks following surgery (T1) and following 52 weeks of DBS optimization (T2). HCs were tested at baseline, 6 weeks following baseline (T1) and 20-24 weeks following baseline (T2). Subsequently, TRD patients entered a randomized, double-blind crossover phase, in which they were tested in an active and a sham stimulation phase. RESULTS: TRD patients did not improve on a test of immediate verbal recognition from baseline to T1, whereas HCs did (group x time: p = 0.001). Both TRD patients and HCs improved over sessions on tests measuring delayed verbal recall, visuospatial memory, planning and object naming (all p < 0.01). Active and sham stimulation did not have an impact on any of the tests differentially. CONCLUSIONS: vALIC DBS neither has a lasting positive nor negative impact on cognition in TRD patients. DBS surgery might have a temporary negative effect on verbal memory.

Capsular stroke modeling based on somatotopic mapping of motor fibers.

Recently, several capsular stroke models have been reported with different targets of destruction. This study was performed to establish an accurate internal capsule (IC) target for capsular stroke modeling in rats. We injected adeno-associated virus serotype 5 (AAV)-CaMKII-EYFP into forelimb motor cortex and AAV-CaMKII-mCherry into hindlimb motor cortex (n = 9) to anterogradely trace the pyramidal fibers and map their somatotopic distribution in the IC. On the basis of the neural tracing results, we created photothrombotic infarct lesions in rat forelimb and hindlimb motor fiber (FMF and HMF) areas of the IC (n = 29) and assessed motor behavior using a forelimb-use asymmetry test, a foot-fault test, and a single-pellet reaching test. We found that the FMFs and HMFs were primarily distributed in the inferior portion of the posterior limb of the IC, with the FMFs located largely ventral to the HMFs but with an area of partial overlap. Photothrombotic lesions in the FMF area resulted in persistent motor deficits. In contrast, lesions in the HMF area did not result in persistent motor deficits. These results indicate that identification of the somatotopic distribution of pyramidal fibers is critical for accurate targeting in animal capsular stroke models: only infarcts in the FMF area resulted in long-lasting motor deficits.

Suitable reference tissues for quantitative susceptibility mapping of the brain.

PURPOSE: Since quantitative susceptibility mapping (QSM) quantifies magnetic susceptibility relative to a reference value, a suitable reference tissue has to be available to compare different subjects and stages of disease. METHODS: To find such a suitable reference tissue for QSM of the brain, melanoma patients with and without brain metastases were measured. Twelve reference regions were chosen and assessed for stability of susceptibility values with respect to multiple intra-individual and inter-individual measurements, age, and stage of disease. RESULTS: Cerebrospinal fluid (CSF), the internal capsule and one region in the splenium of the corpus callosum are the regions with the smallest standard deviations of the mean susceptibility value. The mean susceptibility is 0.010 ± 0.014 ppm for CSF in the atrium of the lateral ventricles (csfpost ), -0.060 ± 0.019 ppm for the posterior limb of the internal capsule (ci2), and -0.008 ± 0.019 ppm for the splenium of the corpus callosum. csfpost and ci2 show nearly no dependence on age or stage of disease, whereas some other regions, e.g., the red nucleus, show moderate dependence on age or disease. CONCLUSION: The internal capsule and CSF appear to be the most suitable reference regions for QSM of the brain in the melanoma patients studied. Both showed virtually no dependence on age or disease and small variations among patients. Magn Reson Med 78:204-214, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Treatment-Resistant Depression: A Randomized Clinical Trial.

IMPORTANCE: Patients with treatment-resistant depression (TRD) do not respond sufficiently to several consecutive treatments for major depressive disorder. Deep brain stimulation (DBS) is a promising treatment for these patients, but presently placebo effects cannot be ruled out. OBJECTIVE: To assess the efficacy of DBS of the ventral anterior limb of the internal capsule (vALIC), controlling for placebo effects with active and sham stimulation phases. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five patients with TRD from 2 hospitals in the Netherlands were enrolled between March 22, 2010, and May 8, 2014. Patients first entered a 52-week open-label trial during which they received bilateral implants of 4 contact electrodes followed by optimization of DBS until a stable response was achieved. A randomized, double-blind, 12-week crossover phase was then conducted with patients receiving active treatment followed by sham or vice versa. Response and nonresponse to treatment were determined using intention-to-treat analyses. INTERVENTIONS: Deep brain stimulation targeted to the vALIC. MAIN OUTCOMES AND MEASURES: The change in the investigator-rated score of the 17-item Hamilton Depression Rating Scale (HAM-D-17) was the main outcome used in analysis of the optimization phase. The primary outcome of the crossover phase was the difference in the HAM-D-17 scores between active and sham DBS. The score range of this tool is 0 to 52, with higher scores representing more severe symptoms. Patients were classified as responders to treatment (≥50% decrease of the HAM-D-17 score compared with baseline) and partial responders (≥25 but <50% decrease of the HAM-D-17 score). RESULTS: Of 25 patients included in the study, 8 (32%) were men; the mean (SD) age at inclusion was 53.2 (8.4) years. Mean HAM-D-17 scores decreased from 22.2 (95% CI, 20.3-24.1) at baseline to 15.9 (95% CI, 12.3-19.5) (P = .001), Montgomery-Åsberg Depression Rating Scale scores from 34.0 (95% CI, 31.8-36.3) to 23.8 (95% CI, 18.4-29.1) (P < .001), and Inventory of Depressive Symptomatology-Self-report scores from from 49.3 (95% CI, 45.4-53.2) to 38.8 (95% CI, 31.6-46.0) (P = .005) in the optimization phase. Following the optimization phase, which lasted 51.6 (22.0) weeks, 10 patients (40%) were classified as responders and 15 individuals (60%) as nonresponders. Sixteen patients entered the randomized crossover phase (9 responders [56%], 7 nonresponders [44%]). During active DBS, patients scored significantly lower on the HAM-D-17 scale (13.6 [95% CI, 9.8-17.4]) than during sham DBS (23.1 [95% CI, 20.6-25.6]) (P < .001). Serious adverse events included severe nausea during surgery (1 patient), suicide attempt (4 patients), and suicidal ideation (2 patients). CONCLUSIONS AND RELEVANCE: Deep brain stimulation of the vALIC resulted in a significant decrease of depressive symptoms in 10 of 25 patients and was tolerated well. The randomized crossover design corroborates that vALIC DBS causes symptom reduction rather than sham. TRIAL REGISTRATION: trialregister.nl Identifier: NTR2118.

Intraoperative functional magnetic resonance imaging for monitoring the effect of deep brain stimulation in patients with obsessive-compulsive disorder.

OBJECTIVES: To investigate the effects of low- and high-frequency deep brain stimulation (DBS) on the nucleus accumbens (ACC) and the adjacent internal capsule in 3 patients with obsessive-compulsive disorder (OCD) using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) under intraoperative conditions. METHODS: After placement of the electrode in the right ACC, the patients underwent an MR scan inside the operating room. BOLD imaging was performed and interpreted using a boxcar paradigm with alternating high-frequency stimulation of the ACC and the internal capsule versus rest. Correlation maps were calculated employing SPM99. RESULTS: During high-frequency stimulation of the right ACC, focal activation could be found in the right striatum, the right frontal lobe and the right hippocampus, whereas low-frequency stimulation was correlated to right insular activation. INTERPRETATION: Intraoperative BOLD-fMRI is feasible during DBS surgery of OCD patients. Our results support the existence of an ipsilateral hemispheric circuit involving the frontal lobe, anterior cingulate, parahippocampal gyrus and striatum. Intraoperative fMRI may be used to acquire additional information regarding the pathophysiology of OCD that can be used to improve the results of DBS in OCD.

Tractography-guided stimulation of somatosensory fibers for thalamic pain relief.

BACKGROUND: The spinothalamocortical tract (STC) is seen as a neural tract responsible for or involved in the generation or transmission of thalamic pain. Either the thalamus itself or the posterior limb of the internal capsule (PLIC) are targets for deep brain stimulation (DBS) in patients with thalamic pain, but due to its low contrast, conventional MRI cannot visualize the STC directly. OBJECTIVES: To show the feasibility of integrating diffusion tensor imaging-based tractography into the stereotactic treatment planning for identification of an object-oriented lead trajectory that allows STC-DBS with multiple electrode contacts. METHODS: Diffusion tensor imaging was performed in 4 patients with thalamic pain. The STC was modeled and integrated into the stereotactic treatment planning for DBS. DBS-lead implantation was done according to trajectory planning along the modeled STC at the level of the PLIC. RESULTS: After implantation, electrode stimulation was possible over a length of more than 20 mm with a tractography-based trajectory along the PLIC part of the STC. After a follow-up of 12 months, pain relief of more than 40% was achieved in 3 of 4 patients with rating on a visual analogue scale. In 1 patient, stimulation failed to reach any long-lasting positive effects. CONCLUSIONS: Integrating tractography data into stereotactic planning of DBS in thalamic pain is technically feasible. It can be used to identify a lead trajectory that allows for multiple contact stimulation along the STC at the level of the PLIC. Due to long-lasting positive stimulation effect, tractography-guided stimulation of sensory fibers seems to be beneficial for thalamic pain relief.

Deep brain stimulation of the ventral striatum/anterior limb of the internal capsule in thalamic pain syndrome: study protocol for a pilot randomized controlled trial.

BACKGROUND: Chronic neuropathic pain in thalamic pain syndrome remains intractable. Its poor response is ascribed to destruction of the integrated neuromatrix in experience of pain. Deep brain stimulation is a promising technique to modulate activity of implicated structures. However, traditional approaches targeting sensori-motor substrates have failed to affect disability. The offending lesion in thalamic pain syndrome that almost invariably destroys sensory pain pathways may render these classical approaches ineffective. Instead, we hypothesize that targeting structures representing emotion and affective behavior-ventral striatum/anterior limb of the internal capsule, may alleviate disability. METHODS/DESIGN: We present the design of our phase I randomized, double-blinded, sham-controlled, crossover trial that examines safety, feasibility and efficacy of our proposed approach. In our ongoing trial, we intend to enroll ten patients with thalamic pain syndrome. Following implantation, patients are randomized to receive active deep brain stimulation to the ventral striatum/anterior limb of the internal capsule or sham for 3 months, after which they are crossed over. The primary endpoint is Pain Disability Index. Other outcomes include visual analog scale, depression and anxiety inventories, quality of life, and functional neuroimaging. DISCUSSION: Designing trials of deep brain stimulation for pain is challenging owing to the ethical-scientific dilemma of introducing a control arm, complicated blinding, heterogeneous etiologies, patient expectations, and inadequate assessment of disability. The quality of evidence in the field is classified as level III (poor) because it mainly includes a multitude of uncontrolled case series reporting variable outcomes, with little regard for the placebo effect related to implantation. Without valid data on efficacy, use of deep brain stimulation for pain remains "off label". We present our trial design to discuss feasibility of conducting sham-controlled phase I studies that may represent significant refinement for the field. Double-blinding would reduce influence of patient expectations and therapeutic confusion amongst investigators. With a cross-over approach, the dilemma regarding including a control group can be mitigated. Use of homogeneous etiology, measurement of disability, depression and quality of life, besides pain perception, all represent strategies to evaluate efficacy rigorously. Functional imaging would serve to define mechanisms underlying observed effects and may help optimize future targeting. TRIAL REGISTRATION: Clinicaltrials.gov NCT01072656.

Bilateral stereotactic anterior capsulotomy for obsessive-compulsive disorder: long-term follow-up.

BACKGROUND AND PURPOSE: Psychosurgery, such as anterior capsulotomy, is a therapeutic option for treatment-resistant obsessive-compulsive disorder (OCD). In this paper, we present a prospective, long-term follow-up study aimed at evaluating both the efficacy and the safety of anterior capsulotomy for the treatment of severe, refractory OCD. METHODS: Twenty-four patients were surgically treated in our centre between 1997 and 2009, 19 of whom were included in this study. Patients were assessed at 3, 6, 12, and 24 months and last follow-up (mean of 7 years) was carried out by phone. OCD symptom severity was evaluated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A patient with an improvement rate of over 35% in the Y-BOCS score was considered a responder, while a patient with a 25% improvement was considered a partial responder. RESULTS: With a mean improvement of 31% in the Y-BOCS score at long-term follow-up, 36.8% of the patients responded fully to the procedure and 10.5% were considered partial responders, for an overall response rate of 47.3% of patients. At the end of the study, 3/19 patients had recovered (Y-BOCS score <8) and 3/19 were in remission (Y-BOCS score <16). No cases of mortality were reported and the overall adverse event rate was 57.9%. Only 2 patients had permanent surgical complications. CONCLUSIONS: Anterior capsulotomy is an effective and safe technique for the treatment of severe refractory OCD in patients who have no other alternative to improve their symptoms.

Predictors of medium and long-term outcome following capsulotomy for obsessive-compulsive disorder: one site may not fit all.

Patients with treatment-refractory obsessive-compulsive disorder (OCD) are sometimes considered for surgical interventions. The identification of reliable predictors of outcome following such interventions would be of great clinical importance, as it would lead to stricter selection of suitable patients, thus avoiding unnecessary surgery and improving the overall response rate. We analyzed data from 24 severe treatment-resistant patients who underwent capsulotomy for OCD and were carefully followed-up one year after the surgery and at long term (mean 10.8 years after surgery). The Yale-Brown Obsessive Compulsive Scale Symptom Checklist was administered to assess the lifetime presence of the most common symptom types. We applied an algorithm to calculate the patients' scores on 4 well-established symptom dimensions: Contamination/cleaning, forbidden thoughts, symmetry/order and hoarding. Multiple regression models were employed to examine whether scores on certain symptom dimensions were predictive of long-term outcome. The presence and number of lifetime symptoms in the symmetry/order domain were associated with greater severity of OCD, depression and anxiety, as well as greater impairment in various functional domains like work, social and family life at both one-year and long-term follow-ups. These results remained consistently significant after controlling for preoperative psychopathology, scores on other OCD symptom dimensions, sex, age, age of onset, duration of follow-up, type of surgical procedure, number of operations and lesion volume. The results could have implications for existing ablative and deep brain stimulation protocols and challenge our current conceptualization of OCD as a unitary diagnostic entity with a single neurobiological substrate.

Focal hand dystonia cured by removal of clinoid meningioma-case report-.

A 40-year-old Asian female presented with an unusual case of focal hand dystonia caused by contralateral clinoid meningioma. Magnetic resonance imaging showed that the tumor compressed the caudate nucleus, lentiform nucleus, cerebral peduncle, internal capsule, and a large portion of the white matter surrounding the basal ganglia. The tumor was gross totally removed via a frontotemporal approach with zygomatic osteotomy, resulting in cure of the focal hand dystonia. Magnetic resonance imaging after surgery showed that the compression of the surrounding brain was released. This case shows that secondary focal hand dystonia caused by extra-axial brain tumor can be cured by surgical removal.

Neuropsychological outcome of ventral capsular/ventral striatal gamma capsulotomy for refractory obsessive-compulsive disorder: a pilot study.

Five refractory obsessive-compulsive patients were assessed using a neuropsychological battery after a modified gamma knife capsulotomy. The surgical technique was not associated with profound cognitive deficits. The authors found improvements in attention, vocabulary, learning, abstract reasoning, and memory.

Post-acute pathological changes in the thalamus and internal capsule in aged mice following controlled cortical impact injury: a magnetic resonance imaging, iron histochemical, and glial immunohistochemical study.

Traumatic brain injury (TBI) is a major cause of neurological disability across all ages, but the elderly are particularly vulnerable and have a worse prognosis than younger individuals. To advance the understanding of long-term pathogenesis induced by TBI in the elderly, aged mice (21 -- 24 months) were given a controlled cortical impact (CCI) injury to the sensorimotor cortex, and their brains were analyzed by MRI and histopathology at 1 and 2 months after CCI injury, a post-acute period. A T2 hypointensity was observed in the ipsilateral thalamus but not in the contralateral thalamus or in the thalamus of sham operated, control mice. The hypointensity was co-localized with increased histochemical staining of iron, a paramagnetic substance that causes a shortening of the T2 relaxation time. Since iron catalyzes reactions that lead to toxic free radicals, the deposition of iron in the thalamus raises the possibility that it promotes pathogenesis following TBI. Astrocyte gliosis and microgliosis were also observed in the ipsilateral thalamus in the post-acute period. The ipsilateral internal capsule displayed a trend for a T2 hypointensity, however, unlike the thalamus it did not have an increase of iron or GFAP staining, but it did have evidence of microgliosis. In summary, areas of T2 hypointensity were revealed in both the thalamus and internal capsule during the post-acute period following CCI injury, but the underlying pathology appeared to be distinct between these regions.