Cholinergic Interneurons Are Differentially Distributed in the Human Striatum

BACKGROUND: The striatum (caudate nucleus, CN, and putamen, Put) is a group of subcortical nuclei involved in planning and executing voluntary movements as well as in cognitive processes. Its neuronal composition includes projection neurons, which connect the striatum with other structures, and interneurons, whose main roles are maintaining the striatal organization and the regulation of the projection neurons. The unique electrophysiological and functional properties of the cholinergic interneurons give them a crucial modulating function on the overall striatal response. METHODOLOGY/PRINCIPLE FINDINGS: This study was carried out using stereological methods to examine the volume and density (cells/mm(3)) of these interneurons, as visualized by choline acetyltransferase (ChAT) immunoreactivity, in the following territories of the CN and Put of nine normal human brains: 1) precommissural head; 2) postcommissural head; 3) body; 4) gyrus and 5) tail of the CN; 6) precommissural and 7) postcommissural Put. The distribution of ChAT interneurons was analyzed with respect to the topographical, functional and chemical territories of the dorsal striatum. The CN was more densely populated by cholinergic neurons than the Put, and their density increased along the anteroposterior axis of the striatum with the CN body having the highest neuronal density. The associative territory of the dorsal striatum was by far the most densely populated. The striosomes of the CN precommissural head and the postcommissural Put contained the greatest number of ChAT-ir interneurons. The intrastriosomal ChAT-ir neurons were abundant on the periphery of the striosomes throughout the striatum. CONCLUSIONS/SIGNIFICANCE: All these data reveal that cholinergic interneurons are differentially distributed in the distinct topographical and functional territories of the human dorsal striatum, as well as in its chemical compartments. This heterogeneity may indicate that the posterior aspects of the CN require a special integration of information by interneurons. Interestingly, these striatal regions have been very much left out in functional studies

National Institutes of Health Toolbox Emotion Battery for English- and Spanish-speaking adults: normative data and factor-based summary scores

Ida Babakhanyan,1,2 Benjamin S McKenna,2 Kaitlin B Casaletto,3 Cindy J Nowinski,4 Robert K Heaton2 1Defense and Veteran’s Brain Injury Center, Camp Pendleton, 2Department of Psychiatry, University of California, San Diego, La Jolla, 3Department of Neurology, University of California, San Francisco, San Francisco, CA, 4Department of Medical Social Sciences, Northwestern University, Chicago, IL, USA Background: The National Institutes of Health Toolbox Emotion Battery (NIHTB-EB) is a “common currency”, computerized assessment developed to measure the full spectrum of emotional health. Though comprehensive, the NIHTB-EB’s 17 scales may be unwieldy for users aiming to capture more global indices of emotional functioning. Methods: NIHTB-EB was administered to 1,036 English-speaking and 408 Spanish-speaking adults as a part of the NIH Toolbox norming project. We examined the factor structure of the NIHTB-EB in English- and Spanish-speaking adults and developed factor analysis-based summary scores. Census-weighted norms were presented for English speakers, and sample-weighted norms were presented for Spanish speakers. Results: Exploratory factor analysis for both English- and Spanish-speaking cohorts resulted in the same 3-factor solution: 1) negative affect, 2) social satisfaction, and 3) psychological well-being. Confirmatory factor analysis supported similar factor structures for English- and Spanish-speaking cohorts. Model fit indices fell within the acceptable/good range, and our final solution was optimal compared to other solutions. Conclusion: Summary scores based upon the normative samples appear to be psychometrically supported and should be applied to clinical samples to further validate the factor structures and investigate rates of problematic emotions in medical and psychiatric populations. Keywords: emotional functioning, NIH Toolbox Emotion Battery, factor analyses, summary scores, normative dat

The everyday experience of living with and managing a neurological condition (the LINC study): study design

Background: The impact of neurological conditions on individuals, families and society is increasing and having a significant economic impact in Canada. While some economic data is known, the human costs of living with a neurological condition are poorly understood and rarely factored into future burden analyses. The “Living with the Impact of a Neurological Condition (LINC)” study aims to fill this gap. It seeks to understand, for children and adults with neurological conditions, the supports and resources that make everyday life possible and meaningful. Methods/design: The LINC study is a nested study using mixed methods. We are interested in the following outcomes specifically: health status; resource utilization; self-management strategies; and participation. Three studies captured data from multiple sources, in multiple ways and from multiple perspectives. Study One: a populationbased survey of adults (n = 1500), aged 17 and over and parents (n = 200) of children aged 5 to 16 with a neurological condition. Study Two: a prospective cohort study of 140 adults and parents carried out using monthly telephone calls for 10 months; and Study Three: a multiple perspective case study (MPCS) of 12 adults and 6 parents of children with a neurological condition. For those individuals who participate in the MPCS, we will have data from all three studies giving us rich, in depth insights into their daily lives and how they cope with barriers to living in meaningful ways. Discussion: The LINC study will collect, for the first time in Canada, data that reflects the impact of living with a neurological condition from the perspectives of the individuals themselves. A variety of tools will be used in a combination, which is unique and innovative. This study will highlight the commonalities of burden that Canadians living with neurological conditions experience as well as their strategies for managing everyday life

Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model.

Blast exposure is associated with traumatic brain injury (TBI), neuropsychiatric symptoms, and long-term cognitive disability. We examined a case series of postmortem brains from U.S. military veterans exposed to blast and/or concussive injury. We found evidence of chronic traumatic encephalopathy (CTE), a tau protein-linked neurodegenerative disease, that was similar to the CTE neuropathology observed in young amateur American football players and a professional wrestler with histories of concussive injuries. We developed a blast neurotrauma mouse model that recapitulated CTE-linked neuropathology in wild-type C57BL/6 mice 2 weeks after exposure to a single blast. Blast-exposed mice demonstrated phosphorylated tauopathy, myelinated axonopathy, microvasculopathy, chronic neuroinflammation, and neurodegeneration in the absence of macroscopic tissue damage or hemorrhage. Blast exposure induced persistent hippocampal-dependent learning and memory deficits that persisted for at least 1 month and correlated with impaired axonal conduction and defective activity-dependent long-term potentiation of synaptic transmission. Intracerebral pressure recordings demonstrated that shock waves traversed the mouse brain with minimal change and without thoracic contributions. Kinematic analysis revealed blast-induced head oscillation at accelerations sufficient to cause brain injury. Head immobilization during blast exposure prevented blast-induced learning and memory deficits. The contribution of blast wind to injurious head acceleration may be a primary injury mechanism leading to blast-related TBI and CTE. These results identify common pathogenic determinants leading to CTE in blast-exposed military veterans and head-injured athletes and additionally provide mechanistic evidence linking blast exposure to persistent impairments in neurophysiological function, learning, and memory

Paediatric endoscopic endonasal dacryocystorhinostomy in congenital nasolacrimal duct obstruction

The original publication can be found at www.springerlink.comObjectives The objectives of this study were to report a series of paediatric patients who underwent endoscopic endonasal dacryocystorhinostomy (DCR) for primary congenital nasolacrimal duct obstruction (NLDO). Methods This is a retrospective, noncomparative review of all consecutive cases in two lacrimal clinics between January 1999 and October 2004. The main outcome measures were patients’ demographics, previous treatments, clinical presentation, operative and postoperative complications, postoperative follow-up and resolution of epiphora. Results Twenty-one patients (15 males) with a mean age of 6±3.5 years (range, 2–14 years) underwent 26 endoscopic DCR operations for congenital NLDO. Sixteen cases were unilateral, and five were bilateral. In 13 cases (50.0%), there was a history of epiphora and chronic dacryocystitis with or without a mucocele. Two cases (7.7%) presented with acute dacryocystitis, and 11 (42.3%) had only a history of epiphora. Previous procedures included probing and irrigation in 25 cases (96.2%) and insertion of Crawford tubes in 19 cases 973.1%). During a mean postoperative follow-up period of 18±8 months, the anatomical success rate (free flow of fluorescein sodium and patency of ostium on nasal endoscopy) was 100%, and the clinical success rate (resolution of epiphora) was 92.3%. Conclusion Endoscopic endonasal DCR is an effective treatment modality for congenital NLDO that compares favourably with the reported success rates of external DCR.Igal Leibovitch, Dinesh Selva, Angelo Tsirbas, Edward Greenrod, John Pater and Peter J. Wormal