DiMANI: diffusion MRI for anatomical nuclei imaging—Application for the direct visualization of thalamic subnuclei

The thalamus is a centrally located and heterogeneous brain structure that plays a critical role in various sensory, motor, and cognitive processes. However, visualizing the individual subnuclei of the thalamus using conventional MRI techniques is challenging. This difficulty has posed obstacles in targeting specific subnuclei for clinical interventions such as deep brain stimulation (DBS). In this paper, we present DiMANI, a novel method for directly visualizing the thalamic subnuclei using diffusion MRI (dMRI). The DiMANI contrast is computed by averaging, voxelwise, diffusion-weighted volumes enabling the direct distinction of thalamic subnuclei in individuals. We evaluated the reproducibility of DiMANI through multiple approaches. First, we utilized a unique dataset comprising 8 scans of a single participant collected over a 3-year period. Secondly, we quantitatively assessed manual segmentations of thalamic subnuclei for both intra-rater and inter-rater reliability. Thirdly, we qualitatively correlated DiMANI imaging data from several patients with Essential Tremor with the localization of implanted DBS electrodes and clinical observations. Lastly, we demonstrated that DiMANI can provide similar features at 3T and 7T MRI, using varying numbers of diffusion directions. Our results establish that DiMANI is a reproducible and clinically relevant method to directly visualize thalamic subnuclei. This has significant implications for the development of new DBS targets and the optimization of DBS therapy

Low-frequency deep brain stimulation reveals resonant beta-band evoked oscillations in the pallidum of Parkinson’s Disease patients

IntroductionEvidence suggests that spontaneous beta band (11–35 Hz) oscillations in the basal ganglia thalamocortical (BGTC) circuit are linked to Parkinson’s disease (PD) pathophysiology. Previous studies on neural responses in the motor cortex evoked by electrical stimulation in the subthalamic nucleus have suggested that circuit resonance may underlie the generation of spontaneous and stimulation-evoked beta oscillations in PD. Whether these stimulation-evoked, resonant oscillations are present across PD patients in the internal segment of the globus pallidus (GPi), a primary output nucleus in the BGTC circuit, is yet to be determined.MethodsWe characterized spontaneous and stimulation-evoked local field potentials (LFPs) in the GPi of four PD patients (five hemispheres) using deep brain stimulation (DBS) leads externalized after DBS implantation surgery.ResultsOur analyses show that low-frequency (2–4 Hz) stimulation in the GPi evoked long-latency (>50 ms) beta-band neural responses in the GPi in 4/5 hemispheres. We demonstrated that neural sources generating both stimulation-evoked and spontaneous beta oscillations were correlated in their frequency content and spatial localization.DiscussionOur results support the hypothesis that the same neuronal population and resonance phenomenon in the BGTC circuit generates both spontaneous and evoked pallidal beta oscillations. These data also support the development of closed-loop control systems that modulate the GPi spontaneous oscillations across PD patients using beta band stimulation-evoked responses

The Economic Consequences of Social-Network Structure

We survey the literature on the economic consequences of the structure of social networks. We develop a taxonomy of "macro" and "micro" characteristics of social-interaction networks and discuss both the theoretical and empirical findings concerning the role of those characteristics in determining learning, diffusion, decisions, and resulting behaviors. We also discuss the challenges of accounting for the endogeneity of networks in assessing the relationship between the patterns of interactions and behaviors

A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals

Background - The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs. Methods - We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity. Results - Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs. Conclusions - When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.The workshops that supported the writing of this manuscript were funded by the Swedish Foundation for Strategic Environmental Research “Mistra”. LNV was funded by Award Number K22ES025811 from the National Institute of Environmental Health Sciences of the National Institutes of Health. TJW was funded by The Clarence Heller Foundation (A123547), the Passport Foundation, the Forsythia Foundation, the National Institute of Environmental Health Sciences (grants ES018135 and ESO22841), and U.S. EPA STAR grants (RD83467801 and RD83543301). JT was funded by the Academy of Finland and Sigrid Juselius. UH was funded by the Danish EPA. KAK was funded by the Canada Research Chairs program grant number 950–230607

Sumerian and Aryan : Racial Theory, Academic Politics and Parisian Assyriology

In the last quarter of the nineteenth century, there was a lively, often acrimonious debate over the existence of the Sumerians. A majority of scholars contended that the Sumerians originated the civilization of ancient Mesopotamia, and invented cuneiform writing, which they passed on, with other elements of civilization, to the Semitic Babylonians and Assyrians who appeared after them in Mesopotamia. A minority, led by Joseph Halévy of the Ecole pratique des Hautes Etudes, asserted that Mesopotamian civilization was a Semitic creation, and that the so-called Sumerian texts were really Semitic texts written in a hieratic mode. This article examines the controversy against the background of nineteenth century notions of race and language, and with reference to the personalities of the protagonists and the academic politics of the times.Sumériens et Aryens : théorie raciale, politique universitaire et assyriologie parisienne Dans le dernier quart du XIXe siècle, un débat animé et souvent acrimonieux eut lieu sur l'existence des Sumériens. La majorité des savants soutenait que les Sumériens avaient donné naissance à la civilisation de l'ancienne Mésopotamie et inventé l'écriture cunéiforme, qu'ils transmirent — avec ďautres éléments de civilisation — aux Sémites babyloniens et assyriens, apparus après eux en Mésopotamie. Une minorité, conduite par Joseph Halévy, de l'Ecole Pratique des Hautes Etudes, affirmait que la civilisation mésopotamienne était une création sémitique et que les soi-disant textes sumériens étaient en réalité des textes sémitiques écrits selon un mode « hiératisant ». Le présent article examine cette controverse à la lumière des notions de race et de langage telles qu'on se les représentait au XIXe siècle, mais aussi en se référant à la personnalité des protagonistes et à la politique universitaire de l'époque.Cooper Jerrold S. Sumerian and Aryan : Racial Theory, Academic Politics and Parisian Assyriology. In: Revue de l'histoire des religions, tome 210, n°2, 1993. pp. 169-205

Last writing: script obsolescence in Egypt, Mesopotamia, and Mesoamerica

Introduction: Setting the questions. By any measure, the creation and development of writing was a cybernetic advance with far-reaching consequences. It allowed writers to communicate with readers who were distant in time and space, extended the storage capacity of human knowledge, including information that ranged from mundane accounting to sacred narrative, bridged visual and auditory worlds by linking icons with meaningful sound, and offered an enduring means of displaying and manipulating assertions about a wide variety of matters. In part, the first writing attracts attention because it contributes to a teleological narrative of progress(Trigger 1998: 42). The invention of writing is thought, with good justification,to undergird and enable present-day society. In its more developed forms, it is indispensable to bureaucracy, propaganda, and administration.Houston, S., Baines, J. & Cooper, J. (2003) Last Writing: Script Obsolescence in Egypt, Mesopotamia, and Mesoamerica, Comparative Studies in Society and History, 45 (3), 430-479. This article was originally published by Cambridge University Press, and is available at http://www.cambridge.org/journals/journal_catalogue.asp?historylinks=ALPHA&mnemonic=CSS ©2003 The Society for Comparative Study of Society and History

Induction of insulin resistance in vivo by amylin and calcitonin gene-related peptide

During hyperinsulinemic glucose-clamp studies, intravenous infusion of calcitonin gene-related peptide (CGRP) in rats antagonized the ability of insulin to stimulate peripheral glucose disposal by 52% (196 ± 7.2 vs. 105 ± 10.5 μmol · kg−1 · min−1, P &amp;lt; 0.05) and to inhibit hepatic glucose output by 54% (P &amp;lt; 0.01). CGRP also inhibited the in vitro effects of insulin to stimulate hexose uptake in cultured BC3H1 myocytes at all insulin concentrations studied. Amylin is a peptide isolated from amyloid deposits in pancreatic islets of type II (non-insulin-dependent) diabetic subjects, is present in normal β-cells, and bears a striking homology to CGRP. When synethetic human amylin was infused during clamp studies, it inhibited the ability of insulin to stimulate glucose disposal by 56% (96.9 ± 9.4 vs. 42.4 ± 5.0 μmol · kg−1 · min−1, P &amp;lt; 0.05) and to suppress hepatic glucose output by 64%. Therefore, amylin and CGRP can cause insulin resistance in vivo and may be implicated in insulinresistant states such as type II diabetes mellitus.</jats:p

Overground versus treadmill walking in Parkinsons disease: Relationship between speed and spatiotemporal gait metrics.

BACKGROUND: Treadmills provide a safe and convenient way to study the gait of people with Parkinsons disease (PD), but outcome measures derived from treadmill gait may differ from overground walking. OBJECTIVE: To investigate how the relationships between gait metrics and walking speed vary between overground and treadmill walking in people with PD and healthy controls. METHODS: We compared 29 healthy controls to 27 people with PD in the OFF-medication state. Subjects first walked overground on an instrumented gait walkway, then on an instrumented treadmill at 85%, 100% and 115% of their overground walking speed. Average stride length and cadence were computed for each subject in both overground and treadmill walking. RESULTS: Stride length and cadence both differed between overground and treadmill walking. Regressions of stride length and cadence on gait speed showed a log-log relationship for both overground and treadmill gait in both PD and control groups. The difference between the PD and control groups during overground gait was maintained for treadmill gait, not only when treadmill speed matched overground speed, but also with ±&nbsp;15% variation in treadmill speed from that value. SIGNIFICANCE: These results show that the impact of PD on stride length and cadence and their relationship to gait speed is preserved in treadmill as compared to overground walking. We conclude that a treadmill protocol is suitable for laboratory use in studies of PD gait therapeutics