Evidence for Altered Basal Ganglia-Brainstem Connections in Cervical Dystonia

Background: There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia. Methodology/Principal Findings: In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients. Conclusions/Significance: These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Geochemistry of granitic aplite-pegmatite dykes and sills and their minerals from the Gravanho-Gouveia area in Central Portugal

Two distinct series of Variscan granitic rocks have been distinguished in the Gravanho-Gouveia area of Portugal, based on field work, variation diagrams for major and trace elements, rare earth patterns and δ18O versus total FeO diagram of rocks, anorthite content of plagioclase, BaO and P2O5 contents of feldspars and AlVI versus Fe2+ diagram for magmatic muscovite. One series consists of a late-orogenic porphyritic biotite > muscovite granite (G1), less evolved beryl-columbite pegmatites and more evolved beryl-columbite pegmatites showing grada- tional contacts. The other series consists of post-orogenic porphyritic muscovite > biotite granodiorite to granite (G2), slightly porphyritic muscovite > biotite granite (G3) and lepidolite pegmatites. In each series, pegmatites are derived from the parent granite magma by fractional crystallization of quartz, plagioclase, K- feldspar, biotite and ilmenite. Some metasomatic effects occur like muscovite replacing feldspars, chlorite in pegmatites of the first series and a late muscovite in pegmatites of the second series, probably due to hydro- thermal fluids. The lepidolite pegmatites contain cassiterite and two generations of rutile. The first magmatic generation consists of homogeneous crystals and the second generation occurs as heterogeneous zoned crystals derived from hydrothermal fluids. The beryl-columbite pegmatites and lepidolite pegmatites also contain the first magmatic generation and the late hydrothermal generation of zoned columbite-group minerals. More evolved beryl-columbite pegmatites were converted into episyenite by intense hydrothermal alteration and regional circulation of fluids in the granitic rocks.This research was financially supported by the FCT project UID/GEO/04035/2013

Clinical characteristics of cervical dystonia patients.

*<p>subjects included in 2006 study using different analyses.</p><p>BFM: Burke Fahn Marsden dystonia rating scale.</p><p>Tsui: Tsui rating scale for cervical dystonia.</p><p>TW: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) for cervical dyston.</p

Group differences for voxel-wise probabilistic diffusion tractography contrast (12 cervical dystonia patients versus 12 matched controls).

*<p>Met significance criteria (p<0.00011 [p<0.05 corrected, or t = 4.70] for t values, and 291 voxels for cluster threshold).</p><p>Negative t values indicate that tractography measures were reduced in cervical dystonia patients relative to control subjects. Positive t values indicate that tractography measures were elevated in cervical dystonia patients relative to control subjects. Note that all regions included in the cluster are reported; however, only one peak within the cluster was required to reach statistical significance (t>4.12). t values are reported for all regions exhibiting peaks of 3.5 or greater. L = left hemisphere; R = right hemisphere; wm = white matter.</p

Group differences for voxel-wise FA contrast (12 cervical dystonia patients versus 12 matched controls).

*<p>Met significance criteria (p<0.00022, [p<0.05, corrected, or t = 4.42] for t values, and 72 voxels for cluster threshold).</p>†<p>p value was within an order of magnitude of the corrected threshold (a trend).</p><p>Positive t values indicate FA values were elevated in cervical dystonia patients relative to control subjects; negative t values indicate FA values were reduced in cervical dystonia patients relative to control subjects. L = left hemisphere; R = right hemisphere; wm = white matter.</p

Significant FA differences in cervical dystonia patients relative to control subjects.

<p>(A) Reduced FA in the left cerebellar white matter in patients. (B) Increased FA adjacent to and overlapping with the left substantia nigra in patients. MNI talairach coordinates are indicated for each image. t maps are superimposed on the average FA map for all 24 subjects in the study, and are thresholded at t = +/−2.5 here for illustrative purposes. The color bar indicates the range of t values in this figure for FA contrasts, from +/−2.5 to the peak positive and negative t values for this contrast. Warm tones (red, orange, yellow) indicate regions in which cervical dystonia patients exhibited elevated FA relative to control subjects. Cool tones (blues) indicate regions in which cervical dystonia patients exhibited reduced FA relative to control subjects. LH: left hemisphere; RH: right hemisphere.</p