Cerebellar Brain Inhibition Is Associated With the Severity of Cervical Dystonia.

PURPOSE: Cerebellar connectivity is thought to be abnormal in cervical dystonia (CD) and other dystonia subtypes, based on evidence from imaging studies and animal work. The authors investigated whether transcranial magnetic stimulation-induced cerebellar brain inhibition (CBI), a measure of cerebellar efficiency at inhibiting motor outflow, is abnormal in patients with CD and/or is associated with clinical features of CD. Because of methodological heterogeneity in CBI reporting, the authors deployed additional controls to reduce potential sources of variability in this study. METHODS: Cerebellar brain inhibition was applied in 20 CD patients and 14 healthy control subjects. Cerebellar brain inhibition consisted of a cerebellar conditioning stimulus delivered at four different interstimulus intervals (ISIs) before a test stimulus delivered to hand muscle representation in the motor cortex. The average ratio of conditioned to unconditioned motor evoked potential was computed for each ISI. Cervical dystonia clinical severity was measured using the Toronto Western Spasmodic Torticollis Rating Scale. Control experiments involved neuronavigated transcranial magnetic stimulation, neck postural control in patients, and careful screening for noncerebellar pathway inhibition via cervicomedullary evoked potentials. RESULTS: There was no difference between CBI measured in healthy control subjects and CD patients at any of the four ISIs; however, CBI efficiency was significantly correlated with worsening CD clinical severity at the 5 ms ISI. CONCLUSIONS: Cerebellar brain inhibition is a variable measure in both healthy control subjects and CD patients; much of this variability may be attributed to experimental methodology. Yet, CD severity is significantly associated with reduced CBI at the 5 ms ISI, suggestive of cerebello-thalamo-cortical tract dysfunction in this disorder.

TMS Motor Mapping Methodology and Reliability: A Structured Review.

Motor cortical representation can be probed non-invasively using a transcranial magnetic stimulation (TMS) technique known as motor mapping. The mapping technique can influence features of the maps because of several controllable elements. Here we review the literature on six key motor mapping parameters, as well as their influence on outcome measures and discuss factors impacting their selection. 132 of 1,587 distinct records were examined in detail and synthesized to form the basis of our review. A summary of mapping parameters, their impact on outcome measures and feasibility considerations are reported to support the design and interpretation of TMS mapping studies.

Microstructural Abnormalities of the Dentatorubrothalamic Tract in Cervical Dystonia.

BACKGROUND: The dentatorubrothalamic tract (DRTT) remains understudied in idiopathic cervical dystonia (CD), despite evidence that the pathway is relevant in the pathophysiology of the disorder. OBJECTIVE: The aim of this study was to examine the DRTT in patients with CD using diffusion tensor imaging (DTI)-based tractography. METHODS: Magnetic resonance imaging scans from 67 participants were collected to calculate diffusion tractography metrics using a binary tractography-based DRTT template. Fractional anisotropy and diffusivity measures of left and right DRTT were computed and compared between 32 subjects with CD and 35 age-matched healthy volunteers. RESULTS: Fractional anisotropy of right DRTT and mean and axial diffusivity of left DRTT were significantly reduced in patients with CD. Similar abnormalities were observed in patients with focal CD and patients with CD without tremor. DTI metrics did not correlate with disease duration or severity. CONCLUSIONS: Significant reductions in DTI measures suggest microstructural abnormalities within the DRTT in CD, characterized by a tractography pattern consistent with decreased axonal integrity. © 2021 International Parkinson and Movement Disorder Society.

Case studies in neuroscience: deep brain stimulation changes upper limb cortical motor maps in dystonia.

Deep brain stimulation of the globus pallidus pars interna (GPi-DBS) is an effective treatment for primary dystonia; however, its therapeutic mechanism is poorly understood. Because improvement is gradual, GPi-DBS treatment likely involves short- and long-term mechanisms. Abnormal plasticity resulting in somatotopic reorganization is involved in the development of dystonia and has been proposed as a possible mechanism for this gradual improvement, yet it has not been directly investigated. We hypothesized that GPi-DBS will lead to progressive changes in the cortical representations (motor maps) of upper limb muscles. Neuronavigated robotic transcranial magnetic stimulation was used to map the cortical representation of five upper limb muscles in six healthy controls and a 45-yr-old female cervical dystonia patient before (Pre) and at four time points (Post5 to Post314), 5 to 314 days after GPi-DBS. Motor map area and volume decreased in all muscles following GPi-DBS, while changes in overlap and center of gravity distance between muscles were variable. Despite these motor map changes, only dystonic tremor improved after a year of DBS; neck position worsened slightly. These preliminary findings suggest that GPi-DBS may reduce the cortical representation and excitability of upper limb muscles in dystonia and that these changes can occur without clinical improvement.NEW & NOTEWORTHY Neuronavigated robotic transcranial magnetic stimulation was used to investigate changes in upper limb muscle representation in a cervical dystonia patient before and at four time points up to 314 days after globus pallidus pars interna deep brain stimulation (GPi-DBS). GPi-DBS altered excitability and motor cortical representation of upper limb muscles; however, these changes were not associated with clinical improvement.

Reproducibility of compartmental subchondral bone morphometry in the mouse tibiofemoral joint.

AIM: Evidence suggests that subchondral bone can be used as a predictor for the onset of osteoarthritis. As such, there is a need to accurately and reproducibly quantify subchondral bone in areas where osteoarthritis develops. In this paper, we present a novel technique for the segmentation of subchondral bone in the tibiofemoral joint and assess the reproducibility of this method with multiple measures and users. METHODS: The right hind leg of seven C57BL/6 mice were excised and imaged in µCT. The menisci and patella were manually segmented and the image data was Gaussian filtered and binarized. An in-house algorithm was used to generate cortical and epiphyseal volumes of interest and standard morphometric indices for bone were computed. The intraclass correlation coefficient (ICC), absolute precision error (PE(SD)), and precision error as a percentage of the coefficient of variation of the repeated measurements (PE(%CV)) were calculated for each index. Additionally, an inter-user study was performed using the same indices and statistics. RESULTS: For repeated measures, ICC ranged from 0.869 (cortical bone volume fraction, femur) to 0.994 (degree of anisotropy, femur). Similarly, PE(%CV) ranged from 0.84% (cortical bone volume fraction, femur) to 5.11% (connectivity density, tibia). For repeated users, no effect was seen in the femur with a slight effect in the tibia. CONCLUSIONS: A novel method for the automatic segmentation of cortical and epiphyseal bone is presented and is shown to be reproducible in C57BL/6 mice. This tool will allow for high-throughput studies of osteoarthritis in animal models.