Search

TMS-evoked cortical responses can be measured using simultaneous electroencephalography (TMS-EEG) to directly quantify cortical connectivity in the human brain. The purpose of this study was to evaluate interhemispheric cortical connectivity between the primary motor cortices (M1s) in participants with chronic stroke and controls using TMS-EEG. Ten participants with chronic stroke and four controls were tested. TMS-evoked responses were recorded at rest and during a typical TMS assessment of transcallosal inhibition (TCI). EEG recordings from peri -central gyral electrodes (C3 and C4) were evaluated using imaginary phase coherence (IPC) analyses to quantify levels of effective interhemispheric connectivity. Significantly increased TMS-evoked beta (15–30 Hz frequency range) IPC was observed in the stroke group during ipsilesional M1 stimulation compared to controls during TCI assessment but not at rest. TMS-evoked beta IPC values were associated with TMS measures of transcallosal inhibition across groups. These results suggest TMS-evoked EEG responses can index abnormal effective interhemispheric connectivity in chronic stroke. [ABSTRACT FROM AUTHOR]

Objective To examine the relationship of transcallosal pathway microstructure and transcallosal inhibition (TCI) with motor function and impairment in chronic stroke. Methods Diffusion-weighted magnetic resonance imaging and transcranial magnetic stimulation (TMS) data were collected from 24 participants with chronic stroke and 11 healthy older individuals. Post-stroke motor function (Wolf Motor Function Test) and level of motor impairment (Fugl-Meyer score) were evaluated. Results Fractional anisotropy (FA) of transcallosal tracts between prefrontal cortices and the mean amplitude decrease in muscle activity during the ipsilateral silent period evoked by TMS over the non-lesioned hemisphere (termed NL-iSP mean ) were significantly associated with level of motor impairment and motor function after stroke ( p < 0.05). A regression model including age, post-stroke duration, lesion volume, lesioned corticospinal tract FA, transcallosal prefrontal tract FA and NL-iSP mean accounted for 84% of variance in motor impairment ( p < 0.01). Both transcallosal prefrontal tract FA (Δ R 2 = 0.12, p = 0.04) and NL-iSP mean (Δ R 2 = 0.09, p = 0.04) accounted for unique variance in motor impairment level. Conclusions Prefrontal transcallosal tract microstructure and TCI are each uniquely associated with motor impairment in chronic stroke. Significance Utilizing a multi-modal approach to assess transcallosal pathways may improve our capacity to identify important neural substrates of motor impairment in the chronic phase of stroke. [ABSTRACT FROM AUTHOR]

Ondansetron is a highly effective antiemetic for the treatment of nausea and vomiting. However, this medication has also been associated with QT prolongation. Pharmacogenomic information on therapeutic response to ondansetron exists, but no investigation has been performed on genetic factors that influence the cardiac safety of this medication. Three patient groups receiving ondansetron were recruited and followed prospectively (pediatric post-surgical patients n = 101; pediatric oncology patients n = 98; pregnant women n = 62). Electrocardiograms were conducted at baseline, and 5- and 30-min post-ondansetron administration, to determine the effect of ondansetron treatment on QT interval. Pharmacogenomic associations were assessed via analyses of comprehensive CYP2D6 genotyping and genome-wide association study data. In the entire cohort, 62 patients (24.1%) met the criteria for prolonged QT, with 1.2% of the cohort exhibiting unsafe QT prolongation. The most significant shift from baseline occurred at five minutes post-ondansetron administration (P = 9.8 × 10−4). CYP2D6 activity score was not associated with prolonged QT. Genome-wide analyses identified novel associations with a missense variant in TLR3 (rs3775291; P = 2.00 × 10−7) and a variant linked to the expression of SLC36A1 (rs34124313; P = 1.97 × 10−7). This study has provided insight into the genomic basis of ondansetron-induced cardiac changes and has emphasized the importance of genes that have been implicated in serotonin-related traits. These biologically-relevant findings represent the first step towards understanding this adverse event with the overall goal to improve the safety of this commonly used antiemetic medication. • This study examined the role of genetics in the cardiac safety of ondansetron. • 1.2% of patients experienced unsafe ondansetron-induced QT prolongation. • 24.1% of patients experienced a shift in QTc after ondansetron treatment. • The biggest shift in QTc occurred at five minutes post-ondansetron administration. • Genome-wide analyses provided new insights into the genetics of this adverse event. [ABSTRACT FROM AUTHOR]