Modulation of Resting Connectivity Between the Mesial Frontal Cortex and Basal Ganglia.

Background: The mesial prefrontal cortex, cingulate cortex, and the ventral striatum are key nodes of the human mesial fronto-striatal circuit involved in decision-making and executive function and pathological disorders. Here we ask whether deep wide-field repetitive transcranial magnetic stimulation (rTMS) targeting the mesial prefrontal cortex (MPFC) influences resting state functional connectivity. Methods: In Study 1, we examined functional connectivity using resting state multi-echo and independent components analysis in 154 healthy subjects to characterize default connectivity in the MPFC and mid-cingulate cortex (MCC). In Study 2, we used inhibitory, 1 Hz deep rTMS with the H7-coil targeting MPFC and dorsal anterior cingulate (dACC) in a separate group of 20 healthy volunteers and examined pre- and post-TMS functional connectivity using seed-based and independent components analysis. Results: In Study 1, we show that MPFC and MCC have distinct patterns of functional connectivity with MPFC-ventral striatum showing negative, whereas MCC-ventral striatum showing positive functional connectivity. Low-frequency rTMS decreased functional connectivity of MPFC and dACC with the ventral striatum. We further showed enhanced connectivity between MCC and ventral striatum. Conclusions: These findings emphasize how deep inhibitory rTMS using the H7-coil can influence underlying network functional connectivity by decreasing connectivity of the targeted MPFC regions, thus potentially enhancing response inhibition and decreasing drug-cue reactivity processes relevant to addictions. The unexpected finding of enhanced default connectivity between MCC and ventral striatum may be related to the decreased influence and connectivity between the MPFC and MCC. These findings are highly relevant to the treatment of disorders relying on the mesio-prefrontal-cingulo-striatal circuit

Inhibition of transporter-mediated hepatic uptake as amechanism for drug-drug interaction between cerivastatin and cyclosporin

ABSTRACT The mechanism involved in the clinically relevant drug-drug interaction (DDI) between cerivastatin (CER) and cyclosporin A (CsA) has not yet been clarified. In the present study, we examined the possible roles of transporter-mediated hepatic uptake in this DDI

Evaluating interhemispheric connectivity during midline object recognition using EEG

Functional integration between two hemispheres is crucial for perceptual binding to occur when visual stimuli are presented in the midline of the visual field. Mima and colleagues (2001) showed using EEG that midline object recognition was associated with task-related decrease in alpha band power (alpha desynchronisation) and a transient increase in interhemispheric coherence. Our objective in the current study was to replicate the results of Mima et al. and to further evaluate interhemispheric effective connectivity during midline object recognition in source space. We recruited 11 healthy adult volunteers and recorded EEG from 64 channels while they performed a midline object recognition task. Task-related power and coherence were estimated in sensor and source spaces. Further, effective connectivity was evaluated using Granger causality. While we were able to replicate the alpha desynchronisation associated with midline object recognition, we could not replicate the coherence results of Mima et al. The data-driven approach that we employed in our study localised the source of alpha desynchronisation over the left occipito-temporal region. In the alpha band, we further observed significant increase in imaginary part of coherency between bilateral occipito-temporal regions during object recognition. Finally, Granger causality analysis between the left and right occipito-temporal regions provided an insight that even though there is bidirectional interaction, the left occipito-temporal region may be crucial for integrating the information necessary for object recognition. The significance of the current study lies in using high-density EEG and applying more appropriate and robust measures of connectivity as well as statistical analysis to validate and enhance our current knowledge on the neural basis of midline object recognition

Reliability of Measuring the Proximal Humeral Bone Mineral Density Using Dual-Energy X-ray Absorptiometry

We established a protocol for assessing the areal bone mineral density (BMD) of the proximal humerus using dual-energy X-ray absorptiometry (DXA). We also investigated the correlation between the BMD of the proximal humerus and that of the lumbar spine and proximal femur to predict the BMD of the proximal humerus. We included female patients aged >60 years who underwent bone density evaluation using DXA. The BMD of the proximal humerus was calculated at seven regions of interest (ROIs): the head of the humerus, lesser tubercle, greater tubercle in two locations, and proximal metaphysis in three locations. The intra- and inter-examiner reliabilities in the setting of the ROIs were examined using intraclass correlation coefficients (ICCs) (1.1) and (2.1), respectively, and the intra-examiner reliability in DXA was examined using ICCs (1.1). The intra- and inter-examiner reliabilities in the setting of ROIs and the intra-examiner reliability in DXA were high in all regions. The BMD of the lumbar spine and proximal femur correlated weakly with that of the humeral head and diaphysis. Our method for measuring the BMD of the proximal humerus was found to be reliable and may be applied in future studies