Perturbations of language network connectivity in primary progressive aphasia.

Aphasias are caused by disruption in structural integrity and interconnectivity within a large-scale distributed language network. We investigated the distribution and behavioral consequences of altered functional connectivity in three variants of primary progressive aphasia (PPA). The goal was to clarify relationships among atrophy, resting connectivity, and the resulting behavioral changes in 73 PPA and 33 control participants. Three core regions of the left perisylvian language network: the inferior frontal gyrus (IFG), middle temporal gyrus (MTG), and anterior temporal lobe (ATL) were evaluated in agrammatic (PPA-G), logopenic (PPA-L), and semantic (PPA-S) PPA variants. All PPA groups showed decreased connectivity between IFG and MTG. The PPA-S group also showed additional loss of connectivity strength between ATL and the other language regions. Decreased connectivity between the IFG and MTG nodes in PPA-G remained significant even when controlled for the effect of atrophy. In the PPA group as a whole, IFG-MTG connectivity strength correlated with repetition and grammar scores, whereas MTG-ATL connectivity correlated with picture naming and single-word comprehension. There was no significant change in the connectivity of homologous regions in the right hemisphere. These results show that language impairments in PPA are associated with perturbations of functional connectivity within behaviorally concordant components of the language network. Altered connectivity in PPA may reflect not only the irreversible loss of cortical components indexed by atrophy, but also the dysfunction of remaining neurons.

Is submucosal bladder pressure monitoring feasible?

There has been recent interest in placing pressure-sensing elements beneath the bladder mucosa to facilitate chronic bladder pressure monitoring. Wired submucosal sensors with the wires passed through detrusor have been demonstrated in vivo, with limited chronic retention, potentially due to the cable tethering the detrusor. Published studies of submucosal implants have shown that high correlation coefficients between submucosal and lumen pressures can be obtained in caprine, feline, and canine models. We have developed a wireless pressure monitor and surgical technique for wireless submucosal implantation and present our initial chronic implantation study here. Pressure monitors were implanted (n = 6) in female calf models (n = 5). Five devices were implanted cystoscopically with a 25-French rigid cystoscope. One device was implanted suprapubically to test device retention with an intact mucosa. Wireless recordings during anesthetized cystometry simultaneous with catheter-based reference vesical pressure measurements during filling and manual bladder compressions were recorded. Individual analysis of normalised data during bladder compressions (n = 12) indicated high correlation (r = 0.85-0.94) between submucosal and reference vesical pressure. The healing response was robust over 4 weeks; however, mucosal erosion occurred 2-4 weeks after implantation, leading to device migration into the bladder lumen and expulsion during urination. Wireless pressure monitors may be successfully placed in a suburothelial position. Submucosal pressures are correlated with vesical pressure, but may differ due to biomechanical forces pressing on an implanted sensor. Fully wireless devices implanted beneath the mucosa have risk of erosion through the mucosa, potentially caused by disruption of blood flow to the urothelium, or an as-yet unstudied mechanism of submucosal regrowth. Further investigation into device miniaturisation, anchoring methods, and understanding of submucosal pressure biomechanics may enable chronic submucosal pressure monitoring. However, the risk of erosion with submucosal implantation highlights the need for investigation of devices designed for chronic intravesical pressure monitoring.

Wireless Bladder Pressure Monitor for Closed-Loop Bladder Neuromodulation.

Conditional neuromodulation is a form of closed-loop bladder control where neurostimulation is applied in reaction to bladder pressure changes. Current methods based on external catheters have limited utility for chronic ambulatory therapy. We have developed a wireless pressure monitor to provide real-time, catheter-free detection of bladder contractions. The device is sized for chronic implantation in the bladder muscle. The pressure monitor consists of an ultra-low-power application specific integrated circuit (ASIC), micro-electro-mechanical (MEMS) pressure sensor, RF antennas, and rechargeable battery. Here we describe an overview of the system, including chronic in vivo test data of a non-hermetic polymer sensor package and chronic testing of the wireless sensor in large animal models. Test results show that the packaging method is viable for chronic encapsulation of implanted pressure sensors. Chronic testing of the pressure monitor revealed some obstacles relating to the chosen implant site within the bladder wall. However, chronic wireless device function was confirmed and data quality was sufficient to detect bladder compressions in large animals, with average correlation coefficient of 0.90.