Correlation of diffusion tensor tractography and intraoperative macrostimulation during deep brain stimulation for Parkinson disease.

Object The purpose of this study was to investigate whether diffusion tensor imaging (DTI) of the corticospinal tract (CST) is a reliable surrogate for intraoperative macrostimulation through the deep brain stimulation (DBS) leads. The authors hypothesized that the distance on MRI from the DBS lead to the CST as determined by DTI would correlate with intraoperative motor thresholds from macrostimulations through the same DBS lead. Methods The authors retrospectively reviewed pre- and postoperative MRI studies and intraoperative macrostimulation recordings in 17 patients with Parkinson disease (PD) treated by DBS stimulation. Preoperative DTI tractography of the CST was coregistered with postoperative MRI studies showing the position of the DBS leads. The shortest distance and the angle from each contact of each DBS lead to the CST was automatically calculated using software-based analysis. The distance measurements calculated for each contact were evaluated with respect to the intraoperative voltage thresholds that elicited a motor response at each contact. Results There was a nonsignificant trend for voltage thresholds to increase when the distances between the DBS leads and the CST increased. There was a significant correlation between the angle and the voltage, but the correlation was weak (coefficient of correlation [R] = 0.36). Conclusions Caution needs to be exercised when using DTI tractography information to guide DBS lead placement in patients with PD. Further studies are needed to compare DTI tractography measurements with other approaches such as microelectrode recordings and conventional intraoperative MRI-guided placement of DBS leads.

Neuronal responses in mouse barrel cortex:Comparison of two signal discriminators

Barrels are discrete cytoarchitectonic neurons cluster located in the layer IV of the somatosensory¦cortex in mice brain. Each barrel is related to a specific whisker located on the mouse snout. The¦whisker-to-barrel pathway is a part of the somatosensory system that is intensively used to explore¦sensory activation induced plasticity in the cerebral cortex.¦Different recording methods exist to explore the cortical response induced by whisker deflection in¦the cortex of anesthetized mice. In this work, we used a method called the Single-Unit Analysis by¦which we recorded the extracellular electric signals of a single barrel neuron using a microelectrode.¦After recording the signal was processed by discriminators to isolate specific neuronal shape (action¦potentials).¦The objective of this thesis was to familiarize with the barrel cortex recording during whisker¦deflection and its theoretical background and to compare two different ways of discriminating and¦sorting cortical signal, the Waveform Window Discriminator (WWD) or the Spike Shape Discriminator (SSD).¦WWD is an electric module allowing the selection of specific electric signal shape. A trigger and a¦window potential level are set manually. During measurements, every time the electric signal passes¦through the two levels a dot is generated on time line. It was the method used in previous¦extracellular recording study in the Département de Biologie Cellulaire et de Morphologie (DBCM) in¦Lausanne.¦SSD is a function provided by the signal analysis software Spike2 (Cambridge Electronic Design). The¦neuronal signal is discriminated by a complex algorithm allowing the creation of specific templates.¦Each of these templates is supposed to correspond to a cell response profile. The templates are saved¦as a number of points (62 in this study) and are set for each new cortical location. During¦measurements, every time the cortical recorded signal corresponds to a defined number of templates¦points (60% in this study) a dot is generated on time line. The advantage of the SSD is that multiple¦templates can be used during a single stimulation, allowing a simultaneous recording of multiple¦signals.¦It exists different ways to represent data after discrimination and sorting. The most commonly used¦in the Single-Unit Analysis of the barrel cortex are the representation of the time between stimulation¦and the first cell response (the latency), the representation of the Response Magnitude (RM) after¦whisker deflection corrected for spontaneous activity and the representation of the time distribution¦of neuronal spikes on time axis after whisker stimulation (Peri-Stimulus Time Histogram, PSTH).¦The results show that the RMs and the latencies in layer IV were significantly different between the¦WWD and the SSD discriminated signal. The temporal distribution of the latencies shows that the¦different values were included between 6 and 60ms with no peak value for SSD while the WWD¦data were all gathered around a peak of 11ms (corresponding to previous studies). The scattered¦distribution of the latencies recorded with the SSD did not correspond to a cell response.¦The SSD appears to be a powerful tool for signal sorting but we do not succeed to use it for the¦Single-Unit Analysis extracellular recordings. Further recordings with different SSD templates settings¦and larger sample size may help to show the utility of this tool in Single-Unit Analysis studies.

A novel optical intracellular imaging approach for potassium dynamics in astrocytes.

Astrocytes fulfill a central role in regulating K+ and glutamate, both released by neurons into the extracellular space during activity. Glial glutamate uptake is a secondary active process that involves the influx of three Na+ ions and one proton and the efflux of one K+ ion. Thus, intracellular K+ concentration ([K+]i) is potentially influenced both by extracellular K+ concentration ([K+]o) fluctuations and glutamate transport in astrocytes. We evaluated the impact of these K+ ion movements on [K+]i in primary mouse astrocytes by microspectrofluorimetry. We established a new noninvasive and reliable approach to monitor and quantify [K+]i using the recently developed K+ sensitive fluorescent indicator Asante Potassium Green-1 (APG-1). An in situ calibration procedure enabled us to estimate the resting [K+]i at 133±1 mM. We first investigated the dependency of [K+]i levels on [K+]o. We found that [K+]i followed [K+]o changes nearly proportionally in the range 3-10 mM, which is consistent with previously reported microelectrode measurements of intracellular K+ concentration changes in astrocytes. We then found that glutamate superfusion caused a reversible drop of [K+]i that depended on the glutamate concentration with an apparent EC50 of 11.1±1.4 µM, corresponding to the affinity of astrocyte glutamate transporters. The amplitude of the [K+]i drop was found to be 2.3±0.1 mM for 200 µM glutamate applications. Overall, this study shows that the fluorescent K+ indicator APG-1 is a powerful new tool for addressing important questions regarding fine [K+]i regulation with excellent spatial resolution.