In vivoblue light illumination for optogenetic inhibition: effect on local temperature and excitability of the rat hippocampus.

Objective.The blue light-activated inhibitory opsin, stGtACR2, is gaining prominence as a neuromodulatory tool due its ability to shunt-inhibit neurons and is being frequently used inin vivoexperimentation. However, experiments involving stGtACR2 use longer durations of blue light pulses, which inadvertently heat up the local brain tissue and confound experimental results. Therefore, the heating effects of illumination parameters used forin vivooptogenetic inhibition must be evaluated.Approach.To assess blue light (473 nm)-induced heating of the brain, we used a computational model as well as direct temperature measurements using a fiber Bragg grating (FBG). The effects of different light power densities (LPDs) and pulse durations on evoked potentials (EP) recorded from dentate gyrus were assessed. For opsin-negative rats, LPDs between 127 and 636 mW mm-2and pulse durations between 20 and 5120 ms were tested while for stGtACR2 expressing rats, LPD of 127 mW mm-2and pulse durations between 20 and 640 ms were tested.Main results.Increasing LPDs and pulse durations logarithmically increased the peak temperature and significantly decreased the population spike (PS) amplitude and latencies of EPs. For a pulse duration of 5120 ms, the tissue temperature increased by 0.6 °C-3.4 °C. All tested LPDs decreased the PS amplitude in opsin-negative rats, but 127 mW mm-2had comparatively minimal effects and a significant effect of increasing light pulse duration was seen from 320 ms and beyond. This corresponded with an average temperature increase of 0.2 °C-1.1 °C at the recorded site. Compared to opsin-negative rats, illumination in stGtACR2-expressing rats resulted in much greater inhibition of EPs.Significance.Our study demonstrates that light-induced heating of the brain can be accurately measuredin vivousing FBG sensors. Such light-induced heating alone can affect neuronal excitability. Useful neuromodulation by the activation of stGtACR2 is still possible while minimizing thermal effects.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.