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Bernstein Conference 2022 abstract. http://bernstein-conference.de

Single-unit recordings in the brain of behaving human subjects provide a unique opportunity to advance our understanding of neural mechanisms of cognition. These recordings are exclusively performed in medical centers during diagnostic or therapeutic procedures. The presence of medical instruments along with other aspects of the hospital environment limit the control of electrical noise compared to animal laboratory environments. Here, we highlight the problem of an increased occurrence of simultaneous spike events on different recording channels in human single-unit recordings. Most of these simultaneous events were detected in clusters previously labeled as artifacts and showed similar waveforms. These events may result from common external noise sources or from different micro-electrodes recording activity from the same neuron. To address the problem of duplicate recorded events, we introduce an open-source algorithm to identify these artificial spike events based on their synchronicity and waveform similarity. Applying our method to a comprehensive dataset of human single-unit recordings, we demonstrate that our algorithm can substantially increase the data quality of these recordings. Given our findings, we argue that future studies of single-unit activity recorded under noisy conditions should employ algorithms of this kind to improve data quality.

Increasing data suggest that for medical school students the stress of academic and psychological demands can impair social emotions that are a core aspect of compassion and ultimately physician competence. Few interventions have proven successful for enhancing physician compassion in ways that persist in the face of suffering and that enable sustained caretaker well-being. To address this issue, the current study was designed to (1) investigate the feasibility of cognitively-based compassion training (CBCT) for second-year medical students, and (2) test whether CBCT decreases depression, enhances compassion, and improves daily functioning in medical students. Compared to the wait-list group, students randomized to CBCT reported increased compassion, and decreased loneliness and depression. Changes in compassion were most robust in individuals reporting high levels of depression at baseline, suggesting that CBCT may benefit those most in need by breaking the link between personal suffering and a concomitant drop in compassion

Background: With the emergence of microglia-modulating therapies there is an urgent need for reliable biomarkers to evaluate microglial activation states., Methods: Using mouse models and human induced pluripotent stem cell-derived microglia (hiMGL), which were genetically modified to yield the most opposite homeostatic ( TREM2- knockout) and disease-associated ( GRN -knockout) states, we identified microglia activity-dependent markers. Non-targeted mass spectrometry was used to identify changes in microglial and cerebrospinal (CSF) proteome of Grn - and Trem2 -knockout mice. Additionally, we analyzed the proteome of GRN - and TREM2 -knockout hiMGL and their conditioned media. Candidate marker proteins were tested in two independent patient cohorts, the ALLFTD cohort with 11 GRN mutation carriers and 12 non-carriers, as well as the proteomic data set available from the European Medical Information Framework Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD)., Findings: We identified proteomic changes between the opposite activation states in mouse microglia and cerebrospinal fluid (CSF), as well as in hiMGL cell lysates and conditioned media. For further verification, we analyzed the CSF proteome of heterozygous GRN mutation carriers suffering from frontotemporal dementia (FTD). We identified a panel of six proteins (FABP3, MDH1, GDI1, CAPG, CD44, GPNMB) as potential indicators for microglial activation. Moreover, we confirmed three of these proteins (FABP3, GDI1, MDH1) to be significantly elevated in the CSF of AD patients. In AD, these markers differentiated amyloid-positive cases with mild cognitive impairment (MCI) from amyloid-negative individuals., Interpretation: The identified candidate proteins reflect microglia activity and may be relevant for monitoring the microglial response in clinical practice and clinical trials modulating microglial activity and amyloid deposition. Moreover, the finding that three of these markers differentiate amyloid-positive from amyloid-negative MCI cases in the AD cohort suggests that these marker proteins associate with a very early immune response to seeded amyloid. This is consistent with our previous findings in the DIAN (Dominantly Inherited Alzheimer's Disease Network) cohort, where soluble TREM2 increases as early as 21 years before symptom onset. Moreover, in mouse models for amyloidogenesis, seeding of amyloid is limited by physiologically active microglia further supporting their early protective role. The biological functions of some of our main candidates (FABP3, CD44, GPNMB) also further emphasize that lipid dysmetabolism may be a common feature of neurodegenerative disorders., Funding: This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy - ID 390857198 to CH, SFL and DP) and a Koselleck Project HA1737/16-1 (to CH).